Abstract:
The present invention provides novel isolated and purified nucleic acid (RNA or DNA) encoding, or complementary to, a canine PepT1 (cPepT1). The present invention also provide a method for determining canine PepT1-transportability of a peptide, or method for determining a peptide with beneficial nutritional property in an animal. The present invention further provides a dietary composition for an animal comprising a peptide identified by the method described above.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
       [0001]    This application claims the benefit of U.S. Provisional Application Serial No. 60/273,263, filed Mar. 2, 2001, under 35 U.S.C. 119(e) and U.S. Provisional Application Serial No. 60/344,088, filed Dec. 26, 2001, under 35 U.S.C. 119(e). 
     
    
     
       BACKGROUND OF THE INVENTION  
         [0002]    In dogs, it is thought that the ability to absorb essential amino acids such as tryptophan and leucine may be limiting to cellular metabolism. Recent research designed to characterize the amino acid absorption capacity of the brush border (lumen facing) membranes of dog enterocytes suggests that peptide absorption may be particularly important given the relatively low amount of free amino acid transport capacity that was observed. Buddington R K, Paulsen D B. Development of the Canine and Feline Gastrointestinal Tract. In: Reinhart G A, Carey D P, eds.  Recent Advances in Canine and Feline Nutrition, Vol. II.  1998  Iams Nutrition Symposium Proceedings.  Wilmington: Orange Frazer Press, 1998; 195-215. Data collected from studies designed to understand the quantitative importance of free versus peptide amino acids in other monogastric animals strongly indicates that peptide-bound amino acids account for the majority of amino acids absorbed by enterocytes from the intestinal lumen (Matthews, D M.  Protein Absorption, Development and Present State of the Subject,  New York: Wiley-Liss, 1991.) and that the rate of peptide-derived amino acid absorption is faster than that by equivalent amounts of free amino acids. Ohkohchi N, Andoh T, Ohi R, Mori S. Defined formula diets alter characteristics of the intestinal transport of amino acid and peptide in growing rats.  J Pediatr Gastroenterol Nutr  May 1990; 10(4):490-6.  
           [0003]    Two types of peptide transporters have been cloned from monogastric animals. Liang R, Fei Y J, Prasad P D, Ramamoorthy S, Han H, Yang-Feng T L, Hediger M A, Ganapathy V, Leibach F H. Human intestinal H+/peptide cotransporter. Cloning, functional expression, and chromosomal localization.  J Biol Chem  Mar. 24, 1995; 270(12):6456-63. Liu W, Liang R, Ramamoorthy S, Fei Y J, Ganapathy M E, Hediger M A, Ganapathy V, Leibach F H. Molecular cloning of PEPT 2, a new member of the H+/peptide cotransporter family, from human kidney.  Biochim Biophys Acta  May 4, 1995; 1235(2):461-6. PepT1 is an H + -dependent, low-affinity (mM), high-velocity, transporter that is predominately localized primarily to the brush border membranes of mature enterocytes of intestinal villi. PepT2 is an H + -dependent, high-affinity (μM), low-velocity, transporter that is expressed in the greatest abundance in the apical membranes of renal proximal tubular epithelial cells. An important feature of the peptide transporters is their ability to recognize and transport most di- and tripeptides, albeit with a range of relative affinities for different peptides. In addition, both transporters recognize the β-lactam antibiotics, and carboxyl-terminal modified free amino acids. The physiologic functions of these transporters are thought to be to absorb di- and tripeptides from the digesta and from the blood, respectively. Although molecular evidence has not been acquired, there is strong biochemical evidence for a different peptide transport protein that functions in the basolateral membrane of these cells. Saito H, Inui K I. Dipeptide transporters in apical and basolateral membranes of the human intestinal cell line Caco-2.  Am J Physiol  August 1993; 265(2 Pt 1):G289-94. Thwaites D T, Brown C D, Hirst B H, Simmons N L. Transepithelial glycylsarcosine transport in intestinal Caco-2 cells mediated by the expression of H + -coupled carriers at both the apical and basal membranes.  J Biol Chem  Apr. 15, 1993; 268(11):7640-2.  
           [0004]    Research with Caco-2 cells indicates that PepT1 transporter mRNA, protein, and activity increases in a manner consistent with a direct effect of increased extracellular substrate concentrations. Walker D, Thwaites D T, Simmons N L, Gilbert H J, Hirst B H. Substrate upregulation of the human small intestinal peptide transporter, hPepT1.  J Physiol  Mar. 15, 1998; 507(Pt 3):697-706. In contrast to mRNAs for essential amino acid transporters, intestinal studies show that the expression of peptide transporter mRNA increases in response to increased dietary protein. Erickson R H, Gum J R Jr, Lindstrom M M, McKean D, Kim Y S. Regional expression and dietary regulation of rat small intestinal peptide and amino acid transporter mRNAs.  Biochem Biophys Res Commun  Nov. 2, 1995; 216(1):249-57. Similarly, expression in intestinal mucosa of PepT1 mRNA and protein increases in response to tissue trauma, whereas the mRNA for essential amino acid transporters decreases. Tanaka H, Miyamoto K I, Morita K, Haga H, Segawa H, Shiraga T, Fujioka A, Kuoda T, Taketani Y, Hisano S, Fukui Y, Kitagawa K, Takeda E. Regulation of the PepT1 peptide transporter in the rat small intestine in response to 5-fluorouracil-induced injury.  Gastroenterology  April 1998; 114(4):714-23.  
           [0005]    Few studies have been conducted to evaluate the potential for the dog to absorb quantitatively significant amounts of essential amino acids in the form of small peptides, and whether this capacity can be regulated by substrate supply. Accordingly, there is still a need to evaluate the potential for the absorption of peptide-bound leucine and tryptophan by putative canine peptide transporters. It would thus be desirable to provide the nucleic acid sequence encoding canine PepT1. It would also be desirable to provide mRNA transcripts corresponding to cPepT1. It would further be desirable to characterize the function of cPepT1 by GlySar uptake and identify di- and tripeptides well recognized by cPepT1, as well as characterize the effect of supplemental peptide substrate on the transport capacity of canine PepT1 (cPepT1).  
         SUMMARY OF THE INVENTION  
         [0006]    The present invention provides novel isolated and purified nucleic acids (RNA or DNA) encoding, or complementary to, canine PepT1 (cPepT1). The nucleic acid may be SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:20 or may be a nucleic acid that hybridizes under moderate or stringent hybridization conditions to any of these sequences. Also provided are peptides encoded by these nucleic acids, such as SEQ ID NO:13 or SEQ ID NO:21.  
           [0007]    The present invention also provides a method for determining canine PepT1-transportability of a peptide, or method for determining a peptide with beneficial nutritional property in an animal, comprising providing an immortalized kidney distal tubule epithelial (Madin-Darby Canine Kidney (MDCK)) cell and a peptide having 2 to 10 amino acids, and determining the amount of the peptide transported into the cell, wherein the amount correlates with the canine PepT1-transportability of the peptide. A peptide with beneficial nutritional properties in an animal is a peptide that contains at least one essential amino acid that is absorbed at a rate higher than the rate of the amino acid if it were free rather than in a peptide-bound form. The peptide may be a dipeptide, tripeptide, or tetrapeptide such as, for example, GlySar, GlyGly, AlaHis, β-AlaHis (carnosine), GlnGln, GlyMet, LeuMet, LeuTrp, MetLeu, MetMet, MetPhe, MetPro, TrpLeu, TrpTrp, GlnGlu, MetGlu, MetLys, TrpGly, MetGlyMetMet (SEQ ID NO:10), TrpGlyGly, LeuArg, ArgLeu, GlyLeu, or ArgTrp. The cell used in the method may be in medium at a pH of between about 5 and 8; or at a pH of about 5.5 to 7.5, or even at about 6 to 6.5. The peptide may be present at a concentration of about 10 nm to about 50 mM.  
           [0008]    The characterization of GlySar uptake by immortalized MDCK cells demonstrates that MDCK cells express PepT1-like activity, confirming detection of PepT1 mRNA expression by MDCK cells and the use of MDCK cells as a model to characterize the biochemical function of canine PepT1.  
           [0009]    The cPepT1 of the present invention is also capable of recognizing a variety of di- and tripeptides, including those that contain the essential amino acids leucine and tryptophan, considered to be of especial importance to canine nutrition. In addition, H + -dependent peptide transport in cultured MDCK cells can be stimulated by at least two of PepT1 substrates, GlySar and carnosine. Moreover, H + -dependent uptake of GlySar by MDCK is sensitive to nutrient deprivation and Insulin-like Growth factor I (IGF-I).  
           [0010]    The present invention further provides a dietary composition with improved nutritional benefit for an animal comprising at least one peptide identified by the method described above.  
           [0011]    The present invention provides a process for altering the absorption of essential amino acids in an animal, such as a dog, comprising the steps of feeding the animal a diet containing the dietary composition described above; and maintaining the animal on the diet for a sufficient period of time to allow the composition to be absorbed by the digestive system of the animal. The diet may comprise about 20 to about 30% crude protein, about 10 to about 20% fat, and about 3 to about 10% dietary fiber.  
           [0012]    As used herein, the term “cPepT1” includes variants or biologically active or inactive fragments of this transport protein. A “variant” of the polypeptide is a cPepT1 protein that is not completely identical to a native cPepT1 protein. A variant cPepT1 protein can be obtained by altering the amino acid sequence by insertion, deletion or substitution of one or more amino acid. The amino acid sequence of the protein is modified, for example by substitution, to create a polypeptide having substantially the same or improved qualities as compared to the native polypeptide. The substitution may be a conserved substitution. A “conserved substitution” is a substitution of an amino acid with another amino acid having a similar side chain. A conserved substitution would be a substitution with an amino acid that makes the smallest change possible in the charge of the amino acid or size of the side chain of the amino acid (alternatively, in the size, charge or kind of chemical group within the side chain) such that the overall peptide retains its spacial conformation but has altered biological activity. For example, common conserved changes might be Asp to Glu, Asn or Gln; His to Lys, Arg or Phe; Asn to Gln, Asp or Glu and Ser to Cys, Thr or Gly. Alanine is commonly used to substitute for other amino acids. The 20 common amino acids can be grouped as follows: alanine, valine, leucine, isoleucine, proline, phenylalanine, tryptophan and methionine having nonpolar side chains; glycine, serine, threonine, cystine, tyrosine, asparagine and glutamine having uncharged polar side chains; aspartate and glutamate having acidic side chains; and lysine, arginine, and histidine having basic side chains. Stryer, L.  Biochemistry  (2d edition) W. H. Freeman and Co. San Francisco (1981), p. 14-15; Lehninger, A.  Biochemistry  (2d ed., 1975), p. 73-75. It is known to those of skill in the art that transport of other, less common, amino acids such as hydroxylysine, or derivatives of any one of the 20 common amino acids listed above would also be within the scope of this invention.  
           [0013]    It is known that variant polypeptides can be obtained based on substituting certain amino acids for other amino acids in the polypeptide structure in order to modify or improve biological activity. For example, through substitution of alternative amino acids, small conformational changes may be conferred upon a polypeptide that result in increased bioactivity. Alternatively, amino acid substitutions in certain polypeptides may be used to provide residues that may then be linked to other molecules to provide peptide-molecule conjugates that retain sufficient properties of the starting polypeptide to be useful for other purposes.  
           [0014]    One can use the hydropathic index of amino acids in conferring interactive biological function on a polypeptide, wherein it is found that certain amino acids may be substituted for other amino acids having similar hydropathic indices and still retain a similar biological activity. Alternatively, substitution of like amino acids may be made on the basis of hydrophilicity. It is noted that substitutions can be made based on the hydrophilicity assigned to each amino acid. In using either the hydrophilicity index or hydropathic index, which assigns values to each amino acid, it is preferred to conduct substitutions of amino acids where these values are ±2, with ±1 being particularly preferred, and those with in ±0.5 being the most preferred substitutions.  
           [0015]    The variant cPepT1 protein comprises at least seven amino acid residues, preferably about 20 to about 700 residues, and more preferably about 50 to about 700 residues, wherein the variant cPepT1 protein has at least 50%, preferably at least about 80%, and more preferably at least about 90% but less than 100%, contiguous amino acid sequence homology or identity to the amino acid sequence of a corresponding native cPepT1 protein.  
           [0016]    The amino acid sequence of the variant cPepT1 protein corresponds essentially to the native cPepT1 protein amino acid sequence. As used herein “correspond essentially to” refers to a polypeptide sequence that will elicit an absorption value substantially the same as the absorption stimulated by native cPepT1 protein. Such absorption may be at least 60% of the level generated by native cPepT1 protein, and may even be at least 80% of the level generated by native cPepT1 protein.  
           [0017]    A variant of the invention may include amino acid residues not present in the corresponding native cPepT1 protein, or may include deletions relative to the corresponding native cPepT1 protein. A variant may also be a truncated “fragment” as compared to the corresponding native cPepT1 protein, i.e., only a portion of a full-length protein. cPepT1 protein variants also include peptides having at least one D-amino acid.  
           [0018]    The cPepT1 protein of the present invention may be expressed from an isolated nucleic acid (DNA or RNA) sequence encoding the cPepT1 protein. Amino acid changes from the native to the variant cPepT1 protein may be achieved by changing the codons of the corresponding nucleic acid sequence. “Recombinant” is defined as a peptide or nucleic acid produced by the processes of genetic engineering. It should be noted that it is well-known in the art that, due to the redundancy in the genetic code, individual nucleotides can be readily exchanged in a codon, and still result in an identical amino acid sequence. The terms “protein,” “peptide” and “polypeptide” are used interchangeably herein. 
       
    
    
     BRIEF DESCRIPTION OF THE FIGURES  
       [0019]    [0019]FIG. 1 is a photograph of an electrophoresis gel showing the partial length canine PepT1 cDNA reaction products generated by reverse transcription-polymerase chain reaction (RT-PCR) methodology. Partial length canine PepT1 (cPepT1, about 783 bp) cDNAs were generated by reverse transcription-polymerase chain reaction (RT-PCR) methodology. RT-PCR reaction products were generated using mRNA isolated from canine jejunal epithelium and two different PCR primer sets. Gel contents are as follows: lane 1, 1 Kb molecular weight DNA ladder; lane 2, negative control PCR reaction (lacks Taq polymerase); lane 3, PCR reaction products using primer set 4 (corresponding to base pairs 83 to 863 of rabbit PepT1); lane 4, PCR reaction products using primer set 10˜780 bp cDNA product using primer set 10 (corresponding to base pairs 85 to 861 of rabbit PepT1). Note the reaction products in lanes 3 and 4 of about 780 base pairs.  
         [0020]    [0020]FIGS. 2A and 2B are photographs of agarose gels showing the representative results of restriction analyses of pCR®II/cPepT1 plasmids generated by TA-cloning of primer set 4-derived RT-PCR cDNA. Restriction analyses of pCR®II/cPepT1 plasmids generated by TA-cloning of primer set 4-derived RT-PCR cDNA are shown in these figures. Data are representative of four cDNA-containing plasmids from a total of fifty-six “positive” bacterial colonies selected by blue/white screening. TA-clones were amplified, pCR®II/cDNA vectors isolated, and Xho I and Kpn I endonucleases restriction products size-separated through 1.2% agarose gels. FIG. 2A is a photograph of an agarose gel showing representative results of the PCR-based analyses of TA-clone 26. In particular, analyses of pCR®II/cPepT1-26 (TA-clone 26) are shown; lane 1, 1 DNA size standard; lane 2, minus endonuclease-restriction control (uncut pCR®II plasmid); lane 3, positive restriction control (Xho I restriction of empty pCR®II vector); lane 4, uncut pCR®II/cPepT1-26 (Clone 26); lane 5, Xho I- and Kpn I-restricted Clone 26. Note that empty pCR®II vector is 3.9 kb in size and that lane 5 contains a product of about 780 bp. FIG. 2B is a photograph of an agarose gel showing representative results of the PCR-based analyses of TA-clone 4 and 6. In particular, analyses of TA-clone 4 and 6 are shown; lane 1, DNA size standard; lane 2, uncut pCR®II/cPepT1-4 (TA-clone 4); lane 3, Xho I- and Kpn I-restricted pCR®II/cPepT1-4; lane 4, uncut pCR®II/cPepT1-6 (TA-clone 6); lane 5, Xho I- and Kpn I-restricted pCR®II/cPepT1-6. Note that empty pCR®II vector is 3.9 kb in size and that lane 3 does not contain a product of about 780 bp, whereas lane 5 does.  
         [0021]    [0021]FIGS. 3A and 3B are photographs showing the representative results of Northern blot identification of cPepT1 mRNA expression by canine tissues and MDCK cells using canine intestinal epithelium-derived RT-PCR cDNA. Arrangement of RNA isolated from tissue or cell homogenates on both blots is as follows: lane 1, kidney (animal #1031A); lane 2, kidney (animal K-9-1); lane 3, MDCK cells; lane 4, jejunal epithelium (animal K-9-4). FIG. 3A is a photograph showing the Northern blot identification of A + RNA (3 μg/lane) that was hybridized with [ 32 P]-cPepT1-26 cDNA. FIG. 3B is a photograph showing the Northern blot identification of total RNA (20 μg/lane) that was hybridized with [ 32 P]-cPepT1-6 cDNA.  
         [0022]    [0022]FIG. 4 is a photograph showing the representative results of Northern blot identification of cPepT1 mRNA expression in canine tissues using full-length rabbit PepT1 cDNA. Ten μg total RNA (lane 1) or 6 μg A + RNA (lanes 2 to 5) were isolated from liver and kidney tissues from three animals. Lane 1, liver (animal #1042A); lane 2, liver (animal #1008A); lane 3, kidney (animal #1008A); lane 4, liver (animal #1031A); lane 5, kidney (animal #1031A).  
         [0023]    [0023]FIG. 5 is the partial-length nucleic acid sequence of canine PepT1 cDNA of the present invention that was cloned from MDCK cells (SEQ ID NO:9). The 381 base pairs of TA clone PepT1-6R-20 shares 79% homology to base pairs 259 to 640 of rabbit PepT1 (GenBank acc no. 473375).  
         [0024]    [0024]FIG. 6 is a graph illustrating the influence of extracellular GlySar concentrations on GlySar uptake by confluent MDCK cells in pH 6.0 media. By graphical evaluation, an apparent K m  of about 4 mM was demonstrated. Each data point is the mean of 5 to 6 observations and all coefficients of variation were less than 15%.  
         [0025]    [0025]FIG. 7 is a graph illustrating the protein content of MDCK cells cultured in DMEM or LHM. Values are the means±SD of protein content of wells (n=12) of MDCK cells after seeding at 60,000 or 120,000 cells/well, culture for 1 d in DMEM, and then culture in DMEM or LHM for 1, 2, 3, or 5 d (Days 2, 3, 4 and 6, respectively). Protein content was determined by the method of Lowry, using bovine serum albumin as the standard.  
         [0026]    [0026]FIG. 8 is a graph illustrating GlySar (2.88 μM) uptake in pH 6.0 or pH 7.4 buffer by MDCK cells cultured in DMEM or LHM. Uptake was measured in the absence (pH 7.4) or presence (pH 6.0) of an extracellular-to-intracellular H +  gradient.  
         [0027]    [0027]FIG. 9 is a graph illustrating H + -dependent [ 3 H]-GlySar (2.88 μM) uptake by MDCK cells cultured in DMEM or LHM. Values were calculated as the difference in GlySar uptake in the presence (pH 6.0 uptake buffer) and absence (pH 7.4 uptake buffer) of an extracellular-to-intercellular H +  proton gradient.  
         [0028]    [0028]FIG. 10 is a graph illustrating pH-dependent GlySar uptake by MDCK cells seeded at 60,000 cells/well and cultured in LHM for 2 days. pH-dependent GlySar (2.88 μM) uptake by MDCK cells cultured with standard conditions. Values represent the H + -dependent GlySar uptake means±SD of wells (n=16) of MDCK cells, calculated as the difference from GlySar uptake in the presence of pH 6.0 or 7.4 buffers.  
         [0029]    [0029]FIG. 11 is a graph illustrating the effect of time on GlySar uptake (100 μM) by MDCK cells. By-minute time course for GlySar (uptake by MDCK cells cultured with standard conditions. Mean±SD GlySar uptake wells of cells (n=6) were assayed at 3.75, 7.5, 15, 30, 60, or 120 min.  
         [0030]    [0030]FIG. 12 is a graph illustrating the effect of GlySar concentration on MDCK cells seeded at 60K/well grown in LHM. The graph indicates the K m  characterization (1.0 mM) of H + -dependent GlySar uptake by MDCK cells. Each value represents the mean±SD uptake of GlySar by wells (n=8) of MDCK cells cultured using standard conditions.  
         [0031]    [0031]FIG. 13 is a graph illustrating the inhibition of peptide uptake by MDCK cells with antibiotics. The mean±SD are the uptake of GlySar by wells (n=5-8) of MDCK cells in the absence or presence of GlySar (1 mM) Penicillin-G (3 mM), cefadroxil (30 μM), or cefadroxil (3 mM).  
         [0032]    [0032]FIG. 14 is a graph illustrating the inhibition of peptide uptake by MDCK cells with Gly-containing peptides. The mean±SD uptake of GlySar by wells (n=7-8) of MDCK cells in the absence or presence of indicated competitor substrates (1 mM).  
         [0033]    [0033]FIG. 15 is a graph illustrating the inhibition of 100 μM GlySar uptake by 1 mM TrpLeu, LeuTrp, Leu, or Trp in the absence (pH 7.5) and presence (no pH designation) of a proton gradient and 1 mM of indicated substrates. Values are the mean±SD uptake of GlySar by wells (n=7-8) of MDCK cells.  
         [0034]    [0034]FIG. 16 is a graph illustrating the inhibition of 100 μM GlySar uptake by MDCK cells in the absence (pH 7.5) and presence (no pH designation) of a proton gradient and 1 mM of Trp-containing peptides. Values are the mean±SD uptake of GlySar by wells (n=7-8) of MDCK cells.  
         [0035]    [0035]FIG. 17 is a graph illustrating the inhibition of 100 μM GlySar uptake by MDCK cells in the absence (pH 7.5) and presence (no pH designation) of a proton gradient and 100 μM of Trp-containing peptides. Values are the mean±SD uptake of GlySar by wells (n=8) of MDCK cells.  
         [0036]    [0036]FIG. 18 is a graph illustrating the IC 50  inhibition of H + -dependent GlySar uptake by TrpLeu and TrpTrp. K 1  values were determined for inhibition of H + -dependent 100 μM GlySar uptake by MDCK cells in the presence of 0, 0.025, 0.1, 0.4, or 1.6 mM TrpTrp or TrpLeu. Values are the mean±SD uptake of GlySar by wells (n=6-8) of MDCK cells.  
         [0037]    [0037]FIG. 19 is a graph illustrating substrate (10 mM) regulation of protein content of MDCK cells cultured in DMEM. In particular, the influence of 10 mM carnosine, glycylphenylalanine (GlyPhe), Phe, or Gly supplementation of DMEM on protein content of MDCK cells was measured.  
         [0038]    [0038]FIG. 20 is a graph illustrating substrate (10 mM) regulation of GlySar uptake by MDCK cells cultured in DMEM. In particular, the influence of 10 mM carnosine, glycylphenylalanine (GlyPhe), Phe, or Gly supplementation of DMEM on H + -dependent uptake of [ 3 H]Glycylsarcosine (GlySar) by MDCK cells was measured.  
         [0039]    [0039]FIG. 21 is a graph illustrating substrate (10 mM) regulation of protein content of MDCK cells cultured in DMEM. In particular, the influence of 10 mM glycylsarcosine (GlySar), glycylproline (GlyPro), glycylphenylalanine (GlyPhe), or carnosine of DMEM on protein content of MDCK cells was measured.  
         [0040]    [0040]FIG. 22 is a graph illustrating substrate (10 mM) regulation of GlySar uptake by MDCK cells cultured in DMEM. In particular, the influence of 10 mM glycylsarcosine (GlySar), glycylproline (GlyPro), glycylphenylalanine (GlyPhe), or carnosine on H + -dependent uptake of [ 3 H]Glycylsarcosine (GlySar) by MDCK cells was measured.  
         [0041]    [0041]FIG. 23 is a graph illustrating the influence of DMEM, nutrient depleted, dexamethasone (Dex), or insulin (ins) on H + -dependent uptake of [ 3 H]Glycylsarcosine (GlySar) by MDCK cells.  
         [0042]    [0042]FIG. 24 is a graph illustrating influence of IGF-I on H + -dependent uptake of [ 3 H]Glycylsarcosine (GlySar) by MDCK cells. 
     
