Abstract:
The present invention relates to the isolation of members of fungal-specific kinase families and their use in identifying compounds that modulate kinase activity and the use of those compounds as antifungal agents for therapeutic treatments and medicaments in animals and plants.

Description:
CROSS-REFERENCE TO RELATED PATENT APPLICATIONS  
       [0001]    This application is a Non-Provisional of U.S. Application No. 60/395,624, filed Jul. 15, 2002, incorporated herein by reference in its entirety. 
     
    
     
       FIELD OF THE INVENTION  
         [0002]    The present invention relates to the isolation of fungal-specific kinases and the identification of compounds and compositions that modulate the activity of fungal-specific kinase enzymes and their use as antifungal agents.  
         BACKGROUND OF THE INVENTION  
         [0003]    More than a million species of fungi belong to the Kingdom Fungi, but only about four hundred are known to cause diseases that afflict humans, animals, and plants. Factors that predispose individuals to the development of fungal diseases include neutropenia, the use of immunosuppressive agents during organ transplantation, intensive chemotherapy and irradiation for hematopoietic malignancies or solid tumors, use of corticosteroids, extensive surgery and prosthetic devices, indwelling venous catheters, hyperalimentation and intravenous drug use, as well as when the balance of the normal flora is altered through antimicrobial therapy.  
           [0004]    The majority of such pathogenic fungal species are classified within the Phyla Zygomycota, Basidiomycota, Ascomycota, or the form group Fungi Imperfecti, but in general, are considered as either yeasts or molds. Yeasts are typically solitary rounded forms that reproduce by budding or fission. Mold spores, on the other hand, germinate to produce branching hyphae filaments that may be uninucleate, binucleate, or multinucleate.  
           [0005]    Mold-like fungi called dermatophytes cause athlete&#39;s foot, groin-related infections and ringworm of the skin or scalp. These fungi live on dead tissues of hair, nails and the outer layer of skin. Poor hygiene, continually moist skin and minor skin or nail injuries increases an individual&#39;s susceptibility to fungal infections. Ringworm symptoms are itchy, red, scaly, slightly raised, expanding rings on the trunk, face or groin and thigh. Pets also can transmit the fungus to humans.  
           [0006]    Aspergillosis is a name given to a wide range of diseases caused by the fungus, Aspergillus, now also known as Emericella. Members of this genus that cause disease in humans include  Aspergillus flavus, Aspergillus fumigatus, Aspergillus glaucus, Aspergillus nidulans, Aspergillus niger  and  Aspergillus terreus . Three principal diseases are allergic bronchopulmonary aspergillosis, pulmonary aspergilloma and invasive aspergillosis. Furthermore, colonization of the respiratory tract is also common. For instance, colonization of the sinuses and lungs, toxicoses, allergic bronchopulmonary aspergillosis, pulmonary aspergilloma, invasive aspergillosis, pulmonary aspergillosis, CNS aspergillosis, sinonasal aspergillosis, osteomyelitis, endophthalmitis, endocarditis, renal abscesses, otomycosis, exogenous endophthalmitis, allergic fungal sinusitis, and urinary tract fungus balls, are among of some of the other diseases caused by Aspergillus infections. Aspergillus also frequently are secondary opportunistic pathogens in patients with tuberculosis, bronchiectasis, other mycoses and carcinoma. Similarly, Aspergillus fungal infections can be a complication resulting from burns, post surgical wounds and intravenous injections.  
           [0007]    Another group of fungi of the genus,  Blastomyces dermatitidis , cause blastomycosis-related diseases. The infection is acquired via inhalation of asexual spores. After 30 to 45 days an acute pulmonary disease indistinguishable from a bacterial pneumonia may occur. Most cases become manifest during a chronic and indolent phase that may affect the lungs, the skin, the bones, the genitourinary tract and other reticuloendothelial organs.  
           [0008]    Yet another major infectious fungus is Candida, which are thin-walled, small fungi that reproduce by budding. Even though there are more that 150 species of Candida, no more than ten cause disease in humans with any frequency. Of these,  Candida albicans  causes almost 100% of cases of oropharyngeal candidiasis and at least 90% of cases of  Candida vulvovaginitis . When Candida produce invasive candidiasis, infection by the other species of Candida are observed. Invasive means the fungus has infected tissues or the blood. Invasive candidiasis, which is also known as systemic candidiasis, is typically seen in individuals that have reduced immunogenecity or weakened immune systems. Almost any organ of the body may be involved.  
           [0009]    Some fungi, however, infect only animals and not humans. For instance, the dermatophyte  Microsporum gallinae  brings about disease in chickens, but not humans. Ringworm in pets and livestock is not uncommon. For example, the dermatophyte  Microsporum canis  may cause ringworm in a variety of mammals, such as cats, dogs and humans. Similarly, cryptococcosis occurs in cats and humans.  
           [0010]    There are a myriad of other fungi that attack and infect plants, such as crops and trees. For example cruciferous crops like cabbage, cauliflower, canola and rutabaga are susceptible to a number of fungal diseases. Pythium and Rhizoctonia fungi rot seeds and older seedlings;  Phoma lingam  ( Leptosphaeria macutans ) often kills seedlings or stunts the growth of surviving plants;  Plasmodiophora brassicae  is a destructive soil-borne disease which affects nearly all cultivated, as well as many wild and weed members of the cabbage family;  Fusarium oxysporum  yellows or wilts plants;  Peronospora parasitica  causes downy mildew. Particularly susceptible hosts include canola, cabbage, broccoli, Brussels sprouts, kale, cauliflower, rutabaga, radish, horseradish, Chinese cabbage and mustards, ornamentals such as stock, wallflower, and aubretia, and many cruciferous weeds. There also exists Common Root Rot caused by Fusarium and Helminthosporium; Septoria Leaf Blotch occurs in wheat and  Pyrenophora trichostoma  infects Spring wheat. Other fungal-induced plant diseases include gray mould and ghost spot diseases of practically all plants by  Botrytis cinerea . Leaf mould is caused by the fungus,  Fulvia fulva , also known as  Cladosporium fulverum . Powdery mildew is a very common disease caused by the fungus  Oidiopsis taurica , also known as  Leveillula taurica . Late Blight is a very devastating disease of tomato, potato, and eggplant, caused by the fungus  Phytophthora infestans.    
           [0011]    Even though fungi and mammalian cells are both eukaryotic cells, the differences that exist between them can be sufficiently distinct that they form the basis of targets for fungal-specific drug interactions. The most convenient and effective approach for treating fungal infections therefore involves administering a drug or compound that targets a unique feature of a fungal cell. In this regard, fungi possess a number of biological traits that distinguish them from other organisms. They possess, for example, chitin, ergosterol, a unique lysine biosynthesis pathway, soluble carbohydrates, unstacked Golgi cisternae and unique microtubules. They also differ from other organisms in a range of biochemical and molecular features such as the regulation of some enzymes and some aspects of mitochondrial codon usage.  
           [0012]    Thus, drugs that specifically target fungal cell wall synthesis, fungal DNA synthesis or enzymes in key fungal biological pathways are extremely useful in destroying or eradicating an infecting fungus, while having minimal toxicity, if any, to the affected subject. Accordingly, there exist established and developing drug treatments used to combat and treat a wide variety of immunological responses, symptoms and diseases caused by fungal infection in mammals. To this end, there are, in general, half a dozen or so groups of compounds, drugs and chemicals that have proven useful in treating certain fungal infections. Allylamines, for example, are a group of drugs that inhibit ergosterol biosynthesis. This sterol occurs in fungi, bacteria, algae, and plants, and is converted into vitamin D2 by ultraviolet light. Such allyamines include amorolfine, butenafine, naftifine and terbinafine. The latter agent, for example, acts by inhibiting squalene epoxidase, an enzyme involved in ergosterol synthesis.  
           [0013]    There also exist azole-based antifungal agents such as fluconazole, itraconazole, ketoconazole, posaconazole, ravuconazole, voriconazole, clotrimazole, econazole, miconazole, oxiconazole, sulconazole, terconazole and tioconazole. These azole antifungal agents also inhibit the synthesis of ergosterol, but by blocking the action of 14-alpha-demethylase.  
           [0014]    Other antifungal agents inhibit 1,3-beta glucan synthase or other enzymes involved in fungal cell wall synthesis. Illustrative of such “glucan synthesis” inhibitors are caspofungin, micafungin, and anidulafungin. There also are agents that target fungal cell membranes, causing the fungus to leak electrolytes. Exemplary of such “polyenes” are Amphotericin B (AmB), AmB lipid complex, AmB colloidal dispersion, liposomal AmB, AmB oral suspension, liposomal nystatin, topical nystatin and pimaricin ophthalmic. Yet other drugs include griseofulvin, which inhibits fungal mitosis; the antimetabolite, flucytosine, which is a DNA substrate analog that leads to incorrect DNA synthesis; and topical drugs such as ciclopirox olamine, haloprogin, tolnaftate, and undecylenate.  
           [0015]    Nevertheless, development of new antifungal agents is difficult because there are relatively few key fungal genes and proteins that are not present in the human genome. Therefore, a need exists to identify fungal genes that are sufficiently distinct from any human counterpart that they can form the basis of fungal-specific drug interactions, and specifically be used to identify drugs targeted against fungi. A number of kinase families have now been identified which are present only in fungal genomes.  
         SUMMARY OF THE INVENTION  
         [0016]    In one aspect of the present invention, a method (“method 1”) for identifying an antifungal agent that inhibits a fungal-specific kinase in a sample is provided. This method comprises determining the activity of the fungal-specific kinase in the sample before and after exposing the sample to a test compound. In one embodiment, the sample is a fungus. In another embodiment, the sample is a preparation of a fungus extract. In another embodiment, the sample is a cell or culture of cells. In another embodiment, the cell or culture of cells may be suspected of containing fungal cells. To this end, the cells may be mammalian, bacterial, insecticidal, or fungal cells. In yet another embodiment, the sample is an isolated and/or purified preparation of the kinase. In a further embodiment, the kinase is recombinantly produced.  
           [0017]    In yet another embodiment, the fungal-specific kinase is selected from the group consisting of KIN1, KIN4, GIN4, RAN, ELM and HAL kinases. In a preferred embodiment, the kinase domain of the kinase has at least 46% sequence identity to a kinase domain of any one of SEQ ID NOs. 1-5. Preferably, the kinase domain has a percentage sequence identity to a kinase domain of any one of SEQ ID NOs. 1-5 of 50%, of 55%, of 60%, of 65%, of 70%, of 75%, of 80%, of 85%, of 90%, or of 95%. In another preferred embodiment, the kinase domain of the kinase has at least 55% sequence identity to a kinase domain of any one of SEQ ID NOs. 6-9. Preferably, the kinase domain has a percentage sequence identity to a kinase domain of any one of SEQ ID NOs. 6-9 of 60%, of 65%, of 70%, of 75%, of 80%, of 85%, of 90%, or of 95%. In a further embodiment, the kinase domain of the kinase has at least 55% sequence identity to a kinase domain of any one of SEQ ID NOs. 10-16. Preferably, the kinase domain has a percentage sequence identity to a kinase domain of any one of SEQ ID NOs. 10-16, of 60%, of 65%, of 70%, of 75%, of 80%, of 85%, of 90%, or of 95%. In one other embodiment, the kinase domain of the kinase has at least 55% sequence identity to a kinase domain of any one of SEQ ID NOs. 17-24. Preferably, the kinase domain has a percentage sequence identity to a kinase domain of any one of SEQ ID NOs. 17-24, of 60%, of 65%, of 70%, of 75%, of 80%, of 85%, of 90%, or of 95%. In another embodiment, the kinase domain of the kinase has at least 38% sequence identity to a kinase domain of any one of SEQ ID NOs. 25-29. Preferably, the kinase domain has a percentage sequence identity to a kinase domain of any one of SEQ ID NOs. 25-29, of 40%, of 45%, of 50%, of 55%, of 60%, of 65%, of 70%, of 75%, of 80%, of 85%, of 90%, or of 95%. In yet another embodiment, the kinase domain of the kinase has at least 30% sequence identity to a kinase domain of any one of SEQ ID NOs. 30-42. Preferably, the kinase domain has a percentage sequence identity to a kinase domain of any one of SEQ ID NOs. 30-42, of 60%, of 65%, of 70%, of 75%, of 80%, of 85%, of 90%, or of 95%.  
           [0018]    In another embodiment, a reduction in fungal-specific kinase activity after the sample is exposed to the test compound indicates that the test compound is an antifungal agent. In a preferred embodiment, the test compound does not inhibit kinase activity of a kinase endogenous to a non-fungal organism. In a preferred embodiment, the non-fungal organism is a mammal, animal, tree or plant. In a more preferred embodiment, the mammal is a goat, sheep, cattle, horse, cat, dog, pig, rat, mouse, primate, or a human. In a most preferred embodiment, the mammal is a human. In one other embodiment, the non-fungal organism is a fish, bird, or a reptile. In another embodiment, the non-fungal organism is a plant selected from the group consisting of barley, wheat, corn, rice, cotton, oak, tomato, potato, Dutch elm, and Chestnut.  
           [0019]    In another embodiment, the test compound identified by method 1 as an antifungal agent reduces fungal growth when applied to a living fungus. In yet another embodiment, fungal growth is reduced in the fungus to which the antifungal agent is applied and/or to fungal progeny. In yet another embodiment, the test compound eradicates a fungus to which it is applied.  
           [0020]    In one other embodiment, kinase activity is determined by comparing protein phosphorylation patterns of the sample in which the fungal-specific kinase is present in the presence and absence of the test compound.  
           [0021]    Another aspect of the present invention is a method (“method 2”) for identifying a compound that has antifungal properties. This method comprises (i) selecting and culturing a fungus sample that contains a kinase having a minimum sequence identity to any one of SEQ ID NOs. 1-42; (ii) treating the fungus sample with a test compound; and (iii) determining, after the treating of step, the level of activity of the fungus in comparison to an untreated control fungus sample. In one embodiment, a decrease in the level of fungus activity of the treated fungus, compared with the control sample, indicates that the test compound is a compound that has antifungal properties.  
           [0022]    In one embodiment of the present invention, a “minimum sequence identity” is the minimum sequence identity that a kinase must have to a kinase domain of the present invention so as to be classified as a fungal-specific kinase.  
           [0023]    Thus, in one embodiment, the minimum sequence identity is at least 46% to KIN1, more preferably to any one of SEQ ID NOs. 1-5. In another embodiment, the percentage sequence identity of a kinase to any one of KIN1, preferably to any one of SEQ ID NOs. 1-5, is 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.  
           [0024]    Similarly, in another embodiment, the minimum sequence identity is at least 55% to KIN4, more preferably to any one of SEQ ID NOs. 6-9. In another embodiment, the percentage sequence identity of a kinase to any one of KIN4, preferably to any one of SEQ ID NOs. 6-9, is 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.  
           [0025]    In another embodiment, the minimum sequence identity is at least 55% to GIN4, more preferably to any one of SEQ ID NOs. 10-16. In another embodiment, the percentage sequence identity of a kinase to any one of GIN4, preferably to any one of SEQ ID NOs. 10-16, is 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.  
           [0026]    In another embodiment, the minimum sequence identity of RAN is at least 55% sequence identity to SEQ ID NOs. 17-24. In another embodiment, the percentage sequence identity of a kinase to any one of RAN, preferably to any one of SEQ ID NOs. 17-24, is 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.  
           [0027]    In another embodiment, the minimum sequence identity is at least 38% to ELM, more preferably to any one of SEQ ID NOs. 25-29. In another embodiment, the percentage sequence identity of a kinase to any one of ELM, preferably to any one of SEQ ID NOs. 25-29, is 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.  
           [0028]    In another embodiment, the minimum sequence identity is at least 30% to HAL, more preferably to any one of SEQ ID NOs. 30-42. In another embodiment, the percentage sequence identity of a kinase to any one of HAL, preferably to any one of SEQ ID NOs. 30-42, is 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95%.  
           [0029]    In one embodiment, the step of determining fungal activity in the fungus sample comprises at least one of determining chitin content or performing an agar dilution assay. In another embodiment, a decrease in chitin staining or reduction in optical density indicates a reduction in growth of the fungus in the fungus sample. The fungus samples described herein that are treated with a test compound or are used in a screening assay for compounds that inhibit endogenous kinases, can be intact fungi or extracts prepared from a fungus.  
           [0030]    The present invention also encompasses the use of a recombinantly produced kinase in a screening assay for compounds that inhibit that kinase. Thus, according to such a method, a recombinantly produced kinase, such as a KIN1, KIN4, GIN4, RAN, ELM, or HAL kinase is exposed to a compound that may or may not affect the kinase activity of that kinase.  
           [0031]    Yet another aspect of the present invention is a method (“method 3”) that comprises administering to a non-fungal organism, a compound capable of inhibiting a kinase in a fungus living in or on the non-fungal organism. In one embodiment, the kinase comprises an amino acid sequence selected from the group consisting of SEQ ID NOs. 1-42. In another embodiment, the kinase comprises an amino acid sequence that has minimum sequence identity of at least 46%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% to a KIN1 family member, or more preferably has minimum sequence identity of at least 46%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% to any one of SEQ ID NOs. 1-5. In another embodiment, the kinase comprises an amino acid sequence that has minimum sequence identity of at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% to a KIN4, a GIN4 or a RAN family member, or more preferably has minimum sequence identity of at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% to any one of SEQ ID NOs. 6-24. In yet another embodiment, the kinase comprises an amino acid sequence that has minimum sequence identity of at least 38%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% to an ELM family member, or more preferably has minimum sequence identity of at least 38%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% to any one of SEQ ID NOs. 25-29. Furthermore, in another embodiment, the kinase comprises an amino acid sequence that has minimum sequence identity of at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% to a HAL family member, or more preferably has minimum sequence identity of at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% to any one of SEQ ID NOs. 30-42.  
           [0032]    In a preferred embodiment, the compound does not inhibit a kinase endogenous to the non-fungal organism.  
           [0033]    In a preferred embodiment, the compound reduces growth of the fungus or eradicates the fungus living in or on the non-fungal organism. In another embodiment, the compound is administered to the non-fungal organism by spraying, injecting, ingesting, inhaling, swallowing or applying a topical cream, gel, liquid, powder, pellet, aerosol or fluid suspension containing the compound to the fungus living in or on the non-fungal organism.  
           [0034]    In a preferred embodiment, the test compound does not inhibit kinase activity of a kinase endogenous to a non-fungal organism. In a preferred embodiment, the non-fungal organism is a mammal, animal, tree or plant. In a more preferred embodiment, the mammal is a goat, sheep, cattle, horse, cat, dog, pig, rat, mouse, primate, or a human. In a most preferred embodiment, the mammal is a human. In one other embodiment, the non-fungal organism is a fish, bird, or a reptile. In another embodiment, the non-fungal organism is a plant selected from the group consisting of barley, wheat, corn, rice, cotton, oak, tomato, potato, Dutch elm, and Chestnut.  
           [0035]    Yet another aspect of the present invention involves identifying kinases (“method 4”) that are fungal-specific and which can be targeted by compounds that inhibit their activity. This method comprises comparing the amino acid sequence of a protein with the kinase domains of SEQ ID NOs. 1-42. In a preferred embodiment, the protein belongs to a fungal-specific kinase family of the present invention if the protein contains a sequence that has a minimum sequence identity (as defined above) to a kinase domain of any one of SEQ ID NOs. 1-42. In a preferred embodiment, the fungal-specific kinase family consists of KIN1, KIN4, GIN4, RAN, ELM and HAL kinase members. In one embodiment the amino acid sequence of the protein is obtained from a public database or a proprietary database. In another embodiment the protein sequence is obtained by sequencing a DNA clone that encodes the protein.  
           [0036]    Accordingly, the present invention provides a method for identifying a compound that inhibits the activity of at least one of KIN1 kinase, KIN4 kinase, GIN4 kinase, RAN kinase, ELM kinase, or HAL kinase in a fungus comprising determining the activity of the kinase before and after exposing the fungus to a test compound, wherein a reduction in kinase activity in the presence of the test compound indicates that the test compound is an antifungal agent, wherein the test compound has minimal toxicity to a non-fungal organism, and wherein the kinase domain of the KIN1 kinase has at least 46% sequence identity to a kinase domain of any one of SEQ ID NOs. 1-5, wherein the kinase domain of the KIN4 kinase has at least 55% sequence identity to a kinase domain of any one of SEQ ID NOs. 6-9, wherein the kinase domain of the GIN4 kinase has at least 55% sequence identity to a kinase domain of any one of SEQ ID NOs. 10-16, wherein the kinase domain of the RAN kinase has at least 55% sequence identity to a kinase domain of any one of SEQ ID NOs. 17-24, wherein the kinase domain of the ELM kinase has at least 38% sequence identity to a kinase domain of any one of SEQ ID NOs. 25-29, and wherein the kinase domain of the HAL kinase has at least 30% sequence identity to a kinase domain of any one of SEQ ID NOs. 30-42.  
           [0037]    In another embodiment, the kinase domain of KIN1 kinase, KIN4 kinase, GIN4 kinase, RAN kinase, ELM kinase, and HAL kinase has between 80-90% sequence identity to a kinase domain of any one of SEQ ID NOs. 1-5, 6-9, 10-16, 17-24, 25-29, 30-42 respectively.  
           [0038]    In any of the methods described herein, the test compound reduces fungal growth or eradicates the fungus. In another embodiment, the kinase activity is determined by comparing protein phosphorylation patterns in the fungus in the presence and absence of the test compound.  
           [0039]    In another aspect, a method of identifying a compound having antifungal properties is provided, comprising (a) culturing a fungus sample; (b) treating the fungus sample with a test compound; (c) determining, after the treating of step (b), the level of activity of the fungus the sample in comparison to an untreated control fungus sample, wherein a decrease in the level of fungus activity of the treated fungus, compared with the control sample, indicates that the test compound is an antifungal agent, wherein the fungus sample is a fungus or a fungus extract, and wherein the fungus comprises at least one of a KIN1 kinase, a KIN4 kinase, a GIN4 kinase, a RAN kinase, an ELM kinase, or a HAL kinase.  
           [0040]    In a preferred embodiment, the kinase domain of the KIN1 kinase has at least 46% sequence identity to a kinase domain of any one of SEQ ID NOs. 1-5, wherein the kinase domain of the KIN4 kinase has at least 55% sequence identity to a kinase domain of any one of SEQ ID NOs. 6-9, wherein the kinase domain of the GIN4 kinase has at least 55% sequence identity to a kinase domain of any one of SEQ ID NOs. 10-16, wherein the kinase domain of the RAN kinase has at least 55% sequence identity to a kinase domain of any one of SEQ ID NOs. 17-24, wherein the kinase domain of the ELM kinase has at least 38% sequence identity to a kinase domain of any one of SEQ ID NOs. 25-29, and wherein the kinase domain of the HAL kinase has at least 30% sequence identity to a kinase domain of any one of SEQ ID NOs. 30-42.  
           [0041]    In one embodiment, the fungus of the present invention is an Ascomycetes, Zygomycota, Deuteromycota, Mycophycophyta, Ascomycota, Gasteromycetes, Myxomycota, Oomycota or Hymenomycetes fungus. In a further embodiment, the fungus is an  Aspergillus flavus, Aspergillus fumigatus, Aspergillus glaucus  group,  Aspergillus nidulans, Aspergillus niger, Aspergillus terreus  group,  Blastomyces dermatitidis, Candida albicans, Candida tropicalis, Candida glabrata, Candida parapsilosis, Candida krusei, Candida lusitaniae, Coccidioides immitis, Histoplasma capsulatum  var.  capsulatum, Paracoccidioides brasiliensis, Sporothrix schenckii , Absidia, Apophysomyces, Cokeromyces, Cunninghamella, Mucor, Rhizomucor, Rhizopus, Saksenaea, Syncephalastrum, Mortierella, Basidiobolus, Conidiobolus, Trichophyton,  Microsporum gallinae, Microsporum canis mycorrhiza , arbuscular mycorrhiza, vesicular-arbuscular mycorrhiza or Ectomycorrhiza.  
           [0042]    In another aspect of the present invention, a pharmaceutical composition is provided for administration to a non-fungal organism. In one embodiment the pharmaceutical composition comprises a compound that inhibits activity of a kinase in a fungus but does not inhibit any kinase that is endogenous to the non-fungal organism infected with the fungus.  
           [0043]    Thus, in one embodiment, the compound in the pharmaceutical composition inhibits a kinase that has kinase domain amino acid sequence that has (i) at least 46% sequence identity to a kinase domain of any one of SEQ ID NOs. 1-5, or (ii) at least 55% sequence identity to a kinase domain of any one of SEQ ID NOs. 6-9, or (iii) at least 55% sequence identity to a kinase domain of any one of SEQ ID NOs. 10-16, or (iv) at least 55% sequence identity to a kinase domain of any one of SEQ ID NOs. 17-24, or (v) at least 38% sequence identity to a kinase domain of any one of SEQ ID NOs. 25-29, and or (vi) at least 30% sequence identity to a kinase domain of any one of SEQ ID NOs. 30-42. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0044]    The present invention contemplates the use of compounds that only target and inhibit the function of fungal kinases and not those endogenous to the infected host. Thus, a suitable antifungal agent of the invention is one that destroys, retards the growth of, or decreases the viability of, a wide range of fungi, while having minimal effects upon the infected, non-fungal organism.  
         [0045]    Definitions  
         [0046]    Antifungal agent: a compound that has antifungal properties is one which destroys or inhibits the growth, reproduction, or other function of a fungus or fungi. An antifungal agent of the invention may exert its antifungal properties upon the fungus to which it is applied, or to subsequent progeny or generations of that fungus. An antifungal agent is also one that inhibits the activity of a kinase endogenous to a fungus or fungal species. Thus, an antifungal agent may exert an effect upon the molecular constituents of a fungus, i.e., a kinase, rather than the macroscopic attributes of the fungus itself. An antifungal agent may be a nucleic acid that inhibits gene expression or causes the degradation of an mRNA transcript associated with a gene product. Thus, the present invention envisions the use of single- and double-stranded DNA and RNA molecules to inhibit gene transcription and mRNA translation. Accordingly, an antifungal agent may act to inhibit or down-regulate gene expression of a fungal-specific kinase by gene silencing, RNA interference or antisense- or sense-technologies. An antifungal agent may include antibodies or peptides. An antifungal agent may also include small chemical compounds such as indolines.  
         [0047]    Ascomycetes: these fungi grow as hyphae with cross-walls (septa) or yeasts; sexual reproduction is by fusion of modified hyphae (or yeasts), sometimes by fusion of a “male” spore (spermatium) with a “female” receptive hypha (trichogyne), leading to development of an ascus containing ascospores.  
         [0048]    Basidiomycota: these fungi grow as hyphae or yeasts; asexual spores are relatively rare; sexual reproduction is by fusion of compatible hyphae, leading ultimately to production of basidiospores on basidia, sometimes on or in a fruiting body (e.g., toadstool).  
         [0049]    Chytridiomycota: typically unicellular, or with primitive chains of cells attached to a food base by tapering rhizoids; sexual reproduction is by fusion of motile gametes; asexual reproduction is by cytoplasmic cleavage in a sporangium, producing motile, uniflagellate zoospores.  
         [0050]    Deuteromycota: these fungi grow as hyphae (with septa) or yeasts; sexual reproduction is absent, rare or unknown; asexual spores (conidia) are formed in various ways from hyphae but never by cytoplasmic cleavage in a sporangium.  
         [0051]    Eradicat s: to “eradicate” is understood to mean to get rid of completely or destroy, so that no detectable level of the material in question (e.g., a living fungus) remains using standard technology.  
         [0052]    External surface: an “external surface” is any surface of an animal or plant that is exposed to, or can be exposed to, the atmosphere, or is not internal of the body or structure of the animal or plant. For instance, skin, hair, eyes, nails, claws, talons, teeth, gums, lips, tongue, the inside of a mouth, hide, fur, scales, bark, stems, leaves, roots, petals, fruit surfaces, or buds.  
         [0053]    Fungus: a “fungus” is any of numerous eukaryotic organisms of the kingdom Fungi, which lack chlorophyll and vascular tissue and range in form from a single cell to a body mass of branched filamentous hyphae that often produce specialized fruiting bodies. The kingdom includes the yeasts, molds, smuts, and mushrooms.  
         [0054]    Fungal activity: the “activity” of a fungus can be assessed by using methods well known in the art, such as monitoring, for example, its viability, growth status, rate of hyphal development or amount. Fungal activity can be measured before and after treatment with a test compound. Any one of these measurements is an indicator of the relative “activity” of a fungal sample.  
         [0055]    Fungal growth: the “growth” of a fungi can be measured, or considered in terms of, its rate of reproduction, hyphae development, or general mass proliferation. For instance, fungal growth can be determined by the rate of apical growth; that is, the rate of growth of the tips of hyphae. The rate of hyphae tip extension, for example, can be extremely rapid and easily quantifiable, growing at rates up to 40 μm per minute. Other assays for fungal cell growth include determining changes in fungal cell mass, volume and number.  
         [0056]    Fungal infection: an “infection” is an invasion by and multiplication of a fungus or fungi in or on a bodily part or tissue, which may produce subsequent tissue injury and progress to disease through a variety of cellular or toxic mechanisms. A fungus may also reside in earth or soil.  
         [0057]    Infected host: an “infected host” is a non-fungal organism that contains a fungus in or on a bodily part or tissue, that is not normally associated with the host; or a host that contains a fungus associated with a non-disease state of the host but the growth and/or abnormally high level of the fungus, or production of chemicals by the fungus, creates an abnormal or diseased state in the host. Examples of an infected host are, but are not limited to, mammals such as goats, sheep, cattle, horses, cats, dogs, pigs, and humans; fish, birds, or reptiles; plants, such as crop plants, trees, shrubs, ornamentals, and grasses.  
         [0058]    Inhibit: to “inhibit” as used herein, means to prevent or decrease the rate of a particular chemical reaction in a fungus or to decrease, limit, or block the action or function of an enzyme endogenous to, or body part of, a fungus. With respect to inhibiting a fungal enzyme, the enzyme may reside within a fungal cell or be in purified or isolated preparation outside of the fungus.  
         [0059]    Internal: a fungus may also infect, reside or be present within the body, tissues or organs of an infected host. Thus, an antifungal agent may target a fungus that infects the blood, for example.  
         [0060]    Exposing (to test compound): a fungus can be exposed to a test compound by directly contacting any part of the fungus or fungal cell to the test compound. The test compound may be a solid, fluid or aerosol that is in contact with an outer surface of the fungus. Alternatively, a test compound may be injected, swallowed, inhaled, topically applied or infused into the infected host, whereupon the compound targets the fungus in vivo.  
         [0061]    Kinase: a kinase is any one of several enzymes that catalyzes the transfer of a phosphate group from one molecule to another. A protein kinase phosphorylates amino acid residues in proteins.  
         [0062]    Kinase activity: the “activity” of a kinase refers to the rate of catalytic or enzymatic function of the enzyme in utilizing a substrate or in phosphorylating, for example, a substrate. Those of skill in the art will recognize that there are a variety of methods for determining kinase activity. See, for example, the methods described below.  
         [0063]    Minimal toxicity: an antifungal agent that has “minimal toxicity” upon a non-fungal organism is one that does not adversely affect, in any way, the function, life or biological processes of the non-fungal organism. That is, the antifungal agent does not, for example, inhibit the activity of a kinase that is endogenous to the non-fungal organism. Minimal toxicity means that the antifungal agent does not kill or inhibit the growth of the non-fungal organism, even though the antifungal agent may kill or inhibit the growth of a fungus living in or on the non-fungal organism.  
         [0064]    Minimum sequence identity: refers to the percentage of sequence identity that is needed for a kinase to be classified to a particular fungal family according the amino acid sequence of its kinase domain. Thus, a kinase is a KIN1 family member if its kinase domain has at least 46% sequence identity to a KIN1 kinase domain, i.e., to any one of SEQ ID NOs. 1-5. Similarly, additional KIN4, GIN4 and RAN family members must have a “minimum sequence identity” of 55% to any one of SEQ ID NOs. 6-24 to be classified accordingly. An ELM family member must have at least 38% sequence identity to an ELM family member kinase domain, as described, for example in any one of SEQ ID NOs. 25-29. A new HAL family member requires a sequence identity of only 30% to any one of SEQ ID NOs. 30-42. Classification of a kinase into one of these fungal families indicates that the kinase most likely does not have a non-fungal analog.  
         [0065]    Modulating a kinase: a kinase enzyme can be modulated such that its catalytic or enzymatic properties, or its rate of activity, are reduced or increased in the presence of a compound, such as an antifungal agent. Preferably, the term “modulate” refers to an inhibition of kinase activity.  
         [0066]    Non-fungal organism: Examples of a “non-fungal organism” include, but are not limited to, mammals such as goats, sheep, cattle, horses, cats, dogs, pigs, and humans; fish, birds, or reptiles; and plants, such as crop plants, trees, shrubs, ornamentals, and grasses.  
         [0067]    Test Compound: a “test compound” is a compound that effects the desired aims of the present invention, i.e., a test compound inhibits the growth of, or outright kills, an infectious fungus and/or its subsequent progeny. Examples of test compounds include peptide mimetics and ATP mimetics.  
         [0068]    Toxic: a “toxic” effect is one that is capable of causing injury, retardation of growth or death, for example, by chemical means. An antifungal agent of the present invention should ideally be toxic against a fungus or fungi and not toxic, or minimally toxic, against the infected host. When a fungus is in soil or earth, an antifungal agent should be not be toxic or should be minimally toxic to the environment surrounding the fungus. For instance, a desirable antifungal treatment would eradicate, or inhibit the growth of, a fungus growing on a tree or plant, but would not detrimentally affect the growth of the tree or plant.  
         [0069]    Zygomycota: typically grow as hyphae without cross-walls (aseptate); sexual reproduction is by fusion of sex organs (gametangia) leading to thick-walled resting spores (zygospores); asexual reproduction is by cytoplasmic cleavage in a sporangium, producing non-motile spores.  
         [0070]    The present invention is directed to the identification of kinases that are unique to fungi by comparing their kinase domains to any of a number of established fungal-specific kinase families. Accordingly, the present invention provides forty-two kinases, belonging to different fungal families, that can be used to identify other kinases that are unique to fungi. That is, additional fungal kinases can be identified based upon their homology or similarity to the forty-two kinases described herein. These, as well as the inventive forty-two kinases can be used to screen for test compounds that inhibit kinase activity. Compounds that inhibit any of these kinases can be used in pharmaceutical or agricultural formulations to inhibit kinases in infectious or undesirable fungi without modulating or inhibiting the activity of a kinase in an infected or non-fungal organism. Accordingly, the present invention provides antifungal agents useful for treating mammals, preferably humans, having fungal infections, as well as agriculturally- and ornamentally-important crops and plants.  
         [0071]    In order to determine which kinase families and kinase members of kinase families are unique to fungi, the amino acid sequences of kinases encoded by genes endogenous to the yeast  Saccharomyces cerevisiae  genome were compared with the sequences of kinases of higher eukaryotes; specifically,  Drosophila melanogaster, Caenorhabditis elegans  and human.  S. cerevisiae  sequences that had no close non-fungal homologs were subsequently identified and were classified into fungal-specific protein kinase families. These kinase sequences were then compared to those of  Schizosaccharomyces pombe , a fungus that is, in evolutionary terms, separated by a billion years from the evolution of  S. cerevisiae . The  S. cerevisiae  sequences were conserved in  S. pombe . Since members of each analyzed fungal-specific kinase family were also found in  S. pombe , it is likely that these kinase families are widely distributed in fungi and are broadly required for fungal survival.  
         [0072]    The invention contemplates that conserved kinase sequences between  S. cerevisiae  and  S. pombe  can be used to design inhibitors to target only these fungal-specific kinases. Since no other close homologs or isoforms were identified in the human genome, such inhibitors would be predicted not to target kinases in human cells.  
         [0073]    The yeast  S. cerevisiae  fungal kinases identified by the present inventors are SEQ ID NOs. 1-2 (belonging to the “KIN1” fungal family); SEQ ID NOs. 6-7 (belonging to the “KIN4” fungal family); SEQ ID NOs. 10-12 (belonging to the “GIN4” fungal family); SEQ ID NOs. 17-19 (belonging to the “RAN” fungal family); SEQ ID NOs. 25-27 (belonging to the “ELM” fungal family); and SEQ ID NOs. 30-38 (belonging to the “HAL” fungal family). Other fungal kinases, which share sequence homology with the endogneous  S. cerevisiae  kinase families include, but are not limited to those isolated from  S. pombe  and  C. albicans . Thus, the “Kin1-like” (SEQ ID NO. 3) kinase of  S. pombe  belongs in the same fungal kinase family as the “kin 1” (SEQ ID NO.1) kinase of  S. cerevisiae  because of their amino acid sequence composition.  
         [0074]    Accordingly, kinases from other fungal species can be classified being fungal-specific with no non-fungal homologs by virtue of the similarities in sequence between their kinase domain and any one of the members of the fungal specific families KIN1, KIN4, GIN4, RAN, ELM and HAL described below. KIN1 family  
         [0075]    The KIN1 family comprises the Kin1 and Kin2 genes of  Saccharomyces cerevisiae , at least two genes (Kin 1 and gi|19113449) from  Schizosaccharomyces pombe  and orf6.8762 from  Candida albicans.    
         [0076]    [0076] S. pombe  mutants of Kin1 display defects in cell polarity and morphology. Mutants in  S. cerevisiae  Kin2 have delayed entry into stationary phase when nutrients are withdrawn, which may be a pathological condion in natural growth.  S. cerevisiae  Kin1 has been implicated in vesicle transport within the cell and may be involved in budding or cell wall formation. The null  S. cerevisiae  mutant is viable; this may be due to redundancy between Kin1 and Kin2, whose kinase domains are more than 90% identical. Thus, an inhibitor of either of these kinases would likely inhibit both, and thus block any vital function redundantly supplied by both genes. Such functions may include response to nutritional stress, cell wall structure or function, and cytokinesis.  
         [0077]    The KIN1 fungal kinases include, in  S. cerevisiae , kin1 (SEQ ID NO.1) and Kin2 (SEQ ID NO. 2); in  S. pombe , Kin1-like (SEQ ID NO. 3) and Kin1 (SEQ ID NO. 4); and in  C. albicans , orf6.8762 (SEQ ID NO. 5). The kinase amino acid sequences of these particular family members appear below. Where appropriate, the public database accession number for a kinase is included so as to indicate its source.  
         [0078]    The bold, underlined portion of each family member denotes its kinase domain. Accordingly, the present invention allows the skilled artisan to identify and classify newly-identified kinases from other fungi as belonging to the KIN1 family if the newly-identified kinase domains share at least 46% amino acid sequence identity with any one of the underlined kinase domains of an indicated family member listed below. Preferably, a KIN1 kinase domain has a percentage sequence identity to a kinase domain of any one of SEQ ID NOs. 1-5 of 50%, of 55%, of 60%, of 65%, of 70%, of 75%, of 80%, of 85%, of 90%, or of 95%.  
                                 S. cerevisiae  kin1               MDDYHVNTAFSMGRGNQQDDGNSESNSMHTQPSTMAPATLRMMGKSPQQQQQQNTPLMPPADIKYANNG   (SEQ ID NO. 1)               NSHQAEQKERQVELEGKSRENAPKPNTTSQSRVSSSQGMPKQFHRKSLGD WEFVETVGAGSMGKVKLAK                   HRYTNEVCAVKIVNRATKAFLHKEQMLPPPKNEQDVLERQKKLEKEISRDKRTIREASLGQILYHPHIC                   RLFEMCTLSNHFYHLFEYVSGGQLLDYIIQHGSIREHQARKFARGIASALIYLHANNIVHRDLKIENIM                   ISDSSEIKIIDFGLSNIYDSRKQLHTFCGSLYFAAPELLKANPYTGPEVDVWSFGVVLFVLVCGKVPFD                   DENSSVLHEKIKQGKVEYPQHLSIEVISLLSKMLVVDPKRRATLKQVVEHHW MVRGFNGPPPSYLPKRV               PLTIEMLDINVLKEMYRLEFIDDVEETRSVLVSIITDPTYVLLSRQYWTLAAKMNAESSDNGNAPNITE               SFEDPTRAYHPMISIYYLTSEMLDRKHAKIRNQQQRQSHENIEKLSEIPESVKQRDVEVNTTANKSEPE               ATLATKDTSVPFTPKNSDGTEPPLHVLIPPRLAMPEQAHTSPTSRKSSDNQRREMEYALSPTPQGNDYQ               QFRVPSTTGDPSEKAKFGNIFRKLSQRRKKTIEQTSVNSNNSINKPVQKTHSRAVSDFVPGFAKPSYDS               NYTMNEPVKTNDSRGGNKGDFPALPADAENMVEKQREKQIEEDIMKLHDINKQNNEVAKGSGREAYAAQ               KFEGSDDDENHPLPPLNVAKGRKLHPSAPAKSVGHARRESLKYMRPPMPSSAYPQQELIDTGFLESSDD               NKSDSLGNVTSQTNDSVSVHSVNAHINSPSVEKELTDEEILQEASRAPAGSMPSIDFPRSLFLKGFFSV               QTTSSKPLPIVRYKIMFVLRKMNIEFKEVKGGFVCMQRFSSNNVAAKREGTPRSIMPLSHHESIRRQGS               NKYSPSSPLTTNSIHQRKTSITETYGDDKHSGTSLENIHQQGDGSEGMTTTEKEPIKFEIHIVKVRIVG               LAGVHFKKISGNTWLYKELASSILKELKL                 S. cerevisiae  Kin2       MPNPNTADYLVNPNFRTSKGGSLSPTPEAFNDTRVAAPATLRMMGKQSGPRNDQQQAPLMPPADIKQGK   (SEQ ID NO. 2)               EQAAQRQNDASRPNGAVELRQFHRRSLGD WEFLETVGAGSMGKVKLVKHRQTKEICVIKIVNRASKAYL                   HKQHSLPSPKMESEILERQKRLEKEIARDKRTVREASLGQILYHPHICRLFEMCTMSNHFYMLFEYVSG                   GQLLDYIIQHGSLKEHHARKFARGIASALQYLHAnNIVHRDLKIENIMISSSGEIKIIDFGLSNIFDYR                   KQLHTFCGSLYFAAPELLKAQPYTGPEVDIWSFGIVLYVLVCGKVPFDDENSSILHEKIKKGKVDYPSH                   LSIEVISLLTRMIVVDPLRRATLKNVEHPWM NRGYDFKAPSYVPNRVPLTPEMIDSQVLKEMYRLEFI               DDIEDTRRSLIRLVTEKEYIQLSQEYWDKLSNAKGLSSSLNNNYLNSTAQQTLIQNHITSNPSQSGYNE               PDSNFEDPTLAYHPLLSIYHLVSEMVARKLAKLQRRQALALQAQAQQRQQQQQVALGTKVALNNNSPDT               MTKNRSPQKEVVPNPGIFQVPAIGTSGTSNNTNTSNKPPLHVMVPPKLTIPEQAHTSPTSRKSSDIHTE               LNGVLKSTPVPVSGEYQQRSASPVVGEHQEKNTIGGIFRRISQSGQSQHPTRQQEPLPEREPPTYMSKS               NEISIKVPKSHSRTISDYIPSARRYPSYVPNSVDVKQKPAKNTTIAPPIRSVSQKQNSDLPALPQNAEL               IVQKQRQKLLQENLDKLQINDNDNNNVNAVVDGINNDNSDHYLSVPKGRKLHPSARAKSVGHARRESLK               FTRPPIPAALPPSDMTNDNGFLGEANKERYNPVSSNFSTVPEDSTTYSNDTNNRLTSVYSQELTEKQIL               EEASKAPPGSMPSIDYPKSMFLKGFFSVQTTSSKPLPIVRHNIISVLTRMNIDFKEVKGGFICVQQRPS               IETAAVPVITTTGVGLDSGKAMDLQNSLDSQLSSSYHSTASSASRNSSIKRQGSYKRGQNNIPLTPLAT               NTHQRNSSIPMSPNYGNQSNGTSGELSSMSLDYVQQQDDILTTSRAQNINNVNGQTEQTNTSGIKERPP               IKFEIHIVKVRIVGLAGVHFKKVSGNTWLYKELASYILKELNL                 S. pombe  Kin1-like (gi|19113449)       MKPNTTNLRNECWDTFSIPKRSQNIKINQSTKHQRSISDFVGTAGPGRQVGN WIIKKTIGAGSMGKVKL     (SEQ ID NO. 3)                 VVNILTGEKAALKMIPFTPNNTSQTVRVQREALLGRLLRHPNICRVIDCIRTPACTYILFEYVPGGQLL                   EYILARGKLDEDLARSFAMQLINALVYLHKNFIVHRDLKIENVLLTQDSRQVKLIDFGLSNFYSKDDLL                   RTYCGSLYFAAPELLDAKPYIGPEVDVWSLGVVIYVMVCGRVPFDDVSVPMLHSKIKSGKLEFPSYISE                   DCCSLIAAMLNVNPRKRCSLEQAAKFPWL KKNSFCLYLPIPLTSIPSTPSIRSHVFKPPFNLKVLQLLH               EHGLASIPELKHELYMAYIERKTTSLVCLYLLGVESLAPALRIPTALPPVYSRHQRHHSEILGAMDLTE               KITAMQCPP                 S. pombe  Kin1 (gi|3560139)       MEYRTNNVPVGNETKSAALNALPKIKISDSPNRHHNLVDAFMQSPSYSTQPKSAVEPLGLSFSPGYISP   (SEQ ID NO. 4)               SSQSPHHGPVRSPSSRKPLPASPSRTRDHSLRVPVSGHSYSADEKPRERRKVIGN YVLGKTIGAGSMGK                   VKVAHHLKTGEQFAIKIVTRLHPDITKAKAAASAEATKAAQSEKNKEIRTVREAALSTLLRHPYICEAR                   DVYITNSHYYMVFEFVDGGQMLDYIISHGKLKEKQARKFVRQIGSALSYLHQNSVVHRDLKIENILISK                   TGDIKIIDFGLSNLYRRQSRLRTFCGSLYFAAPELLNAQPYIGPEVDVWSFGIVLYVLVCGKVPFDDQN                   MSALHAKIKKGTVEYPSYLSSDCKGLLSRHLVTDPLKRATLEEVLNHPWM IRNYEGPPASFAPERSPIT               LPLDPEIIREMNGFDFGPPEKIVRELTKVISSEAYQSLAKTGFYSGPNSADKKKSFFEFRIRHAAHDIE               NPILPSLSMNTDIYDAFHPLISIYYLVSERRVYEKGGNWNRIAKTPVSSVPSSPVQPTSYNRTLPPMPE               VVAYKGDEESPRVSRNTSLARRKPLPDTESHSPSPSATSSIKKNPSSIFRRFSSRRKQNKSSTSTLQIS               APLETSQSPPTPRTKPSHKPPVSYKNKLVTQSAIGRSTSVREGRYAGISSQMDSLNMDSTGPSASNMAN               APPSVRNNRVLNPRGASLGHGRMSTSTTNRQKQILNETMGNPVDKNSTSPSKSTDKLDPIKPVFLKGLF               SVSTTSTKSTESIQRDLIRVMGMLDIEYKEIKGGYACLYKPQGIRTPTKSTSVHTRRKPSYGSNSTTDS               YGSVPDTVPLDDNGESPASNLAFEIYIVKVPILSLRGVSFHRISGNSWQYKTLASRILNELKL                 C. albicans  orf6.8762       MNNQDPDSQYHNKKVYPPNLPSIPPPPQQPLSGRPATPRMLRSISGTLKSKTELAHSDKGQESNNETKN   (SEQ lID NO. 5)               SNSPHYVPDTHTRQPPPESLKSNIQAPTAVHGNQQKGSLLPPPSIPNPNTMKPAPTPTGVDQPPAKQKP               SPAPKQPQPQQQQQQQQQQQFHRKSIGD WNFVKTIGAGSMGKVKLAQHNATHEICAVKIIPRAAKLYQR                   AHANDPPPQTTQEAAQRHKEFEKEVARDRRTIREGALGRLLYHPFICRLYEMVPMTNHYYMLFEYIEGG                   QMLDYIVAHGSLKERHARKFARGIASALDYCHRNNVVHRDLRIENIMINEKGDIKIIDFGLSNLYAPKN                   LLKTYCGSLYFAAPELLSAKPYIGPEVDVWSFGVVLYVLVCGKVPFDDQSVSVLHEKIKKGNVEYPAFL                   SRECVSLLSRMLVVDPTKRASLYEVCSHPWM NKGYDYKVNNYLPRREPLRLPLDPEIIKTIANFELGTV               QGVADELTSILTSVEYQMSCENWYKITETGREYASSQNAQILPDPTGGFHPLVSIYYLVDEMRKRKKAK               EEALKAQRRAQVPTIAVPTPKQQQQQQPQPAQPQPQPQPEVSQPLPEPKPVPPEEIINPAVATQAQANM               TAPKIVETFSETPQRTLDPSKQSVDEKPSAPGPSIAVPEQAHTTSVPSSFVKTQTSIDEDQLSIPEQQS               PRTSTPQTLDPAKVVGGSSGSAISAPNAGSGAGFNSLLRRLSSKKYKGASSPKRSTSPSPNVEGLSPQP               TKADPMVRRGVSMKVTAKEKQTNTRPPKSELIKKKPQHGRSSSTSNKMQGFIPVEYLPPLPTIDTNTNT               IVSDGAKQQNLTVPSTARHMHPTARAKSVGGGHMRKLSYGRVSHGSQNPLPPLPTSMASQNSQEVVGKD               TSEGFFDDVQLDDVGYQEVPQLTESEIIEQYNISKPNSMPSIEHCKTLFLKGFFSVQTTSAKPLPVIRY               NIINVLSKLGVKFQEVKGGFVCMHTPSVQPSHSNELDEENKLYGDAFKSKSSDSFEAAEPEGSKTPSRQ               PSLQLPSHTPTTPSGPKSHKSSNSIGSIGGNVPRRKFSIGNAFNTYRKKNGSQVMMPPNTPATAKVIHG               LYDDDDKERNGEDDDDEDDYGYDDSADSLNGYGGGSDMLISSRIEQRAKHQRTVSSSSQKASKSPLKFE               IHIVKVPLVGLYGVQFKKILGNTWNYKTLASQILNEMNL          
 
