Abstract:
The present invention provides novel sequences encoding  Staphylococcus pseudintermedius  proteins/nucleic acids potentially useful in the treatment and/or prevention of canine disorders. In particular, the various protein and/or nucleic acid sequences described herein may find application as vaccines for use in treating and/or preventing a variety of canine diseases and/or conditions caused or contributed to by  Staphylococcus pseudintermedius.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application is a continuation-in-part of PCT/GB2010/001916, filed Oct. 15, 2010, which claims the benefit under 35 U.S.C. §119(e) to U.S. Provisional Application No. 61/252,026, filed Oct. 15, 2009, both of which are hereby incorporated by reference in their entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention provides novel staphylococcal cell wall associated proteins, genes encoding the same and vaccines for use in treating/preventing Staphylococcal infections. 
       BACKGROUND OF THE INVENTION 
       [0003]    Skin diseases are a major cause of morbidity in dogs and an important animal welfare issue (Hill et al, 2006). In particular, superficial bacterial folliculitis (pyoderma) caused by  Staphylococcus pseudintermedius  (formerly known as  Staphylococcus intermedius ) is one of the most common diseases seen in small animal veterinary practice, worldwide (Hill et al, 2006). Superficial pyoderma is characterized by the formation of follicular pustules and is often associated with pruritus, alopecia, erythema and swelling. This may develop into deep pyoderma which typically includes pain, crusting, odor, and exudation of blood and pus. The disease often occurs as a secondary infection in dogs with atopic dermatitis (AD) resulting from a type I hypersensitivity reaction (IgE antibody-associated) to environmental allergens (Hill et al, 2006). Treatment of canine pyoderma is often difficult without resorting to aggressive, medium-term administration of systemic antibacterial agents to prevent relapse of infection, and such therapy predisposes to the development of bacterial resistance that may be transferred to bacteria infecting humans (Guardabassi et al, 2004). Worringly, methicillin-resistant  S. pseudintermedius  has recently emerged as a major problem in veterinary clinics worldwide (Bannoehr et al, 2007). Although rare, several episodes of life-threatening infections of humans by  S. pseudintermedius  have been reported with the typical route of transmission being through dog bite wounds (Bannoehr et al, 2007). Previously, crude vaccine preparations based on  Staphylococcus aureus  phage lysate or  S. pseudintermedius  autogenous bacterin have shown promise as adjunctive therapies for treatment of pyoderma (Curtis et al, 2006), and a rationally-designed effective vaccine would be a highly desirable means to reducing or eliminating the suffering associated with the disease. 
         [0004]    Accordingly, the present invention aims to obviate one or more of the problems associated with the prior art. 
       SUMMARY OF THE INVENTION 
       [0005]    The present invention is based upon the identification of novel gene sequences encoding proteins potentially useful in the treatment and/or prevention of canine disorders. In particular, the proteins encoded by the genes described herein, may find application in the treatment and/or prevention of diseases caused or contributed to by the bacterial pathogen  Staphylococcus pseudintermedius.    
         [0006]    The inventors have identified a number of  Staphylococcus pseudintermedius  genes encoding proteins which may broadly be classed as members of the cell-wall anchored (CWA) family of proteins. In certain embodiments, these CWA proteins may be further grouped as surface proteins known as Microbial Surface Components Recognising adhesive Matrix Molecules (MSCRAMM). It should be understood that while a number microbial organisms may be known to express MSCRAMM type proteins, the term “MSCRAMM” describes the phenotypic function of a wide range of diverse surface-associated proteins of Gram-positive bacteria. As such, while MSCRAMM proteins may all possess cell-wall anchor motifs and signal sequences for cell wall transportation, the proteins belonging to this group may otherwise be structurally diverse. Furthermore, bacterial species within a particular genus, for example the genus  Staphylococcus , may possess unique MSCRAMM profiles. 
         [0007]    In view of the above, the present invention relates to a group of surface expressed proteins derived from  Staphylococcus pseudintermedius  that may be referred to either as CWA or MSCRAMM proteins. 
         [0008]    As such, a first aspect of this invention provides an isolated and/or substantially purified  Staphylococcus pseudintermedius  CWA or MSCRAMM nucleic acid or protein sequence comprising a nucleic acid or amino acid sequence homologous or identical to any one of the nucleic acid or amino acid sequences provided as SEQ ID NOS: 1-38 below. 
         [0000]                          SEQ ID NO: 1            atggaaaacaaaaacttttttagtattcgtaaactatctattggtgtagg               ttcttgcttaatcgcgagttctttacttgtaaacacgccaagttttgctg               aagaaacagataatgcgaacattaatgacgcacaacaaaacgccttttat               gaaattttacatttgccaaacttaactgaagagcaacaaaatggattcat               ccaaagtcttaaagatgatccaagtgtgagcaacgacattttagtagaag               ctaagaaattaaatgacactcaagctaaacctgattacagtgaagcacaa               caaaatgcattttatgaaattttacatttgtcaaacttaactgaagagca               acaaaatggattcatccaaagtcttaaagatgatccaagtgtgagcaacg               acattttagtagaagctaagaagttaaatgacactcaagctaaacctgat               tacagtgaagcacaacaaaatgcattttatgaaattttacatttgtcaaa               cttaactgaagagcaacaaaatgggttcatccaaagccttaaagatgatc               caagtgtaagtaaagaaattttagcagaagctaagaagttaaatgatagt               caagcacctaaagttgataaagctaaaaaaactgacaaagctgaagcgaa               agcagatgataaagctaaaggtgaagaagccaaaaaatctgaagacaaaa               aagatagcaaagcagataaggcaaaatcgaaaaacgctacacatgttgtt               aaacctggtgaaactttagataatattgctaaagatcatcatacaactgt               tgataaaattgctaaagataacaaaataaaagataaaaatgtgattaaac               taggtcaaaaacttgttgttgataaacaaaaagcaactcaaggaaaacaa               gaagctgtagcgaaaaatgaagtgaaggctttacctaatactggtgaaaa               tgatgatatcgcattattcagcacaacagttgcgggtggcgtaagtatcg               ctttaggttcattattattaggaagaaacagaaaaactagctaa            
The protein sequence translated from SEQ ID NO 1 is designated SEQ ID NO: 2 and is shown below:
 
         [0000]                                      SEQ ID NO: 2            MENKNFFSIRKLSIGVGSCLIASSLLVNTPSFAEETDNANINDAQQNAFY               EILHLPNLTEEQQNGFIQSLKDDPSVSNDILVEAKKLNDTQAKPDYSEAQ               QNAFYEILHLSNLTEEQQNGFIQSLKDDPSVSNDILVEAKKLNDTQAKPD               YSEAQQNAFYEILHLSNLTEEQQNGFIQSLKDDPSVSKEILAEAKKLNDS               QAPKVDKAKKTDKAEAKADDKAKGEEAKKSEDKKDSKADKAKSKNATHVV               KPGETLDNIAKDHHTTVDKIAKDNKIKDKNVIKLGQKLVVDKQKATQGKQ               EAVAKNEVKALPNTGENDDIALFSTTVAGGVSIALGSLLLGRNRKTS                    SEQ ID NO: 3            atggaaaacaaaaactttttcagcattcgtaaattatcaattggggtggg               ttcatgtttaatcgcgagctctttacttgtgaatacaccaagtttcgcag               aagaaggagataataacgcagaagcgcaacaaaacgctttctctgaggta               gtaaaattacctaaccttagcgaagaacaacgtaatggtttcattcaaag               ccttaaagatgatccaagtacaagtcaagatgtgcttaatgaagctaaaa               aattaaatgatagtcaagagggatctcaacctgctcctgattacagtgat               gaacaacaaaatgcattttatgaaattttacaccttccaaacttaactga               agaacaacgcaatggctatattcaaagtcttaaagatgacccaagtgtaa               gcgctaatattcttgttgaagctaaaaatatgaatgttaaccaaacacct               acacaacctgcgccaagtttcgatgaagcgcaacaaaatgcattctatga               gattgtaaacttaccaaatcttactgaagagcaacgtaacggtttcatcc               aaagccttaaagacgatccaagtgtaagtaaagatatccttgttgaagct               aaaaagttaaatgacagccaagcaaaacctgattacagtgaagcgcaaca               aaatgcattttatgaaattttacaccttccaaacttaactgaagaacaac               gtaacggtttcatccaaagccttaaagacgatccgagtgtaagtagtgat               attcttgctgaagctaagaaattaaatgacagccaagcgcctaaagaaga               caacaacgtaaaagacaataattcaggtgaaaacaaagctgaagacaaag               gcaacaaagaaaacaaagctgaagataaaggcagcaaagaagacaaagct               gaagataaaggcagcaaagaagacaaagctgaagataaaggcagcaaaga               agacaaagctgaagataaaggcagcaaagaagacaaagctgaagataaag               gcagcatagaagataaagctaaagacaaagacaacaaagaaggcaaagct               gcagacaaaggtatggacaaagcgaaagatgcaatgcatgtcgttcaacc               tggtgaaacagtagaaaaaattgctaaagctaataacacaactgtagaac               aaatcgctaaagataatcatttagaagataaaaacatgattttaccaggt               caaaaacttgttgttgacaaccaaaaagcaatgaaagacagccaagaagc               taaagcaaaccacgaaatgaaagctttacctgaaacaggtgaagaaaacg               atatggcattattcggtacatcacttacaggtggtcttagcttagcatta               ggtttatacatcttaggacgtggcagaaaaacaaactaa            
The protein sequence translated from SEQ ID NO 3 is designated SEQ ID NO: 4 and is shown below:
 