    
     DEFINITIONS  
       [0043]    The term “gene” is used broadly to refer to any segment of nucleic acid associated with a biological function. Thus, genes include coding sequences and/or the regulatory sequences required for their expression. For example, gene refers to a nucleic acid fragment that expresses mRNA, functional RNA, or specific protein, including regulatory sequences. Genes also include nonexpressed DNA segments that, for example, form recognition sequences for other proteins. Genes can be obtained from a variety of sources, including cloning from a source of interest or synthesizing from known or predicted sequence information, and may include sequences designed to have desired parameters.  
         [0044]    The term “native gene” refers to gene that is present in the genome of an untransformed cell.  
         [0045]    “Naturally occurring” is used to describe an object that can be found in nature as distinct from being artificially produced by man. For example, a protein or nucleotide sequence present in an organism (including a virus), which can be isolated from a source in nature and which has not been intentionally modified by man in the laboratory, is naturally occurring.  
         [0046]    A “marker gene” encodes a selectable or screenable trait.  
         [0047]    The term “chimeric gene” refers to any gene that contains 1) DNA sequences, including regulatory and coding sequences, that are not found together in nature, or 2) sequences encoding parts of proteins not naturally adjoined, or 3) parts of promoters that are not naturally adjoined. Accordingly, a chimeric gene may comprise regulatory sequences and coding sequences that are derived from different sources, or comprise regulatory sequences and coding sequences derived from the same source, but arranged in a manner different from that found in nature.  
         [0048]    A “transgene” refers to a gene that has been introduced into the genome by transformation and is stably maintained. Transgenes may include, for example, genes that are either heterologous or homologous to the genes of a particular cell to be transformed. Additionally, transgenes may comprise native genes inserted into a non-native organism, or chimeric genes. The term “endogenous gene” refers to a native gene in its natural location in the genome of an organism. A “foreign” gene refers to a gene not normally found in the host organism but that is introduced by gene transfer.  
         [0049]    The terms “protein,” “peptide” and “polypeptide” are used interchangeably herein.  
         [0050]    Expression cassettes will comprise the transcriptional initiation region of the invention linked to a nucleotide sequence of interest. Such an expression cassette is provided with a plurality of restriction sites for insertion of the gene of interest to be under the transcriptional regulation of the regulatory regions. The expression cassette may additionally contain selectable marker genes.  
         [0051]    The transcriptional cassette will include in the 5′-3′ direction of transcription, a transcriptional and translational initiation region, a DNA sequence of interest, and a transcriptional and translational termination region. The termination region may be native with the transcriptional initiation region, may be native with the DNA sequence of interest, or may be derived from another source.  
         [0052]    An oligonucleotide for use in probing or amplification reactions may be about 30 or fewer nucleotides in length (e.g., 9, 12, 15, 18, 20, 21 or 24, or any number between 9 and 30). Generally specific primers are upwards of 14 nucleotides in length. For optimum specificity and cost effectiveness, primers of 16-24 nucleotides in length may be preferred. Those skilled in the art are well versed in the design of primers for use processes such as PCR. If required, probing can be done with entire restriction fragments of the gene disclosed herein which may be 100&#39;s or even 1000&#39;s of nucleotides in length.  
         [0053]    “Coding sequence” refers to a DNA or RNA sequence that codes for a specific amino acid sequence and excludes the non-coding sequences. It may constitute an “uninterrupted coding sequence”, i.e., lacking an intron, such as in a cDNA or it may include one or more introns bounded by appropriate splice junctions. An “intron” is a sequence of RNA which is contained in the primary transcript but which is removed through cleavage and re-ligation of the RNA within the cell to create the mature mRNA that can be translated into a protein.  
         [0054]    The terms “open reading frame” and “ORF” refer to the amino acid sequence encoded between translation initiation and termination codons of a coding sequence. The terms “initiation codon” and “termination codon” refer to a unit of three adjacent nucleotides (‘codon’) in a coding sequence that specifies initiation and chain termination, respectively, of protein synthesis (mRNA translation).  
         [0055]    A “functional RNA” refers to an antisense RNA, ribozyme, or other RNA that is not translated.  
         [0056]    The term “RNA transcript” refers to the product resulting from RNA polymerase catalyzed transcription of a DNA sequence. When the RNA transcript is a perfect complementary copy of the DNA sequence, it is referred to as the primary transcript or it may be a RNA sequence derived from post-transcriptional processing of the primary transcript and is referred to as the mature RNA. “Messenger RNA” (mRNA) refers to the RNA that is without introns and that can be translated into protein by the cell. “cDNA” refers to a single- or a double-stranded DNA that is complementary to and derived from mRNA.  
         [0057]    “Regulatory sequences” and “suitable regulatory sequences” each refer to nucleotide sequences located upstream (5′ non-coding sequences), within, or downstream (3′ non-coding sequences) of a coding sequence, and which influence the transcription, RNA processing or stability, or translation of the associated coding sequence. Regulatory sequences include enhancers, promoters, translation leader sequences, introns, and polyadenylation signal sequences. They include natural and synthetic sequences as well as sequences which may be a combination of synthetic and natural sequences. As is noted above, the term “suitable regulatory sequences” is not limited to promoters.  
         [0058]    “5′ non-coding sequence” refers to a nucleotide sequence located 5′ (upstream) to the coding sequence. It is present in the fully processed mRNA upstream of the initiation codon and may affect processing of the primary transcript to mRNA, mRNA stability or translation efficiency. (Turner et al.,  Molecular Biotechnology,  3:225 (1995)).  
         [0059]    “3′ non-coding sequence” refers to nucleotide sequences located 3′ (downstream) to a coding sequence and include polyadenylation signal sequences and other sequences encoding regulatory signals capable of affecting mRNA processing or gene expression. The polyadenylation signal is usually characterized by affecting the addition of polyadenylic acid tracts to the 3′ end of the mRNA precursor.  
         [0060]    The term “translation leader sequence” refers to that DNA sequence portion of a gene between the promoter and coding sequence that is transcribed into RNA and is present in the fully processed mRNA upstream (5′) of the translation start codon. The translation leader sequence may affect processing of the primary transcript to mRNA, mRNA stability or translation efficiency.  
         [0061]    The term “mature” protein refers to a post-translationally processed polypeptide without its signal peptide. “Precursor” protein refers to the primary product of translation of an mRNA. “Signal peptide” refers to the amino terminal extension of a polypeptide, which is translated in conjunction with the polypeptide forming a precursor peptide and which is required for its entrance into the secretory pathway. The term “signal sequence” refers to a nucleotide sequence that encodes the signal peptide.  
         [0062]    The term “intracellular localization sequence” refers to a nucleotide sequence that encodes an intracellular targeting signal. An “intracellular targeting signal” is an amino acid sequence that is translated in conjunction with a protein and directs it to a particular sub-cellular compartment. “Endoplasmic reticulum (ER) stop transit signal” refers to a carboxy-terminal extension of a polypeptide, which is translated in conjunction with the polypeptide and causes a protein that enters the secretory pathway to be retained in the ER. “ER stop transit sequence” refers to a nucleotide sequence that encodes the ER targeting signal.  
         [0063]    “Promoter” refers to a nucleotide sequence, usually upstream (5′) to its coding sequence, that controls the expression of the coding sequence by providing the recognition for RNA polymerase and other factors required for proper transcription. “Promoter” includes a minimal promoter that is a short DNA sequence comprised of a TATA-box and other sequences that serve to specify the site of transcription initiation, to which regulatory elements are added for control of expression. “Promoter” also refers to a nucleotide sequence that includes a minimal promoter plus regulatory elements that is capable of controlling the expression of a coding sequence or functional RNA. This type of promoter sequence consists of proximal and more distal upstream elements, the latter elements often referred to as enhancers. Accordingly, an “enhancer” is a DNA sequence which can stimulate promoter activity and may be an innate element of the promoter or a heterologous element inserted to enhance the level or tissue specificity of a promoter. It is capable of operating in both orientations (normal or flipped), and is capable of functioning even when moved either upstream or downstream from the promoter. Both enhancers and other upstream promoter elements bind sequence-specific DNA-binding proteins that mediate their effects. Promoters may be derived in their entirety from a native gene, or be composed of different elements derived from different promoters found in nature, or even be comprised of synthetic DNA segments. A promoter may also contain DNA sequences that are involved in the binding of protein factors which control the effectiveness of transcription initiation in response to physiological or developmental conditions.  
         [0064]    The “initiation site” is the position surrounding the first nucleotide that is part of the transcribed sequence, which is also defined as position+1. With respect to this site all other sequences of the gene and its controlling regions are numbered. Downstream sequences (i.e. further protein encoding sequences in the 3′ direction) are denominated positive, while upstream sequences (mostly of the controlling regions in the 5′ direction) are denominated negative.  
         [0065]    Promoter elements, particularly a TATA element, that are inactive or that have greatly reduced promoter activity in the absence of upstream activation are referred to as “minimal or core promoters.” In the presence of a suitable transcription factor, the minimal promoter functions to permit transcription. A “minimal or core promoter” thus consists only of all basal elements needed for transcription initiation, e.g., a TATA box and/or an initiator.  
         [0066]    “Inducible promoter” refers to those regulated promoters that can be turned on in one or more cell types by an external stimulus, such as a chemical, light, hormone, stress, or a pathogen.  
         [0067]    “Operably-linked” refers to the association of nucleic acid sequences on single nucleic acid fragment so that the function of one is affected by the other. For example, a regulatory DNA sequence is said to be “operably linked to” or “associated with” a DNA sequence that codes for an RNA or a polypeptide if the two sequences are situated such that the regulatory DNA sequence affects expression of the coding DNA sequence (i.e., that the coding sequence or functional RNA is under the transcriptional control of the promoter). Coding sequences can be operably-linked to regulatory sequences in sense or antisense orientation.  
         [0068]    “Expression” refers to the transcription and/or translation of an endogenous gene or a transgene in cells. For example, in the case of antisense constructs, expression may refer to the transcription of the antisense DNA only. In addition, expression refers to the transcription and stable accumulation of sense (mRNA) or functional RNA. Expression may also refer to the production of protein.  
         [0069]    The analysis of transcription start points in practically all promoters has revealed that there is usually no single base at which transcription starts, but rather a more or less clustered set of initiation sites, each of which accounts for some start points of the mRNA. Since this distribution varies from promoter to promoter the sequences of the reporter mRNA in each of the populations would differ from each other. Since each mRNA species is more or less prone to degradation, no single degradation rate can be expected for different reporter mRNAs. It has been shown for various eukaryotic promoter sequences that the sequence surrounding the initiation site (‘initiator’) plays an important role in determining the level of RNA expression directed by that specific promoter. This includes also part of the transcribed sequences. The direct fusion of promoter to reporter sequences would therefore lead to much suboptimal levels of transcription.  
         [0070]    A commonly used procedure to analyze expression patterns and levels is through determination of the ‘steady state’ level of protein accumulation in a cell. Commonly used candidates for the reporter gene, known to those skilled in the art are 9-glucuronidase (GUS), growth hormone (GH), Chloramphenicol Acetyl Transferase (CAT) and proteins with fluorescent properties, such as Green Fluorescent Protein (GFP) from  Aequora Victoria.  In principle, however, many more proteins are suitable for this purpose, provided the protein does not interfere with essential cell functions. For quantification and determination of localization a number of tools are suited. Detection systems can readily be created or are available which are based on e.g. immunochemical, enzymatic, fluorescent detection and quantification. Protein levels can be determined in cell extracts or in intact tissue using in situ analysis of protein expression.  
         [0071]    Generally, individual transformed lines with one chimeric promoter reporter construct will vary in their levels of expression of the reporter gene. Also frequently observed is the phenomenon that such transformants do not express any detectable product (RNA or protein). The variability in expression is commonly ascribed to ‘position effects, although the molecular mechanisms underlying this inactivity are usually not clear.  
         [0072]    “Non-specific expression” refers to constitutive expression or low level, basal (‘leaky’) expression in nondesired cells or tissues from a ‘regulated promoter’.  
         [0073]    “Antisense inhibition” refers to the production of antisense RNA transcripts capable of suppressing the expression of protein from an endogenous gene or a transgene.  
         [0074]    “Co-suppression” and “transwitch” each refer to the production of sense RNA transcripts capable of suppressing the expression of identical or substantially similar transgene or endogenous genes (U.S. Pat. No. 5,231,020).  
         [0075]    “Homologous to” refers to the similarity between the nucleotide sequence of two nucleic acid molecules or between the amino acid sequences of two protein molecules. Estimates of such homology are provided by either DNA-DNA or DNA-RNA hybridization under conditions of stringency as is well understood by those skilled in the art (as described in Haines and Higgins (eds.), Nucleic Acid Hybridization, IRL Press, Oxford, U.K.), or by the comparison of sequence similarity between two nucleic acids or proteins.  
         [0076]    The term “substantially similar” refers to nucleotide and amino acid sequences that represent equivalents of the instant inventive sequences. For example, altered nucleotide sequences which simply reflect the degeneracy of the genetic code but nonetheless encode amino acid sequences that are identical to the inventive amino acid sequences are substantially similar to the inventive sequences. In addition, amino acid sequences that are substantially similar to the instant sequences are those wherein overall amino acid identity is 95% or greater to the instant sequences. Modifications to the instant invention that result in equivalent nucleotide or amino acid sequences is well within the routine skill in the art. Moreover, the skilled artisan recognizes that equivalent nucleotide sequences encompassed by this invention can also be defined by their ability to hybridize, under stringent conditions (0.1×SSC, 0.1% SDS, 65° C.), with the nucleotide sequences that are within the literal scope of the instant claims.  
         [0077]    “Transgene activation system” refers to the expression system comprised of an inactive transgene and a chimeric site-specific recombinase gene, functioning together, to effect transgene expression in a regulated manner. The specificity of the recombination will be determined by the specificity of regulated promoters as well as the use of wild-type or mutant site-specific sequences. Both elements of the system can be chromosomally integrated and inherited independently.  
         [0078]    “Target gene” refers to a gene on the replicon that expresses the desired target coding sequence, functional RNA, or protein. The target gene is not essential for replicon replication. Additionally, target genes may comprise native non-viral genes inserted into a non-native organism, or chimeric genes, and will be under the control of suitable regulatory sequences. Thus, the regulatory sequences in the target gene may come from any source, including the virus.  
         [0079]    “Transcription Stop Fragment” refers to nucleotide sequences that contain one or more regulatory signals, such as polyadenylation signal sequences, capable of terminating transcription. Examples include the 3′ non-regulatory regions of genes encoding nopaline synthase and the small subunit of ribulose bisphosphate carboxylase.  
         [0080]    “Translation Stop Fragment” refers to nucleotide sequences that contain one or more regulatory signals, such as one or more termination codons in all three frames, capable of terminating translation. Insertion of a translation stop fragment adjacent to or near the initiation codon at the 5′ end of the coding sequence will result in no translation or improper translation. Excision of the translation stop fragment by site-specific recombination will leave a site-specific sequence in the coding sequence that does not interfere with proper translation using the initiation codon.  
         [0081]    “Blocking fragment” refers to a DNA fragment that is flanked by site specific sequences that can block the transcription and/or the proper translation of a coding sequence resulting in an inactive transgene. When the blocking fragment contains polyadenylation signal sequences and other sequences encoding regulatory signals capable of terminating transcription, it can block the transcription of a coding sequence when placed in the 5′ non-translated region, i.e., between the transcription start site and the ORF. When inserted in the coding sequence a blocking fragment can block proper translation by disrupting its open reading frame. DNA rearrangement by site-specific recombination can restore transcription and/or proper translatability. For example, excision of the blocking fragment by site-specific recombination leaves behind a site-specific sequence that allows transcription and/or proper translatability. A Transcription or Translational Stop Fragment will be considered a blocking fragment.  
         [0082]    The terms “in cis” and “in trans” refer to the presence of DNA elements, such as the viral origin of replication and the replication protein(s) gene, on the same DNA molecule or on a different DNA molecule, respectively.  
         [0083]    The terms “cis-acting sequence” and “cis-acting element” refer to DNA or RNA sequences whose functions require them to be on the same molecule. An example of a cis-acting sequence on the replicon is the viral replication origin.  
         [0084]    The terms “trans-acting sequence” and “trans-acting element” refer to DNA or RNA sequences whose function does not require them to be on the same molecule.  
         [0085]    “Cis-acting viral sequences” refers to viral sequences necessary for viral replication (such as the replication origin) and in cis orientation.  
         [0086]    “Transactivating gene” refers to a gene encoding a transactivating protein. It can encode a viral replication protein(s) or a site-specific replicase. It can be a natural gene, for example, a viral replication gene, or a chimeric gene, for example, when regulatory sequences are operably-linked to the open reading frame of a site-specific recombinase or a viral replication protein. “Transactivating genes” may be chromosomally integrated or transiently expressed.  
         [0087]    “Wild-type” refers to the normal gene, virus, or organism found in nature without any known mutation.  
         [0088]    “Genome” refers to the complete genetic material of an organism. The term “nucleic acid” refers to deoxyribonucleotides or ribonucleotides and polymers thereof in either single- or double-stranded form, composed of monomers (nucleotides) containing a sugar, phosphate and a base which is either a purine or pyrimidine. Unless specifically limited, the term encompasses nucleic acids containing known analogs of natural nucleotides which have similar binding properties as the reference nucleic acid and are metabolized in a manner similar to naturally occurring nucleotides. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions) and complementary sequences as well as the sequence explicitly indicated. Specifically, degenerate codon substitutions may be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed-base and/or deoxyinosine residues (Batzer et al.,  Nucleic Acid Res.,  19, 5081 (1991); Ohtsuka et al.,  J. Biol. Chem.,  260, 2605 (1985); Rossolini et al.,  Mol. Cell. Probes,  8, 91 (1994)). A “nucleic acid fragment” is a fraction of a given nucleic acid molecule. In higher animals, deoxyribonucleic acid (DNA) is the genetic material while ribonucleic acid (RNA) is involved in the transfer of information contained within DNA into proteins. A “genome” is the entire body of genetic material contained in each cell of an organism. The term “nucleotide sequence” refers to a polymer of DNA or RNA which can be single- or double-stranded, optionally containing synthetic, non-natural or altered nucleotide bases capable of incorporation into DNA or RNA polymers. The terms “nucleic acid” or “nucleic acid sequence” may also be used interchangeably with gene, cDNA, DNA and RNA encoded by a gene.  
         [0089]    The invention encompasses isolated or substantially purified nucleic acid or protein compositions. In the context of the present invention, an “isolated” or “purified” DNA molecule or an “isolated” or “purified” polypeptide is a DNA molecule or polypeptide that, by the hand of man, exists apart from its native environment and is therefore not a product of nature. An isolated DNA molecule or polypeptide may exist in a purified form or may exist in a non-native environment such as, for example, a transgenic host cell. For example, an “isolated” or “purified” nucleic acid molecule or protein, or biologically active portion thereof, is substantially free of other cellular material, or culture medium when produced by recombinant techniques, or substantially free of chemical precursors or other chemicals when chemically synthesized. Preferably, an “isolated” nucleic acid is free of sequences (preferably protein encoding sequences) that naturally flank the nucleic acid (i.e., sequences located at the 5′ and 3′ ends of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated nucleic acid molecule can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb, or 0.1 kb of nucleotide sequences that naturally flank the nucleic acid molecule in genomic DNA of the cell from which the nucleic acid is derived. A protein that is substantially free of cellular material includes preparations of protein or polypeptide having less than about 30%, 20%, 10%, 5%, (by dry weight) of contaminating protein. When the protein of the invention, or biologically active portion thereof, is recombinantly produced, preferably culture medium represents less than about 30%, 20%, 10%, or 5% (by dry weight) of chemical precursors or non-protein-of-interest chemicals. Fragments and variants of the disclosed nucleotide sequences and proteins or partial-length proteins encoded thereby are also encompassed by the present invention. By “fragment” is intended a portion of the nucleotide sequence or a portion of the amino acid sequence, and hence a portion of the polypeptide or protein, encoded thereby. Alternatively, fragments of a nucleotide sequence that are useful as hybridization probes generally do not encode fragment proteins retaining biological activity. Thus, fragments of a nucleotide sequence may range from at least about 9 nucleotides, about 12 nucleotides, about 20 nucleotides, about 50 nucleotides, about 100 nucleotides or more.  
         [0090]    By “variants” is intended substantially similar sequences. For nucleotide sequences, variants include those sequences that, because of the degeneracy of the genetic code, encode the identical amino acid sequence of the native protein. Naturally occurring allelic variants such as these can be identified with the use of well-known molecular biology techniques, as, for example, with polymerase chain reaction (PCR) and hybridization techniques. Variant nucleotide sequences also include synthetically derived nucleotide sequences, such as those generated, for example, by using site-directed mutagenesis which encode the native protein, as well as those that encode a polypeptide having amino acid substitutions. Generally, nucleotide sequence variants of the invention will have at least 40, 50, 60, to 70%, e.g., preferably 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, to 79%, generally at least 80%, e.g., 81%-84%, at least 85%, e.g., 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, to 98% sequence identity to the native nucleotide sequence.  
         [0091]    By “variant” polypeptide is intended a polypeptide derived from the native protein by deletion (so-called truncation) or addition of one or more amino acids to the N-terminal and/or C-terminal end of the native protein; deletion or addition of one or more amino acids at one or more sites in the native protein; or substitution of one or more amino acids at one or more sites in the native protein. Such variants may results form, for example, genetic polymorphism or from human manipulation. Methods for such manipulations are generally known in the art.  
         [0092]    Thus, the polypeptides of the invention may be altered in various ways including amino acid substitutions, deletions, truncations, and insertions. Methods for such manipulations are generally known in the art. For example, amino acid sequence variants of the polypeptides can be prepared by mutations in the DNA. Methods for mutagenesis and nucleotide sequence alterations are well known in the art. See, for example, Kunkel,  Proc. Natl. Acad. Sci. USA,  82, 488 (1985); Kunkel et al.,  Methods in Enzymol.,  154, 367 (1987); U.S. Pat. No. 4,873,192; Walker and Gaastra, eds.,  Techniques in Molecular Biology,  MacMillan Publishing Company, New York (1983) and the references cited therein. Guidance as to appropriate amino acid substitutions that do not affect biological activity of the protein of interest may be found in the model of Dayhoff et al.,  Atlas of Protein Sequence and Structure,  Natl. Biomed. Res. Found., Washington, C.D. (1978), herein incorporated by reference. Conservative substitutions, such as exchanging one amino acid with another having similar properties, are preferred.  
         [0093]    Thus, the genes and nucleotide sequences of the invention include both the naturally occurring sequences as well as mutant forms. Likewise, the polypeptides of the invention encompass both naturally occurring proteins as well as variations and modified forms thereof. Such variants will continue to possess the desired activity. The deletions, insertions, and substitutions of the polypeptide sequence encompassed herein are not expected to produce radical changes in the characteristics of the polypeptide. However, when it is difficult to predict the exact effect of the substitution, deletion, or insertion in advance of doing so, one skilled in the art will appreciate that the effect will be evaluated by routine screening assays.  
         [0094]    “Expression cassette” as used herein means a DNA sequence capable of directing expression of a particular nucleotide sequence in an appropriate host cell, comprising a promoter operably linked to the nucleotide sequence of interest which is operably linked to termination signals. It also typically comprises sequences required for proper translation of the nucleotide sequence. The coding region usually codes for a protein of interest but may also code for a functional RNA of interest, for example antisense RNA or a nontranslated RNA, in the sense or antisense direction. The expression cassette comprising the nucleotide sequence of interest may be chimeric, meaning that at least one of its components is heterologous with respect to at least one of its other components. The expression cassette may also be one which is naturally occurring but has been obtained in a recombinant form useful for heterologous expression. The expression of the nucleotide sequence in the expression cassette may be under the control of a constitutive promoter or of an inducible promoter which initiates transcription only when the host cell is exposed to some particular external stimulus. In the case of a multicellular organism, the promoter can also be specific to a particular tissue or organ or stage of development.  
         [0095]    The proteins of the invention may be altered in various ways including amino acid substitutions, deletions, truncations, and insertions. Methods for such manipulations are generally known in the art. Methods for mutagenesis and nucleotide sequence alterations are well known in the art. See, for example, Kunkel,  Proc. Natl. Acad. Sci. USA,  82:488-492 (1985); Kunkel et al.,  Methods in Enzymol.  154:367-382 (1987); U.S. Pat. No. 4,873,192; Walker and Gaastra, eds. (1983)  Techniques in Molecular Biology  (MacMillan Publishing Company, New York) and the references cited therein. Guidance as to appropriate amino acid substitutions that do not affect biological activity of the protein of interest may be found in the model of Dayhoff et al. (1978)  Atlas of Protein Sequence and Structure  (Natl. Biomed. Res. Found., Washington, D.C.), herein incorporated by reference. Conservative substitutions, such as exchanging one amino acid with another having similar properties, may be preferred.  
         [0096]    Thus, the genes and nucleotide sequences of the invention include both the naturally occurring sequences as well as mutant forms. Likewise, the proteins of the invention encompass both naturally occurring proteins as well as variations and modified forms thereof. Such variants will continue to possess the desired disease resistance activity. Obviously, the mutations that will be made in the DNA encoding the variant must not place the sequence out of reading frame and preferably will not create complementary regions that could produce secondary mRNA structure. See, EP Patent Application Publication No. 75,444.  
         [0097]    The deletions, insertions, and substitutions of the protein sequence encompassed herein are not expected to produce radical changes in the characteristics of the protein. However, when it is difficult to predict the exact effect of the substitution, deletion, or insertion in advance of doing so, one skilled in the art will appreciate that the effect will be evaluated by routine screening assays. Hybridization of such sequences may be carried out under stringent conditions.  
         [0098]    “Stringent hybridization conditions” and “stringent hybridization wash conditions” in the context of nucleic acid hybridization experiments such as Southern and Northern hybridization are sequence dependent, and are different under different environmental parameters. Longer sequences hybridize specifically at higher temperatures. An extensive guide to the hybridization of nucleic acids is found in Tijssen,  Laboratory Techniques in Biochemistry and Molecular biology—Hybridization with Nucleic Acid Probes,  page 1, chapter 2 “Overview of principles of hybridization and the strategy of nucleic acid probe assays” Elsevier, New York (1993). Generally, highly stringent hybridization and wash conditions are selected to be about 5° C. lower than the thermal melting point (T m ) for the specific sequence at a defined ionic strength and pH. Typically, under “stringent conditions” a probe will hybridize to its target subsequence, but to no other sequences. For example, by “stringent conditions” or “stringent hybridization conditions” is intended conditions under which a probe will hybridize to its target sequence to a detectably greater degree than to other sequences (e.g., at least 2-fold over background). By controlling the stringency of the hybridization and/or washing conditions, target sequences that are 100% complementary to the probe can be identified (homologous probing). Alternatively, stringency conditions can be adjusted to allow some mismatching in sequences so that lower degrees of similarity are detected (heterologous probing). Generally, a probe is less than about 1000 nucleotides in length, preferably less than 500 nucleotides in length.  
         [0099]    Typically, stringent conditions will be those in which the salt concentration is less than about 1.5 M Na ion, typically about 0.01 to 1.0 M Na ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30° C. for short probes (e.g., 10 to 50 nucleotides) and at least about 60° C. for long probes (e.g., greater than 50 nucleotides). Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide.  
         [0100]    Exemplary low stringency conditions include hybridization with a buffer solution of 30 to 35% formamide, 1 M NaCl, 1% SDS (sodium dodecyl sulphate) at 37° C., and a wash in 1× to 2×SSC (20×SSC=3.0 M NaCl/0.3 M trisodium citrate) at 50 to 55° C. Exemplary moderate stringency conditions include hybridization in 40 to 45% formamide, 1.0 M NaCl, 1% SDS at 37° C., and a wash in 0.5× to 1× SSC at 55 to 60° C. Exemplary high stringency conditions include hybridization in 50% formamide, 1 M NaCl, 1% SDS at 37° C., and a wash in 0.1×SSC at 60 to 65° C.  
         [0101]    Specificity is typically the function of post-hybridization washes, the critical factors being the ionic strength and temperature of the final wash solution. For DNA-DNA hybrids, the T m  can be approximated from the equation of Meinkoth and Wahl  Anal. Biochem.  138:267-284 (1984); T m  81.5° C.+16.6 (log M)+0.41 (% GC)−0.61 (% form)−500/L; where M is the molarity of monovalent cations, % GC is the percentage of guanosine and cytosine nucleotides in the DNA, % form is the percentage of formamide in the hybridization solution, and L is the length of the hybrid in base pairs. The T m  is the temperature (under defined ionic strength and pH) at which 50% of a complementary target sequence hybridizes to a perfectly matched probe.  
         [0102]    Very stringent conditions are selected to be equal to the T m  for a particular probe. An example of stringent hybridization conditions for hybridization of complementary nucleic acids which have more than 100 complementary residues on a filter in a Southern or Northern blot is 50% formamide with 1 mg of heparin at 42° C., with the hybridization being carried out overnight. An example of highly stringent conditions is 0.15 M NaCl at 72° C. for about 15 minutes. An example of stringent wash conditions is a 0.2×SSC wash at 65° C. for 15 minutes (see, Sambrook, infra, for a description of SSC buffer). Often, a high stringency wash is preceded by a low stringency wash to remove background probe signal. An example of medium stringency for a duplex of, e.g., more than 100 nucleotides, is 1×SSC at 45° C. for 15 minutes. An example low stringency wash for a duplex of, e.g., more than 100 nucleotides, is 4-6×SSC at 40° C. for 15 minutes. For short probes (e.g., about 10 to 50 nucleotides), stringent conditions typically involve salt concentrations of less than about 1.0M Na ion, typically about 0.01 to 1.0 M Na ion concentration (or other slats) at pH 7.0 to 8.3, and the temperature is typically at least about 30° C. Stringent conditions can also be achieved with the addition of destabilizing agents such as formamide. In general, a signal to noise ratio of 2× (or higher) than that observed for an unrelated probe in the particular hybridization assay indicates detection of a specific hybridization. Nucleic acids that do not hybridize to each other under stringent conditions are still substantially identical if the proteins that they encode are substantially identical. This occurs, e.g., when a copy of a nucleic acid is created using the maximum codon degeneracy permitted by the genetic code.  
         [0103]    The following are examples of sets of hybridization/wash conditions that may be used to clone homologous nucleotide sequences that are substantially identical to reference nucleotide sequences of the present invention: a reference nucleotide sequence preferably hybridizes to the reference nucleotide sequence in 7% sodium dodecyl sulfate (SDS), 0.5 M NaPO 4 , 1 mM EDTA at 50° C. with washing in 2×SSC, 0.1% SDS at 50° C., more desirably in 7% sodium dodecyl sulfate (SDS), 0.5 M NaPO 4 , 1 mM EDTA at 50° C. with washing in 1×SSC, 0.1% SDS at 50° C., more desirably still in 7% sodium dodecyl sulfate (SDS), 0.5 M NaPO 4 , 1 mM EDTA at 50° C. with washing in 0.5×SSC, 0.1% SDS at 50° C., preferably in 7% sodium dodecyl sulfate (SDS), 0.5 M NaPO 4 , 1 mM EDTA at 50° C. with washing in 0.1×SSC, 0.1% SDS at 50° C., more preferably in 7% sodium dodecyl sulfate (SDS), 0.5 M NaPO 4 , 1 mM EDTA at 50° C. with washing in 0.1×SSC, 0.1% SDS at 65° C.  
         [0104]    T m  is reduced by about 1° C. for each 1% of mismatching; thus, T m , hybridization, and/or wash conditions can be adjusted to hybridize to sequences of the desired identity. For example, if sequences with &gt;90% identity are sought, the T m  can be decreased 10° C. Generally, stringent conditions are selected to be about 5° C. lower than the thermal melting point (T m ) for the specific sequence and its complement at a defined ionic strength and pH. However, severely stringent conditions can utilize a hybridization and/or wash at 1, 2, 3, or 4° C. lower than the thermal melting point (T m ); moderately stringent conditions can utilize a hybridization and/or wash at 6, 7, 8, 9, or 10° C. lower than the thermal melting point (T m ); low stringency conditions can utilize a hybridization and/or wash at 11, 12, 13, 14, 15, or 20° C. lower than the thermal melting point (T m ). Using these parameters, hybridization and wash compositions, and desired T, those of ordinary skill will understand that variations in the stringency of hybridization and/or wash solutions are inherently described. If the desired degree of mismatching results in a T of less than 45° C. (aqueous solution) or 32° C. (formamide solution), it is preferred to increase the SSC concentration so that a higher temperature can be used. An extensive guide to the hybridization of nucleic acids is found in Tijssen (1993) Laboratory Techniques in Biochemistry and Molecular Biology-Hybridization with Nucleic Acid Probes, Part 1, Chapter 2 (Elsevier, New York); and Ausubel et al., eds. (1995) Current Protocols in Molecular Biology, Chapter 2 (Greene Publishing and Wiley-Interscience, New York). See Sambrook et al. (1989) Molecular Cloning: A Laboratory Manual (2d ed., Cold Spring Harbor Laboratory Press, Plainview, N.Y.).  
         [0105]    Generally, stringent conditions are selected to be about 5° C. lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH. However, stringent conditions encompass temperatures in the range of about 1° C. to about 20° C., depending upon the desired degree of stringency as otherwise qualified herein. Nucleic acids that do not hybridize to each other under stringent conditions are still substantially identical if the polypeptides they encode are substantially identical. This may occur, e.g., when a copy of a nucleic acid is created using the maximum codon degeneracy permitted by the genetic code. One indication that two nucleic acid sequences are substantially identical is when the polypeptide encoded by the first nucleic acid is immunologically cross reactive with the polypeptide encoded by the second nucleic acid.  
         [0106]    “Vector” is defined to include, inter alia, any plasmid, cosmid, or phage in double or single stranded linear or circular form which may or may not be self transmissible or mobilizable, and which can transform prokaryotic or eukaryotic host either by integration into the cellular genome or exist extrachromosomally (e.g. autonomous replicating plasmid with an origin of replication).  
         [0107]    Specifically included are shuttle vectors by which is meant a DNA vehicle capable, naturally or by design, of replication in two different host organisms, which may be selected from actinomycetes and related species, bacteria and eucaryotic (e.g. higher cell, mammalian, yeast or fungal cells).  
         [0108]    Preferably the nucleic acid in the vector is under the control of, and operably linked to, an appropriate promoter or other regulatory elements for transcription in a host cell such as a microbial, e.g. bacterial, or animal cell. The vector may be a bi-functional expression vector which functions in multiple hosts. In the case of genomic DNA, this may contain its own promoter or other regulatory elements and in the case of cDNA this may be under the control of an appropriate promoter or other regulatory elements for expression in the host cell.  
         [0109]    “Cloning vectors” typically contain one or a small number of restriction endonuclease recognition sites at which foreign DNA sequences can be inserted in a determinable fashion without loss of essential biological function of the vector, as well as a marker gene that is suitable for use in the identification and selection of cells transformed with the cloning vector. Marker genes typically include genes that provide tetracycline resistance, hygromycin resistance or ampicillin resistance.  
         [0110]    “Operably linked” means joined as part of the same nucleic acid molecule, suitably positioned and oriented for transcription to be initiated from the promoter. DNA operably linked to a promoter is “under transcriptional initiation regulation” of the promoter.  
         [0111]    “Chimeric” is used to indicate that a DNA sequence, such as a vector or a gene, is comprised of more than one DNA sequences of distinct origin with are fused together by recombinant DNA techniques resulting in a DNA sequence, which does not occur naturally.  
         [0112]    The terms “heterologous DNA sequence,” “exogenous DNA segment” or “heterologous nucleic acid,” as used herein, each refer to a sequence that originates from a source foreign to the particular host cell or, if from the same source, is modified from its original form. Thus, a heterologous gene in a host cell includes a gene that is endogenous to the particular host cell but has been modified through, for example, the use of DNA shuffling. The terms also include non-naturally occurring multiple copies of a naturally occurring DNA sequence. Thus, the terms refer to a DNA segment that is foreign or heterologous to the cell, or homologous to the cell but in a position within the host cell nucleic acid in which the element is not ordinarily found. Exogenous DNA segments are expressed to yield exogenous polypeptides.  
         [0113]    A “homologous” DNA sequence is a DNA sequence that is naturally associated with a host cell into which it is introduced.  
         [0114]    The following terms are used to describe the sequence relationships between two or more nucleic acids or polynucleotides: (a) “reference sequence”, (b) “comparison window”, (c) “sequence identity”, (d) “percentage of sequence identity”, and (e) “substantial identity”.  
         [0115]    As used herein, “reference sequence” is a defined sequence used as a basis for sequence comparison. A reference sequence may be a subset or the entirety of a specified sequence; for example, as a segment of a full length cDNA or gene sequence, or the complete cDNA or gene sequence.  
         [0116]    As used herein, “comparison window” makes reference to a contiguous and specified segment of a polynucleotide sequence, wherein the polynucleotide sequence in the comparison window may comprise additions or deletions (i.e., gaps) compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two sequences. Generally, the comparison window is at least 20 contiguous nucleotides in length, and optionally can be 30, 40, 50, 100, or longer. Those of skill in the art understand that to avoid a high similarity to a reference sequence due to inclusion of gaps in the polynucleotide sequence a gap penalty is typically introduced and is subtracted from the number of matches.  
         [0117]    Methods of alignment of sequences for comparison are well known in the art. Thus, the determination of percent identity between any two sequences can be accomplished using a mathematical algorithm. Preferred, non-limiting examples of such mathematical algorithms are the algorithm of Myers and Miller,  CABIOS  4:11-17 (1988); the local homology algorithm of Smith et al.  Adv. Appl. Math.  2:482 (1981); the homology alignment algorithm of Needleman and Wunsch  J. Mol. Biol.  48:443-453 (1970); the search-for-similarity-method of Pearson and Lipman  Proc. Natl. Acad. Sci.  85:2444-2448 (1988); the algorithm of Karlin and Altschul,  Proc. Nath. Acad Sci. USA  872264 (1990), modified as in Karlin and Altschul,  Proc. Nath. Acad. Sci. USA  90:5873-5877 (1993).  
         [0118]    Computer implementations of these mathematical algorithms can be utilized for comparison of sequences to determine sequence identity. Such implementations include, but are not limited to: CLUSTAL in the PC/Gene program (available from Intelligenetics, Mountain View, Calif.); the ALIGN program (Version 2.0) and GAP, BESTFIT, BLAST, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Version 8 (available from Genetics Computer Group (GCG), 575 Science Drive, Madison, Wis., USA). Alignments using these programs can be performed using the default parameters. The CLUSTAL program is well described by Higgins et al.  Gene  73:237 244 (1988); Higgins et al.  CABIOS  5:151-153 (1989); Corpet et al.  Nucleic Acids Res.  16:10881-90 (1988); Huang et al.  CABIOS  8:155-65 (1992); and Pearson et al.  Meth. Mol. Biol.  24:307-331 (1994). The ALIGN program is based on the algorithm of Myers and Miller, supra. The BLAST programs of Altschul et al.,  J. Mol. Biol.  215:403 (1990), are based on the algorithm of Karlin and Altschul supra. To obtain gapped alignments for comparison purposes, Gapped BLAST (in BLAST 2.0) can be utilized as described in Altschul et al.  Nucleic Acids Res.  25:3389 (1997). Alternatively, PSI-BLAST (in BLAST 2.0) can be used to perform an iterated search that detects distant relationships between molecules. See Altschul et al., supra. When utilizing BLAST, Gapped BLAST, PSI-BLAST, the default parameters of the respective programs (e.g. BLASTN for nucleotide sequences, BLASTX for proteins) can be used. The BLASTN program (for nucleotide sequences) uses as defaults a wordlength (W) of 11, an expectation (E) of 10, a cutoff of 100, M=5, N=−4, and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a wordlength (W) of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff &amp; Henikoff,  Proc. Natl. Acad. Sci. USA,  89, 10915 (1989)). See http://www.ncbi.nlm.nih.gov. Alignment may also be performed manually by inspection.  
         [0119]    For purposes of the present invention, comparison of nucleotide sequences for determination of percent sequence identity disclosed herein is preferably made using the BlastN program (version 1.4.7 or later) with its default parameters or any equivalent program. By “equivalent program” is intended any sequence comparison program that, for any two sequences in question, generates an alignment having identical nucleotide or amino acid residue matches and an identical percent sequence identity when compared to the corresponding alignment generated by the preferred program.  
         [0120]    As used herein, “sequence identity” or “identity” in the context of two nucleic acid or polypeptide sequences makes reference to the residues in the two sequences that are the same when aligned for maximum correspondence over a specified comparison window. When percentage of sequence identity is used in reference to proteins it is recognized that residue positions which are not identical often differ by conservative amino acid substitutions, where amino acid residues are substituted for other amino acid residues with similar chemical properties (e.g., charge or hydrophobicity) and therefore do not change the functional properties of the molecule. When sequences differ in conservative substitutions, the percent sequence identity may be adjusted upwards to correct for the conservative nature of the substitution. Sequences that differ by such conservative substitutions are said to have “sequence similarity” or “similarity.” Means for making this adjustment are well known to those of skill in the art. Typically this involves scoring a conservative substitution as a partial rather than a full mismatch, thereby increasing the percentage sequence identity. Thus, for example, where an identical amino acid is given a score of 1 and a non-conservative substitution is given a score of zero, a conservative substitution is given a score between zero and 1. The scoring of conservative substitutions is calculated, e.g., as implemented in the program PC/GENE (Intelligenetics, Mountain View, Calif.).  
         [0121]    As used herein, “percentage of sequence identity” means the value determined by comparing two optimally aligned sequences over a comparison window, wherein the portion of the polynucleotide sequence in the comparison window may comprise additions or deletions (i.e., gaps) as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two sequences. The percentage is calculated by determining the number of positions at which the identical nucleic acid base or amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison, and multiplying the result by 100 to yield the percentage of sequence identity.  
         [0122]    The term “substantial identity” of polynucleotide sequences means that a polynucleotide comprises a sequence that has at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, or 79%, preferably at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, or 89%, more preferably at least 90%, 91%, 92%, 93%, or 94%, and most preferably at least 95%, 96%, 97%, 98%, or 99% sequence identity, compared to a reference sequence using one of the alignment programs described using standard parameters. One of skill in the art will recognize that these values can be appropriately adjusted to determine corresponding identity of proteins encoded by two nucleotide sequences by taking into account codon degeneracy, amino acid similarity, reading frame positioning, and the like. Substantial identity of amino acid sequences for these purposes normally means sequence identity of at least 70%, more preferably at least 80%, 90%, and most preferably at least 95%.  
         [0123]    Another indication that nucleotide sequences are substantially identical is if two molecules hybridize to each other under stringent conditions. Generally, stringent conditions are selected to be about 5° C. lower than the thermal melting point (T m ) for the specific sequence at a defined ionic strength and pH. However, stringent conditions encompass temperatures in the range of about 1° C. to about 20° C., depending upon the desired degree of stringency as otherwise qualified herein. Nucleic acids that do not hybridize to each other under stringent conditions are still substantially identical if the polypeptides they encode are substantially identical. This may occur, e.g., when a copy of a nucleic acid is created using the maximum codon degeneracy permitted by the genetic code. One indication that two nucleic acid sequences are substantially identical is when the polypeptide encoded by the first nucleic acid is immunologically cross reactive with the polypeptide encoded by the second nucleic acid.  
         [0124]    The term “substantial identity” in the context of a peptide indicates that a peptide comprises a sequence with at least 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, or 79%, preferably 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, or 89%, more preferably at least 90%, 91%, 92%, 93%, or 94%, or even more preferably, 95%, 96%, 97%, 98% or 99%, sequence identity to the reference sequence over a specified comparison window. Preferably, optimal alignment is conducted using the homology alignment algorithm of Needleman and Wunsch  J. Mol. Biol.  48:443-453 (1970). An indication that two peptide sequences are substantially identical is that one peptide is immunologically reactive with antibodies raised against the second peptide. Thus, a peptide is substantially identical to a second peptide, for example, where the two peptides differ only by a conservative substitution.  
       DETAILED DESCRIPTION OF THE INVENTION  
       [0125]    This invention relates to peptide amino acid absorption in the dog, and more particularly, to separate, whole or partial-length, complementary DNA encoding putative canine low-affinity, high-capacity H + /peptide transport proteins (cPepT1), mRNA transcripts corresponding to cPepT1, characterization of cPepT1 by glycylsarcosine (GlySar) uptake, identification of dipeptides, tripeptides, and tetrapeptides well recognized by cPepT1, and the effect of supplemental peptide substrate on the transport capacity of cPepT1.  
         [0126]    The invention also provides a pet food composition comprising at least one dipeptide, tripeptide, or tetrapeptide that provides enhanced uptake of amino acids by PepT1. A typical canine diet for use in the present invention may also, for example, contain about 20 to about 30% crude protein, about 10 to about 20% fat, and about 10% total dietary fiber. However, no specific ratios or percentages of these or other nutrients are required.  
         [0127]    The inventors have discovered a method for identifying peptides (e.g. dipeptides, tripeptides, or tetrapeptides) that increase transport of amino acids by PepT1 using MDCK cells, particularly when incubated with lactalbumin hydrolysate and assayed at optimum time post-seeding, as indicated in Example 2.  
         [0128]    In order that the invention may be more readily understood, reference is made to the following examples which are intended to illustrate the invention, but not limit the scope thereof.  
       EXAMPLE 1  
     Generation of Partial-length Canine PepT1 cDNA  
       [0129]    Partial Cloning of Canine PepT1 (cPepT1) from Small Intestinal Epithelium  
         [0130]    Initial attempts (over 150) to partially clone the putative canine PepT1 cDNA by reverse transcriptase-polymerase chain reaction (RT-PCR) methodology failed. The source of mRNA was canine liver tissue that had been frozen for about 6 months (supplied by Dr. Randal Buddington, Mississippi State University) and oligomer primers were based on the rabbit PepT1 sequence. Subsequently, frozen canine “mid” small intestine (jejunal) tissue segments became available (supplied by Dr. Buddington) and a partial length cDNA of about 780 base pairs (bp) was cloned by RT-PCR. Total RNA was isolated from jejunal epithelium scraped from intestinal sections using a standard acidic phenol-chloroform protocol. One μg of mRNA was isolated from total RNA using POLY A TRACT SYSTEM® (Promega, Madison, Wis.) and reversed transcribed using murine leukemia virus reverse transcriptase (Perkin Elmer, Foster City, Calif.) and oligo(dT) primers (Gibco BRL, Grand Island, N.Y.). Successful PCR reactions were 50 μL and contained 1 μM MgCl 2  and Taq polymerase (Perkin Elmer). Twenty-five thermal cycles of 94° C. for 1 min, 40° C. for 45 sec, and 72° C. for 1 min were used. The cycles were preceded by a 55 sec denaturization of the RT product at 95° C., followed by a 10 min extension of RT-PCR products at 72° C. More than 150 RT-PCR reactions testing ten different primer sets were required to achieve this protocol. The resulting cDNA using Primer Set 4 (FIG. 1) was TA-cloned into the pCR®II vector (Invitrogen, Carlsbad, Calif.), plasmid-containing colonies selected by blue/white screening, and amplified following instructions of the manufacturer. Restriction analyses of recovered pCR®II/cDNA plasmids revealed that four of fifty-six clones contained cDNA consistent with rabbit PepT1 cDNA (FIG. 2).  
         [0131]    Northern Blot Analysis of cPepT1 Expression in Dog Tissue and MDCK Cells  
         [0132]    The potential expression of cPepT1 mRNA by canine kidney, small intestinal epithelium, and immortalized kidney distal tubule epithelial cells (Madin-Darby Canine Kidney, MDCK) was evaluated by Northern analyses using cDNA derived from canine jejunal epithelium (FIG. 3). RNA were subjected to 1% gel electrophoresis in the presence of 0.02 M formaldehyde, transferred by downward capillary action to 0.45-μm nylon membranes (Hybond-N, Amersham, Arlington Heights, Ill.), and covalently cross-linked by ultra-violet light. cDNA were randomly labeled with [ 32 P]-CTP using a kit (Gibco BRL), purified through Sephadex-50 columns (Amersham Pharmacia, Piscataway, N.J.), and hybridized with blots at 56° C. for 18 h. The blots were then washed 2 times at 56° C. for 15 min and once at 57° C. for 10 min. Autoradiographs were exposed to blots at 80° C. for 24 h and the size of the transcript determined by regression of hybridized bands against the migration distance of 18S (1.9 kb) and 28S (4.9 kb) RNA.  
         [0133]    Each canine tissue-derived cDNA (TA-clone 26, FIG. 3A; TA-clone 6, FIG. 3B) hybridized to three mRNA species in dog kidney, dog small intestinal epithelium, and MDCK cells. To confirm identification of PepT1 mRNA by these canine cDNAs, RNA isolated from dog kidney and liver tissues were probed for expression of PepT1 mRNA using a full-length rabbit PepT1 cDNA (FIG. 4; rabbit PepT1 cDNA supplied by Drs. F. Leibach and V. Ganapathy, Medical College of Georgia). The results also demonstrated the expression of the same three PepT1 mRNA species by dog tissues, indicating that the full-length rabbit PepT1 cDNA and the cDNA derived from canine tissue in the present study identified the same transcripts. The mean/SD of transcript sizes calculated from these three blots were 4.2/0.22, 2.75/0.26, and 1.46/0.42 kb, respectively. Collectively, these data indicate that liver, intestinal epithelial, and MDCK cells express the same size and number of PepT1 transcripts. In comparison, various tissues of chicken, sheep, cow, pig, rabbit, rat, human, and Caco2 cells are reported to express a single transcript, with the principle difference in size being between chicken (1.9) and mammalian species (2.8, 2.8, 2.9, 2.9, 3.0, 3.1, 2.9, respectively  
         [0134]    Partial Cloning and Sequence Identification of Canine PepT1 (cPepT1) cDNA from MDCK Cells  
         [0135]    To confirm the positive Northern analysis, identification of PepT1 mRNA expression using cDNA generated from dog small intestinal epithelium, RT-PCR methodologies were used to generate a PepT1 cDNA from MDCK cells. The target cDNA region was a subset of the cDNA generated by RT-PCR from canine small intestine (bp 83 to 887 of rabbit PepT1). Accordingly, PCR primers that corresponded to bp 259 to 619 of rabbit PepT1 (GenBank acc. no. U06467) were used to generate a partial-length “canine PepT1” (cPepT1) cDNA from mRNA isolated from MDCK cells. RNA was collected from cells that were plated at 30,000 cm 2  on rat tail collagen-coated dishes and cultured for 3 days in 10% fetal calf serum/DMEM. Reverse transcription of 5 μg of total RNA by SUPERSCRIPT® II reverse transcriptase (Gibco-BRL) was performed using random and oligo(dT) primers, per instructions of the manufacturer (Gibco-BRL). All PCR reactions contained 2 mM MgCl 2  and thermal cycling using Taq polymerase included 30 cycles at 94° C. for 2 min, 55° C. for 1 min, and 72° C. for 2 min. The cycles were preceded by a 10 min denaturization of the RT product at 94° C., followed by a 10 min extension of RT-PCR products at 72° C. More than one hundred RT-PCR reactions were required to achieve this protocol.  
         [0136]    The resulting cDNA of about 380 bp was TA-cloned, into the site of pCR®II vector (as described above), amplified, bacterial colonies evaluated by blue/white screening, and pCR®II/cDNA plasmids evaluated for cDNA by Eco RI/Pst I restriction analysis (as described above). Restriction analyses of recovered plasmids revealed that six of thirty-six clones contained cDNA consistent with rabbit PepT1 cDNA . Two of the confirmed plasmids were amplified in bacteria, recovered, and sent for sequencing by the University of Florida DNA Sequencing Core Facility (Gainesville). Sequence comparisons of this 380 bp cDNA (FIG. 5) to PepT1 sequences of other species using BLAST 2.0.14. software (blast@ncbi.nlm.nih.gov) revealed that the canine sequence shares sequence homology of 79% to rabbit (bp 259 to 640; GenBank acc. no. 473375), 83% to rat (bp 213 to 593; GenBank acc. no. D50664.1), 83% to mouse (bp 213 to 589; GenBank acc. no. AF205540), and 87% to human (bp 285 to 665; GenBank ace. no. 473375 and U13173) PepT1 sequences.  
         [0137]    Demonstration of PepT1-like Transport Activity in MDCK Cells  
         [0138]    As seen in FIGS. 3 and 5, MDCK cells express a canine homolog of mammalian PepT1 mRNA. Potential expression of PepT1 transport activity (H + -dependent, dipeptide inhibitable, low-affinity dipeptide transport) by confluent MDCK cells was evaluated using whole-cell transport techniques and glycylsarcosine (GlySar) as a model dipeptide substrate. Cells were seeded at 60,000 cells/cm 2  into 24-well trays that had been coated with rat tail collagen or poly-L-lysine and cultured (95% O 2 :5% CO 2  at 37° C.) for 3 d in media consisting of Dulbecco&#39;s Modified Eagle Medium/10% fetal calf serum/1% antimicrobial antibacterial medium. Absorption (pmols/mg protein) of [ 3 H]-glycyl-L-sarcosine (GlySar; 6 mCi/mL, Moravek Biochemicals, Brea, Calif.) was determined using the 24-well cluster tray method and representative scintillation counting. Before transport, cells were incubated at 37° C. for 30 min in 25 mM Hepes/Tris (pH 7.5), 140 mM NaCl, 5.4 mM KCl, 1.8 mM CaCl 2 , 0.8 mM MgSO 4 , and 5 mM glucose (uptake buffer) to normalize intracellular amino acid and peptide pools. Transport was initiated by the addition of 0.25 mL of uptake buffer that contained 2.88 μm GlySar. After 30 min of uptake at 37° C., transport was terminated by rapid washing of cells with 4×2 mL 4° C. uptake buffer. Cellular protein was precipitated with 10% trichloroacetic acid and the supernatant recovered and counted to determine radioactivity ( 3 H) content. Cellular protein was then solubilized in 0.2 N NaOH and 0.2% SDS and quantified by the Lowry procedure, using bovine serum albumin as a standard. The amount of H + -dependent GlySar absorbed was calculated as the difference between uptake in pH 6.0 and pH 7.5 uptake buffers. The amount of competitor substrate-inhibitable GlySar uptake was calculated as the quotient of GlySar uptake in the absence and presence of 10 mM competitor substrate (dipeptide or amino acid) multiplied by 100%.  
         [0139]    GlySar uptake in the presence of an intracellularly H +  gradient (extracellular pH of 6.0) was 2.3-fold higher in cells plated on collagen, and 1.7-fold higher when grown on poly-L-lysine, than uptake in pH 7.5 medium (Table 1). H + -dependent uptake of GlySar by MDCK cells was inhibited by 88 or 92% by the presence of 10 mM LeuTrp or TrpLeu when grown on collagen, and 87 or 92% when grown on poly-L-lysine, respectively (Table 1).  
                                                                                             TABLE 1                           Influence of extracellular pH and competitor substrates on uptake of       [ 3 H]-glycylsarcosine by MDCK cells cultured on collagen- or       poly-L-lysine-coated trays.       Cells were cultured as described in text and uptake compared in       pH 7.5 or 6.0 media that contained 2.88 [ 3 H]-glycylsarcosine       for 30 min.                        Glysylsarcosine   %                   uptake pmol   inhibition           Extracellular   Competitor   30 min −1  mg −1     of pH 6.0       n   pH   substrate (mM)   protein   uptake                    Collagen-coated            5   7.5   none   19.9 ± 2.80   na 1         5   6.0   none   65.3 ± 7.95   100       5   6.0   LeuTrp (10)   7.68 ± 1.37   11.7       5   6.0   TrpLeu (10)   5.21 ± 0.39   8.0       4   6.0   Leucine (10)   63.0 ± 4.00   96.3            Poly-L-lysine-coated            4   7.5   none   15.52 ± 1.06    na       5   6.0   none   42.31 ± 4.03    100       5   6.0   LeuTrp (10)   5.50 ± 0.58   13.0       5   6.0   TrpLeu (10)   3.44 ± 0.27   8.1       4   6.0   Leucine (10)   41.93 ± 2.70    100                          
 