         [0079]    KIN4 family  
         [0080]    The KIN4 family comprises two genes in  S. cerevisiae , Kin4 and YPL141 C; one known gene in  S. pombe , gi|10185124 (SPAC140.05), and one from  C. albicans , orf6.4215. While KIN4 family members are related to the eukaryotic AMP-activated protein kinase (AMPK) family, their sequence similarity is sufficiently distinct so as to distinguish the two families.  
         [0081]    YPL141 C is implicated in the cell cycle because the production of its mRNA transcript correlates with control of the cell cycle, i.e., the levels of YPL141 C mRNA peaks at M phase, or at S/G2 phase. See, for instance, Spellman et al.,  Molecular Biology of the Cell,  9 (12): 3273-97, 1998.  
         [0082]    Mutants in both  S. cerevisiae  KIN4 genes are viable. Due to the high similarity between Kin4 and YPL141 C kinase domains (77% sequence identity and 87% sequence similarity) these two  S. cerevisiae  KIN4 family members may serve mutually redundant functions. As such, an inhibitor of one gene would likely inhibit both, possibly revealing vital functions of this family.  
         [0083]    The KIN4 family members include, in  S. cerevisiae , Kin4 (SEQ ID NO. 6) and YPL141C (SEQ ID NO. 7); in  S. pombe , SPAC140.05 (SEQ ID NO. 9); and  C. albicans  orf6.4215 (SEQ ID NO. 8). The kinase amino acid sequences of these particular family members appear below. Where appropriate, the public database accession number for a kinase is included so as to indicate its source.  
         [0084]    The bold, underlined portion of each family member denotes its kinase domain. Accordingly, the present invention allows the skilled artisan to identify and classify newly-identified kinases from other fungi as belonging to the KIN4 family if the newly-identified kinase domains share at least 55% amino acid sequence identity with any one of the kinase domains of an indicated family member listed below. Preferably, the KIN4 kinase domain has a percentage sequence identity to a kinase domain of any one of SEQ ID NOs. 6-9 of 60%, of 65%, of 70%, of 75%, of 80%, of 85%, of 90%, or of 95%.  
                                 S. cerevisiae  Kin4               MASVPKRHTYGGNVVTDRDRHSLQRNNEILHPIHKNQRKHATFGP YIIGSTLGEGEFGKVKLGWTKASS     (SEQ ID NO. 6)                 SNEVPKQVAIKLIRRDTIKKDADKEIKIYREINALKHLTHPNIIYLEEVLQNSKYIGIVLEFVSGGEFY                   KYIQRKRRLKESSACRLFAQLISGVNYMHYKGLVHRDLKLENLLLDKHENLVITDFGFVNEFFEDNELM                   KTSCGSPCYAAPELVVSTKAYEARKADVWSCGVILYAMLAGYLPWDDDHENPTGDDIARLYKYITQTPL                   KFPEYITPIPRDLLRRILVPNPRRRINLQTIKRHVWL KPHEAFLSIQPNYWDEHLQKERPKPPNKGDVG               RHSTYSSSASSYSKSRDRNSLIIESTLEQHRMSPQLATSRPASPTFSTGSKVVLNDTKNDMKESNINGE               RTSASCRYTRDSKGNGQTQIEQVSARHSSRGNKHTSVAGLVTIPGSPTTARTRNAPSSKLTEHVKDSSQ               TSFTQEEFHRIGNYHVPRSRPRPTSYYPGLSRNTADNSLADIPVNKLGSNGRLTDAKDPVPLNAIHDTN               KATISNNSIMLLSEGPAAKTSPVDYHYAIGDLNHGDKPITEVIDKINKDLTHKAAENGFPRESIDPEST               STILVTKEPTNSTDEDHVESQLENVGHSSNKSDASSDKDSKKIYEKKRFSFMSLYSSLNGSRSTVESRT               SKGNAPPVSSRNPSGQSNRSNIKITQQQPRNLSDRVPNPDKKINDNRIRDNAPSYAESENPGRSVRASV               MVSTLREENRSELSNEGNNVEAQTSTARKVLNFFKRRSMRV                 S. cerevisiae  YPL141C       MSYTNKRHTYYGGFTNDLSDTFQYPQRTDEQRRKHVTFGP YILGSTLGEGEFGKVKLGWPKNFSNSSNS     (SEQ ID NO. 7)                 TFDFPKQVAIKLIKRDSISNDYRKEVKIYREINALKHLSHPNIVKLEEVLQNSRYIGIVLEYACGGEFY                   KYIQKKRRLKEMNACRLFSQLISGVHYIHSKGLVHRDLKLENLLLDKNENLVITDFGFVNEFCSRNELM                   KTSCGSPCYAAPELVISAEPYEARKADIWSCGVILYAILAGYLPWDDDPNNPEGSDIGRLYNYINSTPL                   KFPDYILPIPRDLLRRMLVSDPKKRINLKQIKKHEWL KPHSSFLSITPDEWDKLNNTQSVFRLAKPRRR               YGSRPQSSCSTSSLGSRSDKRDSLVIDSTLITFPAPPQESQNHIITRPASIASDQRLSPIRRSNRHNRS               NSAASVALQAVVNADREYVLSHEQSLSPVQNIRQTTGNMTASLSPPPAISPGDIIIETTPIKRNTISGS               SIVPSLEEESSTTMQTSKIQPNNMASSQNHQYNKNKTQNSLQSAKNFYRTSSSSHTKPRPTSYHPGSYT               TPPYNSNTLSIYEINEKAKSSASSQTLNQRDTSPFDSTPYLALDTCITSSSSIESSPKLITHGQFSVAK               PSVDLQSVSGDLIKYKRDADVVTRIYDEKYKQKRKSLRYSGIFSDISCDTVTEESDELRPPESPLQQHE               GQESIDKAKTEDTSEKGSKSSNIAKATAQKHVNNHLERSLNEAESTKKRFSFLSLYSYDTSKSSLYSSM               DSKRKPSPPSQRRPKKDDSYQTNSKNHYITASNMQTSHQVSKDLPAPTMVQNKCTLETKKAVRSNRSSI               MVSEVNKASVDNKAAQSPEHSTAKRVLGFFKRRSMKI                 C. albicans  orf6.4215       MSTIPSQVEINFNKIHQRSNSSSSTSSYRIPSGNSCIPRTVEMPSLPPTSTHHQHQQMPSSSSHAHIAK   (SEQ ID NO. 8)               KIHREVRFGA YILGSTLGEGEFGKVKLGWRKDGKHPSQVAIKLIKRSTITKDSDSEIKIHREINSLKLL                   NHPNIVNLVEVMKSGKYIGIVLEYASGGELFDYILQHKYLKENVAKKLFAQLVSGVDYMHAKGLIHRDL                   KLENLLLDKHRNVIISDFGFVNSYNRDKNDLMKTSCGSPCYAAPELVLSQTAYEGRKVDIWSLGVILYA                   MLAGYLPFDDDPENEDGSDIIKLYHYICKTPLTFPEYVSPLARDLLRKIIVSDPKKRISIDDIRNHPWL                 SSHANLLSIRQPEWDKVHSEKQQPIAVEPPQPNKRYSMINERTNSSSLMSPAPRVTHTQPLSSHARSYS               STSISLLYSSPSATPSMANAVTNGEGATTTTTNGSINESNDTLQLSGTPSPKKPSTVSPVRGHQKSASI               SNSYSSASIALKAVVHEENRLHNHQQSQQYIPRSSTISTIVESPTKANTATETETTDGNKILLPPPSKD               AQKLPHAAKKPRPTSYHPSSMSSALIHNNQNPTDVLKMPSPINFPMTQFISTSPPKSNGSLNDSGNFTN               CSPKATSRRNSVVTHVHVNGVLSKENLIHSSSSPDNKRNSVLSYLEDKIDTLELTESHSPSKNTFEEIV               DAAIATPEINQVPVFDSQTSPNGIGLDIKMKEFDETSLVVEKKSKETVSDSKSEESTKETQQQENVVMY               EPIVPVEEYIKKPEEVNSVEAKQPEEVKSEDKSLQGQKSQQQQQQPEKHSADIGKTKVDLKKSASQKKK               VKEESIKKQKDVDSKPIERRHTIAARRHHNDENKENKDVKKRNRFSLLSFYSSYNSSNSNVSLATSKVP               SNSENNTTVLKPTSMNTTRKVLEPSNETNIMRKETKQTNSNGSTTSKSTTSSSSSSAPAASSSSSSSTS               KRASTATKETSAARKVMDFFKRRSVRVG                 S. pombe  SPAC 140.05 (gi|7523475)       MNAQPFHNNTSDVQSFQDIISNSYQKPLSLVDSTDRALPDSSLSSLSRSTFQFHKHHLSGNENPQPSSE   (SEQ ID NO. 9)               SPYFTNNERLNSSSFPQIHDNQLSPSFNTSYQAIPSSSSNRSRGGPYTPSIRDDSLLALLSFSSNBRLH               SMPSQLQPFNNASSYTTPMAPFTASFSNKVSHSAYPTRRLPSQAKKTSAIERVPVNLNFLQSDNLVVQS               SPQTNFENFEFPKKIPSKEDLETREVLLLPPQTSKLSNKMLDTKSFTDVNKISQQGFVEISSNSSKVTP               NTSLHQSFGIASSSSNNYMQTSSELTSSTEKMNGSHPLQLSNKSLLSIHLMQSKNQGHVSMTGSDKLSS               HVQSETENAPVSKPSKPNTLTEDEKPLQSTKLPGNSLTVGELYQEPKSIQLPELSVSRTTYSAQSSSVK               NCNERIPSAKALKKQKHLVPENKSKLQYVWQKKESLPYANLTSASNTHFFLSENQNDTSERLTRTLRKS               TKNYTFGS YILGRTIGTGEFGKVKLGWPLPKANSTIHRSTPQVVIKIVLSTKQNCQTSRLMREVAILKG                   LGNNRPHIVKYLDFVKTKHHFGIVLDYVNGGELFDYILARRRLEDSVACRLFAQLISGVAYLHSRGVVH                   RDPYSESY            
 
         [0085]    GIN4 Family  
         [0086]    The GIN4 fungal-specific kinase family includes three genes from  S. cerevisiae  GIN4 (SEQ ID NO. 10), HSL1 (SEQ ID NO. 11) and KCC4 (SEQ ID NO. 12); two genes from  C. albicans , orf6.4613 (SEQ ID NO. 15) and orf6.6556 (SEQ ID NO. 16); and the CDR2 (SEQ ID NO. 13) and CDR1 (SEQ ID NO. 14) genes from  S. pombe.    
         [0087]    All three  S. cerevisiae  members possess similar, and partially redundant, functions from nutrient sensing and developing cell structure to control of cell division. All three genes, GIN4, HSL1 and KCC4, are required during cytokinesis to organize septins within the neck of the bud. The protein products of these genes signal the state of the cytoskeleton to the Swe1 mitotic checkpoint in order to allow mitosis to continue, and also are required for mitotic arrest during nitrogen deprivation.  
         [0088]    Cdr1 in  S. pombe  phosphorylates and negatively regulates the Wee1 mitotic control gene and is involved in mitosis and nutrient sensing.  
         [0089]    An inhibitor of one family member would likely inhibit other family members, causing defects in cell cycle or cytokinesis. A GIN4-family inhibitor might also cause fungal cells to ignore stress signals, thereby inducing cell mitosis and proliferation. However, in the absence of nutrients these processes most likely would lead to death of the fungus and its progeny by starvation.  
         [0090]    The bold, underlined portion of each family member denotes its kinase domain. Accordingly, the present invention allows the skilled artisan to identify and classify newly-identified kinases from other fungi as belonging to the GIN4 family if the newly-identified kinase domains share at least 55% amino acid sequence identity with any one of the kinase domains of an indicated family member listed below. Preferably, the GIN4 kinase domain has a percentage sequence identity to a kinase domain of any one of SEQ ID NOs. 10-16, of 60%, of 65%, of 70%, of 75%, of 80%, of 85%, of 90%, or of 95%.  
                                 S. cerevisiae  GIN4               MAINGNSIPAIKDNTIGP WKLGETLGLGSTGKVQLALNGSTGQEAAVKVISKAVFNTGNVSGTSIVGST     (SEQ ID NO. 10)                 TPDALPYGIEREIIIWCLLNHPNVLRLYDVWETNTDLYLVLEYAEKGELFNLLVERGPLPEHEAIRFFR                   QIIIGVSYCHALGIVHRDLKPENLLLDHKYNIKIADFGMAALETEGKLLETSCGSPHYAAPEIVSGIPY                   QGFASDVWSCGVILFALLTGRLPFDEEDGNIRTLLLKVQKGEFEMPSDDEISREAQDLIRKILTVDPER                   RIKTRDILKHPLL QKYPSIRDSKSIRGLPREDTYLTPLSESNSSIDATILQWLVILWHGRDPEGIKEKL               REPGANAEKTLYALLYRFKCDTQKELIKQQQVKKRQSISSVSVSPSKKVSTTPQRRRNRESLISVTSSR               KKPISFNKFTASSASSSNLTTPGSSKRLSKNFSSKKKLSTIVNQSSPTPASRNKRASVINVEKNQKRAS               IFSTTKKNKRSSRSIKRMSLIPSMKRESVTTKLMSTYAKLAEDDDWEYIEKETKRTSSNFATLIDEIFE               YEKYEQIRKEKEELERKVREAKAREELERRRRKQEEKERARKLLEKEDLKRKQEELKKQIEIDISDLEQ               ELSKHKEEKLDGNIRSISAPMENEEKNINHLEVDIDNILRRRNFSLQTRPVSRLDPGIMFSSPTEEVSP               VEPKRTENERLTTEKKILETIRRSKFLGSSFNIDKELKLSKMEYPSIIAPQRLSEERVVSDSNDGYESL               ILPKDGNGVSQLKDSTATTAPVSDGRLRKISEIRVPQFTRKSRHFSESNKRLSVLSMYSTKESFTNLVD               ILKNGNLDVNNQQSQRIPTPRSADDSEFLFETVNEEAEYTGNSSNDERLYDVGDSTIKDKSALKLNFAD               RFNGSNEAKQTDNLHLPILPPLNGDNELRKQNSQEGDQAHPKIKSMIPESGSSSHTEKEEENEEKEEKK               PEQHKQEEDQEKREKVVDDMEPPLNKSVQKIREKNAGSQAKDHSKDHLKEHKQDKNTAIGNGSFFRKFS               KSSDKTMELYAKISAKQLFNGLEKLLRGWTQYGLKNIKSHPNNLTLTGKLSSDNIFSLRSTLFEVNIYP               RGKMSVVQFKKVSGSFKAVKKLNEVENVLNKEGVLQK                 S. cerevisiae  HSL1       MTGHVSKTSHVPKGRPSSLAKKAAKRAMAKVNSNPKRASGHLERVVQSVNDATKRLSQPDSTVSVATKS   (SEQ ID NO. 11)               SKRKSRDTVGP WKLGKTLGKGSSGRVRLAKNMETGQLAAIKIVPKKKAFVHCSNNGTVPNSYSSSMVTS                   NVSSPSIASREHSNHSQTNPYGIEREIVIMKLISHTNVMALFEVWENKSELYLVLEKVDGGELFDYLVS                   KGKLPEREAIHYFKQIVEGVSYCHSFNICHRDLKPENLLLDKKNRRIKIADFGMAALELPNKLLKTSCG                   SPHYASPEIVMGRPYHGGPSDVWSCGIVLFALLTGHLPFNDDNIKKLLLKVQSGKYQMPSNLSSEARDL                   ISKILVIDPEKRITTQEILKHPLI KKYDDLPVNKVLRKKMRKNMARGKSNSDLHLLNNVSPSIVTLHSK               GEIDESILRSLQILWHGVSRELITAKLLQKPMSEEKLFYSLLLQYKQRHSISLSSSSENKKSATESSVN               EPRIEYASKTANNTGLRSENNDVKTLHSLEIHSEDTSTVNQNNAITGVNTEINAPVLAQKSQFSINTLS               QPESDKAEAEAVTLPPAIPIFNASSSRIFRNSYTSISSRSRRSLRLSNSRLSLSASTSRETVHDNEMPL               PQLPKSPSRYSLSRRAIHASPSTKSIHKSLSRKNIAATVAARRTLQISISASKRSLYSLQSKRSLNLND               LLVFDDPLPSKKPASENVNKSEPHSLESDSDFEILCDQILFGNALDRILEEEEDNEKERDTQRQRQNDT               KSSADTFTISGVSTNKENEGPEYPTKIEKMQFNMSYKPSENMSGLSSFPIFEKENTLSSSYLEEQKPKR               AALSDITNSFNKMNKQEGMRIEKKIQREQLQKKNDRPSPLKPIQHQELRVNSLPNDQGKPSLSLDPRRN               ISQPVNSKVESLLQGLKFKKEPASHWTHERGSLFMSEHVEDEKPVKASDVSIESSYVPLTTVATSSRDP               SVLAESSTIQKPMLSLPSSFLNTSMTFKNLSQILADDGDDKHLSVPQNQSRSVAMSHPLRKQSAKTSLT               PRSNLNANLSVKRNQGSPGSYLSNDLDGISDMTFAMEIPTNTFTAQAIQLMNNDTDNNKINTSPKASSF               TKEKVIKSAAYISKEKEPDNSDTNYIPDYTIPNTYDEKAINIFEDAPSDEGSLNTSSSESDSRASVHRK               AVSIDTMATTNVLTPATNVRVSLYWNNNSSGIPRETTEEILSKLRLSPENPSNTHMQKRFSSTRGSRDS               NALGISQSLQSMFKDLEEDQDGHTSQPLILESSMSYSKRRPSEESVNPKQRVTMLFDEEEEESKKVGGG               KIKEEHTKLDNKISEESSQLVLPVVEKKENANNTENNYSKIPKPSTIKVTKDTAMESNTQTHTKKPILK               SVQNVEVEEAPSSDKKNWFVKLFQNFSSHNNATKASKNHVTNISFDDAHMLTLNEFNKNSIDYQLKNLD               HKFGRKVVEYDCKFVKGNFKFKIKITSTPNASSVITVKKRSKHSNTSSNKAFEKFNDDVERVIRNAGRS                 S. cerevisiae  KCC4       MTVANTETHSAAKPSSTIGP WKLGETLGFGSTGKVQLAQHERTGHRTAVKVISKSIFNNNGNHSNDDSV     (SEQ ID NO. 12)                 LPYNIEREIVIMKLLSHPNVLSLYDVWETNNNLYLILEYAEKGELFNLLVDHGPLPEREAINCFRQIII                   GISYCHALGIVHRDLKPENLLLDSFYNIKIADFGMAALQTDADLLETSCGSPHYAAPEIVSGLPYEGFA                   SDVWSCGVILFALLTGRLPFDEENGNVRDLLLKVQKGQPEMPNDTEISRDAQDLIGKILVVDPRQRIKI                   RDILSHPLL KKYQTIKDSKSIKDLPRENTYLYPLADSNNHTSASIDDSILQNLVVLWHGRHADDIVSKL               KENGTNKEKILYALLYRFKLDSVRGSNKKNRNKIKKTKKNKRSSTLSSSSSLLLNNRSIQSTPRRRTSK               RHSREFSSSRKRSSFLLSSNPTDSSPIPLRSSKRITHINVASANTQATPSGVPNPHKPNSKKRSSKRLS               YMPNTKRSSLTSKSLSNFTNLIDDDDWEYIEKDAKRTSSNFATLIDEIFEPEKFELAKREKAELQRKVQ               EAKRQSVNAQKINEDEFGSEVSDGMKELKKINDKVSSPLINYEFSQQELLQDIDTLLTNRYQLSSYTRP               ISRLDPGLTPVTETLPNNLKEKTALLQDTEKKTIETIRRSKFLGSLLNVRGGLSPGKSELAPIEESPIV               STTPLIYNDRMEPRRISDVEVPHFTRKSKHFTTANNRRSVLSLYAKDSIKDLNEFLIKEDPDLPPQGST               DNESRSEDPEIAESITDSRNIQYDEDDSKDGDNVNNDNILSDFPQGVGISQEYDMKDKNPNQSPISKSA               EPTLVVKLPSLSSFQGKNASGLGLYQREPSKVTLPSLTSNNSSVGENIEDGAEKGTESEKIAASLSDDD               LKEDNDKKDNDTVNAPTTVKKPPNSVLLKKFSKGKILELEIHAKIPEKRLYEGLHKLLEGWKQYGLKNL               VFNITNMIITGKLVNDSILFLRSTLFEIMVLPNGDGRSLIKFNKKTGSTKTLTKLATEIQIILQKEGVL               DK                 S. pombe  CDR2 (gi|2058369)       MSTISEVGP WELGLSLGSGGPNSSRLAKHRETGQLAVVKPIVGWSELTSSQQARIEGELVLLRLIEHPN     (SEQ ID NO. 13)                 VLQLIDVISAQEQLFVVVEYMPGGELFDCMLRKGSFTEQDTAKFLWQILCGLEYCHKLHICHRDLKPEN                   LYLDAHGSIKIGEFGNASIQQPGKLLQTSCGSPHYASPEIIMGRSYDGCASDIWSCGIIFFALLTGKLP                   FDDDNIRSLLLKVCQGQFEMPSNISPQAQHLLYRMLDVDSSTRITMEQIREHPFL SCFVHPNISIPIIS               APIQPIDPLIVQHLSLVFRCSDDPMPLYEKLASQSPLVEKTLYTLLSRHLHPPSSAAVDRNRAVVDDLL               GTAASNGQQMDEEEIEQAINIPTLAPYPISYAAESVPRPATSASPFLTPVTTSGTFNYSFNATNPQSIL               QRPATTSSAVPQLPKSVTPGLAYPHDSSMLSSNYRPPSALSPRNFNVSINDPEVQLSRRATSLDMSNDF               RMNENDPSIVGNLAASNFPTGMGPPRKRVTSRMSEHTGNRVVSFPRGSAFNPRVTRFNVGNEQFSNNID               NNNYNQPYANATMNNSRRLRTPSGERSMRADLSQSPASYDSLNVPKHRRRQSLFSPSSTKKKLSGSPFQ               PKRSFLRRLFSSEPSCKCVYASLVASELEHEILEVLRRWQLLGIGIADIIYDSVSASISARIKRQNSLN               LKPVRFRISVLAEFFGSQAVFVLESGSSTTFDHLATEFQLIFEDKGFLDNLELSYFQASASRPVSRMSV               SSSPFAVFRQRQSVQS                 S. pombe  CDR1 (gi|7708585)       MVKRHKNTIGV WRLGKTLGTGSTSCVRLAKHAKTGDLAAIKIIPIRYASIGMEILMMRLLRHPNILRLY     (SEQ ID NO. 14)                 DVWTDHQHNYLALEYVPDGELFHYIRKHGPLSEREAAHYLSQILDAVAHCHRFRFRHRDLKLENILIKV                   NEQQIKIADFGMATVEPNDSCLENYCGSLHYLAPEIVSHKPYRGAPADVWSCGVILYSLLSNKLPFGGQ                   NTDVIYNKIRHGAYDLPSSISSAAQDLLHRHLDVNPSTRITIPEVFSHPFL MGCTSLSSMDSTTPPTPS               LSIDEIDPLVVDCMCVLWKKSSSKKVVRRLQQRDDNDEKYVYKVLSEILRDDMLKKQRFDENKYLSLYD               LIHDNNLFTKASISTTSLVKSNVSTNSRKSSNFEDELARRVSSPLSALNQMSQSPIPIRVSSDKDYDSY               ACHEVVSNPSTLDDDYNYMFVCPPEEYTYSTDNVRTDSLDLQSLPTPTLEQLESVPFNRYGYVRIFPST               TLSSTASGYYTPDSLSTPEPSIDGLTNLDDVQVGGFVQGSGNQNRRPISFPVISNMQPNITNVRSASAP               LCSSPVPSRRYSQYATNARYTPRKVSSGSVLRKISSFFRKD                 C. albicans  ORF6.4613       MSTVVNRRSSHQFDSPSNHLDHSSSMNVDKVVQSVTNATKRLSQISTNTNNSNKKRKTQNKIGP WKLGR     (SEQ ID NO. 15)                 TLGRGSTGRVRLAKNTTTGQLAAVKIVPKSNFKKLENPKYKRSKEDATRLPYGIEREIIINKLISHPNI                   MGLYDVWENKNDLYLILEYIEGGELFDYLIKRGKLQEYEAINYFKQIINGINYLHQFNICHRDLKPENL                   LLDFNKNIKIADFGMAALEVKEKLLETSCGSPHYASPEIVAGKNYHGAPSDIWSCGIILFALLTGHLPF                   DDENIRKLLLKVQSGKFNMPPELSFEAKDLITKHLKVNPRERITIDAILTHPLL AKYPEPTVSYSSTTT               LDINSINIKQIESVDKIDKEILKNLSVLFHNCDEKTIISRLLSPNRCPEKMFYYLLMKYRNEHLSNSNS               FNSSNDVDSARSLPRSTSYVKTTVTDHATGEKHTTVKKIQQSSSIYSNRSLLKKSTSAKGNVLSNITNR               PNTPKQFSASSSFNKKKALHSKTQIYASRSRNASSRSLKSNSSTGRNGNNASVTSVNKIPEITGATVLQ               PIPSMAMNRGDEQQNKTKKNLTGTFGNKSLLNFQLICEEVFENDKENSKPVSKTPVSQLPPPPPPPIET               PTSRTNSVKRGKTWSLARRERELAEQVRQRNEARENKLKAEELARKELEQEKKRIAEEKKRLEQQEREL               DEKQKLQEKQKAALEKLQKHQSAHDFEGLFASNRRSVTDMAPSSGMSSLDPRAHMVSRANTIGSPNLSS               SSVNIDENASKVLHKFGIDVAPSPKRFSRASKTSTSKNLSSFLAPTVSRNLSSQLKTSSSKNLAGYLHG               TTDTNGSAIAAKKKDDSTNEALTIEEFNAKERTSMSPSISKASVNKPNSNQSSYYRSMFSDNGNDDNVT               KVRTGESHLSVQEEEEMDMENAIDEDISLIPNPRFSRFSFGGLLGSNTVANEEGDWTIMNSTLNHSNTV               VRGTHNKSSTMLGLGIKMRDTTTIKEDEEFEDEKPFISVPSSEDDEGNTHKNKRGGLRDSGNYDFDEEH               SVASTANTEYSDVASQGQQMPGSHTIHQLETELSNFDLLSYRVADIGKVNKHKFSIVDSKETLLKNHSS               DEATIEVKEDNNEHDFNDKIKQHYDDNGDSEEDDEDEDEEEEDDDDDDDARSSFEARPHSHNYSLAEIT               SESPVGGGYESPSIANDFKKSRHSTGIFSTTQFPRSPYVVNNNGDSNKDENSQQQTKHMLNDGHKGLIT               SPVQDTFGSKKPVESNSLFRRLSLNPNRAAPKAPAPPPPSAPISSAAKANISQPLSSPTKGHNRFSRIS               IGSKNMLQKEDKSTKSNWFKKFFHSLTTPSAKDQSGNSSSKVASKDIKIIDTSLTAAQLIRVIKYQLEL               KKIEGSISKVDIDEEFGLISGVIPSKFANGRKLKFKIEVIDLINSSSLHVIKMKGNDKGFQSLVNIVTF               IIKKEEQDKISRR                 C. albicans  ORF6.6556       MPHSRQPSISSSIMSQSNHNHPQKIGP WKLGKTLGRGATGRVLLATHQTTGQKAAVKVVSKSELQDEET     (SEQ ID NO. 16)                 EKNGDGLPYGIEREIIIMKLLTHPNVLRLYDVWETSKALYLVLEYVEGGELFDLLVERGPLPEVEAIKY                   FRQIILGTAYCHALGICHRDLKPENLLLDSQLNVKLADFGHAALESNGKLLETSCGSPHYAAPEIVSGL                   KYHGAASDVWSCGVILFALLTGRLPFDDENIRNLLLKVQAGNFEMPVDEVSREARDLIARMLEVDPMRR                   ISTEKILRHPLL TKYPMSNEDLISEKSLPHPQTGYKSLGSVRNIDKQILSNLTILWNDRPEEEIVDCLL               KDGSNPEKTFYALLMRYKHNQEDNTNNNSPKKSTSFNNKVVRSGSKYSLNGTPRRKPASHISVSRPTSF               QYKSNPGAGATANRNSVARHSVASSANNSPRKSPYKSPYRSPYRSPYKSPSKRYSYNQSPTKSPYGRRS               NSQRQFENEPLKAKPRNIYNEIVDAQSNFSLPPSLPPSLPSKDSRYMIDEPNQPQLQQPALSQVPENPI               VDESPDLMQSAKISSGKRNSIIGKNNNNSNSNKRMSKRKSIRASMTTGLKRNSITMKLLSTYAKLSGDD               DWEYMDKQTKRTSATFAALCDKIFNQEDYDEEDEQLVDPEEKEAKEYERLMELERKKHEAELKARRELE               KKKRRQKRRSILSSKKLSIIVKNDADPNNSEQELVDEGIKQPKRQSKNLTALRALSEGNHASEELTLED               VENLKRRSASQPVPKRRQTPVLTRRPVSRLDPLWQAHENEQLDRAKDALEQEWRDSQKRSSTVSRKKVN               RESMISVMDDIVEEDQGRVNRRSTRNTYYERERDYELPEPTVEDSNLTDDYMTEIRKSRLLNSQLNVRD               PLNEKRKSEPKTLISNVQIPSVTRKSRNFTTSNKRLSVLSMYSTKESYRDLNSIINSPDENPEQHQNMN               KPALRTSIADRLDKAGLAEPEYETETDGEDKVSVIDLDDHLADRRTSYYDGSGKRASRASTTKRYNVHS               SSGQRPKSKVPDLPKNDYDDTFVSNSDEVHKRQYKSMVSDESSASDDVFDKIKLPDGKSTKSSIDELAN               GTSTSGHRKPKIRHSQPGPEMLIPHLNGGIESSQPMSKVRGNNSSGHDDSVPPPPPAHKVNKKPLDDKT               NFPPPEVDPKRKGSFFRKLSWGSKKTIENNTNAATNTTTQQQLPSPAESKEEKPKSSFFRWFSSSNTPS               AAEIRKFNTILPKHEMSTALFALLNSWSNFGLKDLRNDQVGYYITGAISKHNSFMLKSCKFRIKINQRD               FNQKSEIVCVRVKGSKVTTDTLFSEIEKVLLKEGVLDK          
 
         [0091]    RAN Family  
         [0092]    The RAN fungal-specific kinase family includes three genes from  S. cerevisiae  KSP1 (SEQ ID NO.17), SKS1 (SEQ ID NO.18) and YDR247W (SEQ ID NO.19); the RAN1 (SEQ ID NO. 20) and SPBC16E9.13 (SEQ ID NO. 21) genes from  S. pombe , and un-named homologs from  Pichia jadinii  (gi|1232133) (SEQ ID NO. 22),  Nectria haematococca  (gi|11256839) (SEQ ID NO. 23) and  C. albicans  (gi|17271026) (SEQ ID NO. 24).  
         [0093]    The RAN kinase family members are implicated in a variety of functions. KSP1, for example, suppresses mutants in SRM1, a GDP exchange factor that is involved in splicing and nuclear export, when it is overexpressed. The SKS1 kinase interacts with a proteasome subunit involved in transcription as well as with telomeres. It may also be used by fungal cells during carbohydrate metabolism in times of nutritional stress. RAN1 regulates mitosis. Furthermore, RNAi interference experiments reveal that the  C. albicans&#39;  kinase, depicted in SEQ ID NO. 24, is required for normal growth.  
         [0094]    The bold, underlined portion of each family member denotes its kinase domain. Accordingly, the present invention allows the skilled artisan to identify and classify newly-identified kinases from other fungi as belonging to the RAN family if the newly-identified kinase domains share at least 55% amino acid sequence identity with any one of the kinase domains of an indicated family member listed below. Preferably, the RAN kinase domain has a percentage sequence identity to a kinase domain of any one of SEQ ID NOs. 17-24, of 60%, of 65%, of 70%, of 75%, of 80%, of 85%, of 90%, or of 95%.  
                                 S. cerevisiae  KSP1               MTLDYEIYKEGGILNNRY QKIEDISEGSYGYVSLAKDVREKRLVAVKYIFKLEDDGQYDGPQDDENDCD     (SEQ ID NO. 17)                 SSDCDDDEDTKVDTDRHENENGNASSNNGSSREKKHNLYKHKKSLISSKVKSRLSNNICLEAMYEVDIQ                   TKIGRHQNIAALLDFFDSYIIMEYCSGGDLYEAIKADAVPKKTKSITHIITQIMDAIEKVHNKGIYHRD                   IKPENILISGIDWTIKLTDWGLATTDKTSMDRNVGSERYHSPELFDSNLDIKERKEPYDCAKVDLWAMG                   IVFLNIVFHKNPFSIANQSDKSFCYFAANREALFDVFSTMAYDFFQVLRYSLTIDPANRDLKMKRTELQ                   NLSEYT LDDEYYNNLDEGYEETMIDGLPPQPVPPSSAPVSLPTPISSSNKQHMPEFKKDFNFNNVNERK               RSDVSQNQNVASGFFKKPSTQQQKFFNQGYNTTLSTHEPAKSAPKFKFKKRNKYGRTDNQFSKPVNIED               RKKSKILKKSRKPLGIPTPNTHMNNFFHDYKARDEFNTRDFFTPPSVQHRYMEGFSNNNNKQYRQNRNY               NNNNNNSNNNHGSNYNNFNNGNSYIKGWWKMFNKYRRPSSSSYTGKSPLSRYNMSYNHNNNSSINGYAR               RGSTTTVQHSPGAYIPPNARNHHVSPTNQFLRVPQSTAPDISTVLGGKPSYQEHYTQDSMDSEGDHDSD               DVLFTLEEGDHDFVNGMDNLSINDHLPHTTVGSHNEVFVHASTNHNNNGNNNHIDTNSTTNQYHRQYTP               PPLTTSLHINNNNNESNELPDLLKSPASSEAHLNLSSGPIDPILTGNIGNRYSHSSDSKELEQERRLSM               EQKFKNGVYVPPHHRKSFNLGTQVPPMNMKTSNEATLSVSHNSVNFGGSYNSRRSSANESNPLHMNKAL               EKLSSSPGAKSSFVGFPKPLLPRNHSSTTIALQNEDVFADSNNDAIIFEDEEYEGESDKMAHGKMEGGD               NESSSTSPDERQIFGPYEIYAQTFAGSTHDKKLGAGRKTSIQDEMVGSLEQYKNNWLILQQQD                 S. cerevisiae  SKS1       MLSDCLLNN FRITAQIGSGAYGLVFHVVDILTSREYAVKTVFKSSSMDEFYNKNGLNNNSQVARTTLLQ     (SEQ ID NO. 18)                 TQLYHFFKSFQKKLFLPSVDLDSILQLTENELNRLPHYREIAFQLRVQSHGNIVKIHQVLESSIATFIV                   HDYYDRDLFTSIVDDKHFVNHGILIKKVFLQLCSALDHCHRLGIYHCDIKPENVLLDRNDNAYLCDFGL                   STKSKYLAPNVCVGSSYYMkPERILYCLNTTTNGIHVDECCSSLPTDTGDIWSLGIILINLTCIRNPWL                   KAHQKEDNTFQHFANDNNVLKKILPISDELFTVLTKILQLNPYTRIDMKTLMSEVSS LTSFTREGPLSQ               VPILSSEVYMTHIIRNENLFLSDLSHFSADQEQQQQQQQQQQQVQEQEQEQKQEQIQNQEQAQQQQEEE               DAEPESDIPSTYNSDGSMEKYEYTNNHNNSTFLTSSMDSTPYQSDIDDVSASKDCKFQQDTLRNRLLCL               QMNFSTLTDGPNEKWLPDY                 S. cerevisiae  YDR247W       MMMFHNCRIN YLITSQIGEGAYGLVYRALDIRTDRQYAIKAVVQSYGVSKEADMGNDKIHKNSVKLQIC     (SEQ ID NO. 19)                 KLAKLFKESKNVVRVPSIDLESIENMSEEDFKKLPHYKEISLHLRVHHHKNIVTIHEVLQSAVCTFIVM                   DYYPTDLFTSIVDNRHFVTNGLLVKKVFLQICSALNYCHEHGIYHCDIKPENLLLDTEDNVFLCDFGLS                   TTSTYIKPNVCIGSSYYMPPERISFDGRVSSSKSGGHKLGKVCPSCNGDLWSLGIILINLTCIRNPWLK                   ADKTEDNTYYYFTKDPNILKQILPLSDDFYSLLSKILQVNPKNRMSLQELMKEVSS ITSFTNEGPLSKV               PPLSKSVYEKFVSPVDNTNENLSPKSYVYMHDSKAAKNLSYTSSSEEEDGIKEGIDDDNGSRSGSFGTL               DTDTGLHSSFTSTSCESDNECSKISNKFSLFEKKFNELRMSSSSLTN                 S.pombe  RAN1 (gi|5689987)       MMRENPELLLGQVLGDS LRFVSIIGAGAYGVVYKAEDIYDGTLYAVKALCKDGLNEKQKKLQARELALH     (SEQ ID NO. 20)                 ARVSSHPYIITLHRVLETEDAIYVVLQYCPNGDLFTYITEKKVYQGNSHLIKTVFLQLISAVEHCHSVG                   IYHRDLKPENIMVGNDVNTVYLADFGLATTEPYSSDPGCGSLFYMSPECQREVKKLSSLSDMLPVTPEP                   IESQSSSFATAPNDVWALGIILINLCCKRNPWKRACSQTDGTYRSYVHNPSTLLSILPISRELNSLLNR                   IFDRNPKTRITLPELSTL VSNCKNLTRRLRPAPLVSSRYLAYQQQQQQQQMNLQQGIQGYPHQGYMPTQ               NIGFPWPPTPQFVSNWNBCATPTIPVSLQVLTPNSSLKVDPTTPLTAPIHATESFWPSAAAAAAAVHNN               ANSYMPITPTPYPNNAKIFGYPNQPPLTPIPFTGFVLHPAPVGRAADAVDPSRKSL                 S.pombe  SPBC16E9.13 (gi|19112587)       MKLLQKKG YKVERPLNKGSYGTVVLAHRLFRTPRCKDLKYAIKCIKKPAYTFLQEVNILRQLSRSRHRN     (SEQ ID NO. 21)                 IIHFVESFEDNVYYYVVLEYCPLGDLYECILNNDFPNAENQPEMIKNIFLQIIDGVAHLHSHGIYHRDL                   KPENFLLSLSEDGSELVVKISDFGLACRDKISYDFGTGSDRYMAPEQFEEVDGAGYSPRAADIWALGIC                   LLNLIFARNPFTYPHEKDPIFADYMLDAMTLFDVFPTLSQDTYNVLRACLCVSPEKRSLAKTREAVLAV                   TKWT TDDEELESFVNEEEEFRASDFMPAEDNVRCTQSDREPLRTPSVLTPANTIQRGLLPSKLPALSDV               DENISTSSSPRSPASLAPVNNSERSYDSGLGESLNNMHIGKSIATAVPVNTKRSPYSCSAPAIVFPNSI               KGNKDHLKFGRSWCDMDEEDEEDIVSFGSNDDFGASDELSSKHIGLADDWNVLSQWNDNS                 Pichia jadinii  (gi|1232133)       MTHTDITGSLINEY RIVKLIGSGAYGLVYQAQNTVTGQQVAIKCISKKSNPSVKKQSDYLTTLLAEHLL     (SEQ ID NO. 22)                 ERDFSLQGLREMSLKRLSMADNIPCPFVREISIHLQVHQHPNVISIHKILDSQVAVFVVMDYYPEGDLF                   VNIVDRQVYARSSGLIKDVFIQLIDVISYCHSKGIYHCDIKPENINCANKGSKVVIGDFGLAVKSKYIQ                   SKTCIGSSYYMAPERLCTMNHSLTRLEYPACKQDIWSLGVILINFCCTRNPWMKACEKDATYSAFKKDP                   KILMEILDISEELWNILCDCFREEPEERISLFELRDRVLK CRSFTVAGPLSRCDSYEQDMDDALECAVP               ANESSVGSNGSLDLPMDHIIEYAQYLQTLSSVKNTAAGNYTQNQFVLDNNIMDNVSIMSNKSFNMNFA                 Nectria haematococca  (gi|1256839)       MQHHAIFGYQTPPASPGFDNPKCTIQQPFAVPRHYPTRPLAPEERLGRVLEGT LQLTEILGTGAYGVVY     (SEQ ID NO. 23)                 LAVDLKTGGKYAVKCLSKFNADGTQLEPRQFAYQQREIRLHWKASNHANVVQMLKIVNDPDCIYVILEY                   CPEGDLFLNITERGQYVGKDELSRNIFLQILDAVEHCHNLGIYHRDLKPENILVTDRGDTVKLADFGLA                   TSDDRSEDYGCGSTFYMSPECLDPSARKPYYMCAPNDVWSLGVILVNLTCGRNPWKQASFQDSTYRAYA                   GSKDFLKTILPLSDELNEILGRIFEPNPEQRITLNEL RTRIMACSRFTMPAVSPPTPPASPDHTTQYVS               TEDAIIDDYDYDSPLSPASSSDDEGSLTSSGSTIDDLDDDFDQERQMPQTPPEYAPHAFDPEEPKEHQL               IYHSQEFVPQKYSGPVPVPVQVPVGVPPQPMLCQPVPPVIQAPVPIQAPCQQHKSYFPIWDMVKYVQHV               PILQHHIPFHQQVPFMPTFQGCY                 C. albicans  (gi|7271026)       DLCYANSII DYNELHLVLIDFGLAMDSATICCNSCRGSSFYMAPERTTNYNTHRLINQLIDMNQYESIE     (SEQ ID NO. 24)                 INGTTVTKSNCKYLPTLAGDIWSLGVLFINITCSRNPWPIASFDNNQNNEVFKNYMLNNNKAVLSKILP                   ISSQFNRLLDRIFKLNPNDRIDLPTLYKEVI RCDFFKDDHYYYAQHQHHHNHNQINNAYNHYQKQPNQA               RPTANQQLYTPPETTTYNSYASDMEEDEISDDEFYSDEEDEDIEDYEEEEEEYFGNEQQQQQQVTTVNG               NFGQVKGTCYYDTKTKTTTYIKPPAAYTLETPSQSVEYC          
 
         [0095]    ELM Family  
         [0096]    This family includes ELM1 (SEQ ID NO. 25), PAK1 (SEQ ID NO. 26) and TOS3 (SEQ ID NO. 27) from  S. cerevisiae ; SSP1 (SEQ ID NO. 28) of  S. pombe ; and orf.7535 (SEQ ID NO. 29) from  C. albicans.    
         [0097]    SSP1 mutants show defects in cell cycle, cell morphology and osmotic stress response. The enzyme is also known to modulate the actin cytoskeleton. Overexpression of PAK1 reveals an interaction with DNA polymerase and hence with cell cycle or DNA damage repair. PAK1 interaction with Tid3, a member of a centromere protein complex, may indicate a further role in cell cycle. ELM1 is required for the cytoskeletal changes underlying cytokinesis, bud development and pseudohyphal growth in  S. cerevisiae . Like members of the GIN4 family, ELM1 is required for proper septin localisation.  
         [0098]    The bold, underlined portion of each family member denotes its kinase domain. Accordingly, the present invention allows the skilled artisan to identify and classify newly-identified kinases from other fungi as belonging to the ELM family if the newly-identified kinase domains share at least 38% amino acid sequence identity with any one of the kinase domains of an indicated family member listed below. Preferably, the ELM kinase domain has a percentage sequence identity to a kinase domain of any one of SEQ ID NOs. 25-29, of 40%, of 45%, of 50%, of 55%, of 60%, of 65%, of 70%, of 75%, of 80%, of 85%, of 90%, or of 95%.  
                                 S. cerevisiae  ELM1               MSPRQLIPTLIPEWAPLSQQSCIREDELDSPPITPTSQTSSFGSSFSQQKPTYSTIIGENIHTILDEIR   (SEQ ID NO. 25)               PYVKKITVSDQDKKTINQ YTLGVSAGSGQFGYVRKAYSSTLGKVVAVKIIPKKPWNAQQYSVNQVMRQI                   QLWKSKGKITTNMSGNEAMRLMNIEKCRWEIFAASRLRNNVHIVRLIECLDSPFSESIWIVTNWCSLGE                   LQWKRDDDEDILPQWKKIVISNCSVSTFAKKILEDMTKGLEYLHSQGCIHRDIKPSNILLDEEEKVAKL                   SDFGSCIFTPQSLPFSDANFEDCFQRELNKIVGTPAFIAPELCHLGNSKRDFVTDGFKLDIWSLGVTLY                   CLLYNELPFFGENEFETYHKIIEVSLSSKINGNTLNDLVIKRLLEKDVTLRISIQDLVKVL SRDQPIDS               RNHSQISSSSVNPVRNEGPVRRFFGRLLTKKGKKKTSGKGKDKVLVSATSKVTPSIHIDEEPDKECFST               TVLRSSPDSSDYCSSLGEEAIQVTDFLDTFCRSNESLPNLTVNNDKQNSDMKTDRSESSSHSSLKIPTP               IKAMIRLKSSPKENGNRTHINCSQDKPSSPLMDRTVGKRTVNNSGARKLAHSSNILNFKAYINSEDSDI               RETVEDVKTYLNFADNGQI                 S. cerevisiae  PAK1       MDRSDKKVNVEEVNVPSNLQIELEKSGTSSSVSLRSPTKSSATNLAGMAEGARDNASIASSSVDSLNML   (SEQ ID NO. 26)               LERQRVRQLNHPQHQQHISSSLAKTPTTTSSFCSSGSSKNKVKETNRISLTYDPVSKRKVLNT YEIIKE                   LGHGQHGKVKLARDILSKQLVAIKIVDRHEKKQRKFFTFIKSSKISENDKIKREIAIMKKCHHKHVVQL                   IEVLDDLKSRKIYLVLEYCSRGEVKWCPPDCMESDAKGPSLLSFQETREILRGVVLGLEYLHYQGIIHR                   DIKPANLLISGDGTVKISDFGVSLAASSTNSSDSSESLDELELAKTVGTPAFPAPEMCLGEDAFTRYNL                   TKENLFRGSCISFMIDIWAVGVTLYCLLFGMLPFFSDFELKLFEKIVNDPLKFPTFKEIQSNKVSKVSC                   EEEYEMAKDLLLKLLEKNPQKRMTIPAIKKHPFV SWDFDHVPENDEKLLSSVLEQKLRFQCNQTDQFEP               ISISKHELKNAVSGVGKKIKESVLKSIPLKDPSDLSNKNYLHPTETTRGRGDANVIVSEGSVLSNIKEL               SANDGCLNTDSDTNININDDDHYSGDDNDGHLTKRELERELNKFDDKHEAGNMVNLPINSSFASLDSFY               IDNFAMARMGMSSPEAGDSVSSVPNLPSAPSSTRLGRSPVFSGVTNQPSPIRPVLPQQKSSFCATGRYD               KSHNSLLRNSSSHLTSYNSGRPSSRTGRMNSRNQNLPKIPNSLSKISTTKLTELRVPKDSEIPSPAKNP               NADRLRRFPVKKNTKTPAIKDPPRININSSDKSGSKNSPIKSLYQRMKQSKDNSKTFEVRRGNFFSHFN               GDDDDSSSQSSVTSSGSESDSELSSTSSSCTSGTQSRNSSNNNAYSETESLPFEFGVDSEDGSGVLLRD               LPNEDQIRPFLDIQPCRRMKVKSSLNLEPPSVSSSSSSSSDEDELILNVGTAGHRRRHNSSKLSELSNS               PQKGSNNFMYSNGSVHDSETTITPQNMDDLTLHQALSRSQPISKPGPLVLPKRLDQKKATTETSNLTDI               VEFNGNNDHRKDKNFDKVLYSRDLLKLALSSTNAGRRRSIPSNKIRGRKDASITMSTNVGNDEHARNTS               CHGDKGQENGAIKQRTHERSRSLTVAELNEEKRRSALP                 S. cerevisiae  TOS3       MVLLKEPVQPLPRSSLLYNNASNSSSRIKETRKVKLLYNPLTKRQILNN FEILATLGNGQYGKVKLARD     (SEQ ID NO. 27)                 LGTGALVAIKILNRFEKRSGYSLQLKVENPRVNQEIEVMKRCHHENVVELYEILNDPESTKVYLVLEYC                   SRGPVKWCPENKMEIKAVGPSILTFQQSRKVVLDVVSGLEYLHSQGITHRDIKPSNLLISSNGTVKISD                   FGVAMSTATGSTNIQSSHEQLLKSRALGTPAFFAPELCSTEKEYSCSTHEIWSLGVTIYCLLFGKLPFN                   ANSGLELFDSIINKPLEFPSYEEMLNGATSGITMEEYTDAKDLLKKLLQKDPDKRIKLADIKVHPFM CH               YGKSDAASVLTNLETFHELKVSPPSSCKRVELVSLPVNSSFASLDSVYMENFDHNNLRTGADRNSTYSP               SIYDANTLSPSAYHNIGSRESSYSSFSSFTSSTAFASQISIQDAPAIGDQQCLIGESGSSLRVNSCEFP               QYTTMSPVGEYPFESTEASLSSTLTPVGNVPQRIKAHLVEGKSNSKDDLRIEADASLVFEASDAQRTRR               RMSLYKL                 S. pombe  SSP1 (gi|9075860)       MGSVNNEEKTLIEPQRLLRKNTWHPEVDDSEVPPSVFPEYPVHKAIQKTSDSFRKRNYSAGDYVIAPLG   (SEQ ID NO. 28)               GEREGSSLTHSWTFQPGKHNQRLYSDNFQEAQRQWKRLQEWGEVKETKKIRKRFDRFSGRKYINH YEII                   KELGRGMHGKVKLGRDTVTRELLAIKIIPKTERRPKLGRANASSQKEKVRREIAILKKCVHPNVVRLRE                   VIDDPSSTKVYLVLEYHSGGEVPWTDCDSPVLSISEARQYFRDVVLGLEYLHYQGIIHRDIKPANLLLN                   SSNCVKISDFGVSYIANAGLNEDIWVELAKTVGTPAFFAPELCWTDLDRPRPKISEAIDVWALGVTLFC                   LLFGRCPFNASMEYELFDKIVNERLNIPSTPDIGEEGRDLLKRLLCKDPEQRITLVEVKLHPWT LDGLK               DPEKWLQNTDPSTVSRVEVSTDEVASAISLVGRLRRKLGKLFRFRRPKARVFDSSSSVPSDSSICRPES               SGNSSIGLSASELSDSFNRLAVNESQKDRERKQVHPVEMGRNSSEKKPRCDFGWDYEAFPNDNQDADDA               CSYNTGDSIPQVSKSINGHFETYSRTSMDTDDVASFESPNAKHEESGMPVVTFRNYENYDANPSNFHPV               VPGFVSSPNLHLAGGSDTPIYCIEHSFTPTN                 C. albicans  ORF.7535       MSTSLSHQELSTEKGQSCPPIPDSNPLNPKSPALRTTSNSTILNSPIETINVNTSSKSNISGESTINGS   (SEQ ID NO. 29)               AYSNSTTVVQPEVFGEAHTTTSTHNSASTRTERNEFPNSHLHQHQQESRNNGESNTPMTSPKHFPTDDL               RHSLFYKAGSAAHHKSATSSKQSSTTSLKDGLNNANTYHFQNTFLDNNVMSDLEESPVPNERNPIQDTG               LGPRSHATKFGVQSTTSLPTTISQSRLPNSNKSSFFPFKSYTSSPVKETKHVFLEYDPITRRKVLNT YE                   ILREIGKGEHGKVKLARDLINNELVAIKIVNRKSRKERPSLRMRKNSSAPVINEYELKVKREIAIMKKC                   RHKHIVALREVLDDLNSLKIYLVLEYMEKGEIKWKKLQSDVAKPTANKCYDANDNEIPCCGNGRMQQRQ                   QSLLTDEDLLSNEFSPNLTFKQSRKIFRDVLLGLEYLHMQGIVHRDIKPANLLVSADNIVKISDFGVSF                   ATSLAENDEGYLVNELDLAKTAGTPAFFAPELCQFDDETATEKLSSSTESHAPPKIDYKIDIWALGVTL                   YCLLFGKVPFNADTEYDLFQVIVKEPLKFPNSIKAFNPPATVTEEEFELAKDLLSKMLDKNNRTRIEIQ                   DIKEHPFT LMDLDNDVDGLHELFHLNGDNPVEPLSFDLDEHDIVSKDEVDNAVIGVGARIKRSLVRAIR               AGGLKDGEIRNKFAALQLEHSRSENSEESSSGYSNYSSSTRLLGYQNGQNYSMILSEGLPVSSATPPPA               LLAAQQKRSSLLSPKSGGISEKNNPHFPSSLAHQIPNTSSPSTCSSSTSMAFQNHFSFAGMRESGKSLL               HDMIESNSNNSSRRGSSAGITVSEAPQIETKRNVGGDLYLKNQSVVETFKGIQLQDDKRRRSSIFSLHS               QIGTNSNKSSLSHELTPTQTGSGASTQQQHQHYSTNYSNIAAPIPVPAPRKQSTSDNEQDIKAPLLHQE               KNVMGKPYLKIGPISIAREDEKSADDHPDSSIISLPLSESFASLDSINDDYLSRKYEEYTNNRKENSKS               EGNVPVISLRRKSSLSESDLTRHVQLKDPFGKFKPDGSEIAEKFKAFNLGNLMKTGGKFALAEHNSSDS               QQIKGNNYQSSDDGIAPKAIVPAISYSSSDSYSSCSSSSFDDEDESDDDEENLTLAFQSKVAPISRANF               LSLTGRAKSHDSNLPTLRQNREKGRQLNPEFQGPIIFHDGLPEFEDVPDGLINSNPIGNNNVNGNSAFN               SGYSYYDNVNPTVVSSNVSTATLTMGMAPSESVETNVEAPAQENAVKVSSPLNPHKNTSSRSDILKDLK               KNTSISFGEILFNDQFNNHYKKDPVYSPFPSAKHLDNDQETIVKESASKFHEHRPTYYRSNSVTIGLLH               RSTHREDDDDVSQTGNDLEQLITKEKQG          
 