         [0000]                                      SEQ ID NO: 4            MENKNFFSIRKLSIGVGSCLIASSLLVNTPSFAEEGDNNAEAQQNAFSEV               VKLPNLSEEQRNGFIQSLKDDPSTSQDVLNEAKKLNDSQEGSQPAPDYSD               EQQNAFYEILHLPNLTEEQRNGYIQSLKDDPSVSANILVEAKNMNVNQTP               TQPAPSFDEAQQNAFYEIVNLPNLTEEQRNGFIQSLKDDPSVSKDILVEA               KKLNDSQAKPDYSEAQQNAFYEILHLPNLTEEQRNGFIQSLKDDPSVSSD               ILAEAKKLNDSQAPKEDNNVKDNNSGENKAEDKGNKENKAEDKGSKEDKA               EDKGSKEDKAEDKGSKEDKAEDKGSKEDKAEDKGSIEDKAKDKDNKEGKA               ADKGMDKAKDAMHVVQPGETVEKIAKANNTTVEQIAKDNHLEDKNMILPG               QKLVVDNQKAMKDSQEAKANHEMKALPETGEENDMALFGTSLTGGLSLAL               GLYILGRGRKTN                    SEQ ID NO: 5            gtgtacaaaaatgaagaagaaaagcattcaataagaaagttatctatagg               agccgcatctgtcattgttgggggactcatgtatggtgttttgggaaatg               atgaagctcaagcgaatgaagatgtcactgaaacaactgggagaaattca               gtgacaacgcaagcttctgagcaacatttgcaagtggaagcagtacctca               agaaggcaataatgtaaatgtatcctctgtaaaagtacctacgaatacgg               caacgcaagcacaagaagatgttgcaagtgtatccgatgttaaagcacat               gctgatgatgcattacaagtacaagaaagtagtcatactgatggtgtttc               ttcagaattcaagcaggagacagcttatgcgaatcctcaaacagctgaga               cagttaaacctaatagtgaagcagtgcatcagtctgaatacgaggataag               caaaaacccgtatcatctagccgcaaagaagatgagactatgcttcagca               gcaacaagttgaagccaaaaatgttgtgagtgcggaggaagtgtctaaag               aagaaaatactcaagtgatgcaatcccctcaagacgttgaacaacatgta               ggtggtaaagatatctctaatgaggttgtagtggataggagtgatatcaa               aggatttaacagcgaaactactattcgacctcatcagggacaaggtggta               ggttgaattatcaattaaagtttcctagcaatgtaaagccaggcgatcag               tttactataaaattatctgacaatatcaatacacatggtgtttctgttga               aagaaccgcaccgagaatcatggctaaaaatactgaaggtgcgacggatg               taattgctgaaggtctagtgttggaagatggtaaaaccatcgtatataca               tttaaagactatgtaaatggcaagcaaaatttgactgctgagttatcagt               gagctatttcgtaagtccggaaaaagtcttgactactgggacacaaacat               tcacgacgatgatcggtaatcattcaacgcaatccaatattgacgtttat               tatgataatagtcattatgtagatggacgtatttcgcaagtgaacaaaaa               agaagctaaatttcaacaaatagcatacattaaccctaatggctatttaa               atggcagggggacaattgcagttaatggtgaagtggtcagtggtacgact               aaagacttaatgcaacctacagtgcgtgtatatcaatataaaggacaagg               tgttcctcctgaaagtattactatagaccctaatatgtgggaagaaatca               gcataaacgatactatggtaagaaaatatgatggtggctatagcttgaat               ctggataccagcaagaatcaaaaatatgccatctattatgaaggggcata               tgatgcgcaagctgacacactgttgtatagaacatatatacagtcattaa               acagttactatccgttcagttaccaaaaaatgaacggtgtgaagttttac               gaaaacagtgcgagtggaagcggtgagttgaaaccgaaaccacctgaaca               accaaaaccagaacctgaaattcaagctgatgtagtagatattattgaag               atagccatgtgattgatataggatggaatacagcagttggagaagaaagt               ggagcaaaccaaggccctcaagaagaaatcacggaaaatcacgacatcga               agtcattgaggaaaacaacttggtggaaatgacagaagatacagcagttg               gagaagaaagtggagcaaaccaaggccctcaagaagaaatcacggaaaat               cacgacatcgaagtcattgaagaaaacaacttagtggaaatgacagaaga               tacagcgttggaagaagaaagtggagcaaatcaaggtcctcaagaagaga               tcacagaaaaccacgatatcgaagtcattgaagaaaacaacttggtggaa               atgacagaagatacagcgttggaagaagaaagtggagcaaatcaaggtcc               tcaagaagagatcacagaaaaccacgacatcgaagtcattgaagaaaata               acttagtagaaatgacagaagatacagcagttggagaagaaagtggagca               aatcaaggtcctcaagaagagatcacagaaaaccacgatatcgaagtcat               tgaggaaaacaacttagtggaaatgacagaagatacagcagttggagaag               aaagtggagcaaaccaaggtcctcaagaagaaatcacggaaaatcacgac               atcgaagtcattgaagaaaacaacttggtggaaatgacagaagatacagc               gttggaagaagaaagtggagcaaatcaaggtcctcaagaagagatcacag               aaaaccacaacatcgaagtcattgaagaaaacaacttggtggaaatgaca               gaagatacagcagttggagaagaaagtggagcaaacccaggacctcaaga               agaagtaacagagaatcaacctcagcaagaagaaatcatggaaaaccaag               aagtcgaaaagaaaggcgatagtaacttggtagaaagtacaaaaactcca               aaggccgaagaatcagttagcgttcagccaactttagaagacaaaaacac               aaagaaccacgttaacacagtagtagtgaatacgaaggtatctgaagtta               aagaaaaggatccccaccatacaaaagcactaccagatacggggacaacc               tctcgaagtcattccatgatgattcctctccttcttgttgctgggtcagt               agtgttgttacgtcgaaagaaaaagcatagtaaggtgaattaa            
The protein sequence translated from SEQ ID NO 5 is designated SEQ ID NO: 6 and is shown below:
 
         [0000]                                      SEQ ID NO: 6            VYKNEEEKHSIRKLSIGAASVIVGGLMYGVLGNDEAQANEDVTETTGRNS               VTTQASEQHLQVEAVPQEGNNVNVSSVKVPTNTATQAQEDVASVSDVKAH               ADDALQVQESSHTDGVSSEFKQETAYANPQTAETVKPNSEAVHQSEYEDK               QKPVSSSRKEDETMLQQQQVEAKNVVSAEEVSKEENTQVMQSPQDVEQHV               GGKDISNEVVVDRSDIKGFNSETTIRPHQGQGGRLNYQLKFPSNVKPGDQ               FTIKLSDNINTHGVSVERTAPRIMAKNTEGATDVIAEGLVLEDGKTIVYT               FKDYVNGKQNLTAELSVSYFVSPEKVLTTGTQTFTTMIGNHSTQSNIDVY               YDNSHYVDGRISQVNKKEAKFQQIAYINPNGYLNGRGTIAVNGEVVSGTT               KDLMQPTVRVYQYKGQGVPPESITIDPNMWEEISINDTMVRKYDGGYSLN               LDTSKNQKYAIYYEGAYDAQADTLLYRTYIQSLNSYYPFSYQKMNGVKFY               ENSASGSGELKPKPPEQPKPEPEIQADVVDIIEDSHVIDIGWNTAVGEES               GANQGPQEEITENHDIEVIEENNLVEMTEDTAVGEESGANQGPQEEITEN               HDIEVIEENNLVEMTEDTALEEESGANQGPQEEITENHDIEVIEENNLVE               MTEDTALEEESGANQGPQEEITENHDIEVIEENNLVEMTEDTAVGEESGA               NQGPQEEITENHDIEVIEENNLVEMTEDTAVGEESGANQGPQEEITENHD               IEVIEENNLVEMTEDTALEEESGANQGPQEEITENHNIEVIEENNLVEMT               EDTAVGEESGANPGPQEEVTENQPQQEEIMENQEVEKKGDSNLVESTKTP               KAEESVSVQPTLEDKNTKNHVNTVVVNTKVSEVKEKDPHHTKALPDTGTT               SRSHSMMIPLLLVAGSVVLLRRKKKHSKVN                    SEQ ID NO: 7            atgaataaatcaagaactaaacattttaattttttatcaaaacgtcagaa               tcggtatgctattcgccacttttcagctggtactgtgtcagtgcttgtag               gagcagctttcttgctaggtgtccatacgagtgatgcatctgctgcagaa               caagatcaaacatctgaagcaaagcaaaacctctttgatgcttccgctat               ttttggcgctttaacagagacgaacgaaaaggtagcacaagtgacgccaa               cagaaaaaaatctttcatcagttgaagaaatgagagataaaggcgcaact               ggaaatggaccatcaataacatcactacaaactgtagaacaaaataatgc               agtacaacctacagcaacacctattaatgacacagaaaattcaaccgaag               cccctatgaaagaacaatcgaatgatgcacaaacgactgacgaaagtaac               aatgccactcagaaaaataatactgaaccccaagcaaacaatgaaatatc               agcgcgtaatgcaaaaacaacagcatatttaacaagtgaaacctttacaa               cagcaacgtctacaactgatatgcctacacagaaacaagaatatccatct               ttagaaaatccaacaaatcaatcgcaaacgaacagagcacaaccaccaac               aatggaagcacccaaactggcagaaggattagacaatctattaaaaaaat               caactttcgaaagtatgtacgtgacaaaaagaaatcaatttgacaaagag               acggcttctaaaacaaaagcatggccgagtgatgttgttccagaaaatca               agtagagatacttgctgatgcaattcaaaatggctatatcaaatctgtaa               atgatgtgaccaataaagcacatacgttatctggacgtgcatggatgtta               gaccacggaacaccaacgacaatagctaatggtttaacacctgttccaga               gggcactaaagtttatttgcggtggatagatcaagatggtgccacttcgc               caatgtatacagcaaaaacgacaagtagattaagcgctgcggatggtaat               caagtgggtccaggtgcttatgctttcgatttacgcacaggttggataga               tgctaaaggaaaacaccacgtatatagagcagtaaagggtcaatattata               aaatatggatcaatgattttagaactaaagacggtaatatcgctacaatg               ttacgtgttgcaggaggatatgttccgggaacgtacgtggattctgtgac               atacaacaatatgggccaatttccattaattggtacaaatatgcaacgta               caggtatctttatgacaacgataccttcagaaaaatatttaatatcaaaa               cattacgtgaaagatacaaaaggtgctgcagcaaatccagccgtcacgat               aattgaaaataactttgtgagcggcaaagtttggatagaaacaggtgctg               gagattatgtgaactcagcgacaggtccaaaccacaatgcgaaagatgtc               gttgcctctggatacaaagtggtcatgtcatcattaacagatcaaggtgc               taaagcctacgatgcgcaagtcaatcgcttgccgaagaaagatcgagcag               aagcagcacgtcaattattaataaaacatccagaatatatcgcagcaact               gtagaagggataacgaatgagtgggggagatatacattgcgtttccctaa               aggcacattcaacaaagaccatctttacggttacgtattggattttgatg               gtgaaattgtaaaaacttattcaggttttacttcaccagagttccggaga               ccgaattataatttgaccgttacaccgcaaacagctccctattatagacc               cgttcgacgtgcatgggtcaatgttaattttgcggttattgaagcaccac               aatctcaaatcgaaataaaagaatttgatgcaacctctaaccctgcgcat               cgtgggcaaacagcaactattgatatcataggtatgcctaaaacttcatt               acttacacgtgtacaatggaaagattcatcgggcagtattgttgaggata               gtggtcctgtttttacggaagaagaggctgaacatatagcggaatttgta               ataccgtctagcgcaaaatcaggcgaagtgtatactgtacaactcgtggt               aggtaatcatatcgtagcttcggactctcttattgtacatgtcaatgaag               aagcggcgacatatcatccgatatacccatcgacaacagtagaatcaggt               caaagagtaacgattccagcacctaagaatatggatggcaaacctttact               agatggcacaacttttgaaaaaggtcatcacgtaccaacttgggctttag               tgaatggtgatggctcgattacagtaaaacctggagaaaaagtagcagag               ggtgagtatgatattccagtgattgtgacatatccagatggttctaaaaa               cacaatctttgcacctgtgaccgttgaagaaaaacaaccaatggcatcgc               aatatgagccaataacaactggagtatcgaaaccatttggaaacccagta               atgccaactgatgtaacagattcaattcaagtaccgaactatccattgga               agggcaacaaccgacagtaacagtggatgatgaaagtcaattaccagatg               gaacaacagaaggttacaaggatatagatgtaacagtgacatacccagac               ggaacaaaggatcgtgtcaaagttccagtcgtaacggaacaacaattaga               tagtgataaatatgatccggtcgcaacaggtatcttgaaaccgtttggta               ctccaacaacagaggaagacgttataaaattagtggagataccgaaatat               ccaacagacttaacacaaccaaaagtaacagtgacggttccaaatacttt               accggatgggcaaacgccaggtaaagtagacgttgatgtgacagtaacgt               atccagatggttccacagatcacatttcagttccagtttggacaaacaag               catctggataaagacaaatataacccaataacgactggggtatcgaaacc               atttggaatcccagtaacgccaactgatgtaacagattcaattcaagtac               cgaactatccattggaagggcaacaactgacagtaacagtggatgatgaa               acacaattaccagatggaacaacagaaggtcacaaggatatagatgtaac               agtgacatacccagacggaacaaaggatcatatcaaagttccagtcgtaa               cggaaaaacaatcagataatgaaaaatatgagccaacaactaacggaatc               acgaaaaagtacggtatccctacgacagaggatgaagtgatagatatagt               tcgaattccatattttccagtagatggcgtgcaacctattgtaacggtaa               atgatcctagactattgccaaatggtcaaaaagaaggtcaaatcaatgtt               ccagtcacagtgacgtatccggatggcacaaaagatctcatgacagttcc               ggttattacaggtaagcaagcagaaaatgaaaaatacgatccaatcacat               taggagtaactaaagattatggtgatcctacaactgcaaacgatgtgaca               aagtcaatccaaataccaacatatccagcaggtggcgaacaaccaatcgc               aacagcggatgatgaaagtcaattaccggatggcacagtagaaggtaaag               tggatattccagtcacagtgacgtatccggatggtactcaggatcatatc               actgtcccagtatttaccaatcaacaacgagataatcaaaaagccagtaa               agctgtgacgaaaatacatggtatatcggtaacaggcactgatatgacag               atactaagaaaaatcataactatccagcaggtggtgaacaacctaaagtt               actgtgaaagatgacgatcaattatcagagggtaaagtcgattcaacagt               gggtgcggataatgtgacaactacagatgatttatcaagcgtaactgcgg               tatctcatggtcatcaaacaagtgtacaaacaacaaaagagaaccaatca               gtgcatgatgaagaggtgacgatcccaacagttgcacatgtgtctacaat               aatgacaggtgtggtaaagggtgagcaagaagcgacggatatcgtggcta               gaccacatgttgaaacaactcaactcccatcaatttcagctcaagcaaca               gttaaaaaactaccagaaacgggtgaaaacaatgaacaatcaggtgtttt               attaggtggatttattgcgttcatgggtagcttacttttattcggcagac               gtcgcaaaccaaagaaagattaa            