         [0140]    To preliminarily characterize the kinetic parameters of peptide transport by MDCK cells, the uptake of GlySar in media that contained pH 6.0 and 0.00064, 0.0025, 0.010, 0.04, 0.160, 0.640, 2.56, or 10.2 mM of GlySar was measured FIG. 6). Total GlySar uptake was by a relatively low-affinity mechanism (apparent K m  of about 4.0 mM) and high uptake velocity. Collectively, these characteristics of GlySar uptake are consistent with functional activity of PepT1 expressed by other species, as opposed to high-affinity, H + -dependent uptake by PepT2 (μm K m ). Accordingly, it is concluded that MDCK cells possess PepT1-like activity, consistent with detection of PepT1 mRNA by RT-PCR (FIGS. 1, 2,  5 ) and Northern blot analyses (FIGS. 3, 4).  
         [0141]    Summary of Example 1  
         [0142]    Separate partial-length canine PepT1 cDNAs (cPepT1) were generated by RT-PCR analyses from dog small intestinal epithelium (n=2; FIGS. 1, 2) and immortalized canine kidney cells (MDCK cells, n=1). The MDCK cDNA was sequenced (FIG. 5) and found to share 79 to 87% sequence identity with PepT1 mRNA expressed by other mammalian species. Northern blot analyses using the intestinal epithelium-derived RT-PCR cDNA confirmed expression of canine PepT1 (cPepT1) by dog tissues (liver, n=3; kidney, n=3; small intestine n=1) and MDCK cells (n=2). The identification of mRNA transcripts corresponding to PepT1 using partial-length canine-derived PepT1 cDNA (FIG. 3) was confirmed by hybridization to full-length rabbit cDNA (FIG. 4). Characterization of GlySar uptake by MDCK cells demonstrated that MDCK cells express PepT1-like activity (Table 1, FIG. 5), confirming detection of PepT1 mRNA expression by MDCK cells and use of MDCK cells as a model to characterize the function of canine PepT1.  
       EXAMPLE 2  
     Experimental Model of MDCK Cells for Evaluating the Effects of Various Peptide and Drug Substrates, and Hormones and/or Growth Factors, on the Expression of PepT1 Activity  
       [0143]    Example 1 above showed that (1) a canine homolog of PepT1 (cPepT1) mRNA cloned from epithelia of the mid small intestine (jejunum) shares high sequence identity with PepT1 expressed by several other species, (2) canine liver, kidney, and jejunal epithelium express a similar pattern of cPepT1 mRNA, and (3) MDCK cells are capable of H + -dependent peptide uptake. Accordingly, MDCK cells are an appropriate model to evaluate the biochemical characteristics of cPepT1. The specific goals of this research were to (1) characterize the functional activity of low-affinity H + -dependent GlySar uptake (PepT1 activity) by MDCK cells and (2) identify di- and tripeptides that are well recognized by cPepT1 (cPepT1), especially those that contain tryptophan and leucine.  
         [0144]    Previous research (Brandsch et al., 1994, Biochem J. 299:253-260) briefly reported that H + -dependent peptide uptake by MDCK cells was greater when cells were grown in a medium that contained lactalbumin hydrolysate (LHM) versus one that contained free amino acids (DMEM). Therefore, in an attempt to establish the most sensitive model possible for evaluating peptide transport systems in MDCK cells, the potential influences of LHM (peptide-containing) versus DMEM (peptide-lacking) media, and subconfluent versus confluent initial cell plating densities were compared. MDCK cells were seeded at either 60,000 cells/well (subconfluent) or 120,000 cells/well (confluent) in DMEM and, after 1 d, cultured in DMEM or LHM media for 1, 2, 3, or 5 d. The amount of protein (index of cell growth) and GlySar uptake (index of peptide uptake capacity) expressed by each well of cells was then determined. As seen in FIG. 7, the amount of cellular protein increased (P&lt;0.05) for both seeding densities and media with time of culture. A time×media interaction was observed, which reflects the greater protein content of cells grown in DMEM at day 6, as compared to those grown in LHM. At days 2, 3, or 4, however, no difference in protein content was observed.  
         [0145]    The uptake of [ 3 H]-GlySar (2.88 μM, 5 μCi/mL) by the MDCK cells described in FIG. 7 was measured in the presence (pH 6.0 uptake buffer) and absence (pH 7.4 uptake buffer) of an extracellular-to-intercellular H +  (proton) gradient. A representative graph (FIG. 8) compares the uptake of GlySar by cells seeded at 60,000/well and cultured in the LHM or DMEM. For both culture media, GlySar uptake in the presence of pH 6.0 was greater (P&lt;0.01) than that in pH 7.4 buffer and displayed a quadratic (P&lt;0.01) response to length of culture, reflecting a buffer×day of culture interaction (P&lt;0.01). DMEM-cultured cells seeded at 120,000/well displayed almost identical uptake characteristics as just described for cells seeded at 60,000/well. In contrast, GlySar uptake in the presence of pH 6.0 buffer at day 3 by LHM-cultured cells was only 28% larger (quantitatively) than that observed by DMEM-cultured cells seeded at 60,000/well.  
         [0146]    To further refine the analysis of media influence on the peptide transport capacity of MDCK cells plated at 60,000 or 120,000 cells per well, the H + -dependent GlySar uptake was calculated as the arithmetic difference between uptake in pH 6.0 and pH 7.4 buffers (FIG. 9). Despite the comparable protein contents of cells observed at day 3 (FIG. 7), cells seeded at 60,000 and grown in LHM media demonstrated about 60% greater capacity for GlySar uptake as did cells grown in DMEM (FIG. 9; day×media interaction, P&lt;0.01). For all cells, the capacity for GlySar uptake per mg of cellular protein was decreased at day 6. This difference was the result of a lesser uptake at pH 6.0 by the LHM-cultured cells, and not the result of a larger pH 7.4 uptake.  
         [0147]    The results of this experiment indicate that culturing cells in media that contains peptides does not increase growth rate but does increase the capacity for peptide uptake if cells are seeded at 60,000/well and cultured for 2 days in LHM. As such, these data are consistent with the induction of PepT1 expression by culture peptide-containing medium and describe an optimal set of culture conditions for characterizing H + -dependent peptide transport activity of the canine PepT1 transporter. These data also confirm, and more thoroughly describe, the stimulating effect of LHM versus DMEM media on peptide transport proteins that was initially reported by Brandsch et al. (1994).  
         [0148]    Using the maximal uptake-stimulating culture parameters determined in Experiment 3, the effect of an extracellular-to-intracellular pH gradient on GlySar uptake was further evaluated to determine a pH level at which maximal GlySar uptake could be achieved, but which would replicate physiologic conditions (FIG. 10). As expected, the presence of a pH gradient stimulated (P&lt;0.001) H + -dependent GlySar uptake, in a quadratic (P&lt;0.01) fashion. Uptake at pH 5.5 or 6.0 was about 2.7 times greater than that achieved at pH 7.5. These results are consistent with the data in FIGS. 8 and 9 and known H + -dependence of mammalian peptide transport proteins. Accordingly, the use pH 6.0 buffers for the characterization of H + -dependent GlySar uptake was incorporated into the standard experimental conditions.  
         [0149]    To determine the appropriate time period to measure initial (linear) rates of GlySar uptake, a by-minute time-course experiment was performed. As seen in FIG. 11, H + -dependent GlySar (100 μM) uptake increased linearly for 1 h and then slowed (quadratic response, P&lt;0.01). GlySar uptake in pH 6.0 buffer at 3.75, 7.5, 15, 30, 60 and 120 min was about 2, 2.1, 2.25, 2.65, 2.79, and 2.62 times more (P&lt;0.001), respectively, than uptake from pH 7.4 buffer. Because uptake was proportional to time of uptake through 1 h, future experiments were conducted using a 30-min time period.  
         [0150]    To confirm that H + -dependent GlySar uptake was saturable, and therefore mediated, the uptake of GlySar from pH 6.0 and 7.4 uptake buffers containing 0.025, 0.1, 0.4, 1.6, 6.4, or 25.6 mM GlySar was evaluated (FIG. 12). Uptake of GlySar was greatest (P&lt;0.001) from the pH 6.0 buffers, at all concentrations. H + -dependent GlySar uptake was saturable, consistent with an apparent K m  for GlySar of about 1.1 mM. These values are consistent with our preliminary trials that estimated a K m  of 1.1 mM for GlySar uptake by MDCK cells using only pH 6.0 uptake buffer and indicate that H + -dependent GlySar uptake is predominately, if not completely, a result of low affinity (mM) H + /peptide cotransporter activity (PepT1). As a comparative value, the reported K m  of for GlySar uptake by the PepT1-expressing Caco-2 cells also is 1.1 mM. It is of interest also to note that GlySar uptake in the absence of a pH gradient (pH 7.4 buffers) also displayed linear (P&lt;0.01) and quadratic (P&lt;0.001) components, (1) reflects that the pH “7.4” buffer was in fact slightly acidic, (2) represents the activity of the putative basalateral peptide transporter running in “reverse”, or (3) indicates the presence of a non-characterized peptide transport system. As a result of this experiment, subsequent H + -dependent peptide transport trials were conducted using 100 μM GlySar, a value well below the K m  but one that will result in increased transport activity, and thus, sensitivity.  
         [0151]    Characteristic hallmarks of low affinity H + /peptide cotransport activity, classically defined using membrane vesicles of several species, and more recently by functional expression studies using human, rat, and rabbit PepT1 cDNA, is the recognition of some, but not all, β-lactam antibiotics. In addition, PepT1 recognition of cefadroxil is low (the K 1  of cefadroxil inhibition of GlySar uptake by PepT1 is 3 mM), whereas recognition of cefadroxil by PepT2 is high (the K i  of cefadroxil inhibition of PepT2 transport of GlySar is 30 μM). To determine whether MDCK cPepT1 activity shared these functional features, the uptake of 100 μM GlySar in the absence and presence of pH 7.5 and pH 6.0 buffer, and, in pH 6.0 buffers, the presence of 1 mM additional GlySar (self-inhibitor control), 3 mM Penicillin-G, 30 μM cefadroxil, or 3 mM cefadroxil was compared (FIG. 13). H + -dependent GlySar uptake was not inhibited by penicillin-G or 30 μM cefadroxil, but was inhibited about 76% by 3 mM cefadroxil. As expected, the presence of 1 mM GlySar self-inhibited 100 μM GlySar uptake by 64%. These results indicate that H+-dependent uptake of GlySar by MDCK cells is by PepT1 activity.  
         [0152]    Other hallmarks of PepT1 function are the decreased ability of Gly-containing peptides to inhibit GlySar, in proportion to their length, and sensitivity to inhibition by carnosine (β-Ala-His). To determine if cPepT1 activity behaves as reported for other PepT1 activities, the relative abilities of 1 mM Gly ([ 3 H]-Gly free amino acid control), GlyGly, [Gly] 4 , or [Gly] 5  to inhibit H + -dependent 100 μM GlySar was determined (FIG. 14). Gly (5.0%) and [Gly] 5  (7.3%) did not influence uptake, whereas GlyGly inhibited and [Gly] 4  tended to inhibit uptake by 63 and 23%, respectively. This pattern of Gly-containing peptides to inhibit GlySar uptake in an inverse proportion to the number of glycyl residues in the canine MDCK cell model is consistent with PepT1 activities reported for other species. Similarly, GlySar uptake was inhibited 50% by 1 mM carnosine (data not shown but listed in Table 2 below).  
         [0153]    Together with the molecular identification of PepT1 mRNA expression in MDCK cells using full-length rabbit cDNA and our canine RT-PCR product (See Example 1 data), the above biochemical characterization data indicate that H + -dependent GlySar uptake activity in MDCK cells is consistent with the low-affinity, high-capacity of the PepT1 transport protein. Collectively, the above experiments resulted in the generation of an experimental regimen for the culture and determination of H + -dependent peptide transport activity in MDCK cells, with which to evaluate the relative substrate preferences of canine PepT1 (cPepT1).  
         [0154]    Accordingly, the following general regimen was used to perform a series of experiments that evaluated the relative abilities of candidate di- (primarily) and tri-peptides to inhibit GlySar uptake by endogenously expressed cPepT1 in MDCK cells:  
         [0155]    1. Sixty thousand cells/well were plated into collagen-coated 24-well trays and cultured at 37° C. in an atmosphere of 95% air/5% CO 2  in DMEM/10% FCS that contained antibiotics for 1 day.  
         [0156]    2. The media was removed and cells were cultured in LHM/10% FCS/antibiotics for 1 day.  
         [0157]    3. The media was removed and cells cultured in LHM/10% FCS (no antibiotics) for 20 h.  
         [0158]    4. The media was removed and cells cultured for 30 min in air at 37° C. in depletion medium (25 mM Hepes/Tris (pH 7.5), 140 mM NaCl, 5.4 mM KCl, 1.8 mM CaCl2, 0.8 mM MgSO 4 , and 5 mM glucose, to normalize intracellular nutrient pools.  
         [0159]    5. Transport was initiated by replacing depletion medium with uptake medium (depletion medium adjusted to pH 6.0 or kept at pH 7.4) that contained 100 μM GlySar (at a specific activity of 5 μCi/mL, with [ 3 H]-GlySar supplying 2.88% of total GlySar substrate) and (or) 1 mM of inhibiting peptide.  
         [0160]    An inhibitory substrate concentration of 1 mM was selected because the literature indicates that typical K m  values for PepT1 ranges from 0.5 to 5 mM. Therefore, by selecting an inhibitor concentration of 1 mM (not expected to completely inhibit uptake), our goal was to more finely delineate the relative abilities of candidate inhibitors than if the typical 5 mM inhibitor concentration (expected to achieve close to 100% inhibition of GlySar uptake) was used. Candidate peptides were selected based on their containing Trp, Leu, Met, and (or) Arg, substrates. In total, 23 inhibitory peptides and 2 drug compounds were screened using this protocol.  
         [0161]    To determine the potential of Trp and Leu absorption as dipeptides by cPepT1, the ability of TrpLeu versus LeuTrp dipeptides to inhibit 100 μM GlySar uptake was evaluated (FIG. 15). The presence of either TrpLeu or LeuTrp in the pH 6.0 uptake buffer abolished H + -dependent GlySar uptake by 117% or 114%, respectively. In contrast, neither Leu nor Trp significantly influenced H + -dependent GlySar uptake. These results indicate that a lesser concentration of inhibitor would be required to delineate the relative recognition of TrpLeu and LeuTrp by cPepT1. With regard to the mechanism of H + -independent GlySar uptake observed throughout these experiments, it is of interest to note that TrpLeu and LeuTrp inhibited H + -independent GlySar uptake by 36% and 46%, respectively.  
         [0162]    To further evaluate the potential of Trp to be absorbed in the form of peptides by cPepT1, the ability of TrpTrp, TrpGly, and TrpGlyGly to inhibit GlySar uptake was compared (FIG. 16). As observed for TrpLeu (FIG. 15), TrpTrp abolished H + -dependent GlySar uptake and inhibited H + -independent uptake by about 22%. TrpGly abolished H + -dependent GlySar uptake but did not influence H + -independent uptake. The tripeptide TrpGlyGly also significantly inhibited GlySar uptake, but to a lesser extent (73%) than did TrpTrp or TrpGly.  
         [0163]    To determine the relative potential of other amino acids (Met, Arg, Lys, Phe, for example) to be absorbed in the peptide-bound form, additional GlySar competitive inhibition experiments were conducted using the above-described regimen and a variety candidate peptides at 1 mM. The results of these experiments are summarized in Table 2, which also includes those experiments described in FIGS. 13, 14,  15 , and  16  for comparative purposes.  
                                                   TABLE 2                           Influence of 1 mM extracellular peptides and antibiotics on 100 μM       glycylsarcosine (GlySar) uptake 1  by MDCK cells.                Extracellular   % inhibition of               Substrate   H + -dependent           (1 mM)   GlySar uptake 4     n                            Positive control (model) substrates                   GlyGly   89   8           [Gly] 4     19   8           [Gly] 5     9   8           Carnosine (β-AlaHis)   50   8           Penicillin-G   0   8           Cefadroxil 2     0   6           Cefadroxil 3     59   5           Treatment substrates           100% inhibition           GlnGln   100   8           GlyLeu   115   8           GlyMet   114   8           LeuMet   114   8           LeuTrp   113   8           MetLeu   122   8           MetMet   100   8           MetPhe   100   8           MetPro   100   8           TrpLeu   116   8           TrpTrp   119   7           &lt;100% inhibition           GlnGlu   83   8           MetGlu   93   8           MetLys   88   8           TrpGly   88   7           MetGlyMetMet (SEQ ID NO:10)   50   8           TrpGlyGly   33   7           LeuArg   32   8           ArgLeu   32   8                                                                      
 
         [0164]    The inhibitors are listed within groupings in order of their relative ability to inhibit 100 μM of GlySar uptake. In addition to the listed peptides, the constituent free amino acids were tested within the appropriate experiment to evaluate whether the peptide-bound or free amino acid was responsible for any affect on GlySar uptake. As expected, the presence of 1 mM constituent free amino acid did not influence GlySar uptake. Inhibition percentages of 50% indicate that the inhibitor substrate was recognized at least as well as was GlySar, given that the K m  of GlySar was determined to be about 1 mM (FIG. 12) and that the substrate was present at 1 mM. Of the 19 treatment peptides evaluated, eleven abolished H + -dependent GlySar uptake, with seven of these also displaying the ability to inhibit H + -independent GlySar uptake. Of the remaining eight peptides tested, four displayed greater than 80% inhibition while four inhibited GlySar uptake by 50% or less. These results indicate that a wide variety of peptides of nutritionally important constituent amino acids are recognized by cPepT1.  
         [0165]    Overall, the observation that cPepT1 activity was sensitive to a number of substrates is typical of PepT1 function. However, what was surprising was the large number of peptides that completely inhibited GlySar uptake. To establish a more sensitive relative inhibitory order among peptides that inhibited GlySar uptake by more than 80%, and, therefore, a more accurate potential for recognition, fourteen peptides were re-screened for their ability to inhibit 100 μM GlySar uptake using the same cell culture and transport regimen but using only 10% of the previous inhibitor concentration (100 μM). The data from an experiment to directly compare the ability of 100 μM Trp-containing peptides are shown in FIG. 17. All Trp-containing peptides inhibited H + -dependent GlySar uptake. However, TrpLeu inhibited more (92%) than did LeuTrp (58%), TrpTrp (62%), or TrpGly (45%). These values and the results of other experiments comparing the relative ability of Leu-, Met-, and Arg-containing peptides are listed in Table 3.  
                                                   TABLE 3                           Influence of 100 μM extracellular peptides on 100 μM glycylsarcosine       (GlySar) uptake 1  by MDCK cells.                Extracellular   % inhibition               substrate   of H + -dependent           (100 μM) 2     GlySar uptake   n                            Trp-containing peptides                   TrpLeu   92   8           TrpTrp   62   8           LeuTrp   58   8           TrpGly   45   8           Leu-containing peptides           TrpLeu   94   8           LeuMet   80   8           MetLeu   77   8           GlyLeu   65   8           Met-containing peptides           MetMet   85   8           MetPhe   84   8           MetGlu   31   8           MetLys   30   8           Arg-containing peptides           ArgLeu   49   8           LeuArg   8.9   8           ArgTrp   8.9   8                                              
 
         [0166]    Overall, four of the peptides inhibited GlySar uptake by at least 80%, six by more than 40%, and four less than 40%, thus establishing a relative ranking for recognition by cPepT1. Among the five Trp-containing peptides (FIG. 17, Table 3), TrpLeu demonstrated the greatest ability to inhibit GlySar uptake. TrpLeu also demonstrated the greatest ability to inhibit GlySar uptake (94%) among the Leu-containing peptides. Among the Met-containing substrates that were directly compared within the same experiment, the neutral peptides, MetMet and MetPhe, inhibited more GlySar uptake than did the anionic (MetGlu) or cationic (MetLys) carboxyl residues. Interestingly, as a group the Arg peptides demonstrated the least inhibitory ability, seemingly in keeping with the apparent lesser recognition by PepT1 of substrates with charged residues. However, it is of interest to note that 100 μM ArgLeu demonstrated a much greater ability to inhibit GlySar uptake than did LeuArg (49 versus 8.9%).  
         [0167]    To confirm the relative ranking of TrpLeu&gt;TrpTrp inhibition of GlySar (Tables 2 and 3), Michaelis-Menton constants for substrate inhibition (K i ) of GlySar uptake by TrpLeu and TrpTrp were generated by graphical analyses of IC 50  experiments (FIG. 18). In keeping with the results achieved in the 100 μM-inhibition studies, TrpLeu inhibited GlySar uptake at lower concentrations than did TrpTrp (K 1 =0.2 versus 0.75 μM, respectively).  
         [0168]    Collectively, the results of cPepT1 competitive inhibition trials using MDCK cells indicate that TrpLeu is better recognized by cPepT1 than any other tested peptide. The results also indicate that a number of Trp-, Leu, and Met-containing peptides also are well recognized by cPepT1. Ultimately, in the intestinal environment, it is the combination of recognition by the transporter and relative resistance of the peptide to luminal and membrane-bound peptidases that will determine how much of a given peptide will be absorbed. In this regard, there is some evidence to suggest that Gly-X peptides are more resistant than other peptides, especially by blood and renal peptidases. If so, then GlyLeu may be a better candidate substrate than TrpLeu to supply Leu. Similarly, tripeptides, as a group, are thought to be relatively resistant to hydrolysis. Thus, more TrpGlyGly may prove to be absorbed in larger amounts by the intestine than TrpLeu.  
         [0169]    An important result of this set of experiments was the establishment of a sensitive experimental regimen/model to evaluate potential affecters of peptide transport capacity. Accordingly, this experimental model of MDCK cells grown in LHM affords an opportunity to evaluate the effects of various peptide and drug substrates, and hormones and (or) growth factors, on the expression of PepT1.  
         [0170]    Thus, the culture of MDCK cells in LHM versus DMEM results in an increase of H + -dependent GlySar uptake (K m =1.1 mM) that is consistent with mammalian PepT1-like activity. Using this stimulated model, the ability of twenty-three di- and tripeptides at 1 mM, and fourteen at 100 μM, extracellular concentrations were screened for their ability to inhibit 100 μM GlySar uptake, as an indicator of recognition by PepT1. Of the Trp- and (or) Leu-containing peptides evaluated, TrpLeu (K i =0.2 μM) and LeuTrp (K 1 =0.75 μM) demonstrated the greatest ability to inhibit GlySar uptake, with TrpLeu demonstrating a relatively higher affinity (lower K 1 ) for PepT1. Of the Met-containing peptides evaluated, four (MetMet, MetPhe, LeuMet, MetLeu) appear particularly well recognized by PepT1. In contrast, as a group, Arg-containing peptides displayed the least inhibition of PepT1 activity. Overall, these results indicate that cPepT1 is capable of recognizing a variety of di- and tripeptides, including, for example, those that contain leucine and tryptophan.  
       EXAMPLE 3  
     Experimental Model to Determine Whether the H + /peptide Transport Capacity Expressed by MDCK Cells is Sensitive to Substrate Regulation  
       [0171]    Trial 1:  
         [0172]    Examples 1 and 2 above demonstrated that Madin-Darby canine kidney (MDCK) cells express PepT1 mRNA and characterized H + -dependent biochemical properties. Therefore, MDCK cells were chosen as the experimental model to determine whether the H + /peptide transport capacity expressed by MDCK cells is sensitive to substrate regulation. Research from Example 2 demonstrated that MDCK cells grown in lactalbumin hydrolysate medium (LHM) had elevated levels of peptide uptake capacity. Accordingly, to avoid potential confounding effects of the peptide-containing LHM and individual treatment peptides, DMEM (contains no peptides) and not LHM was selected as the appropriate medium to test the influence of extracellular peptides on canine PepT1 functional capacity of MDCK cells. GlyPhe was selected as a substrate because it has been reported to increase brush border membrane content of PepT1, (Shiraga T, Miyamoto K, Tanaka H, Yamamoto H, Taketani Y, Morita K, Tamai I, Tsuji A, Takada E. Cellular and molecular mechanisms of dietary regulation on rat intestinal H + /peptide transporter PepT1.  Gastroenterology  1999; 116:354-362), whereas Phe and Gly were tested as constituent free amino acid treatment controls. Carnosine was selected because of its high content in meat-based diets.  
         [0173]    Cell culture. All cells were plated (60,000/2 cm 2 well) and cultured (95% air/5% CO 2 , 37° C.) for 24 h in Dulbecco&#39;s Modified Eagle Media/10% fetal calf serum (FCS)/1% Antibiotic/Antimicrobial solution (ABAM) (DMEM media). Following these initial common culture conditions, cells then were cultured in DMEM, or DMEM that contained 10 mM of Carnosine, GlyPhe, Phe, or Gly. Media were changed every 24 h. Media treatments (n=8) were as follows:  
         [0174]    DMEM  
         [0175]    DMEM+10 mM Carnosine  
         [0176]    DMEM+10 mM GlyPhe  
         [0177]    DMEM+10 mM Phe  
         [0178]    DMEM+10 mM Gl  
         [0179]    Uptake measurements. The measurement of [ 3 H]Glysarcosine uptake was performed by using a 24-well cluster tray method (Kilberg M S. Measurement of amino acid transport by hepatocytes in suspension and monolayer culture.  Methods Enzym  1989; 173:564-575. Matthews J C, Aslanian A, McDonald K K, Yang W, Malandro M S, Novak D A, Kilberg M S. An expression system for mammalian amino acid transport using a stably maintained episomal vector.  Anal Biochem  1997; 254:208-214), and used in Examples 1 and 2. Cells were cultured for 30 min in air at 37° C. in depletion medium (25 mM Hepes/Tris (pH 7.5), 140 mM NaCl, 5.4 mM KCl, 1.8 mM CaCl2, 0.8 mM MgSO4, and 5 mM glucose), to normalize intracellular nutrient pools before transport. The transport assays are initiated by replacing depletion medium with uptake medium (Depletion medium adjusted to pH 6.0) that contained 100 μM GlySar (5 μCi/mL, with [ 3 H]-GlySar supplying 2.88% of total GlySar). After a 30 minute incubation period, transport was terminated with four rinses of 4° C. depletion medium (pH 7.5). Two hundred and twenty μL of 10% trichloroacetic acid was added to each well, and the radioactivity of the supernatant quantified by liquid scintillation counting. The cells of each well are solubilized in 0.2 N NaOH/0.2% SDS and the protein quantified by using the modified Lowry assay, using bovine serum as a standard. Id. Peptide uptake will be reported as pmol* mg −1  protein* 30 min −1 . Uptake measurements were taken after 24, 48, and 72 hours of culture in treatment media.  
         [0180]    Results. The previous research characterizing H + -dependent peptide transport by MDCK cells (Example 2 above) clearly showed that transport velocity is dependent on protein content. Therefore, to make a valid comparison of various treatment parameters on GlySar uptake, the protein content of compared treatment groups must not differ. Accordingly, the influence of culture media on MDCK cellular protein was evaluated (FIG. 19). All media treatments supported cellular growth from 1 to 3 d and no difference in protein content among treatments was observed. Similarly, no difference in uptake velocity (capacity) was observed among treatment groups, for any culture period (FIG. 20).  
         [0181]    Trial 2  
         [0182]    The results from Trial 1 suggest that either canine PepT1 is not sensitive to substrate regulation or that the substrates and(or) stimulation time were inadequate to influence H + -dependent peptide uptake in MDCK cells. Again, DMEM was selected as the basal medium to allow the effect of individual peptides on peptide transport activity to be evaluated. To evaluate the latter two possibilities, a second trial was conducted that included a culture period of 9 d. GlySar was added as another potential affecter of H + -dependent peptide transport capacity because 10 mM GlySar it is reported capable of stimulating increased PepT1 activity (Adibi S. The oligopeptide transporter PepT1 in human intestine: biology and function.  Gastroenterology  1997; 113:332-340) in Caco-2 cells. GlyPro was added as a treatment because of its high content in muscle tissue, thus is likely to be abundant in meat-based diets.  
         [0183]    Cell culture. The MDCK cell line was maintained as described previously in the Methods section of Trial 1. Following initial and common culture conditions, cells were cultured in DMEM, or DMEM that contained 10 mM GlySar, GlyPro, GlyPhe, or Carnosine. Media were changed every 24 h. Media treatments (n=8) were as follows:  
         [0184]    DMEM  
         [0185]    DMEM+10 mM GlySar  
         [0186]    DMEM+10 mM GlyPro  
         [0187]    DMEM+10 mM GlyPhe  
         [0188]    DMEM+10 mM Carnosine  
         [0189]    Uptake measurements. The measurement of [ 3 H]Glysarcosine uptake was performed by using the 24-well cluster tray method as previously described in the Methods section of Trial 1. Peptide uptake will be reported as pmol* mg −1  protein* 30 min −1 . Uptake measurements were taken after 4, 12, 24, 36, 72, 120, 168, and 216 hours of culture in treatment media.  
         [0190]    Results. Protein content in all treatment groups increased linearly from 4 to 216 h (9 d) of culture, for all treatment groups (FIG. 21). However, within a culture period, protein contents of treatment groups did not differ. Over the 216-h culture period, protein increased about 4.5 times, from about 40 to 220 μg/well. In contrast to Trial 1 results, media treatment did influence GlySar uptake capacity (FIG. 22). In addition, a treatment×time effect was observed that represents differences in the time of culture required for GlySar and carnosine treatment stimulation of GlySar uptake capacity. Specifically, GlySar containing DMEM culture treatment resulted in an increase in GlySar uptake capacity of about 30% over DMEM control media by 24 h of culture time. This level of increase was maintained through 216 h. In contrast, culture in carnosine-containing media did not result in a significant (23%) increase of GlySar uptake capacity over that by DMEM-cultured cells until 72 h of culture. This stimulation then steadily increased to 291% over 216 h of culture. The nature of stimulated uptake between the two peptide substrates also differed. That is, the magnitude of carnosine-stimulated GlySar uptake was essentially constant from 72 to 216 h, whereas that for GlySar culture decreased during this period. Collectively, these data indicate that H + -dependent peptide transport in cultured MDCK cells can be stimulated by at least two of PepT1 substrates, GlySar and carnosine.  
         [0191]    Trial 3  
         [0192]    The data from Trial 2 indicate that H + -dependent GlySar uptake capacity by fed MDCK cells can be upregulated by the inclusion of 10 mM GlySar for at least 24 h and 10 mM carnosine for at least 72 h. It is of equal interest to understand if H + -dependent GlySar uptake capacity is sensitive to nutrient deprivation and(or) stimulation by glucocorticoids. A preliminary study indicates that fasting increases the expression of PepT1 in rat small intestine epithelia. Thamotharan M, Bawani S, Zhou X, Adibi S. Functional and molecular expression of intestinal oligopeptide transporter (PepT1) after a brief fast.  Metabolism  1999; 48:681-684.  
         [0193]    To initiate investigation of potential influence of fasting and glucocorticoids on MDCK cells expression of GlySar uptake capacity, the H + -dependent uptake of GlySar was evaluated over a 72 period of nutrient deprived or fed and cultured with dexamethasone (Dex) and compared to that by cells cultured in DMEM or DMEM that contained insulin (negative control) (Trial 3A). The “nutrient deprived” treatment actually contained 5 mM glucose and appropriate salts to ensure adequate basal metabolic conditions.  
         [0194]    Although recruitment of PepT1 protein and activity appears sensitive to insulin-stimulated recruitment from cytosolic vesicles in Caco-2 cells (Thamotharan M, Bawani S, Zhou X, Adibi S. Hormonal regulation of oligopeptide transporter PepT1 after a brief fast.  Am J Physiol  1999; 276:C821-826, MDCK cells are reported to be insensitive to insulin, likely as an inability to express the insulin receptor. Hofmann C, Crettaz M, Bruns P, Hessel P, Hadawi G. Cellular responses elicited by insulin mimickers in cells lacking detectable plasma membrane insulin receptors.  J Cell Biol  1985; 27:401-414. In contrast to the lack of insulin sensitivity, IGF-I is known to stimulate DNA synthesis and cell proliferation in MDCK cells. Sukegawa I, Hizuka N, Takano K, Asakawa K, Shizume K. Characterization of IGF-1 receptors on MDCK cell line.  Endocrinol Japan  1987; 34(3):339-346. Mouzon S H, Kahn R. Insulin-like growth factor-mediated phosphorylation and proto-ontogeny induction in MDCK cells.  Mol Endocrinol  1991; 5:51-60. The understanding that MDCK cells are apparently insensitive to insulin stimulation yet are sensitive to IGF-I stimulation appears to be a paradox given that the supraphysiologic levels of both substrates employed in the perspective studies and the known ability of insulin to cross react with the IGF-I receptor. Accordingly, another trial (Trial 3B) was conducted to evaluate the influence of increasing IGF-I concentrations on H + -dependent GlySar uptake by MDCK of the same plating stock.  
         [0195]    Trial 3A:  
         [0196]    Cell culture. MDCK cells were maintained as described in Trial 1, except that cells were cultured for only 1 d before transport trials were performed. Following initial and common culture conditions, cells were cultured in a “nutrient depleted” buffer (Hepes/Tris (pH 7.5), 140 mM NaCl, 5.4 mM KCl, 1.8 mM CaCl 2 , 0.8 mM MgSO 4 ) that contained 5 mM glucose as an energy source, but that lacked amino acid or vitamin sources. In contrast, cells cultured in DMEM, or DMEM that contained 5 nM Dex, 500 nM Dex, 5 nM insulin, or 500 nM insulin, were adequately nourished. Media treatments (n=4) were as follows:  
         [0197]    Nutrient depleted  
         [0198]    DMEM  
         [0199]    DMEM+5 nM Dex  
         [0200]    DMEM+500 nM Dex  
         [0201]    DMEM+5 nM Insulin  
         [0202]    DMEM+500 nM Insulin  
         [0203]    Uptake measurements. The measurement of [ 3 H]Glysarcosine uptake was performed by using the 24-well cluster tray method as previously described in the Methods section of Trial 1. Peptide uptake is reported as pmol* mg −1  protein*30 min −1 . Uptake measurements were taken after 30 min and 4 h of culture in treatment media.  
         [0204]    Trial 3B:  
         [0205]    Trial 3B was conducted in the same manner as described for Trail 3A, except that cells were cultured in DMEM or DMEM that contained 1 nM IGF-1, 5 nM IGF-1, 25 nM IGF-1, or 100 nM IGF-1. Uptake measurements were taken after 30 min and 4 h of culture time. Media treatments (n=4) were as follows:  
         [0206]    DMEM (pH 6 measurement)  
         [0207]    DMEM (pH 7.5 measurement)  
         [0208]    DMEM+1 nM IGF-1  
         [0209]    DMEM+5 nM IGF-1  
         [0210]    DMEM+25 nM IGF-1  
         [0211]    DMEM+100 nM IGF-1  
         [0212]    Results. Protein content of the treatments within Trails 3A or 3B did not differ. After 4 h of culture, however, the capacity for H + -dependent peptide uptake was reduced 35% in cells deprived of nutrients but adequate in energy (FIG. 23). In contrast, dexamethasone had no effect on GlySar uptake. As expected, and consistent with the concept that MDCK cells are insulin-insensitive, the presence of insulin for 4 h had no effect on GlySar uptake capacity. Similarly, culture of cells with increasing amounts of IGF-I elicited no significant stimulation of H + -dependent GlySar uptake (FIG. 24). Quantitatively, however, 1 to 25 nM of IGF-I tended to increase GlySar uptake capacity by 10 to 15%.  
         [0213]    Given the noted restrictions of Trail 3, and the low number of observations (n=4) results from trial 3A and 3B suggest that H + -dependent uptake of GlySar by MDCK is sensitive to nutrient deprivation and, perhaps, IGF-I.  
       EXAMPLE 4  
       [0214]    [0214]                                         PepT1 Sequence       Clone12 (5 th  round; SEQ ID NO:11) Primer Pair is GSP3-4;       GSP3-1R using regular RT-PCR                                  catcttcttcatcgtggt caatgagttctgtgaaagattttcctactatg                   gaatgagagcactcctgattctgtacttcagacggttcatcgggtgggac               gataatctgtccacggccatctaccacacgtttgtggctctgtgctacct               gacgccgatcctcggcgcactgatcgcagactcctggctgggaaagttca               agacaatcgtgtcactctccattgctacacaattggacaggcggtcactg               cagtaagctcaattaatgacctcacagactataacaaagatggaactcct               gacaatctgtccgtgcatgtggcactgtccatgattggcctggccctgat               agctctgggaactggaggaataaagccctgtgtgtctgcatttggtggag               accagtttgaagagggccaggaaaaacaaagaaacagattcttttccatc               ttttatttggccattaatgctggaagcttgatttccactattgtcactcc               catgctcagagttcacgaatgtggaatttacagtcagaaagcttgttacc               cactggcatttggggttcctgctgctctcatggccgtatctctgattgta               tttgtcattggcagtggaatgtacaagaagtttcagccccagggtaatgt               catgggtaaagttgtcaagtgcattggttttgccctcaaaaataggttta               ggcaccggagtaagcagtttcccaagagggagcactggctggactgggct               aaagagaaatacgatgagcggctcatctctcaaattaagatggtcacaaa               agtgatgttcttgtacatcccactcccaatgttctgggccctgtttgacc               agcagggctccaggtggacactgcaagcaacagctatgagtgggaaaatt               ggacttcttgaagttcagccagatcagatgcagactgtgaatgccatctt               gattgtcgtcatggtccccatcatggatgccgtggtgtaccctctgattg               caaaatgtggcttcaatttcacctccttgaagaggatgacagttggaatg               ttcctggcttccatggccttcgtgatggcggcgattgttcagctggaaat               tgataaaactcttccagtcttccccaaacaaaatgaagtccaaatcaaag               tactgaatataggaaatggtgccatgaatgtatcttttcctggagcggtg               gtgacagttagccaaatgagtcaatcagatggatttatgacttttgatgt               agacaaactgacaagtataaacatttcttccactggatcaccagtcattc               cagtgacttataactttgagcagggccatcgccatacccttctagtatgg               gcccccaataattaccgagtggtaaaggatggcctt aaccagaagcc                   agaaaaagggag                      
         [0215]    Amplification Conditions  
                                                                                                                       Initiale   Denatur-   An-   Amplifi-                   Denaturat   ation   nealing   cation   Extension   Cooling                                    Temp   94° C.   94° C.   55° C.   72° C.   72° C.   4° C.       Min.   10 min   2 min   1.5 min   2 min   10 min   inf.            Cycle   1   35   1                  
 
         [0216]    [0216]                                         Clone37 beginning (6th round; SEQ ID NO:12) Primer       pair is GSP3-9; AUAP using 3′RACE Protocol                                  gccatcgccatacccttcta gtatgggcccccaataattaccgagtggta                   aaggatggccttaaccagaagccagaaaaaggagaaaatggaatcagatt               tataaatagtcttaatgagagcctcaacatcaccatgggcgacaaagttt               atgtgaatgtcaccagtcacaatgccagcgagtatcagttctttttcttt               tctttgggcacaaaaaacattacaataagttcaacacaacgatctcacaa               aattgtacaaaagttctccaatcatccaaccttgaatttggtagtgcata               tacctatgtaatcggaacgcagagcactggctgccctgaattgcatatgt               ttgaagatatttcacccaacacagttaacatggctctgcagatcccgcag               tacttcctcatcacctgcggcgaggtggttttctctgtcacaggactgga               gttctcatattctcaggccccctccaacatgaagtcggtgcttcaggcgg               gatggctgctgacagtggcttgttggcaacatcattgtgctcattgtggc               aggagcaggccagttcagtgaacagtgggctgaatacatcctatttgcgg               cattgcttctggttgtctgtgtaatatttgccatcatggcccggttttac               acttacgtcaatccagcagagattg                    
         [0217]    Amplification Conditions  
                                                                                                                       Initiale   Denatur-   An-   Amplifi-                   Denaturat   ation   nealing   cation   Extension   Cooling                                    Temp   94° C.   94° C.   52° C.   72° C.   72° C.   4° C.       Min.   10   2 min   1.5 min   2   10   inf.            Cycle   1   30   1                  
 