         [0099]    HAL Family  
         [0100]    The HAL kinase family includes 7 genes from  S. cerevisiae  HAL5 (SEQ ID NO. 30), KKQ8 (SEQ ID NO. 31), NPR1 (SEQ ID NO. 32), PRR2 (SEQ ID NO. 33), PTK1 (SEQ ID NO. 34), PTK2 (SEQ ID NO. 35), SAT4 (SEQ ID NO. 36), YDL025C (SEQ ID NO. 37) and YOR267C (SEQ ID NO. 38). Since many are involved in transporting ions, protons and small molecules, they are intrinsically responsible for generating responses to environmental stress, e.g., to salt, pH, and osmosis, toxins and drug resistance. For instance, HAL5 (SEQ ID NO. 30) and SAT4 kinases are involved reponding to changes in salt and pH, in conjunction with activated potassium transporters. The PTK1 (SEQ ID NO. 34) and PTK2 (SEQ ID NO. 35) HAL kinases are used in polyamine transport, in part by regulation of proton pumps. YOR267C (SEQ ID NO. 38) regulates the PMA1 proton pump. PRR2 (SEQ ID NO. 33) may be involved in the pheromone mating response. Other, non- S. cerevisiae  HAL family members include the SPAC29A4 (SEQ ID NO. 39) and SPCC1020 (SEQ ID NO. 40) of  S. pombe  and gi|3850140 (SEQ ID NO.41) and ORFx1 (SEQ ID NO. 42) isolated from  C. albicans.    
         [0101]    The bold, underlined portion of each family member denotes its kinase domain. Accordingly, the present invention allows the skilled artisan to identify and classify newly-identified kinases from other fungi as belonging to the HAL family if the newly-identified kinase domains share at least 30% amino acid sequence identity with any one of the kinase domains of an indicated family member listed below. Preferably, the HAL kinase domain has a percentage sequence identity to a kinase domain of any one of SEQ ID NOs. 30-42, of 60%, of 65%, of 70%, of 75%, of 80%, of 85%, of 90%, or of 95%.  
                                 S. cerevisiae  HAL5               MGDEKLSRHTSLKRARSLSESIKGLFKPSGISGSNNAAAPSSRPGQDQAHSHQTARIITSNVSSPSISP   (SEQ ID NO. 30)               VHSPVLQAAPKHHKLGVPNIAKLSLSPSREPSLNSENEMFSQESFISEKDEDEANLLEREDLQNKKEEK               ARAKHVRSKEAYVPHHRYTVGSDEVERQPRERLKNFPQNAGSSNPANSNANHVLDQENNFSIDAMLDYD               EESKLRRRNSLGVRNHSNRTRSRKNSLSTPRSPPMKNGNGGMNSNATNNVGNGTGNRIYMRGRNHSDSI               SASSLPKFQEIECKCILDLGHFKVFENGYHEHSLRVLPIITNNKNVDSGDEKDADASVNSGDDGDNDSE               ANMHKQKSVFSLSGLFKSHKDGNQQQQQQQQQEENGEQINLEKAFSIIPSQRFIKSQTLKKSRTSNLKN               GNNDELMKNDGKNIPQIVNPNAAVGVEELKLINALSEKIRKGLKSENTKGNNGEGRSNSNKQEDSDDTE               GKAGTTNDDTSHKPCSQKY GKSIGVVGAGAYGVVKICARCKTAKDVLPYSTYSNGKKLFFAVKELKPKP                   GDQIDKFCTRLTSEFIIGHSLSHPHFEANAMIAGNVSRTTPPK1WFNAPNILKILDLMEYSNSFVEVME                   FCASGDLYSLLTRNNISNESNNGSSRLIQTVKEGSGSPLHPLEADCFMKQLLNGVQYNHDHGIAHCDLK                   PENILFQPNGLLKICDFGTSSVFQTAWEKHVHFQSGAMGSEPYVAPEEFIRDAEYDPRLVDCWSCGIVY                   CTMVHGQYLWKIAIPEKDSLFKSFLSEIKDDGQFYLFEELRHVSSELNRLRKIALYRTFQVDPTKRITI                   EQLLQSSWM RKTKCCVVYRHLHTKVSK                 S. cerevisiae  KKQ8       MMDSKTLTASMVMQEEKKRQQPVTRRVRSFSESFKMLFRPPRSRDSSPINVTRIPYRSSSTSPKRSSEP   (SEQ ID NO. 31)               PRRSTVSAQILDPKNSPIRQRSYTLKCCTPGLSHPFRQTGSGASNSPTRHRSISGEEQEIVNSLPEYKR               SASHTFHGIRRPRSRSSSVSSCDSSNGTTSSSDSQWANDSLLDDSDNDLTPYRGSNKDILKSKDRAPYN               YIDDYNKKALRRATSYPNPLPSKQFYNERLYTRRSHPDEESLESLPRFAGADVQCIIEQNGFKVYEDGS               HEHNIKLSGVIAKLEKGNSLPAHRQGSLSRPRLGITLSGLFKHHKNECDIENALSLLPNVEKSQTNHEK               RTGQSPNDSNRSSPTQGREDYLKIVNPDASLGSDELKLINSLSSRIHKSLQNYLQEKNLKPAECIGEQA               PTFQDNY GHPVGLVGAGAYGEVKLCARLRNEKDSPPFETYHDSKYIYYAVKELKPKPDSDLEKFCTKIT                   SEFIIGHSLSHYHKNGKKPAPNILNVFDILEDSSSFIEVMEFCPAGDLYGMLVGKSKLKGRLHPLEADC                   FMKQLLHGVKFMHDHGIAHCDLKPENILFYPHGLLKICDFGTSSVFQTAWERRVHAQKGIIGSEPYVAP                   EEFVDGEYYDPRLIDCWSCGVVYITMILGHYLWKVASREKDMSYDEFYKEMQRKNQFRVFEELKHVNSE                   LATNRKIALYRIFQWEPRKRISVGKLLDMQWM KSTNCCLIYDST                 S. cerevisiae  NPR1       MSSLTRLLQEKRKNETSNSSPRTSADTLTTTPESQSLDLHSRNKSSSHIGSVSNSSSSDRNRANVPVPG   (SEQ ID NO. 32)               SVTTVTQIYSEEDSSSTAGSSLDDRNQFSSSFLNANFAHTASFYGTSAQSRDRFGSLINDQGTAGLSSH               GGSFAAQNRITSRLSTTSHTSGRAIPSLSSSIPYSVPNSNKDNNSSNSNSSSLSSSWLETYAGGMPNNI               THESNVISSPKVDSVEPRFVISKQKLQKASMDSNNANATQSRSISRSGSFSSQLGNFFFSKNSKESSNS               NSAGMSFSANSNGPSPNIKNPNVTNGSTPIPKPIRARQSSIYSASRQPTGSYTDNFYGSPSSVHDHLPP               SQSVPRSQHSSIGDLKRFFKKSSNSNLSSNSNNVIPNGSPLSSGIAVPSHSHSSSHFAAGNNSYSTSYN               GNGDTIYSHSHGGSGIPFSKRY IKTGADLGAGAGGSVKLAQRISDNKIFAVKEFRTKFENESKRDYVKK                   ITSEYCIGTTLNHPNIIETIEIVYEIWRILQVMEYCEYDLFAIVMSIKMSYEEICCCFKQILTGVQYLH                   SIGLAHRDLKLDNCVINEKGIVKLIDFGAAVVFSYPFSKNLVEASGIVGSDPYLAPEVCIFAKYDPRPV                   DIWSSAIIFACMILKKFPWKIPKLRDNSFKLFCSGRDCDSLSSLVTRTPDPPSYDESHSTEKKKPESSS                   NNVSDPNNVNIGPQRLLHSLPEETQHIVGRMIDLAPACRGNIEEIMEDPW IRSIDMCHLVEDGLSFKVV               RGEDHHHTQVDQSEAHIAGLEKKKKKQNNQ                 S. cerevisiae  PRR2       MSLSRILRYNQRNNKTTASLTAEHAYSDNWAYSVSLGDPTSVGVNMAAKTGEALNKSYDSVFSSLPVAD   (SEQ ID NO. 33)               SVPRTDFTASSRDDENTDVQKLTTSWMEKIDTKMPENISKIDSNIISSPMVSKVEARFIVPKGRLRKNS               TDFTSSFSNSLSLPKSYGKLIFFTSKKNSSSTKKNLANDISDNKHNNNSSNTIGHNIPVTTATATCDEI               ACTSTEHEYNVYEEERMFTTRVYSLEDSVSSLSTNPLDDTYSEAVQVNTRHIEDTESTAHIRKHSYTTS               LSSIKRLFKITSFSNNNSNSCDHQESTVADDCAISSSLKETTSSPVSTGSFSLMIENEDSDRDQIIQAL               YSNIEASTDLVSRKY RDLDVVLGEGSGGKVKLVQRVLDNKVFALKEYRSKKKRESERKYIKNIISEYCI                   ASTLKNPNICETLEILYEKGKIFQILEYCEYDLFSLVMSEKMKYEEICCLFKQLINGVKYLHIGLSHR                   DLKLDNCVVTRRGILKLIDFGASSVFHYPLSSQMIEANGIVGSDPYLSPEVFYFNEYDPRALDVWSVGI                   IFFCHITRRFPWKYPKVKDVQFKAFCSGRGVSSFKDLVTRPATDDSNNYDNDGYEEGVIDMGPNFILHR                   LPEETHKIMRRILEVSPFRRITINGILQDGWI KEIETCQVVGAASPNEASLRIINKGNHIHTNIDQRYA               HIGGLHQRT                 S. cerevisiae  PTK1       MTVSHNHSTKISQQPISSVSAFKFFGKKLLSSSHGNKLKKKASLPPDFHSTSTNDSESSSPKLPNSLKT   (SEQ ID NO. 34)               SRRANSFAHTTMSKRSLSSASTKILPPAGSSTSISRGNRHSSTSRNLSNSKFSSERLVYNPYGVSTPST               SLSSVSTSMKKDPDLGFYLHDGDSKIRMLPIPIVDPNEYLPDEMKEASIQLSDNFVFD DENKTIGWGGS                   CEVRKIRSKYRKKDVFALKKLNMIYNETPEKFYNAAPKEFIIAKQLSHHVHITNTFLLVKVPTTVYTTR                   GWGFVMELGLRDLFAMIQKSGWRHVALAEKFCIFKQVACGVKFCHDQGIAHRDLKPENVLLSPDGVCKL                   TDFGISDWYHHGSTRPVQPCQEVRRDDRLAPYAPPEVMFYDSKKRYDTELQQPYDPRALDCYGLGIILM                   TLV NNVIPFLESCSFDTGFRDYCDAYENFIRLHDRAFRNRAITARGREWSITWLEISRTDMHLAWHGGS               LTQKPPPATPSTTSSKTHGSKELRLVLMPTTNMCVRNLLSKPLRTRIRGVSISLQMLLQPHPPQTHSLR               TESPSGQW                 S. cerevisiae  PTK2       MAGNGKDKEVDKSPSVSTLKLLGKRLFNSSSHTDNSSLLLSAEQLGNGRSLRKRPTSPSISGSGSGGNS   (SEQ ID NO. 35)               PSSSAGARQRSASLHRRKNNASVGFSNGSVSSHKSSVALQDLIKHNNNPYLNSPSDILGTGTGIASTRD               RDRAVLDREKEKERARNKERNTHHAGLPQRSNSMASHHFPNENIVYNPYGISPNHARPDTAFADTLNTN               KENDLSFYMHDGNSKIRMLPLPIANPNDFLPEDMKQYSVHLTDNFVFDTDN KPIGSGGSSEVRKVKSSY                   RQKDVYALKKLNMIYHESPEKFYKRCSKEFIIAKHLSHNVHITFEFYLLKVPTTTYTTRGWGFIMELGV                   KDLFQLMERTGWKNVPFNEKYCLFKQVAQGIKFCHDNGIAHRDLKPENVLISKEGICKLTDFGISDNYH                   VIPHDYTSPVKTCQGMIGSPPYTPPEVMYFDAKKHYPEKFQKPYNPLAMDSYALGIMLITMINNIIPFI                   DSCNTDARFREFEVSYDNFINHQNPHFRDKGCRKPGPGSEYSLARNFKNTDATRIAWRLADPNPATRYT                   MDDLFNDPFF QQIETCVEPNDDDLVRVPELRKSTSTNDFSENSLDAPHDQEVIHTSNPFLKKETLTSKP               RSMLEIAESPSLKQKSKVKDSAKTKTHDVGDEGGNESTKPKQQDKKENLKKDEVKNGDKDKVIEEATTT               NVDSILEKPTPTSTKVEDNLSEDDSTMKELKSMLNSTPTTPTHNGPTPLPAKAGTQLDKRMSDLSLKSE               TPASTKNFSAPNVSSSSNSLRSLGSPSVSSSKKKKVIHHHLDITNSVTNMSSVSAFISR                 S. cerevisiae  SAT4       MTGMNDNNAAIPQQTPRKHALSSKVMQLFRSGSRSSRQGKASSNIQPPSNINTNVPSASKSAKFGLHTP   (SEQ ID NO. 36)               TTATPRVVSNPSNTAGVSKPGMYMPEYYQSASPSHSSSSASLNNHIDINTSKSSSAASLTSSVSALSLS               PTSAINISSKSLSPKFSHHSNSNTAITPAPTPTASNINNVNKITNTSAPICGRFLVHKDGTHEHHLKNA               KRQEKLSTMIKNMVGASKLRGEAKSAVPDIIMDPKTTLKSNKNPPTLFAGFMKQVVDMDDKYPEGAPTS               GALNCPERDIYRSDQKDSKNNTHNITTTKKDRQCFAEKY GRCQEVLGKGAFGVVRICQKKNVSSQDGNK                   SEKLYAVKEFKRRTSESAEKYSKRLTSEFCISSSLHHTNIVTTLDLFQDAKGEYCEVMEYCAGGDLFTL                   VVAAGKLEYMEADCFFKQLIRGVVYNHEMGVCHRDLKPENLLLTHDGVLKITDFGNSECFKHAWEKNIH                   LSGGVCGSSPYIAPEEYIKEEFDPRPVDIWACGVIYMAMRTGRQLWSSAEKDDPFYMNYLKGRKEKGGY                   EPIESLKRARCRNVIYSMLDPVPYRRINGKQILNSEWG REIKCCHNGRALK                 S. cerevisiae  YDL025C       MVKETFLHSSSSTSLSSLFRPTKLKMLSAKIFNGGGNQSYSKTDDVSRSSSRSSKKNTDSDQEDQIKYN   (SEQ ID NO. 37)               KPNDRRSTIGKSPQGNGALSKESHVVASSTLTGISPTSAKKAPIDYSPSRPLPNNHNPVRTGHTVPHLP               HSIHNPINYIHQGSKDAFHHPHPVRSTAHSNKSTVSSAKSDTPSSNLSYQAHMHPVEILQKQIEDKHFM               DSQASTPGSVELQHNSSSGSDDTSSRKKKSLRLTRFFKKIHNDYHDNHHHHHHHNRGSTPTKPKLNLNT               NENIVESNGKALYETDNPVELLEKY GIPGRKLGEGASGSVSVVERTDGKLFACKMFRKPHLNNEGTNQS                   QLANYSKKVTTEPCIGSTLHHENIVETLDHLTEGDTYLLVMEYAPYDFFNLVMSNLMTQDEVNCYFKQL                   CHGVNYLHSMGLAHRDLKLDNCVVTKDGILKLIDFGSAVVFQYPYEDTIVKSHGIVGSDPYLAPELLKQ                   TSYDPRVADVWSIAIIFYCMVLKRFPWKAPKKSFNSFRLFTEEPEDEDDIVRGPNKILRLLPRHSRTII                   GRMLALEPKQRVLWQDVVKDDWL VSVPSCEVDPTSGDLVEKPKNHKHHLVTEEELNELTKQHGNKDSN                 S. cerevisiae  YOR267C       MPNLLSRNPFHGHHNDHHHDRENSSNNPPQLIRSSKSFLNFIGRKQSNDSLRSEKSTDSMKSTTTTTNY   (SEQ ID NO. 38)               TTTNLNNNTHSHSNATSISTNNYNNNYETNHHHNISHGLHDYTSPASPKQTHSMAELKRFFRPSVNKKL               SMSQLRSKKHSTHSPPPSKSTSTVNLNNHYRAQHPHGFTDHYAHTQSAIPPSTDSILSLSNNINIYHDD               CILAQKY GKLGKLLGSGAGGSVKVLVRPTDGATFAVKEFRPRKPNESVKEYAKKCTAEFCIGSTLHHPN                   VIETVDVFSDSKQNKYYEVMEYCPIDFFAVVMTGKMSRGEINCCLKQLTEGVKYLHSHGLAHRDLKLDN                   CVMTSQGILKLIDFGSAVVFRYPFEDGVTHAHGIVGSDPYLAPEVITSTKSYDPQCVDIWSIGIIYCCM                   VLKRFPWKAPRDSDDNFRLYCMPDDIEHDYVESARRHEELLKERKEKRQRFLNHSDCSAINQQQPABES                   NLKTVQNQVPNTPASIQGKSDNKPDIVEEETEENKEDDSNNDKESTPDNDKESTIDIKISKNENKSTVV                   SANPKKVDADADADCDANGDSNGRVDCKANSDCNDKTDCNANNDCSNESDCNAKVDTNVNTAANANPDM                   VPQNNPQQQQQQQQQQQQQQQQQQQQHHHHQHQNQDKAHSIASDNKSSQQHRGPHHKKIIHGPYRLLRL                   LPHASRPIMSRILQVDPKKRATLDDIFNDEWF AAIAACTMDSKNKVIRAPGHHHTLVREENAHLETYKV                 S. pombe  SPAC29A4 (gi|2239225, ortholog of SAT4)       MGEKDKLHEISSKFASLGLGSLKSTPKARETTEPPPPSSQQPPSTPNGKEAASPSALKQNVRPSLNSVQ   (SEQ ID NO. 39)               QTPASIDAVASSSNVSLQSQQPLSKPVVSSKPNQTTAMPPPSNNPSRHVSSTSNKPAAVSPNPAAHHAE               LPSGSVPPSASVSRANSTATTTPHKAGVVSNPAAANVHVLSVAASPNPSTPSNGPAPVSTTATPSRNPV               TRLQRIFSQNSVSRQNSRTGRGAAVANTEETNSTGGSETGGAANSSSTSNPSSAKWSRFTVYDDASHTH               QLRPARRQEKLGKMLKDFLAGNSKKREEERIAKEAADAQHQLSLVQSWINGYGQEKLADKKDPAKVSAS               FVEKY GRCQEVIGRGAFGVVRIAHKVDPQNSGSETLYAVKEFRRKPAESQKKYTKRLTSEFCISSSLRH                   PNVIHTLDLIQDGKGDYCEVMELCSGGDLYTLIMAAGRLEPMEADCFFKQLMRGVDYLHDMGVAHRDLK                   PENLLLTVSGSLKITDFGNGECFRMAWEKEAHMTCGLCGSAPYIAPEEYTESEFDPRAVDVWACGVIYM                   AMRTGRRLWRVAKKSEDEYYSRYLHDRKNESGYEPIEMLERSRCRNTLYNILHPNPTYRLTAKQIMKSE                   WV RSITLCEAGNAGL                 S. pombe  SPCC1020 (gi|3130053)       MSVTPPNVQFNLNGDSDHKSDNSSSSLENKLDTELKITSPPRNPPQRLHPVDFSEHADTDDDMNHPLPR   (SEQ ID NO. 40)               VQSPVHIKNHIDPKLAEDRYRSSAARHFEPISIPPSAITSEDEDDYHGSANSSTVLPPRTENALHAASP               KPSGSTGYTSPALSQNSGSGGEGESDEGSFNTQHHRSPIFQAYPSSEDLVGDPNDPYRRTRRAPIKTNP               HDIPSQFIFRKLGLHHGKHGHHGHSGSLSLKSLVPNHHDKHDKHDKHEKMHSSLDLRRFFKSHQKTDKE               KKPSVSKSKSSANLQDDHFGLFKKY GKFGRMLGSGAGGSVRIMKRSSDGKIFAVKEFRARRPTETEREY                   ARKVTAEFCIGSALHHTNIIETLDIVEENKKFYEVMEYAPYDMFSIVMSGKMTMPEVYCCFKQLLSGVA                   YLHSMGLAHRDLKLDNLVVDSNCFVKIIDFGSAVVFKYPFEADIVEATGVVGSDPYLAPETLVRKLYDP                   RAVDIWSSAIIFCCHALRRFPWKYPKLSDNSFRLFCMKQPSNNAESPSDILADIKKQRLVEQGCEPIRK                   TDESHSPNSKTDNSSTHKQELYGPWRLLRLLPRETRAVIAHMLELDPVKRYDIHRVFAINWI NDISMCH               MENGKVIHSPTHVHNLVASEESPAPPAKH                 C. albicans  (gi|3850140)       MTKEHSIRNIFKKDKTPDNGSATATPSSSHTGLSKLFHKESKPITPPMKRTPSVSSLKRRNTNPSQTSG   (SEQ ID NO. 41)               ISLNHNHHHHQDSQNHNDATTSGGNIHSSTPVNRSRSNSDRLGHVPPTGRKVLSKAETFTHLQQLDTRN               AAKNQLRNHRIPSNHLSSPLSAAPHSDKIVYNPYGLNKTATQERPKNTSFYLSGVNDGERVLSNPVASP               NDYLPAELQQQHVNLLED FEIDVGTKKLGDGGSSDVRIINSCHHKKDLYALKKFTLLSKETDEDFYKRV                   SEEYKIHRKAAISRHVVDAFAILRIQSQSNLTRGWGMVMEFCGGGDLFSVIVKPGWKSTPLAEKYCLFK                   QIAYGVKFLHDHDIVHRDLKPENVLLDANGLAKLCDFGVSEFGHEVPEDFSSPVKLSTAYVGSPPYAPP                   EVMLLKEKSSTEIKAFAYDPFKMDCWGLGMLLFCLVYGGVPFQQSSPNDHAFRDYKFSHKRFCTDHATF                   KSNQGYPRGPGSEFKLAAKFENNGASRVAWKLCDPSENTRYTMDMLFDDPWF QSVEMCIYESPDQEVNP               FVLPGTGENIDTHSVSGYSSVNNSQAPSRRGTFTSRPVGSGAGSGYNSHDESSNGLSSSFRSMLDLKDI               PQKITKTDEPLPSNSSVHSNDSSSAPAKSKLDHPSSPGSLLSPSTPALQSIPADRVAQTTSPINASLPA               VEESDIEHESESEIQGDETESSGLQVLPPIDDVVAASPSSLTHEPQEQVLDSVESCISLPPNRDQAFAG               KDGEMCSLVDLKPAALKSATDLQLGADGMCNLGYKIKKHHHTEVSNVSNSSRR                 C. albicans  ORFx1       MSSLTKLLHESTSTLASPVLSRNTSEVTFKDQGRRTPEILNISDTVDAKSPGITIDVSKPKPSPIDTDG   (SEQ ID NO. 42)               MNVEPQAVHGFDPSPNTKVSFSSPFSPTSPFTRQSSNSFSSNQAFQNTRGAVASPRYIKNNSVSHSSVF               MGGESLSSSIPYSAPGGGRGNPASHSGNTGSLQRENSFSSLNTSDSNSSAHIPNLPNGQPINSIHIQSP               QVSASSIDSRFVVSKQRIAQAQAQASLSSSQRS&amp;SQSGLSFFFSQKSKPAVKRDSTTDLGAFYNNSYQD               RDAPIVSGSPNSLSSAESTVSYGSSAPTRHNSMANLKRFFKKSTPTTSQPVGTSNLSSSLRSASSGASG               ANNIPNSLNGQTNNGYQSPSSFSASTSNTSYSQSPGTNSSSVTRSSTLQNKVNYHERRQSVSGIVNNSQ               QLPFSKRYH SKNAESLGAGAGGSVRLLTRVSDGLTFAVKEFRAKYQNESKRDYAKKITGEYCIGSTLKH                   PNIIETVEICYENERIHQVMEYCDFDLFAIVMSNKMSREEINCCFKQILAGVHYLHSMGLAHRDLKLDN                   CVIDKRGIVKIIDFGSAVVFSYPFTKTLIEAQGIVGSDPYLAPEVCVFNKYDPRPVDVWSVAIIYCCMM                   LKKFPWKVPKLSDSSFKLFASRGEFIPISEHLKKTPNDMEKSNSNGSSGGGLSNLEDISEALEDEITAG                   AKQKPSTTGQNGATANGKDHTSSETGANRLLLALPEDCRRLIGRMVELAPACRITIDEVLNDSWL KSVN               MCTVEESSPGVFEVIKCEDHEHTQVDQSKAHIAAFEKNKKK          
 
         [0102]    DNA encoding any one of these kinase domains or full-length sequences can be cloned into an expression vector and expressed in a suitable expression system. The resultant kinase protein can then be purified, tested for kinase activity and then exposed to test compounds to determine if that activity changes, in particular if the kinase activity reduced. Similarly, a gene encoding any fungal kinase that has the indicated sequence identity across its kinase domain, with one of the above-described fungal kinase family members, may be isolated, expressed and also used to determine which test compounds modulate kinase activity. Such compounds can be used to inhibit fungi and can be used to treat fungal infections.  
         [0103]    A fungus that contains a kinase having a sequence of any one of SEQ ID NOs. 1-42, or that contains a kinase that has a minimum sequence identity across its kinase domain, may be exposed to the test compound(s) to determine if inhibiting kinase activity has a biological consequence, such as death or retardation of growth of the fungus. Accordingly, a test compound used to target a fungus containing a kinase classified to one of these families, should not have any effect, i.e., a modulatory, inhibitory, or deleterious effect upon kinase activity in a non-fungal organism.  
         [0104]    In general, determining kinase activity is a well known method in the field to which the art of this invention pertains. Indeed, there are many kits, reagents and products available commercially that perform this type of assay. In general, it is possible to determine the extent of kinase activity by determining the rate, level or ability of the kinase to phosphorylate a substrate protein. Determining phosphorylation levels and patterns of a kinase is well within the capability of the skilled artisan. Such a test can be performed on an isolated or purified kinase or from a preparation of lysed fungal cells. A control kinase, such as that from a non-fungal organism, can be tested alongside the target fungal kinase. Ideally, the phosphorylation pattern and levels of the non-fungal kinase substrate is unchanged after exposure to a test compound, while the fungal form is altered to reflect reduced or even abolished kinase activity. The art is also replete with techniques for determining the activity of a variety of kinases. For instance, there exist assays for determining Src-family protein tyrosine kinase activity by measuring the consumption of the exogenous substrate, enolase; there exist protein kinase C assays, histone kinase assays, and in vitro kinase assay protocols. An in vivo kinase activity kit is available commercially, through Clontech to determine the activity of kinases in signal transduction pathways. A compilation of kinase assay protocols is available as of Jun. 7, 2002, from the website, http://bric.postech.ac.kr/protocols/general_methology/general_protocol — 42 .html.  
         [0105]    Very generally, the amount of a radioactively-labeled ATP molecule, e.g. [gamma-32P] ATP, that is recorded by a scintillation counter, for example, after a kinase reaction with substrate is used to indicate the activity of the kinase. The specific activity is typically related in cpm/pmol and when assaying a purified kinase, the catalytic rate is best expressed during its linear range in mol phosphate transferred from ATP to substrate/min/mg of kinase. Highly active kinases transfer on the order of micromol phosphate/min/mg of kinase. Indeed, U.S. Pat. No. 6,399,319, describes a protein kinase assay for identification of fungicides, by exposing the kinase to a phosphate donor ([gamma-33 P]ATP) and substrate. The amount of radioactive phosphate measured after the reaction is terminated is an indicator of kinase activity with and without the presence of a potential candidate fungicide.  
         [0106]    There exist, therefore, several established assays that one may employ to determine the extent, if any, to which a compound has antifungal properties. For example, one may screen compounds for their ability to eradicate or slow down the growth of a fungus in culture, by staining the fungus or measuring the density, or concentration, of spore formation after a period of incubation with a test compound.  
         [0107]    Accordingly, a method of identifying a compound having antifungal properties, may comprise (a) culturing a fungus sample that contains at least one of SEQ ID NOs. 1-42; (b) treating the fungus sample with a test compound; and then (c) determining the level of activity of the fungus in comparison to an untreated control fungus sample. An antifungal agent would be one that brings about a decrease in the level of fungus activity (measured by activity, viability, growth status or amount of fungus) of the treated fungus.  
         [0108]    Chitin-Stain Antifungal Assay  
         [0109]    Chitin is typically present in fungal hyphae and, therefore, is a good indicator of the abundance or growth of a fungus. Thus, staining for chitin levels is a quick and convenient method for determining fungal growth in the presence of a test compound, i.e., a potential fungicide.  
         [0110]    Accordingly, one may use a iodine-potassium iodide solution (2 gm KI in 100 ml water and add 0.2 gm 12) in 1% sulfuric acid to stain for the presence of chitin in a cultured fungal sample before and after exposure to the test compound. Typically, a high concentration of chitosans stain dark violet, whereas lower amounts stain light blue. With this particular assay, however, cellulose may also be stained. For this reason, if necessary, cellulose can be removed by flooding with Schweitzer&#39;s reagent (saturated copper hydroxide in ammonium hydroxide) prior to iodine-potassium iodide treatment.  
         [0111]    Agar Dilution Antifungal Assay  
         [0112]    Another assay for antifungal activity is described in U.S. Pat. No. 5,837,726. In that document antifungal properties were determined by an agar dilution assay on microtiter plates. This assay monitors the growth of fungal spores in the presence of a test substance. In short, a spore preparation of a fungus is prepared by streaking out spores from a fungal stock suspension onto an agar plate for germination. After incubating the spores for 37° C. for a period of time, the spores are washed, counted and stored at 40° C. From this preparation, a spore suspension of known concentration can be made.  
         [0113]    The next step involves aliquoting serial dilutions of a test substance into a microtiter plate to which agar is added and allowed to solidify. The spore suspension is then also aliquoted into each well and the plate incubated at 35° C. for 48 hours. The concentration of spore germination in the microtiter plate is determined by taking OD 650  readings in a microtiter plate reader. According to the methodology of the &#39;726 patent, at OD 650 , a value of “0” reflects 100% growth inhibition (or 0% growth); a value of 1 corresponds to 75% growth inhibition; a value of 2 corresponds to 50% growth inhibition; a value of 3 corresponds to 25% growth inhibition; and a value of 4 corresponds to no growth inhibition.  
     
       
       
         1 
         
           
             42  
           
           
             1  
             1064  
             PRT  
             Saccharomyces cerevisiae  
           
            1 

Met Asp Asp Tyr His Val Asn Thr Ala Phe Ser Met Gly Arg Gly Asn 
  1               5                  10                  15 

Gln Gln Asp Asp Gly Asn Ser Glu Ser Asn Ser Met His Thr Gln Pro 
             20                  25                  30 

Ser Thr Met Ala Pro Ala Thr Leu Arg Met Met Gly Lys Ser Pro Gln 
         35                  40                  45 

Gln Gln Gln Gln Gln Asn Thr Pro Leu Met Pro Pro Ala Asp Ile Lys 
     50                  55                  60 

Tyr Ala Asn Asn Gly Asn Ser His Gln Ala Glu Gln Lys Glu Arg Gln 
 65                  70                  75                  80 

Val Glu Leu Glu Gly Lys Ser Arg Glu Asn Ala Pro Lys Pro Asn Thr 
                 85                  90                  95 

Thr Ser Gln Ser Arg Val Ser Ser Ser Gln Gly Met Pro Lys Gln Phe 
            100                 105                 110 

His Arg Lys Ser Leu Gly Asp Trp Glu Phe Val Glu Thr Val Gly Ala 
        115                 120                 125 

Gly Ser Met Gly Lys Val Lys Leu Ala Lys His Arg Tyr Thr Asn Glu 
    130                 135                 140 

Val Cys Ala Val Lys Ile Val Asn Arg Ala Thr Lys Ala Phe Leu His 
145                 150                 155                 160 

Lys Glu Gln Met Leu Pro Pro Pro Lys Asn Glu Gln Asp Val Leu Glu 
                165                 170                 175 

Arg Gln Lys Lys Leu Glu Lys Glu Ile Ser Arg Asp Lys Arg Thr Ile 
            180                 185                 190 

Arg Glu Ala Ser Leu Gly Gln Ile Leu Tyr His Pro His Ile Cys Arg 
        195                 200                 205 

Leu Phe Glu Met Cys Thr Leu Ser Asn His Phe Tyr Met Leu Phe Glu 
    210                 215                 220 

Tyr Val Ser Gly Gly Gln Leu Leu Asp Tyr Ile Ile Gln His Gly Ser 
225                 230                 235                 240 

Ile Arg Glu His Gln Ala Arg Lys Phe Ala Arg Gly Ile Ala Ser Ala 
                245                 250                 255 

Leu Ile Tyr Leu His Ala Asn Asn Ile Val His Arg Asp Leu Lys Ile 
            260                 265                 270 

Glu Asn Ile Met Ile Ser Asp Ser Ser Glu Ile Lys Ile Ile Asp Phe 
        275                 280                 285 

Gly Leu Ser Asn Ile Tyr Asp Ser Arg Lys Gln Leu His Thr Phe Cys 
    290                 295                 300 

Gly Ser Leu Tyr Phe Ala Ala Pro Glu Leu Leu Lys Ala Asn Pro Tyr 
305                 310                 315                 320 

Thr Gly Pro Glu Val Asp Val Trp Ser Phe Gly Val Val Leu Phe Val 
                325                 330                 335 

Leu Val Cys Gly Lys Val Pro Phe Asp Asp Glu Asn Ser Ser Val Leu 
            340                 345                 350 

His Glu Lys Ile Lys Gln Gly Lys Val Glu Tyr Pro Gln His Leu Ser 
        355                 360                 365 

Ile Glu Val Ile Ser Leu Leu Ser Lys Met Leu Val Val Asp Pro Lys 
    370                 375                 380 

Arg Arg Ala Thr Leu Lys Gln Val Val Glu His His Trp Met Val Arg 
385                 390                 395                 400 

Gly Phe Asn Gly Pro Pro Pro Ser Tyr Leu Pro Lys Arg Val Pro Leu 
                405                 410                 415 

Thr Ile Glu Met Leu Asp Ile Asn Val Leu Lys Glu Met Tyr Arg Leu 
            420                 425                 430 

Glu Phe Ile Asp Asp Val Glu Glu Thr Arg Ser Val Leu Val Ser Ile 
        435                 440                 445 

Ile Thr Asp Pro Thr Tyr Val Leu Leu Ser Arg Gln Tyr Trp Thr Leu 
    450                 455                 460 

Ala Ala Lys Met Asn Ala Glu Ser Ser Asp Asn Gly Asn Ala Pro Asn 
465                 470                 475                 480 

Ile Thr Glu Ser Phe Glu Asp Pro Thr Arg Ala Tyr His Pro Met Ile 
                485                 490                 495 

Ser Ile Tyr Tyr Leu Thr Ser Glu Met Leu Asp Arg Lys His Ala Lys 
            500                 505                 510 

Ile Arg Asn Gln Gln Gln Arg Gln Ser His Glu Asn Ile Glu Lys Leu 
        515                 520                 525 

Ser Glu Ile Pro Glu Ser Val Lys Gln Arg Asp Val Glu Val Asn Thr 
    530                 535                 540 

Thr Ala Met Lys Ser Glu Pro Glu Ala Thr Leu Ala Thr Lys Asp Thr 
545                 550                 555                 560 

Ser Val Pro Phe Thr Pro Lys Asn Ser Asp Gly Thr Glu Pro Pro Leu 
                565                 570                 575 

His Val Leu Ile Pro Pro Arg Leu Ala Met Pro Glu Gln Ala His Thr 
            580                 585                 590 

Ser Pro Thr Ser Arg Lys Ser Ser Asp Asn Gln Arg Arg Glu Met Glu 
        595                 600                 605 

Tyr Ala Leu Ser Pro Thr Pro Gln Gly Asn Asp Tyr Gln Gln Phe Arg 
    610                 615                 620 

Val Pro Ser Thr Thr Gly Asp Pro Ser Glu Lys Ala Lys Phe Gly Asn 
625                 630                 635                 640 

Ile Phe Arg Lys Leu Ser Gln Arg Arg Lys Lys Thr Ile Glu Gln Thr 
                645                 650                 655 

Ser Val Asn Ser Asn Asn Ser Ile Asn Lys Pro Val Gln Lys Thr His 
            660                 665                 670 

Ser Arg Ala Val Ser Asp Phe Val Pro Gly Phe Ala Lys Pro Ser Tyr 
        675                 680                 685 

Asp Ser Asn Tyr Thr Met Asn Glu Pro Val Lys Thr Asn Asp Ser Arg 
    690                 695                 700 

Gly Gly Asn Lys Gly Asp Phe Pro Ala Leu Pro Ala Asp Ala Glu Asn 
705                 710                 715                 720 

Met Val Glu Lys Gln Arg Glu Lys Gln Ile Glu Glu Asp Ile Met Lys 
                725                 730                 735 

Leu His Asp Ile Asn Lys Gln Asn Asn Glu Val Ala Lys Gly Ser Gly 
            740                 745                 750 

Arg Glu Ala Tyr Ala Ala Gln Lys Phe Glu Gly Ser Asp Asp Asp Glu 
        755                 760                 765 

Asn His Pro Leu Pro Pro Leu Asn Val Ala Lys Gly Arg Lys Leu His 
    770                 775                 780 

Pro Ser Ala Arg Ala Lys Ser Val Gly His Ala Arg Arg Glu Ser Leu 
785                 790                 795                 800 

Lys Tyr Met Arg Pro Pro Met Pro Ser Ser Ala Tyr Pro Gln Gln Glu 
                805                 810                 815 

Leu Ile Asp Thr Gly Phe Leu Glu Ser Ser Asp Asp Asn Lys Ser Asp 
            820                 825                 830 

Ser Leu Gly Asn Val Thr Ser Gln Thr Asn Asp Ser Val Ser Val His 
        835                 840                 845 

Ser Val Asn Ala His Ile Asn Ser Pro Ser Val Glu Lys Glu Leu Thr 
    850                 855                 860 

Asp Glu Glu Ile Leu Gln Glu Ala Ser Arg Ala Pro Ala Gly Ser Met 
865                 870                 875                 880 

Pro Ser Ile Asp Phe Pro Arg Ser Leu Phe Leu Lys Gly Phe Phe Ser 
                885                 890                 895 

Val Gln Thr Thr Ser Ser Lys Pro Leu Pro Ile Val Arg Tyr Lys Ile 
            900                 905                 910 

Met Phe Val Leu Arg Lys Met Asn Ile Glu Phe Lys Glu Val Lys Gly 
        915                 920                 925 

Gly Phe Val Cys Met Gln Arg Phe Ser Ser Asn Asn Val Ala Ala Lys 
    930                 935                 940 

Arg Glu Gly Thr Pro Arg Ser Ile Met Pro Leu Ser His His Glu Ser 
945                 950                 955                 960 

Ile Arg Arg Gln Gly Ser Asn Lys Tyr Ser Pro Ser Ser Pro Leu Thr 
                965                 970                 975 

Thr Asn Ser Ile His Gln Arg Lys Thr Ser Ile Thr Glu Thr Tyr Gly 
            980                 985                 990 

Asp Asp Lys His Ser Gly Thr Ser Leu Glu Asn Ile His Gln Gln Gly 
        995                1000                1005 

Asp Gly Ser Glu Gly Met Thr Thr Thr Glu Lys Glu Pro Ile Lys Phe 
   1010                1015                1020 

Glu Ile His Ile Val Lys Val Arg Ile Val Gly Leu Ala Gly Val His 
1025               1030                1035                1040 

Phe Lys Lys Ile Ser Gly Asn Thr Trp Leu Tyr Lys Glu Leu Ala Ser 
               1045                1050                1055 

Ser Ile Leu Lys Glu Leu Lys Leu 
           1060 

 
           
             2  
             1147  
             PRT  
             Saccharomyces cerevisiae  
           
            2 

Met Pro Asn Pro Asn Thr Ala Asp Tyr Leu Val Asn Pro Asn Phe Arg 
  1               5                  10                  15 

Thr Ser Lys Gly Gly Ser Leu Ser Pro Thr Pro Glu Ala Phe Asn Asp 
             20                  25                  30 

Thr Arg Val Ala Ala Pro Ala Thr Leu Arg Met Met Gly Lys Gln Ser 
         35                  40                  45 

Gly Pro Arg Asn Asp Gln Gln Gln Ala Pro Leu Met Pro Pro Ala Asp 
     50                  55                  60 

Ile Lys Gln Gly Lys Glu Gln Ala Ala Gln Arg Gln Asn Asp Ala Ser 
 65                  70                  75                  80 

Arg Pro Asn Gly Ala Val Glu Leu Arg Gln Phe His Arg Arg Ser Leu 
                 85                  90                  95 

Gly Asp Trp Glu Phe Leu Glu Thr Val Gly Ala Gly Ser Met Gly Lys 
            100                 105                 110 

Val Lys Leu Val Lys His Arg Gln Thr Lys Glu Ile Cys Val Ile Lys 
        115                 120                 125 

Ile Val Asn Arg Ala Ser Lys Ala Tyr Leu His Lys Gln His Ser Leu 
    130                 135                 140 

Pro Ser Pro Lys Asn Glu Ser Glu Ile Leu Glu Arg Gln Lys Arg Leu 
145                 150                 155                 160 

Glu Lys Glu Ile Ala Arg Asp Lys Arg Thr Val Arg Glu Ala Ser Leu 
                165                 170                 175 

Gly Gln Ile Leu Tyr His Pro His Ile Cys Arg Leu Phe Glu Met Cys 
            180                 185                 190 

Thr Met Ser Asn His Phe Tyr Met Leu Phe Glu Tyr Val Ser Gly Gly 
        195                 200                 205 

Gln Leu Leu Asp Tyr Ile Ile Gln His Gly Ser Leu Lys Glu His His 
    210                 215                 220 

Ala Arg Lys Phe Ala Arg Gly Ile Ala Ser Ala Leu Gln Tyr Leu His 
225                 230                 235                 240 

Ala Asn Asn Ile Val His Arg Asp Leu Lys Ile Glu Asn Ile Met Ile 
                245                 250                 255 

Ser Ser Ser Gly Glu Ile Lys Ile Ile Asp Phe Gly Leu Ser Asn Ile 
            260                 265                 270 

Phe Asp Tyr Arg Lys Gln Leu His Thr Phe Cys Gly Ser Leu Tyr Phe 
        275                 280                 285 

Ala Ala Pro Glu Leu Leu Lys Ala Gln Pro Tyr Thr Gly Pro Glu Val 
    290                 295                 300 

Asp Ile Trp Ser Phe Gly Ile Val Leu Tyr Val Leu Val Cys Gly Lys 
305                 310                 315                 320 

Val Pro Phe Asp Asp Glu Asn Ser Ser Ile Leu His Glu Lys Ile Lys 
                325                 330                 335 

Lys Gly Lys Val Asp Tyr Pro Ser His Leu Ser Ile Glu Val Ile Ser 
            340                 345                 350 

Leu Leu Thr Arg Met Ile Val Val Asp Pro Leu Arg Arg Ala Thr Leu 
        355                 360                 365 

Lys Asn Val Val Glu His Pro Trp Met Asn Arg Gly Tyr Asp Phe Lys 
    370                 375                 380 

Ala Pro Ser Tyr Val Pro Asn Arg Val Pro Leu Thr Pro Glu Met Ile 
385                 390                 395                 400 

Asp Ser Gln Val Leu Lys Glu Met Tyr Arg Leu Glu Phe Ile Asp Asp 
                405                 410                 415 

Ile Glu Asp Thr Arg Arg Ser Leu Ile Arg Leu Val Thr Glu Lys Glu 
            420                 425                 430 

Tyr Ile Gln Leu Ser Gln Glu Tyr Trp Asp Lys Leu Ser Asn Ala Lys 
        435                 440                 445 

Gly Leu Ser Ser Ser Leu Asn Asn Asn Tyr Leu Asn Ser Thr Ala Gln 
    450                 455                 460 

Gln Thr Leu Ile Gln Asn His Ile Thr Ser Asn Pro Ser Gln Ser Gly 
465                 470                 475                 480 

Tyr Asn Glu Pro Asp Ser Asn Phe Glu Asp Pro Thr Leu Ala Tyr His 
                485                 490                 495 

Pro Leu Leu Ser Ile Tyr His Leu Val Ser Glu Met Val Ala Arg Lys 
            500                 505                 510 

Leu Ala Lys Leu Gln Arg Arg Gln Ala Leu Ala Leu Gln Ala Gln Ala 
        515                 520                 525 

Gln Gln Arg Gln Gln Gln Gln Gln Val Ala Leu Gly Thr Lys Val Ala 
    530                 535                 540 

Leu Asn Asn Asn Ser Pro Asp Ile Met Thr Lys Met Arg Ser Pro Gln 
545                 550                 555                 560 

Lys Glu Val Val Pro Asn Pro Gly Ile Phe Gln Val Pro Ala Ile Gly 
                565                 570                 575 

Thr Ser Gly Thr Ser Asn Asn Thr Asn Thr Ser Asn Lys Pro Pro Leu 
            580                 585                 590 

His Val Met Val Pro Pro Lys Leu Thr Ile Pro Glu Gln Ala His Thr 
        595                 600                 605 

Ser Pro Thr Ser Arg Lys Ser Ser Asp Ile His Thr Glu Leu Asn Gly 
    610                 615                 620 

Val Leu Lys Ser Thr Pro Val Pro Val Ser Gly Glu Tyr Gln Gln Arg 
625                 630                 635                 640 

Ser Ala Ser Pro Val Val Gly Glu His Gln Glu Lys Asn Thr Ile Gly 
                645                 650                 655 

Gly Ile Phe Arg Arg Ile Ser Gln Ser Gly Gln Ser Gln His Pro Thr 
            660                 665                 670 

Arg Gln Gln Glu Pro Leu Pro Glu Arg Glu Pro Pro Thr Tyr Met Ser 
        675                 680                 685 

Lys Ser Asn Glu Ile Ser Ile Lys Val Pro Lys Ser His Ser Arg Thr 
    690                 695                 700 

Ile Ser Asp Tyr Ile Pro Ser Ala Arg Arg Tyr Pro Ser Tyr Val Pro 
705                 710                 715                 720 

Asn Ser Val Asp Val Lys Gln Lys Pro Ala Lys Asn Thr Thr Ile Ala 
                725                 730                 735 

Pro Pro Ile Arg Ser Val Ser Gln Lys Gln Asn Ser Asp Leu Pro Ala 
            740                 745                 750 

Leu Pro Gln Asn Ala Glu Leu Ile Val Gln Lys Gln Arg Gln Lys Leu 
        755                 760                 765 

Leu Gln Glu Asn Leu Asp Lys Leu Gln Ile Asn Asp Asn Asp Asn Asn 
    770                 775                 780 

Asn Val Asn Ala Val Val Asp Gly Ile Asn Asn Asp Asn Ser Asp His 
785                 790                 795                 800 

Tyr Leu Ser Val Pro Lys Gly Arg Lys Leu His Pro Ser Ala Arg Ala 
                805                 810                 815 

Lys Ser Val Gly His Ala Arg Arg Glu Ser Leu Lys Phe Thr Arg Pro 
            820                 825                 830 

Pro Ile Pro Ala Ala Leu Pro Pro Ser Asp Met Thr Asn Asp Asn Gly 
        835                 840                 845 

Phe Leu Gly Glu Ala Asn Lys Glu Arg Tyr Asn Pro Val Ser Ser Asn 
    850                 855                 860 

Phe Ser Thr Val Pro Glu Asp Ser Thr Thr Tyr Ser Asn Asp Thr Asn 
865                 870                 875                 880 

Asn Arg Leu Thr Ser Val Tyr Ser Gln Glu Leu Thr Glu Lys Gln Ile 
                885                 890                 895 

Leu Glu Glu Ala Ser Lys Ala Pro Pro Gly Ser Met Pro Ser Ile Asp 
            900                 905                 910 

Tyr Pro Lys Ser Met Phe Leu Lys Gly Phe Phe Ser Val Gln Thr Thr 
        915                 920                 925 

Ser Ser Lys Pro Leu Pro Ile Val Arg His Asn Ile Ile Ser Val Leu 
    930                 935                 940 

Thr Arg Met Asn Ile Asp Phe Lys Glu Val Lys Gly Gly Phe Ile Cys 
945                 950                 955                 960 

Val Gln Gln Arg Pro Ser Ile Glu Thr Ala Ala Val Pro Val Ile Thr 
                965                 970                 975 

Thr Thr Gly Val Gly Leu Asp Ser Gly Lys Ala Met Asp Leu Gln Asn 
            980                 985                 990 

Ser Leu Asp Ser Gln Leu Ser Ser Ser Tyr His Ser Thr Ala Ser Ser 
        995                1000                1005 

Ala Ser Arg Asn Ser Ser Ile Lys Arg Gln Gly Ser Tyr Lys Arg Gly 
   1010                1015                1020 

Gln Asn Asn Ile Pro Leu Thr Pro Leu Ala Thr Asn Thr His Gln Arg 
1025               1030                1035                1040 

Asn Ser Ser Ile Pro Met Ser Pro Asn Tyr Gly Asn Gln Ser Asn Gly 
               1045                1050                1055 

Thr Ser Gly Glu Leu Ser Ser Met Ser Leu Asp Tyr Val Gln Gln Gln 
           1060                1065                1070 

Asp Asp Ile Leu Thr Thr Ser Arg Ala Gln Asn Ile Asn Asn Val Asn 
       1075                1080                1085 

Gly Gln Thr Glu Gln Thr Asn Thr Ser Gly Ile Lys Glu Arg Pro Pro 
   1090                1095                1100 

Ile Lys Phe Glu Ile His Ile Val Lys Val Arg Ile Val Gly Leu Ala 
1105               1110                1115                1120 

Gly Val His Phe Lys Lys Val Ser Gly Asn Thr Trp Leu Tyr Lys Glu 
               1125                1130                1135 

Leu Ala Ser Tyr Ile Leu Lys Glu Leu Asn Leu 
           1140                1145 

 
           
             3  
             423  
             PRT  
             Schizosaccharomyces pombe  
           
            3 

Met Lys Pro Asn Thr Thr Asn Leu Arg Asn Glu Cys Trp Asp Thr Phe 
  1               5                  10                  15 

Ser Ile Pro Lys Arg Ser Gln Asn Ile Lys Ile Asn Gln Ser Thr Lys 
             20                  25                  30 

His Gln Arg Ser Ile Ser Asp Phe Val Gly Thr Ala Gly Pro Gly Arg 
         35                  40                  45 

Gln Val Gly Asn Trp Ile Ile Lys Lys Thr Ile Gly Ala Gly Ser Met 
     50                  55                  60 

Gly Lys Val Lys Leu Val Val Asn Ile Leu Thr Gly Glu Lys Ala Ala 
 65                  70                  75                  80 

Leu Lys Met Ile Pro Phe Thr Pro Asn Asn Thr Ser Gln Thr Val Arg 
                 85                  90                  95 

Val Gln Arg Glu Ala Leu Leu Gly Arg Leu Leu Arg His Pro Asn Ile 
            100                 105                 110 

Cys Arg Val Ile Asp Cys Ile Arg Thr Pro Ala Cys Thr Tyr Ile Leu 
        115                 120                 125 

Phe Glu Tyr Val Pro Gly Gly Gln Leu Leu Glu Tyr Ile Leu Ala Arg 
    130                 135                 140 

Gly Lys Leu Asp Glu Asp Leu Ala Arg Ser Phe Ala Met Gln Leu Ile 
145                 150                 155                 160 

Asn Ala Leu Val Tyr Leu His Lys Asn Phe Ile Val His Arg Asp Leu 
                165                 170                 175 

Lys Ile Glu Asn Val Leu Leu Thr Gln Asp Ser Arg Gln Val Lys Leu 
            180                 185                 190 

Ile Asp Phe Gly Leu Ser Asn Phe Tyr Ser Lys Asp Asp Leu Leu Arg 
        195                 200                 205 

Thr Tyr Cys Gly Ser Leu Tyr Phe Ala Ala Pro Glu Leu Leu Asp Ala 
    210                 215                 220 

Lys Pro Tyr Ile Gly Pro Glu Val Asp Val Trp Ser Leu Gly Val Val 
225                 230                 235                 240 

Ile Tyr Val Met Val Cys Gly Arg Val Pro Phe Asp Asp Val Ser Val 
                245                 250                 255 

Pro Met Leu His Ser Lys Ile Lys Ser Gly Lys Leu Glu Phe Pro Ser 
            260                 265                 270 

Tyr Ile Ser Glu Asp Cys Cys Ser Leu Ile Ala Ala Met Leu Asn Val 
        275                 280                 285 

Asn Pro Arg Lys Arg Cys Ser Leu Glu Gln Ala Ala Lys Phe Pro Trp 
    290                 295                 300 

Leu Lys Lys Asn Ser Phe Cys Leu Tyr Leu Pro Ile Pro Leu Thr Ser 
305                 310                 315                 320 

Ile Pro Ser Thr Pro Ser Ile Arg Ser His Val Phe Lys Pro Pro Phe 
                325                 330                 335 

Asn Leu Lys Val Leu Gln Leu Leu His Glu His Gly Leu Ala Ser Ile 
            340                 345                 350 

Pro Glu Leu Lys His Glu Leu Tyr Met Ala Tyr Ile Glu Arg Lys Thr 
        355                 360                 365 

Thr Ser Leu Val Cys Leu Tyr Leu Leu Gly Val Glu Ser Leu Ala Pro 
    370                 375                 380 

Ala Leu Arg Ile Pro Thr Ala Leu Pro Pro Val Tyr Ser Arg His Gln 
385                 390                 395                 400 

Arg His His Ser Glu Ile Leu Gly Ala Met Asp Leu Thr Glu Lys Ile 
                405                 410                 415 

Thr Ala Met Gln Cys Pro Pro 
            420 

 
           
             4  
             891  
             PRT  
             Schizosaccharomyces pombe  
           
            4 

Met Glu Tyr Arg Thr Asn Asn Val Pro Val Gly Asn Glu Thr Lys Ser 
  1               5                  10                  15 

Ala Ala Leu Asn Ala Leu Pro Lys Ile Lys Ile Ser Asp Ser Pro Asn 
             20                  25                  30 

Arg His His Asn Leu Val Asp Ala Phe Met Gln Ser Pro Ser Tyr Ser 
         35                  40                  45 

Thr Gln Pro Lys Ser Ala Val Glu Pro Leu Gly Leu Ser Phe Ser Pro 
     50                  55                  60 

Gly Tyr Ile Ser Pro Ser Ser Gln Ser Pro His His Gly Pro Val Arg 
 65                  70                  75                  80 

Ser Pro Ser Ser Arg Lys Pro Leu Pro Ala Ser Pro Ser Arg Thr Arg 
                 85                  90                  95 

Asp His Ser Leu Arg Val Pro Val Ser Gly His Ser Tyr Ser Ala Asp 
            100                 105                 110 

Glu Lys Pro Arg Glu Arg Arg Lys Val Ile Gly Asn Tyr Val Leu Gly 
        115                 120                 125 

Lys Thr Ile Gly Ala Gly Ser Met Gly Lys Val Lys Val Ala His His 
    130                 135                 140 

Leu Lys Thr Gly Glu Gln Phe Ala Ile Lys Ile Val Thr Arg Leu His 
145                 150                 155                 160 

Pro Asp Ile Thr Lys Ala Lys Ala Ala Ala Ser Ala Glu Ala Thr Lys 
                165                 170                 175 

Ala Ala Gln Ser Glu Lys Asn Lys Glu Ile Arg Thr Val Arg Glu Ala 
            180                 185                 190 

Ala Leu Ser Thr Leu Leu Arg His Pro Tyr Ile Cys Glu Ala Arg Asp 
        195                 200                 205 

Val Tyr Ile Thr Asn Ser His Tyr Tyr Met Val Phe Glu Phe Val Asp 
    210                 215                 220 

Gly Gly Gln Met Leu Asp Tyr Ile Ile Ser His Gly Lys Leu Lys Glu 
225                 230                 235                 240 

Lys Gln Ala Arg Lys Phe Val Arg Gln Ile Gly Ser Ala Leu Ser Tyr 
                245                 250                 255 

Leu His Gln Asn Ser Val Val His Arg Asp Leu Lys Ile Glu Asn Ile 
            260                 265                 270 

Leu Ile Ser Lys Thr Gly Asp Ile Lys Ile Ile Asp Phe Gly Leu Ser 
        275                 280                 285 

Asn Leu Tyr Arg Arg Gln Ser Arg Leu Arg Thr Phe Cys Gly Ser Leu 
    290                 295                 300 

Tyr Phe Ala Ala Pro Glu Leu Leu Asn Ala Gln Pro Tyr Ile Gly Pro 
305                 310                 315                 320 

Glu Val Asp Val Trp Ser Phe Gly Ile Val Leu Tyr Val Leu Val Cys 
                325                 330                 335 

Gly Lys Val Pro Phe Asp Asp Gln Asn Met Ser Ala Leu His Ala Lys 
            340                 345                 350 

Ile Lys Lys Gly Thr Val Glu Tyr Pro Ser Tyr Leu Ser Ser Asp Cys 
        355                 360                 365 

Lys Gly Leu Leu Ser Arg Met Leu Val Thr Asp Pro Leu Lys Arg Ala 
    370                 375                 380 

Thr Leu Glu Glu Val Leu Asn His Pro Trp Met Ile Arg Asn Tyr Glu 
385                 390                 395                 400 

Gly Pro Pro Ala Ser Phe Ala Pro Glu Arg Ser Pro Ile Thr Leu Pro 
                405                 410                 415 

Leu Asp Pro Glu Ile Ile Arg Glu Met Asn Gly Phe Asp Phe Gly Pro 
            420                 425                 430 

Pro Glu Lys Ile Val Arg Glu Leu Thr Lys Val Ile Ser Ser Glu Ala 
        435                 440                 445 

Tyr Gln Ser Leu Ala Lys Thr Gly Phe Tyr Ser Gly Pro Asn Ser Ala 
    450                 455                 460 

Asp Lys Lys Lys Ser Phe Phe Glu Phe Arg Ile Arg His Ala Ala His 
465                 470                 475                 480 

Asp Ile Glu Asn Pro Ile Leu Pro Ser Leu Ser Met Asn Thr Asp Ile 
                485                 490                 495 

Tyr Asp Ala Phe His Pro Leu Ile Ser Ile Tyr Tyr Leu Val Ser Glu 
            500                 505                 510 

Arg Arg Val Tyr Glu Lys Gly Gly Asn Trp Asn Arg Ile Ala Lys Thr 
        515                 520                 525 

Pro Val Ser Ser Val Pro Ser Ser Pro Val Gln Pro Thr Ser Tyr Asn 
    530                 535                 540 

Arg Thr Leu Pro Pro Met Pro Glu Val Val Ala Tyr Lys Gly Asp Glu 
545                 550                 555                 560 

Glu Ser Pro Arg Val Ser Arg Asn Thr Ser Leu Ala Arg Arg Lys Pro 
                565                 570                 575 

Leu Pro Asp Thr Glu Ser His Ser Pro Ser Pro Ser Ala Thr Ser Ser 
            580                 585                 590 

Ile Lys Lys Asn Pro Ser Ser Ile Phe Arg Arg Phe Ser Ser Arg Arg 
        595                 600                 605 

Lys Gln Asn Lys Ser Ser Thr Ser Thr Leu Gln Ile Ser Ala Pro Leu 
    610                 615                 620 

Glu Thr Ser Gln Ser Pro Pro Thr Pro Arg Thr Lys Pro Ser His Lys 
625                 630                 635                 640 

Pro Pro Val Ser Tyr Lys Asn Lys Leu Val Thr Gln Ser Ala Ile Gly 
                645                 650                 655 