The protein sequence translated from SEQ ID NO 7 is designated SEQ ID NO: 8 and is shown below:
 
         [0000]                                      SEQ ID NO: 8            MNKSRTKHFN FLSKRQNRYA IRHFSAGTVS VLVGAAFLLG               VHTSDASAAE QDQTSEAKQN LFDASAIFGA LTETNEKVAQ               VTPTEKNLSS VEEMRDKGAT GNGPSITSLQ TVEQNNAVQP               TATPINDTEN STEAPMKEQS NDAQTTDESN NATQKNNTEP               QANNEISARN AKTTAYLTSE TFTTATSTTD MPTQKQEYPS               LENPTNQSQT NRAQPPTMEA PKLAEGLDNL LKKSTFESMY               VTKRNQFDKE TASKTKAWPS DVVPENQVEI LADAIQNGYI               KSVNDVTNKA HTLSGRAWML DHGTPTTIAN GLTPVPEGTK               VYLRWIDQDG ATSPMYTAKT TSRLSAADGN QVGPGAYAFD               LRTGWIDAKG KHHVYRAVKG QYYKIWINDF RTKDGNIATM               LRVAGGYVPG TYVDSVTYNN MGQFPLIGTN MQRTGIFMTT               IPSEKYLISK HYVKDTKGAA ANPAVTIIEN NFVSGKVWIE               TGAGDYVNSA TGPNHNAKDV VASGYKVVMS SLTDQGAKAY               DAQVNRLPKK DRAEAARQLL IKHPEYIAAT VEGITNEWGR               YTLRFPKGTF NKDHLYGYVL DFDGEIVKTY SGFTSPEFRR               PNYNLTVTPQ TAPYYRPVRR AWVNVNFAVI EAPQSQIEIK               EFDATSNPAH RGQTATIDII GMPKTSLLTR VQWKDSSGSI               VEDSGPVFTE EEAEHIAEFV IPSSAKSGEV YTVQLVVGNH               IVASDSLIVH VNEEAATYHP IYPSTTVESG QRVTIPAPKN               MDGKPLLDGT TFEKGHHVPT WALVNGDGSI TVKPGEKVAE               GEYDIPVIVT YPDGSKNTIF APVTVEEKQP MASQYEPITT               GVSKPFGNPV MPTDVTDSIQ VPNYPLEGQQ PTVTVDDESQ               LPDGTTEGYK DIDVTVTYPD GTKDRVKVPV VTEQQLDSDK               YDPVATGILK PFGTPTTEED VIKLVEIPKY PTDLTQPKVT               VTVPNTLPDG QTPGKVDVDV TVTYPDGSTD HISVPVWTNK               HLDKDKYNPI TTGVSKPFGI PVTPTDVTDS IQVPNYPLEG               QQLTVTVDDE TQLPDGTTEG HKDIDVTVTY PDGTKDHIKV               PVVTEKQSDN EKYEPTTNGI TKKYGIPTTE DEVIDIVRIP               YFPVDGVQPI VTVNDPRLLP NGQKEGQINV PVTVTYPDGT               KDLMTVPVIT GKQAENEKYD PITLGVTKDY GDPTTANDVT               KSIQIPTYPA GGEQPIATAD DESQLPDGTV EGKVDIPVTV               TYPDGTQDHI TVPVFTNQQR DNQKASKAVT KIHGISVTGT               DMTDTKKNHN YPAGGEQPKV TVKDDDQLSE GKVDSTVGAD               NVTTTDDLSS VTAVSHGHQT SVQTTKENQS VHDEEVTIPT               VAHVSTIMTG VVKGEQEATD IVARPHVETT QLPSISAQAT               VKKLPETGEN NEQSGVLLGG FIAFMGSLLL FGRRRKPKKD                    SEQ ID NO: 9            atgtttaatcaacaaaaacaacactatggtatccggaaatatgcaatcgg               gacttcatcagtattattaggcatgacattatttatcacacatgacgcaa               ctgcatctgcagctgaaaacaatacaactgcaaagacagagacaaatcaa               gcagcaacaatttcttctcgcacttcgccaaccgacgtcgctcaacctaa               tgcagacacgaatgctacaacggcgactaaagagacaacaccacaatcag               attcaacagcattaccgcaagcagcagcgcaacctcaaacgggccaaaca               gcatcgaaagacacagtagatacaaataaaacgcaaacagcagattccac               aaccgctcctcctgtgacagacgcgccaaaagctaatgacgacacaacac               agccagaagctgcgactgtagccaaaaaagaagatgctcagacaccatcg               actgcagaccctacaccacaagcgcaacaaccgcctcagtcaaaagcacc               tcaagaaacgcaacaacaatcaacagttgaagatacaacgccacaacaaa               acgcatcaactgaagcacaccctaaaaatgtagataccgcttcaacaaaa               caacaacaaacaacgccatcaaccgcaccgacaccttacacacaacaagc               agacgaagcaatgacagatgtcacaacaaccagtgtcgacagcaacgtac               agccgttagcccctgcagaagatcaacctaaaaatacgaacacagctgac               aaagcaaccgttgcgacaccaccacgtgacaatgctaagactgctgatcc               gaacaaaaagatgacacgtgcagcaacgacacaacaagatgatgccgtcg               atacattgaagtcaaaagaaatgacagcaacgatcgataaaagttttcca               gccgttaaatattacacgttgaaaaatggtaaaaaagtcgatgcacaact               gacggatgcacgtcaaatcatcgtcaatggtgaagtcattacaccaacag               tcaaatacaacaaaattgatgatcatacggctgaatatgacttaacagca               caaaatgattcacgttcgattgatgccaattttaaatttcgtttatcagt               tgaaggtaagaccgttgatttacaaatgacagattacacgaacaacaaca               cagatccacaaaacgtcattcgcaactttagctttgtaagtcaatcgctc               gtatctgtaaacaatcaacagaaaaatgccaaactgcaaacatcgaaact               gtctacaaatacaatgaaaagcggcgataaatcatatcatatcgatgaaa               atttcaaaaacgacttcaacgactttatgatgtacggtttcgtgtcaaat               gatgattacagtgcaggattgtggagtaacgcacaaattggcgtcggcat               tggtgaacaagacttcttacgtgtctacgcacagtctatacaaacagata               tcggggtcgctgtcggtttaggctcaatgccatggtttatccaaaaagac               gctgcacatccagatgcgaaaaatcaaggactactcccacatgtcaaagt               tgcaattgcggaagatgaaaatcaagatggtgaaattaactggcaagacg               gtgcaattgcttatcgtagcattatgaacaatccatatggtgccgaagaa               gtacctgaccttgttgggtaccgtatcgcgatgaactttggttctcaagc               gcaaaacccatttttaaagacgttagatggtgtgaaaaaattctatctca               atacagatggtttagggcaatccattttattaaaaggttataacagtgaa               ggccacgactctggtcatttagattacgcgaatattggtcaacgtatagg               tggcgtgaaagactttaaaacgttacttcaaaaaggggcagattatggcg               cacgtttcggtcttcatgtgaatgcatctgaaacatatccagagtctcaa               gcattcaatcctgccctcttacgtaaagatgcgaatggaaactatatgta               tggctggaactggctcgatcaaggctttaacatcgatgcagattacgatt               taatacacgggcgtaaagaacgcttcgaagcactcaaacaaattgtcggt               gatgacctcgactttatttatgtcgatgtatgggggaatggacaatccgg               cgacaatacagcttggccatcacatcaattagccaaagaaatcaacgact               taggatggcgcgtcggtgtcgaatggggtcacggtatggaatatgactcc               acgttccaacattgggcagccgacttaacgtatggatcgtaccaaaataa               agggattaactcagaggtagcacgcttcttacgcaaccatcaaaaagatt               catgggtcggtaactatccaaaatactcaggtgcagctgacttcccattg               ctcggcggttatgacatgaaagattttgaaggttggcaaggtcgtaacga               ttactctgcttacattaaaaatattttcaatgttgatgtaccaacaaagt               ttttacaacattataaagtgatgcgtattgtcgatggtgagcctgttaaa               atgactgccaatggtcaaacgattgactggacaccagaaatgcaagtcga               tttacaaaatgaagccggtgatcaagtcactgttaaacgtaaatctaacg               actatgaaaacgacactgacaactaccgctcacgtacaatcgaattgaat               ggtcgcacagtactcgatggcgattcataccttttaccatggaattggga               tgcgaacggccaaccattaactggcgataacgaaaaattatatcactgga               ataaaaaaggcggttcaacgacttggacactgcctgaatcatgggataca               gaccaagtcgtgctatacgaattatctgaaacgggtcgtaagtcaccacg               tacagtggcagtgaaagaccatcaagtgacactcgataatattaaagcag               acacaccgtatgtcgtttataaagtcgcacaaccagacaacacagatgtg               aactggagcgaagacatgcacgtgaaagatgccggcttcaactcacaaca               actgacaccttggacaatcgaaggcaatcgagataaagtgagcatcgaaa               agtcgacaacatcaaatgaaatgctaaaaatcgatagtccaacaaaaaca               acgcaattaacgcaacaattgacaggtttagtgccaggacaacgttacgc               tgtctatgttggcatcgataaccgcagtgatgcagcggcgcatattgcag               tgacacataacggtaaaacgctcgcaagtaacgaaacaggtcaatcgatc               gcgaaaaactatgtgaaagcagatgcacatagtaacaatgctgcgacgtt               taaaaatggcggtagttacttccaaaacatgtacgtgtacttcgttgcgc               cagaagatggtaaagcagacttgacgattcaacgcgacccaggtgaaggg               gccacttatttcgatgatattcgtgtgttagaaaataacgcgaatctcct               tcaaaacggcacattcaaccaagacttcgaaaatgtaccacaagggttat               tcccgttcgtcgtgtcagaagttgaaggcgttgaagataatcgcgttcac               ttatctgaaaagcacgcaccgtatacacaacgcggatggaataataaacg               tgtcgatgatgtcattgatggcaaatggtcacttaaagtaaacggtcaaa               caggtaaagataaaatggtcatccaaacgattccgcaaaacttctacttc               gaaccaggaaaaacgtatgaagtgtcatttgattatgaagcaggttctga               tgatacgtatgcatttgcgacaggtagtggggacatttctaaaaatcgta               actttgaaaagacaccattgaaaaatacagtcgatggtggcaaagcgaaa               cgggtgacatttaaagtgacgggtgatgaaaatggtcaaacttggatcgg               tatttactcaacgaaaacacccaatgatccacgaggcgtgaaaaatggca               atcaaatcaacttcgaagggacgaaagatttcattctagacaacctttct               atccgtgaaattgacgcaccgaagcctgatgccacacaagaaagcggtga               tagcgcaccaatgaatgaaacagatgagcgtaacgtcaattcaaacggta               cattagccgatcatagtgagacaactgatgtcaatgtcagtgcaacggca               gatgatacagcagtcaaaggcgaaatgacgacaaacagaacagatgcacc               aactgttacactgcctgaagcaacgatagtagatgaaggcacgtcaaatc               ctgtcactacaacaccaacgaatacaacacaagctatgacaaataaggct               gatgagatgccacaaacgatgaacaatgttcctttaactagcatcgctac               cgatatgatgcagtctcatgcggtggattccatggcagcaacactagcag               ctacaaatcaagtggcggcacctgtgcgtcaaacagcaggacctatgcaa               catggtatggacagtgcttcaacgcaacacgcacccatacaagttgacaa               tgtcacagcaccaccattaccagatgaacagtttgccgaattacctaaaa               ctggggatacgactccaaatacacgtggacctttaatggcgatgatagtt               ggcgcagtcttaacagcattcggattcagacgccaacgtaaagaaaaata               g            
The protein sequence translated from SEQ ID NO 9 is designated SEQ ID NO: 10 and is shown below:
 