         [0218]    [0218]                           Merge Sequence (SEQ ID NO:8) is:           catcttcttcatcgtggtcaatgagttctgtgaaagattttcctatggaa               tgagagcactcctgattctgtacttcagacggttcatcgggtgggacgat               aatctgtccacggccatctaccacacgtttgtggctctgtgctacctgac               gccgatcctcggcgcactgatcgcagactcctggctgggaaagttcaaga               caatcgtgtcactctccattgtctacacaattggacaggcggtcactgca               gtaagctcaattaatgacctcacagactataacaaagatggaactcctga               caatctgtccgtgcatgtggcactgtccatgattggcctggccctgatag               ctctgggaactggaggaataaagccctgtgtgtctgcatttggtggagac               cagtttgaagagggccaggaaaaacaaagaaacagattcttttccatctt               ttatttggccattaatgctggaagcttgatttccactattgtcactccca               tgctcagagttcacgaatgtggaatttacagtcagaaagcttgttaccca               ctggcatttggggttcctgctgctctcatggccgtatctctgattgtatt               tgtcattggcagtggaatgtacaagaagtttcagccccagggtaagtcat               gggtaaagttgtcaagtgcattggttttgccctcaaaaataggtttaggc               accggagtaagcagtttcccaagagggagcactggctggactgggctaaa               gagaaatacgatgagcggctcatctctcaaattaagatggtcacaaaagt               gatgtcttgtacatcccactcccaatgttctgggccctgtttgaccagca               gggctccaggtggacactgcaagcaagcaacagctatgagtgggaaaatt               ggacttcttgaagttcagccagatcagatgcagactgtgaatgccatctt               gattgtcgtcatggtccccatcatggatgccgtggtgtaccctctgattg               caaaatgtggcttcaatttcacctccttgaagaggatgacagttggaatg               ttcctggcttccatggccttcgtgatggcggcgattgttcagctggaaat               tgataaaactcttccagtcttccccaaacaaaatgaagtccaaatcaaag               tactgaatataggaaatggtgccatgaatgtatcttttcctggagcggtg               gtgacagttagccaaatgagtcaatcagatggatttatgacttttgatgt               agacaaactgacaagtataaacatttcttccactggatcaccagcattcc               agtgacttataactttgagcagg gccatcgccatacccttcta gtatggg               cccccaataattaccgagtggtaaaggatggccttaaccagaagccagaa               aaaggagaaaatggaatcagatttataaatagtcttaatgagagcctcaa               catcaccatgggcgacaaagtttatgtgaatgtcaccagtcacaatgcca               gcgagtatcagttcttttctttgggcacaaaaaacattacaataagttca               acacaacagatctcacaaaaffgtacaaaagttctccaatcatccaaccf               fgaatttggtagtgcatatacctatgtaatcggaacgcagagcactggct               gccctgaattgcatatgtttgaagatafftcacccaacacagttaacatg               gctctgcagatcccgcagtacttcctcatcacctgcggcgaggtggtttt               ctctgtcacaggactggagttctcatattctcaggccccctccaacatga               agtcggtgcttcaggcgggatggctgctgacagtggct   tgttggcaacat                       cattgtgctcattgtggcaggagcaggccagttcagtgaacagtgggctgc                       aatacatcctatttgcggcattgcttctggttgtctgtgtaatatttgcc                       atcatggccczgttttacacttacgtcaatccagcagagattg                
         [0219]    [0219]                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         Multiple Alignment of Nucleotide Full Length Sequences                Sequence 1:   XM_007063 Homosapiens     3045 bp                   Sequence 2:   AY027496Ovis   2829 bp               Sequence 3:   D50306Rat   2900 bp               Sequence 4:   NM_053079 Musmusculus     3128 bp               Sequence 5:   U13808 Oryctolaguscunic     2709 bp               Sequence 6:   AY029615 Gallusgallus     2914 bp               Sequence 7:   SequencetosubmitGenbak   1840 bp                    Start of Pairwise alignments                   Aligining. . .                Sequences (4:5) Aligned. Score: 65               Sequences (1:2) Aligned. Score: 65               Sequences (2:3) Aligned. Score: 66               Sequences (3:4) Aligned. Score: 88               Sequences (4:6) Aligned. Score: 48               Sequences (2:4) Aligned. Score: 64               Sequences (1:3) Aligned. Score: 67               Sequences (3:5) Aligned. Score: 66               Sequences (4:7) Aligned. Score: 80               Sequences (2:5) Aligned. Score: 77               Sequences (3:6) Aligned. Score: 48               Sequences (5:6) Aligned. Score: 51               Sequences (1:4) Aligned. Score: 76               Sequences (3:7) Aligned. Score: 81               Sequences (5:7) Aligned. Score: 79               Sequences (2:6) Aligned. Score: 50               Sequences (6:7) Aligned. Score: 70               Sequences (1:5) Aligned. Score: 67               Sequences (2:7) Aligned. Score: 83               Sequences (1:6) Aligned. Score: 49               Sequences (1:7) Aligned. Score: 85               Guide tree file created:               [/net/nfs0/vol1/production/w3nobody/tmp/999267.834538-239427.aln]               Start of Multiple Alignment               There are 6 groups               Aligning. . .                     Group 1:   Sequences: 2   Score: 48218                   Group 2:   Sequences: 3   Score: 43200               Group 3:   Sequences: 2   Score: 42027               Group 4:   Sequences: 5   Score: 39817               Group 5:   Sequences: 6   Score: 30418               Group 6:   Sequences: 7   Score: 33857                    Alignment Score 249395                   CLUSTAL-Alignment file created               [/net/nfs0/voll/production/w3nobody/tmp/999267.834538-239427.aln]               Your Multiple Sequence Alignment:               999267.834538-239427.aln               CLUSTAL W (1.81) multiple sequence alignment                    (SEQ ID NO:3)                D50306Rat   -----------------------------------CTGAACTCCTGCTTG   15                        (SEQ ID NO:4)                NM_053079 Musmusculus     --------------------------------------------------                        (SEQ ID NO:1)                XM_007063 Homosapiens     --------------------------------------------------                        (SEQ ID NO:2)                AY027496Ovis   -----GAAACAACATCTTTAGCACGGATTCCTCCCACCTGGACTCCTCGC   45                        (SEQ ID NO:5)                U13707 Oryctolaguscunic     ------------------------------------------------                        (SEQ ID NO:6)                SequencetosubmitGenbak   ------------------------------------------------                        (SEQ ID NO:6)                AY029615 Gallusgallus     GCTCTCTGTCCGTCCCTCGGTCCCTCCGTCCCTCCGTCCCCGCGCGGCCG   50                   D50306Rat   CCAGTCGCCGGTCAGGAGCCTCGGAGCCACAATGGGGATGTCCAAGT   65       NM_053079 Musmusculus     ---GTCGCCCGTCCGGAGCCTTGGAGCCACCACAATGGGGATGTCCAAGT   47       XM_007063 Homosapiens     --------------------------------------GAATGTCCAAAT   12       AY027496Ovis   TCGCCAGTCGCAGGGAGCCCTCGGAGCCGCCAGCATGGGAATGTCCGTGC   95       U13707 Oryctolaguscunic     ------------------------------CACCATGGGAATGTCTAAGT   95       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     CCAGCAGCGTGCCGGCCCCATGGCTGCAAAAAGTAAGAGTAAGGGCCGAT   100               D50306Rat   CT---CGGGGTTGCTTTGGCTACCCATTGAGCATCTTCTTCATCGTGGTC   112       NM_053079 Musmusculus     CT---CGGGGTTGCTTCGGTTACCCGTTGCATCTTCTTCATCGTGGTC   94       XM_007063 Homosapiens     CA---CACAGTTTCTTTGGTTATCCCCTGAGCATCTTCTTCATCGTGGTC   59       AY027496Ovis   CG---AAGAGCTGCTTCGGTTACCCCTTAGCATCTTCTTCATCGTGGTC   142       U13707 Oryctolaguscunic     CA---CTGAGCTGCTTCGGCTATCCCCTGAGCATCTTCTTCATCGTGGTC   67       SequencetosubmitGenbak   ------------------------------CATCTTCTTCATCGTGGCT   19       AY029615 Gallusgallus     CAGTGCCGAACTGCTTTGGCTACCCCTTGAGCATCTTCTTCATCGTCATC   150                                          ***************  **               D50306Rat   AATGAATTCTGTGAAAGATTCTCCTACTATGGGATGCGAGCTCTCCTGGT   162       NM_053079 Musmusculus     AATGAATTCTGTGAAAGATTCTCCTACTATGGCATGCGAGCACTCCTGGT   144       XM_007063 Homosapiens     AATGAGTTTTGCGAAAGATTTTCCTACTATGGCATGCGAGCACTTCTGGT   109       AY027496Ovis   AATGAGTTCTGCGAAAGGTTCTCTTACTATGGAATGCGAGCAATCCTGAT   192       U13707 Oryctolaguscunic     AATGAGTTCTGCGAAAGGTTCTCCTACTATGGAATGCGAGCAATCCTGAT   117       SequencetosubmitGenbak   AATGAGTTCTGTGAAAGATTTTCCTACTATGGAATGCGAGCAATCCTGAT   69       AY029615 Gallusgallus     AATGAGTTCTGCGAGAGGTTCTCCTACTATGGCATGCGAGCAATGCTCGT   200           ***** ** ** ** ** ** ** ******** *** ****  * **  *               D5030GRat   TCTGTACTTCAGGAACTTCCTTGGCTGGGATGATGACCTCTCCACGGCCA   212       NM_053079 Musmusculus     TCTGTACTTCAGGAACTTCCTCGGCTGGGACGACAATCTCTCCACGGCCA   194       XM_007063 Homosapiens     TCTGTACTTCACAAATTTCATCAGCTGGGATGATAACCTGTCCACCGCCA   159       AY027496Ovis   CCTGTACTTCCAACGTTTCCTGGGCTGGAACGACAACCTGGGCACCGCCA   242       U13707 Oryctolaguscunic     TCTGTACTTCAGAAACTTCATCGGCTGGGACGACAACCTGTCCACGGTCA   167       SequencetosubmitGenbak   TCTGTACTTCAGACGGTTCATCGGGTGGGACGATAATCTGTCCACGGCCA   119       AY029615 Gallusgallus     ATTGTATTTCAAGTACTTCCTGCGGTGGGATGACAACTTTTCTACAGCCA   250             **** ***      *** *  * *** * **  *  *    ** * **               D50306Rat   TCTACCATACGTTTGTTGCCCTCTGCTACCTGACTCCAATTCTTGGAGCT   262       NM_053079 Musmusculus     TTTACCATACGTTCGTTGCCCTCTGCTACCTGACTCCAATTCTTGGAGCT   244       XM_007063 Homosapiens     TCTACCATACGTTTGTGGCTCTGTGCTACCTGACGCCAATTCTCGGAGCT   209       AY027496Ovis   TCTATCACACGTTCGTCGCCCTGTGCTACCTGACGCCCATCCTCGGAGCT   292       U13707 Oryctolaguscunic     TCTACCACACGTTCGTCGCGCTGTGCTACCTCACGCCCATTCTCGGAGCT   217       SequencetosubmitGenbak   TCTACCACACGTTTGTGGCTCTGTGCTACCTCACGCCCATTCTCGGAGCT   169       AY029615 Gallusgallus     TCTACCACACGTTTGTTGCTCTGTGCTACTTGACGCCCATCCTGGGAGCG   300           * ** ** ***** ** ** ** ****** * ** ** ** ** ** **               D50306Rat   CTGATCGCAGACTCGTGGCTGGGGAAGTTCAAGACAATTGTCTGACTATC   312       NM_053079 Musmusculus     CTGATCGCAGACTCGTGGCTGGGGAAGTTCAAGACAATTGTTTCACTATC   294       XM_007063 Homosapiens     CTTATCGCCGACTCGTGGCTGGGAAAGTTCAAGACAATTGTTTCACTCTC   259       AY027496Ovis   CTCATCGCCGACTCCTGGCTGGGGAAGTTCAAGACCATTGTGTCGCTGTC   342       U13707 Oryctolaguscunic     CTCATCGCCGACGCGTGGCTGGGGAAGTTCAAGACCATCGTGTCGCTGTC   267       SequencetosubmitGenbak   CTGATCGCAGACTCCTGGCTGGGAAAGTTCAAGACAATCGTGTCACTCTC   269       AYO29615 Gallusgallus     CTCATTGCAGACTCATGGCTGGGAAAGTTTAAGACCATTGTCTCCCTGTC   350           ** ** ** *** * ******** ***** ***** ** ** *  ** **               D50306Rat   CATCGTCTACACGATCGGACAGGCCGTCATCTCAGTGAGCTCAATTAATG   362       NM_053079 Musmusculus     CATCGTCTACACGATTGGACAAGCAGTCATCTCGGTGAGCTCAATTAATG   344       XM_007063 Homosapiens     CATTGTCTACACAATTGGACAAGCAGTCACCTCAGTAAGCTCCATTAATG   309       AY027496Ovis   CATCGTCTACACCATTGGGCAGGTAGTCATCGCTGTGAGCTCAATTAATG   392       U13707 Oryctolaguscunic     CATCGTCTACACCATCGGACAAGCAGTCACCTCCCTCAGCTCCGTCAATG   317       SequencetosubmitGenbak   CATTGTCTACACAATTGGACAGGCGGTCACTGCAGTAAGCTCAATTAATG   269       AY029615 Gallusgallus     CATTGTCTATACAATTGGGCAGGCAGTCATGGCTGTAAGCTCCATAAACG   400           *** ***** ** ** ** ** *  ****   *  * *****  * ** *               D50306Rat   ACCTTACAGACCATGACCACGACGGCAGTCCTAACAACCTTCCTTTGCAC   412       NM_053079 Musmusculus     ACCTCACAGACCACGACCACAATGGCAGTCCTGACAGCCTTCCCGTGCAC   394       XM_007063 Homosapiens     ACCTCACAGACCACAACCATGATGGCACCCCCGACAGCCTTCCTGTGCAC   359       AY027496Ovis   ACCTCACTGACTTCAACCATGATGGAACCCCAAACAATATTTCTGTGCAC   442       U13707 Oryctolaguscunic     AGCTCACAGACAACAACCATGACGGGACCCCCGACAGCCTCCCTGTGCAC   367       SequencetosubmitGenbak   ACCTCACAGACTATAACAAAGATGGAACTCCTGACAATCTGTCCGTGCAT   319       AY029615 Gallusgallus     ACATGACAGATCAAAACAGAGATGGCAATCCTGATAATATTGCGGTGCAC   450           *  * ** **     **    * ** *  **  * *   *  *  ****               D50306Rat   GTAGCACTGTCCATGATCGGCCTGGCCCTGATAGCCCTTGGTACAGGAGG   462       NM_053079musmusculus   GTAGCACTGTCCATGGTTGGCCTGGCCCTGATAGCCCTTGGTACAGGAGG   444       XM_007063 Homosapiens     GTGGTGCTGTCCTTGATCGGCCTGGCCCTGATAGCTCTCGGGACTGGAGG   409       AY0274696Ovis   GTGGCACTCTCCATGATTGGCCTGGTCCTGATAGCTCTGGGTACCGGAGG   492       U13707 Oryctolaguscunic     GTGGCGGTGTGCATGATCGGCCTGCTCCTGATAGCCCTCGGGACAGGAGG   417       SequencetosubmitGenbak   GTGGCACTGTCCATGATTGGCCTGGCCCTGATAGCTCTGGGAACTGGAGG   369       AY029615 Gallusgallus     ATTGCCCTGTCTATGACTGGCTTGATTCTCATCGCGCTTGGAACTGGTGG   500            * *   * *   **   *** **   ** ** ** ** ** ** ** **               D50306Rat   AATCAAGCCCTGTGTGTCTGCATTTGGTGGCGATCAGTTTGAAGAGGGTC   512       NM_053079 Musmusculus     AATCAAGCCCTGTGTGTCTGCGTTTGGTGGCGATCAGTTTGAAGAGGGTC   494       XM_007063 Homosapiens     AATCAAACCCTGTGTGTCTGCGTTTGGTGGAGATCAGTTTGAAGAGGGCC   459       AY027496Ovis   GATAAAGCCTTGCGTGTCTGCATTTGGCGGAGATCAGTTTGAAGAGGGCC   542       U13707Oryctolaquscunic   AATCAAGCCCTGTGTGTCTGCCTTTGGCGGCGATCAGTTTGAGGAGGGCC   467       SequencetosubmitGenbak   AATAAAGCCCTGTGTGTCTGCATTTGGTGGAGACCAGTTTGAAGAGGGCC   419       AY029615 Gallusgallus     GATCAAACCTTGTGTCTCAGCATTTGGTGGGGATCAGTTTGAAGAACATC   550            ** ** ** ** ** ** ** ***** ** ** ******** **    *               D50306Rat   AGGAAAAACAGCGAAACCGGTTCTTTTCCATCTTTTATTTGGCTATCAAC   562       NM_053079 Musmusculus     AGGAAAAACAGCGAAACCGGTTCTTTTCCATCTTTTATTTGGCTATCAAC   544       XM_007063 Homosapiens     AGGAGAAACAAAGAAACAGATTTTTTTCCATCTTTTACTTGGCTATTAAT   509       AY027496Ovis   AGGAAAAGCAAAGGAACAGATTTTTTTCCATCTTTTATTTGGCCATTAAT   592       U13707 Oryctolaguscunic     AGGAAAAGCAAAGAAACCGGTTTTTTTCCATCTTTTACTTGGCCATTAAC   517       SequencetosubmitGenbak   AGGAAAAACAAAGAAACAGATTCTTTTCCATCTTTTATTTGGCCATTAAT   469       AY029615 Gallusgallus     AGGAAAAACAAAGAAGTAGATTCTTCTCTATCTTTTATTTGTCCATTAAT   600           **** ** **  * *   * ** ** ** ******** *** * ** **               D50306Rat   GCAGGAAGCCTGCTCTCCACGATCATCACTCCCATACTCAGAGTTCAGCA   612       NM_053079 Musmusculus     GGGGGAAGCCTGCTCTCCACGATCATCACTCCCATACTCAGAGTTCAACA   594       XM_007063 Homosapiens     GCTGGAAGTTTGCTTTCCACAATCATCACACCCATGCTCAGAGTTCAACA   559       AY027496Ovis   GCTGGAAGTTTGCTTTCTACTATCATCACCCCCATGCTCAGAGTTCAGGT   642       U13707 Oryctolaguscunic     GCTGGGAGTCTGCTGTCCACAATCATCACCCCCATGGTCAGAGTTCAACA   567       SequencetosubmitGenbak   GCTGGAAGCTTGATTTCCACTATTGTCACTCCCATGCTCAGAGTTCACGA   519       AY029615 Gallusgallus     GCTGGAAGTCTCATATCCACTATAATCACCCCAATTCTCAGAGCTCAAGA   650           *  ** **  *  * ** ** **  **** ** **  ****** ***               D50306Rat   GTGCGGAATCCACAGCCAACAAGCTTGTTACCCACTGGCCTTTGGGGTTC   662       NM_053079 Musmusculus     GTGCGGAATCCACAGTCAACAAGCTTGTTACCCACTGGCCTTCGGGGTTC   644       XM_007063 Homosapiens     ATGTGGAATTCACAGTAAACAAGCTTGTTACCCACTGGCCTTTGGGGTTC   609       AY027496Ovis   ATGCGGAATTCACAGTAAGCAAGCTTGTTACCCCCTGGCCTTTGGGGTTC   692       U13707 Oryctolaguscunic     ATGTGGAATTCACGTTAAACAAGCTTGCTACCCACTGGCCTTTGGGATTC   617       SequencetosubmitGenbak   ATGTGGAATTTACAGTCAGATAAGCTTGTTACCACTGGCATTTGGGGTTC   569       AY029615 Gallusgallus     ATGTGGCATTCACAGCAGACAGCAGTGCTACCCGCTGGCATTTGGAGTTC   700            ** ** **  **       *    ** ***** ***** ** **  ***               D5030GRat   CGGCAGCTCTCATGGCTGTTGCCCTAATTGTGTTTGTCCTCGGCAGTGGA   712       NM_053079 Musmusculus     CAGCGGCTCTCATGGCTGTTGCCCTAATTCGTGTTTGTCCTTGGCAGTGGA   694       XM_007063 Homosapiens     CTGCTGCTCTCATGGCTGTAGCCCTGATTCGTGTTTGTCCTTGGCAGTGGG   659       AY027496Ovis   CTGCTGCACTCATGGCTGTATCTCTGATCCGTGTTTGTCATTGGCAGTGGA   742       U13707 Oryctolaguscunic     CTGCTATCCTCATGGCTGTATCCCTGATCCGTGTTCATCATCGGCAGTGGG   667       SequencetosubmitGenbak   CTGCTGCTCTCATGGCCGTATCTCTGATTCGTATTTGTCATTGGCAGTGGA   619       AY029615 Gallusgallus     CCGCTGCCCTCATGGCTGTTTCATTAGTTGTGTTCATAGCTGGAAGTGGA   750           * **    ******** **  *  *  * ** **  *    ** *****               D50306Rat   ATGTACAAGAAGTTTCAGCCCCAGGGCAACATCATGGGCAAAGTGGCCAA   762       NM_053079 Musmusculus     ATGTACAAGAAGTTCCAGCCCCAGGGCAACATCATGGGCAAAGTGGCCAA   744       XM_007063 Homosapiens     ATGTACAAGAAGTTCAAGCCACAGGGCAACATCATGGGTAAAGTGGCCAA   709       AY027496Ovis   ATGTACAAGAAGGTCCAGCCCCAGGGTAACATCATGTCTAAAGTTGCCAG   792       U13707 Oryctolaguscunic     ATGTACAAGAAGTTCAAGCCGCAGGGGAACATCCTGAGCAAAGTGGTGAA   717       SequencetosubmitGenbak   ATGTACAAGAAGTTTCAGCCCCAGGGTAATGTCATGGGTAAAGTTGTCAA   669       AY029615 Gallusgallus     ATGTACAAAAAAGTTCAACCGCAAGGCAATATAATGGTTCGAGTTTGTAA   800           ******** **  *  * ** ** ** **  * **     ***    *               D50306Rat   GTGCATTGGCTTTGCCATCAAAAACAGGTTTCGGCACCGAAGTAAGGCAT   812       NM_053079 Musmusculus     GTGCATTGGTTTTGCCATCAAAAACAGGTTTCGGCACCGAAGTAAGGCAT   794       XM_007063 Homosapiens     GTGCATCGGTTTTGCCATCAAAAATAGATTTAGGCATCGGAGTAAGGCAT   759       AY027496Ovis   GTGCATTGGGTTTGCCATCAAAAATAGGATTAGCCATCGGAGTAAGAAAT   842       U13707 Oryctolaguscunic     GTGCATCTGCTTTGCCATCAAAAATAGGTTTAGGCGCCGCAGTAAGCAGT   767       SequencetosubmitGenbak   GTGCATTGGTTTTGCCCTCAAAAATAGGTTTAGGCACCGGAGTAAGCAGT   719       AY029615 Gallusgallus     ATGCATTGGATTTGCCATTAAAAACAGGTTTCGGCATCGCAGCAAAGAGT   850            *****  * ****** * ***** **  ** * ** ** ** **    *               D50306Rat   TTCCCAAGAGGGAACACTGGCTGGACTGGGCTAAAGAGAAATACGATGAG   862       NM_053079 Musmusculus     ATCCCAAGAGGGAGCACTGGCTGGACTGGGCTAAAGAGAAATACGACGAG   844       XM_007063 Homosapiens     TTCCCAAGAGGGAGCACTGGCTGGACTGGGCTAAAGAGAAATACGATGAG   809       AY027496Ovis   TTCCTAAGAGGGAGCACTGGCTGGACTGGGCTAGCGAGAAATATGATGAG   892       U13707 Oryctolaguscunic     TTCCCAAGAGGGCGCACTGGCTGGACTGGGCTAAGGAGAAATACGACGAG   817       SequencetosubmitGenbak   TTCCCAAGAGGGAGCACTGGCTGGACTGGGCTAAAGAGAAATACGATGAG   769       AY029615 Gallusgallus     ATCCCAAAAGAGAGCACTGGCTAGACTGGGCAAGCGAGAAGTATGATAAA   900                                    *** ** ** *  ******** ******** *  ***** ** **  *               D50306Rat   AGGCTCATCTCGCAGATTAAGATGGTGACGAAGGTGATGTTCCTGTACAT   912       NM_053079Musmusculs   CGGCTCATCTCACAGATTAAGATGGTCACGAAGGTGATGTTCCTGTTCAT   894       XM_007063 Homosapiens     CGGCTCATCTCCCAAATTAAGATGGTTACGAGGGTGATGTTCCTGTATAT   859       AY027496Ovis   CGGCTCATCTCTCAAATTAAGATGGTTACAAGGGTGATGTTCCTGTACAT   942       U13707 Oryctolaguscunic     CGGCTTATCGCGCAGATCAAGATGGTTACGAGGGTGCTGTTCCTGTACAT   867       SequencetosubmitGenbak   CGGCTCATCTCTCAAATTAAGATGGTCACAAAAGTGATGTTCTTGTACAT   819       AY029615 Gallusgallus     CGACTGATTGCTCAGACCAAGATGGTGTTGAAGGTGCTTTTCCTTTACAT   950                                    * ** **  * ** *  ********    *  *** * *** * *  **               D50306Rat   TCCCCTCCCCATGTTTTGGGCCTTGTTTGACCAGCAGGGTTCCAGGTGGA   962       NM_053079 Musmusculus     CCCACTCCCCATGTTCTGGGGCCTGTTTGACCAACAAGGGTCCAGATGGA   944       XM_007063 Homosapiens     TCCACTCCCAATGTTCTGGGCCTTGTTTGACCAGCAGGGCTCCAGGTGGA   909       AY027496Ovis   TCCTCTCCCCATGTTCTGGGCCTTGTTTGATCAGCAGGGCTCCAGGTGGA   992       U13707 Oryctolaguscunic     CCCCACTCCCCATGTTCTGGGCCTTGTTTGATCAGCAGGGTTCCAGATGGA   917       SequencetosubmitGenbak   CCCACTCCCAATGTTCTGGGCCCTGTTTGACCAGCAGGGCTCCAGGTGGA   869       AY029615 Gallusgallus     CCCTCTCCCGATGTTCTGGGCACTTTTTGACCAGCAGGGATCGAGATGGA   1000                                    ** ***** ***** ****   * ***** ** ** ** ** ** ****               D50306Rat   CACTGCAAGCAACGACCATCACTGGGAAAATTGGAACAATTGAGATTCAG   1012       NM_053079 Musmusculus     CACTGCAAGCAACGACCATGAATGGGAAAATTGGAGCAAATGAAATTCAG   994       XM_007063 Homosapiens     CACTGCAGGCAACAACTATGTCCGGGAAAATCGGAGCTCTTGAAATTCAG   959       AY027496Ovis   CACTGCAAGCAACGACCATGAGTGGGAAGATTGGAATCATTGAAATCCAG   1042       U13707 Oryctolaguscunic     CGCTGCAAGCGACGACCATGTCCGGGAGAATTGGAATCCTTGAAATTCAG   967       SequencetosubmitGenbak   CACTGCAAGCAACAGCTATGAGTGGGAAAATTGGACTTCTTGAAGTTCAG   919       AY029615 Gallusgallus     CACTGCAAGCCACAACTATGGATGGGGACTTTGGAGCTATGCAGATTCAG   1050           *  *****  **  **   *  ***    ***     * ***        *   *  ***               D50306Rat CCGGACCAGATGCAGACGGTGAACGCCATCTTGATTGTCATCATGGTCCC   1062       NM_053079 Musmusculus     CCGGACCAGATGCAGACGGTGAATGCCATCCTGAATGTCAACAATGGCCC   1044       XM_007063 Homosapiens     CCCGATCAGATGCAGACCGTGAACGCCATCCTGATCGTGATCATGGTCCC   1009       AY027496Ovis   CCGGATCAGATGCAGACGGTGAACGCCATCCTGATCGTCGTCATGGTCCC   1092       U13707 Oryctolaguscunic     CCGGATCAGATGCAGACTGTGAACACCATCTTGATTATTATCCTGGTCCC   1017       SequencetosubmitGenbak   CCAGATCAGATGCAGACTGTGAATGCCATCTTGATTGTCGTCATGGTCCC   969       AY029615 Gallusgallus     CCAGACCAATGCAGACTGTCAATCCAATCCTGATTATAATAATGGTCCC   1100                                     ** ** ** ******** ** **  * *** ***   *       * ***               D50306Rat   CATTGTGGACGCCGTGGTGTATCCGCTCATTGTGGTTTCAACT   1112       NM_053079 Musmusculus     CAATGTGGACGCCGTTGTGTACCGCTCAATTGCAAAATGTGGTTTCAACT   1094       XM_007063 Homosapiens     GATCTTCGATGCTGTGCTGTACCCTCTCATTGCAAAATGTGGCTTCAATT   1059       AY027496Ovis   CATCGTGGATGCCGTGGTATATCCTCTGATCGCAAAGTGTGGTTTAAATT   1142       U13707 Oryctolaguscunic     CATCATGGACGCCGTGGTGTATCCTCTGATTGCAAAGTGTGGCCTCAACT   1067       SequencetosubmitGenbak   CATCATGGATGCCGTGGTGTACCCTCTGATTGCAAAATGTGGCTTCAATT   1019       AY029615 Gallusgallus     AGTTGTAGATGCTGTGATTTATCCTTTAATCCAGAAATGCAAGATCAATT   1150                                        * ** ** **  * ** *     **    ** **     * ** *               D50306Rat   TCACCTCCCTGAAGAAGATGACCGTTGGGATGTTCCTGGCATCCATGGCC   1162       NM_053079 Musmusculus     TCACATCCCTGAAGAAGATGACTGTTGGGATGTTCCTGGCGTCCATGGCC   1144       XM_007063 Homosapiens     TCACCTCCTTGAAGAAGATGGCAGTTGGCATGGTCCTGGCCTCCATGGCC   1109       AY027496Ovis   TCACCTCCCTGAAGAAGATGACCGTCGGCATGTTTCTGGCCTCCATGGCT   1192       U13707 Oryctolaguscunic     TCACCTCTCTGAAGAAGATGACGATTGGGATGTTCCTGGCTTCCATGGCC   1117       SequencetosubmitGenbak   TCACCTCCTTGAAGAGGATGACAGTTGGAATGTTCCTGGCTTCCATGGCC   1069       AY029615 Gallusgallus     TTACGCCCCTGAGGAGGATCACTGTTGGCATGTTCCTTGCTGGTCTGGCT   1200                                     * **  *  *** ** ***  *  * ** *** * ** **     ****               D50306Rat   TTTGTGGTGGCTGCAATTGTGCAGGTGGAAATCGATAAACTCTTCCAGT   1212       NM_053079 Musmusculus     TTTGTGGTGGCTGCAATTGTGCAGGTGGAAATCGATAAAACTCTTCCAGT   1194       XM_007063 Homosapiens     TTTGTGGTGGCTGCCATCGTGCAGGTGGAAATCGATAAAACTCTTCCAGT   1159       AY027496Ovis   TTCGTGGCAGCTGCCATCGTGCAGGTGGACATTGACAAAACTCTGCCCGT   1242       U13707 Oryctolaguscunic     TTCGTGGCAGCTGCAATCCTGCAGGTGGAAATCGATAAAACTCTTCCTGT   1167       SequencetosubmitGenbak   TTCGTGATGGCGGCGATTGTTCAGCTGGAAATTGATAAAACTCTTCCAGT   1119       AY029615 Gallusgallus     TTCGTTGCTGCTGCTCTTTTGCAAGTGCAAATAGATAAAACTCTTCCAGT   1250                                   ** **    ** **  *  * **  ** * ** ** ******** ** **               D50306Rat   CTTCCCCAGCGGAAATCAAGTTCAAATTAAGGTCTTGAACATTGGAAACA   1262       NM_053079 Musmusculus     CTTCCCTGGTGGAAATCAAGTCCAAATTAAGGTCTTGAACATCGGAAACA   1244       XM_007063 Homosapiens     CTTCCCCAAAGGAAACGAAGTCCAAATTAAAGTTTTGAATATAGGAAACA   1209       AY027496Ovis   CTTCCCCAAAGGAAATGAAGTCCAAATCAAAGTCCTGAATATAGGAAATA   1292       U13707 Oryctolaguscunic     CTTCCCCAAAGCCAATGAAGTCCAAATTAAGTTCTGAATGTAGGAAGTG   1217       SequencetosubmitGenbak   CTTCCCCAAACAAAATGAAGTCCAAATCAAAGTACTGAATATAGGAAATG   1169       AY029615 Gallusgallus     TTTCCCTGCAGCTGGACAGGCCCAAATCAAAATAATAAATCTAGGTGATA   1300                                 ****          * *  ***** **  *  * **  * **                   D50306Rat   ATGACATGGCCGTGTATTTTCCTGGAAAGAATGTGACAGTTGCCCAAATG   1312       NM_053079 Musmusculus     ATAACATGACCGTGCATTTTCCTGGAAAATAGTGTGACGCTTGCCCAAATG   1294       XM_007063 Homosapiens     ATACCATGAATATATCTCTTCCTGGAGAGATGGTGACACTTGGCCCAATG   1259       AY027496Ovis   ATAGCATGACCGTGTCTTTTCCCGGAACGACAGCAGTGACATGTGACCAGATG   1342       U13707 Oryctolaguscunic     CAGAACATGATCATCTCTCTTCCTGGGCAGACGGTGACGCTCAACCAGATG   1267       SequencetosubmitGenbak   GTGCCATGAATGTATCTTTTCCTGGAGCGGTGGTGACAGTTAGCCAAATG   1219       AY029615 Gallusgallus     GCAATGCGAATGT-TACATTTCTGCCTAATCTTCAGAACGTGACTGTCCT   1349                                             *    *     ** * *                   *                    D50306Rat   TCTCA---GACAGACACATT-CATGACTTTCGATGTAGACCAGCTGACAA   1358       NM_053079 Musmusculus     TCTCA---GACAGACACGTT-CATGACTTTCGATATAGACAAGCTGACAA   1340       XM_007063 Homosapiens     TCTCA---AACAAATGCATT-TATGACTTTTGATGTAAACAAACTGACAA   1305       AY027496Ovis   TCTCA---AACAAACGGATT-TCTGACTTTCAACGTAGACAACCT---AA   1385       U13797 Oryctolaguscunic     TCTCA---AACGAATGAATT-CATGACTTTCAATGAAGACACACTGACAA   1313       SequencetosubmitGenbak   AGTCA---ATCAGATGGATT-TATGACTTTTGATGTAGACAAACTGACAA   1265       AY029615 Gallusgallus     TCCCATGGAGTCAACAGGCTACAGGATGTGTTTGAGTCTTCCCAGCTAAAAT   1399                                      **        *     *    **  **  *      *   **   *               D50306Rat   GCATAAACGTGTCTTCTCCCGG-ATCTCCAGGCGTCACCACGGTAGCTCA   1407       NM_053079 Musmusculus     GCATAAACATATCTTCCTCTGG-ATCCCCAGGAGTCACCACAGTAGCTCA   1389       XM_007063 Homosapiens     GGATAAACATTTCTTCTCCTGG-ATCACCAG---TCACTGCTGTAACTGA   1351       AY027496Ovis   GTATAAACATTTCTTCTACTGG-AACACCAG---TCACTCCAGTAACTCA   1431       U13707 Oryctolaguscunic     GCATAACATCACTTCC-GG-ATCACAAG---TCACCATGATCACACC   1356       SequencetosubmitGenbak   GTATAAACATTTCTTCCACTGG-ATCACCAG---TCACCATGATCACACC   1311       AY029615 Gallusgallus     CTGTAATGGTAAATTTTGGGAGTGAGAGTAGAAGTGAAAATATCGACTCA   1449                                      ***   *   **      *       **   * *         *                 D50306Rat   -TGAGTTTGAGCCGGGTCACCGGCACACCCTTCTAGTGTGGGGCCCCAAT   1456       NM_053079 Musmusculus     -TGATTTTGAGCAGGGTCACCGGCACAACCTTCTAGTGTGGGAACCCAGT   1438       XM_007063 Homosapiens     -CGACTTCAAGCAGGGCCAACGCCACACGCTTCTAGTGTGGGCCCCCAAT   1400       AY027496Ovis   -TAACTTTGAGTCCGGCCATCGCCATACCCTTCTCGTCTGGGCCCCAAGT   1480       U13707 Oryctolaguscunic     -CAGCCTTGAGGCAGGCCAGCGCCACACCCTGCTGGTGTGGGCCCCCAAT   1405       SequencetosubmitGenbak   -TAACTTTGAGCAGGGCCATCGCCATACCCTTCTAGTATGGGCCCCCAAT   1360       AY029615 Gallusgallus     ATAAGCAGCAATACGCATACTGTCACCATCAAGAATGCAGCAGCCGGCAT   1499                                           *    *   *  * **    *         *    *    *               D50306Rat   CTATACCGTGTGGTAAA-AGACGGTCTTAACCAAAAGCCAGAGAAAGGGG   1505       NM_053079 Musmusculus     CAATACCGTGTGGTAAA-AGATGGTCCTAACCAAAAGCCAGAGAAAGGGG   1487       XM_007063 Homosapiens     CACTACCAGGTGGTAAA-GGATGGTCTTAACCAGAAGCCAGAAAAAGGGG   1449       AY027496Ovis   AACTACCAAGTGGTAAA-AGATGGCCTTAACCAGAAGCCAGAAAAAGGGA   1529       U13707 Oryctolaguscunic     AACTACCGAGTGGTCAA-TGACGGCCTGACCCAGAAGTCAGACAAAGGAG   1454       SequencetosubmitGenbak   AATTACCGAGTGGTAAA-GGATGGCCTTAACCAGAAGCCAGAAAAAGGAG   1409       AY029615 Gallusgallus     TGTTTCTAGCTTGCGGTCTGATAATTTCACATCAAAACCAGAAGAAGGAA   1549                                      * *    * *      **       *     **  ****  ****                D50306Rat   AGAACGGAATCAGATTCGTCAGCACCCTTAACGAGATGATCACCATCAAA   1555       NM_053079 Musmusculus     AGAACGGAATCAGGTTTGTCAACACCCTTAACGAGATGGTCACCAACAAA   1537       XM_007063 Homosapiens     AAAATGGAATCAGATTTGTAAATACTTTTAACGAGCTCATCACCATCACA   1499       AY027496Ovis   GAAATGGAATCAGATTCGTTAATGCTTTTGGCGAGAGCTTCGGCGTCACA   1579       U13707 Oryctolaguscunic     AAAATGGAATCAGGTTTGTGAACACTTACAGCCAGCCCATCAACGTCACG   1504       SequencetosubmitGenbak   AAAATGGAATCAGATTTATAAATAGTCTTAATGAGAGCCTCAACATCACC   1459       AY029615 Gallusgallus     AGAATCTAGTCAGGTTTGTAAATAATTTGCCTCAGACAGTCAACATCACT   1599                                     **   * **** **  * *            **    **  *  **                D50306Rat   ATGAGTGGAAAAGTGTACGAAAATGTCACCAGTCACAG-CGCCAGCAACT   1604       NM_053079 Musmusculus     ATGAGTGGGAAAGTATATGAAAAATTCACAAGTCACAA-CGCCAGCGGCT   1586       XM_007063 Homosapiens     ATGAGTGGGAAAGTTTATGCAAACATCAGCAGCTACAA-TGCCAGCACAT   1548       AY027496Ovis   ATGGATGGGGAAGTTTACAACAATGTCTCCGGTCACAA-TGCCAGTGAAT   1628       U13707 Oryctolaguscunic     ATGAGCGGGAAAGTTTACGAACACATCGCCAGCTACAA-TGCCAGCGAGT   1553       SequencetosubmitGenbak   ATGGGCGACAAAGTTTATGTGAATGTCACCAGTCACAA-TGCCAGCGAGT   1508       AY029G15 Gallusgallus     ATGGGTGACACGACTTTTG-GAATACTGGAAGAGACAAGTATCAGTAATT   1648                                   ***   *       *      *        *  ***     ***    *               D50306Rat   ATCAGTTTTTCCCTTCTGGCCAAAAAGACTACACAATAAACACCACAGA-   1653       NM_053079 Musmusculus     ACAAGTTCCTCCCTTCTGGCGAAAAGCAGTACACAATAAACACCACGGC-   1635       XM_007063 Homosapiens     ACCAGTTTTTTCCTTCTGGCATAAAAGGCTTCACAATAAGCTCAACAGA-   1597       AY027496Ovis   ATCTTTTTTTCTCTTCTGGCGTAAAGAGCTTCACAATAAACTCACCAGA-   1677       U13707 Oryctolaguscunic     ATCAGTTTTTCACTTCTGGAGTAAAGGGCTTCACCGTCAGCTCGGCAGG-   1602       SequencetosubmitGenbak   ATCAGTTCTTTTCTTTGGGCACAAAAAACATTACAATAAGTTCAACACAA   1558       AY029615 Gallusgallus     ACAGTCCGTTCTCAGGAGGAAGAACATATGATATAGTGATAACTGCAGG-   1697                                    *        *  *    **   **        *   *  *   *  *               D50306Rat   --GATTGCACCAAACTGTTCATCTGATTTTAAATCTTCCAACCTTGACTT   1701       NM_053079 Musmusculus     --GGTGGCACCAACCTGTCTAACTGATTTTAAATCTTCCAACCTTGACTT   1683       XM_007063 Homosapiens     --GATTCCGCCACAATGTCAACCTAATTTCAATACTTTCTACCTTGAATT   1645       AY027496Ovis   --GATTTCACAACAGTGTGAAAAACAGTTCAAAACATCCTACCTTGAATT   1725       U13707 Oryctolaguscunic     --CATCTCGGAGCAGTGCAGGCGGGACTTTGAGTCTCCGTACCTGGAGTT   1650       SequencetosubmitGenbak   CAGATCTCACAAAATTGTACAAAAGTTCTCCAATCATCCAACCTTGAATT   1608       AY029615 Gallusgallus     -----TTCAACTAATTGCAAACC-AACTTCAGAG-----AAATTAGGATA   1736                                          *       **           *           *  * *  *               D50306Rat   CGGCAGCGCGTACACCTACGTGATCAGAAGTAGGGCGAGTGATGGCTGCC   1751       NM_053079 Musmusculus     TGGCAGCGCGTATACCTACGTGATCCGA---AGGGCGAGTGATGGCTGCC   1730       XM_007063 Homosapiens     TGGTAGTGCTTATACCTATATAGTCCAA---AGGAAGAATGACAGCTGCC   1692       AY027496Ovis   TGGTAGTGCGTTTACCTATGTAATCAGC---AGAAAGAGTGACGGTTGCC   1772       U13707 Oryctolaguscunic     TGGCAGCGCGTACACGTACCTGATCACG---AGCCAGGCTACTGGCTGCC   1697       SequencetosubmitGenbak   TGGTAGTGCATATACCTATGTAATCGGA---ACGCAGAGCACTGGCTGCC   1655       AY029615 Gallusgallus     TGGTGGTGCTTATACGATCGTAATTAAT---GAGTGTTCTGGAGATGTGA   1783                                     **  * ** *  **     *  *                                        D50306Rat   TGGAAGTGAAGGAATTCGAAGACATCCCACCCAACACGGTGAACATGGCC   1801       NM_053079 Musmusculus     TGGAAGTGAAGGAATTTGAAGACATCCCACCCAACACTGTGAACATGGCT   1780       XM_007063 Homosapiens     CTGAAGTGAAGGTGTTTGAAGATATTTCAGCCAACACAGTTAACATGGCT   1742       AY027496Ovis   CCGAACCAAAGATTTTCGAAGACATCTCCCCCAACACAGTCAGCATGGCT   1822       U13707 Oryctolaguscunic     CCCAAGTGACGGAGTTTGAAGATATTCCGCCCAACACAAYHAACATGGCT   1747       SequencetosubmitGenbak   CTGAATTGCATATGTTTGAAGATATTTCACCCAACACAGTTAACATGGCT   1705       AY029615 Gallusgallus     CTCAATTAAGATACATTGAAGATATCCAACCCAATACAGTCCATATGGCT   1833                                      **          * ***** **    **** **  *    ****               D50306Rat   CTGCAGATCCCACAGTACTTCCTCCTCACCTGCGGCGAGGTGGTCTTCTC   1851       NM_053079 Musmusculus     CTGCAGATCCCACAGTACTTCCTTCTCACCTGCGGCGAGGTGGTCTTCTC   1830       XM_007063 Homosapiens     CTGCAAATCCCGCAGTATTTTCTTCTCACCTGTGGCGAAGTGGTCTTCTC   1792       AY027496Ovis   CTGCAGATCCCCCAGTACTTCCTCCTCACCTGTGGCGAGGTGGTCTTCTC   1872       U13707 Oryctolaguscunic     TGGCAAATCCCACAGTACTTCCTCATCACCTCTGGCGAGGTGGTCTTCTC   1797       SequencetosubmitGenbak   CTGCAGATCCCGCAGTACTTCCTCATCACCTGCGGCGAGGTGGTTTTCTC   1755       AY029615 Gallusgallus     TGGCAGATCCCTCAGTATTTCATACTTACATGTGGAGAAGTAGTCTTCTC   1883                                     *** ***** ***** **  *  * ** *  ** ** ** ** *****               D50306Rat   TGTCACAGGACTGGAGTTCTCCTATTCCCAGGCCCCGTCTAACATGAAGT   1901       NM_053079 Musmusculus     TGTCACAGGACTGGAGTTCTCTTATTCCCAGGCTCCGTCTAACATGAAGT   1880       XM_007063 Homosapiens     TGTCACGGGATTGGAATTCTCATATTCTCAGGCTCCTTCCAACATGAAGT   1842       AY027496Ovis   CATCACCGGCCTGGAGTTCTCCTATTCTCAGGCTCCTTCCAACATGAAGT   1922       U13707 Oryctolaguscunic     CATCACGGGCCTGGAGTTCTCCTATTCTCAGGCTCCTTCCAACATGAAGT   1847       SequencetosubmitGenbak   TGTCACAGGACTGGAGTTCTCATATTCTCAGGCCCCCTCCAACATGAAGT   1805       AY029615 Gallusgallus     TGTCACTGGGCTGGAGTTTTCATACTCACAGGCACCATCTAATATGAAGT   1933                                     **** **  **** ** ** ** ** ***** ** ** ** *******               D50306Rat   CCGTGCTTCAGGCAGOATGGCTTCTAACCGTGGCCATCGGTAATATCATT   1951       NM_053079 Musmusculus     CCGTGCTTCAGGCAGGCTGGCTTCTAACTGTGGCGGTCGGCAATATCATT   1930       XM_007063 Homosapiens     CGGTGCTTCAGGCAGGATGGCTGCTGACCGTGGCTGTTGGCAACATCATT   1892       AY027496Ovis   CGGTACTTCAGGCAGGATGGCTGTTGACCGTGGCCGTTGGCAACATCATC   1972       U13707 Oryctolaguscunic     CGGTGCTGCAGGACCGGTGGCTGCTGACGGTGGCTGTGGGCAACATCATT   1897       SequencetosubmitGenbak   CGGTGCTTCAGGCGGGATGGCTGCTGACAGTGGCT---------------   1840       AY029615 Gallusgallus     CAGTGCTGCAAGCAGGATGGCTGCTAACAGTGGCTGTCGCATAACATAATT   1983                                   * ** ** ** *  * *****  * ** *****                              D50306Rat   GTCCTCATTGTGGCTGAGGCAGGCCACTTCGACAAACAGTGGGCTGAGTA   2001       NM_053079 Musmusculus     GTGCTCATCGTGGCAGGGGCGGGGCACTTCCCCAAACAGTGGGCTGAGTA   1980       XM_007063 Homosapiens     GTGCTCATCGTGGCAGGGGCAGGCCAGTTCAGCAAACAGTGGGCCGAGTA   1942       AY027496Ovis   GTGCTTATTGTGGCAGGAGCAGGCCAGTTCAGTGAACAGTGGGCCCAGTA   2022       U13707 Oryctolaguscunic     GTGCTCATCGTGGCCGGCGCGGGCCAGATCAACAAGCAGTGGGCCGAGTA   1947       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     GTCCTTATCGTGGCTGGAGCATCCAAACTCAGTGAGCAGTGGGCAGAATA   2033               D50306Rat   TGTTCTGTTCGCCTCCTTGCTCCTGGTCGTCTGCATCATATTTGCCATTA   2051       NM_053079 Musmusculus     CATTCTGTTTGCCTCATTGCTTCTGGTTGTCTGCGTGATATTCGCCATCA   2030       XM_007063 Homosapiens     CATTCTATTTGCCGCGTTGCTTCTGGTCGTCTCTGTGTAATTTTTGCCATCA   1992       AY027496Ovis   CGTTCTGTTTGCGGCATTGCTTCTGGTCGTCTGTGTAATATTTGCCATCA   2072       U13707 Oryctolaguscunic     CATCCTCTTTGCCGCCCTGCTCCTGGTCGTCGTCATATTTGCCATCA   1997       SequencetosubmitGenbak   -----------------------------------------------       AY029615 Gallusgallus     TGTTCTCTTTGCTGCCTTGCTTTTTGCAGTTTGCATTATTTTTGCTGTCA   2083               D50306Rat   TGGCCCGATTCTACACCTACATCAACCCAGCAGAGATCGAGGCACAGTTC   2101       NM_053079 Musmusculus     TGGCTCGATTCTACACCTACATCAACCCAGCAGAGATTGAAGCACAGTTT   2080       XM_007063 Homosapiens     TGGCTCGGTTCTATACTTACATCAACCCAGCGGAGATCGAAGCTCAATTT   2042       AY027496Ovis   TGGCTCGATTCTATACGTATGTCAACCCCGCAGAGATTGAAGCTCAGTTT   2122       U13707 Oryctolaguscunic     TGGCTCGATTCTATACGTATGTCAACCCGGCCGAGATCGAGGCTCAGTTT   2047       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     TGGCATATTTTTATACATATACTGATCCAAATGAGGTTGAAGCCCGGCTT   2133               D50306Rat   GATGAGGATGAGAAGAAAAAGGGCGTAGGGAAGGAA---AACCCGTATTC   2148       NM_053079 Musmusculus     GATGAGGATGAGAAGAAAAAGGGCATAGGAAAGGAA---AACCCGTATTC   2127       XM_007063 Homosapiens     GATGAGGATGAAAAGAAAAACAGACTGGAAAAGAGT---AACCCATATTT   2089       AY027496Ovis   GATGAGGATGACAAGGAGGATGACCTGGAAAAGAGT---AACCCATACGC   2169       U13707 Oryctolaguscunic     GAAGAAGATGAGAAGAAAAAGAACCCAGAAAAGAAC-GACCTCTACCC   2094       SequencetosubmitGenbak   ------------------------------------------------       AY029615 Gallusgallus     GATGAAGAAGAAAAGAAAGAAACAAATAAAACAGGATCCAGACTTGCACGG   2183               D50306Rat   CTCG---TTGGAACCTGTCTCACAGACAAACATGTGAAGATCAGAAAGCA   2195       NM_053079 Musmusculus     TTCA---TTGGAACCAGTCTCACAGACAAATATGTGAAGGGCAGAAGGCA   2174       XM_007063 Homosapiens     CATG---TCAGGGGCCAATTCACAGPAACAGATGTGAAGGTCAGGAGGCA   2136       AY027496Ovis   CAAG---CTGGACTTCGTCTCACAGACACAAATGTGAATGTCAGGAAGCA   2216       U13707 Oryctolaguscunic     CTCC---GTGGCGCCCGTCTCACAGACACACAGATGTGA--GTCTGGAGGCG   2139       SequencetosubmitGenbak   ----------------------------------------------------       AY029615 Gallusgallus     AAAAGAATCTGAAGCTGTCTCTCAGATGTAGAAG-GTGTATTCAAGAGCA   2232               D50306Rat   AGTGGAGAACATACCAAGTC--CAGCATTCACCATGACCTCTGCCC--AA   2241       NM_053079 Musmusculus     AATTGGAGAAAGATCAAGTT--CAACATGAGCCCTGACCTCTGTCC--AA   2220       XM_007063 Homosapiens     AGTGGAGGATGGACTGGGCC--C-GCAGATGCCCTGACCTCTGCCCCCAG   2183       AY027496Ovis   AGCGGACGC-GGGGCTGGGC--CAGGGTGTGCCCAGGGGTCTGTCCCATG   2263       U13707 Oryctolaguscunic     -GTGTAGGA-GGCCCACGCC--TGGCGTGCACTGTGACCTCTGTCCGA-G   2184       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     TTTGTAAATCATGGTAGCCTGTTAACTGTCCCTGCAATAACAGGAATCAG   2282               D50306Rat   GGGACAGGACCCTCCACCACAGAGTCCTTGCTGGAGAAAGACTTCAGACA   2291       NM_053079 Musmusculus     GGGACAGGACACTCCACCACAGAGTCCCTGATGGAGAAAGACCTCAGAAG   2270       XM_007063 Homosapiens     GTAGCAGGACACTCCATTGGATGGCCCCTGATG-AGGAAGACTTCAGAAT   2232       AY027496Ovis   GGGGCAGGACACTCTGTTGGGTGGCCTCTGATG-GGGAAGACTTCAGAAC   2312       U13707 Oryctolaguscunic     GGCGCAGGACGTACCCCTGGGCAGCCCCGGAAG-GGGAGGACTTGAGAAC   2233       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     GGTATTGCTGACATCACTGGGTAATATACCTTGTGGGAGAGACTAAGAAA   2332               D50306Rat   TGTGAGCCAAAATAATAACAAAGCAGGTTTTCAGGCTGACGGCTGTGAAT   2341       NM_053079 Musmusculus     TGTGAGCCAGAATAATAACAAAGCAGGTTTTCTAACCAACAGCTGTGAAC   2320       XM_007063 Homosapiens     TGGGAACTAAACCATGAATGC--TATTTTCTTTTTTCTTTTTCTTTTCTT   2280       AY027496Ovis   TGTGGACCAAACCAAGACAGC--TGCTTTCTC-AGCAGCCGGCAATGAAC   2359       U13707 Oryctolaguscunic     TGTGAACCAGACCACGAAAGC--TATGTTCTG-AGCAGCCAGTGATGAGT   2280       SequencetosubmitGenbak   --------------------------------------------------       AY029G15 Gallusgallus     CACTGTTCTGACTTAACATAC--AGCCTCTTGGGAAGCAAGACGAAATG   2379               D50306Rat   CTGAAACTCTAGGGGAGCCTTTTT------------------------------------   2365       NM_053079 Musmusculus     CTGAAACTCTAGGGGAGCCTTTTTTATTTAAAAAAATTTTTTTTTTAATT   2370       XM_007063 Homosapiens     TTTTTTTTTT-------TTTTTTTTTTTGAGACAGAGTTTTGCTCTTGTT   2323       AY027496Ovis   CTGAAACTCCAAAAGACGTCCTTTT--------------------------   2384       U13707 Oryctolaguscunic     CCAAAACTCTGAAAGAAATCTTGTT-------------------------   2305       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     ATTAATCTCTTGTACAGAAGCTGGC-------------------------   2404               D50306Rat   ---------------------------------------------------       NM_053079 Musmusculus     TTTTAAATTTTTTTTATTTTTATTTTTTTTTCGTTGTTTGTTTGTTTCGA   2420       XM_007063 Homosapiens     GTCCAGGCTGGAGTGCAATGGCACGATCTCAGCTCACTGC---------A   2364       AY027496Ovis   --------------------------------------------------       U13707 Oryctolaguscunic     --------------------------------------------------       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     --------------------------------------------------               D50306Rat   --------------------------------------------------       NM_053079 Musmusculus     GACAGGGTTTCTCGTGTGTAGCCCTTGGTTGTCCTGGAACTCACTCTGTA   2470       XM_007063 Homosapiens     ACCTCCGCCTCCCAGGTTCAAGTAATTCTCCTGCCTCAGCCTCCCGAGTG   2414       AY027496Ovis   --------------------------------------------------       U13707 Oryctolaguscunic     --------------------------------------------------       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     --------------------------------------------------               D50306Rat   --------------------------------------------------       NM_053079 Musmusculus     GACCAGACTGGCCTCAAACTCAGAAATCCACCTGCCCCTGCCCCTGCCCC   2520       XM_007063 Homosapiens     GCTGGGATTAGCGGCA----------------------------------   2430       AY027496Ovis   --------------------------------------------------       U13707 Oryctolaguscunic     --------------------------------------------------       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     --------------------------------------------------               D50306Rat   --------------------------------------------------       NM_053079 Musmusculus     TGCCCCTGCCCCTGCCCCTGCCTCTGCCTCTGCCTCCCAAGTGCTGGATT   2570       XM_007063 Homosapiens     ------TGCACCACCACGCCCAGCTATTTTTGTATTTTTAGTAGAGAT--   2472       AY027496Ovis   --------------------------------------------------       U13707 Oryctolaguscunic     ---------------------------------------------------       SequencetosubmitGenbak   ---------------------------------------------------       AY029615 Gallusgallus     --------------------------------------------------               D50306Rat   -----------------------------AATTTGTTTTTCTTGAGACAA   2386       NM_053079 Musmusculus     TGGAGGCATGCACCACCATGCCCAGCTATAATTTTTTTTTTTTAAGACAG   2620       XM_007063 Homosapiens     ---GGGGTTTCACCATGTTGGCCAGG-ATGGTCTCGATCTCTTGACCTGG   2518       AY027496Ovis   --------------------------------------------------       U13707 Oryctolaguscunic     ---------------------------------------------------       SequencetosubmitGenbak   ---------------------------------------------------       AY029615 Gallusgallus     ---------------------------------------------------               D50306Rat   GGTATCTCTGTGTAACCCTGGCTATCCTGGAACTCACTCTATAGACCAGG   2436       NM_053079 Musmusculus     GGATTCTCTGTATAAGCCTGACTGCCCTGCAACTTGCTCTATAGACCAGG   2670       XM_007063 Homosapiens     TGA---TCTGCCCACCTCGGCCTGCCAAAGTGCTGGGATTACAGGCTTGA   2565       AY027496Ovis   ---------------------------------------------------       U13707 Oryctolaguscunic     ---------------------------------------------------       SequencetosubmitGenbak   ---------------------------------------------------       AY029615 Gallusgallus     --------------------------ATCCTGAGGAAACTCCTGCAGAATTTG   2431               D50306Rat   CTGGCCTCGAACTCACAGATATCTGTCTGTCTGCCTCTGCCTCCTAAGTACTGG   2486       NM_053079 Musmusculus     CTGGCCTTGAACTCACAGAGATCTGCCTGCCTGCCTCTTCCTCCTAAGTACTGG   2720       XM_007063 Homosapiens     GCTACCGCGCCCGGCCGTGAACGCTATTTTCTAAGCAGCC--AGCAGTGA   2613       AY027496Ovis   ------------------------GTTTGTTTGTTTTTAG--AGAAGTCT   2408       U13707 Oryctolaguscunic     ------------------------G------------------AAAGTCT   2313       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     CACTCTTAAAATGTACCTCAAGCTCAATACCATAGCATAA-AAATATTGA   2480               D50306Rat   GATTCAAGGCATGTACGGCAACTGCCCAGCTAAAATATTATTTATAACAT   2536       NM_053079 Musmusculus     GATTTCAGGCATGCACCACAACTGCCCAGCTAAAATATTATTTATAATAT   2770       XM_007063 Homosapiens     ATCTAAAACTCTGGAAGAAGTCTTCTGTTTGAAAGGCTTATTTAAGCCAC   2663       AY027496Ovis   TATTTAAAGCGCACAC-ACACGCACACGCACACA-------------CAT   2444       U13707 Oryctolaguscunic     TATTTAAAACACACAC-ACACACACACACACACA-------------CAC   2349       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     AATTGCACTTGGCACTATTAGACACTCTAAAAAGATGTATTTT----TAT   2526               D50306Rat   GCACTTTCTGGGTTTTTTGTTTTTAAAACATACTTTTTTTTTTAACACTG   2586       NM_053079 Musmusculus     GCACTTTCTGG----TTTGTTTTTG--------TTTTTCTTTTAA-ACTG   2807       XM_007063 Homosapiens     ACGTACACACA-----CTGTCTTAGA-------GTACTGTGAGCCCACCC   2701       AY027496Ovis   GCACACACACA------CACTTTTAT----------AAGAGTCCATACTC   2478        U13707 Oryctolaguscunic     ACACACTTTTC------CAACACTG------------ACAGCCTAC---C   2378       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     ACTGTATTTCAATTTTATAATGTGGAGGGGTGGGGAAAAAGGTGTTGCCA   2576               D50306Rat   GGCCATTTCTAACATTTCTGCCACAGAAGTGGATTTAGCTCAGATTAA--   2634       NM_053079 Musmusculus     GGCTGTATCTTACATTTCTGCCACAGAAATGAACTTAGCTCAGATTAACT   2857       XM_007063 Homosapiens     CACATTGGTCATCTTCCCTATCACACAAATGATGTTATTTTGGACTAGCT   2751       AY027496Ovis   TGCCTGAACTCCTTTTCCTAACACACAAATAAAGTTATTTTGGACTAACT   2528       U13707 Oryctolaguscunic     CATGTTAACTCCTTCTCTACCAATGCAAATGCTGTTATTTTGGACTAACT   2428       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     AGAAATAGTAATTGAAGCCAAACTGTCTGCGTGACCCTTCTAGCCTCACT   2626               D50306Rat   -----TTTTGAAAAGGTAACAGTACTGTTTTTTT-----------TCCTT   2668       NM_053079 Musmusculus     T--AATTTTGAAAAGGCAATAGTATTGTTTTTT---------------CT   2890       XM_007063 Homosapiens     T--AATTTTGAAATGGTAACAAAGTTTCCTACTGTTCATTTCT   2799       AY027496Ovis   TGAATTTTTGAAATGGTGGCCAAGCTCCATACGT-----------GCATT   2567       U13707 Oryctolaguscunic     T-AATTTTGAACACTGTT-CTATGTTGCTTGTAT-----------TC--T   2463       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     GTTACTTGAAAGCAGGTCAC-ATGTGCCTTAAATT---------CTTTTC   2666               D50306Rat   AATGCTCTTA-TGAAAACAATGTTGAA-----------------TTTACA   2700       NM_053079 Musmusculus     AACAGTTTTA-TGAAAACAATATTGAA-----------------TTTACA   2922       XM_007063 Homosapiens     AATACTCTTA-CGAAAACTATTCTAAAGGAGGCAGGAGCCAAGGCCAAAA   2848       AY027496Ovis   CGCACACTCTGTGCAAACAATGTTAAAGGAGGCAAAAAGTGA----ATGG   2613       U13707 Oryctolaguscunic     AACATCCTTAGGAAAGGCAATGTTAAGAGAGGCAGGAGGCAATGCCAAAG   2513       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     TATGTCCTTA---AGAATAATAGGAGAAAG----------------GTTC   2697               D50306Rat   GAGGGCTT-------TTTTAGCAGTGTGTAGTGAGTGTCAGCTGATTCGA   2743       NM_053079 Musmusculus     GAGGGCTT-------TTTTAATAGTGTGTAATGAGTATCAACTGATTCAA   2965       XM_007063 Homosapiens     GTGAACGTACAGG--TTTGAAATGGCTGTGATAAGGACCAGCTGGTATTA   2896       AY027496Ovis   TTGGGGCTTTTGA-ATAGTACGTGTTCATAATAAGGACCGGCTGGTATTA   2662       U13707 Oryctolaguscunic     TTGAATATGTAGGTGTCAGAATGGTATATACCACATATTACTTAGTATTA   2563       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     TTAGATTTC------TCAGATTAAAATGT-CTCTGCTCCACATAGCAGGA   2740               D50306Rat   GCTAATAACCTTACCTCGGGGTTTTT----------------------GT   2771       NM_053079 Musmusculus     GCTAATTGCTTTACCTTGGGGTTTTTTTGTTTGTTTGTTTGTTTGTTTGT   3015       XM_007063 Homosapiens     ACTGATAACTTTACCTTTGGGTTTTT----------------------GT   2924       AY027496Ovis   ACTGATAACTCTACCTTCTGTTTTTA-----------------------   2688       U13707 Oryctolaguscunic     ACTGAAAACCTCAACTTTGAGGTTTT----------------------   2589       SequencetosubmitGenbak   ------------------------------------------------       AY029615 Gallusgallus     ACTTGGACATGCACTGTGATGTGCTT----------------------T   2767               D50306Rat   TTCTTTGTTTTCCTGGTCTCCTTTGCCTGACCTCTTTTTAAATTATGTGT   2821       NM_053079 Musmusculus     TTGTTTGTTTTTCTAGTCTCCTTTGCCTTACCTCTTTTTAAATTATGTGT   3065       XM_007063 Homosapiens     TATTTTGTTTTTCTAGTCCCT--------ACCTGTGTTTAAATTATGGAT   2966       AY027496Ovis   -GTTCTGTTTTT-CCATTCCCT-------ACCTCTTTGTAAATTATGGAT   2729       U13707 Oryctolaguscunic     -GTTCTATTTTTTCCACTCCTT-------ACCTCTTTTTAACCTGTGGAC   2631       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     ATGTGCCTATTATTAACTGCCCATTGGTATGTTCTTAATTAATTGTGT-T   2816               D50306Rat   AA---TTCAAAAGACTATTCAAGTGAT-GGTTAGTCATGAGTCGT--GAC   2865       NM_053079 Musmusculus     AA---TTCAAAAGACTA----------------GTCATGAGTTGT--GAA   3094       XM_007063 Homosapiens     AA---CTCGAAAGACAGCTCAGGTGAA-GGCCAGTAATGATTTTTTTGAA   3012       AY027496Ovis   TAACCTTTGAAAAACCACTCAGGTAAA-GGCAAGTCATGATTTTT-GGA   2776       U13707 Oryctolaguscunic     AA--CTCAAAAGGACCACTCAGATAAA-GGCCAGTAAAGATTTTT--TTT   2676       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     AA----TGGGATGTCCACTGAGGTGAACAGACAATGGCAAATTATATTTT   2862               D50306Rat   GTTTGACTGGTGTGAAGTAAATTCTTGTTCTTAAG---------------   2900       NM_053079 Musmusculus     GTTTCACTGGTCTGAAATAAATTCTAGTTCTTAA----------------   3128       XM_007063 Homosapiens     GTTTCAATGGTGTGAAATAAATTTCTGTTCTTA-----------------   3045       AY027496Ovis   GTCTCAACGGTATGAAATAAACTCTCATTCTCAAGAAAAAAAAAAAAAAA   2826       U13707 Oryctolaguscunic     GCCGTTTTG--ATGAAATAAAATAATGTTCCTAAG---------------   2709       SequencetosubmitGenbak   --------------------------------------------------       AY029615 Gallusgallus     GAATAACCACCAAGAATAAAACTTGTGTTGTAACAAAAAAAAAAAAAAAA   2912               D50306Rat   ---       NM_053079 Musmusculus     ---       XM_007063 Homosapiens     ---       AY027496Ovis   AAA   2829       U13707 Oryctolaguscunic     ---       SequencetosubmitGenbak   ---       AY029615 Gallusgallus     AA-   2914                    Alignment of Nucleotides Full Length Sequence of Canine and Human                Sequence 1: SequencetosubmitGenbank   1840 bp                   Sequence 2: XM_0070G3 Homosapiens     3045 bp                    Start of Pairwise alignments                   Aligning. . .                