Arg Ser Thr Ser Val Arg Glu Gly Arg Tyr Ala Gly Ile Ser Ser Gln 
            660                 665                 670 

Met Asp Ser Leu Asn Met Asp Ser Thr Gly Pro Ser Ala Ser Asn Met 
        675                 680                 685 

Ala Asn Ala Pro Pro Ser Val Arg Asn Asn Arg Val Leu Asn Pro Arg 
    690                 695                 700 

Gly Ala Ser Leu Gly His Gly Arg Met Ser Thr Ser Thr Thr Asn Arg 
705                 710                 715                 720 

Gln Lys Gln Ile Leu Asn Glu Thr Met Gly Asn Pro Val Asp Lys Asn 
                725                 730                 735 

Ser Thr Ser Pro Ser Lys Ser Thr Asp Lys Leu Asp Pro Ile Lys Pro 
            740                 745                 750 

Val Phe Leu Lys Gly Leu Phe Ser Val Ser Thr Thr Ser Thr Lys Ser 
        755                 760                 765 

Thr Glu Ser Ile Gln Arg Asp Leu Ile Arg Val Met Gly Met Leu Asp 
    770                 775                 780 

Ile Glu Tyr Lys Glu Ile Lys Gly Gly Tyr Ala Cys Leu Tyr Lys Pro 
785                 790                 795                 800 

Gln Gly Ile Arg Thr Pro Thr Lys Ser Thr Ser Val His Thr Arg Arg 
                805                 810                 815 

Lys Pro Ser Tyr Gly Ser Asn Ser Thr Thr Asp Ser Tyr Gly Ser Val 
            820                 825                 830 

Pro Asp Thr Val Pro Leu Asp Asp Asn Gly Glu Ser Pro Ala Ser Asn 
        835                 840                 845 

Leu Ala Phe Glu Ile Tyr Ile Val Lys Val Pro Ile Leu Ser Leu Arg 
    850                 855                 860 

Gly Val Ser Phe His Arg Ile Ser Gly Asn Ser Trp Gln Tyr Lys Thr 
865                 870                 875                 880 

Leu Ala Ser Arg Ile Leu Asn Glu Leu Lys Leu 
                885                 890 

 
           
             5  
             1212  
             PRT  
             Candida albicans  
           
            5 

Met Asn Asn Gln Asp Pro Asp Ser Gln Tyr His Asn Lys Lys Val Tyr 
  1               5                  10                  15 

Pro Pro Asn Leu Pro Ser Ile Pro Pro Pro Pro Gln Gln Pro Leu Ser 
             20                  25                  30 

Gly Arg Pro Ala Thr Pro Arg Met Leu Arg Ser Ile Ser Gly Thr Leu 
         35                  40                  45 

Lys Ser Lys Thr Glu Leu Ala His Ser Asp Lys Gly Gln Glu Ser Asn 
     50                  55                  60 

Asn Glu Thr Lys Asn Ser Asn Ser Pro His Tyr Val Pro Asp Thr His 
 65                  70                  75                  80 

Thr Arg Gln Pro Pro Pro Glu Ser Leu Lys Ser Asn Ile Gln Ala Pro 
                 85                  90                  95 

Thr Ala Val His Gly Asn Gln Gln Lys Gly Ser Leu Leu Pro Pro Pro 
            100                 105                 110 

Ser Ile Pro Asn Pro Asn Thr Met Lys Pro Ala Pro Thr Pro Thr Gly 
        115                 120                 125 

Val Asp Gln Pro Pro Ala Lys Gln Lys Pro Ser Pro Ala Pro Lys Gln 
    130                 135                 140 

Pro Gln Pro Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Phe His 
145                 150                 155                 160 

Arg Lys Ser Ile Gly Asp Trp Asn Phe Val Lys Thr Ile Gly Ala Gly 
                165                 170                 175 

Ser Met Gly Lys Val Lys Leu Ala Gln His Asn Ala Thr His Glu Ile 
            180                 185                 190 

Cys Ala Val Lys Ile Ile Pro Arg Ala Ala Lys Leu Tyr Gln Arg Ala 
        195                 200                 205 

His Ala Asn Asp Pro Pro Pro Gln Thr Thr Gln Glu Ala Ala Gln Arg 
    210                 215                 220 

His Lys Glu Phe Glu Lys Glu Val Ala Arg Asp Arg Arg Thr Ile Arg 
225                 230                 235                 240 

Glu Gly Ala Leu Gly Arg Leu Leu Tyr His Pro Phe Ile Cys Arg Leu 
                245                 250                 255 

Tyr Glu Met Val Pro Met Thr Asn His Tyr Tyr Met Leu Phe Glu Tyr 
            260                 265                 270 

Ile Glu Gly Gly Gln Met Leu Asp Tyr Ile Val Ala His Gly Ser Leu 
        275                 280                 285 

Lys Glu Arg His Ala Arg Lys Phe Ala Arg Gly Ile Ala Ser Ala Leu 
    290                 295                 300 

Asp Tyr Cys His Arg Asn Asn Val Val His Arg Asp Leu Lys Ile Glu 
305                 310                 315                 320 

Asn Ile Met Ile Asn Glu Lys Gly Asp Ile Lys Ile Ile Asp Phe Gly 
                325                 330                 335 

Leu Ser Asn Leu Tyr Ala Pro Lys Asn Leu Leu Lys Thr Tyr Cys Gly 
            340                 345                 350 

Ser Leu Tyr Phe Ala Ala Pro Glu Leu Leu Ser Ala Lys Pro Tyr Ile 
        355                 360                 365 

Gly Pro Glu Val Asp Val Trp Ser Phe Gly Val Val Leu Tyr Val Leu 
    370                 375                 380 

Val Cys Gly Lys Val Pro Phe Asp Asp Gln Ser Val Ser Val Leu His 
385                 390                 395                 400 

Glu Lys Ile Lys Lys Gly Asn Val Glu Tyr Pro Ala Phe Leu Ser Arg 
                405                 410                 415 

Glu Cys Val Ser Leu Leu Ser Arg Met Leu Val Val Asp Pro Thr Lys 
            420                 425                 430 

Arg Ala Ser Leu Tyr Glu Val Cys Ser His Pro Trp Met Asn Lys Gly 
        435                 440                 445 

Tyr Asp Tyr Lys Val Asn Asn Tyr Leu Pro Arg Arg Glu Pro Leu Arg 
    450                 455                 460 

Leu Pro Leu Asp Pro Glu Ile Ile Lys Thr Ile Ala Asn Phe Glu Leu 
465                 470                 475                 480 

Gly Thr Val Gln Gly Val Ala Asp Glu Leu Thr Ser Ile Leu Thr Ser 
                485                 490                 495 

Val Glu Tyr Gln Met Ser Cys Glu Asn Trp Tyr Lys Ile Thr Glu Thr 
            500                 505                 510 

Gly Arg Glu Tyr Ala Ser Ser Gln Asn Ala Gln Ile Leu Pro Asp Pro 
        515                 520                 525 

Thr Gly Gly Phe His Pro Leu Val Ser Ile Tyr Tyr Leu Val Asp Glu 
    530                 535                 540 

Met Arg Lys Arg Lys Lys Ala Lys Glu Glu Ala Leu Lys Ala Gln Arg 
545                 550                 555                 560 

Arg Ala Gln Val Pro Thr Ile Ala Val Pro Thr Pro Lys Gln Gln Gln 
                565                 570                 575 

Gln Gln Gln Pro Gln Pro Ala Gln Pro Gln Pro Gln Pro Gln Pro Glu 
            580                 585                 590 

Val Ser Gln Pro Leu Pro Glu Pro Lys Pro Val Pro Pro Glu Glu Ile 
        595                 600                 605 

Ile Asn Pro Ala Val Ala Thr Gln Ala Gln Ala Asn Met Thr Ala Pro 
    610                 615                 620 

Lys Ile Val Glu Thr Phe Ser Glu Thr Pro Gln Arg Thr Leu Asp Pro 
625                 630                 635                 640 

Ser Lys Gln Ser Val Asp Glu Lys Pro Ser Ala Pro Gly Pro Ser Ile 
                645                 650                 655 

Ala Val Pro Glu Gln Ala His Thr Thr Ser Val Pro Ser Ser Phe Val 
            660                 665                 670 

Lys Thr Gln Thr Ser Ile Asp Glu Asp Gln Leu Ser Ile Pro Glu Gln 
        675                 680                 685 

Gln Ser Pro Arg Thr Ser Thr Pro Gln Thr Leu Asp Pro Ala Lys Val 
    690                 695                 700 

Val Gly Gly Ser Ser Gly Ser Ala Ile Ser Ala Pro Asn Ala Gly Ser 
705                 710                 715                 720 

Gly Ala Gly Phe Asn Ser Leu Leu Arg Arg Leu Ser Ser Lys Lys Tyr 
                725                 730                 735 

Lys Gly Ala Ser Ser Pro Lys Arg Ser Thr Ser Pro Ser Pro Asn Val 
            740                 745                 750 

Glu Gly Leu Ser Pro Gln Pro Thr Lys Ala Asp Pro Met Val Arg Arg 
        755                 760                 765 

Gly Val Ser Met Lys Val Thr Ala Lys Glu Lys Gln Thr Asn Thr Arg 
    770                 775                 780 

Pro Pro Lys Ser Glu Leu Ile Lys Lys Lys Pro Gln His Gly Arg Ser 
785                 790                 795                 800 

Ser Ser Thr Ser Asn Lys Met Gln Gly Phe Ile Pro Val Glu Tyr Leu 
                805                 810                 815 

Pro Pro Leu Pro Thr Ile Asp Thr Asn Thr Asn Thr Ile Val Ser Asp 
            820                 825                 830 

Gly Ala Lys Gln Gln Asn Leu Thr Val Pro Ser Thr Ala Arg His Met 
        835                 840                 845 

His Pro Thr Ala Arg Ala Lys Ser Val Gly Gly Gly His Met Arg Lys 
    850                 855                 860 

Asp Ser Tyr Gly Arg Val Ser His Gly Ser Gln Asn Pro Leu Pro Pro 
865                 870                 875                 880 

Leu Pro Thr Ser Met Ala Ser Gln Asn Ser Gln Glu Val Val Gly Lys 
                885                 890                 895 

Asp Thr Ser Glu Gly Phe Phe Asp Asp Val Gln Leu Asp Asp Val Gly 
            900                 905                 910 

Tyr Gln Glu Val Pro Gln Leu Thr Glu Ser Glu Ile Ile Glu Gln Tyr 
        915                 920                 925 

Asn Ile Ser Lys Pro Asn Ser Met Pro Ser Ile Glu His Cys Lys Thr 
    930                 935                 940 

Leu Phe Leu Lys Gly Phe Phe Ser Val Gln Thr Thr Ser Ala Lys Pro 
945                 950                 955                 960 

Leu Pro Val Ile Arg Tyr Asn Ile Ile Asn Val Leu Ser Lys Leu Gly 
                965                 970                 975 

Val Lys Phe Gln Glu Val Lys Gly Gly Phe Val Cys Met His Thr Pro 
            980                 985                 990 

Ser Val Gln Pro Ser His Ser Asn Glu Leu Asp Glu Glu Asn Lys Leu 
        995                1000                1005 

Tyr Gly Asp Ala Phe Lys Ser Lys Ser Ser Asp Ser Phe Glu Ala Ala 
   1010                1015                1020 

Glu Pro Glu Gly Ser Lys Thr Pro Ser Arg Gln Pro Ser Leu Gln Leu 
1025               1030                1035                1040 

Pro Ser His Thr Pro Thr Thr Pro Ser Gly Pro Lys Ser His Lys Ser 
               1045                1050                1055 

Ser Asn Ser Ile Gly Ser Ile Gly Gly Asn Val Pro Arg Arg Lys Phe 
           1060                1065                1070 

Ser Ile Gly Asn Ala Phe Asn Thr Tyr Arg Lys Lys Asn Gly Ser Gln 
       1075                1080                1085 

Val Met Met Pro Pro Asn Thr Pro Ala Thr Ala Lys Val Ile His Gly 
   1090                1095                1100 

Leu Tyr Asp Asp Asp Asp Lys Glu Arg Asn Gly Glu Asp Asp Asp Asp 
1105               1110                1115                1120 

Glu Asp Asp Tyr Gly Tyr Asp Asp Ser Ala Asp Ser Leu Asn Gly Tyr 
               1125                1130                1135 

Gly Gly Gly Ser Asp Met Leu Ile Ser Ser Arg Ile Glu Gln Arg Ala 
           1140                1145                1150 

Lys His Gln Arg Thr Val Ser Ser Ser Ser Gln Lys Ala Ser Lys Ser 
       1155                1160                1165 

Pro Leu Lys Phe Glu Ile His Ile Val Lys Val Pro Leu Val Gly Leu 
   1170                1175                1180 

Tyr Gly Val Gln Phe Lys Lys Ile Leu Gly Asn Thr Trp Asn Tyr Lys 
1185               1190                1195                1200 

Thr Leu Ala Ser Gln Ile Leu Asn Glu Met Asn Leu 
               1205                1210 

 
           
             6  
             800  
             PRT  
             Saccharomyces cerevisiae  
           
            6 

Met Ala Ser Val Pro Lys Arg His Thr Tyr Gly Gly Asn Val Val Thr 
  1               5                  10                  15 

Asp Arg Asp Arg His Ser Leu Gln Arg Asn Asn Glu Ile Leu His Pro 
             20                  25                  30 

Ile His Lys Asn Gln Arg Lys His Ala Thr Phe Gly Pro Tyr Ile Ile 
         35                  40                  45 

Gly Ser Thr Leu Gly Glu Gly Glu Phe Gly Lys Val Lys Leu Gly Trp 
     50                  55                  60 

Thr Lys Ala Ser Ser Ser Asn Glu Val Pro Lys Gln Val Ala Ile Lys 
 65                  70                  75                  80 

Leu Ile Arg Arg Asp Thr Ile Lys Lys Asp Ala Asp Lys Glu Ile Lys 
                 85                  90                  95 

Ile Tyr Arg Glu Ile Asn Ala Leu Lys His Leu Thr His Pro Asn Ile 
            100                 105                 110 

Ile Tyr Leu Glu Glu Val Leu Gln Asn Ser Lys Tyr Ile Gly Ile Val 
        115                 120                 125 

Leu Glu Phe Val Ser Gly Gly Glu Phe Tyr Lys Tyr Ile Gln Arg Lys 
    130                 135                 140 

Arg Arg Leu Lys Glu Ser Ser Ala Cys Arg Leu Phe Ala Gln Leu Ile 
145                 150                 155                 160 

Ser Gly Val Asn Tyr Met His Tyr Lys Gly Leu Val His Arg Asp Leu 
                165                 170                 175 

Lys Leu Glu Asn Leu Leu Leu Asp Lys His Glu Asn Leu Val Ile Thr 
            180                 185                 190 

Asp Phe Gly Phe Val Asn Glu Phe Phe Glu Asp Asn Glu Leu Met Lys 
        195                 200                 205 

Thr Ser Cys Gly Ser Pro Cys Tyr Ala Ala Pro Glu Leu Val Val Ser 
    210                 215                 220 

Thr Lys Ala Tyr Glu Ala Arg Lys Ala Asp Val Trp Ser Cys Gly Val 
225                 230                 235                 240 

Ile Leu Tyr Ala Met Leu Ala Gly Tyr Leu Pro Trp Asp Asp Asp His 
                245                 250                 255 

Glu Asn Pro Thr Gly Asp Asp Ile Ala Arg Leu Tyr Lys Tyr Ile Thr 
            260                 265                 270 

Gln Thr Pro Leu Lys Phe Pro Glu Tyr Ile Thr Pro Ile Pro Arg Asp 
        275                 280                 285 

Leu Leu Arg Arg Ile Leu Val Pro Asn Pro Arg Arg Arg Ile Asn Leu 
    290                 295                 300 

Gln Thr Ile Lys Arg His Val Trp Leu Lys Pro His Glu Ala Phe Leu 
305                 310                 315                 320 

Ser Ile Gln Pro Asn Tyr Trp Asp Glu His Leu Gln Lys Glu Arg Pro 
                325                 330                 335 

Lys Pro Pro Asn Lys Gly Asp Val Gly Arg His Ser Thr Tyr Ser Ser 
            340                 345                 350 

Ser Ala Ser Ser Tyr Ser Lys Ser Arg Asp Arg Asn Ser Leu Ile Ile 
        355                 360                 365 

Glu Ser Thr Leu Glu Gln His Arg Met Ser Pro Gln Leu Ala Thr Ser 
    370                 375                 380 

Arg Pro Ala Ser Pro Thr Phe Ser Thr Gly Ser Lys Val Val Leu Asn 
385                 390                 395                 400 

Asp Thr Lys Asn Asp Met Lys Glu Ser Asn Ile Asn Gly Glu Arg Thr 
                405                 410                 415 

Ser Ala Ser Cys Arg Tyr Thr Arg Asp Ser Lys Gly Asn Gly Gln Thr 
            420                 425                 430 

Gln Ile Glu Gln Val Ser Ala Arg His Ser Ser Arg Gly Asn Lys His 
        435                 440                 445 

Thr Ser Val Ala Gly Leu Val Thr Ile Pro Gly Ser Pro Thr Thr Ala 
    450                 455                 460 

Arg Thr Arg Asn Ala Pro Ser Ser Lys Leu Thr Glu His Val Lys Asp 
465                 470                 475                 480 

Ser Ser Gln Thr Ser Phe Thr Gln Glu Glu Phe His Arg Ile Gly Asn 
                485                 490                 495 

Tyr His Val Pro Arg Ser Arg Pro Arg Pro Thr Ser Tyr Tyr Pro Gly 
            500                 505                 510 

Leu Ser Arg Asn Thr Ala Asp Asn Ser Leu Ala Asp Ile Pro Val Asn 
        515                 520                 525 

Lys Leu Gly Ser Asn Gly Arg Leu Thr Asp Ala Lys Asp Pro Val Pro 
    530                 535                 540 

Leu Asn Ala Ile His Asp Thr Asn Lys Ala Thr Ile Ser Asn Asn Ser 
545                 550                 555                 560 

Ile Met Leu Leu Ser Glu Gly Pro Ala Ala Lys Thr Ser Pro Val Asp 
                565                 570                 575 

Tyr His Tyr Ala Ile Gly Asp Leu Asn His Gly Asp Lys Pro Ile Thr 
            580                 585                 590 

Glu Val Ile Asp Lys Ile Asn Lys Asp Leu Thr His Lys Ala Ala Glu 
        595                 600                 605 

Asn Gly Phe Pro Arg Glu Ser Ile Asp Pro Glu Ser Thr Ser Thr Ile 
    610                 615                 620 

Leu Val Thr Lys Glu Pro Thr Asn Ser Thr Asp Glu Asp His Val Glu 
625                 630                 635                 640 

Ser Gln Leu Glu Asn Val Gly His Ser Ser Asn Lys Ser Asp Ala Ser 
                645                 650                 655 

Ser Asp Lys Asp Ser Lys Lys Ile Tyr Glu Lys Lys Arg Phe Ser Phe 
            660                 665                 670 

Met Ser Leu Tyr Ser Ser Leu Asn Gly Ser Arg Ser Thr Val Glu Ser 
        675                 680                 685 

Arg Thr Ser Lys Gly Asn Ala Pro Pro Val Ser Ser Arg Asn Pro Ser 
    690                 695                 700 

Gly Gln Ser Asn Arg Ser Asn Ile Lys Ile Thr Gln Gln Gln Pro Arg 
705                 710                 715                 720 

Asn Leu Ser Asp Arg Val Pro Asn Pro Asp Lys Lys Ile Asn Asp Asn 
                725                 730                 735 

Arg Ile Arg Asp Asn Ala Pro Ser Tyr Ala Glu Ser Glu Asn Pro Gly 
            740                 745                 750 

Arg Ser Val Arg Ala Ser Val Met Val Ser Thr Leu Arg Glu Glu Asn 
        755                 760                 765 

Arg Ser Glu Leu Ser Asn Glu Gly Asn Asn Val Glu Ala Gln Thr Ser 
    770                 775                 780 

Thr Ala Arg Lys Val Leu Asn Phe Phe Lys Arg Arg Ser Met Arg Val 
785                 790                 795                 800 

 
           
             7  
             865  
             PRT  
             Saccharomyces cerevisiae  
           
            7 

Met Ser Tyr Thr Asn Lys Arg His Thr Tyr Tyr Gly Gly Phe Thr Asn 
  1               5                  10                  15 

Asp Leu Ser Asp Thr Phe Gln Tyr Pro Gln Arg Thr Asp Glu Gln Arg 
             20                  25                  30 

Arg Lys His Val Thr Phe Gly Pro Tyr Ile Leu Gly Ser Thr Leu Gly 
         35                  40                  45 

Glu Gly Glu Phe Gly Lys Val Lys Leu Gly Trp Pro Lys Asn Phe Ser 
     50                  55                  60 

Asn Ser Ser Asn Ser Thr Phe Asp Phe Pro Lys Gln Val Ala Ile Lys 
 65                  70                  75                  80 

Leu Ile Lys Arg Asp Ser Ile Ser Asn Asp Tyr Arg Lys Glu Val Lys 
                 85                  90                  95 

Ile Tyr Arg Glu Ile Asn Ala Leu Lys His Leu Ser His Pro Asn Ile 
            100                 105                 110 

Val Lys Leu Glu Glu Val Leu Gln Asn Ser Arg Tyr Ile Gly Ile Val 
        115                 120                 125 

Leu Glu Tyr Ala Cys Gly Gly Glu Phe Tyr Lys Tyr Ile Gln Lys Lys 
    130                 135                 140 

Arg Arg Leu Lys Glu Met Asn Ala Cys Arg Leu Phe Ser Gln Leu Ile 
145                 150                 155                 160 

Ser Gly Val His Tyr Ile His Ser Lys Gly Leu Val His Arg Asp Leu 
                165                 170                 175 

Lys Leu Glu Asn Leu Leu Leu Asp Lys Asn Glu Asn Leu Val Ile Thr 
            180                 185                 190 

Asp Phe Gly Phe Val Asn Glu Phe Cys Ser Arg Asn Glu Leu Met Lys 
        195                 200                 205 

Thr Ser Cys Gly Ser Pro Cys Tyr Ala Ala Pro Glu Leu Val Ile Ser 
    210                 215                 220 

Ala Glu Pro Tyr Glu Ala Arg Lys Ala Asp Ile Trp Ser Cys Gly Val 
225                 230                 235                 240 

Ile Leu Tyr Ala Ile Leu Ala Gly Tyr Leu Pro Trp Asp Asp Asp Pro 
                245                 250                 255 

Asn Asn Pro Glu Gly Ser Asp Ile Gly Arg Leu Tyr Asn Tyr Ile Asn 
            260                 265                 270 

Ser Thr Pro Leu Lys Phe Pro Asp Tyr Ile Leu Pro Ile Pro Arg Asp 
        275                 280                 285 

Leu Leu Arg Arg Met Leu Val Ser Asp Pro Lys Lys Arg Ile Asn Leu 
    290                 295                 300 

Lys Gln Ile Lys Lys His Glu Trp Leu Lys Pro His Ser Ser Phe Leu 
305                 310                 315                 320 

Ser Ile Thr Pro Asp Glu Trp Asp Lys Leu Asn Asn Thr Gln Ser Val 
                325                 330                 335 

Phe Arg Leu Ala Lys Pro Arg Arg Arg Tyr Gly Ser Arg Pro Gln Ser 
            340                 345                 350 

Ser Cys Ser Thr Ser Ser Leu Gly Ser Arg Ser Asp Lys Arg Asp Ser 
        355                 360                 365 

Leu Val Ile Asp Ser Thr Leu Ile Thr Phe Pro Ala Pro Pro Gln Glu 
    370                 375                 380 

Ser Gln Asn His Ile Ile Thr Arg Pro Ala Ser Ile Ala Ser Asp Gln 
385                 390                 395                 400 

Arg Leu Ser Pro Ile Arg Arg Ser Asn Arg His Asn Arg Ser Asn Ser 
                405                 410                 415 

Ala Ala Ser Val Ala Leu Gln Ala Val Val Asn Ala Asp Arg Glu Tyr 
            420                 425                 430 

Val Leu Ser His Glu Gln Ser Leu Ser Pro Val Gln Asn Ile Arg Gln 
        435                 440                 445 

Thr Thr Gly Asn Met Thr Ala Ser Leu Ser Pro Pro Pro Ala Ile Ser 
    450                 455                 460 

Pro Gly Asp Ile Ile Ile Glu Thr Thr Pro Ile Lys Arg Asn Thr Ile 
465                 470                 475                 480 

Ser Gly Ser Ser Ile Val Pro Ser Leu Glu Glu Glu Ser Ser Thr Thr 
                485                 490                 495 

Met Gln Thr Ser Lys Ile Gln Pro Asn Asn Met Ala Ser Ser Gln Asn 
            500                 505                 510 

His Gln Tyr Asn Lys Asn Lys Thr Gln Asn Ser Leu Gln Ser Ala Lys 
        515                 520                 525 

Asn Phe Tyr Arg Thr Ser Ser Ser Ser His Thr Lys Pro Arg Pro Thr 
    530                 535                 540 

Ser Tyr His Pro Gly Ser Tyr Thr Thr Pro Pro Tyr Asn Ser Asn Thr 
545                 550                 555                 560 

Leu Ser Ile Tyr Glu Ile Asn Glu Lys Ala Lys Ser Ser Ala Ser Ser 
                565                 570                 575 

Gln Thr Leu Asn Gln Arg Asp Thr Ser Pro Phe Asp Ser Thr Pro Tyr 
            580                 585                 590 

Leu Ala Leu Asp Thr Cys Ile Thr Ser Ser Ser Ser Ile Glu Ser Ser 
        595                 600                 605 

Pro Lys Leu Ile Thr His Gly Gln Phe Ser Val Ala Lys Pro Ser Val 
    610                 615                 620 

Asp Leu Gln Ser Val Ser Gly Asp Leu Ile Lys Tyr Lys Arg Asp Ala 
625                 630                 635                 640 

Asp Val Val Thr Arg Ile Tyr Asp Glu Lys Tyr Lys Gln Lys Arg Lys 
                645                 650                 655 

Ser Leu Arg Tyr Ser Gly Ile Phe Ser Asp Ile Ser Cys Asp Thr Val 
            660                 665                 670 

Thr Glu Glu Ser Asp Glu Leu Arg Pro Pro Glu Ser Pro Leu Gln Gln 
        675                 680                 685 

His Glu Gly Gln Glu Ser Ile Asp Lys Ala Lys Thr Glu Asp Thr Ser 
    690                 695                 700 

Glu Lys Gly Ser Lys Ser Ser Asn Ile Ala Lys Ala Thr Ala Gln Lys 
705                 710                 715                 720 

His Val Asn Asn His Leu Glu Arg Ser Leu Asn Glu Ala Glu Ser Thr 
                725                 730                 735 

Lys Lys Arg Phe Ser Phe Leu Ser Leu Tyr Ser Tyr Asp Thr Ser Lys 
            740                 745                 750 

Ser Ser Leu Tyr Ser Ser Met Asp Ser Lys Arg Lys Pro Ser Pro Pro 
        755                 760                 765 

Ser Gln Arg Arg Pro Lys Lys Asp Asp Ser Tyr Gln Thr Asn Ser Lys 
    770                 775                 780 

Asn His Tyr Ile Thr Ala Ser Asn Met Gln Thr Ser His Gln Val Ser 
785                 790                 795                 800 

Lys Asp Leu Pro Ala Pro Thr Met Val Gln Asn Lys Cys Thr Leu Glu 
                805                 810                 815 

Thr Lys Lys Ala Val Arg Ser Asn Arg Ser Ser Ile Met Val Ser Glu 
            820                 825                 830 

Val Asn Lys Ala Ser Val Asp Asn Lys Ala Ala Gln Ser Pro Glu His 
        835                 840                 845 

Ser Thr Ala Lys Arg Val Leu Gly Phe Phe Lys Arg Arg Ser Met Lys 
    850                 855                 860 

Ile 
865 

 
           
             8  
             994  
             PRT  
             Candida albicans  
           
            8 

Met Ser Thr Ile Pro Ser Gln Val Glu Ile Asn Phe Asn Lys Ile His 
  1               5                  10                  15 

Gln Arg Ser Asn Ser Ser Ser Ser Thr Ser Ser Tyr Arg Ile Pro Ser 
             20                  25                  30 

Gly Asn Ser Cys Ile Pro Arg Thr Val Glu Met Pro Ser Leu Pro Pro 
         35                  40                  45 

Thr Ser Thr His His Gln His Gln Gln Met Pro Ser Ser Ser Ser His 
     50                  55                  60 

Ala His Ile Ala Lys Lys Ile His Arg Glu Val Arg Phe Gly Ala Tyr 
 65                  70                  75                  80 

Ile Leu Gly Ser Thr Leu Gly Glu Gly Glu Phe Gly Lys Val Lys Leu 
                 85                  90                  95 

Gly Trp Arg Lys Asp Gly Lys His Pro Ser Gln Val Ala Ile Lys Leu 
            100                 105                 110 

Ile Lys Arg Ser Thr Ile Thr Lys Asp Ser Asp Ser Glu Ile Lys Ile 
        115                 120                 125 

His Arg Glu Ile Asn Ser Leu Lys Leu Leu Asn His Pro Asn Ile Val 
    130                 135                 140 

Asn Leu Val Glu Val Met Lys Ser Gly Lys Tyr Ile Gly Ile Val Leu 
145                 150                 155                 160 

Glu Tyr Ala Ser Gly Gly Glu Leu Phe Asp Tyr Ile Leu Gln His Lys 
                165                 170                 175 

Tyr Leu Lys Glu Asn Val Ala Lys Lys Leu Phe Ala Gln Leu Val Ser 
            180                 185                 190 

Gly Val Asp Tyr Met His Ala Lys Gly Leu Ile His Arg Asp Leu Lys 
        195                 200                 205 

Leu Glu Asn Leu Leu Leu Asp Lys His Arg Asn Val Ile Ile Ser Asp 
    210                 215                 220 

Phe Gly Phe Val Asn Ser Tyr Asn Arg Asp Lys Asn Asp Leu Met Lys 
225                 230                 235                 240 

Thr Ser Cys Gly Ser Pro Cys Tyr Ala Ala Pro Glu Leu Val Leu Ser 
                245                 250                 255 

Gln Thr Ala Tyr Glu Gly Arg Lys Val Asp Ile Trp Ser Leu Gly Val 
            260                 265                 270 

Ile Leu Tyr Ala Met Leu Ala Gly Tyr Leu Pro Phe Asp Asp Asp Pro 
        275                 280                 285 

Glu Asn Glu Asp Gly Ser Asp Ile Ile Lys Leu Tyr His Tyr Ile Cys 
    290                 295                 300 

Lys Thr Pro Leu Thr Phe Pro Glu Tyr Val Ser Pro Leu Ala Arg Asp 
305                 310                 315                 320 

Leu Leu Arg Lys Ile Ile Val Ser Asp Pro Lys Lys Arg Ile Ser Ile 
                325                 330                 335 

Asp Asp Ile Arg Asn His Pro Trp Leu Ser Ser His Ala Asn Leu Leu 
            340                 345                 350 

Ser Ile Arg Gln Pro Glu Trp Asp Lys Val His Ser Glu Lys Gln Gln 
        355                 360                 365 

Pro Ile Ala Val Glu Pro Pro Gln Pro Asn Lys Arg Tyr Ser Met Ile 
    370                 375                 380 

Asn Glu Arg Thr Asn Ser Ser Ser Leu Met Ser Pro Ala Pro Arg Val 
385                 390                 395                 400 

Thr His Thr Gln Pro Leu Ser Ser His Ala Arg Ser Tyr Ser Ser Thr 
                405                 410                 415 

Ser Ile Ser Leu Leu Tyr Ser Ser Pro Ser Ala Thr Pro Ser Met Ala 
            420                 425                 430 

Asn Ala Val Thr Asn Gly Glu Gly Ala Thr Thr Thr Thr Thr Asn Gly 
        435                 440                 445 

Ser Ile Asn Glu Ser Asn Asp Thr Leu Gln Leu Ser Gly Thr Pro Ser 
    450                 455                 460 

Pro Lys Lys Pro Ser Thr Val Ser Pro Val Arg Gly His Gln Lys Ser 
465                 470                 475                 480 

Ala Ser Ile Ser Asn Ser Tyr Ser Ser Ala Ser Ile Ala Leu Lys Ala 
                485                 490                 495 

Val Val His Glu Glu Asn Arg Leu His Asn His Gln Gln Ser Gln Gln 
            500                 505                 510 

Tyr Ile Pro Arg Ser Ser Thr Ile Ser Thr Ile Val Glu Ser Pro Thr 
        515                 520                 525 

Lys Ala Asn Thr Ala Thr Glu Thr Glu Thr Thr Asp Gly His Lys Ile 
    530                 535                 540 

Leu Leu Pro Pro Pro Ser Lys Asp Ala Gln Lys Leu Pro His Ala Ala 
545                 550                 555                 560 

Lys Lys Pro Arg Pro Thr Ser Tyr His Pro Ser Ser Met Ser Ser Ala 
                565                 570                 575 

Leu Ile His Asn Asn Gln Asn Pro Thr Asp Val Leu Lys Met Pro Ser 
            580                 585                 590 

Pro Ile Asn Phe Pro Met Thr Gln Phe Ile Ser Thr Ser Pro Pro Lys 
        595                 600                 605 

Ser Asn Gly Ser Leu Asn Asp Ser Gly Asn Phe Thr Asn Cys Ser Pro 
    610                 615                 620 

Lys Ala Thr Ser Arg Arg Asn Ser Val Val Thr His Val His Val Asn 
625                 630                 635                 640 

Gly Val Leu Ser Lys Glu Asn Leu Ile His Ser Ser Ser Ser Pro Asp 
                645                 650                 655 

Asn Lys Arg Asn Ser Val Leu Ser Tyr Leu Glu Asp Lys Ile Asp Thr 
            660                 665                 670 

Leu Glu Leu Thr Glu Ser His Ser Pro Ser Lys Asn Thr Phe Glu Glu 
        675                 680                 685 

Ile Val Asp Ala Ala Ile Ala Thr Pro Glu Ile Asn Gln Val Pro Val 
    690                 695                 700 

Phe Asp Ser Gln Thr Ser Pro Asn Gly Ile Gly Leu Asp Ile Lys His 
705                 710                 715                 720 

Lys Glu Phe Asp Glu Thr Ser Leu Val Val Glu Lys Lys Ser Lys Glu 
                725                 730                 735 

Thr Val Ser Asp Ser Lys Ser Glu Glu Ser Thr Lys Glu Thr Gln Gln 
            740                 745                 750 

Gln Glu Asn Val Val Met Tyr Glu Pro Ile Val Pro Val Glu Glu Tyr 
        755                 760                 765 

Ile Lys Lys Pro Glu Glu Val Asn Ser Val Glu Ala Lys Gln Pro Glu 
    770                 775                 780 

Glu Val Lys Ser Glu Asp Lys Ser Leu Gln Gly Gln Lys Ser Gln Gln 
785                 790                 795                 800 

Gln Gln Gln Gln Pro Glu Lys His Ser Ala Asp Ile Gly Lys Thr Lys 
                805                 810                 815 

Val Asp Leu Lys Lys Ser Ala Ser Gln Lys Lys Lys Val Lys Glu Glu 
            820                 825                 830 

Ser Ile Lys Lys Gln Lys Asp Val Asp Ser Lys Pro Ile Glu Arg Arg 
        835                 840                 845 

His Thr Ile Ala Ala Arg Arg His His Asn Asp Glu Asn Lys Glu Asn 
    850                 855                 860 

Lys Asp Val Lys Lys Arg Asn Arg Phe Ser Leu Leu Ser Phe Tyr Ser 
865                 870                 875                 880 

Ser Tyr Asn Ser Ser Asn Ser Asn Val Ser Leu Ala Thr Ser Lys Val 
                885                 890                 895 

Pro Ser Asn Ser Glu Asn Asn Thr Thr Val Leu Lys Pro Thr Ser Met 
            900                 905                 910 

Asn Thr Thr Arg Lys Val Leu Glu Pro Ser Asn Glu Thr Asn Ile Met 
        915                 920                 925 

Arg Lys Glu Thr Lys Gln Thr Asn Ser Asn Gly Ser Thr Thr Ser Lys 
    930                 935                 940 

Ser Thr Thr Ser Ser Ser Ser Ser Ser Ala Pro Ala Ala Ser Ser Ser 
945                 950                 955                 960 

Ser Ser Ser Ser Thr Ser Lys Arg Ala Ser Thr Ala Thr Lys Glu Thr 
                965                 970                 975 

Ser Ala Ala Arg Lys Val Met Asp Phe Phe Lys Arg Arg Ser Val Arg 
            980                 985                 990 

Val Gly 

 
           
             9  
             629  
             PRT  
             Schizosaccharomyces pombe  
           
            9 

Met Asn Ala Gln Pro Phe His Asn Asn Thr Ser Asp Val Gln Ser Phe 
  1               5                  10                  15 

Gln Asp Ile Ile Ser Asn Ser Tyr Gln Lys Pro Leu Ser Leu Val Asp 
             20                  25                  30 

Ser Thr Asp Arg Ala Leu Pro Asp Ser Ser Leu Ser Ser Leu Ser Arg 
         35                  40                  45 

Ser Thr Phe Gln Phe His Lys His His Leu Ser Gly Asn Glu Asn Pro 
     50                  55                  60 

Gln Pro Ser Ser Glu Ser Pro Tyr Phe Thr Asn Asn Glu Arg Leu Asn 
 65                  70                  75                  80 

Ser Ser Ser Phe Pro Gln Ile His Asp Asn Gln Leu Ser Pro Ser Phe 
                 85                  90                  95 

Asn Thr Ser Tyr Gln Ala Ile Pro Ser Ser Ser Ser Asn Arg Ser Arg 
            100                 105                 110 

Gly Gly Pro Tyr Thr Pro Ser Ile Arg Asp Asp Ser Leu Leu Ala Leu 
        115                 120                 125 

Leu Ser Phe Ser Ser Asn His Arg Leu His Ser Met Pro Ser Gln Leu 
    130                 135                 140 

Gln Pro Phe Asn Asn Ala Ser Ser Tyr Thr Thr Pro Met Ala Pro Phe 
145                 150                 155                 160 

Thr Ala Ser Phe Ser Asn Lys Val Ser His Ser Ala Tyr Pro Thr Arg 
                165                 170                 175 

Arg Leu Pro Ser Gln Ala Lys Lys Thr Ser Ala Ile Glu Arg Val Pro 
            180                 185                 190 

Val Asn Leu Asn Phe Leu Gln Ser Asp Asn Leu Val Val Gln Ser Ser 
        195                 200                 205 

Pro Gln Thr Asn Phe Glu Asn Phe Glu Phe Pro Lys Lys Ile Pro Ser 
    210                 215                 220 

Lys Glu Asp Leu Glu Thr Arg Glu Val Leu Leu Leu Pro Pro Gln Thr 
225                 230                 235                 240 

Ser Lys Leu Ser Asn Lys Asn Leu Asp Thr Lys Ser Phe Thr Asp Val 
                245                 250                 255 

Asn Lys Ile Ser Gln Gln Gly Phe Val Glu Ile Ser Ser Asn Ser Ser 
            260                 265                 270 

Lys Val Thr Pro Asn Thr Ser Leu His Gln Ser Phe Gly Ile Ala Ser 
        275                 280                 285 

Ser Ser Ser Asn Asn Tyr Met Gln Thr Ser Ser Glu Leu Thr Ser Ser 
    290                 295                 300 

Thr Glu Lys Met Asn Gly Ser His Pro Leu Gln Leu Ser Asn Lys Ser 
305                 310                 315                 320 

Leu Leu Ser Ile His Leu Met Gln Ser Lys Asn Gln Gly His Val Ser 
                325                 330                 335 

Met Thr Gly Ser Asp Lys Leu Ser Ser His Val Gln Ser Glu Thr Glu 
            340                 345                 350 

Asn Ala Pro Val Ser Lys Pro Ser Lys Pro Asn Thr Leu Thr Glu Asp 
        355                 360                 365 

Glu Lys Pro Leu Gln Ser Thr Lys Leu Pro Gly Asn Ser Leu Thr Val 
    370                 375                 380 

Gly Glu Leu Tyr Gln Glu Pro Lys Ser Ile Gln Leu Pro Glu Leu Ser 
385                 390                 395                 400 

Val Ser Arg Thr Thr Tyr Ser Ala Gln Ser Ser Ser Val Lys Asn Cys 
                405                 410                 415 

Asn Glu Arg Ile Pro Ser Ala Lys Ala Leu Lys Lys Gln Lys His Leu 
            420                 425                 430 

Val Pro Glu Asn Lys Ser Lys Leu Gln Tyr Val Trp Gln Lys Lys Glu 
        435                 440                 445 

Ser Leu Pro Tyr Ala Asn Leu Thr Ser Ala Ser Asn Thr His Phe Phe 
    450                 455                 460 

Leu Ser Glu Asn Gln Asn Asp Thr Ser Glu Arg Leu Thr Arg Thr Leu 
465                 470                 475                 480 

Arg Lys Ser Thr Lys Asn Tyr Thr Phe Gly Ser Tyr Ile Leu Gly Arg 
                485                 490                 495 

Thr Ile Gly Thr Gly Glu Phe Gly Lys Val Lys Leu Gly Trp Pro Leu 
            500                 505                 510 

Pro Lys Ala Asn Ser Thr Ile His Arg Ser Thr Pro Gln Val Val Ile 
        515                 520                 525 

Lys Ile Val Leu Ser Thr Lys Gln Asn Cys Gln Thr Ser Arg Leu Met 
    530                 535                 540 

Arg Glu Val Ala Ile Leu Lys Gly Leu Gly Asn Asn His Pro His Ile 
545                 550                 555                 560 

Val Lys Tyr Leu Asp Phe Val Lys Thr Lys His His Phe Gly Ile Val 
                565                 570                 575 

Leu Asp Tyr Val Asn Gly Gly Glu Leu Phe Asp Tyr Ile Leu Ala Arg 
            580                 585                 590 

Arg Arg Leu Glu Asp Ser Val Ala Cys Arg Leu Phe Ala Gln Leu Ile 
        595                 600                 605 

Ser Gly Val Ala Tyr Leu His Ser Arg Gly Val Val His Arg Asp Pro 
    610                 615                 620 

Tyr Ser Glu Ser Tyr 
625 

 
           
             10  
             1142  
             PRT  
             Saccharomyces cerevisiae  
           
            10 

Met Ala Ile Asn Gly Asn Ser Ile Pro Ala Ile Lys Asp Asn Thr Ile 
  1               5                  10                  15 

Gly Pro Trp Lys Leu Gly Glu Thr Leu Gly Leu Gly Ser Thr Gly Lys 
             20                  25                  30 

Val Gln Leu Ala Arg Asn Gly Ser Thr Gly Gln Glu Ala Ala Val Lys 
         35                  40                  45 

Val Ile Ser Lys Ala Val Phe Asn Thr Gly Asn Val Ser Gly Thr Ser 
     50                  55                  60 

Ile Val Gly Ser Thr Thr Pro Asp Ala Leu Pro Tyr Gly Ile Glu Arg 
 65                  70                  75                  80 

Glu Ile Ile Ile Met Lys Leu Leu Asn His Pro Asn Val Leu Arg Leu 
                 85                  90                  95 

Tyr Asp Val Trp Glu Thr Asn Thr Asp Leu Tyr Leu Val Leu Glu Tyr 
            100                 105                 110 

Ala Glu Lys Gly Glu Leu Phe Asn Leu Leu Val Glu Arg Gly Pro Leu 
        115                 120                 125 

Pro Glu His Glu Ala Ile Arg Phe Phe Arg Gln Ile Ile Ile Gly Val 
    130                 135                 140 

Ser Tyr Cys His Ala Leu Gly Ile Val His Arg Asp Leu Lys Pro Glu 
145                 150                 155                 160 

Asn Leu Leu Leu Asp His Lys Tyr Asn Ile Lys Ile Ala Asp Phe Gly 
                165                 170                 175 

Met Ala Ala Leu Glu Thr Glu Gly Lys Leu Leu Glu Thr Ser Cys Gly 
            180                 185                 190 

Ser Pro His Tyr Ala Ala Pro Glu Ile Val Ser Gly Ile Pro Tyr Gln 
        195                 200                 205 

Gly Phe Ala Ser Asp Val Trp Ser Cys Gly Val Ile Leu Phe Ala Leu 
    210                 215                 220 

Leu Thr Gly Arg Leu Pro Phe Asp Glu Glu Asp Gly Asn Ile Arg Thr 
225                 230                 235                 240 

Leu Leu Leu Lys Val Gln Lys Gly Glu Phe Glu Met Pro Ser Asp Asp 
                245                 250                 255 

Glu Ile Ser Arg Glu Ala Gln Asp Leu Ile Arg Lys Ile Leu Thr Val 
            260                 265                 270 

Asp Pro Glu Arg Arg Ile Lys Thr Arg Asp Ile Leu Lys His Pro Leu 
        275                 280                 285 

Leu Gln Lys Tyr Pro Ser Ile Arg Asp Ser Lys Ser Ile Arg Gly Leu 
    290                 295                 300 

Pro Arg Glu Asp Thr Tyr Leu Thr Pro Leu Ser Glu Ser Asn Ser Ser 
305                 310                 315                 320 

Ile Asp Ala Thr Ile Leu Gln Asn Leu Val Ile Leu Trp His Gly Arg 
                325                 330                 335 

Asp Pro Glu Gly Ile Lys Glu Lys Leu Arg Glu Pro Gly Ala Asn Ala 
            340                 345                 350 

Glu Lys Thr Leu Tyr Ala Leu Leu Tyr Arg Phe Lys Cys Asp Thr Gln 
        355                 360                 365 

Lys Glu Leu Ile Lys Gln Gln Gln Val Lys Lys Arg Gln Ser Ile Ser 
    370                 375                 380 

Ser Val Ser Val Ser Pro Ser Lys Lys Val Ser Thr Thr Pro Gln Arg 
385                 390                 395                 400 

Arg Arg Asn Arg Glu Ser Leu Ile Ser Val Thr Ser Ser Arg Lys Lys 
                405                 410                 415 

Pro Ile Ser Phe Asn Lys Phe Thr Ala Ser Ser Ala Ser Ser Ser Asn 
            420                 425                 430 

Leu Thr Thr Pro Gly Ser Ser Lys Arg Leu Ser Lys Asn Phe Ser Ser 
        435                 440                 445 

Lys Lys Lys Leu Ser Thr Ile Val Asn Gln Ser Ser Pro Thr Pro Ala 
    450                 455                 460 

Ser Arg Asn Lys Arg Ala Ser Val Ile Asn Val Glu Lys Asn Gln Lys 
465                 470                 475                 480 

Arg Ala Ser Ile Phe Ser Thr Thr Lys Lys Asn Lys Arg Ser Ser Arg 
                485                 490                 495 

Ser Ile Lys Arg Met Ser Leu Ile Pro Ser Met Lys Arg Glu Ser Val 
            500                 505                 510 

Thr Thr Lys Leu Met Ser Thr Tyr Ala Lys Leu Ala Glu Asp Asp Asp 
        515                 520                 525 

Trp Glu Tyr Ile Glu Lys Glu Thr Lys Arg Thr Ser Ser Asn Phe Ala 
    530                 535                 540 

Thr Leu Ile Asp Glu Ile Phe Glu Tyr Glu Lys Tyr Glu Gln Ile Arg 
545                 550                 555                 560 

Lys Glu Lys Glu Glu Leu Glu Arg Lys Val Arg Glu Ala Lys Ala Arg 
                565                 570                 575 

Glu Glu Leu Glu Arg Arg Arg Arg Lys Gln Glu Glu Lys Glu Arg Ala 
            580                 585                 590 

Arg Lys Leu Leu Glu Lys Glu Asp Leu Lys Arg Lys Gln Glu Glu Leu 
        595                 600                 605 

Lys Lys Gln Ile Glu Ile Asp Ile Ser Asp Leu Glu Gln Glu Leu Ser 
    610                 615                 620 

Lys His Lys Glu Glu Lys Leu Asp Gly Asn Ile Arg Ser Ile Ser Ala 
625                 630                 635                 640 

Pro Met Glu Asn Glu Glu Lys Asn Ile Asn His Leu Glu Val Asp Ile 
                645                 650                 655 

Asp Asn Ile Leu Arg Arg Arg Asn Phe Ser Leu Gln Thr Arg Pro Val 
            660                 665                 670 

Ser Arg Leu Asp Pro Gly Ile Met Phe Ser Ser Pro Thr Glu Glu Val 
        675                 680                 685 

Ser Pro Val Glu Pro Lys Arg Thr Glu Asn Glu Arg Leu Thr Thr Glu 
    690                 695                 700 

Lys Lys Ile Leu Glu Thr Ile Arg Arg Ser Lys Phe Leu Gly Ser Ser 
705                 710                 715                 720 

Phe Asn Ile Asp Lys Glu Leu Lys Leu Ser Lys Met Glu Tyr Pro Ser 
                725                 730                 735 

Ile Ile Ala Pro Gln Arg Leu Ser Glu Glu Arg Val Val Ser Asp Ser 
            740                 745                 750 

Asn Asp Gly Tyr Glu Ser Leu Ile Leu Pro Lys Asp Gly Asn Gly Val 
        755                 760                 765 

Ser Gln Leu Lys Asp Ser Thr Ala Thr Thr Ala Pro Val Ser Asp Gly 
    770                 775                 780 

Arg Leu Arg Lys Ile Ser Glu Ile Arg Val Pro Gln Phe Thr Arg Lys 
785                 790                 795                 800 

Ser Arg His Phe Ser Glu Ser Asn Lys Arg Leu Ser Val Leu Ser Met 
                805                 810                 815 

Tyr Ser Thr Lys Glu Ser Phe Thr Asn Leu Val Asp Ile Leu Lys Asn 
            820                 825                 830 

Gly Asn Leu Asp Val Asn Asn Gln Gln Ser Gln Arg Ile Pro Thr Pro 
        835                 840                 845 

Arg Ser Ala Asp Asp Ser Glu Phe Leu Phe Glu Thr Val Asn Glu Glu 
    850                 855                 860 

Ala Glu Tyr Thr Gly Asn Ser Ser Asn Asp Glu Arg Leu Tyr Asp Val 
865                 870                 875                 880 

Gly Asp Ser Thr Ile Lys Asp Lys Ser Ala Leu Lys Leu Asn Phe Ala 
                885                 890                 895 

Asp Arg Phe Asn Gly Ser Asn Glu Ala Lys Gln Thr Asp Asn Leu His 
            900                 905                 910 

Leu Pro Ile Leu Pro Pro Leu Asn Gly Asp Asn Glu Leu Arg Lys Gln 
        915                 920                 925 

Asn Ser Gln Glu Gly Asp Gln Ala His Pro Lys Ile Lys Ser Met Ile 
    930                 935                 940 

Pro Glu Ser Gly Ser Ser Ser His Thr Glu Lys Glu Glu Glu Asn Glu 
945                 950                 955                 960 

Glu Lys Glu Glu Lys Lys Pro Glu Gln His Lys Gln Glu Glu Asp Gln 
                965                 970                 975 

Glu Lys Arg Glu Lys Val Val Asp Asp Met Glu Pro Pro Leu Asn Lys 
            980                 985                 990 

Ser Val Gln Lys Ile Arg Glu Lys Asn Ala Gly Ser Gln Ala Lys Asp 
        995                1000                1005 

His Ser Lys Asp His Leu Lys Glu His Lys Gln Asp Lys Asn Thr Ala 
   1010                1015                1020 

Ile Gly Asn Gly Ser Phe Phe Arg Lys Phe Ser Lys Ser Ser Asp Lys 
1025               1030                1035                1040 

Thr Met Glu Leu Tyr Ala Lys Ile Ser Ala Lys Gln Leu Phe Asn Gly 
               1045                1050                1055 

Leu Glu Lys Leu Leu Arg Gly Trp Thr Gln Tyr Gly Leu Lys Asn Ile 
           1060                1065                1070 

Lys Ser His Pro Asn Asn Leu Thr Leu Thr Gly Lys Leu Ser Ser Asp 
       1075                1080                1085 

Asn Ile Phe Ser Leu Arg Ser Thr Leu Phe Glu Val Asn Ile Tyr Pro 
   1090                1095                1100 

Arg Gly Lys Met Ser Val Val Gln Phe Lys Lys Val Ser Gly Ser Phe 
1105               1110                1115                1120 

Lys Ala Val Lys Lys Leu Val Asn Glu Val Glu Asn Val Leu Asn Lys 
               1125                1130                1135 

Glu Gly Val Leu Gln Lys 
           1140 

 
           
             11  
             1518  
             PRT  
             Saccharomyces cerevisiae  
           
            11 

Met Thr Gly His Val Ser Lys Thr Ser His Val Pro Lys Gly Arg Pro 
  1               5                  10                  15 

Ser Ser Leu Ala Lys Lys Ala Ala Lys Arg Ala Met Ala Lys Val Asn 
             20                  25                  30 

Ser Asn Pro Lys Arg Ala Ser Gly His Leu Glu Arg Val Val Gln Ser 
         35                  40                  45 

Val Asn Asp Ala Thr Lys Arg Leu Ser Gln Pro Asp Ser Thr Val Ser 
     50                  55                  60 

Val Ala Thr Lys Ser Ser Lys Arg Lys Ser Arg Asp Thr Val Gly Pro 
 65                  70                  75                  80 

Trp Lys Leu Gly Lys Thr Leu Gly Lys Gly Ser Ser Gly Arg Val Arg 
                 85                  90                  95 

Leu Ala Lys Asn Met Glu Thr Gly Gln Leu Ala Ala Ile Lys Ile Val 
            100                 105                 110 

Pro Lys Lys Lys Ala Phe Val His Cys Ser Asn Asn Gly Thr Val Pro 
        115                 120                 125 

Asn Ser Tyr Ser Ser Ser Met Val Thr Ser Asn Val Ser Ser Pro Ser 
    130                 135                 140 

Ile Ala Ser Arg Glu His Ser Asn His Ser Gln Thr Asn Pro Tyr Gly 
145                 150                 155                 160 

Ile Glu Arg Glu Ile Val Ile Met Lys Leu Ile Ser His Thr Asn Val 
                165                 170                 175 

Met Ala Leu Phe Glu Val Trp Glu Asn Lys Ser Glu Leu Tyr Leu Val 
            180                 185                 190 

Leu Glu Tyr Val Asp Gly Gly Glu Leu Phe Asp Tyr Leu Val Ser Lys 
        195                 200                 205 

Gly Lys Leu Pro Glu Arg Glu Ala Ile His Tyr Phe Lys Gln Ile Val 
    210                 215                 220 