         [0000]                                      SEQ ID NO: 10            MFNQQKQHYGIRKYAIGTSSVLLGMTLFITHDATASAAENNTTAKTETNQ               AATISSRTSPTDVAQPNADTNATTATKETTPQSDSTALPQAAAQPQTGQT               ASKDTVDTNKTQTADSTTAPPVTDAPKANDDTTQPEAATVAKKEDAQTPS               TADPTPQAQQPPQSKAPQETQQQSTVEDTTPQQNASTEAHPKNVDTASTK               QQQTTPSTAPTPYTQQADEAMTDVTTTSVDSNVQPLAPAEDQPKNTNTAD               KATVATPPRDNAKTADPNKKMTRAATTQQDDAVDTLKSKEMTATIDKSFP               AVKYYTLKNGKKVDAQLTDARQIIVNGEVITPTVKYNKIDDHTAEYDLTA               QNDSRSIDANFKFRLSVEGKTVDLQMTDYTNNNTDPQNVIRNFSFVSQSL               VSVNNQQKNAKLQTSKLSTNTMKSGDKSYHIDENFKNDFNDFMMYGFVSN               DDYSAGLWSNAQIGVGIGEQDFLRVYAQSIQTDIGVAVGLGSMPWFIQKD               AAHPDAKNQGLLPHVKVAIAEDENQDGEINWQDGAIAYRSIMNNPYGAEE               VPDLVGYRIAMNFGSQAQNPFLKTLDGVKKFYLNTDGLGQSILLKGYNSE               GHDSGHLDYANIGQRIGGVKDFKTLLQKGADYGARFGLHVNASETYPESQ               AFNPALLRKDANGNYMYGWNWLDQGFNIDADYDLIHGRKERFEALKQIVG               DDLDFIYVDVWGNGQSGDNTAWPSHQLAKEINDLGWRVGVEWGHGMEYDS               TFQHWAADLTYGSYQNKGINSEVARFLRNHQKDSWVGNYPKYSGAADFPL               LGGYDMKDFEGWQGRNDYSAYIKNIFNVDVPTKFLQHYKVMRIVDGEPVK               MTANGQTIDWTPEMQVDLQNEAGDQVTVKRKSNDYENDTDNYRSRTIELN               GRTVLDGDSYLLPWNWDANGQPLTGDNEKLYHWNKKGGSTTWTLPESWDT               DQVVLYELSETGRKSPRTVAVKDHQVTLDNIKADTPYVVYKVAQPDNTDV               NWSEDMHVKDAGFNSQQLTPWTIEGNRDKVSIEKSTTSNEMLKIDSPTKT               TQLTQQLTGLVPGQRYAVYVGIDNRSDAAAHIAVTHNGKTLASNETGQSI               AKNYVKADAHSNNAATFKNGGSYFQNMYVYFVAPEDGKADLTIQRDPGEG               ATYFDDIRVLENNANLLQNGTFNQDFENVPQGLFPFVVSEVEGVEDNRVH               LSEKHAPYTQRGWNNKRVDDVIDGKWSLKVNGQTGKDKMVIQTIPQNFYF               EPGKTYEVSFDYEAGSDDTYAFATGSGDISKNRNFEKTPLKNTVDGGKAK               RVTFKVTGDENGQTWIGIYSTKTPNDPRGVKNGNQINFEGTKDFILDNLS               IREIDAPKPDATQESGDSAPMNETDERNVNSNGTLADHSETTDVNVSATA               DDTAVKGEMTTNRTDAPTVTLPEATIVDEGTSNPVTTTPTNTTQAMTNKA               DEMPQTMNNVPLTSIATDMMQSHAVDSMAATLAATNQVAAPVRQTAGPMQ               HGMDSASTQHAPIQVDNVTAPPLPDEQFAELPKTGDTTPNTRGPLMAMIV               GAVLTAFGFRRQRKEK                    SEQ ID NO: 11            atgacaagaaaatttagggaatttaagaaaagtttaagtgaagaaaaagc               aagagtgaaactttacaagtcaggtaaaaactgggttaaagctggaatta               aagaatttcagttattaaaagcattaggcttatcttttttaagccatgac               attgtaaaggatgaaaatggagaagtaacgacacaatttggggaacagtt               gaagaaaaatgcattaagaacaactgcttttgcgggtggaatgttcacag               ttaatatgttgcatgaccaacaagcatttgcggcgtcggatgcacctata               acttctgaactggcaaccaaaagtcaaactattggcgatcaaacatcaat               tgttattgaaaagtctacatcgtcagatcaatcaacgaacccaataacag               aaagtgaaagtaaacacgattctgaaagtatctcattatctgagcatcaa               acatcagagtcaacaagtctttcaacgtcaacttccaaatcaatatcaac               ttcagtagaggaatcagaatcaacatcaaaagattctcatactaaaactc               aagatagtcaatcagatagtcatcagtcaacaagtcaagaggtaaatggc               tcttccaaccacgagcaatcaacaccacacactgcacaaagtcttacgag               cctatctattgagagccaaacgtcgacttcaaatacatcattgaaggaaa               ctaaagaaggggaattgtcaaaaaacctttcgaagttatctcaaaatcaa               aacatcaaacttcatgaagaacatacgatgcgttcagcagatttgagctc               aggttatacaggatttagagcggcttactatgtaccaagatcaagaacaa               caccaacgacaaaagtctacacagggcaaggaagcttcagaggtagaggt               agaattaaatataatattttctacaaagttgtcgttacaagtaatggcaa               agaaatgaagatccgctatacattgagtcaagatgatccaaacacgtcta               atgttgaaaaacctaggtgggcaggacagaaacgatttggtattcataat               acttgggatgaaggtcctggtcgcgggcaattaaagttagggtcggcatt               cggcaaaccaacagttatacaaggagaaactagaccgaattatggtagct               gggttggcacacctataacgaaatatgtttcaggcgatcgtacaaatggt               ttttactggcaagctgctgtacttgcaccgagacatggagagaagggaga               aggaatcacagcagaaattacagttcctattgttaacccttctggaagat               ttaattgggaattccatcctgtcggtcaacaggacggagttggtggcaaa               actgactactttgaaaatgtatggattcgagactatgacccatattacaa               atatattcaaactaaggaaggcagagcctcagtttcgcactctatttctc               aggtgaaagcaagtgaatcgagatcgacatcgctcatacaatcggagtct               attagaagatcacagtccatatctgagagtgaatctattgtagccgcaag               tcattcggcaagtgtagcaaaatcgcaatccatctcgagaagtcaatctg               tggcgaaatcacaatcgatctcaagaagtcagtcgatcgcacacagccga               tcagcaagtgtggcaaaatcgcaatccatctcaagaagtcagtcgatcgc               acacagccgatcagcaagtgtggcaaaatcacaatcgatttcaagaagtc               agtcgatcgcacacagccgatcagcaagtgtggcgaaatctcaatcgatt               tcaagaagtcagtcaattgcgcagagccaatcagcaagtgtggcaaaatc               acagtcgatttcaagaagtcagtcaattgcgcagagccaatcagcaagtg               tggcgaaatcgcaatcgatttcaagaagtcagtcgattgcacatagccga               tcagcaagtgtagcggaatcacagtcgatttcaagaagtcagtcgattgc               gaatagccaatctgtagcagcgagtgaatcagagagtctatcaatatcat               tgtctaaaaagcagtcaatatcgatgagtaattctgaaagtgcagcaaaa               tcacactcgctttcggtgaaaaggtctaactggattaaaaagtcaaaagc               ggcttcagtaagaaagtcacattcactttcggtaagaaaatctaattcgg               cgaaaaggtcacatgctatttcggtaagaaagtcaaagtcattatcagtt               aaaaagtcaatttcgcagagccaatcagcaagtgtggcgaaatcgcaatc               gatttcaagaagtcaatcagtagcagcgagtgagtcggcatcgctaagta               agtcgaagagcacatcgctcagtaactcagtgagtgcagagaaatcgacg               tcattaagtcgttcagcaagtgtagcaaaatcgcaatcgatttcaagaag               ccaatcagtagtagcgagcgaatcggcatcgttaagtaagtcgaagagca               catcgctcagtaactcagtgagtgcagagaaatcgacgtcattaagtcga               tcagcaagtgtagcaaaatcgcaatcgatttcaagaagccaatcggtggc               agcgagcgaatcggcatcgttaagtaagtcgaagagcacatcgctcagta               actcagtgagtgcagagaaatcgacgtcattaagtcgatcagcaagtgta               gcaaaatcgcaatcgatttcaagaagccaatcggtggcagcgagcgaatc               ggcatcgttaagtaagtcgaagagcacatcgctcagtaactcagtgagtg               cagagaaatcgacgtcattaagtcgatcagcaagtgtggcaaaatcgcaa               tcgatttcaagaagccaatcagtagtagcgagcgaatcggcatcgttaag               taagtcgaagagcacatcgctcagtaactcagtgagtgcagagaaatcga               cgtcattaagtcgatcagcaagtgtagcaaaatcgcaatcgatttcaaga               agccaatcggtggcagcgagcgaatcggcatcgttaagtaagtcgaagag               cacatcgctcagtaactcagtgagtgcagagaaatcgacgtcattaagtc               gatcagcaagtgtggcaaaatcgcaatcgatttcaagaagccagtcagta               gcagcaagtgagtcggcatcattaagtaagtcgaagagcacatctttaag               caactcagtgagtgtagagaaatcgacgtcattaagtcgatcagcaagtg               tggcgaaatcgcaatcgatttcaagaagtcaatcagtagcagcgagtgag               tcggcatcgctaagtaagtcgaagagcacatcgctcagtaactcagtgag               tgcagagaaatcgacgtcattaagtcgttcagcaagtgtagcaaaatcgc               aatcgatttcaagaagccagtcagtagcagcaagtgagtcggcatcattg               agtaaatcaacaagtacgtcaacaagtgactcagatagcgcgtcaacatc               aacatctgtatcagatagcgattcagcttcattgagtaagtcgactagta               catcaacaagcgattcagacagcgcgtcagcatcattgagcaagtcaaca               agtacatcaacgagcgactcagatagcgcatcgacatcaacatcagtatc               agatagcgactccgcatcgttgagtaaatcgacaagcacgtcaacaagtg               attcagacagcacgtctacttcattgagtaagtcgacaagtacatcgaca               agtgattcagatagtgcgtcaaaatcaacgtcagtatcagacagtacgtc               cgcatcattgagtaaatcgacaagcacgtcaacaagtgattcagatagtg               catcaaaatcaacgtcggtatcagatagcacgtcagcatcattaagaaag               tcggcaagtacgtcaacgagtgactcagacagcacgtctacttcattgag               taagtcgacaagtacatcgacaagtgattcagatagtgcatcaaaatcaa               catcagtatcagatagcgattcagcttcattgagtaagtcgactagtaca               tcaacaagcgattcagatagtgcgtcaaaatcaacgtcggtatcagatag               cgactccgcatcgttgagtaagtcgacaagtacgtcaacaagcgattcag               acagtgcatcaaaatcaacgtcggtatcagacagtacgtcaacatcatta               agtaagtcgacaagtacatcaacaagcgattcagatagtgcgtcaacatc               gacatcagtatcggacagtacgtctgcatcattgagtaagtcgacaagca               catcgacaagtgattcagatagcgcatcaacatcagtgtcagatagcgat               tcagcatcactaagcaagtcaacaagtacatcgacaagcgattcagacag               cgtatcaacatcaacatcagtatcagatagtgattccgcgtcattaagta               agtcgacaagtacgtcaacaagcgattcagatagtgcgtcaaaatcaaca               tcagtatcagatagcacgtcaacatcattgagtaaatcaacaagtacatc               gacaagtgactcagatagtgcgtcaacatcggtatcagacagtacgtccg               catcattgagtaaatcgacaagcacgtcaacaagtgattcagatagtgca               tcaaaatcaacatcagtatcagatagcgattcagcatcattaagcaagtc               gacaagtacatcgacaagtgattcagatagtgcgtcaacatcaacgtcag               tgtcagatagcgattcagcttcattaagcaaatcaacaagtacgtcaaca               agtgactcagatagcgcatcaacatcattaagcaagtcaacaagtacatc               gacaagcgattcagacagtacgtctacatcattaagtaagtcaacaagta               catcaacaagtgattcggatagtgcgtcaaaatcaacatcagtatcagat               agcgactcagcttcattaagcaagtcgacaagtacgtcaacaagtgactc               agacagtgcgtcaaaatcaacatctgtgtcagatagcgactccgcatcgt               tgagtaagtcgacaagtacgtcaacgagcgattcggatagtgcgtcaaaa               tcaacatcagtatcagatagtgaatccgcgtcattaagcaagtcgacaag               cacatcgacaagtgactcagatagtgcgtcaacatcgacatcggtatcag               acagcacatcagtttcattaagcaagtcgacaagcacgtcaacaagcgat               tcagacagtacgtctacttcattaagcaagtcgacaagcacgtcaacaag               tgactcagatagtgactcagcttcgttgagtaaatcgacaagcacgtcaa               cgagcgattcagatagcgtgtcaacatcaacatctgtgtcagatagcgat               tcagcttcattaagcaaatcgacaagtacatcaacaagcgattcagatag               tgcgtcaacatcaacgtcggtatcagatagcggctccgcatcgttgagta               agtcgacaagtacgtcaacgagcgattcagacagtgcatcaaaatcaacg               tcggtatcagatagtgattcagcatcactaagcaaatcgacaagcacgtc               aacaagtgactcagacagtgcgtcaacatcgacatcggtatcagatagca               catccgcgtcgttaagcaagtcgacaagtacgtcaacaagtgattcagac               agcgcatcgacatcaacatcagtatcagatagcgactccgcatcgttgag               taaatcgacaagcacgtcaacaagtgattcggacagtgcgtcaaaatcaa               catcagtgtcagatagcgattcagcttcattgagtaagtcgacaagcacg               tcaacaagcgaatcagacagcgcgtcaaaatcaacgtcagtgtcagatag               cgattccgcatcattaagtaaatcgacaagcacgtcaacaagtgactcag               atagtgcatcgacatcaacgtcagtatcagatagtgattccgcgtcatta               agcaagtcgacaagtacgtcaacaagtgactcagacagtgcgtcaaaatc               aacatcagtatcagatagcgattccgcatcattgagtaagtcgacaagca               cgtcaacaagcgaatcagacagtgcgtcaacatcgacattagtatcggat               agtacgtcggtttcattgagccaatcaacaagtgtggataaagatagtac               agcgaagggatcgacagaattagtaaatgttgcatcactttcaatcagtg               cgagtcaatcaagtagtttatctgcttcaacatccacatcgattgaaaag               tctgagtctacatcaacaagtggctcaaattcaactaatgcgtcgttaag               tagctcatcttcacttagtacatcagcaagtacttctgtaagcgaagtga               catctgtcacacattctgaaaatgatttaagtgcatctaacgatagagat               acatccggatcagtaagtcaatttgcttctgaaaatacatcattaagtga               ttctgcatcaattagtggcgaagtttctagtagtacgtccgcgtcaactt               cgaaatcatcatcactttcagcaagcgcgttacatgataagcatgtatca               gaaagcacttctgcatcattaagtagtggagattcaagtcgtgcttcggc               atcagtgtcaacgtcattatcagaatcagatagtgcgttaatagactctg               aatcaattagcgtttccgagcacacatcaacattacaatcaggtagtcat               tcactatcacaacaacaatcagcagaattatcacaatcagagcaaacatc               acaatcacaacgcatttcaacaagtgcgtcagtatcggctatgaaatcag               aaagtgctgctaaggtatctgaatcgctatctacgtctcaatcaaaagta               gatagtcaatcacaatcggtatctgaatcagcgagcaactcacgagtgtc               aagagattcaaaatcaacaagcgcttcaatgcatcgatcattgtcagagt               cagtatctcaaagtatgtcacttattgatcagtcagaaagtgattcaaca               tctatatcgatttcgacgtcaatcagtgatgaagactctatgctgtattc               