Sequences (1:2) Aligned. Score: 85               Guide tree file created:               [/net/nfs0/vol1/production/w3nobody/tmp/305133.38341-239044.dnd]               Start of Multiple Alignment               There are 1 groups               Aligning. . .                Group 1: Sequences: 2 Score:31290               Alignment Score 10725               CLUSTAL-Alignment file created               [/net/nfs0/vol1/production/w3nobody/tmp/305133.88341-239044.aln]               Your Multiple Sequence Alignment:               305133.88341-239044.aln               CLUSTAL W (1.81) multiple sequence alignment                    (SEQ ID NO:7)                SequencetosubmitGenbank   ----------------------------------------CATCTTCTTC   10                        (SEQ ID NO:1)                XM_007063 Homosapiens     GAATGTCCAAATCACACAGTTTCTTTGGTTATCCCCTGAGCATCTTCTTC   50                                                   **********               SequencetosubmitGenbank   ATCGTGGTCAATGAGTTCTGTGAAAGATTTTCCTACTATGGAATGAGAGC   60       XM_007063 Homosapiens     ATCGTGGTCAATGAGTTTTGCGAAAGATTTTCCTACTATGGAATGCGAGC   100                                   ***************** ** ************************ ****               SequencetosubmitGenbank   ACTCCTGATTCTGTACTTCAGACGGTTCATCGGGTGGGACGATAATCTGT   110       XM_007063 Homosapiens     AATCCTGATTCTGTACTTCACAAATTTCATCAGCTGGGATGATAACCTGT   150                                   * ****************** *   ****** * ***** ***** ****               SequencetosubmitGenbank   CCACGGCCATCTACCACACGTTTGTGGCTCTGTGCTACCTGACGCCGATC   160       XM_007063 Homosapiens     CCACCGCCATCTACCATACGTTTGTGGCTCTGTGCTACCTGACGCCAATT   200                                   **** *********** ***************************** **               SequencetosubmitGenbank   CTCGGCGCACTGATCGCAGACTCCTGGCTGGGAAAGTTCAAGACAATCGT   210       XM_007063 Homosapiens     CTCGGAGCTCTTATCGCCGACTCGTGGCTGGGAAAGTTCAAGACCATTGT   250                                    ***** ** ** ***** ***** ******************** ** **               SequencetosubmitGenbank   GTCACTCTCCATTGTCTACACAATTGGACAGGTCACTGCAGTAAGCT   260       XM_007063 Homosapiens     GTCGCTCTCCATTGTCTACACAATTGGACAAGCAGTCACCTCAGTAAGCT   300                                    *** ************************** ** *****  *********               SequencetosubmitGenbank   CAATTAATGACCTCACAGACTATAACAAAGATGGAACTCCTGACAATCTG   310       XM_007063 Homosapiens     CCATTAATGACCTCACAGACCACAACCATGATGGCACCCCCGACAGCCTT   350                                   * ****************** * *** * ***** ** ** ****  **               SequencetosubmitGenbank   TCCGTGCATGTGGCACTGTCCATGATTGGCCTGGCCCTGATAGCTCTGGG   360       XM_007063 Homosapiens     CCTGTGCACGTGGTGCTGTCCTTGATCGGCCTGGCCCTGATAGCTCTCGG   400                                   * ***** ****  ****** **** *********************** **               SequencetosubmitGenbank   AACTGGAGGAATAAAGCCCTGTGTGTCTGCATTTGGTGGAGACCAGTTTG   410       XM_007063 Homosapiens     GACTGGAGGAATCAAACCCTGTGTGTCTGCGTTTGGTGGAGATCAGTTTG   450                                    *********** ** ************** *********** *******               SequencetosubmitGenbank   AAGAGGGCCAGGAAAAACAAAGAAACAGATTCTTTTCCATCTTTTATTTG   450       XM_007063 Homosapiens     AAGAGGGCCAGGAGAAACAAAGAAACAGATTTTTTTCCATCTTTTACTTG   500                                   ************* ***************** ************** ***               SequencetosubmitGenbank   GCCATTAATGCTGGAAGCTTGATTTCCACTATTGTCACTCCCATGCTCAG   510       XM_007063 Homosapiens     GCTATTAATGCTGGAAGTTTGCTTTCCACAATCATCACACCCATGCTCAG   550                                   ** ************** *** ******* **  **** ***********               SequencetosubmitGenbank   AGTTCACGAATGTGGAATTTACAGTCAGAAAGCTTGTTACCCACTGGCAT   560       XM_007063 Homosapiens     AGTTCAACAATGTGGAATTCACAGTAAACAAGCTTGTTACCCACTGGCCT   600                                   ******  *********** ***** *  ******************* *               SequencetosubmitGenbank   TTGGGGTTCCTGCTGCTCTCATGGCCGTATCTCTGATTGTATTTGTCATT   610       XM_007063 Homosapiens     TTGGGGTTCCTGCTGCTCTCATGGCTGTAGCCCTGATTGTGTTTGTCCTT   650                                   ************************* *** * ******** ****** **               SequencetosubmitGenbank   GGCAGTGGAATGTACAAGAAGTTTCAGCCCAGGGTAATGTCATGGGTAA   660       XM_007063 Homosapiens     GGCAGTGGGATGTACAAGAAGTTCAAGCCACAGGGCAACATCATGGGTAA   700                                   ******** **************  **** ***** **  **********               SequencetosubmitGenbank   AGTTGTCAAGTGCATTGGTTTTGCCCTCAAAAATAGGTTTAGGCACCGGA   710       XM_007063 Homosapiens     AGTGGCCAAGTGCATCGGTTTTGCCATCAAAAATAGATTTAGGCATCGGA   750                                   *** * ********* ********* ********** ******** ****               SequencetosubmitGenbank   GTAAGCAGTTTCCCAAGAGGGAGCACTGGCTGGACTGGGCTAAAGAGAAA   760       XM_007063 Homosapiens     GTAAGGCATTTCCCAAGAGGGAGCACTGGCTGGACTGGGCTAAAGAGAAA   800                                   *****   ******************************************               SequencetosubmitGenbank   TACGATGAGCGGCTCATCTCTCAAATTAAGATGGTCACAAAAGTGATGTT   810       XM_007063 Homosapiens     TACGATGAGCGGCTCATCTCCCAAATTAAGATGGTTACGAGGGTGATGTT   850                                   ******************** ***************** ** *  ********               SequencetosubmitGenbank   CTTGTACATCCCACTCCCAATGTTCTGGGCCCTGTTTGACCAGCAGGGCT   860       XM_007063 Homosapiens     CCTGTATATTCCACTCCCAATGTTCTGGGCCTTGTTTGACCAGCAGGGCT   900                                   * **** ** ********************* ******************               SequencetosubmitGenbank   CCAGGTGGACACTGCAAGCAACAGCTATGAGTGGGAAAATTGGACTTCTT   910       XM_007063 Homosapiens     CCAGGTGGACACTGCAGGCAACAACTATGTCCGGGAAAATCGGAGCTCTT   950                                   **************** ****** *****   ******** *** ****               SequencetosubmitGenbank   GAAGTTCAGCCAGATCAGATGCAGACTGTGAATGCCATCTTGATTGTCGT   960       XM_007063 Homosapiens     GAAATTCAGCCCGATCAGATGCAGACCGTGAACGCCATCCTGATCGTGAT   1000                                   *** ******* ************** ***** ****** **** **  *               SequencetosubmitGenbank   CATGGTCCCCATCATGGATGCCGTGGTGTACCCTCTGATTGCAAAATGTG   1010       XM_007063 Homosapiens     CATGGTCCCGATCTTCGATGCTGTGCTGTACCCTCTCATTGCAAAATGTG   1050                                   ********* *** * ***** *** ********** *************               SequencetosubmitGenbank   GCTTCAATTTCACCTCCTTGAAGAGGATGACAGTTGGAATGTTCCTGGCT   1060       XM_007063 Homosapiens     GCTTCAATTTCACCTCCTTGAAGAAGATGGCAGTTGGCATGGTCCTGGCC   1100                                   ************************ **** ******* *** *******               SequencetosubmitGenbank   TCCATGGCCTTCGTGATGGCGGCGATTGTTCAGCTGGAAATTGATAAAAC   1110       XM_007063 Homosapiens     TCCATGGCCTTTGTGGTGGCTGCCATCGTGCAGGTGGAAATCGATAAAAC   1150                                   *************** *** **** ** ** ** *** ******* ********               SequencetosubmitGenbank   TCTTCCAGTCTTCCCCAAACAAAATGAAGTCCAAATCAAAGTACTGAATA   1160       XM_007063 Homosapiens     TCTTCCAGTCTTCCCCAAAGGAAACGAAGTCCAAATTAAAGTTTTGAATA   1200                                   *******************  *** *********** *****   ******               SequencetosubmitGenbank   TAGGAAATGGTGCCATGAATGTATCTTTTCCTGGAGCGGTGGTGACAGTT   1210       XM_007063 Homosapiens     TAGGAAACAATACCATGAATATATCTCTTCCTGGAGAGATGGTGACACTT   1250                                   *******   * ******** ***** ********* * ******** **               SequencetosubmitGenbank   AGCCAAATGAGTCAATCAGATGGATTTATGACTTTTGATGTAGACAAACT   1260       XM_007063 Homosapiens     GGCCCAATGTCTCAAACAAATGCATTTATGACTTTTGATGTAAACAAACT   1300                                    *** ****  **** ** *** ******************* *******               SequencetosubmitGenbank   GACAAGTATAAACATTTCTTCCACTGGATCACCAGTCATTCCAGTGACTT   1310       XM_007063 Homosapiens     GACAAGGATAAACATTTCTTCTCCTGGATCACCAGTCACTGCTGTAACTG   1350                                   ****** **************  *************** * * ** ***                SequencetosubmitGenbank   ATAACTTTGAGCAGGGCCATCGCCATACCCTTCTAGTATGGGCCCCCAAT   1360       XM_007063 Homosapiens     ACGACTTCAAGCAGGGCCAACGCCACACGCTTCTAGTGTGGGCCCCCAAT   1400                                   *  ****  ********** ***** ** ******** ************               SequencetosubmitGenbank   AATTACCGAGTGGTAAAGGATGGCCTTAACCAGAAGCCAGAAAAAGGAGA   1410       XM_007063 Homosapiens     CACTACCAGGTGGTAAAGGATGGTCTTAACCAGAAGCCAGAAAAAGGGGA   1450                                    * ****  ************** *********************** **               SequencetosubmitGenbank   AAATGGAATCAGATTTATAAATAGTCTTAATCTTAATGAGAGCCTCAACATCACCA   1460       XM_007063 Homosapiens     AAATGGAATCAGATTTGTAAATACTTTTAACGACGCTCATCACCATCACAA   1500                                   **************** ****** * **** ***  * *** ****** *               SequencetosubmitGenbank   TGGGCGACAAAGTTTATGTGAATGTCACCAGTCACAATGCCAGCGAGTAT   1510       XM_007063 Homosapiens     TGAGTGGGAAAGTTTATGCAAACATCAGCAGCTACAATGCCAGCACATAC   1550                                   ** * *  **********  **  *** ***  ***********   **               SequencetosubmitGenbank   CAGTTCTTTTCTTTGGGCACAAAAAACATTACAATAAGTTCAACACAACA   1560       XM_007063 Homosapiens     CAGTTTTTTCCTTCTGGCATAAAAGGCTTCACAATAAGCTCAACAT---A   1597                                   ***** *** ***  **** ****  * * ******** ******    *               SequencetosubmitGenbank   GATCTCACAAAATTGTACAAAAGTTCTCCAATCATCCAACCTTGAATTTG   1610       XM_007063 Homosapiens     GATTCCGCCACAATGTCAACCTAATTTCAATACTTTCTACCTTGAATTTG   1647                                   ***  * * * * ***  *     * ** *  * * * ************               SequencetosubmitGenbank   GTAGTGCATATACCTATGTAATCGGAACGCAGAGCACTGGCTGCCCTGAA   1660       XM_007063 Homosapiens     GTAGTGCTTATACCTATATAGTCCAAAGGAAGAATGACAGCTGCCCTGAA   1697                                   ******* ********* ** **  ** * ***      ***********               SequencetosubmitGenbank   TTGCATATGTTTGAAGATATTTCACCCAACACAGTTAACATGGCTCTGCA   1710       XM_007063 Homosapiens     GTGAAGGTGTTTGAAGATATTTCAGCCAACACAGTTAACATGGCTCTGCA   1747                                    ** *  ***************** *************************               SequencetosubmitGenbank   GATCCCGCAGTACTTCCTCATCACCTGCGGCGAGGTGGTTTTCTCTGTCA   1760       XM_007063 Homosapiens     AATCCCGCAGTATTTTCTTCTCACCTGTGGCGAAGTGGTCTTCTCTGTCA   1797                                    *********** ** **  ******* ***** ***** **********               SequencetosubmitGenbank   CAGGACTGGAGTTCTCATATTCTCAGGCCCCCTCCAACATGAATCGGTG   1810       XM_007063 Homosapiens     CGGGATTGGAATTCTCATATTCTCAGGCTCCTTCCAACATGAAGTCGGTG   1847                                   * *** **** ***************** ** ******************               SequencetosubmitGenbank   CTTCAGGCGGGATGGCTGCTGACAGTGGCT--------------------   1840       XM_007063 Homosapiens     CTTCAGGCAGGATGGCTGCTGACCGTGGCTGTTGGCAACATCATTGTGCT   1987                                   ******** ************** ******                                   SequencetosubmitGenbank   --------------------------------------------------       XM_007063 Homosapiens     CATCGTGGCAGGGGCAGGCCAGTTCAGCAAACAGTGGGCCGAGTACATTC   1947               SequencetosubmitGenbank   --------------------------------------------------       XM_007063 Homosapiens     TATTTGCCGCGTTGCTTCTGGTCGTCTGTGTAATTTTTGCCATCATGGCT   1997               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     CGGTTCTATACTTACATCAACCCAGCGGAGATCGAAGCTCAATTTGATGA   2047               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     GGATGAAAAGAAAAACAGACTGGAAAAGAGTAACCCATATTTCATGTCAG   2097               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     GGGCCAATTCACAGAAACAGATGTGAAGGTCAGGAGGCAAGTGGAGGATG   2147               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     GACTGGGCCCGCAGATGCCCTGACCTCTGCCCCCAGGTAGCAGGACACTC   2197               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     CATTGGATGGCCCCTGATGAGGAAGACTTCAGAATTGGGAACTAAACCAT   2247               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     GAATGCTATTTTCTTTTTTCTTTTTCTTTTCTTTTTTTTTTTTTTTTTTT   2297               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     TTTTGAGACAGAGTTTTGCTCTTGTTGTCCAGGCTGGAGTGCAATGGCAC   2347               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     GATCTCAGCTCACTGCAACCTCCGCCTCCCAGGTTCAAGTAATTCTCCTG   2397               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     CCTCAGCCTCCCGAGTGGCTGGGATTAGCGGCATGCACCACCACGCCCAG   2447               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     CTATTTTTGTATTTTTAGTAGAGATGGGGTTTCACCATGTTGGCCAGGAT   2497               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     GGTCTCGATCTCTTGACCTGGTGATCTGCCCACCTCGGCCTGCCAAAGTG   2547               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     CTGGGATTACAGGCTTGAGCTACCGCGCCCGGCCGTGAACGCTATTTTCT   2597               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     AAGCAGCCAGCAGTGAATCTAAAACTCTGGAAGAAGTCTTCTGTTTGAAA   2647               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     GGCTTATTTAAGCCACACGTACACACACTGTCTTAGAGTACTGTGAGCCC   2697               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     ACCCCACATTGGTCATCTTCCCTATCACACAAATGATGTTATTTTGGACT   2747               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     AGCTTAATTTTGAAATGGTAACAAAGTTTCCTATTCCATACTGTTGATTT   2797               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     CTAATACTCTTACGAAAACTATTCTAAAGGAGGCCAGGAGCCAAGGCCAAA   2847               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     AGTGAACGTACAGGTTTGAAATGGCTGTGATAAGGACCAGCTGGTATTAA   2897               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     CTGATAACTTTACCTTTGGGTTTTTGTTATTTTGTTTTTCTAGTCCCTAC   2947               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     CTGTGTTTAAATTATGGATAACTCGAAAGACAGCTCAGGTGAAGGCCAGT   2997               SequencetosubmitGenbank   ---------------------------------------------------       XM_007063 Homosapiens     AATGATTTTTTTGAAGTTTCAATGGTGTGAAATAAATTTCTGTTCTTA   3045                    Protein Sequence of Canine                        5′3′ Frame 2                       catcttcttcatcgtggtcaatgagttctgtgaaagattttcctactatggaatgagagca   (SEQ ID NO:8)         I  F  F  I  V  V  N  E  F  C  E  R  F  S  Y  Y  G  M  R  A    (SEQ ID NO:13)               ctcctgattctgtacttcagacggttcatcgggtgggacgataatctgtccacggccatc        L  L  I  L  Y  F  R  R  F  I  G  W  D  D  N  L  S  T  A  I               taccacacgtttgtggctctgtgctacctgacgccgatcctcggcggcactgatcgcagac        Y  H  T  F  V  A  L  C  Y  L  T  P  I  L  G  A  L  I  A  D               tcctggctgggaaagttcaagacaatcgtgtcactctccattgtctacacaattggacag        S  W  L  G  K  F  K  T  I  V  S  L  S  I  V  Y  T  I  G  Q               gcggtcactgcagtaagctcaattaatgacctcacagactataacaaagatggaactcct        A  V  T  A  V  S  S  I  N  D  L  T  D  Y  N  K  D  G  T  P               gacaatctgtccgtgcatgtggcactgtccatgattggcctggccctgatagctctggga        D  N  L  S  V  H  V  A  L  S  M  I  G  L  A  L  I  A  L  G               actggaggaataaagccctgtgtgtctgcatttggtggagaccagtttgaagagggccag        T  G  G  I  K  P  C  V  S  A  F  G  G  D  Q  F  E  E  G  Q               gaaaaacaaagaaacagattcttttccatcttttatttggccattaatgctggaagcttg        E  K  Q  R  N  R  F  F  S  I  F  Y  L  A  I  N  A  G  S  L               atttccactattgtcactcccatgctcagagttcacgaatgtggaatttacagtcagaaa        I  S  T  I  V  T  P  M  L  R  V  H  E  C  C  I  Y  S  O  K               gcttgttacccactggcatttggggttcctgctgctctcatggccgtatctctgattgta        A  C  Y  P  L  A  F  G  V  P  A  A  L  M  A  V  S  L  I  V               tttgtcattggcagtggaatgtacaagaagtttcagccccagggtaatgtcatgggtaaa        F  V  I  G  S  G  M  Y  K  K  E  Q  P  Q  C  N  V  M  G  K               gttgtcaagtgcattggttttgccctcaaaaataggtttaggcaccggagtaagcagttt        V  V  K  C  I  G  F  A  L  K  N  R  F  R  H  R  S  K  Q  F               cccaagagggagcactggctggactgggctaaagagaaatacgatgagcggctcatctct        P  K  R  E  H  W  L  D  W  A  K  E  K  Y  D  E  R  L  I  S               caaattaagatggtcacaaaagtgatgttcttgtacatcccactcccaatgttctgggcc        Q  I  K  M  V  T  K  V  M  F  L  Y  I  P  L  P  M  F  W  A               ctgtttgaccagcagggctccaggtggacactgcaagcaacagctatgagtgggaaaatt        L  F  D  Q  Q  G  S  R  W  T  L  Q  A  T  A  M  S  G  K  I               ggacttcttgaagttcagccagatcagatgcagactgtgaatgccatcttgattgtcgtc        G  L  L  E  V  Q  P  D  Q  M  Q  T  V  N  A  I  L  I  V  V               atggtccccatcatggatgccgtggtgtaccctctgattgcaaaatgtggcttcaatttc        M  V  P  I  M  D  A  V  V  Y  P  L  I  A  K  C  G  F  N  F               acctccttgaagaggatgacagttggaatgttcctggcttccatggccttcgtgatggcg        T  S  L  K  R  M  T  V  G  M  F  L  A  S  M  A  F  V  M  A               gcgattgttcagctggaaattgataaaactcttccagtcttccccaaacaaaatgaagct        A  I  V  Q  L  E  I  D  K  T  L  P  V  F  P  K  Q  N  E  V               caaatcaaagtactgaatataggaaatggtgccatgaatgtatcttttcctggagcggtg        Q  I  K  V  L  N  I  G  N  G  A  M  N  V  S  F  P  G  A  V               gtgacagttagccaaatgagtcaatcagatggatttatgacttttgatgtagacaaactg        V  T  V  S  Q  M  S  Q  S  D  G  E  M  T  F  D  V  D  K  L               acaagtataaacatttcttccactggatcaccagtcattccagtgacttataactttgag        T  S  I  N  I  S  S  T  G  S  P  V  I  P  V  T  Y  N  F  E               cagggccatcgccatacccttctagtatgggcccccaataattaccgagtggtaaaggat        Q  G  H  R  H  T  L  L  V  W  A  P  N  N  Y  R  V  V  K  D               ggccttaaccagaagccagaaaaaggagaaaatggaatcagatttataaatagtcttaat        G  L  N  Q  K  P  H  K  G  E  N  G  I  R  F  I  N  S  L  N               gagagcctcaacatcaccatgggcgacaaagtttatgtgaatgtcaccagtcacaatgcc        E  S  L  N  I  T  M  G  D  K  V  Y  V  N  V  T  S  H  N  A               agcgagtatcagttcttttctttgggcacaaaaaacattacaataagttcaacacaacag        S  E  Y  Q  F  F  S  L  G  T  K  N  I  T  I  S  S  T  Q  Q               atctcacaaaattgtacaaaagttctccaatcatccaaccttgaatttggtagtgcatat        I  S  Q  N  C  T  K  V  L  Q  S  S  N  L  E  E  G  S  A  Y               acctatgtaatcggaacgcagagcactggctgccctgaattgcatatgtttgaagatatt        T  Y  V  I  G  T  Q  S  T  G  C  P  E  L  H  M  F  E  D  I               tcacccaacacagttaacatggctctgcagatcccgcagtacttcctcatcacctgcggc        S  P  N  T  V  N  M  A  L  Q  I  P  Q  Y  F  L  I  T  C  G               gaggtggttttctctgtcacaggactggagttctcatattctcaggccccctccaacatg        E  V  V  F  S  V  T  G  L  E  F  S  Y  S  Q  A  P  S  N  M               aagtcggtgcttcaggcgggatggctgctgacagtggcttgttggcaacatcattgtgct        K  S  V  L  Q  A  G  W  L  L  T  V  A  C  W  Q  H  H  C  A               cattgtggcaggagcaggccagttcagtgaacagtgggctgaatacatcctatttgcggc        H  C  G  R  S  R  P  V  Q  -  T  V  G  -  I  H  P  I  C  G               attgcttctggttgtctgtgtaatatttgccatcatggcccggttttacacttacgtcaa        I  A  S  G  C  L  C  N  I  C  H  H  G  P  V  L  H  L  R  Q               tccagcagagattg        S  S  R  D                      5′3′ Frame 2   (SEQ ID NO:13)                    IFFIVVNEFCERFSYYGMRALLILYFRRFIGWDDNLSTAIYHTFVALCYLTPILGALIAD               SWLGKFKTIVSLSIVYTIGQAVTAVSSINDLTDYNKDGTPDNLSVHVALSMIGLALIALG               TGGIKPCVSAFGGDQFEEGQEKQRNRFFSIFYLATNAGSLISTIVTPMLRVHECGIYSQK               ACYPLAFGVPAPIMAVSLIVFVIGSGMYKKFQPQGNVMGKVVKCIGFALKNRFRHRSKQF               PKREHWLDWAKEKYDERLISQIKNVTKVMFLYIPLRMFWALFDQQGSRWTLQATAMSGKI               GLLEVQPDQMQTVNAILIVVMVPIMDAVVYPLIAKCGFNFTSLKRMTVGMFLASMAFVMA               AIVQLETDKTLPVFPKQNEVQIKVLNIGNGAMNVSFPGAVVTVSQMSQSDGFMTFDVDKL               TSINISSTGSPVIPVTYNFEQGHRHTLLVWAPNNYRVVKDGLNQKPEKGENGIRFINSLN               ESLNITMGDKVYVNVTSHNASEYQFFSLGTKNITISSTQQISQNCTKVLQSSNLEFGSAY               TYVIGTQSTGCPELHMFEDISPNTVNMALQIPQYFLITCGEVVFSVTGLEFSYSQAPSNM               KSVLQAGWLLTVACWQHHCAHCGRSRPVQ-TVG-IHPICGIASGCLCNICHHGPVLHLRQ               SSRD                    Multiple Alignment of Amino-Acid Sequences                        Sequence 1: Caninesubmitted   662 aa                   Sequence 2: XM_007063 Homosapiens ProteinSeq   706 aa               Sequence 3: DS0306RatProteinSequence   710 aa               Sequence 4: NM_053079 Musmusculus ProteinSeq   709 aa               Sequence 5: AY027496Ovis   707 aa               Sequence 6: U13707 Oryctolaguscunic ProteinS   707 aa               Sequence 7: Ay029615 Gallusgallus ProteinSeq   714 aa                    Start of Pairwise alignments                   Aligning . . .                Sequences (1:2) Aligned. Score: 76               Sequences (2:3) Aligned. Score: 84               Sequences (3:4) Aligned. Score: 91               Sequences (4:5) Aligned. Score: 80               Sequences (1:3) Aligned. Score: 77               Sequences (2:4) Aligned. Score: 83               Sequences (3:5) Aligned. Score: 82               Sequences (4:6) Aligned. Score: 76               Sequences (1:4) Aligned. Score: 75               Sequences (2:5) Aligned. Score: 82               Sequences (3:6) Aligned. Score: 77               Sequences (4:7) Aligned. Score: 63               Sequences (1:5) Aligned. Score: 77               Sequences (2:6) Aligned. Score: 80               Sequences (1:6) Aligned. Score: 72               Sequences (3:7) Aligned. Score: 64               Sequences (5:6) Aligned. Score: 77               Sequences (1:7) Aligned. Score: 60               Sequences (2:7) Aligned. Score: 63               Sequences (6:7) Aligned. Score: 61               Sequences (5:7) Aligned. Score: 64               Guide tree file created:               [/net/nfs0/vol1/prosuction/w3nobody/tmp/936042.678539-441485.dnd]               Start of Multiple Alignment               There are 6 groups               Aligning. . .                Group 1: Sequences: 2 Score:14016               Group 2: Sequences: 2 Score:14858               Group 3: Sequences: 4 Score:13893               Group 4: Sequences: 5 Score:14022               Group 5: Sequences: 6 Score:12718               Group 6: Sequences: 7 Score:12338               Alignment Score 68091               CLUSTAL-Alignment file created               [/net/nfs0/vol1/production/W3nobody/tmp/936042.678539-441485.aln]               Your Multiple Sequence Alignment:               936042.678539-441485.aln               CLUSTAL W (1.81) multiple sequence alignment                    (SEQ ID NO:14)                XM_007063 Homosapiens ProteinSeq   ---MSKSHS-----FFGYPLSIFFIVVNEFCERFSYYGMRAILILYFTNF   42                        (SEQ ID NO:18)                U13707 Oryctolaguscunic Proteins   -MGMSKSLS-----CFGYPLSIFFIVVNEFCERFSYYGMRALLILYFRNF   44                        (SEQ ID NO:15)                D50306RatProteinSequence   -MGMSKSRG-----CFGYPLSIFFIVVNEFCERFSYYGMRALLVLYFRNF   44                        (SEQ ID NO:16)                NM_053079 Musmusculus ProteinSeq   -MGMSKSRG-----CFGYPLSIFFIVVNEFCERFSYYGMRALLVLYFRNF   44                        (SEQ ID NO:17)                AY027496Ovis   -MGMSVPKS-----CFGYPLSIFFIVVNEFCERFSYYGMRALLILYFQRF   44                        (SEQ ID NO:13)                Caninesubmitted   ---------------------IFFIVVNEFCERFSYYGMRALLILYFRRF   29                        (SEQ ID NO:19)                Ay029615 Gallusgallus ProteinSeq   MAAKSKSKGRSVPNCFGYPLSIFFIVINEFCERFSYYGMRAVLVLYFKYF   50                   XM_007063 Homosapiens ProteinSeq   ISWDDNLSTAIYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIG   92       U13707 Oryctolaguscunic ProteinS   IGWDDNLSTVIYHTFVALCYLTPILGALIADAWLGKFKTIVWLSIVYTIG   94       D50306RatProteinSequence   LGWDDDLSTAIYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIG   94       NM_053079 Musmusculus ProteinSeq   LGWDDNLSTAIYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIG   94       AY027496Ovis   LGWNDNLGTATYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIG   94       Caninesubmitted   IGWDDNLSTAIYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIG   79       AY029615 Gallusgallus ProteinSeq   LRWDDNFSTATYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIG   100                                          : *:*::.*.*********************:********* ********               XM_007063 Homosapiens ProteinSeq   QAVTSVSSTNDLTDHNHDGTPDSLPVHVVLSLIGLALIALGTGGIKPCVS   142       U13707 Oryctolaguscunic ProteinS   QAVTSLSSVNELTDNNHDGTPDSLPVHVAVCMIGLLLIALGTGGIKPCVS   144       D50306RatProteinSequence   QAVTSVSSINDLTDHDHDGSPNNLPLHVALSMIGLALIALGTGGIKPCVS   144       NM_053079 Musmusculus ProteinSeq   QAVISVSSINDLTDHDHNGSPDSLPVHVALSMVGLALIALGTGGIKPCVS   144       AY027496Ovis   QVVTAVSSINDLTDFNHDGTPNNISVHVALSMIGLVLIALGTGGIKPCVS   144       Caninesubmitted   QAVTAVSSTNDLTDYNKDGTPDNLSVHCALSMIGLALIALGTGGIKPCVS   129       AY029615 Gallusgallus ProteinSeq   QAVMAVSSINDMTDQNRDGNPDNIAVHIALSMYGLILIALGTGGIKPCVS   150                                          *.* ::**:*::** :::*.*:.:.:.:*:.:.: ** **************               XM_007063 Homosapiens ProteinSeq   AFGGDQFEEGQEKQRNRFFSTFYLAINAGSLLSTIITPMLRVQQCGIHSK   192       U13707 Oryctolaguscunic ProteinS   AFGGDQFEEGQEKQRNRFFSTFYLAINAGSLLSTIITPMLRVQQCGIHSK   194       D50306RatProteinSequence   AFGGDQFEEGQEKQRNRFFSIFYLAINAGSLLSTIITPILRVQQCGIHSQ   194       NM_053079 Musmusculus ProteinSeq   AFGGDQFEEGQEKQRNRFFSIFYLAINGGSLLSTIITPILRVQQCGIHSQ   194       AY027496Ovis   AFGGDQFEEGQEKQRNRFFSIFYLAINAGSLLSTIITPMLRVQVCGIHSK   194       Caninesubmitted   AFGGDQFEEGQEKQRNRFFSTFYLAINAGSLISTIVTPMLRVHECGIYSQ   179       AY029615 Gallusgallus ProteinSeq   AFGGDQFEEHQEKQRSRFFSIFYLSINAGSLISTIITPILRAQECGIHSR   200                                          ********* *****.********:**.***:***:**::*.: ***: :               XM_007063 Homosapiens ProteinSeq   QACYPLAFGVPAALMAVALTVFVLGSGMYKKFKPQGNIMGKVAKCIGFAI   242       U13707 Oryctolaguscunic ProteinS   QACYPLAFGIPAILMAVSLIVFIIGSGMYKKFKPQGNILSKVVKCICFAI   244       D50306RatProteinSequence   QACYPLAFGVPAALMAVALIVFVLGSGMYKKFQPGNIMGKVAKCIGFAI   244       NM_053079 Musmusculus ProteinSeq   QACYPLAFGVPAALMAVALIVFVLGSGMYKKFQPQGNIMGKVAKCIGFAI   244       AY027496Ovis   QACYPLAFGVPAALMAVSLIVEVIGSGMYKKFQPGNIMSKVARCIGFAI   244       Caninesubmitted   KACYPLAFGVPAALMAVSLIVFVIGSGMYKKFQPQGNVMGKVVKCIGFAL   229       AY029615 Gallusgallus ProteinSeq   QQCYPLAFGVPAALMAVSLWFIAGSGMYKKVQPQGNIMVRVCKCIGFAI   250                                          : *******:** ****:*:**: *******.:****:: :* :** **:               XM_007063 Homosapiens ProteinSeq   KNRFRHRSKAFPKREHWLDWAKEKYDERLISQIKMVTRVMFLYIPLPMFW   292       U13707 Oryctolaguscunic ProteinS   KNRFRHRSKQFPKRAHWLDWAKEKYDERLIAQIKMVTRVLFLYIPLPMFW   294       D50306RatProteinSequence   KNRFRHRSKAFPKREHWLDWAKEKYDERLISQIKMVTKVMFLYIPLPMFW   294       NM_053079 Musmusculus ProteinSeq   KNRFRHRSKAYPKREHWLDWAKEKYDERLISQIKMVTKVMFLFIPLPMFW   294       AY027496Ovis   KNRISHRSKKFPKREHWLDWASEKYDERLISQIKMVTRVMFLYIPLPMFW   294       Caninesubmitted   KNRFRHRSKQFPKREHWLDWAKEKYDERLISQIKMVTKVMFLYIPLPMFW   279       AY029615 Gallusgallus ProteinSeq   KNRFRHRSKEYPKREHWLDWASEKYDKRLIAQTKMVLKVLFLYIPLPMFW   300                                          ***: **** :*** ******.****:***:* *** :*:**:*******               XM_007063 Homosapiens ProteinSeq   ALFDQQGSRWTLQATTMSGKTGALEIQPDQMQTVNAILIVIMPVPIFDAVL   342       U13707 Oryctolaguscunic ProteinS   ALFDQQGSRWTLQATTMSGRIGILEIQPDQMQTVNTILIIILVPIMDAVV   344       D50306RatProteinSequence   ALFDQQGSRWTLQATTMTGKIGTTEIQPDQMQTVNAILIVIMVPIVDAVV   344       NM_053079 Musmusculus ProteinSeg   GLFDQQGSRWTLQATTMNGKIGANEIQPDQMQTVNAILNVNNGPNVDAVV   344       AY027496Ovis   ALFDQQGSRWTLQATTMSGKIGIIEIQPDQMQTVNAILIVVMVPIVDAVV   344       Caninesubmitted   ALFDQQGSRWTLQATANSGKIGLLEVQPDQMQTVNAILIVVMVPIMDAVV   329       AY029615 Gallusgallus ProteinSeq   ALFDQQGSRWTLQATTMDGDFGAMQIQPDQMQTVNPILIIIMVPVVDAVI   350                                          .**************:* * :*  ::*********.** :   * .***:               XM_007063 Homosapiens ProteinSeq   YPLTAKCGFNFTSLKKMAVGMVLASMAFVVAAIVQVEIDKTLPVFPKGNE   392       U13707 Oryctolaguscunic ProteinS   YPLIAKCGLNFTSLKKMTIGMFLASMAFVAAAILQVEIDKTLPVFPKANE   394       D50306RatProteinSequence   YPLIAKCGFNFTSLKKMTVGMFLASMAFVVAAIVQVEIDKTLPVFPSGNQ   394       NM_053079 Musmusculus ProteinSeq   YRSTAKCGFNFTSLKKMTVGMFLASMAFVVAAIVQVWIDKTLPVEPGGNQ   394       AY027496Ovis   YPLIAKCGLNFTSLKKMTVGMFLASMAFVAAAIVQVDIDKTLPVFPKGNE   394       Caninesubmitted   YPLIAKCGFNFTSLKRMTVGMFLASMAFVMAAIVQLEIDKTLPVFPKQNE   379       AY029615 Gallusgallus ProteinSeq   YPLIQKCKINFTPLRRITVGMFLAGLAFVAAALLQVQIDKTLPVFPAAGQ   400                                          *  * ** :***.*:::::**.**.:*** **::*::*********  .:               XM_007063 Homosapiens ProteinSeq   VQTKVLNIGNNTMNISLPG--EMVTLGPMSQTNAFMTFDVNKLTRINISS   440       U13707 Oryctolaguscunic ProteinS   VQTKVLNVGSENMTTSLPG--QTVTLNQMSQTNEFMTFNEDTLTSINITS   442       D50306RatProteinSequence   VQTKVLNTGNNDMAVYFPG--KNVTVAQMSQTDTFMTFDVDQLTSINVISS   442       NM_053079 Musmusculus ProteinSeq   VQTKVLNIGNNNMTVHFPG--NSVTLAQMSTDTFMTFDIDKLTSINISS   442       AY027496Ovis   VQIKVLNIGNNSMTVSFPG--TTVTCDQMSQTNGFLTFNVDNLS-INISS   441       Caninesubmitted   VQTKVLNTGNGANNVSFPG--AVVTVSQMSQSDGFMTFDVDKLTSINISS   427       AY029615 Gallusgallus ProteinSeq   AQIKTINLGDSNANVTFLPNLQNVTVLPMESTG-YRMFESSQLKSVMVNF   449                                          .***::*:*.    : :      **   *..:. :  *: . *. : :.               XM_007063 Homosapiens ProteinSeq   PGSP-VTAVTDDFKQGQRHTLLVWAPNHYQVVK-DGLNQKPEKGENGIRF   488       U13707 Oryctolaguscunic Proteins   -GSQ-VTMITPSLEAGQRHTLLVWAPNNYRVVN-DGLTQKSDKGENGIRF   489       D50306RatProteinSequence   PGSPGVTTVAHEFEPGHRHTLLVWGPNLYRVVK-DGLNQKPEKGENGIRF   491       NM_053079 Musmusculus ProteinSeq   SGSPGVTTVAHDFEQGHRHNLLVWEPSQYRVVK-DGPNQKPEKGRNGIRF   491       AY027496Ovis   TGTP-VTPVTHNFESGHRHTLLVWAPSNYQVVK-DGLNQKPEKGRNGIRF   489       Caninesubmitted   TGSP-VIPVTYNFEQGHRHTLLVWAPNNYRVVK-DGLNQKPEKGENGIRF   475       AY029615 Gallusgallus ProteinSeq   GSESRSENTDSISSNTHTVTTKNAAAGIVSSLRSDNFTSKPEEGKNLVRF   499                                           .      :    .  :  .:    ..    :. *. ..*.::*.* :**               XM_007063 Homosapiens ProteinSeq   VNTFNELTTITMSGKVYANISSYNASTYQFFPSGIKGFTISSTE-IPPQC   537       U13707 Oryctolaguscunic ProteinS   VNTYSQPTNVTMSGKVYEHIASYNASEYQFFTSGVKGFTVSSAG-ISEQC   538       D50306RatProteinSeguence   VSTLNEMITTKMSGKVYENVTSHSASNYQFFPSGQKDYTINTTE-IAPNC   540       NM_053079 Musmusculus ProteinSeq   VNTLNEMVTNKMSGKVYEKFTSHNASGYKFLPSGEKQYTINTTA-VAPTC   540       AY027496Ovis   VNAFGESFGVTMDGEVYNNVSGHNASEYLFFSSGVKSFTINSPE-ISQQC   538       Caninesubmitted   INSLNESLNITMGDKVYVNVTSHNASEYQFFSLGTKNITISSTQQISQNC   525       AY029615 Gallusgallus ProteinSeq   VNNLPQTVNITMGDTTFGILEETSISNYSPFSGGRTYDIVITAG   -STNC   547                                           :.   : .  .*.. .:  .   . * *  :. * .   : :.   .  *               XM_007063 Homosapiens ProteinSeq   QPNFNTFYLEFGSAYTYTVQ-RKNDSCPEVKVFEDISANTVNMALQIPQY   586       U13707 Oryctolaguscunic ProteinS   RRDFESPYLEFGSAYTYLIT-SQATGCPQVTEFEDIPPNTMNMAWQIPQY   587       D50306RatProteinSequence   SSDFKSSNLDFGSAYTYVTRSRASDGCLEVKEFEDIPPNTVNMALQIPQY   590       NM_053079 Musmusculus ProteinSeq   LTDFKSSNLDFGSAYTYVIR-RASDGCLEVKEFEDIPPNTVNMALQIPQY   589       AY027496Ovis   EKQFKTSYLEFGSAFTYVIS-RKSDGCPEKIFEDISPNTVSMALQIPQY   587       Caninesubmitted   TKVLQSSNLEFGSAYTYVIG-TQSTGCPELHMFEDISPNTVNMALQIPQY   574       AY029615 Gallusgallus ProteinSeq   KP--TSEKLGYGGAYTTVTN-ECSGDCTQLRYIEDIQPNTVHMAWQIPQY   594                                               :  * :*.*:* ::      .  :   :*** .**: ** *****               XM_007063 Homosapiens ProteinSeq   FLLTCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIVAG   636       U13707 Oryctolaguscunic ProteinS   FLITSGEVVFSITGLEFSYSQAPSNMKSVLQDRWLLTVAVGNIIVLIVAG   637       D50306RatProteinSequence   FLLTCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAIGNIIVLIVAE   640       NM_053079 Musmusculus ProteinSeq   FLLTCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAGNIIVLIVAG   639       AY027496Ovis   FLLTCGEVVFSITGLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIVAG   637       Caninesubmitted   FLITCGEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVACWQHHCAHHCAHCGR   624       AY029615 Gallusgallus ProteinSeq   FTLTCCEVVFSVTGLEFSYSQAPSNMKSVLQAGWLLTVAGNIIVLIVAG   644                                           *::*.******:*******************  ******  :      .               XM_007063 Homosapiens ProteinSeq   AGQFSKQWAEYILFAALLLVVCVIFAIMARFYTYINPAEIEAQFDEDEKK   686       U13707 Oryctolaguscunic ProteinS   AGQINKQWAEYILFAALLLVVCVIFAIMARFYTYVNPAEIEAQFEEDEKK   687       D50306RatProteinSequence   AGHFDKQWAEYVLFASLLLVVCIIFAIMARFYTYINPAEIEAQFDEDEKK   690       NM_053079 Musmusculus ProteinSeq   AGHFPKQWAEYILFASLLLVVCVIFAIMARFYTYINPAEIEAQFDEDEKK   689       AY027496Ovis   AGQFPKQWAEYVLFAALLLVVCIIFAIMARFYTYVNPAEIEAQFDEDDKE   687       Caninesubmitted   SRPVQ-TVG-----------IHPICGIASGCLCNICHHGPVLHLRQSSRD   662       AY029615 Gallusgallus ProteinSeq   ASKLSEQWAEYVLFAALLFAVCIIFAVMAYFYTYTDPNEVEAQLDEEEKK   694                                           :  .    .           :  * .: :             :: :..:.               XM_007063 Homosapiens ProteinSeq   NRLEKSNPYFMSGANSQKQM   706       U13707 Oryctolaguscunic ProteinS   KNPEKNDLYPSVAPVSQTQM   707       D50306RatProteinSequence   KGVGKENPYSSLEPVSQTNM   710       NM_053079 Musmusculus ProteinSeq   KGIGKENPYSSLEPVSQTQM   709       AY027496Ovis   DDLEKSNPYAKLDFVSQTQM   707       Caninesubmitted   --------------------       AY029615 Gallusgallus ProteinSeq   KQIKQDPDLHGKESEAVSQM   714                    Alignment of Amino-Acid Sequences for Canine and Human                        Sequence format is Pearson                       Sequence 1: XM_007063 Homosapiens ProteinSeq   706 aa               Sequence 2: Caninesubmittedclone37   662 aa                    Start of Pairwise alignments                   Aligning. . .                Sequences (1:2) Aligned. Score: 76               Guide tree file created:               [/net/nfs0/vol1/production/w3nobody/tmp/789481.229198-238519.dnd]               Start of Multiple Alignment               There are 1 groups               Aligning. . .                Group 1: Sequences: 2 Score:12826               Alignment Score 3129               CLUSTAL-Alignment file created               [/net/nfs0/vol1/production/w3nobody/tmp/789481.229198-238519.aln]               Your Multiple Sequence Alignment:               789481.229198-238519.aln               CLUSTAL W (1.81) multiple sequence alignment                    (SEQ ID NO:14)                XM_007063 Homosapiens ProteinSeq   MSKSHSFFGYPLSIFFIVVNEFCERFSYYGMRAILILYFTNFISWDDNLS   50                        (SEQ ID NO:13)                Caninesubmittedclone37   -------------IFFIVVNEFCERFSYYGMRALLILYFRRFIGWDDNLS   37                                                        ********************:***** .**.******               XM_007063 Homosapiens ProteinSeq   TAIYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIGQAVTSVSS   100       Caninesubmittedclone37   TAIYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIGQAVTAVSS   87                                          *********************************************:***               XM_007063 Homosapiens ProteinSeq   INDLTDHNHDGTPDSLPVHVVKSLIGLIALGTGGIKPCVSAFGGDQFE   150       Caninesubmittedclone37   INDLTDYNKDGTPDNLSVHVALSMIGLALIALGTGGIKPCVSFGGDQFE   137                                          ******:*:*****.*.***.**:**************************               XM_007063 Homosapiens ProteinSeq   EGQEKQRNRFFSIFYLAINAGSLLSTIITPMLRVQQCGIHSKQACPLAF   200       Caninesubmittedclone37   EGQEKQRNRFFSIFYLAINAGSLISTIVTPMLRVHECGIYSQKACYPLAF   187                                          ***********************:***:******::***:*::*******               XM_007063 Homosapiens ProteinSeq   GVPAALMAVALIVFVLGSGMYKKFKPQGNIMGKVAKCIGFAIKNRFRHRS   250       Caninesubmittedclone37   GVPAALMAVSLIVFVIGSGMYKKFQPGNVMGKVVKCIGFALKNRFRHRS   237                                          *********:*****:********:****:****.******:********               XM_007063 Homosapiens ProteinSeq   KSFPKREHWLDWAKEKYDERLISQIKMVTRVMFLYIPLPMFWALFDQQGS   300       Caninesubmittedclone37   KQFPKREWLDWAKEKYDERLISQIKMVTKVMFLYIPLPMFWALFDQQGS   287                                          * ****************************:********************               XM_007063 Homosapiens ProteinSeq   RWTLQATTMSGKIGALEIQPDQMQTVNAILIVIMVPIFDAVLYPLIAKCG   350       Caninesubmittedclone37   RWTLQATAMSGKIGLLEVQPDQMQTVNAILIVVMVPIMDAVVYPLIAKCG   337                                          *******:****** **:**************:****:***:********               XM_007063 Homosapiens ProteinSeq   FNFTSLKKMAVGMVLADMAFVVAAIVQVEIDKTLPVFPKGNEVQIKVLNI   400       Caninesubmittedclone37   FNFTSLKRMTVGMFLASMAFAVMAAIVQLEIDKTLPVFPKQNEVQIKVLNI   387                                          *******:*:***.*******:*****:*********** **********               XM_007063 Homosapiens ProteinSeq   GNNTMNISLPGEMVTLGPMSQTNAFMTFDVNKLTRINISSPGSPVTAVTD   450       Caninesubmittedclone37   GNGAMNVSFPGAVVTVSQMSQSDGFMTFDVDKLTSINISSTGSPVIPVTY   437                                          **.:**:*:** :**:. ***::.******:*** *****,**** .**               XM_007063 Homosapiens ProteinSeq   DFKQGQRHTLLVWAPNHYQVVKDGLNQKPEKGENGIRFVNTFNELITITM   500       Caninesubmittedclone37   NFEQGHRHTLLVWAPNNYRVVKDGLNQKPEKGENGIRFINSLNESLNITM   487                                          :*:**:**********:*:*******************:*::** :.***               XM_007063 Homosapiens ProteinSeq   SGKVYANISSYNASTYQFFPSGIKGFTISST-EIPPQCQPNFNTFYLEFG   549       Caninesubmittedclone37   GDKVYVNVTSHNASEYQFFSLGTKNITISSTQQISQNCTKVLQSSNLEFG   537                                          ..***.*::*:*** ****. * *.:***** :*. :*   :::  ****               XM_007063 Homosapiens ProteinSeq   SAYTYIVQRKNDSCPEVKVFEDISANTVNMALQIPQYFLLTCGEVVFSVT   599       Caninesubmittedclone37   SAYTYVIGTQSTGCPELHMFEDISPNYVNMALQIPQYFLITCGEVVFSVT   587                                          *****::  :. .***:::*****.**************;**********               XM_007063 Homosapiens ProteinSeq   GLEFSYSQAPSNMKSVLQAGWLLTVAVGNIIVLIVAGAGQFSKQWAEYIL   649       Caninesubmittedclone37   GLEFSYSQAPSNMKSVLQAGWLLTVACWQHHCAHCGRSRPVQ-TVG----   632                                          **************************  :      . :  ..   .                  XM_007063 Homosapiens ProteinSeq   FAALLLVVCVIFAIMARFYTYINPAEIEAQFDEDEKKNRLENKSNPYFMSG   699       Caninesubmittedclone37   -------IHPICGIASGLCNICHHGPVLHLRQSSRD-------------   662                                                :  * .* :     *       :: :..:.               XM_007063 Homosapiens ProteinSeq   ANSQKQM   706       Caninesubmittedclone37   -------            
         [0220]    After analyzing the protein sequence and performing alignment with other species, the underlined, italicized was removed for submission to Genbank.  
                           Sequence to submit to Genbank (SEQ ID NO:7)                   catcttcttcatcgtggtcaatgagttctgtgaaagattttcctactatggaatgagagcactcctgattctgtacttcagacgg               ttcatcgggtgggacgataatctgtccacggccatctaccacacgtttgtggctctgtgctacctgacgccgatcctcggc               gcactgatcgcagactcctggctgggaaagttcaagacaatcgtgtcactctccattgtctacacaattggacaggcggtc               actgcagtaagctcaattaatgacctcacagactataacaaagatggaactcctgacaatctgtccgtgcatgtggcactgt               ccatgattggcctggccctgatagctctgggaactggaggaataaagccctgtgtgtctgcatttggtggagaccagtttg               aagagggccaggaaaaacaaagaaacagattcttttccatcttttatttggccattaatgctggaagcttgatttccactattg               tcactcccatgctcagagttcacgaatgtggaatttacagtcagaaagcttgttacccactggcatttggggttcctgctgct               ctcatggccgtatctctgattgtatttgtcattggcagtggaatgtacaagaagtttcagccccagggtaatgtcatgggtaa               agttgtcaagtgcattggttttgccctcaaaaataggtttaggcaccggagtaagcagtttcccaagagggagcactggct               ggactgggctaaagagaaatacgatgagcggctcatctctcaaattaagatggtcacaaaagtgatgttcttgtacatccc               actcccaatgttctgggccctgtttgaccagcagggctccaggtggacactgcaagcaacagctatgagtgggaaaattg               gacttcttgaagttcagccagatcagatgcagactgtgaatgccatcttgattgtcgtcatggtccccatcatggatgccgt               ggtgtaccctctgattgcaaaatgtggcttcaatttcacctccttgaagaggatgacagttggaatgttcctggcttccatgg               ccttcgtgatggcggcgattgttcagctggaaattgataaaactcttccagtcttccccaaacaaaatgaagtccaaatcaa               agtactgaatataggaaatggtgccatgaatgtatcttttcctggagcggtggtgacagttagccaaatgagtcaatcagat               ggatttatgacttttgatgtagacaaactgacaagtataaacatttcttccactggatcaccagtcattccagtgacttataact               ttgagcagggccatcgccatacccttctagtatgggcccccaataattaccgagtggtaaaggatggccttaaccagaag               ccagaaaaaggagaaaatggaatcagatttataaatagtcttaatgagagcctcaacatcaccatgggcgacaaagtttat               gtgaatgtcaccagtcacaatgccagcgagtatcagttcttttctttgggcacaaaaaacattacaataagttcaacacaac               agatctcacaaaattgtacaaaagttctccaatcatccaaccttgaatttggtagtgcatatacctatgtaatcggaacgcag               agcactggctgccctgaattgcatatgtttgaagatatttcacccaacacagttaacatggctctgcagatcccgcagtactt               cctcatcacctgcggcgaggtggttttctctgtcacaggactggagttctcatattctcaggccccctccaacatgaagtcg               gtgcttcaggcgggatggctgctgacagtggct               Canine PepT1 Nucleotide Sequence (SEQ ID NO:20)               atgggcatgtccaagtcatatggttgctttggttaccccttgagcatcttcttcatcgtggtcaatgagttctgtgaaagatttt               cctactatggaatgagagcactcctgattctgtacttcagacggttcatcgggtgggacgataatctgtccacggccatcta               ccacacgtttgtggctctgtgctacctgacgccgatcctcggcgcgcactgatcagactcctggctgggaaagttcaaga               caatcgtgtcactctcattgtctacacaattggacaggcggtcactgcagtaggctcaattaatgacctcacagactatgg               caaagatggaactcctgacaatctgtccgtgcatgtggcactgtccatgattggcctggccctgatagctctgggaactgg               aggaataaagccctgtgtgtctgcatttggtggagaccagtttgaagagggccaggaaaaacaaagaaacagattctttt               ccatcttttatttggccattaatgctggaagcttgatttccactattgtcactcccatgcttcacgaatgtggaatttac               agtcagaaagcttgttacccactggcatttggggttcctgctgctctcatggccgtatctctgattgtatttgtcattggcagt               ggaatgtacaagaagtttcagccccagggtaatgtcatgggtaaagttgtcaagtgcattggttttgccctcaaaaataggt               ttaggcaccggagtaagcagtttcccaagagggagcactggctggactgggctaaagagaaatacgatgagcggctca               tctctcaaattaagatggtcacaaaagtgatgttcttgtacatcccactcccaatgttctgggccctgtttgaccagcagggc               tccaggtggacactgcaagcaacagctatgagtgggaaaattggacttcttgaagttcagccagatcagatgcagactgt               gaatgccatcttgattgtcgtcatggtccccatcatggatgccgtggtgtaccctctGattgcaaaatgtggcttcaatttca               cctccttgaagaggatgacagttggaatgttcctggcttccatggccttcgtgatggcggcgattgttcagctggaaattga               taaaactcttccagtcttccccaaacaaaatgaagtccaaatcaaagtactgaatataggaaatggtgccatgaatgtatctt               ttcctggagcggtggtgacagttagccaaatgagtcaatcagatggatttatgacttttgatgtagacaaactgacaagtat               aaacatttcttccactggatcaccagtcattccagtgacttataactttgagcagggccatcgccatacccttctagtatggg               cccccaataattaccgagtggtaaaggatggccttaaccagaagccagaaaaaggagaaaatggaatcagatttataaat               agtcttaatgagagcctcaacatcaccatgggcgacaaagtttatgtgaatgtcaccagtcacaatgccagcgagtatcag               ttcttttctttgggcacaaaaaacattacaataagttcaacacaacagatctcacaaaattgtacaaaagttctccaatcatcc               aaccttgaatttggtagtgcatatacctatgtaatcggaacgcagagcactggctgccctgaattgcatatgtttgaagatat               ttcacccaacacagttaacatggctctgcagatcccgcagtacttcctcatcacctgcggcgaggtggttttctctgtcaca               ggactggagttctcatattctcaggccccctccaacatgaagtcggtgcttcaggcgggatggctgctgacagtggctgtt               ggcaacatcattgtgctcattgtggcaggagcaggccagttcagtgaacagtgggctgaatacatcctatttgcggcattg               cttctggttgtctgtgtaatatttgccatggcccggttttacacttacgtcaatccagcagagattgaagctcagtttgacg               acgatgagaaaaagaacctggaaaagatgaatgtatattccacggtaactccggtctcacagacacagatg               Canine PepT1 Amino Acid Sequence (SEQ ID NO:21)               MGMSKSYGCFGYPLSIFFIVVNEFCERFSYYGMRALLILYFRRFIGWDDNLS               TAIYHTFVALCYLTPILGALIADSWLGKFKTIVSLSIVYTIGQAVTAVSSINDL               TDYNKDGTPDNLSVHVALSMIGLALIALGTGGIKPCVSAFGGDQFEEGQEK                QRNRFFSIFYLAINAGSLISTIVTPMLRVHECGIYSQKACYPLAFGVPAALMA               VSLIVFVIGSGMYKKFQPQGNVMGKVVKCIGFALKNFRHRSKQFPKREH               WLDWAKEKYDERLISQIKMVTKVMFLYIPLPMFWALFDQQGSRWTLQATA               MSGKIGLLEVQPDQMQTVNAILIVVMVPIMDAVVYPLIAKCGFNFTSLKRM               TVGMFLASMAFVMAAIVQLEIDKTLPVFPKQNEVQIKVLNGNGAMNVSFP               GAVVTVSQMSQSDGFMTFDVDKLTSINISSTGSPVIPVTYNFEQGHRHTLLV               WAPNNYRVVKDGLNQKPEKGENGIRFINSLNESLNITMGDKVYVNVTSHN               ASEYQFFSLGTKNITISSTQQISQNCTKVLQSSNLEFGSAYTYVIGTQSTGCPE               LHMFEDISPNTVNMALQIPQYFLITCGEVVFSVTGLEFSYSQAPSNMKSVLQ               AGWLLLTVAVGNIIVLIVAGAGQFSEQWAEYILFAALLLVVCVIFAIMARFYT               YVNPAEIEAQFDDDEKKNLEKMNVYSTVTPVSQTQM          
 