Glu Gly Val Ser Tyr Cys His Ser Phe Asn Ile Cys His Arg Asp Leu 
225                 230                 235                 240 

Lys Pro Glu Asn Leu Leu Leu Asp Lys Lys Asn Arg Arg Ile Lys Ile 
                245                 250                 255 

Ala Asp Phe Gly Met Ala Ala Leu Glu Leu Pro Asn Lys Leu Leu Lys 
            260                 265                 270 

Thr Ser Cys Gly Ser Pro His Tyr Ala Ser Pro Glu Ile Val Met Gly 
        275                 280                 285 

Arg Pro Tyr His Gly Gly Pro Ser Asp Val Trp Ser Cys Gly Ile Val 
    290                 295                 300 

Leu Phe Ala Leu Leu Thr Gly His Leu Pro Phe Asn Asp Asp Asn Ile 
305                 310                 315                 320 

Lys Lys Leu Leu Leu Lys Val Gln Ser Gly Lys Tyr Gln Met Pro Ser 
                325                 330                 335 

Asn Leu Ser Ser Glu Ala Arg Asp Leu Ile Ser Lys Ile Leu Val Ile 
            340                 345                 350 

Asp Pro Glu Lys Arg Ile Thr Thr Gln Glu Ile Leu Lys His Pro Leu 
        355                 360                 365 

Ile Lys Lys Tyr Asp Asp Leu Pro Val Asn Lys Val Leu Arg Lys Met 
    370                 375                 380 

Arg Lys Asp Asn Met Ala Arg Gly Lys Ser Asn Ser Asp Leu His Leu 
385                 390                 395                 400 

Leu Asn Asn Val Ser Pro Ser Ile Val Thr Leu His Ser Lys Gly Glu 
                405                 410                 415 

Ile Asp Glu Ser Ile Leu Arg Ser Leu Gln Ile Leu Trp His Gly Val 
            420                 425                 430 

Ser Arg Glu Leu Ile Thr Ala Lys Leu Leu Gln Lys Pro Met Ser Glu 
        435                 440                 445 

Glu Lys Leu Phe Tyr Ser Leu Leu Leu Gln Tyr Lys Gln Arg His Ser 
    450                 455                 460 

Ile Ser Leu Ser Ser Ser Ser Glu Asn Lys Lys Ser Ala Thr Glu Ser 
465                 470                 475                 480 

Ser Val Asn Glu Pro Arg Ile Glu Tyr Ala Ser Lys Thr Ala Asn Asn 
                485                 490                 495 

Thr Gly Leu Arg Ser Glu Asn Asn Asp Val Lys Thr Leu His Ser Leu 
            500                 505                 510 

Glu Ile His Ser Glu Asp Thr Ser Thr Val Asn Gln Asn Asn Ala Ile 
        515                 520                 525 

Thr Gly Val Asn Thr Glu Ile Asn Ala Pro Val Leu Ala Gln Lys Ser 
    530                 535                 540 

Gln Phe Ser Ile Asn Thr Leu Ser Gln Pro Glu Ser Asp Lys Ala Glu 
545                 550                 555                 560 

Ala Glu Ala Val Thr Leu Pro Pro Ala Ile Pro Ile Phe Asn Ala Ser 
                565                 570                 575 

Ser Ser Arg Ile Phe Arg Asn Ser Tyr Thr Ser Ile Ser Ser Arg Ser 
            580                 585                 590 

Arg Arg Ser Leu Arg Leu Ser Asn Ser Arg Leu Ser Leu Ser Ala Ser 
        595                 600                 605 

Thr Ser Arg Glu Thr Val His Asp Asn Glu Met Pro Leu Pro Gln Leu 
    610                 615                 620 

Pro Lys Ser Pro Ser Arg Tyr Ser Leu Ser Arg Arg Ala Ile His Ala 
625                 630                 635                 640 

Ser Pro Ser Thr Lys Ser Ile His Lys Ser Leu Ser Arg Lys Asn Ile 
                645                 650                 655 

Ala Ala Thr Val Ala Ala Arg Arg Thr Leu Gln Asn Ser Ala Ser Lys 
            660                 665                 670 

Arg Ser Leu Tyr Ser Leu Gln Ser Ile Ser Lys Arg Ser Leu Asn Leu 
        675                 680                 685 

Asn Asp Leu Leu Val Phe Asp Asp Pro Leu Pro Ser Lys Lys Pro Ala 
    690                 695                 700 

Ser Glu Asn Val Asn Lys Ser Glu Pro His Ser Leu Glu Ser Asp Ser 
705                 710                 715                 720 

Asp Phe Glu Ile Leu Cys Asp Gln Ile Leu Phe Gly Asn Ala Leu Asp 
                725                 730                 735 

Arg Ile Leu Glu Glu Glu Glu Asp Asn Glu Lys Glu Arg Asp Thr Gln 
            740                 745                 750 

Arg Gln Arg Gln Asn Asp Thr Lys Ser Ser Ala Asp Thr Phe Thr Ile 
        755                 760                 765 

Ser Gly Val Ser Thr Asn Lys Glu Asn Glu Gly Pro Glu Tyr Pro Thr 
    770                 775                 780 

Lys Ile Glu Lys Asn Gln Phe Asn Met Ser Tyr Lys Pro Ser Glu Asn 
785                 790                 795                 800 

Met Ser Gly Leu Ser Ser Phe Pro Ile Phe Glu Lys Glu Asn Thr Leu 
                805                 810                 815 

Ser Ser Ser Tyr Leu Glu Glu Gln Lys Pro Lys Arg Ala Ala Leu Ser 
            820                 825                 830 

Asp Ile Thr Asn Ser Phe Asn Lys Met Asn Lys Gln Glu Gly Met Arg 
        835                 840                 845 

Ile Glu Lys Lys Ile Gln Arg Glu Gln Leu Gln Lys Lys Asn Asp Arg 
    850                 855                 860 

Pro Ser Pro Leu Lys Pro Ile Gln His Gln Glu Leu Arg Val Asn Ser 
865                 870                 875                 880 

Leu Pro Asn Asp Gln Gly Lys Pro Ser Leu Ser Leu Asp Pro Arg Arg 
                885                 890                 895 

Asn Ile Ser Gln Pro Val Asn Ser Lys Val Glu Ser Leu Leu Gln Gly 
            900                 905                 910 

Leu Lys Phe Lys Lys Glu Pro Ala Ser His Trp Thr His Glu Arg Gly 
        915                 920                 925 

Ser Leu Phe Met Ser Glu His Val Glu Asp Glu Lys Pro Val Lys Ala 
    930                 935                 940 

Ser Asp Val Ser Ile Glu Ser Ser Tyr Val Pro Leu Thr Thr Val Ala 
945                 950                 955                 960 

Thr Ser Ser Arg Asp Pro Ser Val Leu Ala Glu Ser Ser Thr Ile Gln 
                965                 970                 975 

Lys Pro Met Leu Ser Leu Pro Ser Ser Phe Leu Asn Thr Ser Met Thr 
            980                 985                 990 

Phe Lys Asn Leu Ser Gln Ile Leu Ala Asp Asp Gly Asp Asp Lys His 
        995                1000                1005 

Leu Ser Val Pro Gln Asn Gln Ser Arg Ser Val Ala Met Ser His Pro 
   1010                1015                1020 

Leu Arg Lys Gln Ser Ala Lys Ile Ser Leu Thr Pro Arg Ser Asn Leu 
1025               1030                1035                1040 

Asn Ala Asn Leu Ser Val Lys Arg Asn Gln Gly Ser Pro Gly Ser Tyr 
               1045                1050                1055 

Leu Ser Asn Asp Leu Asp Gly Ile Ser Asp Met Thr Phe Ala Met Glu 
           1060                1065                1070 

Ile Pro Thr Asn Thr Phe Thr Ala Gln Ala Ile Gln Leu Met Asn Asn 
       1075                1080                1085 

Asp Thr Asp Asn Asn Lys Ile Asn Thr Ser Pro Lys Ala Ser Ser Phe 
   1090                1095                1100 

Thr Lys Glu Lys Val Ile Lys Ser Ala Ala Tyr Ile Ser Lys Glu Lys 
1105               1110                1115                1120 

Glu Pro Asp Asn Ser Asp Thr Asn Tyr Ile Pro Asp Tyr Thr Ile Pro 
               1125                1130                1135 

Asn Thr Tyr Asp Glu Lys Ala Ile Asn Ile Phe Glu Asp Ala Pro Ser 
           1140                1145                1150 

Asp Glu Gly Ser Leu Asn Thr Ser Ser Ser Glu Ser Asp Ser Arg Ala 
       1155                1160                1165 

Ser Val His Arg Lys Ala Val Ser Ile Asp Thr Met Ala Thr Thr Asn 
   1170                1175                1180 

Val Leu Thr Pro Ala Thr Asn Val Arg Val Ser Leu Tyr Trp Asn Asn 
1185               1190                1195                1200 

Asn Ser Ser Gly Ile Pro Arg Glu Thr Thr Glu Glu Ile Leu Ser Lys 
               1205                1210                1215 

Leu Arg Leu Ser Pro Glu Asn Pro Ser Asn Thr His Met Gln Lys Arg 
           1220                1225                1230 

Phe Ser Ser Thr Arg Gly Ser Arg Asp Ser Asn Ala Leu Gly Ile Ser 
       1235                1240                1245 

Gln Ser Leu Gln Ser Met Phe Lys Asp Leu Glu Glu Asp Gln Asp Gly 
   1250                1255                1260 

His Thr Ser Gln Ala Asp Ile Leu Glu Ser Ser Met Ser Tyr Ser Lys 
1265               1270                1275                1280 

Arg Arg Pro Ser Glu Glu Ser Val Asn Pro Lys Gln Arg Val Thr Met 
               1285                1290                1295 

Leu Phe Asp Glu Glu Glu Glu Glu Ser Lys Lys Val Gly Gly Gly Lys 
           1300                1305                1310 

Ile Lys Glu Glu His Thr Lys Leu Asp Asn Lys Ile Ser Glu Glu Ser 
       1315                1320                1325 

Ser Gln Leu Val Leu Pro Val Val Glu Lys Lys Glu Asn Ala Asn Asn 
   1330                1335                1340 

Thr Glu Asn Asn Tyr Ser Lys Ile Pro Lys Pro Ser Thr Ile Lys Val 
1345               1350                1355                1360 

Thr Lys Asp Thr Ala Met Glu Ser Asn Thr Gln Thr His Thr Lys Lys 
               1365                1370                1375 

Pro Ile Leu Lys Ser Val Gln Asn Val Glu Val Glu Glu Ala Pro Ser 
           1380                1385                1390 

Ser Asp Lys Lys Asn Trp Phe Val Lys Leu Phe Gln Asn Phe Ser Ser 
       1395                1400                1405 

His Asn Asn Ala Thr Lys Ala Ser Lys Asn His Val Thr Asn Ile Ser 
   1410                1415                1420 

Phe Asp Asp Ala His Met Leu Thr Leu Asn Glu Phe Asn Lys Asn Ser 
1425               1430                1435                1440 

Ile Asp Tyr Gln Leu Lys Asn Leu Asp His Lys Phe Gly Arg Lys Val 
               1445                1450                1455 

Val Glu Tyr Asp Cys Lys Phe Val Lys Gly Asn Phe Lys Phe Lys Ile 
           1460                1465                1470 

Lys Ile Thr Ser Thr Pro Asn Ala Ser Ser Val Ile Thr Val Lys Lys 
       1475                1480                1485 

Arg Ser Lys His Ser Asn Thr Ser Ser Asn Lys Ala Phe Glu Lys Phe 
   1490                1495                1500 

Asn Asp Asp Val Glu Arg Val Ile Arg Asn Ala Gly Arg Ser 
1505               1510                1515 

 
           
             12  
             1037  
             PRT  
             Saccharomyces cerevisiae  
           
            12 

Met Thr Val Ala Asn Thr Glu Thr His Ser Ala Ala Lys Pro Ser Ser 
  1               5                  10                  15 

Thr Ile Gly Pro Trp Lys Leu Gly Glu Thr Leu Gly Phe Gly Ser Thr 
             20                  25                  30 

Gly Lys Val Gln Leu Ala Gln His Glu Arg Thr Gly His Arg Thr Ala 
         35                  40                  45 

Val Lys Val Ile Ser Lys Ser Ile Phe Asn Asn Asn Gly Asn His Ser 
     50                  55                  60 

Asn Asp Asp Ser Val Leu Pro Tyr Asn Ile Glu Arg Glu Ile Val Ile 
 65                  70                  75                  80 

Met Lys Leu Leu Ser His Pro Asn Val Leu Ser Leu Tyr Asp Val Trp 
                 85                  90                  95 

Glu Thr Asn Asn Asn Leu Tyr Leu Ile Leu Glu Tyr Ala Glu Lys Gly 
            100                 105                 110 

Glu Leu Phe Asn Leu Leu Val Asp His Gly Pro Leu Pro Glu Arg Glu 
        115                 120                 125 

Ala Ile Asn Cys Phe Arg Gln Ile Ile Ile Gly Ile Ser Tyr Cys His 
    130                 135                 140 

Ala Leu Gly Ile Val His Arg Asp Leu Lys Pro Glu Asn Leu Leu Leu 
145                 150                 155                 160 

Asp Ser Phe Tyr Asn Ile Lys Ile Ala Asp Phe Gly Met Ala Ala Leu 
                165                 170                 175 

Gln Thr Asp Ala Asp Leu Leu Glu Thr Ser Cys Gly Ser Pro His Tyr 
            180                 185                 190 

Ala Ala Pro Glu Ile Val Ser Gly Leu Pro Tyr Glu Gly Phe Ala Ser 
        195                 200                 205 

Asp Val Trp Ser Cys Gly Val Ile Leu Phe Ala Leu Leu Thr Gly Arg 
    210                 215                 220 

Leu Pro Phe Asp Glu Glu Asn Gly Asn Val Arg Asp Leu Leu Leu Lys 
225                 230                 235                 240 

Val Gln Lys Gly Gln Phe Glu Met Pro Asn Asp Thr Glu Ile Ser Arg 
                245                 250                 255 

Asp Ala Gln Asp Leu Ile Gly Lys Ile Leu Val Val Asp Pro Arg Gln 
            260                 265                 270 

Arg Ile Lys Ile Arg Asp Ile Leu Ser His Pro Leu Leu Lys Lys Tyr 
        275                 280                 285 

Gln Thr Ile Lys Asp Ser Lys Ser Ile Lys Asp Leu Pro Arg Glu Asn 
    290                 295                 300 

Thr Tyr Leu Tyr Pro Leu Ala Asp Ser Asn Asn His Thr Ser Ala Ser 
305                 310                 315                 320 

Ile Asp Asp Ser Ile Leu Gln Asn Leu Val Val Leu Trp His Gly Arg 
                325                 330                 335 

His Ala Asp Asp Ile Val Ser Lys Leu Lys Glu Asn Gly Thr Asn Lys 
            340                 345                 350 

Glu Lys Ile Leu Tyr Ala Leu Leu Tyr Arg Phe Lys Leu Asp Ser Val 
        355                 360                 365 

Arg Gly Ser Asn Lys Lys Asn Arg Asn Lys Ile Lys Lys Thr Lys Lys 
    370                 375                 380 

Asn Lys Arg Ser Ser Thr Leu Ser Ser Ser Ser Ser Leu Leu Leu Asn 
385                 390                 395                 400 

Asn Arg Ser Ile Gln Ser Thr Pro Arg Arg Arg Thr Ser Lys Arg His 
                405                 410                 415 

Ser Arg Glu Phe Ser Ser Ser Arg Lys Arg Ser Ser Phe Leu Leu Ser 
            420                 425                 430 

Ser Asn Pro Thr Asp Ser Ser Pro Ile Pro Leu Arg Ser Ser Lys Arg 
        435                 440                 445 

Ile Thr His Ile Asn Val Ala Ser Ala Asn Thr Gln Ala Thr Pro Ser 
    450                 455                 460 

Gly Val Pro Asn Pro His Lys Arg Asn Ser Lys Lys Arg Ser Ser Lys 
465                 470                 475                 480 

Arg Leu Ser Tyr Met Pro Asn Thr Lys Arg Ser Ser Leu Thr Ser Lys 
                485                 490                 495 

Ser Leu Ser Asn Phe Thr Asn Leu Ile Asp Asp Asp Asp Trp Glu Tyr 
            500                 505                 510 

Ile Glu Lys Asp Ala Lys Arg Thr Ser Ser Asn Phe Ala Thr Leu Ile 
        515                 520                 525 

Asp Glu Ile Phe Glu Pro Glu Lys Phe Glu Leu Ala Lys Arg Glu Lys 
    530                 535                 540 

Ala Glu Leu Gln Arg Lys Val Gln Glu Ala Lys Arg Gln Ser Val Asn 
545                 550                 555                 560 

Ala Gln Lys Ile Asn Glu Asp Glu Phe Gly Ser Glu Val Ser Asp Gly 
                565                 570                 575 

Met Lys Glu Leu Lys Lys Ile Asn Asp Lys Val Ser Ser Pro Leu Ile 
            580                 585                 590 

Asn Tyr Glu Phe Ser Gln Gln Glu Leu Leu Gln Asp Ile Asp Thr Leu 
        595                 600                 605 

Leu Thr Asn Arg Tyr Gln Leu Ser Ser Tyr Thr Arg Pro Ile Ser Arg 
    610                 615                 620 

Leu Asp Pro Gly Leu Thr Pro Val Thr Glu Thr Leu Pro Asn Asn Leu 
625                 630                 635                 640 

Lys Glu Lys Thr Ala Leu Leu Gln Asp Thr Glu Lys Lys Ile Ile Glu 
                645                 650                 655 

Thr Ile Arg Arg Ser Lys Phe Leu Gly Ser Leu Leu Asn Val Arg Gly 
            660                 665                 670 

Gly Leu Ser Pro Gly Lys Ser Glu Leu Ala Pro Ile Glu Glu Ser Pro 
        675                 680                 685 

Ile Val Ser Thr Thr Pro Leu Ile Tyr Asn Asp Arg Met Glu Pro Arg 
    690                 695                 700 

Arg Ile Ser Asp Val Glu Val Pro His Phe Thr Arg Lys Ser Lys His 
705                 710                 715                 720 

Phe Thr Thr Ala Asn Asn Arg Arg Ser Val Leu Ser Leu Tyr Ala Lys 
                725                 730                 735 

Asp Ser Ile Lys Asp Leu Asn Glu Phe Leu Ile Lys Glu Asp Pro Asp 
            740                 745                 750 

Leu Pro Pro Gln Gly Ser Thr Asp Asn Glu Ser Arg Ser Glu Asp Pro 
        755                 760                 765 

Glu Ile Ala Glu Ser Ile Thr Asp Ser Arg Asn Ile Gln Tyr Asp Glu 
    770                 775                 780 

Asp Asp Ser Lys Asp Gly Asp Asn Val Asn Asn Asp Asn Ile Leu Ser 
785                 790                 795                 800 

Asp Phe Pro Gln Gly Val Gly Ile Ser Gln Glu Tyr Asp Met Lys Asp 
                805                 810                 815 

Lys Asn Pro Asn Gln Ser Pro Ile Ser Lys Ser Ala Glu Pro Thr Leu 
            820                 825                 830 

Val Val Lys Leu Pro Ser Leu Ser Ser Phe Gln Gly Lys Asn Ala Ser 
        835                 840                 845 

Gly Leu Gly Leu Tyr Gln Arg Glu Pro Ser Lys Val Thr Leu Pro Ser 
    850                 855                 860 

Leu Thr Ser Asn Asn Ser Ser Val Gly Glu Asn Ile Glu Asp Gly Ala 
865                 870                 875                 880 

Glu Lys Gly Thr Glu Ser Glu Lys Ile Ala Ala Ser Leu Ser Asp Asp 
                885                 890                 895 

Asp Leu Lys Glu Asp Asn Asp Lys Lys Asp Asn Asp Thr Val Asn Ala 
            900                 905                 910 

Pro Thr Thr Val Lys Lys Pro Pro Asn Ser Val Leu Leu Lys Lys Phe 
        915                 920                 925 

Ser Lys Gly Lys Ile Leu Glu Leu Glu Ile His Ala Lys Ile Pro Glu 
    930                 935                 940 

Lys Arg Leu Tyr Glu Gly Leu His Lys Leu Leu Glu Gly Trp Lys Gln 
945                 950                 955                 960 

Tyr Gly Leu Lys Asn Leu Val Phe Asn Ile Thr Asn Met Ile Ile Thr 
                965                 970                 975 

Gly Lys Leu Val Asn Asp Ser Ile Leu Phe Leu Arg Ser Thr Leu Phe 
            980                 985                 990 

Glu Ile Met Val Leu Pro Asn Gly Asp Gly Arg Ser Leu Ile Lys Phe 
        995                1000                1005 

Asn Lys Lys Thr Gly Ser Thr Lys Thr Leu Thr Lys Leu Ala Thr Glu 
   1010                1015                1020 

Ile Gln Ile Ile Leu Gln Lys Glu Gly Val Leu Asp Lys 
1025               1030                1035 

 
           
             13  
             775  
             PRT  
             Schizosaccharomyces pombe  
           
            13 

Met Ser Thr Ile Ser Glu Val Gly Pro Trp Glu Leu Gly Leu Ser Leu 
  1               5                  10                  15 

Gly Ser Gly Gly Pro Asn Ser Ser Arg Leu Ala Lys His Arg Glu Thr 
             20                  25                  30 

Gly Gln Leu Ala Val Val Lys Pro Ile Val Gly Trp Ser Glu Leu Thr 
         35                  40                  45 

Ser Ser Gln Gln Ala Arg Ile Glu Gly Glu Leu Val Leu Leu Arg Leu 
     50                  55                  60 

Ile Glu His Pro Asn Val Leu Gln Leu Ile Asp Val Ile Ser Ala Gln 
 65                  70                  75                  80 

Glu Gln Leu Phe Val Val Val Glu Tyr Met Pro Gly Gly Glu Leu Phe 
                 85                  90                  95 

Asp Cys Met Leu Arg Lys Gly Ser Phe Thr Glu Gln Asp Thr Ala Lys 
            100                 105                 110 

Phe Leu Trp Gln Ile Leu Cys Gly Leu Glu Tyr Cys His Lys Leu His 
        115                 120                 125 

Ile Cys His Arg Asp Leu Lys Pro Glu Asn Leu Tyr Leu Asp Ala His 
    130                 135                 140 

Gly Ser Ile Lys Ile Gly Glu Phe Gly Met Ala Ser Ile Gln Gln Pro 
145                 150                 155                 160 

Gly Lys Leu Leu Gln Thr Ser Cys Gly Ser Pro His Tyr Ala Ser Pro 
                165                 170                 175 

Glu Ile Ile Met Gly Arg Ser Tyr Asp Gly Cys Ala Ser Asp Ile Trp 
            180                 185                 190 

Ser Cys Gly Ile Ile Phe Phe Ala Leu Leu Thr Gly Lys Leu Pro Phe 
        195                 200                 205 

Asp Asp Asp Asn Ile Arg Ser Leu Leu Leu Lys Val Cys Gln Gly Gln 
    210                 215                 220 

Phe Glu Met Pro Ser Asn Ile Ser Pro Gln Ala Gln His Leu Leu Tyr 
225                 230                 235                 240 

Arg Met Leu Asp Val Asp Ser Ser Thr Arg Ile Thr Met Glu Gln Ile 
                245                 250                 255 

Arg Glu His Pro Phe Leu Ser Cys Phe Val His Pro Asn Ile Ser Ile 
            260                 265                 270 

Pro Ile Ile Ser Ala Pro Ile Gln Pro Ile Asp Pro Leu Ile Val Gln 
        275                 280                 285 

His Leu Ser Leu Val Phe Arg Cys Ser Asp Asp Pro Met Pro Leu Tyr 
    290                 295                 300 

Glu Lys Leu Ala Ser Gln Ser Pro Leu Val Glu Lys Thr Leu Tyr Thr 
305                 310                 315                 320 

Leu Leu Ser Arg His Leu His Pro Pro Ser Ser Ala Ala Val Asp Arg 
                325                 330                 335 

Asn Arg Ala Val Val Asp Asp Leu Leu Gly Thr Ala Ala Ser Asn Gly 
            340                 345                 350 

Gln Gln Met Asp Glu Glu Glu Ile Glu Gln Ala Ile Asn Ile Pro Thr 
        355                 360                 365 

Leu Ala Pro Tyr Pro Ile Ser Tyr Ala Ala Glu Ser Val Pro Arg Pro 
    370                 375                 380 

Ala Thr Ser Ala Ser Pro Phe Leu Thr Pro Val Thr Thr Ser Gly Thr 
385                 390                 395                 400 

Phe Asn Tyr Ser Phe Asn Ala Thr Asn Pro Gln Ser Ile Leu Gln Arg 
                405                 410                 415 

Pro Ala Thr Thr Ser Ser Ala Val Pro Gln Leu Pro Lys Ser Val Thr 
            420                 425                 430 

Pro Gly Leu Ala Tyr Pro His Asp Ser Ser Met Leu Ser Ser Asn Tyr 
        435                 440                 445 

Arg Pro Pro Ser Ala Leu Ser Pro Arg Asn Phe Asn Val Ser Ile Asn 
    450                 455                 460 

Asp Pro Glu Val Gln Leu Ser Arg Arg Ala Thr Ser Leu Asp Met Ser 
465                 470                 475                 480 

Asn Asp Phe Arg Met Asn Glu Asn Asp Pro Ser Ile Val Gly Asn Leu 
                485                 490                 495 

Ala Ala Ser Asn Phe Pro Thr Gly Met Gly Pro Pro Arg Lys Arg Val 
            500                 505                 510 

Thr Ser Arg Met Ser Glu His Thr Gly Asn Arg Val Val Ser Phe Pro 
        515                 520                 525 

Arg Gly Ser Ala Phe Asn Pro Arg Val Thr Arg Phe Asn Val Gly Asn 
    530                 535                 540 

Glu Gln Phe Ser Asn Asn Ile Asp Asn Asn Asn Tyr Asn Gln Pro Tyr 
545                 550                 555                 560 

Ala Asn Ala Thr Met Asn Asn Ser Arg Arg Leu Arg Thr Pro Ser Gly 
                565                 570                 575 

Glu Arg Ser Met Arg Ala Asp Leu Ser Gln Ser Pro Ala Ser Tyr Asp 
            580                 585                 590 

Ser Leu Asn Val Pro Lys His Arg Arg Arg Gln Ser Leu Phe Ser Pro 
        595                 600                 605 

Ser Ser Thr Lys Lys Lys Leu Ser Gly Ser Pro Phe Gln Pro Lys Arg 
    610                 615                 620 

Ser Phe Leu Arg Arg Leu Phe Ser Ser Glu Pro Ser Cys Lys Cys Val 
625                 630                 635                 640 

Tyr Ala Ser Leu Val Ala Ser Glu Leu Glu His Glu Ile Leu Glu Val 
                645                 650                 655 

Leu Arg Arg Trp Gln Leu Leu Gly Ile Gly Ile Ala Asp Ile Ile Tyr 
            660                 665                 670 

Asp Ser Val Ser Ala Ser Ile Ser Ala Arg Ile Lys Arg Gln Asn Ser 
        675                 680                 685 

Leu Asn Leu Lys Pro Val Arg Phe Arg Ile Ser Val Leu Ala Glu Phe 
    690                 695                 700 

Phe Gly Ser Gln Ala Val Phe Val Leu Glu Ser Gly Ser Ser Thr Thr 
705                 710                 715                 720 

Phe Asp His Leu Ala Thr Glu Phe Gln Leu Ile Phe Glu Asp Lys Gly 
                725                 730                 735 

Phe Leu Asp Asn Leu Glu Leu Ser Tyr Phe Gln Ala Ser Ala Ser Arg 
            740                 745                 750 

Pro Val Ser Arg Met Ser Val Ser Ser Ser Pro Phe Ala Val Phe Arg 
        755                 760                 765 

Gln Arg Gln Ser Val Gln Ser 
    770                 775 

 
           
             14  
             593  
             PRT  
             Schizosaccharomyces pombe  
           
            14 

Met Val Lys Arg His Lys Asn Thr Ile Gly Val Trp Arg Leu Gly Lys 
  1               5                  10                  15 

Thr Leu Gly Thr Gly Ser Thr Ser Cys Val Arg Leu Ala Lys His Ala 
             20                  25                  30 

Lys Thr Gly Asp Leu Ala Ala Ile Lys Ile Ile Pro Ile Arg Tyr Ala 
         35                  40                  45 

Ser Ile Gly Met Glu Ile Leu Met Met Arg Leu Leu Arg His Pro Asn 
     50                  55                  60 

Ile Leu Arg Leu Tyr Asp Val Trp Thr Asp His Gln His Met Tyr Leu 
 65                  70                  75                  80 

Ala Leu Glu Tyr Val Pro Asp Gly Glu Leu Phe His Tyr Ile Arg Lys 
                 85                  90                  95 

His Gly Pro Leu Ser Glu Arg Glu Ala Ala His Tyr Leu Ser Gln Ile 
            100                 105                 110 

Leu Asp Ala Val Ala His Cys His Arg Phe Arg Phe Arg His Arg Asp 
        115                 120                 125 

Leu Lys Leu Glu Asn Ile Leu Ile Lys Val Asn Glu Gln Gln Ile Lys 
    130                 135                 140 

Ile Ala Asp Phe Gly Met Ala Thr Val Glu Pro Asn Asp Ser Cys Leu 
145                 150                 155                 160 

Glu Asn Tyr Cys Gly Ser Leu His Tyr Leu Ala Pro Glu Ile Val Ser 
                165                 170                 175 

His Lys Pro Tyr Arg Gly Ala Pro Ala Asp Val Trp Ser Cys Gly Val 
            180                 185                 190 

Ile Leu Tyr Ser Leu Leu Ser Asn Lys Leu Pro Phe Gly Gly Gln Asn 
        195                 200                 205 

Thr Asp Val Ile Tyr Asn Lys Ile Arg His Gly Ala Tyr Asp Leu Pro 
    210                 215                 220 

Ser Ser Ile Ser Ser Ala Ala Gln Asp Leu Leu His Arg Met Leu Asp 
225                 230                 235                 240 

Val Asn Pro Ser Thr Arg Ile Thr Ile Pro Glu Val Phe Ser His Pro 
                245                 250                 255 

Phe Leu Met Gly Cys Thr Ser Leu Ser Ser Met Asp Ser Thr Thr Pro 
            260                 265                 270 

Pro Thr Pro Ser Leu Ser Ile Asp Glu Ile Asp Pro Leu Val Val Asp 
        275                 280                 285 

Cys Met Cys Val Leu Trp Lys Lys Ser Ser Ser Lys Lys Val Val Arg 
    290                 295                 300 

Arg Leu Gln Gln Arg Asp Asp Asn Asp Glu Lys Tyr Val Tyr Lys Val 
305                 310                 315                 320 

Leu Ser Glu Ile Leu Arg Asp Asp Met Leu Lys Lys Gln Arg Phe Asp 
                325                 330                 335 

Glu Asn Lys Tyr Leu Ser Leu Tyr Asp Leu Ile His Asp Asn Asn Leu 
            340                 345                 350 

Phe Thr Lys Ala Ser Ile Ser Thr Thr Ser Leu Val Lys Ser Asn Val 
        355                 360                 365 

Ser Thr Asn Ser Arg Lys Ser Ser Asn Phe Glu Asp Glu Leu Ala Arg 
    370                 375                 380 

Arg Val Ser Ser Pro Leu Ser Ala Leu Asn Gln Met Ser Gln Ser Pro 
385                 390                 395                 400 

Ile Pro Ile Arg Val Ser Ser Asp Lys Asp Tyr Asp Ser Tyr Ala Cys 
                405                 410                 415 

His Glu Val Val Ser Asn Pro Ser Thr Leu Asp Asp Asp Tyr Asn Tyr 
            420                 425                 430 

Met Phe Val Cys Pro Pro Glu Glu Tyr Thr Tyr Ser Thr Asp Asn Val 
        435                 440                 445 

Arg Thr Asp Ser Leu Asp Leu Gln Ser Leu Pro Thr Pro Thr Leu Glu 
    450                 455                 460 

Gln Leu Glu Ser Val Pro Phe Asn Arg Tyr Gly Tyr Val Arg Ile Phe 
465                 470                 475                 480 

Pro Ser Thr Thr Leu Ser Ser Thr Ala Ser Gly Tyr Tyr Thr Pro Asp 
                485                 490                 495 

Ser Leu Ser Thr Pro Glu Pro Ser Ile Asp Gly Leu Thr Asn Leu Asp 
            500                 505                 510 

Asp Val Gln Val Gly Gly Phe Val Gln Gly Ser Gly Asn Gln Asn Arg 
        515                 520                 525 

Arg Pro Ile Ser Phe Pro Val Ile Ser Asn Met Gln Pro Asn Ile Thr 
    530                 535                 540 

Asn Val Arg Ser Ala Ser Ala Pro Leu Cys Ser Ser Pro Val Pro Ser 
545                 550                 555                 560 

Arg Arg Tyr Ser Gln Tyr Ala Thr Asn Ala Arg Tyr Thr Pro Arg Lys 
                565                 570                 575 

Val Ser Ser Gly Ser Val Leu Arg Lys Ile Ser Ser Phe Phe Arg Lys 
            580                 585                 590 

Asp 

 
           
             15  
             1462  
             PRT  
             Candida albicans  
           
            15 

Met Ser Thr Val Val Asn Arg Arg Ser Ser His Gln Phe Asp Ser Pro 
  1               5                  10                  15 

Ser Asn His Leu Asp His Ser Ser Ser Met Asn Val Asp Lys Val Val 
             20                  25                  30 

Gln Ser Val Thr Asn Ala Thr Lys Arg Leu Ser Gln Ile Ser Thr Asn 
         35                  40                  45 

Thr Asn Asn Ser Asn Lys Lys Arg Lys Thr Gln Asn Lys Ile Gly Pro 
     50                  55                  60 

Trp Lys Leu Gly Arg Thr Leu Gly Arg Gly Ser Thr Gly Arg Val Arg 
 65                  70                  75                  80 

Leu Ala Lys Asn Thr Thr Thr Gly Gln Leu Ala Ala Val Lys Ile Val 
                 85                  90                  95 

Pro Lys Ser Asn Phe Lys Lys Leu Glu Asn Pro Lys Tyr Lys Arg Ser 
            100                 105                 110 

Lys Glu Asp Ala Thr Arg Leu Pro Tyr Gly Ile Glu Arg Glu Ile Ile 
        115                 120                 125 

Ile Met Lys Leu Ile Ser His Pro Asn Ile Met Gly Leu Tyr Asp Val 
    130                 135                 140 

Trp Glu Asn Lys Asn Asp Leu Tyr Leu Ile Leu Glu Tyr Ile Glu Gly 
145                 150                 155                 160 

Gly Glu Leu Phe Asp Tyr Leu Ile Lys Arg Gly Lys Leu Gln Glu Tyr 
                165                 170                 175 

Glu Ala Ile Asn Tyr Phe Lys Gln Ile Ile Asn Gly Ile Asn Tyr Leu 
            180                 185                 190 

His Gln Phe Asn Ile Cys His Arg Asp Leu Lys Pro Glu Asn Leu Leu 
        195                 200                 205 

Leu Asp Phe Asn Lys Asn Ile Lys Ile Ala Asp Phe Gly Met Ala Ala 
    210                 215                 220 

Leu Glu Val Lys Glu Lys Leu Leu Glu Thr Ser Cys Gly Ser Pro His 
225                 230                 235                 240 

Tyr Ala Ser Pro Glu Ile Val Ala Gly Lys Asn Tyr His Gly Ala Pro 
                245                 250                 255 

Ser Asp Ile Trp Ser Cys Gly Ile Ile Leu Phe Ala Leu Leu Thr Gly 
            260                 265                 270 

His Leu Pro Phe Asp Asp Glu Asn Ile Arg Lys Leu Leu Leu Lys Val 
        275                 280                 285 

Gln Ser Gly Lys Phe Asn Met Pro Pro Glu Leu Ser Phe Glu Ala Lys 
    290                 295                 300 

Asp Leu Ile Thr Lys Met Leu Lys Val Asn Pro Arg Glu Arg Ile Thr 
305                 310                 315                 320 

Ile Asp Ala Ile Leu Thr His Pro Leu Leu Ala Lys Tyr Pro Glu Pro 
                325                 330                 335 

Thr Val Ser Tyr Ser Ser Thr Thr Thr Leu Asp Ile Asn Ser Ile Asn 
            340                 345                 350 

Ile Lys Gln Ile Glu Ser Val Asp Lys Ile Asp Lys Glu Ile Leu Lys 
        355                 360                 365 

Asn Leu Ser Val Leu Phe His Asn Cys Asp Glu Lys Thr Ile Ile Ser 
    370                 375                 380 

Arg Leu Leu Ser Pro Asn Arg Cys Pro Glu Lys Met Phe Tyr Tyr Leu 
385                 390                 395                 400 

Leu Met Lys Tyr Arg Asn Glu His Leu Ser Asn Ser Asn Ser Phe Asn 
                405                 410                 415 

Ser Ser Asn Asp Val Asp Ser Ala Arg Ser Leu Pro Arg Ser Thr Ser 
            420                 425                 430 

Tyr Val Lys Thr Thr Val Thr Asp His Ala Thr Gly Glu Lys His Thr 
        435                 440                 445 

Thr Val Lys Lys Ile Gln Gln Ser Ser Ser Ile Tyr Ser Asn Arg Ser 
    450                 455                 460 

Leu Leu Lys Lys Ser Thr Ser Ala Lys Gly Asn Val Leu Ser Asn Ile 
465                 470                 475                 480 

Thr Asn Arg Pro Asn Thr Pro Lys Gln Phe Ser Ala Ser Ser Ser Phe 
                485                 490                 495 

Asn Lys Lys Lys Ala Leu His Ser Lys Thr Gln Ile Tyr Ala Ser Arg 
            500                 505                 510 

Ser Arg Asn Ala Ser Ser Arg Ser Leu Lys Ser Asn Ser Ser Thr Gly 
        515                 520                 525 

Arg Asn Gly Asn Asn Ala Ser Val Thr Ser Val Asn Lys Ile Pro Glu 
    530                 535                 540 

Ile Thr Gly Ala Thr Val Leu Gln Pro Ile Pro Ser Met Ala Met Asn 
545                 550                 555                 560 

Arg Gly Asp Glu Gln Gln Asn Lys Thr Lys Lys Asn Leu Thr Gly Thr 
                565                 570                 575 

Phe Gly Asn Lys Ser Leu Leu Asn Phe Gln Leu Ile Cys Glu Glu Val 
            580                 585                 590 

Phe Glu Asn Asp Lys Glu Asn Ser Lys Pro Val Ser Lys Thr Pro Val 
        595                 600                 605 

Ser Gln Leu Pro Pro Pro Pro Pro Pro Pro Ile Glu Thr Pro Thr Ser 
    610                 615                 620 

Arg Thr Asn Ser Val Lys Arg Gly Lys Thr Trp Ser Leu Ala Arg Arg 
625                 630                 635                 640 

Glu Arg Glu Leu Ala Glu Gln Val Arg Gln Arg Asn Glu Ala Arg Glu 
                645                 650                 655 

Asn Lys Leu Lys Ala Glu Glu Leu Ala Arg Lys Glu Leu Glu Gln Glu 
            660                 665                 670 

Lys Lys Arg Ile Ala Glu Glu Lys Lys Arg Leu Glu Gln Gln Glu Arg 
        675                 680                 685 

Glu Leu Asp Glu Lys Gln Lys Leu Gln Glu Lys Gln Lys Ala Ala Leu 
    690                 695                 700 

Glu Lys Leu Gln Lys His Gln Ser Ala His Asp Phe Glu Gly Leu Phe 
705                 710                 715                 720 

Ala Ser Asn Arg Arg Ser Val Thr Asp Met Ala Pro Ser Ser Gly Met 
                725                 730                 735 

Ser Ser Leu Asp Pro Arg Ala His Met Val Ser Arg Ala Asn Thr Ile 
            740                 745                 750 

Gly Ser Pro Asn Leu Ser Ser Ser Ser Val Asn Ile Asp Glu Asn Ala 
        755                 760                 765 

Ser Lys Val Leu His Lys Phe Gly Ile Asp Val Ala Pro Ser Pro Lys 
    770                 775                 780 

Arg Phe Ser Arg Ala Ser Lys Thr Ser Thr Ser Lys Asn Leu Ser Ser 
785                 790                 795                 800 

Phe Leu Ala Pro Thr Val Ser Arg Asn Leu Ser Ser Gln Leu Lys Thr 
                805                 810                 815 

Ser Ser Ser Lys Asn Leu Ala Gly Tyr Leu His Gly Thr Thr Asp Thr 
            820                 825                 830 

Asn Gly Ser Ala Ile Ala Ala Lys Lys Lys Asp Asp Ser Thr Asn Glu 
        835                 840                 845 

Ala Leu Thr Ile Glu Glu Phe Asn Ala Lys Glu Arg Thr Ser Met Ser 
    850                 855                 860 

Pro Ser Ile Ser Lys Ala Ser Val Asn Lys Arg Asn Ser Asn Gln Ser 
865                 870                 875                 880 

Ser Tyr Tyr Arg Ser Met Phe Ser Asp Asn Gly Asn Asp Asp Asn Val 
                885                 890                 895 

Thr Lys Val Arg Thr Gly Glu Ser His Leu Ser Val Gln Glu Glu Glu 
            900                 905                 910 

Glu Met Asp Met Glu Asn Ala Ile Asp Glu Asp Ile Ser Leu Ile Pro 
        915                 920                 925 

Asn Pro Arg Phe Ser Arg Phe Ser Phe Gly Gly Leu Leu Gly Ser Asn 
    930                 935                 940 

Thr Val Ala Asn Glu Glu Gly Asp Trp Thr Ile Met Asn Ser Thr Leu 
945                 950                 955                 960 

Asn His Ser Asn Thr Val Val Arg Gly Thr His Asn Lys Ser Ser Thr 
                965                 970                 975 

Met Leu Gly Leu Gly Ile Lys Met Arg Asp Thr Thr Thr Ile Lys Glu 
            980                 985                 990 

Asp Glu Glu Phe Glu Asp Glu Lys Pro Phe Ile Ser Val Pro Ser Ser 
        995                1000                1005 

Glu Asp Asp Glu Gly Asn Thr His Lys Asn Lys Arg Gly Gly Leu Arg 
   1010                1015                1020 

Asp Ser Gly Asn Tyr Asp Phe Asp Glu Glu His Ser Val Ala Ser Thr 
1025               1030                1035                1040 

Ala Asn Thr Glu Tyr Ser Asp Val Ala Ser Gln Gly Gln Gln Met Pro 
               1045                1050                1055 

Gly Ser His Thr Ile His Gln Leu Glu Thr Glu Leu Ser Asn Phe Asp 
           1060                1065                1070 

Leu Leu Ser Tyr Arg Val Ala Asp Ile Gly Lys Val Asn Lys His Lys 
       1075                1080                1085 

Pro Ser Ile Val Asp Ser Lys Glu Thr Leu Leu Lys Asn His Ser Ser 
   1090                1095                1100 

Asp Glu Ala Thr Ile Glu Val Lys Glu Asp Asn Asn Glu His Asp Phe 
1105               1110                1115                1120 

Asn Asp Lys Ile Lys Gln His Tyr Asp Asp Asn Gly Asp Ser Glu Glu 
               1125                1130                1135 

Asp Asp Glu Asp Glu Asp Glu Glu Glu Glu Asp Asp Asp Asp Asp Asp 
           1140                1145                1150 

Asp Ala Arg Ser Ser Phe Glu Ala Arg Pro His Ser His Asn Tyr Ser 
       1155                1160                1165 

Leu Ala Glu Ile Thr Ser Glu Ser Pro Val Gly Gly Gly Tyr Glu Ser 
   1170                1175                1180 

Pro Ser Ile Ala Asn Asp Phe Lys Lys Ser Arg His Ser Thr Gly Ile 
1185               1190                1195                1200 

Phe Ser Thr Thr Gln Phe Pro Arg Ser Pro Tyr Val Val Asn Asn Asn 
               1205                1210                1215 

Gly Asp Ser Asn Lys Asp Glu Asn Ser Gln Gln Gln Thr Lys His Met 
           1220                1225                1230 

Leu Asn Asp Gly His Lys Gly Leu Ile Thr Ser Pro Val Gln Asp Thr 
       1235                1240                1245 

Phe Gly Ser Lys Lys Pro Val Glu Ser Asn Ser Leu Phe Arg Arg Leu 
   1250                1255                1260 

Ser Leu Asn Pro Asn Arg Ala Ala Pro Lys Ala Pro Ala Pro Pro Pro 
1265               1270                1275                1280 

Pro Ser Ala Pro Ile Ser Ser Ala Ala Lys Ala Asn Ile Ser Gln Pro 
               1285                1290                1295 

Leu Ser Ser Pro Thr Lys Gly His Asn Arg Phe Ser Arg Ile Ser Ile 
           1300                1305                1310 

Gly Ser Lys Asn Met Leu Gln Lys Glu Asp Lys Ser Thr Lys Ser Asn 
       1315                1320                1325 

Trp Phe Lys Lys Phe Phe His Ser Leu Thr Thr Pro Ser Ala Lys Asp 
   1330                1335                1340 

Gln Ser Gly Asn Ser Ser Ser Lys Val Ala Ser Lys Asp Ile Lys Ile 
1345               1350                1355                1360 

Ile Asp Thr Ser Leu Thr Ala Ala Gln Leu Ile Arg Val Ile Lys Tyr 
               1365                1370                1375 

Gln Leu Glu Leu Lys Lys Ile Glu Gly Ser Ile Ser Lys Val Asp Ile 
           1380                1385                1390 

Asp Glu Glu Phe Gly Leu Ile Ser Gly Val Ile Pro Ser Lys Phe Ala 
       1395                1400                1405 

Asn Gly Arg Lys Leu Lys Phe Lys Ile Glu Val Ile Asp Leu Ile Asn 
   1410                1415                1420 

Ser Ser Ser Leu His Val Ile Lys Met Lys Gly Asn Asp Lys Gly Phe 
1425               1430                1435                1440 

Gln Ser Leu Val Asn Ile Val Thr Phe Ile Ile Lys Lys Glu Glu Gln 
               1445                1450                1455 

Asp Lys Ile Ser Arg Arg 
           1460 

 
           
             16  
             1349  
             PRT  
             Candida albicans  
           
            16 

Met Pro His Ser Arg Gln Pro Ser Ile Ser Ser Ser Ile Met Ser Gln 
  1               5                  10                  15 

Ser Asn His Asn His Pro Gln Lys Ile Gly Pro Trp Lys Leu Gly Lys 
             20                  25                  30 

Thr Leu Gly Arg Gly Ala Thr Gly Arg Val Leu Leu Ala Thr His Gln 
         35                  40                  45 

Thr Thr Gly Gln Lys Ala Ala Val Lys Val Val Ser Lys Ser Glu Leu 
     50                  55                  60 

Gln Asp Glu Glu Thr Glu Lys Asn Gly Asp Gly Leu Pro Tyr Gly Ile 
 65                  70                  75                  80 

Glu Arg Glu Ile Ile Ile Met Lys Leu Leu Thr His Pro Asn Val Leu 
                 85                  90                  95 

Arg Leu Tyr Asp Val Trp Glu Thr Ser Lys Ala Leu Tyr Leu Val Leu 
            100                 105                 110 

Glu Tyr Val Glu Gly Gly Glu Leu Phe Asp Leu Leu Val Glu Arg Gly 
        115                 120                 125 

Pro Leu Pro Glu Val Glu Ala Ile Lys Tyr Phe Arg Gln Ile Ile Leu 
    130                 135                 140 

Gly Thr Ala Tyr Cys His Ala Leu Gly Ile Cys His Arg Asp Leu Lys 
145                 150                 155                 160 

Pro Glu Asn Leu Leu Leu Asp Ser Gln Leu Asn Val Lys Leu Ala Asp 
                165                 170                 175 

Phe Gly Met Ala Ala Leu Glu Ser Asn Gly Lys Leu Leu Glu Thr Ser 
            180                 185                 190 

Cys Gly Ser Pro His Tyr Ala Ala Pro Glu Ile Val Ser Gly Leu Lys 
        195                 200                 205 

Tyr His Gly Ala Ala Ser Asp Val Trp Ser Cys Gly Val Ile Leu Phe 
    210                 215                 220 

Ala Leu Leu Thr Gly Arg Leu Pro Phe Asp Asp Glu Asn Ile Arg Asn 
225                 230                 235                 240 

Leu Leu Leu Lys Val Gln Ala Gly Asn Phe Glu Met Pro Val Asp Glu 
                245                 250                 255 

Val Ser Arg Glu Ala Arg Asp Leu Ile Ala Arg Met Leu Glu Val Asp 
            260                 265                 270 

Pro Met Arg Arg Ile Ser Thr Glu Lys Ile Leu Arg His Pro Leu Leu 
        275                 280                 285 

Thr Lys Tyr Pro Met Ser Asn Glu Asp Leu Ile Ser Glu Lys Ser Leu 
    290                 295                 300 

Pro His Pro Gln Thr Gly Tyr Lys Ser Leu Gly Ser Val Arg Asn Ile 
305                 310                 315                 320 

Asp Lys Gln Ile Leu Ser Asn Leu Thr Ile Leu Trp Asn Asp Arg Pro 
                325                 330                 335 

Glu Glu Glu Ile Val Asp Cys Leu Leu Lys Asp Gly Ser Asn Pro Glu 
            340                 345                 350 

Lys Thr Phe Tyr Ala Leu Leu Met Arg Tyr Lys His Asn Gln Glu Asp 
        355                 360                 365 

Asn Thr Asn Asn Asn Ser Pro Lys Lys Ser Thr Ser Phe Asn Asn Lys 
    370                 375                 380 

Val Val Arg Ser Gly Ser Lys Tyr Ser Leu Asn Gly Thr Pro Arg Arg 
385                 390                 395                 400 

Lys Arg Ala Ser His Ile Ser Val Ser Arg Pro Thr Ser Phe Gln Tyr 
                405                 410                 415 

Lys Ser Asn Pro Gly Ala Gly Ala Thr Ala Asn Arg Asn Ser Val Ala 
            420                 425                 430 

Arg His Ser Val Ala Ser Ser Ala Asn Asn Ser Pro Arg Lys Ser Pro 
        435                 440                 445 

Tyr Lys Ser Pro Tyr Arg Ser Pro Tyr Arg Ser Pro Tyr Lys Ser Pro 
    450                 455                 460 

Ser Lys Arg Tyr Ser Tyr Asn Gln Ser Pro Thr Lys Ser Pro Tyr Gly 
465                 470                 475                 480 

Arg Arg Ser Asn Ser Gln Arg Gln Phe Glu Asn Glu Pro Leu Lys Ala 
                485                 490                 495 

Lys Pro Arg Asn Ile Tyr Asn Glu Ile Val Asp Ala Gln Ser Asn Phe 
            500                 505                 510 

Ser Leu Pro Pro Ser Leu Pro Pro Ser Leu Pro Ser Lys Asp Ser Arg 
        515                 520                 525 

Tyr Met Ile Asp Glu Pro Asn Gln Pro Gln Leu Gln Gln Pro Ala Leu 
    530                 535                 540 

Ser Gln Val Pro Glu Asn Pro Ile Val Asp Glu Ser Pro Asp Leu Met 
545                 550                 555                 560 

Gln Ser Ala Lys Ile Ser Ser Gly Lys Arg Asn Ser Ile Ile Gly Lys 
                565                 570                 575 

Asn Asn Asn Asn Ser Asn Ser Asn Lys Arg Met Ser Lys Arg Lys Ser 
            580                 585                 590 

Ile Arg Ala Ser Met Thr Thr Gly Leu Lys Arg Asn Ser Ile Thr Met 
        595                 600                 605 

Lys Leu Leu Ser Thr Tyr Ala Lys Leu Ser Gly Asp Asp Asp Trp Glu 
    610                 615                 620 

Tyr Met Asp Lys Gln Thr Lys Arg Thr Ser Ala Thr Phe Ala Ala Leu 
625                 630                 635                 640 

Cys Asp Lys Ile Phe Asn Gln Glu Asp Tyr Asp Glu Glu Asp Glu Gln 
                645                 650                 655 

Leu Val Asp Pro Glu Glu Lys Glu Ala Lys Glu Tyr Glu Arg Leu Met 
            660                 665                 670 

Glu Leu Glu Arg Lys Lys His Glu Ala Glu Leu Lys Ala Arg Arg Glu 
        675                 680                 685 

Leu Glu Lys Lys Lys Arg Arg Gln Lys Arg Arg Ser Ile Leu Ser Ser 
    690                 695                 700 

Lys Lys Leu Ser Ile Ile Val Lys Asn Asp Ala Asp Pro Asn Asn Ser 
705                 710                 715                 720 

Glu Gln Glu Leu Val Asp Glu Gly Ile Lys Gln Pro Lys Arg Gln Ser 
                725                 730                 735 

Lys Asn Leu Thr Ala Leu Arg Ala Leu Ser Glu Gly Asn His Ala Ser 
            740                 745                 750 

Glu Glu Leu Thr Leu Glu Asp Val Glu Asn Leu Lys Arg Arg Ser Ala 
        755                 760                 765 

Ser Gln Pro Val Pro Lys Arg Arg Gln Thr Pro Val Leu Thr Arg Arg 
    770                 775                 780 

Pro Val Ser Arg Leu Asp Pro Leu Trp Gln Ala His Glu Asn Glu Gln 
785                 790                 795                 800 

Leu Asp Arg Ala Lys Asp Ala Leu Glu Gln Glu Trp Arg Asp Ser Gln 
                805                 810                 815 

Lys Arg Ser Ser Thr Val Ser Arg Lys Lys Val Asn Arg Glu Ser Met 
            820                 825                 830 

Ile Ser Val Met Asp Asp Ile Val Glu Glu Asp Gln Gly Arg Val Asn 
        835                 840                 845 

Arg Arg Ser Thr Arg Asn Thr Tyr Tyr Glu Arg Glu Arg Asp Tyr Glu 
    850                 855                 860 

Leu Pro Glu Pro Thr Val Glu Asp Ser Asn Leu Thr Asp Asp Tyr Met 
865                 870                 875                 880 

Thr Glu Ile Arg Lys Ser Arg Leu Leu Asn Ser Gln Leu Asn Val Arg 
                885                 890                 895 

Asp Pro Leu Asn Glu Lys Arg Lys Ser Glu Pro Lys Thr Leu Ile Ser 
            900                 905                 910 

Asn Val Gln Ile Pro Ser Val Thr Arg Lys Ser Arg Asn Phe Thr Thr 
        915                 920                 925 

Ser Asn Lys Arg Leu Ser Val Leu Ser Met Tyr Ser Thr Lys Glu Ser 
    930                 935                 940 