tatgagtgattccgcatcgatcagtactaaggcatcaagtagtatgtcta               cttcgacaagcgaagagcatgccaacagtcattctcagtctgaatcgaca               gcatcggttgaagtatctcaagaaatgagtgcatcggcttcaacaagcaa               atctgagtctcaatcagagtcagtatcagtaagtaacgaagaatcaaata               tctcatctatgcaagagtcttttgtagagagtgcaaaagcatcgcgtagt               gcatctatgagcgttgcaaaatctgaagcctctgaatcacagctattaag               tgagtctaatgcttcggtaagccaatcagcaagcacaagtagtaaagcat               cagcaagtacgtcagaatctatttcaacgtcactcagcgtatctgaagca               actcatggaaaaccgagaaatcattcagaaagtgcatcagcaagtcaatt               attagaagaaaatgagtcattaagcgattcagcatcaacaagtgttgaag               attcagaaagtgcatcagcatctctgtcggtgtatcaatcacaatcagca               agtgcattgaaatcaacacatgcatcagaaaaagcttcagtgaatacaag               tgcaaacgcatcgaagcgtgcatcagcatcgacatctatctctaactcga               aatctaaagtcattgcgagtgaatcgaagtcaacaagcatatcaacatat               gaatcgttgtcaatatcgactagtaaagaacaatcaacgcgtgtatcagt               gagtgagtcgacatcaacgtctaaagtgaagtcagaaagcgactcggcat               caacgtcgacatctgaatcaatctcaattagcgcaaatcgttcaggttac               acatcgtctaaacgttcggtacaaatgagtgaagcacaatcaacgagcga               ttcattatcagtaatgcaatctgaaggttcagtaagtgtatcgcaatctt               taagtatatcagataagacatcacagtccttatcggaatcaatatcgcat               tcagaaagtgactctgatagtaactcagtgtctattagtcaagagacatc               tgaacaacattcggtgtcagacagtgactcgatgtcaatttcggaaagcg               aatctattgcatatagtcaatcagcgagtgaatcagaatcaacaagtatc               gcaaaatctgatagtatttcgaactcattatctgtttcattaagtgaatc               agaaagtgaagcaagcacatcagcttcagtgagtacatctgaaagtacgt               ctgtaaagggttctctatcaacaagtatcttgaacagtcaatcagcatct               actcatcaatcaacagaagcttctcaaagtacatcaacttcaaaagttga               ggaagcatcattgagtgactctgcttctgtatcagattcacaatcacttt               caatgagtcatgagaaatcacaaagtgcatcgacttcaaaatctacgagt               ctgtcaaaaactatttctgagtcagagtctgtgagtgcatcaacatcaac               aagtgaagctgtaagtacagaagcaagcgaatttgtatcagcagtagact               cattgagtcaagtaacttctaacggaagcacaacgaaagaagatgcgagt               acatttgtatccacagtagattcattgaaagacaaagcatcaaataatgg               tacaccatcagagtttgcgtcagcagtgaaatcaacacacgcatcagtga               gtgtgtcagcatcagaaagtacgtcagcatcaacatcaacaagtgaagct               gtaagtacagaagcaagcgaatttgtatcagcagtgaattcgttgagtga               agcgacttctaacggaagcacaacgaaagaagatgcgagtacatttgtat               ccacagtagattcattgaaagacaaagcatcaaataatggtacaccatca               gagtttgcgtcagcagtgaaatcaacacacgcatcagtgagtgtgtcagc               atcagaaagtacatcagcatcaacatcaacaagtgaagctgtaagtacag               aagcaagcgaatttgtatcagcagtagactcattgagtcaagtaacttct               aacggaagcacaacgaaagaagatgcaagcacatttgtatccacagtaga               ttcattgaaagataaagcatcaaacaatggtacaccatcagaatttgaat               cagttgtgaaatcagtacacggatcaatgagtgcatcagcaagtgcgtca               acatcagcatctacatcagcatctacatctacaagtgaagctgcaagtgc               agaagcaagcgaattagaatcagtaaggaaatcattatccaatggagcat               caaacggtagcacagcaagagaaggtgcaagcacatttgtatcaacggta               gattcattgaaagataaagcatcaaacaatggtacagcatcagaatttga               atcagttgtgaagtcagtacacggatcaacaagtgcatcagcaagtgcgt               caacgtcagcatcaacatcagcaagtgaatcagcaagtacagaagcaagt               gaatttgtatcagcagtggcatcattaagcagttcagcatggaacggaag               cactacaggagaaggtgcaagcacatttgtatcaacagttgattcatcga               aagattcagcgtcagacaaagcttcaccatcagaatcagaatcagttgtg               aagtcagtacacggatcaacgagtacatcagcaagtgtgtcagcgtcggc               aagtacatcagcatcgacatcaacaagtgaagctgtaagcacagaagcaa               gtgagtttgtatcagcagtgaactcattaagcagtgaagcatcgaacggc               agcacaacaagagaaggtgcaagcacatttgtatcaacagtagattcatt               gaaagacaaagcatcaaacaatggtacagcatcagaatttgaatcagttg               tgaagtcagtacacggatcaatgagtacatcagcaagtgtgtcagcatca               gaaagtacgtcggcatcgacatcgacaagtgaagctgtaagtacagaagc               aagcgagtcagcatcgataagtgtatcaatgtcagtgagcgcatcaacaa               gtgcttcaatgagcgtatcagtgtcaaacagtgtgtcagtgagtgactct               atttcagtaagtgcatcaacaagtgaacctaactcggtaagcacttctat               gagtagttctctttcaacatcggcatcaacgccatcagaaattacttcaa               gttcgtcatcaagcgattcagcgacagttcaaaaagtagtttctaaagat               gaacagcacgctacaaataaagttgaaaaattacctgacacaggtcaatc               aacgacacaaactggtttattgggtggagtaggtgctttacttacaggcc               ttggtttactcaaaaaatcaagaaaacaaaaagatgaagaaacatcatca               catgaataa            
The protein sequence translated from SEQ ID NO 11 is designated SEQ ID NO: 12 and is shown below:
 
         [0000]                                      SEQ ID NO: 12            MTRKFREFKK SLSEEKARVK LYKSGKNWVK AGIKEFQLLK               ALGLSFLSHD IVKDENGEVT TQFGEQLKKN ALRTTAFAGG               MFTVNMLHDQ QAFAASDAPI TSELATKSQT IGDQTSIVIE               KSTSSDQSTN PITESESKHD SESISLSEHQ TSESTSLSTS               TSKSISTSVE ESESTSKDSH TKTQDSQSDS HQSTSQEVNG               SSNHEQSTPH TAQSLTSLSI ESQTSTSNTS LKETKEGELS               KNLSKLSQNQ NIKLHEEHTM RSADLSSGYT GFRAAYYVPR               SRTTPTTKVY TGQGSFRGRG RIKYNIFYKV VVTSNGKEMK               IRYTLSQDDP NTSNVEKPRW AGQKRFGIHN TWDEGPGRGQ               LKLGSAFGKP TVIQGETRPN YGSWVGTPIT KYVSGDRTNG               FYWQAAVLAP RHGEKGEGIT AEITVPIVNP SGRFNWEFHP               VGQQDGVGGK TDYFENVWIR DYDPYYKYIQ TKEGRASVSH               SISQVKASES RSTSLIQSES IRRSQSISES ESIVAASHSA               SVAKSQSISR SQSVAKSQSI SRSQSIAHSR SASVAKSQSI               SRSQSIAHSR SASVAKSQSI SRSQSIAHSR SASVAKSQSI               SRSQSIAQSQ SASVAKSQSI SRSQSIAQSQ SASVAKSQSI               SRSQSIAHSR SASVAESQSI SRSQSIANSQ SVAASESESL               SISLSKKQSI SMSNSESAAK SHSLSVKRSN WIKKSKAASV               RKSHSLSVRK SNSAKRSHAI SVRKSKSLSV KKSISQSQSA               SVAKSQSISR SQSVAASESA SLSKSKSTSL SNSVSAEKST               SLSRSASVAK SQSISRSQSV VASESASLSK SKSTSLSNSV               SAEKSTSLSR SASVAKSQSI SRSQSVAASE SASLSKSKST               SLSNSVSAEK STSLSRSASV AKSQSISRSQ SVAASESASL               SKSKSTSLSN SVSAEKSTSL SRSASVAKSQ SISRSQSVVA               SESASLSKSK STSLSNSVSA EKSTSLSRSA SVAKSQSISR               SQSVAASESA SLSKSKSTSL SNSVSAEKST SLSRSASVAK               SQSISRSQSV AASESASLSK SKSTSLSNSV SVEKSTSLSR               SASVAKSQSI SRSQSVAASE SASLSKSKST SLSNSVSAEK               STSLSRSASV AKSQSISRSQ SVAASESASL SKSTSTSTSD               SDSASTSTSV SDSDSASLSK STSTSTSDSD SASASLSKST               STSTSDSDSA STSTSVSDSD SASLSKSTST STSDSDSTST               SLSKSTSTST SDSDSASKST SVSDSTSASL SKSTSTSTSD               SDSASKSTSV SDSTSASLRK SASTSTSDSD STSTSLSKST               STSTSDSDSA SKSTSVSDSD SASLSKSTST STSDSDSASK               STSVSDSDSA SLSKSTSTST SDSDSASKST SVSDSTSTSL               SKSTSTSTSD SDSASTSTSV SDSTSASLSK STSTSTSDSD               SASTSVSDSD SASLSKSTST STSDSDSVST STSVSDSDSA               SLSKSTSTST SDSDSASKST SVSDSTSTSL SKSTSTSTSD               SDSASTSVSD STSASLSKST STSTSDSDSA SKSTSVSDSD               SASLSKSTST STSDSDSAST STSVSDSDSA SLSKSTSTST               SDSDSASTSL SKSTSTSTSD SDSTSTSLSK STSTSTSDSD               SASKSTSVSD SDSASLSKST STSTSDSDSA SKSTSVSDSD               SASLSKSTST STSDSDSASK STSVSDSESA SLSKSTSTST               SDSDSASTST SVSDSTSVSL SKSTSTSTSD SDSTSTSLSK               STSTSTSDSD SDSASLSKST STSTSDSDSV STSTSVSDSD               SASLSKSTST STSDSDSAST STSVSDSGSA SLSKSTSTST               SDSDSASKST SVSDSDSASL SKSTSTSTSD SDSASTSTSV               SDSTSASLSK STSTSTSDSD SASTSTSVSD SDSASLSKST               STSTSDSDSA SKSTSVSDSD SASLSKSTST STSESDSASK               STSVSDSDSA SLSKSTSTST SDSDSASTST SVSDSDSASL               SKSTSTSTSD SDSASKSTSV SDSDSASLSK STSTSTSESD               SASTSTLVSD STSVSLSQST SVDKDSTAKG STELVNVASL               SISASQSSSL SASTSTSIEK SESTSTSGSN STNASLSSSS               SLSTSASTSV SEVTSVTHSE NDLSASNDRD TSGSVSQFAS               ENTSLSDSAS ISGEVSSSTS ASTSKSSSLS ASALHDKHVS               ESTSASLSSG DSSRASASVS TSLSESDSAL IDSESISVSE               HTSTLQSGSH SLSQQQSAEL SQSEQTSQSQ RISTSASVSA               MKSESAAKVS ESLSTSQSKV DSQSQSVSES ASNSRVSRDS               KSTSASMHRS LSESVSQSMS LIDQSESDST SISISTSISD               EDSMLYSMSD SASISTKASS SMSTSTSEEH ANSHSQSEST               ASVEVSQEMS ASASTSKSES QSESVSVSNE ESNISSMQES               FVESAKASRS ASMSVAKSEA SESQLLSESN ASVSQSASTS               SKASASTSES ISTSLSVSEA THGKPRNHSE SASASQLLEE               NESLSDSAST SVEDSESASA SLSVYQSQSA SALKSTHASE               KASVNTSANA SKRASASTSI SNSKSKVIAS ESKSTSISTY               ESLSISTSKE QSTRVSVSES TSTSKVKSES DSASTSTSES               ISISANRSGY TSSKRSVQMS EAQSTSDSLS VMQSEGSVSV               SQSLSISDKT SQSLSESISH SESDSDSNSV SISQETSEQH               SVSDSDSMSI SESESIAYSQ SASESESTSI AKSDSISNSL               SVSLSESESE ASTSASVSTS ESTSVKGSLS TSILNSQSAS               THQSTEASQS TSTSKVEEAS LSDSASVSDS QSLSMSHEKS               QSASTSKSTS LSKTISESES VSASTSTSEA VSTEASEFVS               AVDSLSQVTS NGSTTKEDAS TFVSTVDSLK DKASNNGTPS               EFASAVKSTH ASVSVSASES TSASTSTSEA VSTEASEFVS               AVNSLSEATS NGSTTKEDAS TFVSTVDSLK DKASNNGTPS               EFASAVKSTH ASVSVSASES TSASTSTSEA VSTEASEFVS               AVDSLSQVTS NGSTTKEDAS TFVSTVDSLK DKASNNGTPS               EFESVVKSVH GSMSASASAS TSASTSASTS TSEAASAEAS               ELESVRKSLS NGASNGSTAR EGASTFVSTV DSLKDKASNN               GTASEFESVV KSVHGSTSAS ASASTSASTS ASESASTEAS               EFVSAVASLS SSAWNGSTTG EGASTFVSTV DSSKDSASDK               ASPSESESVV KSVHGSTSTS ASVSASASTS ASTSTSEAVS               TEASEFVSAV NSLSSEASNG STTREGASTF VSTVDSLKDK               ASNNGTASEF ESVVKSVHGS MSTSASVSAS ESTSASTSTS               EAVSTEASES ASISVSMSVS ASTSASMSVS VSNSVSVSDS               ISVSASTSEP NSVSTSMSSS LSTSASTPSE ITSSSSSSDS               ATVQKVVSKD EQHATNKVEK LPDTGQSTTQ TGLLGGVGAL               LTGLGLLKKS RKQKDEETSS HE                    SEQ ID NO: 13            atgaaaaagtctagaaaaaagcgtatcgattttttacctaaccgtcaaaa               tcgatatgcgatacgtcgtttttcagtaggcactgcgtcaattctcgttg               gagcaacattaatttttggaattcattcaaatgatgcatcggcagcagta               gaagacgcaacatctcaagaagcaggaacaactaacgaaaattcaaatag               tacagaagaagcaacaacaaacgaaagtacaactgttgaagcaccaacaa               gtgaagaagcaacaacggaagagcaatcagtagaggcgccaacaagtgaa               