         [0221]    All publications, patents and patent documents are incorporated by reference herein, as though individually incorporated by reference. The invention has been described with reference to various specific and preferred embodiments and techniques. However, it should be understood that many variations and modifications may be made while remaining within the scope of the invention.  
     
       
       
         1 
         
           
             21  
           
           
             1  
             3045  
             DNA  
             Homo sapiens  
           
            1 

gaatgtccaa atcacacagt ttctttggtt atcccctgag catcttcttc atcgtggtca     60 

atgagttttg cgaaagattt tcctactatg gaatgcgagc aatcctgatt ctgtacttca    120 

caaatttcat cagctgggat gataacctgt ccaccgccat ctaccatacg tttgtggctc    180 

tgtgctacct gacgccaatt ctcggagctc ttatcgccga ctcgtggctg ggaaagttca    240 

agaccattgt gtcgctctcc attgtctaca caattggaca agcagtcacc tcagtaagct    300 

ccattaatga cctcacagac cacaaccatg atggcacccc cgacagcctt cctgtgcacg    360 

tggtgctgtc cttgatcggc ctggccctga tagctctcgg gactggagga atcaaaccct    420 

gtgtgtctgc gtttggtgga gatcagtttg aagagggcca ggagaaacaa agaaacagat    480 

ttttttccat cttttacttg gctattaatg ctggaagttt gctttccaca atcatcacac    540 

ccatgctcag agttcaacaa tgtggaattc acagtaaaca agcttgttac ccactggcct    600 

ttggggttcc tgctgctctc atggctgtag ccctgattgt gtttgtcctt ggcagtggga    660 

tgtacaagaa gttcaagcca cagggcaaca tcatgggtaa agtggccaag tgcatcggtt    720 

ttgccatcaa aaatagattt aggcatcgga gtaaggcatt tcccaagagg gagcactggc    780 

tggactgggc taaagagaaa tacgatgagc ggctcatctc ccaaattaag atggttacga    840 

gggtgatgtt cctgtatatt ccactcccaa tgttctgggc cttgtttgac cagcagggct    900 

ccaggtggac actgcaggca acaactatgt ccgggaaaat cggagctctt gaaattcagc    960 

ccgatcagat gcagaccgtg aacgccatcc tgatcgtgat catggtcccg atcttcgatg   1020 

ctgtgctgta ccctctcatt gcaaaatgtg gcttcaattt cacctccttg aagaagatgg   1080 

cagttggcat ggtcctggcc tccatggcct ttgtggtggc tgccatcgtg caggtggaaa   1140 

tcgataaaac tcttccagtc ttccccaaag gaaacgaagt ccaaattaaa gttttgaata   1200 

taggaaacaa taccatgaat atatctcttc ctggagagat ggtgacactt ggcccaatgt   1260 

ctcaaacaaa tgcatttatg acttttgatg taaacaaact gacaaggata aacatttctt   1320 

ctcctggatc accagtcact gctgtaactg acgacttcaa gcagggccaa cgccacacgc   1380 

ttctagtgtg ggcccccaat cactaccagg tggtaaagga tggtcttaac cagaagccag   1440 

aaaaagggga aaatggaatc agatttgtaa atacttttaa cgagctcatc accatcacaa   1500 

tgagtgggaa agtttatgca aacatcagca gctacaatgc cagcacatac cagttttttc   1560 

cttctggcat aaaaggcttc acaataagct caacagagat tccgccacaa tgtcaaccta   1620 

atttcaatac tttctacctt gaatttggta gtgcttatac ctatatagtc caaaggaaga   1680 

atgacagctg ccctgaagtg aaggtgtttg aagatatttc agccaacaca gttaacatgg   1740 

ctctgcaaat cccgcagtat tttcttctca cctgtggcga agtggtcttc tctgtcacgg   1800 

gattggaatt ctcatattct caggctcctt ccaacatgaa gtcggtgctt caggcaggat   1860 

ggctgctgac cgtggctgtt ggcaacatca ttgtgctcat cgtggcaggg gcaggccagt   1920 

tcagcaaaca gtgggccgag tacattctat ttgccgcgtt gcttctggtc gtctgtgtaa   1980 

tttttgccat catggctcgg ttctatactt acatcaaccc agcggagatc gaagctcaat   2040 

ttgatgagga tgaaaagaaa aacagactgg aaaagagtaa cccatatttc atgtcagggg   2100 

ccaattcaca gaaacagatg tgaaggtcag gaggcaagtg gaggatggac tgggcccgca   2160 

gatgccctga cctctgcccc caggtagcag gacactccat tggatggccc ctgatgagga   2220 

agacttcaga attgggaact aaaccatgaa tgctattttc ttttttcttt ttcttttctt   2280 

tttttttttt tttttttttt tgagacagag ttttgctctt gttgtccagg ctggagtgca   2340 

atggcacgat ctcagctcac tgcaacctcc gcctcccagg ttcaagtaat tctcctgcct   2400 

cagcctcccg agtggctggg attagcggca tgcaccacca cgcccagcta tttttgtatt   2460 

tttagtagag atggggtttc accatgttgg ccaggatggt ctcgatctct tgacctggtg   2520 

atctgcccac ctcggcctgc caaagtgctg ggattacagg cttgagctac cgcgcccggc   2580 

cgtgaacgct attttctaag cagccagcag tgaatctaaa actctggaag aagtcttctg   2640 

tttgaaaggc ttatttaagc cacacgtaca cacactgtct tagagtactg tgagcccacc   2700 

ccacattggt catcttccct atcacacaaa tgatgttatt ttggactagc ttaattttga   2760 

aatggtaaca aagtttccta ttccatactg ttcatttcta atactcttac gaaaactatt   2820 

ctaaaggagg caggagccaa ggccaaaagt gaacgtacag gtttgaaatg gctgtgataa   2880 

ggaccagctg gtattaactg ataactttac ctttgggttt ttgttatttt gtttttctag   2940 

tccctacctg tgtttaaatt atggataact cgaaagacag ctcaggtgaa ggccagtaat   3000 

gatttttttg aagtttcaat ggtgtgaaat aaatttctgt tctta                   3045 

 
           
             2  
             2829  
             DNA  
             Ovis aries  
           
            2 

gaaacaacat ctttagcacg gattcctccc acctggactc ctcgctcgcc agtcgcaggg     60 

agccctcgga gccgccagca tgggaatgtc cgtgccgaag agctgcttcg gttacccctt    120 

aagcatcttc ttcatcgtgg tcaatgagtt ctgcgaaagg ttctcttact atggaatgag    180 

agcactcctg atcctgtact tccaacgttt cctgggctgg aacgacaacc tgggcaccgc    240 

catctatcac acgttcgtcg ccctgtgcta cctgacgccc atcctcggag ctctcatcgc    300 

cgactcctgg ctggggaagt tcaagacgat cgtgtcgctg tccatcgtct acaccattgg    360 

gcaggtagtc atcgctgtga gctcaattaa tgacctcact gacttcaacc atgatggaac    420 

cccaaacaat atttctgtgc acgtggcact ctccatgatt ggcctggtcc tgatagctct    480 

gggtaccgga gggataaagc cttgcgtgtc tgcatttggc ggagatcagt ttgaagaggg    540 

ccaggaaaag caaaggaaca gatttttttc catcttttat ttggccatta atgctggaag    600 

tttgctttct actatcatca cccccatgct cagagttcag gtatgcggaa ttcacagtaa    660 

gcaagcttgt taccccctgg cctttggggt tcctgctgca ctcatggctg tatctctgat    720 

cgtgtttgtc attggcagtg gaatgtacaa gaaggtccag ccccagggta acatcatgtc    780 

taaagttgcc aggtgcattg ggtttgccat caaaaatagg attagccatc ggagtaagaa    840 

atttcctaag agggagcact ggctggactg ggctagcgag aaatatgatg agcggctcat    900 

ctctcaaatt aagatggtta caagggtgat gttcctgtac attcctctcc ccatgttctg    960 

ggccttgttt gatcagcagg gctccaggtg gacactgcaa gcaacgacca tgagtgggaa   1020 

gattggaatc attgaaatcc agccggatca gatgcagacg gtgaacgcca tcctgatcgt   1080 

cgtcatggtc cccatcgtgg atgccgtggt atatcctctg atcgcaaagt gtggtttaaa   1140 

tttcacctcc ctgaagaaga tgaccgtcgg catgtttctg gcctccatgg ctttcgtggc   1200 

agctgccatc gtgcaggtgg acattgacaa aactctgccc gtcttcccca aaggaaatga   1260 

agtccaaatc aaagtcctga atataggaaa taatagcatg accgtgtctt ttcccggaac   1320 

gacagtgaca tgtgaccaga tgtctcaaac aaacggattt ctgactttca acgtagacaa   1380 

cctaagtata aacatttctt ctactggaac accagtcact ccagtaactc ataactttga   1440 

gtccggccat cgccataccc ttctcgtctg ggccccaagt aactaccaag tggtaaaaga   1500 

tggccttaac cagaagccag aaaaagggag aaatggaatc agattcgtta atgcttttgg   1560 

cgagagcttc ggcgtcacaa tggatgggga agtttacaac aatgtctccg gtcacaatgc   1620 

cagtgaatat ctttttttct cttctggcgt aaagagcttc acaataaact caccagagat   1680 

ttcacaacag tgtgaaaaac agttcaaaac atcctacctt gaatttggta gtgcgtttac   1740 

ctatgtaatc agcagaaaga gtgacggttg ccccgaacca aagattttcg aagacatctc   1800 

ccccaacaca gtcagcatgg ctctgcagat cccccagtac ttcctcctca cctgtggcga   1860 

ggtggtcttc tccatcaccg gcctggagtt ctcctattct caggctcctt ccaacatgaa   1920 

gtcggtactt caggcaggat ggctgttgac cgtggccgtt ggcaacatca tcgtgcttat   1980 

tgtggcagga gcaggccagt tcagtgaaca gtgggccgag tacgttctgt ttgcggcatt   2040 

gcttctggtc gtctgcataa tatttgccat catggctcga ttctatacgt atgtcaaccc   2100 

cgcagagatt gaagctcagt ttgatgagga tgacaaggag gatgacctgg aaaagagtaa   2160 

cccatacgcc aagctggact tcgtctcaca gacacaaatg tgaatgtcag gaagcaagcg   2220 

gacgcggggc tgggccaggg tgtgcccagg ggtctgtccc atgggggcag gacactctgt   2280 

tgggtggcct ctgatgggga agacttcaga actgtggacc aaaccaagac agctgctttc   2340 

tcagcagccg gcaatgaacc tgaaactcca aaagacgtcc ttttgtttgt ttgtttttag   2400 

agaagtctta tttaaagcgc acacacacgc acacgcacac acatgcacac acacacactt   2460 

ttataagagt ccatactctg cctgaactcc ttttcctaac acacaaataa agttattttg   2520 

gactaacttg aatttttgaa atggtggcca agctccatac gtgcattcgc acactctgtg   2580 

caaacaatgt taaaggaggc aaaaagtgaa tggttggggc ttttgaatag tacgtgttca   2640 

taataaggac cggctggtat taactgataa ctctaccttc tgtttttagt tctgtttttc   2700 

cattccctac ctctttgtaa attatggatt aacctttgaa aaaccactca ggtaaaggca   2760 

agtcatgatt tttggagtct caacggtatg aaataaactc tcattctcaa gaaaaaaaaa   2820 

aaaaaaaaa                                                           2829 

 
           