Tyr Arg Asp Leu Asn Ser Ile Ile Asn Ser Pro Asp Glu Asn Pro Glu 
945                 950                 955                 960 

Gln His Gln Asn Met Asn Lys Pro Ala Leu Arg Thr Ser Ile Ala Asp 
                965                 970                 975 

Arg Leu Asp Lys Ala Gly Leu Ala Glu Pro Glu Tyr Glu Thr Glu Thr 
            980                 985                 990 

Asp Gly Glu Asp Lys Val Ser Val Ile Asp Leu Asp Asp His Leu Ala 
        995                1000                1005 

Asp Arg Arg Thr Ser Tyr Tyr Asp Gly Ser Gly Lys Arg Ala Ser Arg 
   1010                1015                1020 

Ala Ser Thr Thr Lys Arg Tyr Asn Val His Ser Ser Ser Gly Gln Arg 
1025               1030                1035                1040 

Pro Lys Ser Lys Val Pro Asp Leu Pro Lys Asn Asp Tyr Asp Asp Thr 
               1045                1050                1055 

Phe Val Ser Asn Ser Asp Glu Val His Lys Arg Gln Tyr Lys Ser Met 
           1060                1065                1070 

Val Ser Asp Glu Ser Ser Ala Ser Asp Asp Val Phe Asp Lys Ile Lys 
       1075                1080                1085 

Leu Pro Asp Gly Lys Ser Thr Lys Ser Ser Ile Asp Glu Leu Ala Asn 
   1090                1095                1100 

Gly Thr Ser Thr Ser Gly His Arg Lys Pro Lys Ile Arg His Ser Gln 
1105               1110                1115                1120 

Pro Gly Pro Glu Met Leu Ile Pro His Leu Asn Gly Gly Ile Glu Ser 
               1125                1130                1135 

Ser Gln Pro Met Ser Lys Val Arg Gly Asn Asn Ser Ser Gly His Asp 
           1140                1145                1150 

Asp Ser Val Pro Pro Pro Pro Pro Ala His Lys Val Asn Lys Lys Pro 
       1155                1160                1165 

Leu Asp Asp Lys Thr Asn Phe Pro Pro Pro Glu Val Asp Pro Lys Arg 
   1170                1175                1180 

Lys Gly Ser Phe Phe Arg Lys Leu Ser Trp Gly Ser Lys Lys Thr Ile 
1185               1190                1195                1200 

Glu Asn Asn Thr Asn Ala Ala Thr Asn Thr Thr Thr Gln Gln Gln Leu 
               1205                1210                1215 

Pro Ser Pro Ala Glu Ser Lys Glu Glu Lys Pro Lys Ser Ser Phe Phe 
           1220                1225                1230 

Arg Trp Phe Ser Ser Ser Asn Thr Pro Ser Ala Ala Glu Ile Arg Lys 
       1235                1240                1245 

Phe Asn Thr Ile Leu Pro Lys His Glu Met Ser Thr Ala Leu Phe Ala 
   1250                1255                1260 

Leu Leu Asn Ser Trp Ser Asn Phe Gly Leu Lys Asp Leu Arg Asn Asp 
1265               1270                1275                1280 

Gln Val Gly Tyr Tyr Ile Thr Gly Ala Ile Ser Lys His Asn Ser Phe 
               1285                1290                1295 

Asn Leu Lys Ser Cys Lys Phe Arg Ile Lys Ile Asn Gln Arg Asp Phe 
           1300                1305                1310 

Asn Gln Lys Ser Glu Ile Val Cys Val Arg Val Lys Gly Ser Lys Val 
       1315                1320                1325 

Thr Thr Asp Thr Leu Phe Ser Glu Ile Glu Lys Val Leu Leu Lys Glu 
   1330                1335                1340 

Gly Val Leu Asp Lys 
1345 

 
           
             17  
             1029  
             PRT  
             Saccharomyces cerevisiae  
           
            17 

Met Thr Leu Asp Tyr Glu Ile Tyr Lys Glu Gly Gly Ile Leu Asn Asn 
  1               5                  10                  15 

Arg Tyr Gln Lys Ile Glu Asp Ile Ser Glu Gly Ser Tyr Gly Tyr Val 
             20                  25                  30 

Ser Leu Ala Lys Asp Val Arg Glu Lys Arg Leu Val Ala Val Lys Tyr 
         35                  40                  45 

Ile Phe Lys Leu Glu Asp Asp Gly Gln Tyr Asp Gly Pro Gln Asp Asp 
     50                  55                  60 

Glu Asn Asp Cys Asp Ser Ser Asp Cys Asp Asp Asp Glu Asp Thr Lys 
 65                  70                  75                  80 

Val Asp Thr Asp Arg His Glu Asn Glu Asn Gly Asn Ala Ser Ser Asn 
                 85                  90                  95 

Asn Gly Ser Ser Arg Glu Lys Lys His Asn Leu Tyr Lys His Lys Lys 
            100                 105                 110 

Ser Leu Ile Ser Ser Lys Val Lys Ser Arg Leu Ser Asn Asn Ile Cys 
        115                 120                 125 

Leu Glu Ala Met Tyr Glu Val Asp Ile Gln Thr Lys Ile Gly Arg His 
    130                 135                 140 

Gln Asn Ile Ala Ala Leu Leu Asp Phe Phe Asp Ser Tyr Ile Ile Met 
145                 150                 155                 160 

Glu Tyr Cys Ser Gly Gly Asp Leu Tyr Glu Ala Ile Lys Ala Asp Ala 
                165                 170                 175 

Val Pro Lys Lys Thr Lys Ser Ile Thr His Ile Ile Thr Gln Ile Met 
            180                 185                 190 

Asp Ala Ile Glu Tyr Val His Asn Lys Gly Ile Tyr His Arg Asp Ile 
        195                 200                 205 

Lys Pro Glu Asn Ile Leu Ile Ser Gly Ile Asp Trp Thr Ile Lys Leu 
    210                 215                 220 

Thr Asp Trp Gly Leu Ala Thr Thr Asp Lys Thr Ser Met Asp Arg Asn 
225                 230                 235                 240 

Val Gly Ser Glu Arg Tyr Met Ser Pro Glu Leu Phe Asp Ser Asn Leu 
                245                 250                 255 

Asp Ile Lys Glu Arg Lys Glu Pro Tyr Asp Cys Ala Lys Val Asp Leu 
            260                 265                 270 

Trp Ala Met Gly Ile Val Phe Leu Asn Ile Val Phe His Lys Asn Pro 
        275                 280                 285 

Phe Ser Ile Ala Asn Gln Ser Asp Lys Ser Phe Cys Tyr Phe Ala Ala 
    290                 295                 300 

Asn Arg Glu Ala Leu Phe Asp Val Phe Ser Thr Met Ala Tyr Asp Phe 
305                 310                 315                 320 

Phe Gln Val Leu Arg Tyr Ser Leu Thr Ile Asp Pro Ala Asn Arg Asp 
                325                 330                 335 

Leu Lys Met Met Arg Thr Glu Leu Gln Asn Leu Ser Glu Tyr Thr Leu 
            340                 345                 350 

Asp Asp Glu Tyr Tyr Asn Asn Leu Asp Glu Gly Tyr Glu Glu Thr Met 
        355                 360                 365 

Ile Asp Gly Leu Pro Pro Gln Pro Val Pro Pro Ser Ser Ala Pro Val 
    370                 375                 380 

Ser Leu Pro Thr Pro Ile Ser Ser Ser Asn Lys Gln His Met Pro Glu 
385                 390                 395                 400 

Phe Lys Lys Asp Phe Asn Phe Asn Asn Val Asn Glu Arg Lys Arg Ser 
                405                 410                 415 

Asp Val Ser Gln Asn Gln Asn Val Ala Ser Gly Phe Phe Lys Lys Pro 
            420                 425                 430 

Ser Thr Gln Gln Gln Lys Phe Phe Asn Gln Gly Tyr Asn Thr Thr Leu 
        435                 440                 445 

Ser Thr His Glu Arg Ala Lys Ser Ala Pro Lys Phe Lys Phe Lys Lys 
    450                 455                 460 

Arg Asn Lys Tyr Gly Arg Thr Asp Asn Gln Phe Ser Lys Pro Val Asn 
465                 470                 475                 480 

Ile Glu Asp Arg Lys Lys Ser Lys Ile Leu Lys Lys Ser Arg Lys Pro 
                485                 490                 495 

Leu Gly Ile Pro Thr Pro Asn Thr His Met Asn Asn Phe Phe His Asp 
            500                 505                 510 

Tyr Lys Ala Arg Asp Glu Phe Asn Thr Arg Asp Phe Phe Thr Pro Pro 
        515                 520                 525 

Ser Val Gln His Arg Tyr Met Glu Gly Phe Ser Asn Asn Asn Asn Lys 
    530                 535                 540 

Gln Tyr Arg Gln Asn Arg Asn Tyr Asn Asn Asn Asn Asn Asn Ser Asn 
545                 550                 555                 560 

Asn Asn His Gly Ser Asn Tyr Asn Asn Phe Asn Asn Gly Asn Ser Tyr 
                565                 570                 575 

Ile Lys Gly Trp Asn Lys Asn Phe Asn Lys Tyr Arg Arg Pro Ser Ser 
            580                 585                 590 

Ser Ser Tyr Thr Gly Lys Ser Pro Leu Ser Arg Tyr Asn Met Ser Tyr 
        595                 600                 605 

Asn His Asn Asn Asn Ser Ser Ile Asn Gly Tyr Ala Arg Arg Gly Ser 
    610                 615                 620 

Thr Thr Thr Val Gln His Ser Pro Gly Ala Tyr Ile Pro Pro Asn Ala 
625                 630                 635                 640 

Arg Asn His His Val Ser Pro Thr Asn Gln Phe Leu Arg Val Pro Gln 
                645                 650                 655 

Ser Thr Ala Pro Asp Ile Ser Thr Val Leu Gly Gly Lys Pro Ser Tyr 
            660                 665                 670 

Gln Glu His Tyr Thr Gln Asp Ser Met Asp Ser Glu Gly Asp His Asp 
        675                 680                 685 

Ser Asp Asp Val Leu Phe Thr Leu Glu Glu Gly Asp His Asp Phe Val 
    690                 695                 700 

Asn Gly Met Asp Asn Leu Ser Ile Asn Asp His Leu Pro His Thr Thr 
705                 710                 715                 720 

Val Gly Ser His Asn Glu Val Phe Val His Ala Ser Thr Asn His Asn 
                725                 730                 735 

Asn Asn Gly Asn Asn Asn His Ile Asp Thr Asn Ser Thr Thr Asn Gln 
            740                 745                 750 

Tyr His Arg Gln Tyr Ile Pro Pro Pro Leu Thr Thr Ser Leu His Ile 
        755                 760                 765 

Asn Asn Asn Asn Asn Glu Ser Asn Glu Leu Pro Asp Leu Leu Lys Ser 
    770                 775                 780 

Pro Ala Ser Ser Glu Ala His Leu Asn Leu Ser Ser Gly Pro Ile Asp 
785                 790                 795                 800 

Pro Ile Leu Thr Gly Asn Ile Gly Asn Arg Tyr Ser His Ser Ser Asp 
                805                 810                 815 

Ser Lys Glu Leu Glu Gln Glu Arg Arg Leu Ser Met Glu Gln Lys Phe 
            820                 825                 830 

Lys Asn Gly Val Tyr Val Pro Pro His His Arg Lys Ser Phe Asn Leu 
        835                 840                 845 

Gly Thr Gln Val Pro Pro Met Asn Met Lys Thr Ser Asn Glu Ala Thr 
    850                 855                 860 

Leu Ser Val Ser His Asn Ser Val Asn Phe Gly Gly Ser Tyr Asn Ser 
865                 870                 875                 880 

Arg Arg Ser Ser Ala Asn Glu Ser Asn Pro Leu His Met Asn Lys Ala 
                885                 890                 895 

Leu Glu Lys Leu Ser Ser Ser Pro Gly Ala Lys Ser Ser Phe Val Gly 
            900                 905                 910 

Phe Pro Lys Pro Leu Leu Pro Arg Asn His Ser Ser Thr Thr Ile Ala 
        915                 920                 925 

Leu Gln Asn Glu Asp Val Phe Ala Asp Ser Asn Asn Asp Ala Ile Ile 
    930                 935                 940 

Phe Glu Asp Glu Glu Tyr Glu Gly Glu Ser Asp Lys Met Ala His Gly 
945                 950                 955                 960 

Lys Met Glu Gly Gly Asp Asn Glu Ser Ser Ser Thr Ser Pro Asp Glu 
                965                 970                 975 

Arg Gln Ile Phe Gly Pro Tyr Glu Ile Tyr Ala Gln Thr Phe Ala Gly 
            980                 985                 990 

Ser Thr His Asp Lys Lys Leu Gly Ala Gly Arg Lys Thr Ser Ile Gln 
        995                1000                1005 

Asp Glu Met Val Gly Ser Leu Glu Gln Tyr Lys Asn Asn Trp Leu Ile 
   1010                1015                1020 

Leu Gln Gln Gln Asp 
1025 

 
           
             18  
             502  
             PRT  
             Saccharomyces cerevisiae  
           
            18 

Met Leu Ser Asp Cys Leu Leu Asn Asn Phe Arg Ile Thr Ala Gln Ile 
  1               5                  10                  15 
Gly Ser Gly Ala Tyr Gly Leu Val Phe His Val Val Asp Ile Leu Thr 
             20                  25                  30 
Ser Arg Glu Tyr Ala Val Lys Thr Val Phe Lys Ser Ser Ser Met Asp 
         35                  40                  45 
Glu Phe Tyr Asn Lys Asn Gly Leu Asn Asn Asn Ser Gln Val Ala Arg 
     50                  55                  60 
Thr Thr Leu Leu Gln Thr Gln Leu Tyr His Phe Phe Lys Ser Phe Gln 
 65                  70                  75                  80 
Lys Lys Leu Phe Leu Pro Ser Val Asp Leu Asp Ser Ile Leu Gln Leu 
                 85                  90                  95 
Thr Glu Asn Glu Leu Asn Arg Leu Pro His Tyr Arg Glu Ile Ala Phe 
            100                 105                 110 
Gln Leu Arg Val Gln Ser His Gly Asn Ile Val Lys Ile His Gln Val 
        115                 120                 125 
Leu Glu Ser Ser Ile Ala Thr Phe Ile Val Met Asp Tyr Tyr Asp Arg 
    130                 135                 140 
Asp Leu Phe Thr Ser Ile Val Asp Asp Lys His Phe Val Asn His Gly 
145                 150                 155                 160 
Ile Leu Ile Lys Lys Val Phe Leu Gln Leu Cys Ser Ala Leu Asp His 
                165                 170                 175 
Cys His Arg Leu Gly Ile Tyr His Cys Asp Ile Lys Pro Glu Asn Val 
            180                 185                 190 
Leu Leu Asp Arg Asn Asp Asn Ala Tyr Leu Cys Asp Phe Gly Leu Ser 
        195                 200                 205 
Thr Lys Ser Lys Tyr Leu Ala Pro Asn Val Cys Val Gly Ser Ser Tyr 
    210                 215                 220 
Tyr Met Ala Pro Glu Arg Ile Leu Tyr Cys Leu Asn Thr Thr Thr Asn 
225                 230                 235                 240 
Gly Ile His Val Asp Glu Cys Cys Ser Ser Leu Pro Thr Asp Thr Gly 
                245                 250                 255 
Asp Ile Trp Ser Leu Gly Ile Ile Leu Ile Asn Leu Thr Cys Ile Arg 
            260                 265                 270 
Asn Pro Trp Leu Lys Ala His Gln Lys Glu Asp Asn Thr Phe Gln His 
        275                 280                 285 
Phe Ala Asn Asp Asn Asn Val Leu Lys Lys Ile Leu Pro Ile Ser Asp 
    290                 295                 300 
Glu Leu Phe Thr Val Leu Thr Lys Ile Leu Gln Leu Asn Pro Tyr Thr 
305                 310                 315                 320 
Arg Ile Asp Met Lys Thr Leu Met Ser Glu Val Ser Ser Leu Thr Ser 
                325                 330                 335 
Phe Thr Arg Glu Gly Pro Leu Ser Gln Val Pro Ile Leu Ser Ser Glu 
            340                 345                 350 
Val Tyr Met Thr His Ile Ile Arg Asn Glu Asn Leu Phe Leu Ser Asp 
        355                 360                 365 
Leu Ser His Phe Ser Ala Asp Gln Glu Gln Gln Gln Gln Gln Gln Gln 
    370                 375                 380 
Gln Gln Gln Gln Val Gln Glu Gln Glu Gln Glu Gln Lys Gln Glu Gln 
385                 390                 395                 400 
Ile Gln Asn Gln Glu Gln Ala Gln Gln Gln Gln Glu Glu Glu Asp Ala 
                405                 410                 415 
Glu Pro Glu Ser Asp Ile Pro Ser Thr Tyr Asn Ser Asp Gly Ser Met 
            420                 425                 430 
Glu Lys Tyr Glu Tyr Thr Asn Asn His Asn Asn Ser Thr Phe Leu Thr 
        435                 440                 445 
Ser Ser Met Asp Ser Thr Pro Tyr Gln Ser Asp Ile Asp Asp Val Ser 
    450                 455                 460 
Ala Ser Lys Asp Cys Lys Phe Gln Gln Asp Thr Leu Arg Asn Arg Leu 
465                 470                 475                 480 
Leu Cys Leu Gln Met Asn Phe Ser Thr Leu Thr Asp Gly Pro Asn Glu 
                485                 490                 495 
Lys Trp Leu Pro Asp Tyr 
            500 

 
           
             19  
             461  
             PRT  
             Saccharomyces cerevisiae  
           
            19 

Met Met Met Phe His Asn Cys Arg Ile Asn Asn Tyr Leu Ile Thr Ser 
  1               5                  10                  15 

Gln Ile Gly Glu Gly Ala Tyr Gly Leu Val Tyr Arg Ala Leu Asp Ile 
             20                  25                  30 

Arg Thr Asp Arg Gln Tyr Ala Ile Lys Ala Val Val Gln Ser Tyr Gly 
         35                  40                  45 

Val Ser Lys Glu Ala Asp Met Gly Asn Asp Lys Ile His Lys Asn Ser 
     50                  55                  60 

Val Lys Leu Gln Lys Lys Leu Ala Lys Leu Phe Lys Glu Ser Lys Asn 
 65                  70                  75                  80 

Val Val Arg Val Pro Ser Ile Asp Leu Glu Ser Ile Glu Asn Met Ser 
                 85                  90                  95 

Glu Glu Asp Phe Lys Lys Leu Pro His Tyr Lys Glu Ile Ser Leu His 
            100                 105                 110 

Leu Arg Val His His His Lys Asn Ile Val Thr Ile His Glu Val Leu 
        115                 120                 125 

Gln Ser Ala Val Cys Thr Phe Ile Val Met Asp Tyr Tyr Pro Thr Asp 
    130                 135                 140 

Leu Phe Thr Ser Ile Val Asp Asn Arg His Phe Val Thr Asn Gly Leu 
145                 150                 155                 160 

Leu Val Lys Lys Val Phe Leu Gln Ile Cys Ser Ala Leu Asn Tyr Cys 
                165                 170                 175 

His Glu His Gly Ile Tyr His Cys Asp Ile Lys Pro Glu Asn Leu Leu 
            180                 185                 190 

Leu Asp Thr Glu Asp Asn Val Phe Leu Cys Asp Phe Gly Leu Ser Thr 
        195                 200                 205 

Thr Ser Thr Tyr Ile Lys Pro Asn Val Cys Ile Gly Ser Ser Tyr Tyr 
    210                 215                 220 

Met Pro Pro Glu Arg Ile Ser Phe Asp Gly Arg Val Ser Ser Ser Lys 
225                 230                 235                 240 

Ser Gly Gly His Lys Leu Gly Lys Val Cys Pro Ser Cys Asn Gly Asp 
                245                 250                 255 

Leu Trp Ser Leu Gly Ile Ile Leu Ile Asn Leu Thr Cys Ile Arg Asn 
            260                 265                 270 

Pro Trp Leu Lys Ala Asp Lys Thr Glu Asp Asn Thr Tyr Tyr Tyr Phe 
        275                 280                 285 

Thr Lys Asp Pro Asn Ile Leu Lys Gln Ile Leu Pro Leu Ser Asp Asp 
    290                 295                 300 

Phe Tyr Ser Leu Leu Ser Lys Ile Leu Gln Val Asn Pro Lys Asn Arg 
305                 310                 315                 320 

Met Ser Leu Gln Glu Leu Met Lys Glu Val Ser Ser Ile Thr Ser Phe 
                325                 330                 335 

Thr Asn Glu Gly Pro Leu Ser Lys Val Pro Pro Leu Ser Lys Ser Val 
            340                 345                 350 

Tyr Glu Lys Phe Val Ser Pro Val Asp Asn Thr Asn Glu Asn Leu Ser 
        355                 360                 365 

Pro Lys Ser Tyr Val Tyr Met His Asp Ser Lys Ala Ala Lys Asn Leu 
    370                 375                 380 

Ser Tyr Thr Ser Ser Ser Glu Glu Glu Asp Gly Ile Lys Glu Gly Ile 
385                 390                 395                 400 

Asp Asp Asp Asn Gly Ser Arg Ser Gly Ser Phe Gly Thr Leu Asp Thr 
                405                 410                 415 

Asp Thr Gly Leu His Ser Ser Phe Thr Ser Thr Ser Cys Glu Ser Asp 
            420                 425                 430 

Asn Glu Cys Ser Lys Ile Ser Asn Lys Phe Ser Leu Phe Glu Lys Lys 
        435                 440                 445 

Phe Asn Glu Leu Arg Met Ser Ser Ser Ser Leu Thr Asn 
    450                 455                 460 

 
           
             20  
             470  
             PRT  
             Schizosaccharomyces pombe  
           
            20 

Met Met Arg Glu Asn Pro Glu Leu Leu Leu Gly Gln Val Leu Gly Asp 
  1               5                  10                  15 

Ser Leu Arg Phe Val Ser Ile Ile Gly Ala Gly Ala Tyr Gly Val Val 
             20                  25                  30 

Tyr Lys Ala Glu Asp Ile Tyr Asp Gly Thr Leu Tyr Ala Val Lys Ala 
         35                  40                  45 

Leu Cys Lys Asp Gly Leu Asn Glu Lys Gln Lys Lys Leu Gln Ala Arg 
     50                  55                  60 

Glu Leu Ala Leu His Ala Arg Val Ser Ser His Pro Tyr Ile Ile Thr 
 65                  70                  75                  80 

Leu His Arg Val Leu Glu Thr Glu Asp Ala Ile Tyr Val Val Leu Gln 
                 85                  90                  95 

Tyr Cys Pro Asn Gly Asp Leu Phe Thr Tyr Ile Thr Glu Lys Lys Val 
            100                 105                 110 

Tyr Gln Gly Asn Ser His Leu Ile Lys Thr Val Phe Leu Gln Leu Ile 
        115                 120                 125 

Ser Ala Val Glu His Cys His Ser Val Gly Ile Tyr His Arg Asp Leu 
    130                 135                 140 

Lys Pro Glu Asn Ile Met Val Gly Asn Asp Val Asn Thr Val Tyr Leu 
145                 150                 155                 160 

Ala Asp Phe Gly Leu Ala Thr Thr Glu Pro Tyr Ser Ser Asp Phe Gly 
                165                 170                 175 

Cys Gly Ser Leu Phe Tyr Met Ser Pro Glu Cys Gln Arg Glu Val Lys 
            180                 185                 190 

Lys Leu Ser Ser Leu Ser Asp Met Leu Pro Val Thr Pro Glu Pro Ile 
        195                 200                 205 

Glu Ser Gln Ser Ser Ser Phe Ala Thr Ala Pro Asn Asp Val Trp Ala 
    210                 215                 220 

Leu Gly Ile Ile Leu Ile Asn Leu Cys Cys Lys Arg Asn Pro Trp Lys 
225                 230                 235                 240 

Arg Ala Cys Ser Gln Thr Asp Gly Thr Tyr Arg Ser Tyr Val His Asn 
                245                 250                 255 

Pro Ser Thr Leu Leu Ser Ile Leu Pro Ile Ser Arg Glu Leu Asn Ser 
            260                 265                 270 

Leu Leu Asn Arg Ile Phe Asp Arg Asn Pro Lys Thr Arg Ile Thr Leu 
        275                 280                 285 

Pro Glu Leu Ser Thr Leu Val Ser Asn Cys Lys Asn Leu Thr Arg Arg 
    290                 295                 300 

Leu Arg Pro Ala Pro Leu Val Ser Ser Arg Tyr Leu Ala Tyr Gln Gln 
305                 310                 315                 320 

Gln Gln Gln Gln Gln Gln Met Asn Leu Gln Gln Gly Ile Gln Gly Tyr 
                325                 330                 335 

Pro His Gln Gly Tyr Met Pro Thr Gln Asn Ile Gly Phe Pro Trp Pro 
            340                 345                 350 

Pro Thr Pro Gln Phe Val Ser Asn Trp Asn His Cys Ala Thr Pro Thr 
        355                 360                 365 

Ile Pro Val Ser Leu Gln Val Leu Thr Pro Asn Ser Ser Leu Lys Val 
    370                 375                 380 

Asp Pro Thr Thr Pro Leu Thr Ala Pro Ile His Ala Thr Glu Ser Phe 
385                 390                 395                 400 

Trp Pro Ser Ala Ala Ala Ala Ala Ala Ala Val His Asn Asn Ala Asn 
                405                 410                 415 

Ser Tyr Met Pro Ile Thr Pro Thr Pro Tyr Pro Asn Asn Ala Lys Ile 
            420                 425                 430 

Phe Gly Tyr Pro Asn Gln Pro Pro Leu Thr Pro Ile Pro Phe Thr Gly 
        435                 440                 445 

Phe Val Leu His Pro Ala Pro Val Gly Arg Ala Ala Asp Ala Val Asp 
    450                 455                 460 

Pro Ser Arg Lys Ser Leu 
465                 470 

 
           
             21  
             474  
             PRT  
             Schizosaccharomyces pombe  
           
            21 

Met Lys Leu Leu Gln Lys Lys Gly Tyr Lys Val Glu Arg Pro Leu Asn 
  1               5                  10                  15 

Lys Gly Ser Tyr Gly Thr Val Val Leu Ala His Arg Leu Phe Arg Thr 
             20                  25                  30 

Pro Arg Cys Lys Asp Leu Lys Tyr Ala Ile Lys Cys Ile Lys Lys Pro 
         35                  40                  45 

Ala Tyr Thr Phe Leu Gln Glu Val Asn Ile Leu Arg Gln Leu Ser Arg 
     50                  55                  60 

Ser Arg His Arg Asn Ile Ile His Phe Val Glu Ser Phe Glu Asp Asn 
 65                  70                  75                  80 

Val Tyr Tyr Tyr Val Val Leu Glu Tyr Cys Pro Leu Gly Asp Leu Tyr 
                 85                  90                  95 

Glu Cys Ile Leu Asn Asn Asp Phe Pro Asn Ala Lys Asn Gln Pro Glu 
            100                 105                 110 

Met Ile Lys Asn Ile Phe Leu Gln Ile Ile Asp Gly Val Ala His Leu 
        115                 120                 125 

His Ser His Gly Ile Tyr His Arg Asp Leu Lys Pro Glu Asn Phe Leu 
    130                 135                 140 

Leu Ser Leu Ser Glu Asp Gly Ser Glu Leu Val Val Lys Ile Ser Asp 
145                 150                 155                 160 

Phe Gly Leu Ala Cys Arg Asp Lys Ile Ser Tyr Asp Phe Gly Thr Gly 
                165                 170                 175 

Ser Asp Arg Tyr Met Ala Pro Glu Gln Phe Glu Glu Val Asp Gly Ala 
            180                 185                 190 

Gly Tyr Ser Pro Arg Ala Ala Asp Ile Trp Ala Leu Gly Ile Cys Leu 
        195                 200                 205 

Leu Asn Leu Ile Phe Ala Arg Asn Pro Phe Thr Tyr Pro His Glu Lys 
    210                 215                 220 

Asp Pro Ile Phe Ala Asp Tyr Met Leu Asp Ala Met Thr Leu Phe Asp 
225                 230                 235                 240 

Val Phe Pro Thr Leu Ser Gln Asp Thr Tyr Asn Val Leu Arg Ala Cys 
                245                 250                 255 

Leu Cys Val Ser Pro Glu Lys Arg Ser Leu Ala Lys Thr Arg Glu Ala 
            260                 265                 270 

Val Leu Ala Val Thr Lys Trp Thr Thr Asp Asp Glu Glu Leu Glu Ser 
        275                 280                 285 

Phe Val Asn Glu Glu Glu Glu Phe Arg Ala Ser Asp Phe Met Pro Ala 
    290                 295                 300 

Glu Asp Asn Val Arg Cys Thr Gln Ser Asp Arg Glu Pro Leu Arg Thr 
305                 310                 315                 320 

Pro Ser Val Leu Thr Pro Ala Asn Thr Ile Gln Arg Gly Leu Leu Pro 
                325                 330                 335 

Ser Lys Leu Pro Ala Leu Ser Asp Val Asp Glu Asn Ile Ser Thr Ser 
            340                 345                 350 

Ser Ser Pro Arg Ser Pro Ala Ser Leu Ala Pro Val Asn Asn Ser Glu 
        355                 360                 365 

Arg Ser Tyr Asp Ser Gly Leu Gly Glu Ser Leu Asn Asn Met His Ile 
    370                 375                 380 

Gly Lys Ser Ile Ala Thr Ala Val Pro Val Asn Thr Lys Arg Ser Pro 
385                 390                 395                 400 

Tyr Ser Cys Ser Ala Pro Ala Ile Val Phe Pro Asn Ser Ile Lys Gly 
                405                 410                 415 

Asn Lys Asp His Leu Lys Phe Gly Arg Ser Trp Cys Asp Met Asp Glu 
            420                 425                 430 

Glu Asp Glu Glu Asp Ile Val Ser Phe Gly Ser Asn Asp Asp Phe Gly 
        435                 440                 445 

Ala Ser Asp Glu Leu Ser Ser Lys His Ile Gly Leu Ala Asp Asp Trp 
    450                 455                 460 

Asn Val Leu Ser Gln Trp Asn Asp Asn Ser 
465                 470 

 
           
             22  
             413  
             PRT  
             Pichia jadinii  
           
            22 

Met Thr His Thr Asp Ile Thr Gly Ser Leu Ile Asn Glu Tyr Arg Ile 
  1               5                  10                  15 

Val Lys Leu Ile Gly Ser Gly Ala Tyr Gly Leu Val Tyr Gln Ala Gln 
             20                  25                  30 

Asn Thr Val Thr Gly Gln Gln Val Ala Ile Lys Cys Ile Ser Lys Lys 
         35                  40                  45 

Ser Asn Pro Ser Val Lys Lys Gln Ser Asp Tyr Leu Thr Thr Leu Leu 
     50                  55                  60 

Ala Glu His Leu Leu Glu Arg Asp Phe Ser Leu Gln Gly Leu Arg Glu 
 65                  70                  75                  80 

Met Ser Leu Lys Arg Leu Ser Met Ala Asp Asn Ile Pro Cys Pro Phe 
                 85                  90                  95 

Val Arg Glu Ile Ser Ile His Leu Gln Val His Gln His Pro Asn Val 
            100                 105                 110 

Ile Ser Ile His Lys Ile Leu Asp Ser Gln Val Ala Val Phe Val Val 
        115                 120                 125 

Met Asp Tyr Tyr Pro Glu Gly Asp Leu Phe Val Asn Ile Val Asp Arg 
    130                 135                 140 

Gln Val Tyr Ala Arg Ser Ser Gly Leu Ile Lys Asp Val Phe Ile Gln 
145                 150                 155                 160 

Leu Ile Asp Val Ile Ser Tyr Cys His Ser Lys Gly Ile Tyr His Cys 
                165                 170                 175 

Asp Ile Lys Pro Glu Asn Ile Met Cys Ala Asn Lys Gly Ser Lys Val 
            180                 185                 190 

Val Ile Gly Asp Phe Gly Leu Ala Val Lys Ser Lys Tyr Ile Gln Ser 
        195                 200                 205 

Lys Thr Cys Ile Gly Ser Ser Tyr Tyr Met Ala Pro Glu Arg Leu Cys 
    210                 215                 220 

Thr Met Asn His Ser Leu Thr Arg Leu Glu Tyr Pro Ala Cys Lys Gly 
225                 230                 235                 240 

Asp Ile Trp Ser Leu Gly Val Ile Leu Ile Asn Phe Cys Cys Thr Arg 
                245                 250                 255 

Asn Pro Trp Met Lys Ala Cys Glu Lys Asp Ala Thr Tyr Ser Ala Phe 
            260                 265                 270 

Lys Lys Asp Pro Lys Ile Leu Met Glu Ile Leu Asp Ile Ser Glu Glu 
        275                 280                 285 

Leu Trp Asn Ile Leu Cys Asp Cys Phe Arg Glu Glu Pro Glu Glu Arg 
    290                 295                 300 

Ile Ser Leu Phe Glu Leu Arg Asp Arg Val Leu Lys Cys Arg Ser Phe 
305                 310                 315                 320 

Thr Val Ala Gly Pro Leu Ser Arg Cys Asp Ser Tyr Glu Gln Asp Met 
                325                 330                 335 

Asp Asp Ala Leu Glu Cys Ala Val Pro Ala Asn Glu Ser Ser Val Gly 
            340                 345                 350 

Ser Asn Gly Ser Leu Asp Leu Pro Met Asp His Ile Ile Glu Tyr Ala 
        355                 360                 365 

Gln Tyr Leu Gln Thr Leu Ser Ser Val Lys Asn Thr Ala Ala Gly Asn 
    370                 375                 380 

Tyr Thr Gln Asn Gln Phe Val Leu Asp Asn Asn Ile Met Asp Asn Val 
385                 390                 395                 400 

Ser Ile Met Ser Asn Lys Ser Phe Asn Met Asn Phe Ala 
                405                 410 

 
           
             23  
             506  
             PRT  
             Nectria haematococca  
           
            23 

Met Gln His His Ala Ile Phe Gly Tyr Gln Thr Pro Pro Ala Ser Pro 
  1               5                  10                  15 

Gly Phe Asp Asn Pro Lys Cys Thr Ile Gln Gln Pro Phe Ala Val Pro 
             20                  25                  30 

Arg His Tyr Pro Thr Arg Pro Leu Ala Pro Glu Glu Arg Leu Gly Arg 
         35                  40                  45 

Val Leu Glu Gly Thr Leu Gln Leu Thr Glu Ile Leu Gly Thr Gly Ala 
     50                  55                  60 

Tyr Gly Val Val Tyr Leu Ala Val Asp Leu Lys Thr Gly Gly Lys Tyr 
 65                  70                  75                  80 

Ala Val Lys Cys Leu Ser Lys Phe Asn Ala Asp Gly Thr Gln Leu Glu 
                 85                  90                  95 

Pro Arg Gln Phe Ala Tyr Gln Gln Arg Glu Ile Arg Leu His Trp Lys 
            100                 105                 110 

Ala Ser Asn His Ala Asn Val Val Gln Met Leu Lys Ile Val Asn Asp 
        115                 120                 125 

Pro Asp Cys Ile Tyr Val Ile Leu Glu Tyr Cys Pro Glu Gly Asp Leu 
    130                 135                 140 

Phe Leu Asn Ile Thr Glu Arg Gly Gln Tyr Val Gly Lys Asp Glu Leu 
145                 150                 155                 160 

Ser Arg Asn Ile Phe Leu Gln Ile Leu Asp Ala Val Glu His Cys His 
                165                 170                 175 

Asn Leu Gly Ile Tyr His Arg Asp Leu Lys Pro Glu Asn Ile Leu Val 
            180                 185                 190 

Thr Asp Arg Gly Asp Thr Val Lys Leu Ala Asp Phe Gly Leu Ala Thr 
        195                 200                 205 

Ser Asp Asp Arg Ser Glu Asp Tyr Gly Cys Gly Ser Thr Phe Tyr Met 
    210                 215                 220 

Ser Pro Glu Cys Leu Asp Pro Ser Ala Arg Lys Pro Tyr Tyr Met Cys 
225                 230                 235                 240 

Ala Pro Asn Asp Val Trp Ser Leu Gly Val Ile Leu Val Asn Leu Thr 
                245                 250                 255 

Cys Gly Arg Asn Pro Trp Lys Gln Ala Ser Phe Gln Asp Ser Thr Tyr 
            260                 265                 270 

Arg Ala Tyr Ala Gly Ser Lys Asp Phe Leu Lys Thr Ile Leu Pro Leu 
        275                 280                 285 

Ser Asp Glu Leu Asn Glu Ile Leu Gly Arg Ile Phe Glu Pro Asn Pro 
    290                 295                 300 

Glu Gln Arg Ile Thr Leu Asn Glu Leu Arg Thr Arg Ile Met Ala Cys 
305                 310                 315                 320 

Ser Arg Phe Thr Met Pro Ala Val Ser Pro Pro Thr Pro Pro Ala Ser 
                325                 330                 335 

Pro Asp His Thr Thr Gln Tyr Val Ser Thr Glu Asp Ala Ile Ile Asp 
            340                 345                 350 

Asp Tyr Asp Tyr Asp Ser Pro Leu Ser Pro Ala Ser Ser Ser Asp Asp 
        355                 360                 365 

Glu Gly Ser Leu Thr Ser Ser Gly Ser Thr Ile Asp Asp Leu Asp Asp 
    370                 375                 380 

Asp Phe Asp Gln Glu Arg Gln Met Pro Gln Thr Pro Pro Glu Tyr Ala 
385                 390                 395                 400 

Pro His Ala Phe Asp Pro Glu Glu Pro Lys Glu His Gln Leu Ile Tyr 
                405                 410                 415 

His Ser Gln Glu Phe Val Pro Gln Lys Tyr Ser Gly Pro Val Pro Val 
            420                 425                 430 

Pro Val Gln Val Pro Val Gly Val Pro Pro Gln Pro Met Leu Cys Gln 
        435                 440                 445 

Pro Val Pro Val Pro Ile Gln Ala Pro Val Pro Ile Gln Ala Pro Cys 
    450                 455                 460 

Gln Gln His Lys Ser Tyr Phe Pro Ile Trp Asp Met Val Lys Tyr Val 
465                 470                 475                 480 

Gln His Val Pro Ile Leu Gln His His Ile Pro Phe His Gln Gln Val 
                485                 490                 495 

Pro Phe Met Pro Thr Phe Gln Gly Cys Tyr 
            500                 505 

 
           
             24  
             315  
             PRT  
             Candida albicans  
           
            24 

Asp Leu Cys Tyr Ala Asn Ser Ile Ile Asp Tyr Asn Glu Leu His Leu 
  1               5                  10                  15 

Val Leu Ile Asp Phe Gly Leu Ala Met Asp Ser Ala Thr Ile Cys Cys 
             20                  25                  30 

Asn Ser Cys Arg Gly Ser Ser Phe Tyr Met Ala Pro Glu Arg Thr Thr 
         35                  40                  45 

Asn Tyr Asn Thr His Arg Leu Ile Asn Gln Leu Ile Asp Met Asn Gln 
     50                  55                  60 

Tyr Glu Ser Ile Glu Ile Asn Gly Thr Thr Val Thr Lys Ser Asn Cys 
 65                  70                  75                  80 

Lys Tyr Leu Pro Thr Leu Ala Gly Asp Ile Trp Ser Leu Gly Val Leu 
                 85                  90                  95 

Phe Ile Asn Ile Thr Cys Ser Arg Asn Pro Trp Pro Ile Ala Ser Phe 
            100                 105                 110 

Asp Asn Asn Gln Asn Asn Glu Val Phe Lys Asn Tyr Met Leu Asn Asn 
        115                 120                 125 

Asn Lys Ala Val Leu Ser Lys Ile Leu Pro Ile Ser Ser Gln Phe Asn 
    130                 135                 140 

Arg Leu Leu Asp Arg Ile Phe Lys Leu Asn Pro Asn Asp Arg Ile Asp 
145                 150                 155                 160 

Leu Pro Thr Leu Tyr Lys Glu Val Ile Arg Cys Asp Phe Phe Lys Asp 
                165                 170                 175 

Asp His Tyr Tyr Tyr Ala Gln His Gln His His His Asn His Asn Gln 
            180                 185                 190 

Ile Asn Asn Ala Tyr Asn His Tyr Gln Lys Gln Pro Asn Gln Ala Arg 
        195                 200                 205 

Pro Thr Ala Asn Gln Gln Leu Tyr Thr Pro Pro Glu Thr Thr Thr Tyr 
    210                 215                 220 

Asn Ser Tyr Ala Ser Asp Met Glu Glu Asp Glu Ile Ser Asp Asp Glu 
225                 230                 235                 240 

Phe Tyr Ser Asp Glu Glu Asp Glu Asp Ile Glu Asp Tyr Glu Glu Glu 
                245                 250                 255 

Glu Glu Glu Tyr Phe Gly Asn Glu Gln Gln Gln Gln Gln Gln Val Thr 
            260                 265                 270 

Thr Val Asn Gly Asn Phe Gly Gln Val Lys Gly Thr Cys Tyr Tyr Asp 
        275                 280                 285 

Thr Lys Thr Lys Thr Thr Thr Tyr Ile Lys Pro Pro Ala Ala Tyr Thr 
    290                 295                 300 

Leu Glu Thr Pro Ser Gln Ser Val Glu Tyr Cys 
305                 310                 315 

 
           
             25  
             640  
             PRT  
             Saccharomyces cerevisiae  
           
            25 

Met Ser Pro Arg Gln Leu Ile Pro Thr Leu Ile Pro Glu Trp Ala Pro 
  1               5                  10                  15 

Leu Ser Gln Gln Ser Cys Ile Arg Glu Asp Glu Leu Asp Ser Pro Pro 
             20                  25                  30 

Ile Thr Pro Thr Ser Gln Thr Ser Ser Phe Gly Ser Ser Phe Ser Gln 
         35                  40                  45 

Gln Lys Pro Thr Tyr Ser Thr Ile Ile Gly Glu Asn Ile His Thr Ile 
     50                  55                  60 

Leu Asp Glu Ile Arg Pro Tyr Val Lys Lys Ile Thr Val Ser Asp Gln 
 65                  70                  75                  80 

Asp Lys Lys Thr Ile Asn Gln Tyr Thr Leu Gly Val Ser Ala Gly Ser 
                 85                  90                  95 

Gly Gln Phe Gly Tyr Val Arg Lys Ala Tyr Ser Ser Thr Leu Gly Lys 
            100                 105                 110 

Val Val Ala Val Lys Ile Ile Pro Lys Lys Pro Trp Asn Ala Gln Gln 
        115                 120                 125 

Tyr Ser Val Asn Gln Val Met Arg Gln Ile Gln Leu Trp Lys Ser Lys 
    130                 135                 140 

Gly Lys Ile Thr Thr Asn Met Ser Gly Asn Glu Ala Met Arg Leu Met 
145                 150                 155                 160 

Asn Ile Glu Lys Cys Arg Trp Glu Ile Phe Ala Ala Ser Arg Leu Arg 
                165                 170                 175 

Asn Asn Val His Ile Val Arg Leu Ile Glu Cys Leu Asp Ser Pro Phe 
            180                 185                 190 

Ser Glu Ser Ile Trp Ile Val Thr Asn Trp Cys Ser Leu Gly Glu Leu 
        195                 200                 205 

Gln Trp Lys Arg Asp Asp Asp Glu Asp Ile Leu Pro Gln Trp Lys Lys 
    210                 215                 220 

Ile Val Ile Ser Asn Cys Ser Val Ser Thr Phe Ala Lys Lys Ile Leu 
225                 230                 235                 240 

Glu Asp Met Thr Lys Gly Leu Glu Tyr Leu His Ser Gln Gly Cys Ile 
                245                 250                 255 

His Arg Asp Ile Lys Pro Ser Asn Ile Leu Leu Asp Glu Glu Glu Lys 
            260                 265                 270 

Val Ala Lys Leu Ser Asp Phe Gly Ser Cys Ile Phe Thr Pro Gln Ser 
        275                 280                 285 

Leu Pro Phe Ser Asp Ala Asn Phe Glu Asp Cys Phe Gln Arg Glu Leu 
    290                 295                 300 

Asn Lys Ile Val Gly Thr Pro Ala Phe Ile Ala Pro Glu Leu Cys His 
305                 310                 315                 320 

Leu Gly Asn Ser Lys Arg Asp Phe Val Thr Asp Gly Phe Lys Leu Asp 
                325                 330                 335 

Ile Trp Ser Leu Gly Val Thr Leu Tyr Cys Leu Leu Tyr Asn Glu Leu 
            340                 345                 350 

Pro Phe Phe Gly Glu Asn Glu Phe Glu Thr Tyr His Lys Ile Ile Glu 
        355                 360                 365 

Val Ser Leu Ser Ser Lys Ile Asn Gly Asn Thr Leu Asn Asp Leu Val 
    370                 375                 380 

Ile Lys Arg Leu Leu Glu Lys Asp Val Thr Leu Arg Ile Ser Ile Gln 
385                 390                 395                 400 

Asp Leu Val Lys Val Leu Ser Arg Asp Gln Pro Ile Asp Ser Arg Asn 
                405                 410                 415 

His Ser Gln Ile Ser Ser Ser Ser Val Asn Pro Val Arg Asn Glu Gly 
            420                 425                 430 

Pro Val Arg Arg Phe Phe Gly Arg Leu Leu Thr Lys Lys Gly Lys Lys 
        435                 440                 445 

Lys Thr Ser Gly Lys Gly Lys Asp Lys Val Leu Val Ser Ala Thr Ser 
    450                 455                 460 

Lys Val Thr Pro Ser Ile His Ile Asp Glu Glu Pro Asp Lys Glu Cys 
465                 470                 475                 480 

Phe Ser Thr Thr Val Leu Arg Ser Ser Pro Asp Ser Ser Asp Tyr Cys 
                485                 490                 495 

Ser Ser Leu Gly Glu Glu Ala Ile Gln Val Thr Asp Phe Leu Asp Thr 
            500                 505                 510 

Phe Cys Arg Ser Asn Glu Ser Leu Pro Asn Leu Thr Val Asn Asn Asp 
        515                 520                 525 

Lys Gln Asn Ser Asp Met Lys Thr Asp Arg Ser Glu Ser Ser Ser His 
    530                 535                 540 

Ser Ser Leu Lys Ile Pro Thr Pro Ile Lys Ala Met Ile Arg Leu Lys 
545                 550                 555                 560 

Ser Ser Pro Lys Glu Asn Gly Asn Arg Thr His Ile Asn Cys Ser Gln 
                565                 570                 575 

Asp Lys Pro Ser Ser Pro Leu Met Asp Arg Thr Val Gly Lys Arg Thr 
            580                 585                 590 

Val Asn Asn Ser Gly Ala Arg Lys Leu Ala His Ser Ser Asn Ile Leu 
        595                 600                 605 

Asn Phe Lys Ala Tyr Ile Asn Ser Glu Asp Ser Asp Ile Arg Glu Thr 
    610                 615                 620 

Val Glu Asp Val Lys Thr Tyr Leu Asn Phe Ala Asp Asn Gly Gln Ile 
625                 630                 635                 640 

 
           
             26  
             1142  
             PRT  
             Saccharomyces cerevisiae  
           
            26 

Met Asp Arg Ser Asp Lys Lys Val Asn Val Glu Glu Val Asn Val Pro 
  1               5                  10                  15 

Ser Asn Leu Gln Ile Glu Leu Glu Lys Ser Gly Thr Ser Ser Ser Val 
             20                  25                  30 

Ser Leu Arg Ser Pro Thr Lys Ser Ser Ala Thr Asn Leu Ala Gly Met 
         35                  40                  45 

Ala Glu Gly Ala Arg Asp Asn Ala Ser Ile Ala Ser Ser Ser Val Asp 
     50                  55                  60 

Ser Leu Asn Met Leu Leu Glu Arg Gln Arg Val Arg Gln Leu Asn His 
 65                  70                  75                  80 

Pro Gln His Gln Gln His Ile Ser Ser Ser Leu Ala Lys Thr Pro Thr 
                 85                  90                  95 

Thr Thr Ser Ser Phe Cys Ser Ser Gly Ser Ser Lys Asn Lys Val Lys 
            100                 105                 110 

Glu Thr Asn Arg Ile Ser Leu Thr Tyr Asp Pro Val Ser Lys Arg Lys 
        115                 120                 125 

Val Leu Asn Thr Tyr Glu Ile Ile Lys Glu Leu Gly His Gly Gln His 
    130                 135                 140 

Gly Lys Val Lys Leu Ala Arg Asp Ile Leu Ser Lys Gln Leu Val Ala 
145                 150                 155                 160 

Ile Lys Ile Val Asp Arg His Glu Lys Lys Gln Arg Lys Phe Phe Thr 
                165                 170                 175 

Phe Ile Lys Ser Ser Lys Ile Ser Glu Asn Asp Lys Ile Lys Arg Glu 
            180                 185                 190 

Ile Ala Ile Met Lys Lys Cys His His Lys His Val Val Gln Leu Ile 
        195                 200                 205 

Glu Val Leu Asp Asp Leu Lys Ser Arg Lys Ile Tyr Leu Val Leu Glu 
    210                 215                 220 

Tyr Cys Ser Arg Gly Glu Val Lys Trp Cys Pro Pro Asp Cys Met Glu 
225                 230                 235                 240 

Ser Asp Ala Lys Gly Pro Ser Leu Leu Ser Phe Gln Glu Thr Arg Glu 
                245                 250                 255 

Ile Leu Arg Gly Val Val Leu Gly Leu Glu Tyr Leu His Tyr Gln Gly 
            260                 265                 270 

Ile Ile His Arg Asp Ile Lys Pro Ala Asn Leu Leu Ile Ser Gly Asp 
        275                 280                 285 

Gly Thr Val Lys Ile Ser Asp Phe Gly Val Ser Leu Ala Ala Ser Ser 
    290                 295                 300 

Thr Asn Ser Ser Asp Ser Ser Glu Ser Leu Asp Glu Leu Glu Leu Ala 
305                 310                 315                 320 

Lys Thr Val Gly Thr Pro Ala Phe Phe Ala Pro Glu Met Cys Leu Gly 
                325                 330                 335 

Glu Asp Ala Phe Thr Arg Tyr Asn Leu Thr Lys Glu Asn Leu Phe Arg 
            340                 345                 350 

Gly Ser Cys Ile Ser Phe Met Ile Asp Ile Trp Ala Val Gly Val Thr 
        355                 360                 365 

Leu Tyr Cys Leu Leu Phe Gly Met Leu Pro Phe Phe Ser Asp Phe Glu 
    370                 375                 380 

Leu Lys Leu Phe Glu Lys Ile Val Asn Asp Pro Leu Lys Phe Pro Thr 
385                 390                 395                 400 

Phe Lys Glu Ile Gln Ser Asn Lys Val Ser Lys Val Ser Cys Glu Glu 
                405                 410                 415 

Glu Tyr Glu Met Ala Lys Asp Leu Leu Leu Lys Leu Leu Glu Lys Asn 
            420                 425                 430 

Pro Gln Lys Arg Met Thr Ile Pro Ala Ile Lys Lys His Pro Phe Val 
        435                 440                 445 

Ser Trp Asp Phe Asp His Val Pro Glu Asn Asp Glu Lys Leu Leu Ser 
    450                 455                 460 

Ser Val Leu Glu Gln Lys Leu Arg Phe Gln Cys Asn Gln Thr Asp Gln 
465                 470                 475                 480 

Phe Glu Pro Ile Ser Ile Ser Lys His Glu Leu Lys Asn Ala Val Ser 
                485                 490                 495 

Gly Val Gly Lys Lys Ile Lys Glu Ser Val Leu Lys Ser Ile Pro Leu 
            500                 505                 510 

Lys Asp Pro Ser Asp Leu Ser Asn Lys Asn Tyr Leu His Pro Thr Glu 
        515                 520                 525 

Thr Thr Arg Gly Arg Gly Asp Ala Asn Val Ile Val Ser Glu Gly Ser 
    530                 535                 540 

Val Leu Ser Asn Ile Lys Glu Leu Ser Ala Asn Asp Gly Cys Leu Asn 
545                 550                 555                 560 

Thr Asp Ser Asp Thr Asn Ile Asn Ile Asn Asp Asp Asp His Tyr Ser 
                565                 570                 575 

Gly Asp Asp Asn Asp Gly His Leu Thr Lys Arg Glu Leu Glu Arg Glu 
            580                 585                 590 

Leu Asn Lys Phe Asp Asp Lys His Glu Ala Gly Asn Met Val Asn Leu 
        595                 600                 605 

Pro Ile Asn Ser Ser Phe Ala Ser Leu Asp Ser Phe Tyr Ile Asp Asn 
    610                 615                 620 

Phe Ala Met Ala Arg Met Gly Met Ser Ser Pro Glu Ala Gly Asp Ser 
625                 630                 635                 640 

Val Ser Ser Val Pro Asn Leu Pro Ser Ala Pro Ser Ser Thr Arg Leu 
                645                 650                 655 

Gly Arg Ser Pro Val Phe Ser Gly Val Thr Asn Gln Pro Ser Pro Ile 
            660                 665                 670 

Arg Pro Val Leu Pro Gln Gln Lys Ser Ser Phe Cys Ala Thr Gly Arg 
        675                 680                 685 

Tyr Asp Lys Ser His Asn Ser Leu Leu Arg Asn Ser Ser Ser His Leu 
    690                 695                 700 

Thr Ser Tyr Asn Ser Gly Arg Pro Ser Ser Arg Thr Gly Arg Met Asn 
705                 710                 715                 720 

Ser Arg Asn Gln Asn Leu Pro Lys Ile Pro Asn Ser Leu Ser Lys Ile 
                725                 730                 735 

Ser Thr Thr Lys Leu Thr Glu Leu Arg Val Pro Lys Asp Ser Glu Ile 
            740                 745                 750 

Pro Ser Pro Ala Lys Asn Pro Asn Ala Asp Arg Leu Arg Arg Phe Pro 
        755                 760                 765 

Val Lys Lys Asn Thr Lys Thr Pro Ala Ile Lys Asp Pro Pro Arg Ile 
    770                 775                 780 

Asn Ile Asn Ser Ser Asp Lys Ser Gly Ser Lys Asn Ser Pro Ile Lys 
785                 790                 795                 800 

Ser Leu Tyr Gln Arg Met Lys Gln Ser Lys Asp Asn Ser Lys Thr Phe 
                805                 810                 815 

Glu Val Arg Arg Gly Asn Phe Phe Ser His Phe Asn Gly Asp Asp Asp 
            820                 825                 830 

Asp Ser Ser Ser Gln Ser Ser Val Thr Ser Ser Gly Ser Glu Ser Asp 
        835                 840                 845 