gaagtaacaacggaagagcaatcagtagaggcaccaacaagtgaagaagt               aacaacggaagagcaatcagtagaagcgccaacaagtgaagaagtaacaa               cggaagagcaatcagtagaagcgccaacaagtgaagaagtaacaacggaa               gagcaatcagtagaggcaccaacaagtgaagaagtaacaacggaagagca               atcagtagaggcaccaactagtgaagaagtaactacggaagagcaatcag               tagaagcaccaacaagtgaagaagcaacaacggaagagcaatcagtagaa               gcaccaacaagtgaagaagcaactacaaaaactcctgtaaaagaagaaac               atcctcaacacaagaaaattcacccacgactacactagaagaacaatttt               caaatgaattcaatcagttaacatctacagaagataaaacaaactacaca               cgtgaatatttaactcaaaacacaaatctttcggcagaacaagtggaagc               aacagttgaacgcttgaatttaagtcaagaaaatgtaacagcccaagata               tctatttcgcattacttaaagatttagctgatcaacaagatgccttatta               ccacgtgtaacacttttggccgctagagattctgagctcacaaacgaagc               gtctatcgctttaactgaaaatagtccaatgttccgcgcagcattagcga               atagtccttctggcaatgatgtggtgtcagaagaagataatattattgtg               gctgatgcactcgcaaatggatacatcaattcacaaacagatgcaacaaa               tgcggcaaatacattgtctggtcgtgcatgggttgtggatacagggacac               cagcgacaatgtcaaacggcttaacagctgttccagaaggcacaaaagtc               tacatgcaatggattgatacagatggcgcggtttcaccagtgtatcaagc               aagcacaacaaataaattgagttcaagtggtggtagccaagtaggtccag               gtgcatatgcatttgatttacgtgaagcatggatagactcaaatggcaaa               gcgcacagatatgaagcgtcaagtggccaatattatcgtttatggattga               tgactacaaaacagtagatgggaatacggcaaccatgttacgccaagcag               gtggtttcttccctggttcatatgttaattcggtgacaggtaacaatatt               ggtcaattcccacttatcggaacgaacatgcaacgtacaggtatctttat               gggtgtgataccaacgaacgattacatgactacagatacaagcaattgga               ttcaagataatgaaggacctatttcaaacccagcagtaacgagcacaagt               gaatttgtcagtggtaaagtatggtctgagacaggttcaggtgactatgc               gaactctgcgacaggtccaaactttaactcaggtgatattgcacgtgaag               gttatcaagttgtcatgtcttcattaacaagtgctggtgcccaagcgtat               aaagcacaagtcgaatcgttgccaacagaccaacaagcggcagcagcaca               ccaattattcaaagaccacccagaatttatttctgcgacagtgacgggta               aaactgatgcaaacggtgcgtatacattacgtttcccttcaggctcattg               agtaaagattatctttatggttatgtgatggataataagggcaacttggt               taagggctattcatcattcacgtcacctttattccgttcgcctaacagta               acttatctttcgcgccacaaacagcgccatatcatagaccagccaaaaat               gcttgggtgaatgtgaactttgcgcttgtagaaacaattgaaacaagtat               agacatcacgaactttgatgtgacagccaacccagcgcaacgtggtgata               cggctatcattgatgtgacttctacagcattgtcaccattacctacgcat               gttgagtggagagattcaaaagggaatgtcgttcaaaaaagtggagatgt               cactacggtagaagaagctgaaacggcaggcacatttactattcctgatg               atgcgaaaacaggtgaaatctatacagtttatattgtttcaggaggcaat               gaagttgcagcagactcactgattgtccaagtgcaagaaaatgcggcaac               ctatgaacctgtatatccaacaacaacagttgaacaagaccaaactgtaa               caattcctacacctacaaatgaagatggtttagcattaccagacggaaca               aagttcgaaggtggcaacaatgtacctgaatgggcaactgtgaatgaaga               tggttctatttcaatttcaccaaatcaagatgtggaaaaaggtaactata               atgtgcctgttgtcgtcacatatccagatggttcaaaagaaacagtattt               gcaccagttttagttcaagaagctgttccaactgcagaacaatacgatcc               aacaattgaaacaattaataaggaatatggtactactgcaacagaagatg               aaattaaaggcgcaatcacaattccggattacccaacagatggagatcaa               ccaacaatcacgattgacgacccaactcaaattccaaatggaacagaaga               aggcacagtgaatgtaggtgtcactgtcacttatccagatggttcaacag               acaaattaacagtaccagtcgttacaggtaagcaagcggataacgataag               tacacaccagaaacaacaccaattacgaaagacttcggtacaggtgtaac               agaagacgaagtgaaaggtgcagtcactgttccggattacccaacagatg               gagaccaaccaacaattacgattgacgacccaagtcagttgcctgatggt               tcaaaagaaggaacaacggatgtcgacgtaacagtggaatatccagacgg               cacaacagatcacatcacagttccagtgactgttggaaagcaagcggata               atgataagtacacaccagaaacaacaccaattacgaaagacttcggtaca               ggtgtaacagaagacgaagtgaaaggtgcagtcactgttccggattaccc               aacagacggtgaccaaccaacaattacaattgatgatccaaatcaattac               cggacggttcacaagaaggtacgactgatgtaaatgtaacagtggaatat               ccagatggcacaacagatcacatcacagttccagtgactgttggaaagca               agcggataatgataagtacacaccagaaacaacaccaattacgaaagact               tcggtacaggtgtaacagaagacgaagtgaaaggtgcagtcactgttccg               gattacccaacagatggagatcaaccaacggttacaattgatgatccaaa               tcaattaccggacggttcacaagaaggtacgactgatgtaaatgtaacag               tggaatatccagacggcacaacagatcacatcacagttccagtgactgtt               ggaaagcaagcggataatgataagtacacaccagaaacaacaccaattac               gaaagacttcggtacaggtgtaacagaagacgaagtgaaaggtgcagtca               ctgttccggattacccaacagacggtgaccaaccaacggttacaattgat               gatccaaatcaattaccggacggttcacaagaaggtacgactgatgtaaa               tgtaacagtggaatatccagatggcacaacagatcacatcacagttccag               tgactgttggaaagcaagcggataacgataagtacacaccagaaacaaca               ccaattacgaaagacttcggtacaggtgtaacagaagacgaagtgaaagg               tgcagtcactgttccggattacccaacagatggagatcaaccaacggtta               caattgacgatccgagtcagttaccagatggctcacaagaaggcacaaca               gatgtgaatgtaacagtggaatatccagatggcacaacagaccacatcac               agttccagtgactgttggtaagcaagcagataacgataagtacacgccag               aaacaacaccaattacgaaagacttcggtacaggtgtaacagaagacgaa               gtgaaaggtgcagtcactgttccggattacccaacagatggagaccaacc               aacaattacaattgacgatccgagtcagttaccagacggttcacaagaag               gtacgactgatgtaaatgtaacagtggaatatccagatggcacaacagat               cacatcacagttccagtgactgttggtaagcaagcagataacgataagta               cacaccagaaacaacaccaattacgaaagacttcggtacaggtgtaacag               aagacgaagtgaaaggtgcagtcactgttccggattacccaacagatgga               gaccaaccaacaattacaattgacgatccgagtcagttaccagacggttc               acaagaaggtacgactgatgtaaatgtaacagtggaatatccagatggca               caacagatcacatcacagttccagtgactgttggaaagcaagcagataac               gataagtacacaccagaaacaacaccaattacgaaagacttcggtacagg               tgtaacagaaggcgaagtgaaagattcaatcacaattcccggttacccaa               cagatggagaccaaccaacaattacaattgacgacccaagtcagttacca               gatggttcacaagaaggtacgactgatgtcgatgtaacagtggaatatcc               agacggcacaacagatcacattacagttccagtgactgttggaaagcaag               cagataacgataagtacacaccagaaacagaaggtgtcaacaaagatcat               ggtacgtcagtaacagaagatgaagtgaaaggtgcagtcactgttccggg               atacccaacagatggagatcaaccaacggttacaattgatgatccaagtc               aattgccggacggttcacaagaaggtacgactgatgtaaatgtaacagtg               gaatatccagacggcacaacagaccacattacagtcccagtaactgttgg               taaacaacctactaaagataacggggctacagataatgatggcgacatga               atcaaggcacagatgaaggaaatagtgctactgatcatggcgacaatgta               aaacaagattcaaacggaaactatacgccggttgaacaacgtgacaatca               tgcgacttcacctgcaacagatatggatccaatgccaagcaatagccaaa               caacttttgatggcataaatgcaaaaggttcaacttcagagaaagcaaac               cataaacaacagtctgagcaattaccagacacaggtgaaagcaatacaca               aaatggtgcacttttaggcggattatttgcagcacttggaggcttattct               taatcggcagacgtcgtaaagaaaaagaaggcaaataa            
The protein sequence translated from SEQ ID NO 13 is designated SEQ ID NO: 14 and is shown below:
 
         [0000]                                      SEQ ID NO: 14            MKKSRKKRID FLPNRQNRYA IRRFSVGTAS ILVGATLIFG               IHSNDASAAV EDATSQEAGT TNENSNSTEE ATTNESTTVE               APTSEEATTE EQSVEAPTSE EVTTEEQSVE APTSEEVTTE               EQSVEAPTSE EVTTEEQSVE APTSEEVTTE EQSVEAPTSE               EVTTEEQSVE APTSEEVTTE EQSVEAPTSE EATTEEQSVE               APTSEEATTK TPVKEETSST QENSPTTTLE EQFSNEFNQL               TSTEDKTNYT REYLTQNTNL SAEQVEATVE RLNLSQENVT               AQDIYFALLK DLADQQDALL PRVTLLAARD SELTNEASIA               LTENSPMFRA ALANSPSGND VVSEEDNIIV ADALANGYIN               SQTDATNAAN TLSGRAWVVD TGTPATMSNG LTAVPEGTKV               YMQWIDTDGA VSPVYQASTT NKLSSSGGSQ VGPGAYAFDL               REAWIDSNGK AHRYEASSGQ YYRLWIDDYK TVDGNTATML               RQAGGFFPGS YVNSVTGNNI GQFPLIGTNM QRTGIFMGVI               PTNDYMTTDT SNWIQDNEGP ISNPAVTSTS EFVSGKVWSE               TGSGDYANSA TGPNFNSGDI AREGYQVVMS SLTSAGAQAY               KAQVESLPTD QQAAAAHQLF KDHPEFISAT VTGKTDANGA               YTLRFPSGSL SKDYLYGYVM DNKGNLVKGY SSFTSPLFRS               PNSNLSFAPQ TAPYHRPAKN AWVNVNFALV ETIETSIDIT               NFDVTANPAQ RGDTAIIDVT STALSPLPTH VEWRDSKGNV               VQKSGDVTTV EEAETAGTFT IPDDAKTGEI YTVYIVSGGN               EVAADSLIVQ VQENAATYEP VYPTTTVEQD QTVTIPTPTN               EDGLALPDGT KFEGGNNVPE WATVNEDGSI SISPNQDVEK               GNYNVPVVVT YPDGSKETVF APVLVQEAVP TAEQYDPTIE               TINKEYGTTA TEDEIKGAIT IPDYPTDGDQ PTITIDDPTQ               IPNGTEEGTV NVGVTVTYPD GSTDKLTVPV VTGKQADNDK               YTPETTPITK DFGTGVTEDE VKGAVTVPDY PTDGDQPTIT               IDDPSQLPDG SKEGTTDVDV TVEYPDGTTD HITVPVTVGK               QADNDKYTPE TTPITKDFGT GVTEDEVKGA VTVPDYPTDG               DQPTITIDDP NQLPDGSQEG TTDVNVTVEY PDGTTDHITV               PVTVGKQADN DKYTPETTPI TKDFGTGVTE DEVKGAVTVP               DYPTDGDQPT VTIDDPNQLP DGSQEGTTDV NVTVEYPDGT               TDHITVPVTV GKQADNDKYT PETTPITKDF GTGVTEDEVK               GAVTVPDYPT DGDQPTVTID DPNQLPDGSQ EGTTDVNVTV               EYPDGTTDHI TVPVTVGKQA DNDKYTPETT PITKDFGTGV               TEDEVKGAVT VPDYPTDGDQ PTVTIDDPSQ LPDGSQEGTT               DVNVTVEYPD GTTDHITVPV TVGKQADNDK YTPETTPITK               DFGTGVTEDE VKGAVTVPDY PTDGDQPTIT IDDPSQLPDG               SQEGTTDVNV TVEYPDGTTD HITVPVTVGK QADNDKYTPE               TTPITKDFGT GVTEDEVKGA VTVPDYPTDG DQPTITIDDP               SQLPDGSQEG TTDVNVTVEY PDGTTDHITV PVTVGKQADN               DKYTPETTPI TKDFGTGVTE GEVKDSITIP GYPTDGDQPT               ITIDDPSQLP DGSQEGTTDV DVTVEYPDGT TDHITVPVTV               GKQADNDKYT PETEGVNKDH GTSVTEDEVK GAVTVPGYPT               DGDQPTVTID DPSQLPDGSQ EGTTDVNVTV EYPDGTTDHI               TVPVTVGKQP TKDNGATDND GDMNQGTDEG NSATDHGDNV               KQDSNGNYTP VEQRDNHATS PATDMDPMPS NSQTTFDGIN               AKGSTSEKAN HKQQSEQLPD TGESNTQNGA LLGGLFAALG               GLFLIGRRRK EKEGK                    SEQ ID NO: 15            atgacagaacgaaaatccccttcatctcaaaacatgcgtcatcgtttagt               