             3  
             2900  
             DNA  
             Rattus norvegicus  
           
            3 

ctgaactcct gcttgccagt cgccggtcag gagcctcgga gccgccacaa tggggatgtc     60 

caagtctcgg ggttgctttg gctacccatt gagcatcttc ttcatcgtgg tcaatgaatt    120 

ctgtgaaaga ttctcctact atgggatgcg agctctcctg gttctgtact tcaggaactt    180 

ccttggctgg gatgatgacc tctccacggc catctaccat acgtttgttg ccctctgcta    240 

cctgactcca attcttggag ctctgatcgc agactcgtgg ctggggaagt tcaagacaat    300 

tgtctcacta tccatcgtct acacgatcgg acaggccgtc atctcagtga gctcaattaa    360 

tgaccttaca gaccatgacc acgacggcag tcctaacaac cttcctttgc acgtagcact    420 

gtccatgatc ggcctggccc tgatagccct tggtacagga ggaatcaagc cctgtgtgtc    480 

tgcatttggt ggcgatcagt ttgaagaggg tcaggaaaaa cagcgaaacc ggttcttttc    540 

catcttttat ttggctatca acgcaggaag cctgctctcc acgatcatca ctcccatact    600 

cagagttcag cagtgcggaa tccacagcca acaagcttgt tacccactgg cctttggggt    660 

tccggcagct ctcatggctg ttgccctaat tgtgtttgtc ctcggcagtg gaatgtacaa    720 

gaagtttcag ccccagggca acatcatggg caaagtggcc aagtgcattg gctttgccat    780 

caaaaacagg tttcggcacc gaagtaaggc atttcccaag agggaacact ggctggactg    840 

ggctaaagag aaatacgatg agaggctcat ctcgcagatt aagatggtga cgaaggtgat    900 

gttcctgtac attcccctcc ccatgttttg ggccttgttt gaccagcagg gttccaggtg    960 

gacactgcaa gcaacgacca tgactgggaa aattggaaca attgagattc agccggacca   1020 

gatgcagacg gtgaacgcca tcttgattgt catcatggtc cccattgtgg acgccgtggt   1080 

gtatccgctc attgcaaaat gtggtttcaa cttcacctcc ctgaagaaga tgaccgttgg   1140 

gatgttcctg gcatccatgg cctttgtggt ggctgcaatt gtgcaggtgg aaatcgataa   1200 

aactcttcca gtcttcccca gcggaaatca agttcaaatt aaggtcttga acattggaaa   1260 

caatgacatg gccgtgtatt ttcctggaaa gaatgtgaca gttgcccaaa tgtctcagac   1320 

agacacattc atgactttcg atgtagacca gctgacaagc ataaacgtgt cttctcccgg   1380 

atctccaggc gtcaccacgg tagctcatga gtttgagccg ggtcaccggc acacccttct   1440 

agtgtggggc cccaatctat accgtgtggt aaaagacggt cttaaccaaa agccagagaa   1500 

aggggagaac ggaatcagat tcgtcagcac ccttaacgag atgatcacca tcaaaatgag   1560 

tggaaaagtg tacgaaaatg tcaccagtca cagcgccagc aactatcagt ttttcccttc   1620 

tggccaaaaa gactacacaa taaacaccac agagattgca ccaaactgtt catctgattt   1680 

taaatcttcc aaccttgact tcggcagcgc gtacacctac gtgatcagaa gtagggcgag   1740 

tgatggctgc ctggaagtga aggaattcga agacatccca cccaacacgg tgaacatggc   1800 

cctgcagatc ccacagtact tcctcctcac ctgcggcgag gtggtcttct ctgtcacagg   1860 

actggagttc tcctattccc aggccccgtc taacatgaag tccgtgcttc aggcaggatg   1920 

gcttctaacc gtggccatcg gtaatatcat tgtcctcatt gtggctgagg caggccactt   1980 

cgacaaacag tgggctgagt atgttctgtt cgcctccttg ctcctggtcg tctgcatcat   2040 

atttgccatt atggcccgat tctacaccta catcaaccca gcagagatcg aggcacagtt   2100 

cgatgaggat gagaagaaaa agggcgtagg gaaggaaaac ccgtattcct cgttggaacc   2160 

tgtctcacag acaaacatgt gaagatcaga aagcaagtgg agaacatacc aagtccagca   2220 

ttcaccatga cctctgccca agggacagga ccctccacca cagagtcctt gctggagaaa   2280 

gacttcagac atgtgagcca aaataataac aaagcaggtt ttcaggctga cggctgtgaa   2340 

tctgaaactc taggggagcc tttttaattt gtttttcttg agacaaggta tctctgtgta   2400 

accctggcta tcctggaact cactctatag accaggctgg cctcgaactc acagatatct   2460 

gtctgcctct gcctcctaag tactgggatt caaggcatgt acggcaactg cccagctaaa   2520 

atattattta taacatgcac tttctgggtt ttttgttttt aaaacatact ttttttttta   2580 

acactgggcc atttctaaca tttctgccac agaagtggat ttagctcaga ttaattttga   2640 

aaaggtaaca gtactgtttt ttttccttaa tgctcttatg aaaacaatgt tgaatttaca   2700 

gagggctttt ttagcagtgt gtagtgagtg tcagctgatt cgagctaata accttacctc   2760 

ggggtttttg tttctttgtt ttcctggtct cctttgcctg acctcttttt aaattatgtg   2820 

taattcaaaa gactattcaa gtgatggtta gtcatgagtc gtgacgtttg actggtgtga   2880 

agtaaattct tgttcttaag                                               2900 

 
           
             4  
             3128  
             DNA  
             Mus musculus  
           
            4 

gtcgcccgtc cggagccttg gagccaccac aatggggatg tccaagtctc ggggttgctt     60 

cggttacccg ttgagcatct tcttcatcgt ggtcaatgaa ttctgtgaaa gattctccta    120 

ctatggcatg cgagcactcc tggttctgta cttcaggaac ttcctcggct gggacgacaa    180 

tctctccacg gccatttacc atacgttcgt tgccctctgc tacctgactc caattcttgg    240 

agctctgatc gcagactcgt ggctggggaa gttcaagaca attgtttcac tatccatcgt    300 

ctacacgatt ggacaagcag tcatctcggt gagctcaatt aatgacctca cagaccacga    360 

ccacaatggc agtcctgaca gccttcccgt gcacgtagca ctgtccatgg ttggcctggc    420 

cctgatagcc cttggtacag gaggaatcaa gccctgtgtg tctgcgtttg gtggcgatca    480 

gtttgaagag ggtcaggaaa aacagcgaaa ccggttcttt tccatctttt atttggctat    540 

caacggggga agcctgctct ccacgatcat cactcccata ctcagagttc aacagtgcgg    600 

aatccacagt caacaagctt gttacccact ggccttcggg gttccagcgg ctctcatggc    660 

tgttgcccta attgtgtttg tccttggcag tggaatgtac aagaagttcc agccccaggg    720 

caacatcatg ggcaaagtgg ccaagtgcat tggttttgcc atcaaaaaca ggtttcggca    780 

ccgaagtaag gcatatccca agagggagca ctggctggac tgggctaaag agaaatacga    840 

cgagcggctc atctcacaga ttaagatggt cacgaaggtg atgttcctgt tcatcccact    900 

ccccatgttc tggggcctgt ttgaccaaca agggtccaga tggacactgc aagcaacgac    960 

catgaatggg aaaattggag caaatgaaat tcagccggac cagatgcaga cggtgaatgc   1020 

catcctgaat gtcaacaatg gccccaatgt ggacgccgtt gtgtaccgct caattgcaaa   1080 

atgtggtttc aacttcacat ccctgaagaa gatgactgtt gggatgttcc tggcgtccat   1140 

ggcctttgtg gtggctgcaa ttgtgcaggt ggaaatcgat aaaactcttc cagtcttccc   1200 

tggtggaaat caagtccaaa ttaaggtctt gaacatcgga aacaataaca tgaccgtgca   1260 

ttttcctgga aatagtgtga cgcttgccca aatgtctcag acagacacgt tcatgacttt   1320 

cgatatagac aagctgacaa gcataaacat atcttcctct ggatccccag gagtcaccac   1380 

agtagctcat gattttgagc agggtcaccg gcacaacctt ctagtgtggg aacccagtca   1440 

ataccgtgtg gtaaaagatg gtcctaacca aaagccagag aaaggggaga acggaatcag   1500 

gtttgtcaac acccttaacg agatggtcac caacaaaatg agtgggaaag tatatgaaaa   1560 

attcacaagt cacaacgcca gcggctacaa gttcctccct tctggcgaaa agcagtacac   1620 

aataaacacc acggcggtgg caccaacctg tctaactgat tttaaatctt ccaaccttga   1680 

ctttggcagc gcgtatacct acgtgatccg aagggcgagt gatggctgcc tggaagtgaa   1740 

ggaatttgaa gacatcccac ccaacactgt gaacatggct ctgcagatcc cacagtactt   1800 

ccttctcacc tgcggcgagg tggtcttctc tgtcacagga ctggagttct cttattccca   1860 

ggctccgtct aacatgaagt ccgtgcttca ggcaggctgg cttctaactg tggcggtcgg   1920 

caatatcatt gtgctcatcg tggcaggggc ggggcacttc cccaaacagt gggctgagta   1980 

cattctgttt gcctcattgc ttctggttgt ctgcgtgata ttcgccatca tggctcgatt   2040 

ctacacctac atcaacccag cagagattga agcacagttt gatgaggatg agaagaaaaa   2100 

gggcatagga aaggaaaacc cgtattcttc attggaacca gtctcacaga caaatatgtg   2160 

aagggcagaa ggcaaattgg agaaagatca agttcaacat gagccctgac ctctgtccaa   2220 

gggacaggac actccaccac agagtccctg atggagaaag acctcagaag tgtgagccag   2280 

aataataaca aagcaggttt tctaaccaac agctgtgaac ctgaaactct aggggagcct   2340 

tttttattta aaaaaatttt ttttttaatt ttttaaattt tttttatttt ttattttttt   2400 

tgcttgtttg tttgtttcga gacagggttt ctcgtgtgta gcccttggtt gtcctggaac   2460 

tcactctgta gaccagactg gcctcaaact cagaaatcca cctgcccctg cccctgcccc   2520 

tgcccctgcc cctgcccctg cctctgcctc tgcctcccaa gtgctggatt tggaggcatg   2580 

caccaccatg cccagctata attttttttt tttaagacag ggattctctg tataagcctg   2640 

actgccctgg aacttgctct atagaccagg ctggccttga actcacagag atctgcctgc   2700 

ctcttcctcc taagtactgg gatttcaggc atgcaccaca actgcccagc taaaatatta   2760 

tttataatat gcactttctg gtttgttttt gtttttcttt taaactgggc tgtatcttac   2820 

atttctgcca cagaaatgaa cttagctcag attaacttaa ttttgaaaag gcaatagtat   2880 

tgttttttct aacagtttta tgaaaacaat attgaattta cagagggctt ttttaatagt   2940 

gtgtaatgag tatcaactga ttcaagctaa ttgctttacc ttggggtttt tttgtttgtt   3000 

tgtttgtttg tttgtttgtt tgtttttcta gtctcctttg ccttacctct ttttaaatta   3060 

tgtgtaattc aaaagactag tcatgagttg tgaagtttca ctggtctgaa ataaattcta   3120 

gttcttaa                                                            3128 

 
           
             5  
             2709  
             DNA  
             Oryctolagus cuniculus  
           
            5 

caccatggga atgtctaagt cactgagctg cttcggctat cccctgagca tcttcttcat     60 

cgtggtcaat gagttctgcg aaaggttctc ctactatggg atgagagcac tcctgattct    120 

gtacttcaga aacttcatcg gctgggacga caacctgtcc acggtcatct accacacgtt    180 

cgtcgcgctg tgctacctca cgcccattct cggagctctc atcgccgacg cgtggctggg    240 

gaagttcaag accatcgtgt ggctgtccat cgtctacacc atcggacaag cagtcacctc    300 

cctcagctcc gtcaatgagc tcacagacaa caaccatgac gggacccccg acagcctccc    360 

tgtgcacgtg gcggtgtgca tgatcggcct gctcctgata gccctcggga caggaggaat    420 

caagccctgt gtgtctgcct ttggcggcga tcagtttgag gagggccagg aaaagcaaag    480 

aaaccggttt ttttccatct tttacttggc cattaacgct gggagtctgc tgtccacaat    540 

catcaccccc atggtcagag ttcaacaatg tggaattcac gttaaacaag cttgctaccc    600 

actggccttt gggattcctg ctatcctcat ggctgtatcc ctgatcgtgt tcatcatcgg    660 

cagtgggatg tacaagaagt tcaagccgca ggggaacatc ctgagcaaag tggtgaagtg    720 

catctgcttt gccatcaaaa ataggtttag gcaccgcagt aagcagtttc ccaagagggc    780 

gcactggctg gactgggcta aggagaaata cgacgagcgg cttatcgcgc agatcaagat    840 

ggttacgagg gtgctgttcc tgtacatccc actccccatg ttctgggcct tgtttgatca    900 

gcagggttcc agatggacgc tgcaagcgac gaccatgtcc gggagaattg gaatccttga    960 

aattcagccg gatcagatgc agactgtgaa caccatcttg attattatcc tggtccccat   1020 

catggacgcc gtggtgtatc ctctgattgc aaagtgtggc ctcaacttca cctctctgaa   1080 

gaagatgacg attgggatgt tcctggcttc catggccttc gtggcagctg caatcctgca   1140 

ggtggaaatc gataaaactc ttcctgtctt ccccaaagcc aatgaagtcc aaattaaagt   1200 

tctgaatgta ggaagtgaga acatgatcat ctctcttcct gggcagacgg tgacgctcaa   1260 

ccagatgtct caaacgaatg aattcatgac tttcaatgaa gacacactga caagcataaa   1320 

catcacttcc ggatcacaag tcaccatgat cacacccagc cttgaggcag gccagcgcca   1380 

caccctgctg gtgtgggccc ccaataacta ccgagtggtc aatgacggcc tgacccagaa   1440 

gtcagacaaa ggagaaaatg gaatcaggtt tgtgaacact tacagccagc ccatcaacgt   1500 

cacgatgagc gggaaagttt acgaacacat cgccagctac aatgccagcg agtatcagtt   1560 

tttcacttct ggagtaaagg gcttcaccgt cagctcggca ggcatctcgg agcagtgcag   1620 

gcgggacttt gagtctccgt acctggagtt tggcagcgcg tacacgtacc tgatcacgag   1680 

ccaggctact ggctgccccc aagtgacgga gtttgaagat attccgccca acacaatgaa   1740 

catggcttgg caaatcccac agtacttcct catcacctct ggcgaggtgg tcttctccat   1800 

cacgggcctg gagttctcct attctcaggc tccttccaac atgaagtcgg tgctgcagga   1860 

ccggtggctg ctgacggtgg ctgtgggcaa catcattgtg ctcatcgtgg ccggcgcggg   1920 

ccagatcaac aagcagtggg ccgagtacat cctctttgcc gccctgctcc tggtcgtctg   1980 

tgtcatattt gccatcatgg ctcgattcta tacgtatgtc aacccggccg agatcgaggc   2040 

tcagtttgaa gaagatgaga agaaaaagaa cccagaaaag aacgacctct acccctccgt   2100 

ggcgcccgtc tcacagacac agatgtgagt ctggaggcgg tgtaggaggc ccacgcctgg   2160 

cgtgcactgt gacctctgtc cgagggcgca ggacgtaccc ctgggcagcc ccggaagggg   2220 

aggacttgag aactgtgaac cagaccacga aagctatgtt ctgagcagcc agtgatgagt   2280 

ccaaaactct gaaagaaatc ttgttgaaag tcttatttaa aacacacaca cacacacaca   2340 

cacacacaca cacacttttc caacactgac agcctaccca tgttaactcc ttctctacca   2400 

atgcaaatgc tgttattttg gactaactta attttgaaca ctgttctatg ttgcttgtat   2460 

tctaacatcc ttaggaaagg caatgttaag agaggcagga ggcaatgcca aagttgaata   2520 

tgtaggtgtc agaatggtat ataccacata ttacttagta ttaactgaaa acctcaactt   2580 

tgaggttttg ttctattttt tccactcctt acctcttttt aacctgtgga caactcaaaa   2640 

ggaccactca gataaaggcc agtaaagatt ttttttgccg ttttgatgaa ataaaataat   2700 

gttcctaag                                                           2709 

 
           
             6  
             2914  
             DNA  
             Gallus gallus  
           
            6 

gctctctgtc cgtccctcgg tccctccgtc cctccgtccc cgcgcggccg ccagcagcgt     60 

gccggcccca tggctgcaaa aagtaagagt aagggccgat cagtgccgaa ctgctttggc    120 

taccccttga gcatcttctt catcgtcatc aatgagttct gcgagaggtt ctcctactat    180 

ggcatgcgag ctgtgctcgt attgtatttc aagtacttcc tgcggtggga tgacaacttt    240 

tctacagcca tctaccacac gtttgttgct ctgtgctact tgacgcccat cctgggagcg    300 

ctcattgcag actcatggct gggaaagttt aagaccattg tctccctgtc cattgtctat    360 

acaattgggc aggcagtcat ggctgtaagc tccataaacg acatgacaga tcaaaacaga    420 

gatggcaatc ctgataatat tgcggtgcac attgccctgt ctatgactgg cttgattctc    480 

atcgcgcttg gaactggtgg gatcaaacct tgtgtctcag catttggtgg ggatcagttt    540 

gaagaacatc aggaaaaaca aagaagtaga ttcttctcta tcttttattt gtccattaat    600 

gctggaagtc tcatatccac tataatcacc ccaattctca gagctcaaga atgtggcatt    660 

cacagcagac agcagtgcta cccgctggca tttggagttc ccgctgccct catggctgtt    720 

tcattagttg tgttcatagc tggaagtgga atgtacaaaa aagttcaacc gcaaggcaat    780 

ataatggttc gagtttgtaa atgcattgga tttgccatta aaaacaggtt tcggcatcgc    840 

agcaaagagt atcccaaaag agagcactgg ctagactggg caagcgagaa gtatgataaa    900 

cgactgattg ctcagaccaa gatggtgttg aaggtgcttt tcctttacat ccctctcccg    960 

atgttctggg cactttttga ccagcaggga tcgagatgga cactgcaagc cacaactatg   1020 

gatggggact ttggagctat gcagattcag ccagaccaaa tgcagactgt caatccaatc   1080 

ctgattataa taatggtccc agttgtagat gctgtgattt atcctttaat ccagaaatgc   1140 

aagatcaatt ttacgcccct gaggaggatc actgttggca tgttccttgc tggtctggct   1200 

ttcgttgctg ctgctctttt gcaagtgcaa atagataaaa ctcttccagt tttccctgca   1260 

gctggacagg cccaaatcaa aataataaat ctaggtgata gcaatgcgaa tgttacattt   1320 

ctgcctaatc ttcagaacgt gactgtcctt cccatggagt caacaggcta caggatgttt   1380 

gagtcttccc agctaaaatc tgtaatggta aattttggga gtgagagtag aagtgaaaat   1440 

atcgactcaa taagcagcaa tacgcatact gtcaccatca agaatgcagc agccggcatt   1500 

gtttctagct tgcggtctga taatttcaca tcaaaaccag aagaaggaaa gaatctagtc   1560 

aggtttgtaa ataatttgcc tcagacagtc aacatcacta tgggtgacac gacttttgga   1620 

atactggaag agacaagtat cagtaattac agtccgttct caggaggaag aacatatgat   1680 

atagtgataa ctgcaggttc aactaattgc aaaccaactt cagagaaatt aggatatggt   1740 

ggtgcttata cgatcgtaat taatgagtgt tctggagatg tgactcaatt aagatacatt   1800 

gaagatatcc aacccaatac agtccatatg gcttggcaga tccctcagta tttcatactt   1860 

acatgtggag aagtagtctt ctctgtcact gggctggagt tttcatactc acaggcacca   1920 

tctaatatga agtcagtgct gcaagcagga tggctgctaa cagtggctgt cggtaacata   1980 

attgtcctta tcgtggctgg agcatccaaa ctcagtgagc agtgggcaga atatgttctc   2040 

tttgctgcct tgctttttgc agtttgcatt atttttgctg tcatggcata tttttataca   2100 

tatactgatc caaatgaggt tgaagcccaa cttgatgaag aagaaaagaa gaaacaaata   2160 

aaacaggatc cagacttgca cggaaaagaa tctgaagctg tctctcagat gtagaaggtg   2220 

tattcaagag catttgtaaa tcatggtagc ctgttaactg tccctgcaat aacaggaatc   2280 

agggtattgc tgacatcact gggtaatata ccttgtggga gagactaaga aacactgttc   2340 

tgacttaaca tacagcctct tgggaagcaa gacgaaatga ttaatctctt gtacagaagc   2400 

tggcatcctg aggaaactcc tgcagaattt gcactcttaa aatgtacctc aagctcaata   2460 

ccatagcatt aaaatattga aattgcactt ggcactatta gacactctaa aaagatgtat   2520 

ttttatactg tatttcaatt ttataatgtg gaggggtggg gaaaaaggtg ttgccaagaa   2580 

atagtaattg aagccaaact gtctgcgtga cccttctagc ctcactgtta cttgaaagca   2640 

ggtcacatgt gccttaaatt cttttctatg tccttaagaa taataggaga aaggttctta   2700 

gatttctcag attaaaatgt ctctgctcca catagcagga acttggacat gcactgtgat   2760 

gtgctttatg tgcctattat taactgccca ttggtatgtt cttaattaat tgtgttaatg   2820 

ggatgtccac tgaggtgaac agacaatggc aaattatatt ttgaataacc accaagaata   2880 

aaacttgtgt tgtaacaaaa aaaaaaaaaa aaaa                               2914 

 
           
             7  
             1840  
             DNA  
             Canis familiaris  
           
            7 

catcttcttc atcgtggtca atgagttctg tgaaagattt tcctactatg gaatgagagc     60 

actcctgatt ctgtacttca gacggttcat cgggtgggac gataatctgt ccacggccat    120 

ctaccacacg tttgtggctc tgtgctacct gacgccgatc ctcggcgcac tgatcgcaga    180 

ctcctggctg ggaaagttca agacaatcgt gtcactctcc attgtctaca caattggaca    240 

ggcggtcact gcagtaagct caattaatga cctcacagac tataacaaag atggaactcc    300 

tgacaatctg tccgtgcatg tggcactgtc catgattggc ctggccctga tagctctggg    360 

aactggagga ataaagccct gtgtgtctgc atttggtgga gaccagtttg aagagggcca    420 

ggaaaaacaa agaaacagat tcttttccat cttttatttg gccattaatg ctggaagctt    480 

gatttccact attgtcactc ccatgctcag agttcacgaa tgtggaattt acagtcagaa    540 

agcttgttac ccactggcat ttggggttcc tgctgctctc atggccgtat ctctgattgt    600 

atttgtcatt ggcagtggaa tgtacaagaa gtttcagccc cagggtaatg tcatgggtaa    660 

agttgtcaag tgcattggtt ttgccctcaa aaataggttt aggcaccgga gtaagcagtt    720 

tcccaagagg gagcactggc tggactgggc taaagagaaa tacgatgagc ggctcatctc    780 

tcaaattaag atggtcacaa aagtgatgtt cttgtacatc ccactcccaa tgttctgggc    840 

cctgtttgac cagcagggct ccaggtggac actgcaagca acagctatga gtgggaaaat    900 

tggacttctt gaagttcagc cagatcagat gcagactgtg aatgccatct tgattgtcgt    960 

catggtcccc atcatggatg ccgtggtgta ccctctgatt gcaaaatgtg gcttcaattt   1020 

cacctccttg aagaggatga cagttggaat gttcctggct tccatggcct tcgtgatggc   1080 

ggcgattgtt cagctggaaa ttgataaaac tcttccagtc ttccccaaac aaaatgaagt   1140 

ccaaatcaaa gtactgaata taggaaatgg tgccatgaat gtatcttttc ctggagcggt   1200 

ggtgacagtt agccaaatga gtcaatcaga tggatttatg acttttgatg tagacaaact   1260 

gacaagtata aacatttctt ccactggatc accagtcatt ccagtgactt ataactttga   1320 

gcagggccat cgccataccc ttctagtatg ggcccccaat aattaccgag tggtaaagga   1380 

tggccttaac cagaagccag aaaaaggaga aaatggaatc agatttataa atagtcttaa   1440 

tgagagcctc aacatcacca tgggcgacaa agtttatgtg aatgtcacca gtcacaatgc   1500 

cagcgagtat cagttctttt ctttgggcac aaaaaacatt acaataagtt caacacaaca   1560 

gatctcacaa aattgtacaa aagttctcca atcatccaac cttgaatttg gtagtgcata   1620 

tacctatgta atcggaacgc agagcactgg ctgccctgaa ttgcatatgt ttgaagatat   1680 

ttcacccaac acagttaaca tggctctgca gatcccgcag tacttcctca tcacctgcgg   1740 

cgaggtggtt ttctctgtca caggactgga gttctcatat tctcaggccc cctccaacat   1800 

gaagtcggtg cttcaggcgg gatggctgct gacagtggct                         1840 

 
           
             8  
             1995  
             DNA  
             Canis familiaris  
           
            8 

catcttcttc atcgtggtca atgagttctg tgaaagattt tcctactatg gaatgagagc     60 

actcctgatt ctgtacttca gacggttcat cgggtgggac gataatctgt ccacggccat    120 

ctaccacacg tttgtggctc tgtgctacct gacgccgatc ctcggcgcac tgatcgcaga    180 

ctcctggctg ggaaagttca agacaatcgt gtcactctcc attgtctaca caattggaca    240 

ggcggtcact gcagtaagct caattaatga cctcacagac tataacaaag atggaactcc    300 

tgacaatctg tccgtgcatg tggcactgtc catgattggc ctggccctga tagctctggg    360 

aactggagga ataaagccct gtgtgtctgc atttggtgga gaccagtttg aagagggcca    420 

ggaaaaacaa agaaacagat tcttttccat cttttatttg gccattaatg ctggaagctt    480 

gatttccact attgtcactc ccatgctcag agttcacgaa tgtggaattt acagtcagaa    540 

agcttgttac ccactggcat ttggggttcc tgctgctctc atggccgtat ctctgattgt    600 

atttgtcatt ggcagtggaa tgtacaagaa gtttcagccc cagggtaatg tcatgggtaa    660 

agttgtcaag tgcattggtt ttgccctcaa aaataggttt aggcaccgga gtaagcagtt    720 

tcccaagagg gagcactggc tggactgggc taaagagaaa tacgatgagc ggctcatctc    780 

tcaaattaag atggtcacaa aagtgatgtt cttgtacatc ccactcccaa tgttctgggc    840 

cctgtttgac cagcagggct ccaggtggac actgcaagca acagctatga gtgggaaaat    900 

tggacttctt gaagttcagc cagatcagat gcagactgtg aatgccatct tgattgtcgt    960 

catggtcccc atcatggatg ccgtggtgta ccctctgatt gcaaaatgtg gcttcaattt   1020 

cacctccttg aagaggatga cagttggaat gttcctggct tccatggcct tcgtgatggc   1080 

ggcgattgtt cagctggaaa ttgataaaac tcttccagtc ttccccaaac aaaatgaagt   1140 

ccaaatcaaa gtactgaata taggaaatgg tgccatgaat gtatcttttc ctggagcggt   1200 

ggtgacagtt agccaaatga gtcaatcaga tggatttatg acttttgatg tagacaaact   1260 

gacaagtata aacatttctt ccactggatc accagtcatt ccagtgactt ataactttga   1320 

gcagggccat cgccataccc ttctagtatg ggcccccaat aattaccgag tggtaaagga   1380 

tggccttaac cagaagccag aaaaaggaga aaatggaatc agatttataa atagtcttaa   1440 

tgagagcctc aacatcacca tgggcgacaa agtttatgtg aatgtcacca gtcacaatgc   1500 

cagcgagtat cagttctttt ctttgggcac aaaaaacatt acaataagtt caacacaaca   1560 

gatctcacaa aattgtacaa aagttctcca atcatccaac cttgaatttg gtagtgcata   1620 

tacctatgta atcggaacgc agagcactgg ctgccctgaa ttgcatatgt ttgaagatat   1680 

ttcacccaac acagttaaca tggctctgca gatcccgcag tacttcctca tcacctgcgg   1740 

cgaggtggtt ttctctgtca caggactgga gttctcatat tctcaggccc cctccaacat   1800 

gaagtcggtg cttcaggcgg gatggctgct gacagtggct tgttggcaac atcattgtgc   1860 

tcattgtggc aggagcaggc cagttcagtg aacagtgggc tgaatacatc ctatttgcgg   1920 

cattgcttct ggttgtctgt gtaatatttg ccatcatggc ccggttttac acttacgtca   1980 

atccagcaga gattg                                                    1995 

 
           
             9  
             381  
             DNA  
             Canis familiaris  
           
            9 

tggctgggga agttcaagac aatcgtgtca ctctccattg tctacacaat tggacaggcg     60 

gtcactgcag taagctcaat taatgacctc acagactata acaaagatgg aactcctgac    120 

aatctgtccg tgtatgtggc actgtccatg attggcctgg ccctgatagc tctgggaact    180 

ggaggaataa agccctgtgt gtctgcattt ggtggagacc agtttgaaga gggccaggaa    240 

aaacaaagaa acagattctt ttccatcttt tatttggcca ttaatgctgg aagcttgatt    300 

tccactattg tcactcccat gctcagagtt cacgaatgtg gaatttacag tcagaaagct    360 

tgctacccac tggcctttgg g                                              381 

 
           
             10  
             4  
             PRT  
             Artificial Sequence  
             
               tetrapeptide  
             
           
            10 

Met Gly Met Met 
 1 

 
           
             11  
             1410  
             DNA  
             Canis familiaris  
           
            11 

catcttcttc atcgtggtca atgagttctg tgaaagattt tcctactatg gaatgagagc     60 

actcctgatt ctgtacttca gacggttcat cgggtgggac gataatctgt ccacggccat    120 

ctaccacacg tttgtggctc tgtgctacct gacgccgatc ctcggcgcac tgatcgcaga    180 

ctcctggctg ggaaagttca agacaatcgt gtcactctcc attgtctaca caattggaca    240 

ggcggtcact gcagtaagct caattaatga cctcacagac tataacaaag atggaactcc    300 

tgacaatctg tccgtgcatg tggcactgtc catgattggc ctggccctga tagctctggg    360 

aactggagga ataaagccct gtgtgtctgc atttggtgga gaccagtttg aagagggcca    420 

ggaaaaacaa agaaacagat tcttttccat cttttatttg gccattaatg ctggaagctt    480 

gatttccact attgtcactc ccatgctcag agttcacgaa tgtggaattt acagtcagaa    540 

agcttgttac ccactggcat ttggggttcc tgctgctctc atggccgtat ctctgattgt    600 

atttgtcatt ggcagtggaa tgtacaagaa gtttcagccc cagggtaatg tcatgggtaa    660 

agttgtcaag tgcattggtt ttgccctcaa aaataggttt aggcaccgga gtaagcagtt    720 

tcccaagagg gagcactggc tggactgggc taaagagaaa tacgatgagc ggctcatctc    780 

tcaaattaag atggtcacaa aagtgatgtt cttgtacatc ccactcccaa tgttctgggc    840 

cctgtttgac cagcagggct ccaggtggac actgcaagca acagctatga gtgggaaaat    900 

tggacttctt gaagttcagc cagatcagat gcagactgtg aatgccatct tgattgtcgt    960 

catggtcccc atcatggatg ccgtggtgta ccctctgatt gcaaaatgtg gcttcaattt   1020 

cacctccttg aagaggatga cagttggaat gttcctggct tccatggcct tcgtgatggc   1080 

ggcgattgtt cagctggaaa ttgataaaac tcttccagtc ttccccaaac aaaatgaagt   1140 

ccaaatcaaa gtactgaata taggaaatgg tgccatgaat gtatcttttc ctggagcggt   1200 

ggtgacagtt agccaaatga gtcaatcaga tggatttatg acttttgatg tagacaaact   1260 

gacaagtata aacatttctt ccactggatc accagtcatt ccagtgactt ataactttga   1320 

gcagggccat cgccataccc ttctagtatg ggcccccaat aattaccgag tggtaaagga   1380 

tggccttaac cagaagccag aaaaagggag                                    1410 

 
           
             12  
             670  
             DNA  
             Canis familiaris  
           
            12 

gccatcgcca tacccttcta gtatgggccc ccaataatta ccgagtggta aaggatggcc     60 

ttaaccagaa gccagaaaaa ggagaaaatg gaatcagatt tataaatagt cttaatgaga    120 

gcctcaacat caccatgggc gacaaagttt atgtgaatgt caccagtcac aatgccagcg    180 

agtatcagtt cttttctttg ggcacaaaaa acattacaat aagttcaaca caacagatct    240 

cacaaaattg tacaaaagtt ctccaatcat ccaaccttga atttggtagt gcatatacct    300 

atgtaatcgg aacgcagagc actggctgcc ctgaattgca tatgtttgaa gatatttcac    360 

ccaacacagt taacatggct ctgcagatcc cgcagtactt cctcatcacc tgcggcgagg    420 

tggttttctc tgtcacagga ctggagttct catattctca ggccccctcc aacatgaagt    480 

cggtgcttca ggcgggatgg ctgctgacag tggcttgttg gcaacatcat tgtgctcatt    540 

gtggcaggag caggccagtt cagtgaacag tgggctgaat acatcctatt tgcggcattg    600 

cttctggttg tctgtgtaat atttgccatc atggcccggt tttacactta cgtcaatcca    660 

gcagagattg                                                           670 

 
           
             13  
             662  
             PRT  
             Canis familiaris  
           
            13 

Ile Phe Phe Ile Val Val Asn Glu Phe Cys Glu Arg Phe Ser Tyr Tyr 
 1               5                  10                  15 

Gly Met Arg Ala Leu Leu Ile Leu Tyr Phe Arg Arg Phe Ile Gly Trp 
            20                  25                  30 

Asp Asp Asn Leu Ser Thr Ala Ile Tyr His Thr Phe Val Ala Leu Cys 
        35                  40                  45 

Tyr Leu Thr Pro Ile Leu Gly Ala Leu Ile Ala Asp Ser Trp Leu Gly 
    50                  55                  60 

Lys Phe Lys Thr Ile Val Ser Leu Ser Ile Val Tyr Thr Ile Gly Gln 
65                  70                  75                  80 

Ala Val Thr Ala Val Ser Ser Ile Asn Asp Leu Thr Asp Tyr Asn Lys 
                85                  90                  95 

Asp Gly Thr Pro Asp Asn Leu Ser Val His Val Ala Leu Ser Met Ile 
            100                 105                 110 

Gly Leu Ala Leu Ile Ala Leu Gly Thr Gly Gly Ile Lys Pro Cys Val 
        115                 120                 125 

Ser Ala Phe Gly Gly Asp Gln Phe Glu Glu Gly Gln Glu Lys Gln Arg 
    130                 135                 140 

Asn Arg Phe Phe Ser Ile Phe Tyr Leu Ala Ile Asn Ala Gly Ser Leu 
145                 150                 155                 160 

Ile Ser Thr Ile Val Thr Pro Met Leu Arg Val His Glu Cys Gly Ile 
                165                 170                 175 

Tyr Ser Gln Lys Ala Cys Tyr Pro Leu Ala Phe Gly Val Pro Ala Ala 
            180                 185                 190 

Leu Met Ala Val Ser Leu Ile Val Phe Val Ile Gly Ser Gly Met Tyr 
        195                 200                 205 

Lys Lys Phe Gln Pro Gln Gly Asn Val Met Gly Lys Val Val Lys Cys 
    210                 215                 220 

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

Pro Lys Arg Glu His Trp Leu Asp Trp Ala Lys Glu Lys Tyr Asp Glu 
                245                 250                 255 

Arg Leu Ile Ser Gln Ile Lys Met Val Thr Lys Val Met Phe Leu Tyr 
            260                 265                 270 

Ile Pro Leu Pro Met Phe Trp Ala Leu Phe Asp Gln Gln Gly Ser Arg 
        275                 280                 285 

Trp Thr Leu Gln Ala Thr Ala Met Ser Gly Lys Ile Gly Leu Leu Glu 
    290                 295                 300 

Val Gln Pro Asp Gln Met Gln Thr Val Asn Ala Ile Leu Ile Val Val 
305                 310                 315                 320 

Met Val Pro Ile Met Asp Ala Val Val Tyr Pro Leu Ile Ala Lys Cys 
                325                 330                 335 

Gly Phe Asn Phe Thr Ser Leu Lys Arg Met Thr Val Gly Met Phe Leu 
            340                 345                 350 

Ala Ser Met Ala Phe Val Met Ala Ala Ile Val Gln Leu Glu Ile Asp 
        355                 360                 365 

Lys Thr Leu Pro Val Phe Pro Lys Gln Asn Glu Val Gln Ile Lys Val 
    370                 375                 380 

Leu Asn Ile Gly Asn Gly Ala Met Asn Val Ser Phe Pro Gly Ala Val 
385                 390                 395                 400 

Val Thr Val Ser Gln Met Ser Gln Ser Asp Gly Phe Met Thr Phe Asp 
                405                 410                 415 

Val Asp Lys Leu Thr Ser Ile Asn Ile Ser Ser Thr Gly Ser Pro Val 
            420                 425                 430 

Ile Pro Val Thr Tyr Asn Phe Glu Gln Gly His Arg His Thr Leu Leu 
        435                 440                 445 

Val Trp Ala Pro Asn Asn Tyr Arg Val Val Lys Asp Gly Leu Asn Gln 
    450                 455                 460 

Lys Pro Glu Lys Gly Glu Asn Gly Ile Arg Phe Ile Asn Ser Leu Asn 
465                 470                 475                 480 

Glu Ser Leu Asn Ile Thr Met Gly Asp Lys Val Tyr Val Asn Val Thr 
                485                 490                 495 

Ser His Asn Ala Ser Glu Tyr Gln Phe Phe Ser Leu Gly Thr Lys Asn 
            500                 505                 510 

Ile Thr Ile Ser Ser Thr Gln Gln Ile Ser Gln Asn Cys Thr Lys Val 
        515                 520                 525 

Leu Gln Ser Ser Asn Leu Glu Phe Gly Ser Ala Tyr Thr Tyr Val Ile 
    530                 535                 540 

Gly Thr Gln Ser Thr Gly Cys Pro Glu Leu His Met Phe Glu Asp Ile 
545                 550                 555                 560 

Ser Pro Asn Thr Val Asn Met Ala Leu Gln Ile Pro Gln Tyr Phe Leu 
                565                 570                 575 

Ile Thr Cys Gly Glu Val Val Phe Ser Val Thr Gly Leu Glu Phe Ser 
            580                 585                 590 

Tyr Ser Gln Ala Pro Ser Asn Met Lys Ser Val Leu Gln Ala Gly Trp 
        595                 600                 605 

Leu Leu Thr Val Ala Cys Trp Gln His His Cys Ala His Cys Gly Arg 
    610                 615                 620 

Ser Arg Pro Val Gln Thr Val Gly Ile His Pro Ile Cys Gly Ile Ala 
625                 630                 635                 640 

Ser Gly Cys Leu Cys Asn Ile Cys His His Gly Pro Val Leu His Leu 
                645                 650                 655 

Arg Gln Ser Ser Arg Asp 
            660 

 
           
             14  
             706  
             PRT  
             Homo sapien  
           
            14 

Met Ser Lys Ser His Ser Phe Phe Gly Tyr Pro Leu Ser Ile Phe Phe 
 1               5                  10                  15 

Ile Val Val Asn Glu Phe Cys Glu Arg Phe Ser Tyr Tyr Gly Met Arg 
            20                  25                  30 

Ala Ile Leu Ile Leu Tyr Phe Thr Asn Phe Ile Ser Trp Asp Asp Asn 
        35                  40                  45 

Leu Ser Thr Ala Ile Tyr His Thr Phe Val Ala Leu Cys Tyr Leu Thr 
    50                  55                  60 

Pro Ile Leu Gly Ala Leu Ile Ala Asp Ser Trp Leu Gly Lys Phe Lys 
65                  70                  75                  80 

Thr Ile Val Ser Leu Ser Ile Val Tyr Thr Ile Gly Gln Ala Val Thr 
                85                  90                  95 

Ser Val Ser Ser Ile Asn Asp Leu Thr Asp His Asn His Asp Gly Thr 
            100                 105                 110 

Pro Asp Ser Leu Pro Val His Val Val Leu Ser Leu Ile Gly Leu Ala 
        115                 120                 125 

Leu Ile Ala Leu Gly Thr Gly Gly Ile Lys Pro Cys Val Ser Ala Phe 
    130                 135                 140 

Gly Gly Asp Gln Phe Glu Glu Gly Gln Glu Lys Gln Arg Asn Arg Phe 
145                 150                 155                 160 

Phe Ser Ile Phe Tyr Leu Ala Ile Asn Ala Gly Ser Leu Leu Ser Thr 
                165                 170                 175 

Ile Ile Thr Pro Met Leu Arg Val Gln Gln Cys Gly Ile His Ser Lys 
            180                 185                 190 

Gln Ala Cys Tyr Pro Leu Ala Phe Gly Val Pro Ala Ala Leu Met Ala 
        195                 200                 205 

Val Ala Leu Ile Val Phe Val Leu Gly Ser Gly Met Tyr Lys Lys Phe 
    210                 215                 220 

Lys Pro Gln Gly Asn Ile Met Gly Lys Val Ala Lys Cys Ile Gly Phe 
225                 230                 235                 240 

Ala Ile Lys Asn Arg Phe Arg His Arg Ser Lys Ala Phe Pro Lys Arg 
                245                 250                 255 

Glu His Trp Leu Asp Trp Ala Lys Glu Lys Tyr Asp Glu Arg Leu Ile 
            260                 265                 270 

Ser Gln Ile Lys Met Val Thr Arg Val Met Phe Leu Tyr Ile Pro Leu 
        275                 280                 285 

Pro Met Phe Trp Ala Leu Phe Asp Gln Gln Gly Ser Arg Trp Thr Leu 
    290                 295                 300 

Gln Ala Thr Thr Met Ser Gly Lys Ile Gly Ala Leu Glu Ile Gln Pro 
305                 310                 315                 320 

Asp Gln Met Gln Thr Val Asn Ala Ile Leu Ile Val Ile Met Val Pro 
                325                 330                 335 

Ile Phe Asp Ala Val Leu Tyr Pro Leu Ile Ala Lys Cys Gly Phe Asn 
            340                 345                 350 

Phe Thr Ser Leu Lys Lys Met Ala Val Gly Met Val Leu Ala Ser Met 
        355                 360                 365 

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

Pro Val Phe Pro Lys Gly Asn Glu Val Gln Ile Lys Val Leu Asn Ile 
385                 390                 395                 400 

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

Gly Pro Met Ser Gln Thr Asn Ala Phe Met Thr Phe Asp Val Asn Lys 
            420                 425                 430 

Leu Thr Arg Ile Asn Ile Ser Ser Pro Gly Ser Pro Val Thr Ala Val 
        435                 440                 445 

Thr Asp Asp Phe Lys Gln Gly Gln Arg His Thr Leu Leu Val Trp Ala 
    450                 455                 460 

Pro Asn His Tyr Gln Val Val Lys Asp Gly Leu Asn Gln Lys Pro Glu 
465                 470                 475                 480 

Lys Gly Glu Asn Gly Ile Arg Phe Val Asn Thr Phe Asn Glu Leu Ile 
                485                 490                 495 

Thr Ile Thr Met Ser Gly Lys Val Tyr Ala Asn Ile Ser Ser Tyr Asn 
            500                 505                 510 

Ala Ser Thr Tyr Gln Phe Phe Pro Ser Gly Ile Lys Gly Phe Thr Ile 
        515                 520                 525 