Ser Glu Leu Ser Ser Thr Ser Ser Ser Cys Thr Ser Gly Thr Gln Ser 
    850                 855                 860 

Arg Asn Ser Ser Asn Asn Asn Ala Tyr Ser Glu Thr Glu Ser Leu Pro 
865                 870                 875                 880 

Phe Glu Phe Gly Val Asp Ser Glu Asp Gly Ser Gly Val Leu Leu Arg 
                885                 890                 895 

Asp Leu Pro Asn Glu Asp Gln Ile Arg Pro Phe Leu Asp Ile Gln Pro 
            900                 905                 910 

Cys Arg Arg Met Lys Val Lys Ser Ser Leu Asn Leu Glu Pro Pro Ser 
        915                 920                 925 

Val Ser Ser Ser Ser Ser Ser Ser Ser Asp Glu Asp Glu Leu Ile Leu 
    930                 935                 940 

Asn Val Gly Thr Ala Gly His Arg Arg Arg His Asn Ser Ser Lys Leu 
945                 950                 955                 960 

Ser Glu Leu Ser Asn Ser Pro Gln Lys Gly Ser Asn Asn Phe Met Tyr 
                965                 970                 975 

Ser Asn Gly Ser Val His Asp Ser Glu Thr Thr Ile Thr Pro Gln Asn 
            980                 985                 990 

Met Asp Asp Leu Thr Leu His Gln Ala Leu Ser Arg Ser Gln Pro Ile 
        995                1000                1005 

Ser Lys Pro Gly Pro Leu Val Leu Pro Lys Arg Leu Asp Gln Lys Lys 
   1010                1015                1020 

Ala Thr Thr Glu Thr Ser Asn Leu Thr Asp Ile Val Glu Phe Asn Gly 
1025               1030                1035                1040 

Asn Asn Asp His Arg Lys Asp Lys Asn Phe Asp Lys Val Leu Tyr Ser 
               1045                1050                1055 

Arg Asp Leu Leu Lys Asp Ala Leu Ser Ser Thr Asn Ala Gly Arg Arg 
           1060                1065                1070 

Arg Ser Ile Pro Ser Asn Lys Ile Arg Gly Arg Lys Asp Ala Ser Ile 
       1075                1080                1085 

Thr Met Ser Thr Asn Val Gly Asn Asp Glu His Ala Arg Asn Thr Ser 
   1090                1095                1100 

Cys His Gly Asp Lys Gly Gln Glu Asn Gly Ala Ile Lys Gln Arg Thr 
1105               1110                1115                1120 

His Glu Arg Ser Arg Ser Leu Thr Val Ala Glu Leu Asn Glu Glu Lys 
               1125                1130                1135 

Arg Arg Ser Ala Leu Pro 
           1140 

 
           
             27  
             559  
             PRT  
             Saccharomyces cerevisiae  
           
            27 

Met Val Leu Leu Lys Glu Pro Val Gln Pro Leu Pro Arg Ser Ser Leu 
  1               5                  10                  15 

Leu Tyr Asn Asn Ala Ser Asn Ser Ser Ser Arg Ile Lys Glu Thr Arg 
             20                  25                  30 

Lys Val Lys Leu Leu Tyr Asn Pro Leu Thr Lys Arg Gln Ile Leu Asn 
         35                  40                  45 

Asn Phe Glu Ile Leu Ala Thr Leu Gly Asn Gly Gln Tyr Gly Lys Val 
     50                  55                  60 

Lys Leu Ala Arg Asp Leu Gly Thr Gly Ala Leu Val Ala Ile Lys Ile 
 65                  70                  75                  80 

Leu Asn Arg Phe Glu Lys Arg Ser Gly Tyr Ser Leu Gln Leu Lys Val 
                 85                  90                  95 

Glu Asn Pro Arg Val Asn Gln Glu Ile Glu Val Met Lys Arg Cys His 
            100                 105                 110 

His Glu Asn Val Val Glu Leu Tyr Glu Ile Leu Asn Asp Pro Glu Ser 
        115                 120                 125 

Thr Lys Val Tyr Leu Val Leu Glu Tyr Cys Ser Arg Gly Pro Val Lys 
    130                 135                 140 

Trp Cys Pro Glu Asn Lys Met Glu Ile Lys Ala Val Gly Pro Ser Ile 
145                 150                 155                 160 

Leu Thr Phe Gln Gln Ser Arg Lys Val Val Leu Asp Val Val Ser Gly 
                165                 170                 175 

Leu Glu Tyr Leu His Ser Gln Gly Ile Thr His Arg Asp Ile Lys Pro 
            180                 185                 190 

Ser Asn Leu Leu Ile Ser Ser Asn Gly Thr Val Lys Ile Ser Asp Phe 
        195                 200                 205 

Gly Val Ala Met Ser Thr Ala Thr Gly Ser Thr Asn Ile Gln Ser Ser 
    210                 215                 220 

His Glu Gln Leu Leu Lys Ser Arg Ala Leu Gly Thr Pro Ala Phe Phe 
225                 230                 235                 240 

Ala Pro Glu Leu Cys Ser Thr Glu Lys Glu Tyr Ser Cys Ser Thr His 
                245                 250                 255 

Glu Ile Trp Ser Leu Gly Val Thr Ile Tyr Cys Leu Leu Phe Gly Lys 
            260                 265                 270 

Leu Pro Phe Asn Ala Asn Ser Gly Leu Glu Leu Phe Asp Ser Ile Ile 
        275                 280                 285 

Asn Lys Pro Leu Glu Phe Pro Ser Tyr Glu Glu Met Leu Asn Gly Ala 
    290                 295                 300 

Thr Ser Gly Ile Thr Met Glu Glu Tyr Thr Asp Ala Lys Asp Leu Leu 
305                 310                 315                 320 

Lys Lys Leu Leu Gln Lys Asp Pro Asp Lys Arg Ile Lys Leu Ala Asp 
                325                 330                 335 

Ile Lys Val His Pro Phe Met Cys His Tyr Gly Lys Ser Asp Ala Ala 
            340                 345                 350 

Ser Val Leu Thr Asn Leu Glu Thr Phe His Glu Leu Lys Val Ser Pro 
        355                 360                 365 

Pro Ser Ser Cys Lys Arg Val Glu Leu Val Ser Leu Pro Val Asn Ser 
    370                 375                 380 

Ser Phe Ala Ser Leu Asp Ser Val Tyr Met Glu Asn Phe Asp His Asn 
385                 390                 395                 400 

Asn Leu Arg Thr Gly Ala Asp Arg Asn Ser Thr Tyr Ser Pro Ser Ile 
                405                 410                 415 

Tyr Asp Ala Asn Thr Leu Ser Pro Ser Ala Tyr His Asn Ile Gly Ser 
            420                 425                 430 

Arg Glu Ser Ser Tyr Ser Ser Phe Ser Ser Phe Thr Ser Ser Thr Ala 
        435                 440                 445 

Phe Ala Ser Gln Ile Ser Ile Gln Asp Ala Pro Ala Ile Gly Asp Gln 
    450                 455                 460 

Gln Cys Leu Ile Gly Glu Ser Gly Ser Ser Leu Arg Val Asn Ser Cys 
465                 470                 475                 480 

Glu Phe Pro Gln Tyr Thr Thr Met Ser Pro Val Gly Glu Tyr Pro Phe 
                485                 490                 495 

Glu Ser Thr Glu Ala Ser Leu Ser Ser Thr Leu Thr Pro Val Gly Asn 
            500                 505                 510 

Val Pro Gln Arg Ile Lys Ala His Leu Val Glu Gly Lys Ser Asn Ser 
        515                 520                 525 

Lys Asp Asp Leu Arg Ile Glu Ala Asp Ala Ser Leu Val Phe Glu Ala 
    530                 535                 540 

Ser Asp Ala Gln Arg Thr Arg Arg Arg Met Ser Leu Tyr Lys Leu 
545                 550                 555 

 
           
             28  
             652  
             PRT  
             Schizosaccharomyces pombe  
           
            28 

Met Gly Ser Val Asn Asn Glu Glu Lys Thr Leu Ile Glu Pro Gln Arg 
  1               5                  10                  15 

Leu Leu Arg Lys Asn Thr Trp His Pro Glu Val Asp Asp Ser Glu Val 
             20                  25                  30 

Pro Pro Ser Val Phe Pro Glu Tyr Pro Val His Lys Ala Ile Gln Lys 
         35                  40                  45 

Thr Ser Asp Ser Phe Arg Lys Arg Asn Tyr Ser Ala Gly Asp Tyr Val 
     50                  55                  60 

Ile Ala Pro Leu Gly Gly Glu Arg Glu Gly Ser Ser Leu Thr His Ser 
 65                  70                  75                  80 

Trp Thr Phe Gln Pro Gly Lys His Asn Gln Arg Leu Tyr Ser Asp Asn 
                 85                  90                  95 

Phe Gln Glu Ala Gln Arg Gln Trp Lys Arg Leu Gln Glu Trp Gly Glu 
            100                 105                 110 

Val Lys Glu Thr Lys Lys Ile Arg Lys Arg Phe Asp Arg Phe Ser Gly 
        115                 120                 125 

Arg Lys Tyr Ile Asn His Tyr Glu Ile Ile Lys Glu Leu Gly Arg Gly 
    130                 135                 140 

Met His Gly Lys Val Lys Leu Gly Arg Asp Thr Val Thr Arg Glu Leu 
145                 150                 155                 160 

Leu Ala Ile Lys Ile Ile Pro Lys Thr Glu Arg Arg Pro Lys Leu Gly 
                165                 170                 175 

Arg Ala Asn Ala Ser Ser Gln Lys Glu Lys Val Arg Arg Glu Ile Ala 
            180                 185                 190 

Ile Leu Lys Lys Cys Val His Pro Asn Val Val Arg Leu Arg Glu Val 
        195                 200                 205 

Ile Asp Asp Pro Ser Ser Thr Lys Val Tyr Leu Val Leu Glu Tyr Met 
    210                 215                 220 

Ser Gly Gly Glu Val Pro Trp Thr Asp Cys Asp Ser Pro Val Leu Ser 
225                 230                 235                 240 

Ile Ser Glu Ala Arg Gln Tyr Phe Arg Asp Val Val Leu Gly Leu Glu 
                245                 250                 255 

Tyr Leu His Tyr Gln Gly Ile Ile His Arg Asp Ile Lys Pro Ala Asn 
            260                 265                 270 

Leu Leu Leu Asn Ser Ser Asn Cys Val Lys Ile Ser Asp Phe Gly Val 
        275                 280                 285 

Ser Tyr Ile Ala Asn Ala Gly Leu Asn Glu Asp Asn Asp Val Glu Leu 
    290                 295                 300 

Ala Lys Thr Val Gly Thr Pro Ala Phe Phe Ala Pro Glu Leu Cys Trp 
305                 310                 315                 320 

Thr Asp Leu Asp Arg Pro Arg Pro Lys Ile Ser Glu Ala Ile Asp Val 
                325                 330                 335 

Trp Ala Leu Gly Val Thr Leu Phe Cys Leu Leu Phe Gly Arg Cys Pro 
            340                 345                 350 

Phe Asn Ala Ser Met Glu Tyr Glu Leu Phe Asp Lys Ile Val Asn Glu 
        355                 360                 365 

Arg Leu Asn Ile Pro Ser Thr Pro Asp Ile Gly Glu Glu Gly Arg Asp 
    370                 375                 380 

Leu Leu Lys Arg Leu Leu Cys Lys Asp Pro Glu Gln Arg Ile Thr Leu 
385                 390                 395                 400 

Val Glu Val Lys Leu His Pro Trp Thr Leu Asp Gly Leu Lys Asp Pro 
                405                 410                 415 

Glu Lys Trp Leu Gln Asn Thr Asp Pro Ser Thr Val Ser Arg Val Glu 
            420                 425                 430 

Val Ser Thr Asp Glu Val Ala Ser Ala Ile Ser Leu Val Gly Arg Leu 
        435                 440                 445 

Arg Arg Lys Leu Gly Lys Leu Phe Arg Phe Arg Arg Pro Lys Ala Arg 
    450                 455                 460 

Val Phe Asp Ser Ser Ser Ser Val Pro Ser Asp Ser Ser Ile Cys Arg 
465                 470                 475                 480 

Pro Glu Ser Ser Gly Asn Ser Ser Ile Gly Leu Ser Ala Ser Glu Leu 
                485                 490                 495 

Ser Asp Ser Phe Asn Arg Leu Ala Val Asn Glu Ser Gln Lys Asp Arg 
            500                 505                 510 

Glu Arg Lys Gln Val His Pro Val Glu Met Gly Arg Asn Ser Ser Glu 
        515                 520                 525 

Lys Lys Pro Arg Cys Asp Phe Gly Trp Asp Tyr Glu Ala Phe Pro Asn 
    530                 535                 540 

Asp Asn Gln Asp Ala Asp Asp Ala Cys Ser Tyr Asn Thr Gly Asp Ser 
545                 550                 555                 560 

Ile Pro Gln Val Ser Lys Ser Ile Asn Gly His Phe Glu Thr Tyr Ser 
                565                 570                 575 

Arg Thr Ser Met Asp Thr Asp Asp Val Ala Ser Phe Glu Ser Pro Asn 
            580                 585                 590 

Ala Lys His Glu Glu Ser Gly Met Pro Val Val Thr Phe Arg Asn Tyr 
        595                 600                 605 

Glu Asn Tyr Asp Ala Asn Pro Ser Asn Phe His Pro Val Val Pro Gly 
    610                 615                 620 

Phe Val Ser Ser Pro Asn Leu His Leu Ala Gly Gly Ser Asp Thr Pro 
625                 630                 635                 640 

Ile Tyr Cys Ile Glu His Ser Phe Thr Pro Thr Asn 
                645                 650 

 
           
             29  
             1408  
             PRT  
             Candida albicans  
           
            29 

Met Ser Thr Ser Leu Ser His Gln Glu Leu Ser Thr Glu Lys Gly Gln 
  1               5                  10                  15 

Ser Cys Pro Pro Ile Pro Asp Ser Asn Pro Leu Asn Pro Lys Ser Pro 
             20                  25                  30 

Ala Leu Arg Thr Thr Ser Asn Ser Thr Ile Leu Asn Ser Pro Ile Glu 
         35                  40                  45 

Thr Ile Asn Val Asn Thr Ser Ser Lys Ser Asn Ile Ser Gly Glu Ser 
     50                  55                  60 

Thr Ile Asn Gly Ser Ala Tyr Ser Asn Ser Thr Thr Val Val Gln Pro 
 65                  70                  75                  80 

Glu Val Phe Gly Glu Ala His Thr Thr Thr Ser Thr His Asn Ser Ala 
                 85                  90                  95 

Ser Thr Arg Thr Glu Arg Asn Glu Phe Pro Asn Ser His Leu His Gln 
            100                 105                 110 

His Gln Gln Glu Ser Arg Asn Asn Gly Glu Ser Asn Thr Pro Met Thr 
        115                 120                 125 

Ser Pro Lys His Phe Pro Thr Asp Asp Leu Arg His Ser Leu Phe Tyr 
    130                 135                 140 

Lys Ala Gly Ser Ala Ala His His Lys Ser Ala Thr Ser Ser Lys Gln 
145                 150                 155                 160 

Ser Ser Thr Thr Ser Leu Lys Asp Gly Leu Asn Asn Ala Asn Thr Tyr 
                165                 170                 175 

His Phe Gln Asn Thr Phe Leu Asp Asn Asn Val Met Ser Asp Leu Glu 
            180                 185                 190 

Glu Ser Pro Val Pro Asn Glu Arg Asn Pro Ile Gln Asp Thr Gly Leu 
        195                 200                 205 

Gly Pro Arg Ser His Ala Thr Lys Phe Gly Val Gln Ser Thr Thr Ser 
    210                 215                 220 

Leu Pro Thr Thr Ile Ser Gln Ser Arg Leu Pro Asn Ser Asn Lys Ser 
225                 230                 235                 240 

Ser Phe Phe Pro Phe Lys Ser Tyr Thr Ser Ser Pro Val Lys Glu Thr 
                245                 250                 255 

Lys His Val Phe Leu Glu Tyr Asp Pro Ile Thr Arg Arg Lys Val Leu 
            260                 265                 270 

Asn Thr Tyr Glu Ile Leu Arg Glu Ile Gly Lys Gly Glu His Gly Lys 
        275                 280                 285 

Val Lys Leu Ala Arg Asp Leu Ile Asn Asn Glu Leu Val Ala Ile Lys 
    290                 295                 300 

Ile Val Asn Arg Lys Ser Arg Lys Glu Arg Pro Ser Leu Arg Met Arg 
305                 310                 315                 320 

Lys Asn Ser Ser Ala Pro Val Ile Asn Glu Tyr Glu Leu Lys Val Lys 
                325                 330                 335 

Arg Glu Ile Ala Ile Met Lys Lys Cys Arg His Lys His Ile Val Ala 
            340                 345                 350 

Leu Arg Glu Val Leu Asp Asp Leu Asn Ser Leu Lys Ile Tyr Leu Val 
        355                 360                 365 

Leu Glu Tyr Met Glu Lys Gly Glu Ile Lys Trp Lys Lys Leu Gln Ser 
    370                 375                 380 

Asp Val Ala Lys Pro Thr Ala Asn Lys Cys Tyr Asp Ala Asn Asp Asn 
385                 390                 395                 400 

Glu Ile Pro Cys Cys Gly Asn Gly Arg Met Gln Gln Arg Gln Gln Ser 
                405                 410                 415 

Leu Leu Thr Asp Glu Asp Leu Leu Ser Asn Glu Phe Ser Pro Asn Leu 
            420                 425                 430 

Thr Phe Lys Gln Ser Arg Lys Ile Phe Arg Asp Val Leu Leu Gly Leu 
        435                 440                 445 

Glu Tyr Leu His Met Gln Gly Ile Val His Arg Asp Ile Lys Pro Ala 
    450                 455                 460 

Asn Leu Leu Val Ser Ala Asp Asn Ile Val Lys Ile Ser Asp Phe Gly 
465                 470                 475                 480 

Val Ser Phe Ala Thr Ser Leu Ala Glu Asn Asp Glu Gly Tyr Leu Val 
                485                 490                 495 

Asn Glu Leu Asp Leu Ala Lys Thr Ala Gly Thr Pro Ala Phe Phe Ala 
            500                 505                 510 

Pro Glu Leu Cys Gln Phe Asp Asp Glu Thr Ala Thr Glu Lys Leu Ser 
        515                 520                 525 

Ser Ser Thr Glu Ser Met Ala Pro Pro Lys Ile Asp Tyr Lys Ile Asp 
    530                 535                 540 

Ile Trp Ala Leu Gly Val Thr Leu Tyr Cys Leu Leu Phe Gly Lys Val 
545                 550                 555                 560 

Pro Phe Asn Ala Asp Thr Glu Tyr Asp Leu Phe Gln Val Ile Val Lys 
                565                 570                 575 

Glu Pro Leu Lys Phe Pro Asn Ser Ile Lys Ala Phe Asn Pro Pro Ala 
            580                 585                 590 

Thr Val Thr Glu Glu Glu Phe Glu Leu Ala Lys Asp Leu Leu Ser Lys 
        595                 600                 605 

Met Leu Asp Lys Asn Asn Arg Thr Arg Ile Glu Ile Gln Asp Ile Lys 
    610                 615                 620 

Glu His Pro Phe Thr Leu Met Asp Leu Asp Asn Asp Val Asp Gly Leu 
625                 630                 635                 640 

His Glu Leu Phe His Leu Asn Gly Asp Asn Pro Val Glu Pro Leu Ser 
                645                 650                 655 

Phe Asp Leu Asp Glu His Asp Ile Val Ser Lys Asp Glu Val Asp Asn 
            660                 665                 670 

Ala Val Ile Gly Val Gly Ala Arg Ile Lys Arg Ser Leu Val Arg Ala 
        675                 680                 685 

Ile Arg Ala Gly Gly Leu Lys Asp Gly Glu Ile Arg Asn Lys Phe Ala 
    690                 695                 700 

Ala Leu Gln Leu Glu His Ser Arg Ser Glu Asn Ser Glu Glu Ser Ser 
705                 710                 715                 720 

Ser Gly Tyr Ser Asn Tyr Ser Ser Ser Thr Arg Leu Leu Gly Tyr Gln 
                725                 730                 735 

Asn Gly Gln Asn Tyr Ser Met Ile Leu Ser Glu Gly Leu Pro Val Ser 
            740                 745                 750 

Ser Ala Thr Pro Pro Pro Ala Leu Leu Ala Ala Gln Gln Lys Arg Ser 
        755                 760                 765 

Ser Leu Leu Ser Pro Lys Ser Gly Gly Ile Ser Glu Lys Asn Asn Pro 
    770                 775                 780 

His Phe Pro Ser Ser Leu Ala His Gln Ile Pro Asn Thr Ser Ser Pro 
785                 790                 795                 800 

Ser Thr Cys Ser Ser Ser Thr Ser Met Ala Phe Gln Asn His Phe Ser 
                805                 810                 815 

Phe Ala Gly Met Arg Glu Ser Gly Lys Ser Leu Leu His Asp Met Ile 
            820                 825                 830 

Glu Ser Asn Ser Asn Asn Ser Ser Arg Arg Gly Ser Ser Ala Gly Ile 
        835                 840                 845 

Thr Val Ser Glu Ala Pro Gln Ile Glu Thr Lys Arg Asn Val Gly Gly 
    850                 855                 860 

Asp Leu Tyr Leu Lys Asn Gln Ser Val Val Glu Thr Phe Lys Gly Ile 
865                 870                 875                 880 

Gln Leu Gln Asp Asp Lys Arg Arg Arg Ser Ser Ile Phe Ser Leu His 
                885                 890                 895 

Ser Gln Ile Gly Thr Asn Ser Asn Lys Ser Ser Leu Ser His Glu Leu 
            900                 905                 910 

Thr Pro Thr Gln Thr Gly Ser Gly Ala Ser Thr Gln Gln Gln His Gln 
        915                 920                 925 

His Tyr Ser Thr Asn Tyr Ser Asn Ile Ala Ala Pro Ile Pro Val Pro 
    930                 935                 940 

Ala Pro Arg Lys Gln Ser Thr Ser Asp Asn Glu Gln Asp Ile Lys Ala 
945                 950                 955                 960 

Pro Leu Leu His Gln Glu Lys Asn Val Met Gly Lys Pro Tyr Leu Lys 
                965                 970                 975 

Ile Gly Pro Ile Ser Ile Ala Arg Glu Asp Glu Lys Ser Ala Asp Asp 
            980                 985                 990 

His Pro Asp Ser Ser Ile Ile Ser Leu Pro Leu Ser Glu Ser Phe Ala 
        995                1000                1005 

Ser Leu Asp Ser Ile Asn Asp Asp Tyr Leu Ser Arg Lys Tyr Glu Glu 
   1010                1015                1020 

Tyr Thr Asn Asn Arg Lys Glu Asn Ser Lys Ser Glu Gly Asn Val Pro 
1025               1030                1035                1040 

Val Ile Ser Leu Arg Arg Lys Ser Ser Leu Ser Glu Ser Asp Leu Thr 
               1045                1050                1055 

Arg His Val Gln Leu Lys Asp Pro Phe Gly Lys Phe Lys Pro Asp Gly 
           1060                1065                1070 

Ser Glu Ile Ala Glu Lys Phe Lys Ala Phe Asn Leu Gly Asn Leu Met 
       1075                1080                1085 

Lys Thr Gly Gly Lys Phe Ala Leu Ala Glu His Asn Ser Ser Asp Ser 
   1090                1095                1100 

Gln Gln Ile Lys Gly Asn Asn Tyr Gln Ser Ser Asp Asp Gly Ile Ala 
1105               1110                1115                1120 

Pro Lys Ala Ile Val Pro Ala Ile Ser Tyr Ser Ser Ser Asp Ser Tyr 
               1125                1130                1135 

Ser Ser Cys Ser Ser Ser Ser Phe Asp Asp Glu Asp Glu Ser Asp Asp 
           1140                1145                1150 

Asp Glu Glu Asn Leu Thr Leu Ala Phe Gln Ser Lys Val Ala Pro Ile 
       1155                1160                1165 

Ser Arg Ala Asn Phe Leu Ser Leu Thr Gly Arg Ala Lys Ser His Asp 
   1170                1175                1180 

Ser Asn Leu Pro Thr Leu Arg Gln Asn Arg Glu Lys Gly Arg Gln Leu 
1185               1190                1195                1200 

Asn Pro Glu Phe Gln Gly Pro Ile Ile Phe His Asp Gly Leu Pro Glu 
               1205                1210                1215 

Phe Glu Asp Val Pro Asp Gly Leu Ile Asn Ser Asn Pro Ile Gly Asn 
           1220                1225                1230 

Asn Asn Val Asn Gly Asn Ser Ala Phe Asn Ser Gly Tyr Ser Tyr Tyr 
       1235                1240                1245 

Asp Asn Val Asn Pro Thr Val Val Ser Ser Asn Val Ser Thr Ala Thr 
   1250                1255                1260 

Leu Thr Met Gly Met Ala Pro Ser Glu Ser Val Glu Thr Asn Val Glu 
1265               1270                1275                1280 

Ala Pro Ala Gln Glu Asn Ala Val Lys Val Ser Ser Pro Leu Asn Pro 
               1285                1290                1295 

His Lys Asn Thr Ser Ser Arg Ser Asp Ile Leu Lys Asp Leu Lys Lys 
           1300                1305                1310 

Asn Thr Ser Ile Ser Phe Gly Glu Ile Leu Phe Asn Asp Gln Phe Asn 
       1315                1320                1325 

Asn His Tyr Lys Lys Asp Pro Val Tyr Ser Pro Phe Pro Ser Ala Lys 
   1330                1335                1340 

His Leu Asp Asn Asp Gln Glu Thr Ile Val Lys Glu Ser Ala Ser Lys 
1345               1350                1355                1360 

Phe His Glu His Arg Pro Thr Tyr Tyr Arg Ser Asn Ser Val Thr Ile 
               1365                1370                1375 

Gly Leu Leu His Arg Ser Thr His Arg Glu Asp Asp Asp Asp Val Ser 
           1380                1385                1390 

Gln Thr Gly Asn Asp Leu Glu Gln Leu Ile Thr Lys Glu Lys Gln Gly 
       1395                1400                1405 

 
           
             30  
             855  
             PRT  
             Saccharomyces cerevisiae  
           
            30 

Met Gly Asp Glu Lys Leu Ser Arg His Thr Ser Leu Lys Arg Ala Arg 
  1               5                  10                  15 

Ser Leu Ser Glu Ser Ile Lys Gly Leu Phe Lys Pro Ser Gly Ile Ser 
             20                  25                  30 

Gly Ser Asn Asn Ala Ala Ala Pro Ser Ser Arg Pro Gly Gln Asp Gln 
         35                  40                  45 

Ala His Ser His Gln Thr Ala Arg Ile Ile Thr Ser Asn Val Ser Ser 
     50                  55                  60 

Pro Ser Ile Ser Pro Val His Ser Pro Val Leu Gln Ala Ala Pro Lys 
 65                  70                  75                  80 

His His Lys Leu Gly Val Pro Asn Ile Ala Lys Leu Ser Leu Ser Pro 
                 85                  90                  95 

Ser Arg Glu Pro Ser Leu Asn Ser Glu Asn Glu Met Phe Ser Gln Glu 
            100                 105                 110 

Ser Phe Ile Ser Glu Lys Asp Glu Asp Glu Ala Asn Leu Leu Glu Arg 
        115                 120                 125 

Glu Asp Leu Gln Asn Lys Lys Glu Glu Lys Ala Arg Ala Lys His Val 
    130                 135                 140 

Arg Ser Lys Glu Ala Tyr Val Pro His His Arg Tyr Thr Val Gly Ser 
145                 150                 155                 160 

Asp Glu Val Glu Arg Gln Pro Arg Glu Arg Leu Lys Asn Phe Pro Gln 
                165                 170                 175 

Asn Ala Gly Ser Ser Asn Pro Ala Asn Ser Asn Ala Asn His Val Leu 
            180                 185                 190 

Asp Gln Glu Asn Asn Phe Ser Ile Asp Ala Met Leu Asp Tyr Asp Glu 
        195                 200                 205 

Glu Ser Lys Leu Arg Arg Arg Asn Ser Leu Gly Val Arg Asn His Ser 
    210                 215                 220 

Asn Arg Thr Arg Ser Arg Lys Asn Ser Leu Ser Thr Pro Arg Ser Pro 
225                 230                 235                 240 

Pro Met Lys Asn Gly Asn Gly Gly Met Asn Ser Asn Ala Thr Asn Asn 
                245                 250                 255 

Val Gly Asn Gly Thr Gly Asn Arg Ile Tyr Met Arg Gly Arg Asn His 
            260                 265                 270 

Ser Asp Ser Ile Ser Ala Ser Ser Leu Pro Lys Phe Gln Glu Ile Glu 
        275                 280                 285 

Cys Lys Cys Ile Leu Asp Leu Gly His Phe Lys Val Phe Glu Asn Gly 
    290                 295                 300 

Tyr His Glu His Ser Leu Arg Val Leu Pro Ile Ile Thr Asn Asn Lys 
305                 310                 315                 320 

Asn Val Asp Ser Gly Asp Glu Lys Asp Ala Asp Ala Ser Val Asn Ser 
                325                 330                 335 

Gly Asp Asp Gly Asp Asn Asp Ser Glu Ala Asn Met His Lys Gln Lys 
            340                 345                 350 

Ser Val Phe Ser Leu Ser Gly Leu Phe Lys Ser His Lys Asp Gly Asn 
        355                 360                 365 

Gln Gln Gln Gln Gln Gln Gln Gln Gln Glu Glu Asn Gly Glu Gln Ile 
    370                 375                 380 

Asn Leu Glu Lys Ala Phe Ser Ile Ile Pro Ser Gln Arg Phe Ile Lys 
385                 390                 395                 400 

Ser Gln Thr Leu Lys Lys Ser Arg Thr Ser Asn Leu Lys Asn Gly Asn 
                405                 410                 415 

Asn Asp Glu Leu Met Lys Asn Asp Gly Lys Asn Ile Pro Gln Ile Val 
            420                 425                 430 

Asn Pro Asn Ala Ala Val Gly Val Glu Glu Leu Lys Leu Ile Asn Ala 
        435                 440                 445 

Leu Ser Glu Lys Ile Arg Lys Gly Leu Lys Ser Glu Asn Thr Lys Gly 
    450                 455                 460 

Asn Asn Gly Glu Gly Arg Ser Asn Ser Asn Lys Gln Glu Asp Ser Asp 
465                 470                 475                 480 

Asp Thr Glu Gly Lys Ala Gly Thr Thr Asn Asp Asp Thr Ser His Lys 
                485                 490                 495 

Pro Cys Ser Gln Lys Tyr Gly Lys Ser Ile Gly Val Val Gly Ala Gly 
            500                 505                 510 

Ala Tyr Gly Val Val Lys Ile Cys Ala Arg Cys Lys Thr Ala Lys Asp 
        515                 520                 525 

Val Leu Pro Tyr Ser Thr Tyr Ser Asn Gly Lys Lys Leu Phe Phe Ala 
    530                 535                 540 

Val Lys Glu Leu Lys Pro Lys Pro Gly Asp Gln Ile Asp Lys Phe Cys 
545                 550                 555                 560 

Thr Arg Leu Thr Ser Glu Phe Ile Ile Gly His Ser Leu Ser His Pro 
                565                 570                 575 

His Phe Glu Ala Asn Ala Met Ile Ala Gly Asn Val Ser Arg Thr Thr 
            580                 585                 590 

Pro Pro Lys His Val Phe Asn Ala Pro Asn Ile Leu Lys Ile Leu Asp 
        595                 600                 605 

Leu Met Glu Tyr Ser Asn Ser Phe Val Glu Val Met Glu Phe Cys Ala 
    610                 615                 620 

Ser Gly Asp Leu Tyr Ser Leu Leu Thr Arg Asn Asn Ile Ser Asn Glu 
625                 630                 635                 640 

Ser Asn Asn Gly Ser Ser Arg Leu Ile Gln Thr Val Lys Glu Gly Ser 
                645                 650                 655 

Gly Ser Pro Leu His Pro Leu Glu Ala Asp Cys Phe Met Lys Gln Leu 
            660                 665                 670 

Leu Asn Gly Val Gln Tyr Met His Asp His Gly Ile Ala His Cys Asp 
        675                 680                 685 

Leu Lys Pro Glu Asn Ile Leu Phe Gln Pro Asn Gly Leu Leu Lys Ile 
    690                 695                 700 

Cys Asp Phe Gly Thr Ser Ser Val Phe Gln Thr Ala Trp Glu Lys His 
705                 710                 715                 720 

Val His Phe Gln Ser Gly Ala Met Gly Ser Glu Pro Tyr Val Ala Pro 
                725                 730                 735 

Glu Glu Phe Ile Arg Asp Ala Glu Tyr Asp Pro Arg Leu Val Asp Cys 
            740                 745                 750 

Trp Ser Cys Gly Ile Val Tyr Cys Thr Met Val Met Gly Gln Tyr Leu 
        755                 760                 765 

Trp Lys Ile Ala Ile Pro Glu Lys Asp Ser Leu Phe Lys Ser Phe Leu 
    770                 775                 780 

Ser Glu Ile Lys Asp Asp Gly Gln Phe Tyr Leu Phe Glu Glu Leu Arg 
785                 790                 795                 800 

His Val Ser Ser Glu Leu Asn Arg Leu Arg Lys Ile Ala Leu Tyr Arg 
                805                 810                 815 

Thr Phe Gln Val Asp Pro Thr Lys Arg Ile Thr Ile Glu Gln Leu Leu 
            820                 825                 830 

Gln Ser Ser Trp Met Arg Lys Thr Lys Cys Cys Val Val Tyr Arg His 
        835                 840                 845 

Leu His Thr Lys Val Ser Lys 
    850                 855 

 
           
             31  
             734  
             PRT  
             Saccharomyces cerevisiae  
           
            31 

Met Met Asp Ser Lys Thr Leu Thr Ala Ser Met Val Met Gln Glu Glu 
  1               5                  10                  15 

Lys Lys Arg Gln Gln Pro Val Thr Arg Arg Val Arg Ser Phe Ser Glu 
             20                  25                  30 

Ser Phe Lys Asn Leu Phe Arg Pro Pro Arg Ser Arg Asp Ser Ser Pro 
         35                  40                  45 

Ile Asn Val Thr Arg Ile Pro Tyr Arg Ser Ser Ser Thr Ser Pro Lys 
     50                  55                  60 

Arg Ser Ser Glu Pro Pro Arg Arg Ser Thr Val Ser Ala Gln Ile Leu 
 65                  70                  75                  80 

Asp Pro Lys Asn Ser Pro Ile Arg Gln Arg Ser Tyr Thr Leu Lys Cys 
                 85                  90                  95 

Cys Thr Pro Gly Leu Ser His Pro Phe Arg Gln Thr Gly Ser Gly Ala 
            100                 105                 110 

Ser Asn Ser Pro Thr Arg His Arg Ser Ile Ser Gly Glu Glu Gln Glu 
        115                 120                 125 

Ile Val Asn Ser Leu Pro Glu Tyr Lys Arg Ser Ala Ser His Thr Phe 
    130                 135                 140 

His Gly Ile Arg Arg Pro Arg Ser Arg Ser Ser Ser Val Ser Ser Cys 
145                 150                 155                 160 

Asp Ser Ser Asn Gly Thr Thr Ser Ser Ser Asp Ser Gln Trp Ala Met 
                165                 170                 175 

Asp Ser Leu Leu Asp Asp Ser Asp Asn Asp Leu Thr Pro Tyr Arg Gly 
            180                 185                 190 

Ser Asn Lys Asp Ile Leu Lys Ser Lys Asp Arg Ala Pro Tyr Asn Tyr 
        195                 200                 205 

Ile Asp Asp Tyr Asn Lys Lys Ala Leu Arg Arg Ala Thr Ser Tyr Pro 
    210                 215                 220 

Asn Pro Leu Pro Ser Lys Gln Phe Tyr Asn Glu Arg Leu Tyr Thr Arg 
225                 230                 235                 240 

Arg Ser His Pro Asp Glu Glu Ser Leu Glu Ser Leu Pro Arg Phe Ala 
                245                 250                 255 

Gly Ala Asp Val Gln Cys Ile Ile Glu Gln Asn Gly Phe Lys Val Tyr 
            260                 265                 270 

Glu Asp Gly Ser His Glu His Asn Ile Lys Leu Ser Gly Val Ile Ala 
        275                 280                 285 

Lys Leu Glu Lys Gly Asn Ser Leu Pro Ala His Arg Gln Gly Ser Leu 
    290                 295                 300 

Ser Arg Pro Arg Leu Gly Ile Thr Leu Ser Gly Leu Phe Lys His His 
305                 310                 315                 320 

Lys Asn Glu Cys Asp Ile Glu Asn Ala Leu Ser Leu Leu Pro Asn Val 
                325                 330                 335 

Glu Lys Ser Gln Thr Asn His Glu Lys Arg Thr Gly Gln Ser Pro Asn 
            340                 345                 350 

Asp Ser Asn Arg Ser Ser Pro Thr Gln Gly Arg Glu Asp Tyr Leu Lys 
        355                 360                 365 

Ile Val Asn Pro Asp Ala Ser Leu Gly Ser Asp Glu Leu Lys Leu Ile 
    370                 375                 380 

Asn Ser Leu Ser Ser Arg Ile His Lys Ser Leu Gln Asn Tyr Leu Gln 
385                 390                 395                 400 

Glu Lys Asn Leu Lys Pro Ala Glu Cys Ile Gly Glu Gln Ala Pro Thr 
                405                 410                 415 

Phe Gln Asp Asn Tyr Gly His Pro Val Gly Leu Val Gly Ala Gly Ala 
            420                 425                 430 

Tyr Gly Glu Val Lys Leu Cys Ala Arg Leu Arg Asn Glu Lys Asp Ser 
        435                 440                 445 

Pro Pro Phe Glu Thr Tyr His Asp Ser Lys Tyr Ile Tyr Tyr Ala Val 
    450                 455                 460 

Lys Glu Leu Lys Pro Lys Pro Asp Ser Asp Leu Glu Lys Phe Cys Thr 
465                 470                 475                 480 

Lys Ile Thr Ser Glu Phe Ile Ile Gly His Ser Leu Ser His Tyr His 
                485                 490                 495 

Lys Asn Gly Lys Lys Pro Ala Pro Asn Ile Leu Asn Val Phe Asp Ile 
            500                 505                 510 

Leu Glu Asp Ser Ser Ser Phe Ile Glu Val Met Glu Phe Cys Pro Ala 
        515                 520                 525 

Gly Asp Leu Tyr Gly Met Leu Val Gly Lys Ser Lys Leu Lys Gly Arg 
    530                 535                 540 

Leu His Pro Leu Glu Ala Asp Cys Phe Met Lys Gln Leu Leu His Gly 
545                 550                 555                 560 

Val Lys Phe Met His Asp His Gly Ile Ala His Cys Asp Leu Lys Pro 
                565                 570                 575 

Glu Asn Ile Leu Phe Tyr Pro His Gly Leu Leu Lys Ile Cys Asp Phe 
            580                 585                 590 

Gly Thr Ser Ser Val Phe Gln Thr Ala Trp Glu Arg Arg Val His Ala 
        595                 600                 605 

Gln Lys Gly Ile Ile Gly Ser Glu Pro Tyr Val Ala Pro Glu Glu Phe 
    610                 615                 620 

Val Asp Gly Glu Tyr Tyr Asp Pro Arg Leu Ile Asp Cys Trp Ser Cys 
625                 630                 635                 640 

Gly Val Val Tyr Ile Thr Met Ile Leu Gly His Tyr Leu Trp Lys Val 
                645                 650                 655 

Ala Ser Arg Glu Lys Asp Met Ser Tyr Asp Glu Phe Tyr Lys Glu Met 
            660                 665                 670 

Gln Arg Lys Asn Gln Phe Arg Val Phe Glu Glu Leu Lys His Val Asn 
        675                 680                 685 

Ser Glu Leu Ala Thr Asn Arg Lys Ile Ala Leu Tyr Arg Ile Phe Gln 
    690                 695                 700 

Trp Glu Pro Arg Lys Arg Ile Ser Val Gly Lys Leu Leu Asp Met Gln 
705                 710                 715                 720 

Trp Met Lys Ser Thr Asn Cys Cys Leu Ile Tyr Asp Ser Thr 
                725                 730 

 
           
             32  
             789  
             PRT  
             Saccharomyces cerevisiae  
           
            32 

Met Ser Ser Leu Thr Arg Leu Leu Gln Glu Lys Arg Lys Asn Glu Thr 
  1               5                  10                  15 

Ser Asn Ser Ser Pro Arg Thr Ser Ala Asp Thr Leu Thr Thr Thr Pro 
             20                  25                  30 

Glu Ser Gln Ser Leu Asp Leu His Ser Arg Asn Lys Ser Ser Ser His 
         35                  40                  45 

Ile Gly Ser Val Ser Asn Ser Ser Ser Ser Asp Arg Asn Arg Ala Asn 
     50                  55                  60 

Val Pro Val Pro Gly Ser Val Thr Thr Val Thr Gln Ile Tyr Ser Glu 
 65                  70                  75                  80 

Glu Asp Ser Ser Ser Thr Ala Gly Ser Ser Leu Asp Asp Arg Asn Gln 
                 85                  90                  95 

Phe Ser Ser Ser Phe Leu Asn Ala Asn Phe Ala His Thr Ala Ser Phe 
            100                 105                 110 

Tyr Gly Thr Ser Ala Gln Ser Arg Asp Arg Phe Gly Ser Leu Ile Asn 
        115                 120                 125 

Asp Gln Gly Thr Ala Gly Leu Ser Ser His Gly Gly Ser Phe Ala Ala 
    130                 135                 140 

Gln Asn Arg Ile Thr Ser Arg Leu Ser Thr Thr Ser His Thr Ser Gly 
145                 150                 155                 160 

Arg Ala Ile Pro Ser Leu Ser Ser Ser Ile Pro Tyr Ser Val Pro Asn 
                165                 170                 175 

Ser Asn Lys Asp Asn Asn Ser Ser Asn Ser Asn Ser Ser Ser Leu Ser 
            180                 185                 190 

Ser Ser Trp Leu Glu Thr Tyr Ala Gly Gly Met Pro Asn Asn Ile Thr 
        195                 200                 205 

His Glu Ser Asn Val Ile Ser Ser Pro Lys Val Asp Ser Val Glu Pro 
    210                 215                 220 

Arg Phe Val Ile Ser Lys Gln Lys Leu Gln Lys Ala Ser Met Asp Ser 
225                 230                 235                 240 

Asn Asn Ala Asn Ala Thr Gln Ser Arg Ser Ile Ser Arg Ser Gly Ser 
                245                 250                 255 

Phe Ser Ser Gln Leu Gly Asn Phe Phe Phe Ser Lys Asn Ser Lys Glu 
            260                 265                 270 

Ser Ser Asn Ser Asn Ser Ala Gly Met Ser Phe Ser Ala Asn Ser Asn 
        275                 280                 285 

Gly Pro Ser Pro Asn Ile Lys Asn Pro Asn Val Thr Asn Gly Ser Thr 
    290                 295                 300 

Pro Ile Pro Lys Pro Ile Arg Ala Arg Gln Ser Ser Ile Tyr Ser Ala 
305                 310                 315                 320 

Ser Arg Gln Pro Thr Gly Ser Tyr Thr Asp Asn Phe Tyr Gly Ser Pro 
                325                 330                 335 

Ser Ser Val His Asp His Leu Pro Pro Ser Gln Ser Val Pro Arg Ser 
            340                 345                 350 

Gln His Ser Ser Ile Gly Asp Leu Lys Arg Phe Phe Lys Lys Ser Ser 
        355                 360                 365 

Asn Ser Asn Leu Ser Ser Asn Ser Asn Asn Val Ile Pro Asn Gly Ser 
    370                 375                 380 

Pro Leu Ser Ser Gly Ile Ala Val Pro Ser His Ser His Ser Ser Ser 
385                 390                 395                 400 

His Phe Ala Ala Gly Asn Asn Ser Tyr Ser Thr Ser Tyr Asn Gly Asn 
                405                 410                 415 

Gly Asp Thr Ile Tyr Ser His Ser His Gly Gly Ser Gly Ile Pro Phe 
            420                 425                 430 

Ser Lys Arg Tyr Ile Lys Thr Gly Ala Asp Leu Gly Ala Gly Ala Gly 
        435                 440                 445 

Gly Ser Val Lys Leu Ala Gln Arg Ile Ser Asp Asn Lys Ile Phe Ala 
    450                 455                 460 

Val Lys Glu Phe Arg Thr Lys Phe Glu Asn Glu Ser Lys Arg Asp Tyr 
465                 470                 475                 480 

Val Lys Lys Ile Thr Ser Glu Tyr Cys Ile Gly Thr Thr Leu Asn His 
                485                 490                 495 

Pro Asn Ile Ile Glu Thr Ile Glu Ile Val Tyr Glu Asn Asp Arg Ile 
            500                 505                 510 

Leu Gln Val Met Glu Tyr Cys Glu Tyr Asp Leu Phe Ala Ile Val Met 
        515                 520                 525 

Ser Asn Lys Met Ser Tyr Glu Glu Ile Cys Cys Cys Phe Lys Gln Ile 
    530                 535                 540 

Leu Thr Gly Val Gln Tyr Leu His Ser Ile Gly Leu Ala His Arg Asp 
545                 550                 555                 560 

Leu Lys Leu Asp Asn Cys Val Ile Asn Glu Lys Gly Ile Val Lys Leu 
                565                 570                 575 

Ile Asp Phe Gly Ala Ala Val Val Phe Ser Tyr Pro Phe Ser Lys Asn 
            580                 585                 590 

Leu Val Glu Ala Ser Gly Ile Val Gly Ser Asp Pro Tyr Leu Ala Pro 
        595                 600                 605 

Glu Val Cys Ile Phe Ala Lys Tyr Asp Pro Arg Pro Val Asp Ile Trp 
    610                 615                 620 

Ser Ser Ala Ile Ile Phe Ala Cys Met Ile Leu Lys Lys Phe Pro Trp 
625                 630                 635                 640 

Lys Ile Pro Lys Leu Arg Asp Asn Ser Phe Lys Leu Phe Cys Ser Gly 
                645                 650                 655 

Arg Asp Cys Asp Ser Leu Ser Ser Leu Val Thr Arg Thr Pro Asp Pro 
            660                 665                 670 

Pro Ser Tyr Asp Glu Ser His Ser Thr Glu Lys Lys Lys Pro Glu Ser 
        675                 680                 685 

Ser Ser Asn Asn Val Ser Asp Pro Asn Asn Val Asn Ile Gly Pro Gln 
    690                 695                 700 

Arg Leu Leu His Ser Leu Pro Glu Glu Thr Gln His Ile Val Gly Arg 
705                 710                 715                 720 

Met Ile Asp Leu Ala Pro Ala Cys Arg Gly Asn Ile Glu Glu Ile Met 
                725                 730                 735 

Glu Asp Pro Trp Ile Arg Ser Ile Asp Met Cys His Leu Val Glu Asp 
            740                 745                 750 

Gly Leu Ser Phe Lys Val Val Arg Gly Glu Asp His His His Thr Gln 
        755                 760                 765 

Val Asp Gln Ser Glu Ala His Ile Ala Gly Leu Glu Lys Lys Lys Lys 
    770                 775                 780 

Lys Gln Asn Asn Gln 
785 

 
           
             33  
             699  
             PRT  
             Saccharomyces cerevisiae  
           
            33 

Met Ser Leu Ser Arg Ile Leu Arg Tyr Asn Gln Arg Asn Asn Lys Thr 
  1               5                  10                  15 

Thr Ala Ser Leu Thr Ala Glu His Ala Tyr Ser Asp Asn Trp Ala Tyr 
             20                  25                  30 

Ser Val Ser Leu Gly Asp Pro Thr Ser Val Gly Val Asn Met Ala Ala 
         35                  40                  45 

Lys Thr Gly Glu Ala Leu Asn Lys Ser Tyr Asp Ser Val Phe Ser Ser 
     50                  55                  60 

Leu Pro Val Ala Asp Ser Val Pro Arg Thr Asp Phe Thr Ala Ser Ser 
 65                  70                  75                  80 

Arg Asp Asp Glu Asn Thr Asp Val Gln Lys Leu Thr Thr Ser Trp Met 
                 85                  90                  95 

Glu Lys Ile Asp Thr Lys Met Pro Glu Asn Ile Ser Lys Ile Asp Ser 
            100                 105                 110 

Asn Ile Ile Ser Ser Pro Met Val Ser Lys Val Glu Ala Arg Phe Ile 
        115                 120                 125 

Val Pro Lys Gly Arg Leu Arg Lys Asn Ser Thr Asp Phe Thr Ser Ser 
    130                 135                 140 

Phe Ser Asn Ser Leu Ser Leu Pro Lys Ser Tyr Gly Lys Leu Ile Phe 
145                 150                 155                 160 

Phe Thr Ser Lys Lys Asn Ser Ser Ser Thr Lys Lys Asn Leu Ala Asn 
                165                 170                 175 

Asp Ile Ser Asp Asn Lys His Asn Asn Asn Ser Ser Asn Thr Ile Gly 
            180                 185                 190 

His Asn Ile Pro Val Thr Thr Ala Thr Ala Thr Cys Asp Glu Ile Ala 
        195                 200                 205 

Cys Thr Ser Thr Glu His Glu Tyr Asn Val Tyr Glu Glu Glu Arg Met 
    210                 215                 220 

Phe Thr Thr Arg Val Tyr Ser Leu Glu Asp Ser Val Ser Ser Leu Ser 
225                 230                 235                 240 

Thr Asn Pro Leu Asp Asp Thr Tyr Ser Glu Ala Val Gln Val Asn Thr 
                245                 250                 255 

Arg His Ile Glu Asp Thr Glu Ser Thr Ala His Ile Arg Lys His Ser 
            260                 265                 270 

Tyr Thr Thr Ser Leu Ser Ser Ile Lys Arg Leu Phe Lys Ile Thr Ser 
        275                 280                 285 

Phe Ser Asn Asn Asn Ser Asn Ser Cys Asp His Gln Glu Ser Thr Val 
    290                 295                 300 

Ala Asp Asp Cys Ala Ile Ser Ser Ser Leu Lys Glu Thr Thr Ser Ser 
305                 310                 315                 320 

Pro Val Ser Thr Gly Ser Phe Ser Leu Met Ile Glu Asn Glu Asp Ser 
                325                 330                 335 

Asp Arg Asp Gln Ile Ile Gln Ala Leu Tyr Ser Asn Ile Glu Ala Ser 
            340                 345                 350 

Thr Asp Leu Val Ser Arg Lys Tyr Arg Asp Leu Asp Val Val Leu Gly 
        355                 360                 365 

Glu Gly Ser Gly Gly Lys Val Lys Leu Val Gln Arg Val Leu Asp Asn 
    370                 375                 380 

Lys Val Phe Ala Leu Lys Glu Tyr Arg Ser Lys Lys Lys Arg Glu Ser 
385                 390                 395                 400 

Glu Arg Lys Tyr Ile Lys Asn Ile Ile Ser Glu Tyr Cys Ile Ala Ser 
                405                 410                 415 

Thr Leu Lys Asn Pro Asn Ile Cys Glu Thr Leu Glu Ile Leu Tyr Glu 
            420                 425                 430 

Lys Gly Lys Ile Phe Gln Ile Leu Glu Tyr Cys Glu Tyr Asp Leu Phe 
        435                 440                 445 

Ser Leu Val Met Ser Glu Lys Met His Tyr Glu Glu Ile Cys Cys Leu 
    450                 455                 460 

Phe Lys Gln Leu Ile Asn Gly Val Lys Tyr Leu His Asp Ile Gly Leu 
465                 470                 475                 480 

Ser His Arg Asp Leu Lys Leu Asp Asn Cys Val Val Thr Arg Arg Gly 
                485                 490                 495 

Ile Leu Lys Leu Ile Asp Phe Gly Ala Ser Ser Val Phe His Tyr Pro 
            500                 505                 510 

Leu Ser Ser Gln Met Ile Glu Ala Asn Gly Ile Val Gly Ser Asp Pro 
        515                 520                 525 

Tyr Leu Ser Pro Glu Val Phe Tyr Phe Asn Glu Tyr Asp Pro Arg Ala 
    530                 535                 540 

Leu Asp Val Trp Ser Val Gly Ile Ile Phe Phe Cys Met Ile Thr Arg 
545                 550                 555                 560 

Arg Phe Pro Trp Lys Tyr Pro Lys Val Lys Asp Val Gln Phe Lys Ala 
                565                 570                 575 

Phe Cys Ser Gly Arg Gly Val Ser Ser Phe Lys Asp Leu Val Thr Arg 
            580                 585                 590 

Pro Ala Thr Asp Asp Ser Asn Asn Tyr Asp Asn Asp Gly Tyr Glu Glu 
        595                 600                 605 

Gly Val Ile Asp Met Gly Pro Asn Phe Ile Leu His Arg Leu Pro Glu 
    610                 615                 620 

Glu Thr His Lys Ile Met Arg Arg Ile Leu Glu Val Ser Pro Phe Arg 
625                 630                 635                 640 

Arg Ile Thr Ile Asn Gly Ile Leu Gln Asp Gly Trp Ile Lys Glu Ile 
                645                 650                 655 

Glu Thr Cys Gln Val Val Gly Ala Ala Ser Pro Asn Glu Ala Ser Leu 
            660                 665                 670 

Arg Ile Ile Asn Lys Gly Asn His Ile His Thr Asn Ile Asp Gln Arg 
        675                 680                 685 

Tyr Ala His Ile Gly Gly Leu His Gln Arg Thr 
    690                 695 

 
           
             34  
             560  
             PRT  
             Saccharomyces cerevisiae  
           
            34 

Met Thr Val Ser His Asn His Ser Thr Lys Ile Ser Gln Gln Pro Ile 
  1               5                  10                  15 

Ser Ser Val Ser Ala Phe Lys Phe Phe Gly Lys Lys Leu Leu Ser Ser 
             20                  25                  30 

Ser His Gly Asn Lys Leu Lys Lys Lys Ala Ser Leu Pro Pro Asp Phe 
         35                  40                  45 

His Ser Thr Ser Thr Asn Asp Ser Glu Ser Ser Ser Pro Lys Leu Pro 
     50                  55                  60 

Asn Ser Leu Lys Thr Ser Arg Arg Ala Asn Ser Phe Ala His Thr Thr 
 65                  70                  75                  80 

Asn Ser Lys Arg Ser Leu Ser Ser Ala Ser Thr Lys Ile Leu Pro Pro 
                 85                  90                  95 