caaagctggtactgtccttttattggttggtagtggactgcaaatgcctt               caacattgtcacacgaaatgacagcgatagctcagacagatgcgactgat               gatttgaaaacattacgtgaaaatgcagataaaaaagtgaaagcgttaca               atatttaaatacggattataaaaatgaatttcttgcgttaattcgtgaat               atgatacgtcgtcaaaaaatattgaagtggttgttgacgaagcagaagca               gccaatcgtctagctcatgacgctcaatcggacgatgaaatacaacctga               attagatgccattgatgaaaaaattagcgcgttaaaggcaaaggttgatg               aaggtcaacgagaatcaactgaagcgcgtcaagatgtaacgtcaacagag               acaaagagtgctgaatcagaaggaagagagccatccactgaaggcgagag               caaagtaaaggagtcatcttcagcacaaacgattgtagcacctcatcatg               gtcaacaagatgtgagcgcactgaaagaccatattaagaacgatgtcgat               acacttaaacaagactatgcaacgcaagacaagcaagtgacaccactcca               gggcattgacagtgcaatcacacgcattgaccatttcgtttcagaaagcg               tggatcacaagtctgacaattattttgaagaaaaacgtcaacatttacaa               aactttgaacaagacattaaaaaacgtacggacatttctgggactgagaa               ggcgactttgcttgatgatgcgaaaacggtagccaaccaactgaacgcgc               aaaatgatacgattttaactgaacttcaacagcatgacgataaacgtgca               gcagttgaatcgatattaggtgagatttttaatgcacaagaagcggctga               acgtgcgaaacagatagatgttaaaggtaaaacagatcaacaattggcaa               acgaaattcatcaacaagcggacggacttatcaaaacgtcgagtgatgat               ttattgttaggaatgttggaaaataattcaaatacacaaggtctagtgga               aagcattttacgaacacgctttgacaaacaagaagcgcacaaaattgccg               gcgaaatcatgcaaggcaagccttcaaatacagcgatactcgaccgcttg               aaagaccattttaaagcgaatggtaaggcgagtggagatgatattttaaa               tgcgttaattaataatacggatgcagatgctgaagtgattgaatcaattc               tagggggccgtcttaatgcagaaaatgcaaaattgattgccgatcgtgta               cagcaagataaaaagaagacacatcaaaacttaaaggcgattgaagacga               acttagtgcgcaagcgaatcgattgttaacgttacggaagcaattgcaac               aaatccgtcataatacgcaaacagatatgaatgacttgtttgcaccactg               cgtcgtattgcaaatattctcggtggtggtttaaatcgtgacgacattca               ctcttcaggtcgtacgaatgacaaattgcagcaactgttaaatcgtgatc               attcgttgttaggtcgtggtggtgatttattcaaacatgattttgcgcca               aagccgaatatcgatccatatcaagcgattaatagtcaaacggcatcaga               aggttttttagatggtttatttgatcaaaatggcgatttcaatttaccga               atacaggtgaaatagtgaagcggacttggctaccgttgggtattttagtc               gttgcaatcggtgtactgatcttaacggtgagatttcataaaaaaacacg               caaacaataa            
The protein sequence translated from SEQ ID NO 15 is designated SEQ ID NO: 16 and is shown below:
 
         [0000]                                      SEQ ID NO: 16            MTERKSPSSQ NMRHRLVKAG TVLLLVGSGL QMPSTLSHEM               TAIAQTDATD DLKTLRENAD KKVKALQYLN TDYKNEFLAL               IREYDTSSKN IEVVVDEAEA ANRLAHDAQS DDEIQPELDA               IDEKISALKA KVDEGQREST EARQDVTSTE TKSAESEGRE               PSTEGESKVK ESSSAQTIVA PHHGQQDVSA LKDHIKNDVD               TLKQDYATQD KQVTPLQGID SAITRIDHFV SESVDHKSDN               YFEEKRQHLQ NFEQDIKKRT DISGTEKATL LDDAKTVANQ               LNAQNDTILT ELQQHDDKRA AVESILGEIF NAQEAAERAK               QIDVKGKTDQ QLANEIHQQA DGLIKTSSDD LLLGMLENNS               NTQGLVESIL RTRFDKQEAH KIAGEIMQGK PSNTAILDRL               KDHFKANGKA SGDDILNALI NNTDADAEVI ESILGGRLNA               ENAKLIADRV QQDKKKTHQN LKAIEDELSA QANRLLTLRK               QLQQIRHNTQ TDMNDLFAPL RRIANILGGG LNRDDIHSSG               RTNDKLQQLL NRDHSLLGRG GDLFKHDFAP KPNIDPYQAI               NSQTASEGFL DGLFDQNGDF NLPNTGEIVK RTWLPLGILV               VAIGVLILTV RFHKKTRKQ                    SEQ ID NO: 17            atgttaaaaaaattaattgttacaggtttgattgctacagcggcgacaca               agtttatgcg catgacacgcaagcggcggaaaagggtgctacagatgct               ccgaatgtgatggttaaggatgaggcgaaaaaagaagtgacaccgataat               ccataaaccgacttgcatttacccgcatctagaaggcgaagatgatgctg               cgtatttaaaacgtatggcaacgaatccaccagaaggcgcagtgccgtac               ggtgtattgaataaagatggatcgattacagaaccgaatacaaatccaca               ttttgatgttttaaaaattgaagatccaaatgcgatgaaagatttggttg               atacaccggcagatgatcaagatacggtaccgagtgatttacaaattgaa               ccaccagcattaataggaccagctactaaacatacggatggtacgggaga               cgcaaaatctaatgatgaccacaaagtaacaaaatcttcgggagcgtcag               cccaagatatgaagaaaaaagacgtgacaacacaaactgcacaaccaaaa               gcagataaaaagatggcgactgcaaaagtagcaccagcgaaacaacaaga               taaagcagccaaaatgttaccagcagcaggggaaccacaagtgaatgcaa               tcagtcaaacagcacttgcactttcaatgatcgcattaggtgtcatcgcg               ttctttacacgacgacgcaaaacaaattaa            
The protein sequence translated from SEQ ID NO 17 is designated SEQ ID NO: 18 and is shown below:
 
         [0000]                                      SEQ ID NO: 18            MLKKLIVTGL IATAATQVYA HDTQAAEKGA TDAPNVMVKD               EAKKEVTPII HKPTCIYPHL EGEDDAAYLK RMATNPPEGA               VPYGVLNKDG SITEPNTNPH FDVLKIEDPN AMKDLVDTPA               DDQDTVPSDL QIEPPALIGP ATKHTDGTGD AKSNDDHKVT               KSSGASAQDM KKKDVTTQTA QPKADKKMAT AKVAPAKQQD               KAAKMLPAAG EPQVNAISQT ALALSMIALG VIAFFTRRRK               TN                    SEQ ID NO: 19            atggtagaatataaaaaagaacatagcgtaaagcgactattaaaattagg               aatcggttcaacgagtattttatgtgttgtatcacctcttttattaacac               atgacgttgttcaagcagcagatatcaataacaggatgccagctttgaat               acattgaagaccacttcttcatatgatcaaagggcacacatggatgaatt               acgaaacgccattacttcagatagtgacactactcaaacaccatcattca               atgagataactgtgtcttcaactaatgaaacggatgcagcgtcaacggaa               aatgtgaacccgagtgatgaggtcccggcaaaggatgaaagtgaatcaac               gacaccgagtacagaacaagacacatctatagaagaaacgggtactgaag               aagtgccatctcatgaagacaatcatcacaacaccccaagtcaagaagag               caaccgtctccgcctgatcaaccaggaacaaacaaagatgaagagagtgg               agaaaaaccgaataaagaaaatcatcggaagccgaatcaaccgaacaaag               accaaccttcaaaagatgagaataaaaaacctgacaaaggaaacaaacca               gcaccaccgtctaaaatgccaaatcgcccggatcaaaaggaagatggttc               aaacaacaccccaccacctgccactgataacggtggaaacagtaatgacg               gtacaacaacgggtcccaatggtggaggtggcagtgaagcaagtccacca               ccgaatgagcaaccgtcaaatggcaatgcaagcgatacccatcaaaacgg               ttcagtttcaagcaccaatcattcgaatcagtatggtacatcggcttatg               atgaatacgcaggtttattgaataataattataaatataatccattgttt               aaagaagaggttgcgcgtttaagtcaatttggaagtcaagatcaacatga               tattgcaagtttgagtcgtaaagaacaattttctcaaaatgcatttttag               atgacttgcaacaaagtacagattattttagatatcaatattttaacccg               ctttccacagagcaatactatcatcgtttagataaacaagtattagcact               cgttacgggggaatttggttcgatgccagatttcaagaaaagtggtgata               agtcattggttaataagcatcagcaagataaagtgaagaaaattgaacag               caaggagaaaatattaatacgcatcatatgaaaaatacgaaagaagatac               aggaaaatcattaagttacaagccgatgatatatattggcattgtcatgg               tcggttttgtcggcctgatcagtatgattttatggaaacgactgcatcat               ttttggaaataa            
The protein sequence translated from SEQ ID NO 19 is designated SEQ ID NO: 20 and is shown below:
 
         [0000]                                      SEQ ID NO: 20            MVEYKKEHSV KRLLKLGIGS TSILCVVSPL LLTHDVVQAA               DINNRMPALN TLKTTSSYDQ RAHMDELRNA ITSDSDTTQT               PSFNEITVSS TNETDAASTE NVNPSDEVPA KDESESTTPS               TEQDTSIEET GTEEVPSHED NHHNTPSQEE QPSPPDQPGT               NKDEESGEKP NKENHRKPNQ PNKDQPSKDE NKKPDKGNKP               APPSKMPNRP DQKEDGSNNT PPPATDNGGN SNDGTTTGPN               GGGGSEASPP PNEQPSNGNA SDTHQNGSVS STNHSNQYGT               SAYDEYAGLL NNNYKYNPLF KEEVARLSQF GSQDQHDIAS               LSRKEQFSQN AFLDDLQQST DYFRYQYFNP LSTEQYYHRL               DKQVLALVTG EFGSMPDFKK SGDKSLVNKH QQDKVKKIEQ               QGENINTHHM KNTKEDTGKS LSYKPMIYIG IVMVGFVGLI               SMILWKRLHH FWK                    SEQ ID NO: 21            gtgattacaaataaaaatatatatagtattcgaaagcataaacttggcgt               ggcatcattcttattggggacattatttgttgtagggcatgcaaataatg               ctgaagcttcagaagtgagcgcaacaacacaagaacataatgtcgagact               gagcaaacaaaaactgagggcgaactaacaactgaggtagcacaacaagc               agtcagcgaatcagcacctatagctgaaaacatgcagaaaacaacatcag               tggcaagtgaaaatgcgaaagaggttacagcttctgatagcacacaagaa               gtcacaaaaactgaagcaaaagatacagcaacaatgaaagattcagaaat               tgcacaacctgtatcagaagtgaataaacctgttactcaaacagctgcac               ccgtagcagaaccatcaacagcaaacaaacaaacttcaccacgacaagta               caagaacttactgcaccaatggacacaaaagtaattaatgtagaaaacgg               aacagatgtgacaagtaaagtgaaagttgaaaaatcgtcaattacagggc               atcagaataaagataaaacatatcatcaatcgaacactgtaaatccacat               aaagctgaacgtgtgacattaaattatgattggtcatttgaaaatggaat               taaagctggtgattattttgacttccaattaagcgataatgtcgatacaa               atggaatatcaacaataaaaaaagtcccacacattatggatagtcaaaat               agcgaacaaattattgcttacggggaaattaatgaaaacaaccgtgtccg               ttaccgatttatggactatgtaaatcaaaaagaaaatttaaaaggtaaat               tgtcattaaacttatttattaaaccagataaagttcaagatgaaggaaaa               atcactgtcacttcacaattgggcaaggaaatgacaagtcaggaatttga               cattaaatatattgatggtgtaaaaagcccttcaggtatcacattaaacg               gtcgtcttgatgaattatcaaaagcagatcaatcatttacgcattattct               atatttaaacctaagcataataacttaactaatgtaactttaagaggcac               agtttcaaataacgcacagcaaaatgaaaaaaatggtcaagttaatgttt               acgaatatattggtcaaggagaattgccacaaagtgcttatgccaatgta               aatgatacgaagcagttcaatgacattactaagagtatgaaatcaatcaa               aaataacagtaatggctatgaaattacttttgacatgaacaaagacaatc               atccttatatcatagtatatcaaggtcactttaacaataatgcaaaagac               tttgatttctcaacaaatgcgacaggttatcaaaatttaaatcaatcgga               atatagttattattggccttacaattattcattcaatttaacatgggata               atggtgttgctttctactctaataatgcaagtggggaagggaacgacaaa               cctgtaccgccgacttatggatatagtccgacagtaaatacaattcaaga               tactcatgcggattatcctgtaatgactttccaacaacctggaactctag               aggagacagaagacagtatgccaatcactacacttaccgaatctggtgag               gatcgtggtgaaaatacttctccaattatcgagacaacagaagattcaca               gcctgttgagtttgaagaagagacaaatcatggcattcaagacgtgacac               ttcatgcagatgctgttgattttgaggaagaaacaaaccatggtgaacaa               gacacggtacaccactctgatgtcgttgaatacgacgaagatacgacaac               tggcatgttaacaggtgccatttctgaccatacaacagaagaaggcacga               