Ser Ser Thr Glu Ile Pro Pro Gln Cys Gln Pro Asn Phe Asn Thr Phe 
    530                 535                 540 

Tyr Leu Glu Phe Gly Ser Ala Tyr Thr Tyr Ile Val Gln Arg Lys Asn 
545                 550                 555                 560 

Asp Ser Cys Pro Glu Val Lys Val Phe Glu Asp Ile Ser Ala Asn Thr 
                565                 570                 575 

Val Asn Met Ala Leu Gln Ile Pro Gln Tyr Phe Leu Leu Thr Cys Gly 
            580                 585                 590 

Glu Val Val Phe Ser Val Thr Gly Leu Glu Phe Ser Tyr Ser Gln Ala 
        595                 600                 605 

Pro Ser Asn Met Lys Ser Val Leu Gln Ala Gly Trp Leu Leu Thr Val 
    610                 615                 620 

Ala Val Gly Asn Ile Ile Val Leu Ile Val Ala Gly Ala Gly Gln Phe 
625                 630                 635                 640 

Ser Lys Gln Trp Ala Glu Tyr Ile Leu Phe Ala Ala Leu Leu Leu Val 
                645                 650                 655 

Val Cys Val Ile Phe Ala Ile Met Ala Arg Phe Tyr Thr Tyr Ile Asn 
            660                 665                 670 

Pro Ala Glu Ile Glu Ala Gln Phe Asp Glu Asp Glu Lys Lys Asn Arg 
        675                 680                 685 

Leu Glu Lys Ser Asn Pro Tyr Phe Met Ser Gly Ala Asn Ser Gln Lys 
    690                 695                 700 

Gln Met 
705 

 
           
             15  
             710  
             PRT  
             Rattus norvegicus  
           
            15 

Met Gly Met Ser Lys Ser Arg Gly Cys Phe Gly Tyr Pro Leu Ser Ile 
 1               5                  10                  15 

Phe Phe Ile Val Val Asn Glu Phe Cys Glu Arg Phe Ser Tyr Tyr Gly 
            20                  25                  30 

Met Arg Ala Leu Leu Val Leu Tyr Phe Arg Asn Phe Leu Gly Trp Asp 
        35                  40                  45 

Asp Asp Leu Ser Thr Ala Ile Tyr His Thr Phe Val Ala Leu Cys Tyr 
    50                  55                  60 

Leu Thr Pro Ile Leu Gly Ala Leu Ile Ala Asp Ser Trp Leu Gly Lys 
65                  70                  75                  80 

Phe Lys Thr Ile Val Ser Leu Ser Ile Val Tyr Thr Ile Gly Gln Ala 
                85                  90                  95 

Val Ile Ser Val Ser Ser Ile Asn Asp Leu Thr Asp His Asp His Asp 
            100                 105                 110 

Gly Ser Pro Asn Asn Leu Pro Leu His Val Ala Leu Ser Met Ile Gly 
        115                 120                 125 

Leu Ala Leu Ile Ala Leu Gly Thr Gly Gly Ile Lys Pro Cys Val Ser 
    130                 135                 140 

Ala Phe Gly Gly Asp Gln Phe Glu Glu Gly Gln Glu Lys Gln Arg Asn 
145                 150                 155                 160 

Arg Phe Phe Ser Ile Phe Tyr Leu Ala Ile Asn Ala Gly Ser Leu Leu 
                165                 170                 175 

Ser Thr Ile Ile Thr Pro Ile Leu Arg Val Gln Gln Cys Gly Ile His 
            180                 185                 190 

Ser Gln Gln Ala Cys Tyr Pro Leu Ala Phe Gly Val Pro Ala Ala Leu 
        195                 200                 205 

Met Ala Val Ala Leu Ile Val Phe Val Leu Gly Ser Gly Met Tyr Lys 
    210                 215                 220 

Lys Phe Gln Pro Gln Gly Asn Ile Met Gly Lys Val Ala Lys Cys Ile 
225                 230                 235                 240 

Gly Phe Ala Ile Lys Asn Arg Phe Arg His Arg Ser Lys Ala Phe Pro 
                245                 250                 255 

Lys Arg Glu His Trp Leu Asp Trp Ala Lys Glu Lys Tyr Asp Glu Arg 
            260                 265                 270 

Leu Ile Ser Gln Ile Lys Met Val Thr Lys Val Met Phe Leu Tyr Ile 
        275                 280                 285 

Pro Leu Pro Met Phe Trp Ala Leu Phe Asp Gln Gln Gly Ser Arg Trp 
    290                 295                 300 

Thr Leu Gln Ala Thr Thr Met Thr Gly Lys Ile Gly Thr Ile Glu Ile 
305                 310                 315                 320 

Gln Pro Asp Gln Met Gln Thr Val Asn Ala Ile Leu Ile Val Ile Met 
                325                 330                 335 

Val Pro Ile Val Asp Ala Val Val Tyr Pro Leu Ile Ala Lys Cys Gly 
            340                 345                 350 

Phe Asn Phe Thr Ser Leu Lys Lys Met Thr Val Gly Met Phe Leu Ala 
        355                 360                 365 

Ser Met Ala Phe Val Val Ala Ala Ile Val Gln Val Glu Ile Asp Lys 
    370                 375                 380 

Thr Leu Pro Val Phe Pro Ser Gly Asn Gln Val Gln Ile Lys Val Leu 
385                 390                 395                 400 

Asn Ile Gly Asn Asn Asp Met Ala Val Tyr Phe Pro Gly Lys Asn Val 
                405                 410                 415 

Thr Val Ala Gln Met Ser Gln Thr Asp Thr Phe Met Thr Phe Asp Val 
            420                 425                 430 

Asp Gln Leu Thr Ser Ile Asn Val Ser Ser Pro Gly Ser Pro Gly Val 
        435                 440                 445 

Thr Thr Val Ala His Glu Phe Glu Pro Gly His Arg His Thr Leu Leu 
    450                 455                 460 

Val Trp Gly Pro Asn Leu Tyr Arg Val Val Lys Asp Gly Leu Asn Gln 
465                 470                 475                 480 

Lys Pro Glu Lys Gly Glu Asn Gly Ile Arg Phe Val Ser Thr Leu Asn 
                485                 490                 495 

Glu Met Ile Thr Ile Lys Met Ser Gly Lys Val Tyr Glu Asn Val Thr 
            500                 505                 510 

Ser His Ser Ala Ser Asn Tyr Gln Phe Phe Pro Ser Gly Gln Lys Asp 
        515                 520                 525 

Tyr Thr Ile Asn Thr Thr Glu Ile Ala Pro Asn Cys Ser Ser Asp Phe 
    530                 535                 540 

Lys Ser Ser Asn Leu Asp Phe Gly Ser Ala Tyr Thr Tyr Val Ile Arg 
545                 550                 555                 560 

Ser Arg Ala Ser Asp Gly Cys Leu Glu Val Lys Glu Phe Glu Asp Ile 
                565                 570                 575 

Pro Pro Asn Thr Val Asn Met Ala Leu Gln Ile Pro Gln Tyr Phe Leu 
            580                 585                 590 

Leu Thr Cys Gly Glu Val Val Phe Ser Val Thr Gly Leu Glu Phe Ser 
        595                 600                 605 

Tyr Ser Gln Ala Pro Ser Asn Met Lys Ser Val Leu Gln Ala Gly Trp 
    610                 615                 620 

Leu Leu Thr Val Ala Ile Gly Asn Ile Ile Val Leu Ile Val Ala Glu 
625                 630                 635                 640 

Ala Gly His Phe Asp Lys Gln Trp Ala Glu Tyr Val Leu Phe Ala Ser 
                645                 650                 655 

Leu Leu Leu Val Val Cys Ile Ile Phe Ala Ile Met Ala Arg Phe Tyr 
            660                 665                 670 

Thr Tyr Ile Asn Pro Ala Glu Ile Glu Ala Gln Phe Asp Glu Asp Glu 
        675                 680                 685 

Lys Lys Lys Gly Val Gly Lys Glu Asn Pro Tyr Ser Ser Leu Glu Pro 
    690                 695                 700 

Val Ser Gln Thr Asn Met 
705                 710 

 
           
             16  
             709  
             PRT  
             Mus musculus  
           
            16 

Met Gly Met Ser Lys Ser Arg Gly Cys Phe Gly Tyr Pro Leu Ser Ile 
 1               5                  10                  15 

Phe Phe Ile Val Val Asn Glu Phe Cys Glu Arg Phe Ser Tyr Tyr Gly 
            20                  25                  30 

Met Arg Ala Leu Leu Val Leu Tyr Phe Arg Asn Phe Leu Gly Trp Asp 
        35                  40                  45 

Asp Asn Leu Ser Thr Ala Ile Tyr His Thr Phe Val Ala Leu Cys Tyr 
    50                  55                  60 

Leu Thr Pro Ile Leu Gly Ala Leu Ile Ala Asp Ser Trp Leu Gly Lys 
65                  70                  75                  80 

Phe Lys Thr Ile Val Ser Leu Ser Ile Val Tyr Thr Ile Gly Gln Ala 
                85                  90                  95 

Val Ile Ser Val Ser Ser Ile Asn Asp Leu Thr Asp His Asp His Asn 
            100                 105                 110 

Gly Ser Pro Asp Ser Leu Pro Val His Val Ala Leu Ser Met Val Gly 
        115                 120                 125 

Leu Ala Leu Ile Ala Leu Gly Thr Gly Gly Ile Lys Pro Cys Val Ser 
    130                 135                 140 

Ala Phe Gly Gly Asp Gln Phe Glu Glu Gly Gln Glu Lys Gln Arg Asn 
145                 150                 155                 160 

Arg Phe Phe Ser Ile Phe Tyr Leu Ala Ile Asn Gly Gly Ser Leu Leu 
                165                 170                 175 

Ser Thr Ile Ile Thr Pro Ile Leu Arg Val Gln Gln Cys Gly Ile His 
            180                 185                 190 

Ser Gln Gln Ala Cys Tyr Pro Leu Ala Phe Gly Val Pro Ala Ala Leu 
        195                 200                 205 

Met Ala Val Ala Leu Ile Val Phe Val Leu Gly Ser Gly Met Tyr Lys 
    210                 215                 220 

Lys Phe Gln Pro Gln Gly Asn Ile Met Gly Lys Val Ala Lys Cys Ile 
225                 230                 235                 240 

Gly Phe Ala Ile Lys Asn Arg Phe Arg His Arg Ser Lys Ala Tyr Pro 
                245                 250                 255 

Lys Arg Glu His Trp Leu Asp Trp Ala Lys Glu Lys Tyr Asp Glu Arg 
            260                 265                 270 

Leu Ile Ser Gln Ile Lys Met Val Thr Lys Val Met Phe Leu Phe Ile 
        275                 280                 285 

Pro Leu Pro Met Phe Trp Gly Leu Phe Asp Gln Gln Gly Ser Arg Trp 
    290                 295                 300 

Thr Leu Gln Ala Thr Thr Met Asn Gly Lys Ile Gly Ala Asn Glu Ile 
305                 310                 315                 320 

Gln Pro Asp Gln Met Gln Thr Val Asn Ala Ile Leu Asn Val Asn Asn 
                325                 330                 335 

Gly Pro Asn Val Asp Ala Val Val Tyr Arg Ser Ile Ala Lys Cys Gly 
            340                 345                 350 

Phe Asn Phe Thr Ser Leu Lys Lys Met Thr Val Gly Met Phe Leu Ala 
        355                 360                 365 

Ser Met Ala Phe Val Val Ala Ala Ile Val Gln Val Glu Ile Asp Lys 
    370                 375                 380 

Thr Leu Pro Val Phe Pro Gly Gly Asn Gln Val Gln Ile Lys Val Leu 
385                 390                 395                 400 

Asn Ile Gly Asn Asn Asn Met Thr Val His Phe Pro Gly Asn Ser Val 
                405                 410                 415 

Thr Leu Ala Gln Met Ser Gln Thr Asp Thr Phe Met Thr Phe Asp Ile 
            420                 425                 430 

Asp Lys Leu Thr Ser Ile Asn Ile Ser Ser Ser Gly Ser Pro Gly Val 
        435                 440                 445 

Thr Thr Val Ala His Asp Phe Glu Gln Gly His Arg His Asn Leu Leu 
    450                 455                 460 

Val Trp Glu Pro Ser Gln Tyr Arg Val Val Lys Asp Gly Pro Asn Gln 
465                 470                 475                 480 

Lys Pro Glu Lys Gly Glu Asn Gly Ile Arg Phe Val Asn Thr Leu Asn 
                485                 490                 495 

Glu Met Val Thr Asn Lys Met Ser Gly Lys Val Tyr Glu Lys Phe Thr 
            500                 505                 510 

Ser His Asn Ala Ser Gly Tyr Lys Phe Leu Pro Ser Gly Glu Lys Gln 
        515                 520                 525 

Tyr Thr Ile Asn Thr Thr Ala Val Ala Pro Thr Cys Leu Thr Asp Phe 
    530                 535                 540 

Lys Ser Ser Asn Leu Asp Phe Gly Ser Ala Tyr Thr Tyr Val Ile Arg 
545                 550                 555                 560 

Arg Ala Ser Asp Gly Cys Leu Glu Val Lys Glu Phe Glu Asp Ile Pro 
                565                 570                 575 

Pro Asn Thr Val Asn Met Ala Leu Gln Ile Pro Gln Tyr Phe Leu Leu 
            580                 585                 590 

Thr Cys Gly Glu Val Val Phe Ser Val Thr Gly Leu Glu Phe Ser Tyr 
        595                 600                 605 

Ser Gln Ala Pro Ser Asn Met Lys Ser Val Leu Gln Ala Gly Trp Leu 
    610                 615                 620 

Leu Thr Val Ala Val Gly Asn Ile Ile Val Leu Ile Val Ala Gly Ala 
625                 630                 635                 640 

Gly His Phe Pro Lys Gln Trp Ala Glu Tyr Ile Leu Phe Ala Ser Leu 
                645                 650                 655 

Leu Leu Val Val Cys Val Ile Phe Ala Ile Met Ala Arg Phe Tyr Thr 
            660                 665                 670 

Tyr Ile Asn Pro Ala Glu Ile Glu Ala Gln Phe Asp Glu Asp Glu Lys 
        675                 680                 685 

Lys Lys Gly Ile Gly Lys Glu Asn Pro Tyr Ser Ser Leu Glu Pro Val 
    690                 695                 700 

Ser Gln Thr Asn Met 
705 

 
           
             17  
             707  
             PRT  
             Ovis aries  
           
            17 

Met Gly Met Ser Val Pro Lys Ser Cys Phe Gly Tyr Pro Leu Ser Ile 
 1               5                  10                  15 

Phe Phe Ile Val Val Asn Glu Phe Cys Glu Arg Phe Ser Tyr Tyr Gly 
            20                  25                  30 

Met Arg Ala Leu Leu Ile Leu Tyr Phe Gln Arg Phe Leu Gly Trp Asn 
        35                  40                  45 

Asp Asn Leu Gly Thr Ala Ile Tyr His Thr Phe Val Ala Leu Cys Tyr 
    50                  55                  60 

Leu Thr Pro Ile Leu Gly Ala Leu Ile Ala Asp Ser Trp Leu Gly Lys 
65                  70                  75                  80 

Phe Lys Thr Ile Val Ser Leu Ser Ile Val Tyr Thr Ile Gly Gln Val 
                85                  90                  95 

Val Ile Ala Val Ser Ser Ile Asn Asp Leu Thr Asp Phe Asn His Asp 
            100                 105                 110 

Gly Thr Pro Asn Asn Ile Ser Val His Val Ala Leu Ser Met Ile Gly 
        115                 120                 125 

Leu Val Leu Ile Ala Leu Gly Thr Gly Gly Ile Lys Pro Cys Val Ser 
    130                 135                 140 

Ala Phe Gly Gly Asp Gln Phe Glu Glu Gly Gln Glu Lys Gln Arg Asn 
145                 150                 155                 160 

Arg Phe Phe Ser Ile Phe Tyr Leu Ala Ile Asn Ala Gly Ser Leu Leu 
                165                 170                 175 

Ser Thr Ile Ile Thr Pro Met Leu Arg Val Gln Val Cys Gly Ile His 
            180                 185                 190 

Ser Lys Gln Ala Cys Tyr Pro Leu Ala Phe Gly Val Pro Ala Ala Leu 
        195                 200                 205 

Met Ala Val Ser Leu Ile Val Phe Val Ile Gly Ser Gly Met Tyr Lys 
    210                 215                 220 

Lys Val Gln Pro Gln Gly Asn Ile Met Ser Lys Val Ala Arg Cys Ile 
225                 230                 235                 240 

Gly Phe Ala Ile Lys Asn Arg Ile Ser His Arg Ser Lys Lys Phe Pro 
                245                 250                 255 

Lys Arg Glu His Trp Leu Asp Trp Ala Ser Glu Lys Tyr Asp Glu Arg 
            260                 265                 270 

Leu Ile Ser Gln Ile Lys Met Val Thr Arg Val Met Phe Leu Tyr Ile 
        275                 280                 285 

Pro Leu Pro Met Phe Trp Ala Leu Phe Asp Gln Gln Gly Ser Arg Trp 
    290                 295                 300 

Thr Leu Gln Ala Thr Thr Met Ser Gly Lys Ile Gly Ile Ile Glu Ile 
305                 310                 315                 320 

Gln Pro Asp Gln Met Gln Thr Val Asn Ala Ile Leu Ile Val Val Met 
                325                 330                 335 

Val Pro Ile Val Asp Ala Val Val Tyr Pro Leu Ile Ala Lys Cys Gly 
            340                 345                 350 

Leu Asn Phe Thr Ser Leu Lys Lys Met Thr Val Gly Met Phe Leu Ala 
        355                 360                 365 

Ser Met Ala Phe Val Ala Ala Ala Ile Val Gln Val Asp Ile Asp Lys 
    370                 375                 380 

Thr Leu Pro Val Phe Pro Lys Gly Asn Glu Val Gln Ile Lys Val Leu 
385                 390                 395                 400 

Asn Ile Gly Asn Asn Ser Met Thr Val Ser Phe Pro Gly Thr Thr Val 
                405                 410                 415 

Thr Cys Asp Gln Met Ser Gln Thr Asn Gly Phe Leu Thr Phe Asn Val 
            420                 425                 430 

Asp Asn Leu Ser Ile Asn Ile Ser Ser Thr Gly Thr Pro Val Thr Pro 
        435                 440                 445 

Val Thr His Asn Phe Glu Ser Gly His Arg His Thr Leu Leu Val Trp 
    450                 455                 460 

Ala Pro Ser Asn Tyr Gln Val Val Lys Asp Gly Leu Asn Gln Lys Pro 
465                 470                 475                 480 

Glu Lys Gly Arg Asn Gly Ile Arg Phe Val Asn Ala Phe Gly Glu Ser 
                485                 490                 495 

Phe Gly Val Thr Met Asp Gly Glu Val Tyr Asn Asn Val Ser Gly His 
            500                 505                 510 

Asn Ala Ser Glu Tyr Leu Phe Phe Ser Ser Gly Val Lys Ser Phe Thr 
        515                 520                 525 

Ile Asn Ser Pro Glu Ile Ser Gln Gln Cys Glu Lys Gln Phe Lys Thr 
    530                 535                 540 

Ser Tyr Leu Glu Phe Gly Ser Ala Phe Thr Tyr Val Ile Ser Arg Lys 
545                 550                 555                 560 

Ser Asp Gly Cys Pro Glu Pro Lys Ile Phe Glu Asp Ile Ser Pro Asn 
                565                 570                 575 

Thr Val Ser Met Ala Leu Gln Ile Pro Gln Tyr Phe Leu Leu Thr Cys 
            580                 585                 590 

Gly Glu Val Val Phe Ser Ile Thr Gly Leu Glu Phe Ser Tyr Ser Gln 
        595                 600                 605 

Ala Pro Ser Asn Met Lys Ser Val Leu Gln Ala Gly Trp Leu Leu Thr 
    610                 615                 620 

Val Ala Val Gly Asn Ile Ile Val Leu Ile Val Ala Gly Ala Gly Gln 
625                 630                 635                 640 

Phe Ser Glu Gln Trp Ala Glu Tyr Val Leu Phe Ala Ala Leu Leu Leu 
                645                 650                 655 

Val Val Cys Ile Ile Phe Ala Ile Met Ala Arg Phe Tyr Thr Tyr Val 
            660                 665                 670 

Asn Pro Ala Glu Ile Glu Ala Gln Phe Asp Glu Asp Asp Lys Glu Asp 
        675                 680                 685 

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

Thr Gln Met 
705 

 
           
             18  
             707  
             PRT  
             Oryctolagus cuniculus  
           
            18 

Met Gly Met Ser Lys Ser Leu Ser Cys Phe Gly Tyr Pro Leu Ser Ile 
 1               5                  10                  15 

Phe Phe Ile Val Val Asn Glu Phe Cys Glu Arg Phe Ser Tyr Tyr Gly 
            20                  25                  30 

Met Arg Ala Leu Leu Ile Leu Tyr Phe Arg Asn Phe Ile Gly Trp Asp 
        35                  40                  45 

Asp Asn Leu Ser Thr Val Ile Tyr His Thr Phe Val Ala Leu Cys Tyr 
    50                  55                  60 

Leu Thr Pro Ile Leu Gly Ala Leu Ile Ala Asp Ala Trp Leu Gly Lys 
65                  70                  75                  80 

Phe Lys Thr Ile Val Trp Leu Ser Ile Val Tyr Thr Ile Gly Gln Ala 
                85                  90                  95 

Val Thr Ser Leu Ser Ser Val Asn Glu Leu Thr Asp Asn Asn His Asp 
            100                 105                 110 

Gly Thr Pro Asp Ser Leu Pro Val His Val Ala Val Cys Met Ile Gly 
        115                 120                 125 

Leu Leu Leu Ile Ala Leu Gly Thr Gly Gly Ile Lys Pro Cys Val Ser 
    130                 135                 140 

Ala Phe Gly Gly Asp Gln Phe Glu Glu Gly Gln Glu Lys Gln Arg Asn 
145                 150                 155                 160 

Arg Phe Phe Ser Ile Phe Tyr Leu Ala Ile Asn Ala Gly Ser Leu Leu 
                165                 170                 175 

Ser Thr Ile Ile Thr Pro Met Val Arg Val Gln Gln Cys Gly Ile His 
            180                 185                 190 

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

Met Ala Val Ser Leu Ile Val Phe Ile Ile Gly Ser Gly Met Tyr Lys 
    210                 215                 220 

Lys Phe Lys Pro Gln Gly Asn Ile Leu Ser Lys Val Val Lys Cys Ile 
225                 230                 235                 240 

Cys Phe Ala Ile Lys Asn Arg Phe Arg His Arg Ser Lys Gln Phe Pro 
                245                 250                 255 

Lys Arg Ala His Trp Leu Asp Trp Ala Lys Glu Lys Tyr Asp Glu Arg 
            260                 265                 270 

Leu Ile Ala Gln Ile Lys Met Val Thr Arg Val Leu Phe Leu Tyr Ile 
        275                 280                 285 

Pro Leu Pro Met Phe Trp Ala Leu Phe Asp Gln Gln Gly Ser Arg Trp 
    290                 295                 300 

Thr Leu Gln Ala Thr Thr Met Ser Gly Arg Ile Gly Ile Leu Glu Ile 
305                 310                 315                 320 

Gln Pro Asp Gln Met Gln Thr Val Asn Thr Ile Leu Ile Ile Ile Leu 
                325                 330                 335 

Val Pro Ile Met Asp Ala Val Val Tyr Pro Leu Ile Ala Lys Cys Gly 
            340                 345                 350 

Leu Asn Phe Thr Ser Leu Lys Lys Met Thr Ile Gly Met Phe Leu Ala 
        355                 360                 365 

Ser Met Ala Phe Val Ala Ala Ala Ile Leu Gln Val Glu Ile Asp Lys 
    370                 375                 380 

Thr Leu Pro Val Phe Pro Lys Ala Asn Glu Val Gln Ile Lys Val Leu 
385                 390                 395                 400 

Asn Val Gly Ser Glu Asn Met Ile Ile Ser Leu Pro Gly Gln Thr Val 
                405                 410                 415 

Thr Leu Asn Gln Met Ser Gln Thr Asn Glu Phe Met Thr Phe Asn Glu 
            420                 425                 430 

Asp Thr Leu Thr Ser Ile Asn Ile Thr Ser Gly Ser Gln Val Thr Met 
        435                 440                 445 

Ile Thr Pro Ser Leu Glu Ala Gly Gln Arg His Thr Leu Leu Val Trp 
    450                 455                 460 

Ala Pro Asn Asn Tyr Arg Val Val Asn Asp Gly Leu Thr Gln Lys Ser 
465                 470                 475                 480 

Asp Lys Gly Glu Asn Gly Ile Arg Phe Val Asn Thr Tyr Ser Gln Pro 
                485                 490                 495 

Ile Asn Val Thr Met Ser Gly Lys Val Tyr Glu His Ile Ala Ser Tyr 
            500                 505                 510 

Asn Ala Ser Glu Tyr Gln Phe Phe Thr Ser Gly Val Lys Gly Phe Thr 
        515                 520                 525 

Val Ser Ser Ala Gly Ile Ser Glu Gln Cys Arg Arg Asp Phe Glu Ser 
    530                 535                 540 

Pro Tyr Leu Glu Phe Gly Ser Ala Tyr Thr Tyr Leu Ile Thr Ser Gln 
545                 550                 555                 560 

Ala Thr Gly Cys Pro Gln Val Thr Glu Phe Glu Asp Ile Pro Pro Asn 
                565                 570                 575 

Thr Met Asn Met Ala Trp Gln Ile Pro Gln Tyr Phe Leu Ile Thr Ser 
            580                 585                 590 

Gly Glu Val Val Phe Ser Ile Thr Gly Leu Glu Phe Ser Tyr Ser Gln 
        595                 600                 605 

Ala Pro Ser Asn Met Lys Ser Val Leu Gln Asp Arg Trp Leu Leu Thr 
    610                 615                 620 

Val Ala Val Gly Asn Ile Ile Val Leu Ile Val Ala Gly Ala Gly Gln 
625                 630                 635                 640 

Ile Asn Lys Gln Trp Ala Glu Tyr Ile Leu Phe Ala Ala Leu Leu Leu 
                645                 650                 655 

Val Val Cys Val Ile Phe Ala Ile Met Ala Arg Phe Tyr Thr Tyr Val 
            660                 665                 670 

Asn Pro Ala Glu Ile Glu Ala Gln Phe Glu Glu Asp Glu Lys Lys Lys 
        675                 680                 685 

Asn Pro Glu Lys Asn Asp Leu Tyr Pro Ser Val Ala Pro Val Ser Gln 
    690                 695                 700 

Thr Gln Met 
705 

 
           
             19  
             714  
             PRT  
             Gallus gallus  
           
            19 

Met Ala Ala Lys Ser Lys Ser Lys Gly Arg Ser Val Pro Asn Cys Phe 
 1               5                  10                  15 

Gly Tyr Pro Leu Ser Ile Phe Phe Ile Val Ile Asn Glu Phe Cys Glu 
            20                  25                  30 

Arg Phe Ser Tyr Tyr Gly Met Arg Ala Val Leu Val Leu Tyr Phe Lys 
        35                  40                  45 

Tyr Phe Leu Arg Trp Asp Asp Asn Phe Ser Thr Ala Ile Tyr His Thr 
    50                  55                  60 

Phe Val Ala Leu Cys Tyr Leu Thr Pro Ile Leu Gly Ala Leu Ile Ala 
65                  70                  75                  80 

Asp Ser Trp Leu Gly Lys Phe Lys Thr Ile Val Ser Leu Ser Ile Val 
                85                  90                  95 

Tyr Thr Ile Gly Gln Ala Val Met Ala Val Ser Ser Ile Asn Asp Met 
            100                 105                 110 

Thr Asp Gln Asn Arg Asp Gly Asn Pro Asp Asn Ile Ala Val His Ile 
        115                 120                 125 

Ala Leu Ser Met Thr Gly Leu Ile Leu Ile Ala Leu Gly Thr Gly Gly 
    130                 135                 140 

Ile Lys Pro Cys Val Ser Ala Phe Gly Gly Asp Gln Phe Glu Glu His 
145                 150                 155                 160 

Gln Glu Lys Gln Arg Ser Arg Phe Phe Ser Ile Phe Tyr Leu Ser Ile 
                165                 170                 175 

Asn Ala Gly Ser Leu Ile Ser Thr Ile Ile Thr Pro Ile Leu Arg Ala 
            180                 185                 190 

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

Gly Val Pro Ala Ala Leu Met Ala Val Ser Leu Val Val Phe Ile Ala 
    210                 215                 220 

Gly Ser Gly Met Tyr Lys Lys Val Gln Pro Gln Gly Asn Ile Met Val 
225                 230                 235                 240 

Arg Val Cys Lys Cys Ile Gly Phe Ala Ile Lys Asn Arg Phe Arg His 
                245                 250                 255 

Arg Ser Lys Glu Tyr Pro Lys Arg Glu His Trp Leu Asp Trp Ala Ser 
            260                 265                 270 

Glu Lys Tyr Asp Lys Arg Leu Ile Ala Gln Thr Lys Met Val Leu Lys 
        275                 280                 285 

Val Leu Phe Leu Tyr Ile Pro Leu Pro Met Phe Trp Ala Leu Phe Asp 
    290                 295                 300 

Gln Gln Gly Ser Arg Trp Thr Leu Gln Ala Thr Thr Met Asp Gly Asp 
305                 310                 315                 320 

Phe Gly Ala Met Gln Ile Gln Pro Asp Gln Met Gln Thr Val Asn Pro 
                325                 330                 335 

Ile Leu Ile Ile Ile Met Val Pro Val Val Asp Ala Val Ile Tyr Pro 
            340                 345                 350 

Leu Ile Gln Lys Cys Lys Ile Asn Phe Thr Pro Leu Arg Arg Ile Thr 
        355                 360                 365 

Val Gly Met Phe Leu Ala Gly Leu Ala Phe Val Ala Ala Ala Leu Leu 
    370                 375                 380 

Gln Val Gln Ile Asp Lys Thr Leu Pro Val Phe Pro Ala Ala Gly Gln 
385                 390                 395                 400 

Ala Gln Ile Lys Ile Ile Asn Leu Gly Asp Ser Asn Ala Asn Val Thr 
                405                 410                 415 

Phe Leu Pro Asn Leu Gln Asn Val Thr Val Leu Pro Met Glu Ser Thr 
            420                 425                 430 

Gly Tyr Arg Met Phe Glu Ser Ser Gln Leu Lys Ser Val Met Val Asn 
        435                 440                 445 

Phe Gly Ser Glu Ser Arg Ser Glu Asn Ile Asp Ser Ile Ser Ser Asn 
    450                 455                 460 

Thr His Thr Val Thr Ile Lys Asn Ala Ala Ala Gly Ile Val Ser Ser 
465                 470                 475                 480 

Leu Arg Ser Asp Asn Phe Thr Ser Lys Pro Glu Glu Gly Lys Asn Leu 
                485                 490                 495 

Val Arg Phe Val Asn Asn Leu Pro Gln Thr Val Asn Ile Thr Met Gly 
            500                 505                 510 

Asp Thr Thr Phe Gly Ile Leu Glu Glu Thr Ser Ile Ser Asn Tyr Ser 
        515                 520                 525 

Pro Phe Ser Gly Gly Arg Thr Tyr Asp Ile Val Ile Thr Ala Gly Ser 
    530                 535                 540 

Thr Asn Cys Lys Pro Thr Ser Glu Lys Leu Gly Tyr Gly Gly Ala Tyr 
545                 550                 555                 560 

Thr Ile Val Ile Asn Glu Cys Ser Gly Asp Val Thr Gln Leu Arg Tyr 
                565                 570                 575 

Ile Glu Asp Ile Gln Pro Asn Thr Val His Met Ala Trp Gln Ile Pro 
            580                 585                 590 

Gln Tyr Phe Ile Leu Thr Cys Gly Glu Val Val Phe Ser Val Thr Gly 
        595                 600                 605 

Leu Glu Phe Ser Tyr Ser Gln Ala Pro Ser Asn Met Lys Ser Val Leu 
    610                 615                 620 

Gln Ala Gly Trp Leu Leu Thr Val Ala Val Gly Asn Ile Ile Val Leu 
625                 630                 635                 640 

Ile Val Ala Gly Ala Ser Lys Leu Ser Glu Gln Trp Ala Glu Tyr Val 
                645                 650                 655 

Leu Phe Ala Ala Leu Leu Phe Ala Val Cys Ile Ile Phe Ala Val Met 
            660                 665                 670 

Ala Tyr Phe Tyr Thr Tyr Thr Asp Pro Asn Glu Val Glu Ala Gln Leu 
        675                 680                 685 

Asp Glu Glu Glu Lys Lys Lys Gln Ile Lys Gln Asp Pro Asp Leu His 
    690                 695                 700 

Gly Lys Glu Ser Glu Ala Val Ser Gln Met 
705                 710 

 
           
             20  
             2124  
             DNA  
             Canis familiaris  
           
            20 

atgggcatgt ccaagtcata tggttgcttt ggttacccct tgagcatctt cttcatcgtg     60 

gtcaatgagt tctgtgaaag attttcctac tatggaatga gagcactcct gattctgtac    120 

ttcagacggt tcatcgggtg ggacgataat ctgtccacgg ccatctacca cacgtttgtg    180 

gctctgtgct acctgacgcc gatcctcggc gcactgatcg cagactcctg gctgggaaag    240 

ttcaagacaa tcgtgtcact ctccattgtc tacacaattg gacaggcggt cactgcagta    300 

agctcaatta atgacctcac agactataac aaagatggaa ctcctgacaa tctgtccgtg    360 

catgtggcac tgtccatgat tggcctggcc ctgatagctc tgggaactgg aggaataaag    420 

ccctgtgtgt ctgcatttgg tggagaccag tttgaagagg gccaggaaaa acaaagaaac    480 

agattctttt ccatctttta tttggccatt aatgctggaa gcttgatttc cactattgtc    540 

actcccatgc tcagagttca cgaatgtgga atttacagtc agaaagcttg ttacccactg    600 

gcatttgggg ttcctgctgc tctcatggcc gtatctctga ttgtatttgt cattggcagt    660 

ggaatgtaca agaagtttca gccccagggt aatgtcatgg gtaaagttgt caagtgcatt    720 

ggttttgccc tcaaaaatag gtttaggcac cggagtaagc agtttcccaa gagggagcac    780 

tggctggact gggctaaaga gaaatacgat gagcggctca tctctcaaat taagatggtc    840 

acaaaagtga tgttcttgta catcccactc ccaatgttct gggccctgtt tgaccagcag    900 

ggctccaggt ggacactgca agcaacagct atgagtggga aaattggact tcttgaagtt    960 

cagccagatc agatgcagac tgtgaatgcc atcttgattg tcgtcatggt ccccatcatg   1020 

gatgccgtgg tgtaccctct gattgcaaaa tgtggcttca atttcacctc cttgaagagg   1080 

atgacagttg gaatgttcct ggcttccatg gccttcgtga tggcggcgat tgttcagctg   1140 

gaaattgata aaactcttcc agtcttcccc aaacaaaatg aagtccaaat caaagtactg   1200 

aatataggaa atggtgccat gaatgtatct tttcctggag cggtggtgac agttagccaa   1260 

atgagtcaat cagatggatt tatgactttt gatgtagaca aactgacaag tataaacatt   1320 

tcttccactg gatcaccagt cattccagtg acttataact ttgagcaggg ccatcgccat   1380 

acccttctag tatgggcccc caataattac cgagtggtaa aggatggcct taaccagaag   1440 

ccagaaaaag gagaaaatgg aatcagattt ataaatagtc ttaatgagag cctcaacatc   1500 

accatgggcg acaaagttta tgtgaatgtc accagtcaca atgccagcga gtatcagttc   1560 

ttttctttgg gcacaaaaaa cattacaata agttcaacac aacagatctc acaaaattgt   1620 

acaaaagttc tccaatcatc caaccttgaa tttggtagtg catataccta tgtaatcgga   1680 

acgcagagca ctggctgccc tgaattgcat atgtttgaag atatttcacc caacacagtt   1740 

aacatggctc tgcagatccc gcagtacttc ctcatcacct gcggcgaggt ggttttctct   1800 

gtcacaggac tggagttctc atattctcag gccccctcca acatgaagtc ggtgcttcag   1860 

gcgggatggc tgctgacagt ggctgttggc aacatcattg tgctcattgt ggcaggagca   1920 

ggccagttca gtgaacagtg ggctgaatac atcctatttg cggcattgct tctggttgtc   1980 

tgtgtaatat ttgccatcat ggcccggttt tacacttacg tcaatccagc agagattgaa   2040 

gctcagtttg acgacgatga gaaaaagaac ctggaaaaga tgaatgtata ttccacggta   2100 

actccggtct cacagacaca gatg                                          2124 

 
           
             21  
             708  
             PRT  
             Canis familiaris  
           
            21 

Met Gly Met Ser Lys Ser Tyr Gly Cys Phe Gly Tyr Pro Leu Ser Ile 
 1               5                  10                  15 

Phe Phe Ile Val Val Asn Glu Phe Cys Glu Arg Phe Ser Tyr Tyr Gly 
            20                  25                  30 

Met Arg Ala Leu Leu Ile Leu Tyr Phe Arg Arg Phe Ile Gly Trp Asp 
        35                  40                  45 

Asp Asn Leu Ser Thr Ala Ile Tyr His Thr Phe Val Ala Leu Cys Tyr 
    50                  55                  60 

Leu Thr Pro Ile Leu Gly Ala Leu Ile Ala Asp Ser Trp Leu Gly Lys 
65                  70                  75                  80 

Phe Lys Thr Ile Val Ser Leu Ser Ile Val Tyr Thr Ile Gly Gln Ala 
                85                  90                  95 

Val Thr Ala Val Ser Ser Ile Asn Asp Leu Thr Asp Tyr Asn Lys Asp 
            100                 105                 110 

Gly Thr Pro Asp Asn Leu Ser Val His Val Ala Leu Ser Met Ile Gly 
        115                 120                 125 

Leu Ala Leu Ile Ala Leu Gly Thr Gly Gly Ile Lys Pro Cys Val Ser 
    130                 135                 140 

Ala Phe Gly Gly Asp Gln Phe Glu Glu Gly Gln Glu Lys Gln Arg Asn 
145                 150                 155                 160 

Arg Phe Phe Ser Ile Phe Tyr Leu Ala Ile Asn Ala Gly Ser Leu Ile 
                165                 170                 175 

Ser Thr Ile Val Thr Pro Met Leu Arg Val His Glu Cys Gly Ile Tyr 
            180                 185                 190 

Ser Gln Lys Ala Cys Tyr Pro Leu Ala Phe Gly Val Pro Ala Ala Leu 
        195                 200                 205 

Met Ala Val Ser Leu Ile Val Phe Val Ile Gly Ser Gly Met Tyr Lys 
    210                 215                 220 

Lys Phe Gln Pro Gln Gly Asn Val Met Gly Lys Val Val Lys Cys Ile 
225                 230                 235                 240 

Gly Phe Ala Leu Lys Asn Arg Phe Arg His Arg Ser Lys Gln Phe Pro 
                245                 250                 255 

Lys Arg Glu His Trp Leu Asp Trp Ala Lys Glu Lys Tyr Asp Glu Arg 
            260                 265                 270 

Leu Ile Ser Gln Ile Lys Met Val Thr Lys Val Met Phe Leu Tyr Ile 
        275                 280                 285 

Pro Leu Pro Met Phe Trp Ala Leu Phe Asp Gln Gln Gly Ser Arg Trp 
    290                 295                 300 

Thr Leu Gln Ala Thr Ala Met Ser Gly Lys Ile Gly Leu Leu Glu Val 
305                 310                 315                 320 

Gln Pro Asp Gln Met Gln Thr Val Asn Ala Ile Leu Ile Val Val Met 
                325                 330                 335 

Val Pro Ile Met Asp Ala Val Val Tyr Pro Leu Ile Ala Lys Cys Gly 
            340                 345                 350 

Phe Asn Phe Thr Ser Leu Lys Arg Met Thr Val Gly Met Phe Leu Ala 
        355                 360                 365 

Ser Met Ala Phe Val Met Ala Ala Ile Val Gln Leu Glu Ile Asp Lys 
    370                 375                 380 

Thr Leu Pro Val Phe Pro Lys Gln Asn Glu Val Gln Ile Lys Val Leu 
385                 390                 395                 400 

Asn Ile Gly Asn Gly Ala Met Asn Val Ser Phe Pro Gly Ala Val Val 
                405                 410                 415 

Thr Val Ser Gln Met Ser Gln Ser Asp Gly Phe Met Thr Phe Asp Val 
            420                 425                 430 

Asp Lys Leu Thr Ser Ile Asn Ile Ser Ser Thr Gly Ser Pro Val Ile 
        435                 440                 445 

Pro Val Thr Tyr Asn Phe Glu Gln Gly His Arg His Thr Leu Leu Val 
    450                 455                 460 

Trp Ala Pro Asn Asn Tyr Arg Val Val Lys Asp Gly Leu Asn Gln Lys 
465                 470                 475                 480 

Pro Glu Lys Gly Glu Asn Gly Ile Arg Phe Ile Asn Ser Leu Asn Glu 
                485                 490                 495 

Ser Leu Asn Ile Thr Met Gly Asp Lys Val Tyr Val Asn Val Thr Ser 
            500                 505                 510 

His Asn Ala Ser Glu Tyr Gln Phe Phe Ser Leu Gly Thr Lys Asn Ile 
        515                 520                 525 

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

Gln Ser Ser Asn Leu Glu Phe Gly Ser Ala Tyr Thr Tyr Val Ile Gly 
545                 550                 555                 560 

Thr Gln Ser Thr Gly Cys Pro Glu Leu His Met Phe Glu Asp Ile Ser 
                565                 570                 575 

Pro Asn Thr Val Asn Met Ala Leu Gln Ile Pro Gln Tyr Phe Leu Ile 
            580                 585                 590 

Thr Cys Gly Glu Val Val Phe Ser Val Thr Gly Leu Glu Phe Ser Tyr 
        595                 600                 605 

Ser Gln Ala Pro Ser Asn Met Lys Ser Val Leu Gln Ala Gly Trp Leu 
    610                 615                 620 

Leu Thr Val Ala Val Gly Asn Ile Ile Val Leu Ile Val Ala Gly Ala 
625                 630                 635                 640 

Gly Gln Phe Ser Glu Gln Trp Ala Glu Tyr Ile Leu Phe Ala Ala Leu 
                645                 650                 655 

Leu Leu Val Val Cys Val Ile Phe Ala Ile Met Ala Arg Phe Tyr Thr 
            660                 665                 670 

Tyr Val Asn Pro Ala Glu Ile Glu Ala Gln Phe Asp Asp Asp Glu Lys 
        675                 680                 685 

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

Gln Thr Gln Met 
705