Ala Gly Ser Ser Thr Ser Ile Ser Arg Gly Asn Arg His Ser Ser Thr 
            100                 105                 110 

Ser Arg Asn Leu Ser Asn Ser Lys Phe Ser Ser Glu Arg Leu Val Tyr 
        115                 120                 125 

Asn Pro Tyr Gly Val Ser Thr Pro Ser Thr Ser Leu Ser Ser Val Ser 
    130                 135                 140 

Thr Ser Met Lys Lys Asp Pro Asp Leu Gly Phe Tyr Leu His Asp Gly 
145                 150                 155                 160 

Asp Ser Lys Ile Arg Met Leu Pro Ile Pro Ile Val Asp Pro Asn Glu 
                165                 170                 175 

Tyr Leu Pro Asp Glu Met Lys Glu Ala Ser Ile Gln Leu Ser Asp Asn 
            180                 185                 190 

Phe Val Phe Asp Asp Glu Asn Lys Thr Ile Gly Trp Gly Gly Ser Cys 
        195                 200                 205 

Glu Val Arg Lys Ile Arg Ser Lys Tyr Arg Lys Lys Asp Val Phe Ala 
    210                 215                 220 

Leu Lys Lys Leu Asn Met Ile Tyr Asn Glu Thr Pro Glu Lys Phe Tyr 
225                 230                 235                 240 

Asn Ala Ala Pro Lys Glu Phe Ile Ile Ala Lys Gln Leu Ser His His 
                245                 250                 255 

Val His Ile Thr Asn Thr Phe Leu Leu Val Lys Val Pro Thr Thr Val 
            260                 265                 270 

Tyr Thr Thr Arg Gly Trp Gly Phe Val Met Glu Leu Gly Leu Arg Asp 
        275                 280                 285 

Leu Phe Ala Met Ile Gln Lys Ser Gly Trp Arg His Val Ala Leu Ala 
    290                 295                 300 

Glu Lys Phe Cys Ile Phe Lys Gln Val Ala Cys Gly Val Lys Phe Cys 
305                 310                 315                 320 

His Asp Gln Gly Ile Ala His Arg Asp Leu Lys Pro Glu Asn Val Leu 
                325                 330                 335 

Leu Ser Pro Asp Gly Val Cys Lys Leu Thr Asp Phe Gly Ile Ser Asp 
            340                 345                 350 

Trp Tyr His His Gly Ser Thr Arg Pro Val Gln Pro Cys Gln Glu Val 
        355                 360                 365 

Arg Arg Asp Asp Arg Leu Ala Pro Tyr Ala Pro Pro Glu Val Met Phe 
    370                 375                 380 

Tyr Asp Ser Lys Lys His Tyr Asp Thr Glu Leu Gln Gln Pro Tyr Asp 
385                 390                 395                 400 

Pro Arg Ala Leu Asp Cys Tyr Gly Leu Gly Ile Ile Leu Met Thr Leu 
                405                 410                 415 

Val Asn Asn Val Ile Pro Phe Leu Glu Ser Cys Ser Phe Asp Thr Gly 
            420                 425                 430 

Phe Arg Asp Tyr Cys Asp Ala Tyr Glu Asn Phe Ile Arg Leu His Asp 
        435                 440                 445 

Arg Ala Phe Arg Asn Arg Ala Ile Thr Ala Arg Gly Arg Glu Trp Ser 
    450                 455                 460 

Ile Thr Trp Leu Glu Ile Ser Arg Thr Asp Met His Leu Ala Trp His 
465                 470                 475                 480 

Gly Gly Ser Leu Thr Gln Lys Pro Pro Pro Ala Thr Pro Ser Thr Thr 
                485                 490                 495 

Ser Ser Lys Thr His Gly Ser Lys Glu Leu Arg Leu Val Leu Met Pro 
            500                 505                 510 

Thr Thr Asn Met Cys Val Arg Asn Leu Leu Ser Lys Pro Leu Arg Thr 
        515                 520                 525 

Arg Ile Arg Gly Val Ser Ile Ser Leu Gln Met Leu Leu Gln Pro His 
    530                 535                 540 

Pro Pro Gln Thr His Ser Leu Arg Thr Glu Ser Pro Ser Gly Gln Trp 
545                 550                 555                 560 

 
           
             35  
             818  
             PRT  
             Saccharomyces cerevisiae  
           
            35 

Met Ala Gly Asn Gly Lys Asp Lys Glu Val Asp Lys Ser Pro Ser Val 
  1               5                  10                  15 

Ser Thr Leu Lys Leu Leu Gly Lys Arg Leu Phe Asn Ser Ser Ser His 
             20                  25                  30 

Thr Asp Asn Ser Ser Leu Leu Leu Ser Ala Glu Gln Leu Gly Asn Gly 
         35                  40                  45 

Arg Ser Leu Arg Lys Arg Pro Thr Ser Pro Ser Ile Ser Gly Ser Gly 
     50                  55                  60 

Ser Gly Gly Asn Ser Pro Ser Ser Ser Ala Gly Ala Arg Gln Arg Ser 
 65                  70                  75                  80 

Ala Ser Leu His Arg Arg Lys Asn Asn Ala Ser Val Gly Phe Ser Asn 
                 85                  90                  95 

Gly Ser Val Ser Ser His Lys Ser Ser Val Ala Leu Gln Asp Leu Ile 
            100                 105                 110 

Lys His Asn Asn Asn Pro Tyr Leu Asn Ser Pro Ser Asp Ile Leu Gly 
        115                 120                 125 

Thr Gly Thr Gly Ile Ala Ser Thr Arg Asp Arg Asp Arg Ala Val Leu 
    130                 135                 140 

Asp Arg Glu Lys Glu Lys Glu Arg Ala Arg Asn Lys Glu Arg Asn Thr 
145                 150                 155                 160 

His His Ala Gly Leu Pro Gln Arg Ser Asn Ser Met Ala Ser His His 
                165                 170                 175 

Phe Pro Asn Glu Asn Ile Val Tyr Asn Pro Tyr Gly Ile Ser Pro Asn 
            180                 185                 190 

His Ala Arg Pro Asp Thr Ala Phe Ala Asp Thr Leu Asn Thr Asn Lys 
        195                 200                 205 

Glu Asn Asp Leu Ser Phe Tyr Met His Asp Gly Asn Ser Lys Ile Arg 
    210                 215                 220 

Met Leu Pro Leu Pro Ile Ala Asn Pro Asn Asp Phe Leu Pro Glu Asp 
225                 230                 235                 240 

Met Lys Gln Tyr Ser Val His Leu Thr Asp Asn Phe Val Phe Asp Thr 
                245                 250                 255 

Asp Asn Lys Pro Ile Gly Ser Gly Gly Ser Ser Glu Val Arg Lys Val 
            260                 265                 270 

Lys Ser Ser Tyr Arg Gln Lys Asp Val Tyr Ala Leu Lys Lys Leu Asn 
        275                 280                 285 

Met Ile Tyr His Glu Ser Pro Glu Lys Phe Tyr Lys Arg Cys Ser Lys 
    290                 295                 300 

Glu Phe Ile Ile Ala Lys His Leu Ser His Asn Val His Ile Thr Asn 
305                 310                 315                 320 

Thr Phe Tyr Leu Leu Lys Val Pro Thr Thr Thr Tyr Thr Thr Arg Gly 
                325                 330                 335 

Trp Gly Phe Ile Met Glu Leu Gly Val Lys Asp Leu Phe Gln Leu Met 
            340                 345                 350 

Glu Arg Thr Gly Trp Lys Asn Val Pro Phe Asn Glu Lys Tyr Cys Leu 
        355                 360                 365 

Phe Lys Gln Val Ala Gln Gly Ile Lys Phe Cys His Asp Asn Gly Ile 
    370                 375                 380 

Ala His Arg Asp Leu Lys Pro Glu Asn Val Leu Ile Ser Lys Glu Gly 
385                 390                 395                 400 

Ile Cys Lys Leu Thr Asp Phe Gly Ile Ser Asp Trp Tyr His Val Ile 
                405                 410                 415 

Pro His Asp Tyr Thr Ser Pro Val Lys Thr Cys Gln Gly Met Ile Gly 
            420                 425                 430 

Ser Pro Pro Tyr Thr Pro Pro Glu Val Met Tyr Phe Asp Ala Lys Lys 
        435                 440                 445 

His Tyr Pro Glu Lys Phe Gln Lys Pro Tyr Asn Pro Leu Ala Met Asp 
    450                 455                 460 

Ser Tyr Ala Leu Gly Ile Met Leu Ile Thr Met Ile Asn Asn Ile Ile 
465                 470                 475                 480 

Pro Phe Ile Asp Ser Cys Asn Thr Asp Ala Arg Phe Arg Glu Phe Glu 
                485                 490                 495 

Val Ser Tyr Asp Asn Phe Ile Asn His Gln Asn Pro His Phe Arg Asp 
            500                 505                 510 

Lys Gly Cys His Lys Pro Gly Pro Gly Ser Glu Tyr Ser Leu Ala Arg 
        515                 520                 525 

Asn Phe Lys Asn Thr Asp Ala Thr Arg Ile Ala Trp Arg Leu Ala Asp 
    530                 535                 540 

Pro Asn Pro Ala Thr Arg Tyr Thr Met Asp Asp Leu Phe Asn Asp Pro 
545                 550                 555                 560 

Phe Phe Gln Gln Ile Glu Thr Cys Val Glu Pro Asn Asp Asp Asp Leu 
                565                 570                 575 

Val Arg Val Pro Glu Leu Arg Lys Ser Thr Ser Thr Asn Asp Phe Ser 
            580                 585                 590 

Glu Asn Ser Leu Asp Ala Pro His Asp Gln Glu Val Ile His Thr Ser 
        595                 600                 605 

Asn Pro Phe Leu Lys Lys Glu Thr Leu Thr Ser Lys Pro Arg Ser Met 
    610                 615                 620 

Leu Glu Ile Ala Glu Ser Pro Ser Leu Lys Gln Lys Ser Lys Val Lys 
625                 630                 635                 640 

Asp Ser Ala Lys Thr Lys Thr His Asp Val Gly Asp Glu Gly Gly Asn 
                645                 650                 655 

Glu Ser Thr Lys Pro Lys Gln Gln Asp Lys Lys Glu Asn Leu Lys Lys 
            660                 665                 670 

Asp Glu Val Lys Asn Gly Asp Lys Asp Lys Val Ile Glu Glu Ala Thr 
        675                 680                 685 

Thr Thr Asn Val Asp Ser Ile Leu Glu Lys Pro Thr Pro Thr Ser Thr 
    690                 695                 700 

Lys Val Glu Asp Asn Leu Ser Glu Asp Asp Ser Thr Met Lys Glu Leu 
705                 710                 715                 720 

Lys Ser Met Leu Asn Ser Thr Pro Thr Thr Pro Thr His Asn Gly Pro 
                725                 730                 735 

Thr Pro Leu Pro Ala Lys Ala Gly Thr Gln Leu Asp Lys Arg Met Ser 
            740                 745                 750 

Asp Leu Ser Leu Lys Ser Glu Thr Pro Ala Ser Thr Lys Asn Phe Ser 
        755                 760                 765 

Ala Pro Asn Val Ser Ser Ser Ser Asn Ser Leu Arg Ser Leu Gly Ser 
    770                 775                 780 

Pro Ser Val Ser Ser Ser Lys Lys Lys Lys Val Ile His His His Leu 
785                 790                 795                 800 

Asp Ile Thr Asn Ser Val Thr Asn Met Ser Ser Val Ser Ala Phe Ile 
                805                 810                 815 

Ser Arg 

 
           
             36  
             603  
             PRT  
             Saccharomyces cerevisiae  
           
            36 

Met Thr Gly Met Asn Asp Asn Asn Ala Ala Ile Pro Gln Gln Thr Pro 
  1               5                  10                  15 

Arg Lys His Ala Leu Ser Ser Lys Val Met Gln Leu Phe Arg Ser Gly 
             20                  25                  30 

Ser Arg Ser Ser Arg Gln Gly Lys Ala Ser Ser Asn Ile Gln Pro Pro 
         35                  40                  45 

Ser Asn Ile Asn Thr Asn Val Pro Ser Ala Ser Lys Ser Ala Lys Phe 
     50                  55                  60 

Gly Leu His Thr Pro Thr Thr Ala Thr Pro Arg Val Val Ser Asn Pro 
 65                  70                  75                  80 

Ser Asn Thr Ala Gly Val Ser Lys Pro Gly Met Tyr Met Pro Glu Tyr 
                 85                  90                  95 

Tyr Gln Ser Ala Ser Pro Ser His Ser Ser Ser Ser Ala Ser Leu Asn 
            100                 105                 110 

Asn His Ile Asp Ile Asn Thr Ser Lys Ser Ser Ser Ala Ala Ser Leu 
        115                 120                 125 

Thr Ser Ser Val Ser Ala Leu Ser Leu Ser Pro Thr Ser Ala Ile Asn 
    130                 135                 140 

Ile Ser Ser Lys Ser Leu Ser Pro Lys Phe Ser His His Ser Asn Ser 
145                 150                 155                 160 

Asn Thr Ala Ile Thr Pro Ala Pro Thr Pro Thr Ala Ser Asn Ile Asn 
                165                 170                 175 

Asn Val Asn Lys Ile Thr Asn Thr Ser Ala Pro Ile Cys Gly Arg Phe 
            180                 185                 190 

Leu Val His Lys Asp Gly Thr His Glu His His Leu Lys Asn Ala Lys 
        195                 200                 205 

Arg Gln Glu Lys Leu Ser Thr Met Ile Lys Asn Met Val Gly Ala Ser 
    210                 215                 220 

Lys Leu Arg Gly Glu Ala Lys Ser Ala Val Pro Asp Ile Ile Met Asp 
225                 230                 235                 240 

Pro Lys Thr Thr Leu Lys Ser Asn Lys Asn Pro Pro Thr Leu Phe Ala 
                245                 250                 255 

Gly Phe Met Lys Gln Val Val Asp Met Asp Asp Lys Tyr Pro Glu Gly 
            260                 265                 270 

Ala Pro Thr Ser Gly Ala Leu Asn Cys Pro Glu Arg Asp Ile Tyr Arg 
        275                 280                 285 

Ser Asp Gln Lys Asp Ser Lys Asn Asn Thr His Asn Ile Thr Thr Thr 
    290                 295                 300 

Lys Lys Asp Arg Gln Cys Phe Ala Glu Lys Tyr Gly Arg Cys Gln Glu 
305                 310                 315                 320 

Val Leu Gly Lys Gly Ala Phe Gly Val Val Arg Ile Cys Gln Lys Lys 
                325                 330                 335 

Asn Val Ser Ser Gln Asp Gly Asn Lys Ser Glu Lys Leu Tyr Ala Val 
            340                 345                 350 

Lys Glu Phe Lys Arg Arg Thr Ser Glu Ser Ala Glu Lys Tyr Ser Lys 
        355                 360                 365 

Arg Leu Thr Ser Glu Phe Cys Ile Ser Ser Ser Leu His His Thr Asn 
    370                 375                 380 

Ile Val Thr Thr Leu Asp Leu Phe Gln Asp Ala Lys Gly Glu Tyr Cys 
385                 390                 395                 400 

Glu Val Met Glu Tyr Cys Ala Gly Gly Asp Leu Phe Thr Leu Val Val 
                405                 410                 415 

Ala Ala Gly Lys Leu Glu Tyr Met Glu Ala Asp Cys Phe Phe Lys Gln 
            420                 425                 430 

Leu Ile Arg Gly Val Val Tyr Met His Glu Met Gly Val Cys His Arg 
        435                 440                 445 

Asp Leu Lys Pro Glu Asn Leu Leu Leu Thr His Asp Gly Val Leu Lys 
    450                 455                 460 

Ile Thr Asp Phe Gly Asn Ser Glu Cys Phe Lys Met Ala Trp Glu Lys 
465                 470                 475                 480 

Asn Ile His Leu Ser Gly Gly Val Cys Gly Ser Ser Pro Tyr Ile Ala 
                485                 490                 495 

Pro Glu Glu Tyr Ile Lys Glu Glu Phe Asp Pro Arg Pro Val Asp Ile 
            500                 505                 510 

Trp Ala Cys Gly Val Ile Tyr Met Ala Met Arg Thr Gly Arg Gln Leu 
        515                 520                 525 

Trp Ser Ser Ala Glu Lys Asp Asp Pro Phe Tyr Met Asn Tyr Leu Lys 
    530                 535                 540 

Gly Arg Lys Glu Lys Gly Gly Tyr Glu Pro Ile Glu Ser Leu Lys Arg 
545                 550                 555                 560 

Ala Arg Cys Arg Asn Val Ile Tyr Ser Met Leu Asp Pro Val Pro Tyr 
                565                 570                 575 

Arg Arg Ile Asn Gly Lys Gln Ile Leu Asn Ser Glu Trp Gly Arg Glu 
            580                 585                 590 

Ile Lys Cys Cys His Asn Gly Arg Ala Leu Lys 
        595                 600 

 
           
             37  
             620  
             PRT  
             Saccharomyces cerevisiae  
           
            37 

Met Val Lys Glu Thr Pro Leu His Ser Ser Ser Ser Thr Ser Leu Ser 
  1               5                  10                  15 

Ser Leu Phe Arg Pro Thr Lys Leu Lys Asn Leu Ser Ala Lys Ile Phe 
             20                  25                  30 

Asn Gly Gly Gly Asn Gln Ser Tyr Ser Lys Thr Asp Asp Val Ser Arg 
         35                  40                  45 

Ser Ser Ser Arg Ser Ser Lys Lys Asn Thr Asp Ser Asp Gln Glu Asp 
     50                  55                  60 

Gln Ile Lys Tyr Asn Lys Pro Asn Asp Arg Arg Ser Thr Ile Gly Lys 
 65                  70                  75                  80 

Ser Pro Gln Gly Asn Gly Ala Leu Ser Lys Glu Ser His Val Val Ala 
                 85                  90                  95 

Ser Ser Thr Leu Thr Gly Ile Ser Pro Thr Ser Ala Lys Lys Ala Pro 
            100                 105                 110 

Ile Asp Tyr Ser Pro Ser Arg Pro Leu Pro Asn Asn His Asn Pro Val 
        115                 120                 125 

Arg Thr Gly His Thr Val Pro His Leu Pro His Ser Ile His Asn Pro 
    130                 135                 140 

Ile Asn Tyr Ile His Gln Gly Ser Lys Asp Ala Phe His His Pro His 
145                 150                 155                 160 

Pro Val Arg Ser Thr Ala His Ser Asn Ile Ser Thr Val Ser Ser Ala 
                165                 170                 175 

Lys Ser Asp Thr Pro Ser Ser Asn Leu Ser Tyr Gln Ala His Met His 
            180                 185                 190 

Pro Val Glu Ile Leu Gln Lys Gln Ile Glu Asp Lys His Phe Met Asp 
        195                 200                 205 

Ser Gln Ala Ser Thr Pro Gly Ser Val Glu Leu Gln His Asn Ser Ser 
    210                 215                 220 

Ser Gly Ser Asp Asp Thr Ser Ser Arg Lys Lys Lys Ser Leu Arg Leu 
225                 230                 235                 240 

Thr Arg Phe Phe Lys Lys Ile His Asn Asp Tyr His Asp Asn His His 
                245                 250                 255 

His His His His His Asn Arg Gly Ser Thr Pro Thr Lys Pro Lys Leu 
            260                 265                 270 

Asn Leu Asn Thr Asn Glu Asn Ile Val Glu Ser Asn Gly Lys Ala Leu 
        275                 280                 285 

Tyr Glu Thr Asp Asn Pro Val Glu Leu Leu Glu Lys Tyr Gly Ile Pro 
    290                 295                 300 

Gly Arg Lys Leu Gly Glu Gly Ala Ser Gly Ser Val Ser Val Val Glu 
305                 310                 315                 320 

Arg Thr Asp Gly Lys Leu Phe Ala Cys Lys Met Phe Arg Lys Pro His 
                325                 330                 335 

Leu Asn Asn Glu Gly Thr Asn Gln Ser Gln Leu Ala Asn Tyr Ser Lys 
            340                 345                 350 

Lys Val Thr Thr Glu Phe Cys Ile Gly Ser Thr Leu His His Glu Asn 
        355                 360                 365 

Ile Val Glu Thr Leu Asp Met Leu Thr Glu Gly Asp Thr Tyr Leu Leu 
    370                 375                 380 

Val Met Glu Tyr Ala Pro Tyr Asp Phe Phe Asn Leu Val Met Ser Asn 
385                 390                 395                 400 

Leu Met Thr Gln Asp Glu Val Asn Cys Tyr Phe Lys Gln Leu Cys His 
                405                 410                 415 

Gly Val Asn Tyr Leu His Ser Met Gly Leu Ala His Arg Asp Leu Lys 
            420                 425                 430 

Leu Asp Asn Cys Val Val Thr Lys Asp Gly Ile Leu Lys Leu Ile Asp 
        435                 440                 445 

Phe Gly Ser Ala Val Val Phe Gln Tyr Pro Tyr Glu Asp Thr Ile Val 
    450                 455                 460 

Lys Ser His Gly Ile Val Gly Ser Asp Pro Tyr Leu Ala Pro Glu Leu 
465                 470                 475                 480 

Leu Lys Gln Thr Ser Tyr Asp Pro Arg Val Ala Asp Val Trp Ser Ile 
                485                 490                 495 

Ala Ile Ile Phe Tyr Cys Met Val Leu Lys Arg Phe Pro Trp Lys Ala 
            500                 505                 510 

Pro Lys Lys Ser Phe Asn Ser Phe Arg Leu Phe Thr Glu Glu Pro Glu 
        515                 520                 525 

Asp Glu Asp Asp Ile Val Arg Gly Pro Asn Lys Ile Leu Arg Leu Leu 
    530                 535                 540 

Pro Arg His Ser Arg Thr Ile Ile Gly Arg Met Leu Ala Leu Glu Pro 
545                 550                 555                 560 

Lys Gln Arg Val Leu Met Asn Asp Val Val Lys Asp Asp Trp Leu Val 
                565                 570                 575 

Ser Val Pro Ser Cys Glu Val Asp Pro Thr Ser Gly Asp Leu Val Glu 
            580                 585                 590 

Lys Pro Lys Asn His Lys His His Leu Val Thr Glu Glu Glu Leu Asn 
        595                 600                 605 

Glu Leu Thr Lys Gln His Gly Asn Lys Asp Ser Asn 
    610                 615                 620 

 
           
             38  
             759  
             PRT  
             Saccharomyces cerevisiae  
           
            38 

Met Pro Asn Leu Leu Ser Arg Asn Pro Phe His Gly His His Asn Asp 
  1               5                  10                  15 

His His His Asp Arg Glu Asn Ser Ser Asn Asn Pro Pro Gln Leu Ile 
             20                  25                  30 

Arg Ser Ser Lys Ser Phe Leu Asn Phe Ile Gly Arg Lys Gln Ser Asn 
         35                  40                  45 

Asp Ser Leu Arg Ser Glu Lys Ser Thr Asp Ser Met Lys Ser Thr Thr 
     50                  55                  60 

Thr Thr Thr Asn Tyr Thr Thr Thr Asn Leu Asn Asn Asn Thr His Ser 
 65                  70                  75                  80 

His Ser Asn Ala Thr Ser Ile Ser Thr Asn Asn Tyr Asn Asn Asn Tyr 
                 85                  90                  95 

Glu Thr Asn His His His Asn Ile Ser His Gly Leu His Asp Tyr Thr 
            100                 105                 110 

Ser Pro Ala Ser Pro Lys Gln Thr His Ser Met Ala Glu Leu Lys Arg 
        115                 120                 125 

Phe Phe Arg Pro Ser Val Asn Lys Lys Leu Ser Met Ser Gln Leu Arg 
    130                 135                 140 

Ser Lys Lys His Ser Thr His Ser Pro Pro Pro Ser Lys Ser Thr Ser 
145                 150                 155                 160 

Thr Val Asn Leu Asn Asn His Tyr Arg Ala Gln His Pro His Gly Phe 
                165                 170                 175 

Thr Asp His Tyr Ala His Thr Gln Ser Ala Ile Pro Pro Ser Thr Asp 
            180                 185                 190 

Ser Ile Leu Ser Leu Ser Asn Asn Ile Asn Ile Tyr His Asp Asp Cys 
        195                 200                 205 

Ile Leu Ala Gln Lys Tyr Gly Lys Leu Gly Lys Leu Leu Gly Ser Gly 
    210                 215                 220 

Ala Gly Gly Ser Val Lys Val Leu Val Arg Pro Thr Asp Gly Ala Thr 
225                 230                 235                 240 

Phe Ala Val Lys Glu Phe Arg Pro Arg Lys Pro Asn Glu Ser Val Lys 
                245                 250                 255 

Glu Tyr Ala Lys Lys Cys Thr Ala Glu Phe Cys Ile Gly Ser Thr Leu 
            260                 265                 270 

His His Pro Asn Val Ile Glu Thr Val Asp Val Phe Ser Asp Ser Lys 
        275                 280                 285 

Gln Asn Lys Tyr Tyr Glu Val Met Glu Tyr Cys Pro Ile Asp Phe Phe 
    290                 295                 300 

Ala Val Val Met Thr Gly Lys Met Ser Arg Gly Glu Ile Asn Cys Cys 
305                 310                 315                 320 

Leu Lys Gln Leu Thr Glu Gly Val Lys Tyr Leu His Ser Met Gly Leu 
                325                 330                 335 

Ala His Arg Asp Leu Lys Leu Asp Asn Cys Val Met Thr Ser Gln Gly 
            340                 345                 350 

Ile Leu Lys Leu Ile Asp Phe Gly Ser Ala Val Val Phe Arg Tyr Pro 
        355                 360                 365 

Phe Glu Asp Gly Val Thr Met Ala His Gly Ile Val Gly Ser Asp Pro 
    370                 375                 380 

Tyr Leu Ala Pro Glu Val Ile Thr Ser Thr Lys Ser Tyr Asp Pro Gln 
385                 390                 395                 400 

Cys Val Asp Ile Trp Ser Ile Gly Ile Ile Tyr Cys Cys Met Val Leu 
                405                 410                 415 

Lys Arg Phe Pro Trp Lys Ala Pro Arg Asp Ser Asp Asp Asn Phe Arg 
            420                 425                 430 

Leu Tyr Cys Met Pro Asp Asp Ile Glu His Asp Tyr Val Glu Ser Ala 
        435                 440                 445 

Arg His His Glu Glu Leu Leu Lys Glu Arg Lys Glu Lys Arg Gln Arg 
    450                 455                 460 

Phe Leu Asn His Ser Asp Cys Ser Ala Ile Asn Gln Gln Gln Pro Ala 
465                 470                 475                 480 

His Glu Ser Asn Leu Lys Thr Val Gln Asn Gln Val Pro Asn Thr Pro 
                485                 490                 495 

Ala Ser Ile Gln Gly Lys Ser Asp Asn Lys Pro Asp Ile Val Glu Glu 
            500                 505                 510 

Glu Thr Glu Glu Asn Lys Glu Asp Asp Ser Asn Asn Asp Lys Glu Ser 
        515                 520                 525 

Thr Pro Asp Asn Asp Lys Glu Ser Thr Ile Asp Ile Lys Ile Ser Lys 
    530                 535                 540 

Asn Glu Asn Lys Ser Thr Val Val Ser Ala Asn Pro Lys Lys Val Asp 
545                 550                 555                 560 

Ala Asp Ala Asp Ala Asp Cys Asp Ala Asn Gly Asp Ser Asn Gly Arg 
                565                 570                 575 

Val Asp Cys Lys Ala Asn Ser Asp Cys Asn Asp Lys Thr Asp Cys Asn 
            580                 585                 590 

Ala Asn Asn Asp Cys Ser Asn Glu Ser Asp Cys Asn Ala Lys Val Asp 
        595                 600                 605 

Thr Asn Val Asn Thr Ala Ala Asn Ala Asn Pro Asp Met Val Pro Gln 
    610                 615                 620 

Asn Asn Pro Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln 
625                 630                 635                 640 

Gln Gln Gln Gln Gln Gln Gln His His His His Gln His Gln Asn Gln 
                645                 650                 655 

Asp Lys Ala His Ser Ile Ala Ser Asp Asn Lys Ser Ser Gln Gln His 
            660                 665                 670 

Arg Gly Pro His His Lys Lys Ile Ile His Gly Pro Tyr Arg Leu Leu 
        675                 680                 685 

Arg Leu Leu Pro His Ala Ser Arg Pro Ile Met Ser Arg Ile Leu Gln 
    690                 695                 700 

Val Asp Pro Lys Lys Arg Ala Thr Leu Asp Asp Ile Phe Asn Asp Glu 
705                 710                 715                 720 

Trp Phe Ala Ala Ile Ala Ala Cys Thr Met Asp Ser Lys Asn Lys Val 
                725                 730                 735 

Ile Arg Ala Pro Gly His His His Thr Leu Val Arg Glu Glu Asn Ala 
            740                 745                 750 

His Leu Glu Thr Tyr Lys Val 
        755 

 
           
             39  
             636  
             PRT  
             Schizosaccharomyces pombe  
           
            39 

Met Gly Glu Lys Asp Lys Leu His Glu Ile Ser Ser Lys Phe Ala Ser 
  1               5                  10                  15 

Leu Gly Leu Gly Ser Leu Lys Ser Thr Pro Lys Ala Arg Glu Thr Thr 
             20                  25                  30 

Glu Pro Pro Pro Pro Ser Ser Gln Gln Pro Pro Ser Thr Pro Asn Gly 
         35                  40                  45 

Lys Glu Ala Ala Ser Pro Ser Ala Leu Lys Gln Asn Val Arg Pro Ser 
     50                  55                  60 

Leu Asn Ser Val Gln Gln Thr Pro Ala Ser Ile Asp Ala Val Ala Ser 
 65                  70                  75                  80 

Ser Ser Asn Val Ser Leu Gln Ser Gln Gln Pro Leu Ser Lys Pro Val 
                 85                  90                  95 

Val Ser Ser Lys Pro Asn Gln Thr Thr Ala Met Pro Pro Pro Ser Asn 
            100                 105                 110 

Asn Pro Ser Arg His Val Ser Ser Thr Ser Asn Lys Pro Ala Ala Val 
        115                 120                 125 

Ser Pro Asn Pro Ala Ala His His Ala Glu Leu Pro Ser Gly Ser Val 
    130                 135                 140 

Pro Pro Ser Ala Ser Val Ser Arg Ala Asn Ser Thr Ala Thr Thr Thr 
145                 150                 155                 160 

Pro His Lys Ala Gly Val Val Ser Asn Pro Ala Ala Ala Asn Val His 
                165                 170                 175 

Val Leu Ser Val Ala Ala Ser Pro Asn Pro Ser Thr Pro Ser Asn Gly 
            180                 185                 190 

Pro Ala Pro Val Ser Thr Thr Ala Thr Pro Ser Arg Asn Pro Val Thr 
        195                 200                 205 

Arg Leu Gln Arg Ile Phe Ser Gln Asn Ser Val Ser Arg Gln Asn Ser 
    210                 215                 220 

Arg Thr Gly Arg Gly Ala Ala Val Ala Asn Thr Glu Glu Thr Asn Ser 
225                 230                 235                 240 

Thr Gly Gly Ser Glu Thr Gly Gly Ala Ala Asn Ser Ser Ser Thr Ser 
                245                 250                 255 

Asn Pro Ser Ser Ala Lys Trp Ser Arg Phe Thr Val Tyr Asp Asp Ala 
            260                 265                 270 

Ser His Thr His Gln Leu Arg Pro Ala Arg Arg Gln Glu Lys Leu Gly 
        275                 280                 285 

Lys Met Leu Lys Asp Phe Leu Ala Gly Asn Ser Lys Lys Arg Glu Glu 
    290                 295                 300 

Glu Arg Ile Ala Lys Glu Ala Ala Asp Ala Gln His Gln Leu Ser Leu 
305                 310                 315                 320 

Val Gln Ser Trp Ile Asn Gly Tyr Gly Gln Glu Lys Leu Ala Asp Lys 
                325                 330                 335 

Lys Asp Pro Ala Lys Val Ser Ala Ser Phe Val Glu Lys Tyr Gly Arg 
            340                 345                 350 

Cys Gln Glu Val Ile Gly Arg Gly Ala Phe Gly Val Val Arg Ile Ala 
        355                 360                 365 

His Lys Val Asp Pro Gln Asn Ser Gly Ser Glu Thr Leu Tyr Ala Val 
    370                 375                 380 

Lys Glu Phe Arg Arg Lys Pro Ala Glu Ser Gln Lys Lys Tyr Thr Lys 
385                 390                 395                 400 

Arg Leu Thr Ser Glu Phe Cys Ile Ser Ser Ser Leu Arg His Pro Asn 
                405                 410                 415 

Val Ile His Thr Leu Asp Leu Ile Gln Asp Gly Lys Gly Asp Tyr Cys 
            420                 425                 430 

Glu Val Met Glu Leu Cys Ser Gly Gly Asp Leu Tyr Thr Leu Ile Met 
        435                 440                 445 

Ala Ala Gly Arg Leu Glu Pro Met Glu Ala Asp Cys Phe Phe Lys Gln 
    450                 455                 460 

Leu Met Arg Gly Val Asp Tyr Leu His Asp Met Gly Val Ala His Arg 
465                 470                 475                 480 

Asp Leu Lys Pro Glu Asn Leu Leu Leu Thr Val Ser Gly Ser Leu Lys 
                485                 490                 495 

Ile Thr Asp Phe Gly Asn Gly Glu Cys Phe Arg Met Ala Trp Glu Lys 
            500                 505                 510 

Glu Ala His Met Thr Cys Gly Leu Cys Gly Ser Ala Pro Tyr Ile Ala 
        515                 520                 525 

Pro Glu Glu Tyr Thr Glu Ser Glu Phe Asp Pro Arg Ala Val Asp Val 
    530                 535                 540 

Trp Ala Cys Gly Val Ile Tyr Met Ala Met Arg Thr Gly Arg His Leu 
545                 550                 555                 560 

Trp Arg Val Ala Lys Lys Ser Glu Asp Glu Tyr Tyr Ser Arg Tyr Leu 
                565                 570                 575 

Met Asp Arg Lys Asn Glu Ser Gly Tyr Glu Pro Ile Glu Met Leu Glu 
            580                 585                 590 

Arg Ser Arg Cys Arg Asn Thr Leu Tyr Asn Ile Leu His Pro Asn Pro 
        595                 600                 605 

Thr Tyr Arg Leu Thr Ala Lys Gln Ile Met Lys Ser Glu Trp Val Arg 
    610                 615                 620 

Ser Ile Thr Leu Cys Glu Ala Gly Asn Ala Gly Leu 
625                 630                 635 

 
           
             40  
             650  
             PRT  
             Schizosaccharomyces pombe  
           
            40 

Met Ser Val Thr Pro Pro Asn Val Gln Phe Asn Leu Asn Gly Asp Ser 
  1               5                  10                  15 

Asp His Lys Ser Asp Asn Ser Ser Ser Ser Leu Glu Asn Lys Leu Asp 
             20                  25                  30 

Thr Glu Leu Lys Ile Thr Ser Pro Pro Arg Asn Pro Pro Gln Arg Leu 
         35                  40                  45 

His Pro Val Asp Phe Ser Glu His Ala Asp Thr Asp Asp Asp Met Asn 
     50                  55                  60 

His Pro Leu Pro Arg Val Gln Ser Pro Val His Ile Lys Asn His Ile 
 65                  70                  75                  80 

Asp Pro Lys Leu Ala Glu Asp Arg Tyr Arg Ser Ser Ala Ala Arg His 
                 85                  90                  95 

Phe Glu Pro Ile Ser Ile Pro Pro Ser Ala Ile Thr Ser Glu Asp Glu 
            100                 105                 110 

Asp Asp Tyr His Gly Ser Ala Asn Ser Ser Thr Val Leu Pro Pro Arg 
        115                 120                 125 

Thr Glu Asn Ala Leu His Ala Ala Ser Pro Lys Pro Ser Gly Ser Thr 
    130                 135                 140 

Gly Tyr Thr Ser Pro Ala Leu Ser Gln Asn Ser Gly Ser Gly Gly Glu 
145                 150                 155                 160 

Gly Glu Ser Asp Glu Gly Ser Phe Asn Thr Gln His His Arg Ser Pro 
                165                 170                 175 

Ile Phe Gln Ala Tyr Pro Ser Ser Glu Asp Leu Val Gly Asp Pro Asn 
            180                 185                 190 

Asp Pro Tyr Arg Arg Thr Arg Arg Ala Pro Ile Lys Thr Asn Pro His 
        195                 200                 205 

Asp Ile Pro Ser Gln Phe Ile Phe Arg Lys Leu Gly Leu His His Gly 
    210                 215                 220 

Lys His Gly His His Gly His Ser Gly Ser Leu Ser Leu Lys Ser Leu 
225                 230                 235                 240 

Val Pro Asn His His Asp Lys His Asp Lys His Asp Lys His Glu Lys 
                245                 250                 255 

His His Ser Ser Leu Asp Leu Arg Arg Phe Phe Lys Ser His Gln Lys 
            260                 265                 270 

Thr Asp Lys Glu Lys Lys Pro Ser Val Ser Lys Ser Lys Ser Ser Ala 
        275                 280                 285 

Asn Leu Gln Asp Asp His Phe Gly Leu Phe Lys Lys Tyr Gly Lys Phe 
    290                 295                 300 

Gly Arg Met Leu Gly Ser Gly Ala Gly Gly Ser Val Arg Ile Met Lys 
305                 310                 315                 320 

Arg Ser Ser Asp Gly Lys Ile Phe Ala Val Lys Glu Phe Arg Ala Arg 
                325                 330                 335 

Arg Pro Thr Glu Thr Glu Arg Glu Tyr Ala Arg Lys Val Thr Ala Glu 
            340                 345                 350 

Phe Cys Ile Gly Ser Ala Leu His His Thr Asn Ile Ile Glu Thr Leu 
        355                 360                 365 

Asp Ile Val Glu Glu Asn Lys Lys Phe Tyr Glu Val Met Glu Tyr Ala 
    370                 375                 380 

Pro Tyr Asp Met Phe Ser Ile Val Met Ser Gly Lys Met Thr Met Pro 
385                 390                 395                 400 

Glu Val Tyr Cys Cys Phe Lys Gln Leu Leu Ser Gly Val Ala Tyr Leu 
                405                 410                 415 

His Ser Met Gly Leu Ala His Arg Asp Leu Lys Leu Asp Asn Leu Val 
            420                 425                 430 

Val Asp Ser Asn Cys Phe Val Lys Ile Ile Asp Phe Gly Ser Ala Val 
        435                 440                 445 

Val Phe Lys Tyr Pro Phe Glu Ala Asp Ile Val Glu Ala Thr Gly Val 
    450                 455                 460 

Val Gly Ser Asp Pro Tyr Leu Ala Pro Glu Thr Leu Val Arg Lys Leu 
465                 470                 475                 480 

Tyr Asp Pro Arg Ala Val Asp Ile Trp Ser Ser Ala Ile Ile Phe Cys 
                485                 490                 495 

Cys Met Ala Leu Arg Arg Phe Pro Trp Lys Tyr Pro Lys Leu Ser Asp 
            500                 505                 510 

Asn Ser Phe Arg Leu Phe Cys Met Lys Gln Pro Ser Asn Asp Ala Glu 
        515                 520                 525 

Ser Pro Ser Asp Ile Leu Ala Asp Ile Lys Lys Gln Arg Leu Val Glu 
    530                 535                 540 

Gln Gly Cys Glu Pro Ile Arg Lys Thr Asp Glu Ser His Ser Pro Asn 
545                 550                 555                 560 

Ser Lys Thr Asp Asn Ser Ser Thr His Lys Gln Glu Leu Tyr Gly Pro 
                565                 570                 575 

Trp Arg Leu Leu Arg Leu Leu Pro Arg Glu Thr Arg Ala Val Ile Ala 
            580                 585                 590 

His Met Leu Glu Leu Asp Pro Val Lys Arg Tyr Asp Ile His Arg Val 
        595                 600                 605 

Phe Ala Asp Asn Trp Ile Asn Asp Ile Ser Met Cys His Met Glu Asn 
    610                 615                 620 

Gly Lys Val Ile His Ser Pro Thr His Val His Asn Leu Val Ala Ser 
625                 630                 635                 640 

Glu Glu Ser Pro Ala Pro Pro Ala Lys His 
                645                 650 

 
           
             41  
             812  
             PRT  
             Candida albicans  
           
            41 

Met Thr Lys Glu His Ser Ile Arg Asn Ile Phe Lys Lys Asp Lys Thr 
  1               5                  10                  15 

Pro Asp Asn Gly Ser Ala Thr Ala Thr Pro Ser Ser Ser His Thr Gly 
             20                  25                  30 

Leu Ser Lys Leu Phe His Lys Glu Ser Lys Pro Ile Thr Pro Pro Met 
         35                  40                  45 

Lys Arg Thr Pro Ser Val Ser Ser Leu Lys Arg Arg Asn Thr Asn Pro 
     50                  55                  60 

Ser Gln Thr Ser Gly Ile Ser Leu Asn His Asn His His His His Gln 
 65                  70                  75                  80 

Asp Ser Gln Asn His Asn Asp Ala Thr Thr Ser Gly Gly Asn Ile His 
                 85                  90                  95 

Ser Ser Thr Pro Val Asn Arg Ser Arg Ser Asn Ser Asp Arg Leu Gly 
            100                 105                 110 

His Val Pro Pro Thr Gly Arg Lys Val Leu Ser Lys Ala Glu Thr Phe 
        115                 120                 125 

Thr His Leu Gln Gln Leu Asp Thr Arg Asn Ala Ala Lys Asn Gln Leu 
    130                 135                 140 

Arg Asn His Arg Ile Pro Ser Asn His Leu Ser Ser Pro Leu Ser Ala 
145                 150                 155                 160 

Ala Pro His Ser Asp Lys Ile Val Tyr Asn Pro Tyr Gly Leu Asn Lys 
                165                 170                 175 

Thr Ala Thr Gln Glu Arg Pro Lys Asn Thr Ser Phe Tyr Leu Ser Gly 
            180                 185                 190 

Val Asn Asp Gly Glu Arg Val Leu Ser Asn Pro Val Ala Ser Pro Asn 
        195                 200                 205 

Asp Tyr Leu Pro Ala Glu Leu Gln Gln Gln His Val Asn Leu Leu Glu 
    210                 215                 220 

Asp Phe Glu Ile Asp Val Gly Thr Lys Lys Leu Gly Asp Gly Gly Ser 
225                 230                 235                 240 

Ser Asp Val Arg Ile Ile Asn Ser Cys His His Lys Lys Asp Leu Tyr 
                245                 250                 255 

Ala Leu Lys Lys Phe Thr Leu Leu Ser Lys Glu Thr Asp Glu Asp Phe 
            260                 265                 270 

Tyr Lys Arg Val Ser Glu Glu Tyr Lys Ile His Arg Lys Ala Ala Ile 
        275                 280                 285 

Ser Arg His Val Val Asp Ala Phe Ala Ile Leu Arg Ile Gln Ser Gln 
    290                 295                 300 

Ser Asn Leu Thr Arg Gly Trp Gly Met Val Met Glu Phe Cys Gly Gly 
305                 310                 315                 320 

Gly Asp Leu Phe Ser Val Ile Val Lys Pro Gly Trp Lys Ser Thr Pro 
                325                 330                 335 

Leu Ala Glu Lys Tyr Cys Leu Phe Lys Gln Ile Ala Tyr Gly Val Lys 
            340                 345                 350 

Phe Leu His Asp His Asp Ile Val His Arg Asp Leu Lys Pro Glu Asn 
        355                 360                 365 

Val Leu Leu Asp Ala Asn Gly Leu Ala Lys Leu Cys Asp Phe Gly Val 
    370                 375                 380 

Ser Glu Phe Gly His Glu Val Pro Glu Asp Phe Ser Ser Pro Val Lys 
385                 390                 395                 400 

Leu Ser Thr Ala Tyr Val Gly Ser Pro Pro Tyr Ala Pro Pro Glu Val 
                405                 410                 415 

Met Leu Leu Lys Glu Lys Ser Ser Thr Glu Ile Lys Ala Phe Ala Tyr 
            420                 425                 430 

Asp Pro Phe Lys Met Asp Cys Trp Gly Leu Gly Met Leu Leu Phe Cys 
        435                 440                 445 

Leu Val Tyr Gly Gly Val Pro Phe Gln Gln Ser Ser Pro Asn Asp His 
    450                 455                 460 

Ala Phe Arg Asp Tyr Lys Phe Ser His Lys Arg Phe Cys Thr Asp His 
465                 470                 475                 480 

His Thr Phe Lys Ser Asn Gln Gly Tyr Pro Arg Gly Pro Gly Ser Glu 
                485                 490                 495 

Phe Lys Leu Ala Ala Lys Phe Glu Asn Asn Gly Ala Ser Arg Val Ala 
            500                 505                 510 

Trp Lys Leu Cys Asp Pro Ser Glu Asn Thr Arg Tyr Thr Met Asp Met 
        515                 520                 525 

Leu Phe Asp Asp Pro Trp Phe Gln Ser Val Glu Met Cys Ile Tyr Glu 
    530                 535                 540 

Ser Pro Asp Gln Glu Val Asn Pro Phe Val Leu Pro Gly Thr Gly Glu 
545                 550                 555                 560 

Asn Ile Asp Thr His Ser Val Ser Gly Tyr Ser Ser Val Asn Asn Ser 
                565                 570                 575 

Gln Ala Pro Ser Arg Arg Gly Thr Phe Thr Ser Arg Pro Val Gly Ser 
            580                 585                 590 

Gly Ala Gly Ser Gly Tyr Asn Ser His Asp Glu Ser Ser Asn Gly Leu 
        595                 600                 605 

Ser Ser Ser Phe Arg Ser Met Leu Asp Leu Lys Asp Ile Pro Gln Lys 
    610                 615                 620 

Ile Thr Lys Thr Asp Glu Pro Leu Pro Ser Asn Ser Ser Val His Ser 
625                 630                 635                 640 

Asn Asp Ser Ser Ser Ala Arg Ala Lys Ser Lys Leu Asp His Pro Ser 
                645                 650                 655 

Ser Pro Gly Ser Leu Leu Ser Pro Ser Thr Pro Ala Leu Gln Ser Ile 
            660                 665                 670 

Pro Ala Asp Arg Val Ala Gln Thr Thr Ser Pro Ile Asn Ala Ser Leu 
        675                 680                 685 

Pro Ala Val Glu Glu Ser Asp Ile Glu His Glu Ser Glu Ser Glu Ile 
    690                 695                 700 

Gln Gly Asp Glu Thr Glu Ser Ser Gly Leu Gln Val Leu Pro Pro Ile 
705                 710                 715                 720 

Asp Asp Val Val Ala Ala Ser Pro Ser Ser Leu Thr His Glu Pro Gln 
                725                 730                 735 

Glu Gln Val Leu Asp Ser Val Glu Ser Cys Ile Ser Leu Pro Pro Asn 
            740                 745                 750 

Arg Asp Gln Ala Phe Ala Gly Lys Asp Gly Glu Met Cys Ser Leu Val 
        755                 760                 765 

Asp Leu Lys Pro Ala Ala Leu Lys Ser Ala Thr Asp Leu Gln Leu Gly 
    770                 775                 780 

Ala Asp Gly Met Cys Asn Leu Gly Tyr Lys Ile Lys Lys His His His 
785                 790                 795                 800 

Thr Glu Val Ser Asn Val Ser Asn Ser Ser Arg Arg 
                805                 810 

 
           
             42  
             800  
             PRT  
             Candida albicans  
           
            42 

Met Ser Ser Leu Thr Lys Leu Leu His Glu Ser Thr Ser Thr Leu Ala 
  1               5                  10                  15 

Ser Pro Val Leu Ser Arg Asn Thr Ser Glu Val Thr Phe Lys Asp Gln 
             20                  25                  30 

Gly Arg Arg Thr Pro Glu Ile Leu Asn Ile Ser Asp Thr Val Asp Ala 
         35                  40                  45 

Lys Ser Pro Gly Ile Thr Ile Asp Val Ser Lys Pro Lys Pro Ser Pro 
     50                  55                  60 

Ile Asp Thr Asp Gly Met Asn Val Glu Pro Gln Ala Val His Gly Phe 
 65                  70                  75                  80 

Asp Pro Ser Pro Asn Thr Lys Val Ser Phe Ser Ser Pro Phe Ser Pro 
                 85                  90                  95 

Thr Ser Pro Phe Thr Arg Gln Ser Ser Asn Ser Phe Ser Ser Asn Gln 
            100                 105                 110 

Ala Phe Gln Asn Thr Arg Gly Ala Val Ala Ser Pro Arg Tyr Ile Lys 
        115                 120                 125 

Asn Asn Ser Val Ser His Ser Ser Val Phe Met Gly Gly Glu Ser Leu 
    130                 135                 140 

Ser Ser Ser Ile Pro Tyr Ser Ala Pro Gly Gly Gly Arg Gly Asn Pro 
145                 150                 155                 160 

Ala Ser His Ser Gly Asn Thr Gly Ser Leu Gln Arg Glu Asn Ser Phe 
                165                 170                 175 

Ser Ser Leu Asn Thr Ser Asp Ser Asn Ser Ser Ala His Ile Pro Asn 
            180                 185                 190 

Leu Pro Asn Gly Gln Pro Ile Asn Ser Ile His Ile Gln Ser Pro Gln 
        195                 200                 205 

Val Ser Ala Ser Ser Ile Asp Ser Arg Phe Val Val Ser Lys Gln Arg 
    210                 215                 220 

Ile Ala Gln Ala Gln Ala Gln Ala Ser Leu Ser Ser Ser Gln Arg Ser 
225                 230                 235                 240 

Asn Ser Gln Ser Gly Leu Ser Phe Phe Phe Ser Gln Lys Ser Lys Pro 
                245                 250                 255 

Ala Val Lys Arg Asp Ser Thr Thr Asp Leu Gly Ala Phe Tyr Asn Asn 
            260                 265                 270 

Ser Tyr Gln Asp Arg Asp Ala Pro Ile Val Ser Gly Ser Pro Asn Ser 
        275                 280                 285 

Leu Ser Ser Ala Glu Ser Thr Val Ser Tyr Gly Ser Ser Ala Pro Thr 
    290                 295                 300 

Arg His Asn Ser Met Ala Asn Leu Lys Arg Phe Phe Lys Lys Ser Thr 
305                 310                 315                 320 

Pro Thr Thr Ser Gln Pro Val Gly Thr Ser Asn Leu Ser Ser Ser Leu 
                325                 330                 335 

Arg Ser Ala Ser Ser Gly Ala Ser Gly Ala Met Asn Ile Pro Asn Ser 
            340                 345                 350 

Leu Asn Gly Gln Thr Asn Asn Gly Tyr Gln Ser Pro Ser Ser Phe Ser 
        355                 360                 365 

Ala Ser Thr Ser Asn Thr Ser Tyr Ser Gln Ser Pro Gly Thr Asn Ser 
    370                 375                 380 

Ser Ser Val Thr Arg Ser Ser Thr Leu Gln Asn Lys Val Asn Tyr His 
385                 390                 395                 400 

Glu Arg Arg Gln Ser Val Ser Gly Ile Val Asn Asn Ser Gln Gln Leu 
                405                 410                 415 

Pro Phe Ser Lys Arg Tyr His Ser Lys Asn Ala Glu Ser Leu Gly Ala 
            420                 425                 430 

Gly Ala Gly Gly Ser Val Arg Leu Leu Thr Arg Val Ser Asp Gly Leu 
        435                 440                 445 

Thr Phe Ala Val Lys Glu Phe Arg Ala Lys Tyr Gln Asn Glu Ser Lys 
    450                 455                 460 

Arg Asp Tyr Ala Lys Lys Ile Thr Gly Glu Tyr Cys Ile Gly Ser Thr 
465                 470                 475                 480 

Leu Lys His Pro Asn Ile Ile Glu Thr Val Glu Ile Cys Tyr Glu Asn 
                485                 490                 495 

Glu Arg Ile His Gln Val Met Glu Tyr Cys Asp Phe Asp Leu Phe Ala 
            500                 505                 510 

Ile Val Met Ser Asn Lys Met Ser Arg Glu Glu Ile Asn Cys Cys Phe 
        515                 520                 525 

Lys Gln Ile Leu Ala Gly Val His Tyr Leu His Ser Met Gly Leu Ala 
    530                 535                 540 

His Arg Asp Leu Lys Leu Asp Asn Cys Val Ile Asp Lys Arg Gly Ile 
545                 550                 555                 560 

Val Lys Ile Ile Asp Phe Gly Ser Ala Val Val Phe Ser Tyr Pro Phe 
                565                 570                 575 

Thr Lys Thr Leu Ile Glu Ala Gln Gly Ile Val Gly Ser Asp Pro Tyr 
            580                 585                 590 

Leu Ala Pro Glu Val Cys Val Phe Asn Lys Tyr Asp Pro Arg Pro Val 
        595                 600                 605 

Asp Val Trp Ser Val Ala Ile Ile Tyr Cys Cys Met Met Leu Lys Lys 
    610                 615                 620 

Phe Pro Trp Lys Val Pro Lys Leu Ser Asp Ser Ser Phe Lys Leu Phe 
625                 630                 635                 640 

Ala Ser Arg Gly Glu Phe Ile Pro Ile Ser Glu Met Leu Lys Lys Thr 
                645                 650                 655 

Pro Asn Asp Met Glu Lys Ser Asn Ser Asn Gly Ser Ser Gly Gly Gly 
            660                 665                 670 

Leu Ser Asn Leu Glu Asp Ile Ser Glu Ala Leu Glu Asp Glu Ile Thr 
        675                 680                 685 

Ala Gly Ala Lys Gln Lys Pro Ser Thr Thr Gly Gln Asn Gly Ala Thr 
    690                 695                 700 

Ala Asn Gly Lys Asp His Thr Ser Ser Glu Thr Gly Ala Asn Arg Leu 
705                 710                 715                 720 

Leu Leu Ala Leu Pro Glu Asp Cys Arg Arg Leu Ile Gly Arg Met Val 
                725                 730                 735 

Glu Leu Ala Pro Ala Cys Arg Ile Thr Ile Asp Glu Val Leu Asn Asp 
            740                 745                 750 

Ser Trp Leu Lys Ser Val Asn Met Cys Thr Val Glu Glu Ser Ser Pro 
        755                 760                 765 

Gly Val Phe Glu Val Ile Lys Cys Glu Asp His Glu His Thr Gln Val 
    770                 775                 780 

Asp Gln Ser Lys Ala His Ile Ala Ala Phe Glu Lys Asn Lys Lys Lys 
785                 790                 795                 800