tggagtacacaactgatggcttattgattgagtttgatgatgaaatgaat               cctaatgtgagcggtcagtacgatgacatcacaacggatacgatagagga               atcatctcatattgacacattcactgaacttgaatctgaatttggtcaac               atgacggtatagtgacatttgaagaagatactatcgttgagaagccgaaa               acagaaaagggtaaccgagtaccacttgtaattgatttatcaacaccaaa               acataaccatcagttcaatattcaacctaccgatccaaatattgatacct               ctgctacgtatcgaattggcaattttgtatggcgcgatgaagatcacaat               ggcgtacaaaatgatggtgaacatggtcttgaaggtgttcttgtcacact               taaaacagctgatggtgtcgttttaaatacaacgacaagtgatgccaatg               gacactaccagttcactaatgttcaaaaaggaaaatatattgttgaattc               actacacctgaaggttatgaagcaacaagcaaacatactacagcgaatac               tgaaaaagactctgatgggttaatcgcaaatatcgatgttactcaagatg               atatgtcaatcgatgctggtttcttcccgttagaaaactggaatcctcag               ccagagccgaaaaaccctgatgatagagagaaaccggcacctgagcaacc               tgatgtacctcagccagaaccgaaaaaccctgatgatagagagaaaccgg               cacctgagcaacctgatgtacctcagccagaaccgaaaaatcctgatgat               agagagaaaccggcacctgagcaacctgatgtacctcaaccagagccgaa               aaatcctgatgataaagagaaaccggcacctgagcaacctgatgtacctc               aaccagagccgaaaaatcctgatgataaagagaaaccggcacctgagcaa               cctgatgcacctcaaccaaagccgatgctcccaggtgaaaaggtgaaacc               caaaccaactcatcccggtgaagctatgcaaacaacacctcaggacaaat               caacatctcaaacagatgaagcacttcctaaaacaggtgaatcatcatca               caatcatctgctttaatcttcggtggtttactcagtctattaggacttgg               tttattacgtcgatcatctaaacaaaaccgttcttcaatgaaataa            
The protein sequence translated from SEQ ID NO 21 is designated SEQ ID NO: 22 and is shown below:
 
         [0000]                                      SEQ ID NO: 22            VITNKNIYSI RKHKLGVASF LLGTLFVVGH ANNAEASEVS               ATTQEHNVET EQTKTEGELT TEVAQQAVSE SAPIAENMQK               TTSVASENAK EVTASDSTQE VTKTEAKDTA TMKDSEIAQP               VSEVNKPVTQ TAAPVAEPST ANKQTSPRQV QELTAPMDTK               VINVENGTDV TSKVKVEKSS ITGHQNKDKT YHQSNTVNPH               KAERVTLNYD WSFENGIKAG DYFDFQLSDN VDTNGISTIK               KVPHIMDSQN SEQIIAYGEI NENNRVRYRF MDYVNQKENL               KGKLSLNLFI KPDKVQDEGK ITVTSQLGKE MTSQEFDIKY               IDGVKSPSGI TLNGRLDELS KADQSFTHYS IFKPKHNNLT               NVTLRGTVSN NAQQNEKNGQ VNVYEYIGQG ELPQSAYANV               NDTKQFNDIT KSMKSIKNNS NGYEITFDMN KDNHPYIIVY               QGHFNNNAKD FDFSTNATGY QNLNQSEYSY YWPYNYSFNL               TWDNGVAFYS NNASGEGNDK PVPPTYGYSP TVNTIQDTHA               DYPVMTFQQP GTLEETEDSM PITTLTESGE DRGENTSPII               ETTEDSQPVE FEEETNHGIQ DVTLHADAVD FEEETNHGEQ               DTVHHSDVVE YDEDTTTGML TGAISDHTTE EGTMEYTTDG               LLIEFDDEMN PNVSGQYDDI TTDTIEESSH IDTFTELESE               FGQHDGIVTF EEDTIVEKPK TEKGNRVPLV IDLSTPKHNH               QFNIQPTDPN IDTSATYRIG NFVWRDEDHN GVQNDGEHGL               EGVLVTLKTA DGVVLNTTTS DANGHYQFTN VQKGKYIVEF               TTPEGYEATS KHTTANTEKD SDGLIANIDV TQDDMSIDAG               FFPLENWNPQ PEPKNPDDRE KPAPEQPDVP QPEPKNPDDR               EKPAPEQPDV PQPEPKNPDD REKPAPEQPD VPQPEPKNPD               DKEKPAPEQP DVPQPEPKNP DDKEKPAPEQ PDAPQPKPML               PGEKVKPKPT HPGEAMQTTP QDKSTSQTDE ALPKTGESSS               QSSALIFGGL LSLLGLGLLR RSSKQNRSSM K                    SEQ ID NO: 23            atggcatttgatggtatgtttacaagaaaaatggtagaagatttacaatt               tctcgtttctgggcgtattcataaaatcaatcaaccggaaaacgatacaa               tcatcatggttataagacagcaacgccaaaatcatcaattgttgttgtcg               attcacccgaattttgcacggattcacctcactacaaaaaaatatgataa               tccatttgaaccgccgatgtttgcgcgcgtctttcgtaaacatttagaag               gtggacgtatccttgccattcgccaaatcggaaatgaccgtcgcatcgaa               atggacgtggaaagtaaagatgaaattggtgacacgattcatcgtacagt               gattttagaaattatgggcaaacatagtaatctcattctcgttaatgaag               aacgtaaaattttagaaggttttaaacaccttacaccaaatacgaatcaa               tttagaaccgtgatgccaggttttcaatatgaagtgccgccaacacaaca               taaacagaacccttatgcatatactggtgcgcaagtgctccaacatattg               atttcaatgcgggcaaaattgatcgccaactgcttcaaacgtttgaaggt               ttttcaccgttaatcacaaaagaaatcacatcaagacgccattttatgac               cacacaaactttacctgaagcttttgacgaagtgatggccgaaacgaaag               cgacaccccaaccggtatttcataaaaataacgaaacaggtaaagaagac               ttttattttatgaagttacatcagttttacgatgattgcgtcacatatga               ttcactccatgaactgctcgaccgtttttatgatgcacgcggtgaacgtg               aacgcgtcaaacaacgtgcaaacgatttagtcaaactcgtccaacaatta               cttcaaaaatatcaaaataaattaagtaagctcgtcgatgaacaagcggg               gactgaagaaaaagaaaatcaacaattgtacggcgagttaatcacagcga               atatttatcaactcaaacctggagatcgccagttagaaacagtaaattat               tatacaggagaaaacgtgactattccgttaaatccacaaaagtcacctgc               tgaaaatgcgcaatactattacaagcaatacaaccgaatgaaaacacgtg               agcgcgaattgacccatcaaattactttaacggaagaaaatatcgcttat               tttgaaaatatcgagcaacagttgtcacacattcaagttcatgaaattga               cgatattcgtgaagaactagcagaacaaggctttatcaaacaaaagaaac               agcagaaaaagaaaaagcaacaaaaaatccagttacaatcctacgtttcg               actgatggcgatacgattttagtcggtaaaaataataagcaaaatgatta               tttaacgaataaacgtgcgcaaaaatcgcatttatggttccatacaaaag               atatcccaggaagccatgtcgtgattttaaatgatgcgccaagtgacaaa               acgattgaagaagcggcgatgattgcagcgtacttttcaaaggcggggca               atcgggacaaattccagtggattatacaacaattcgcaatgtgcataagc               cgagtggcagtaaacctggatttgtaacgtacgataaccagaagacgctt               tacgcaacgccggattatgacatgattcgtcgattgaaagctgaagaagc               gtaa            
The protein sequence translated from SEQ ID NO 23 is designated SEQ ID NO: 24 and is shown below:
 
         [0000]                                      SEQ ID NO: 24            MAFDGMFTRK MVEDLQFLVS GRIHKINQPE NDTIIMVIRQ               QRQNHQLLLS IHPNFARIHL TTKKYDNPFE PPMFARVFRK               HLEGGRILAI RQIGNDRRIE MDVESKDEIG DTIHRTVILE               IMGKHSNLIL VNEERKILEG FKHLTPNTNQ FRTVMPGFQY               EVPPTQHKQN PYAYTGAQVL QHIDFNAGKI DRQLLQTFEG               FSPLITKEIT SRRHFMTTQT LPEAFDEVMA ETKATPQPVF               HKNNETGKED FYFMKLHQFY DDCVTYDSLH ELLDRFYDAR               GERERVKQRA NDLVKLVQQL LQKYQNKLSK LVDEQAGTEE               KENQQLYGEL ITANIYQLKP GDRQLETVNY YTGENVTIPL               NPQKSPAENA QYYYKQYNRM KTRERELTHQ ITLTEENIAY               FENIEQQLSH IQVHEIDDIR EELAEQGFIK QKKQQKKKKQ               QKIQLQSYVS TDGDTILVGK NNKQNDYLTN KRAQKSHLWF               HTKDIPGSHV VILNDAPSDK TIEEAAMIAA YFSKAGQSGQ               IPVDYTTIRN VHKPSGSKPG FVTYDNQKTL YATPDYDMIR               RLKAEEA                    SEQ ID NO: 25            atggtcaaaaaatttggttataaaacacctacaatcgttgcacttacttt               ggctggaactgcattttctgcacaccaagccaatgccgctgaacaagttg               cacctgaaaaaacacctacgaatgtacttgatgatcaatacgcattaaaa               caagctgatgatgcgaaacaaacgacacaaggaacaacacttgcaggttc               aaaagaatacaaggatccttcacaaattgatacgactcaagtcgatacag               cagcacaaactgaaacgcccgtagaaggagggcaacaagacgcacaacaa               cctactacaactgatgaagcgacatcaacagatcatactgtatcaaaagg               tacaaacgaaagtgcatcacctgcaacagcttctatagatgaaggaacat               taaacgcacaagtcaattcagatgaaacggctactaaccgtacacaagac               gtcactgaaaatgtgacaaaatatccttatcattcaagtgaaatcgatac               acatgaagacgcaactgtgtcaccagatacatatcatgcactggacacgc               atgcgcaacaaccttcagcaatggatgtaagcgattcaacatcagcacaa               actgaagcgacgcaagtaaatacgtcaacaaatgtaaatgacaaagaggc               cgtttcgacaacagaagatgcacctactacacaacttcaagcagctgtac               aatctgaagccaacaaagaagcgaaggcaactactgaaacagctcaaaat               aaaacacctcaagttgaaaagaaagcaacagcaactcaaaatacagcaca               gttagcaacggggcatcaggatattactgacaaagtctcaaaacgcgtag               cagtgacaaatgaaacgaaagcggatgccacaacagcgaaaacacaagca               cctacttcagtgacacatcaagctgatacacaagcaaaaacgataacaga               caagaaggcaacaacttacagtgcacaaaccgcaactgaccaagacataa               atgcgaatccggacggtccaacacctccacgcgttggcggtaaagggggt               ccccctgcttcactttcactccaatcgactggtcaaacagcattccgttc               agctgtcgctagtaaaccgagtgcatatcaacctaaagtgaaatcgtcta               ttaatgactatattcgtaagcaaaactacaaagtgcctgtatatgaagaa               gattattcaagttacttccctaaatacggttatcgtaatggtgtcggtaa               acctgagggcatcatcgtgcatgatacagcaaatgacaactctacaattg               atggcgaaatcagttacatgaaaagaaattatcaaaatgctttcgtacat               ggctttattaatggtcaacgtattgttgaaacgcaacctacagattattt               agcatggggtgcaggtgcgattgcgaatgaacgctttattcatatcgaac               tcgttcatgttcacagtaaagaagatttcgcacgtcaaatgaacaatatg               gcagattatgcggcgacgaacttacaatattatggcctttctccagatag               tgcggaatatgatggtcgtgggacagtttggacacatgatgctgtttcta               gatttttaggtggtacagaccataccgatccgcacggctatttaaaacaa               catggttattcctttgatgcgttgtatgatttaatcaatgaaaaatatca               agtgaaaatgggttatgcctcacctgctaactcgtcttcaaaaccatcaa               caaatactggcttaacagttaaaaacacaacaggtttcggccgtattaac               acaacaaatagcggtttatatacgaccgtttatgatcaaaaaggtaaagc               gacgaatcaaacgaatcaaacgttaaaagttacaaaagaagcgacgttaa               atggcaacaaattctatttaatgagtgatgcaaaatctaatcaaacactc               ggttgggtcaaatcaaacgacgcaacatatcaagctgcccaagctgagaa               aaaagtaacgaaaacgtatactgtcaaaccaggaacaacagtatatcaag               tgccttggggtgcctcatctcaaacagtaggcaaagctccaggtacgtca               aaccaatcattcaaatcaacgaaagaacaaactgttgcgaaaacgaaatg               gctttatgggacagttggcaaagtgacaggctggattaatgcaagtagtg               ttgtagcaaatgatcaaaaaccatcgacgaataccgcactaaaagtaaca               actgacactggtctcggtcgcattaaagacaaaaatagtggtttatacgc               aacggtatatgataaaactggtaaaagcacttcagccactaaccaaacat               taaaagtaacgaaaaaagcaagtgtcaatggccaatcattctatttagta               tcagattatgctaaaggtacaaatgttggttgggtgaaacagtcagatgt               cgaatatcaaacaagtaaagccccttctaaagtgaatcaaaattatacga               ttaaatcgggtgcgaaattgtatcaagtgccttggggtacaagtaaacaa               gttgccggtacagtgacaggtgctgcgacacaaacatttaaggcaacaca               atctcaaactgtaggtaaagcaacatacttgtatgggacagttggcaaat               tatctggttggattaattcaacagcattagcagctcaaaaaacaacaacg               aatgttactaaaacaatttctcaaatcggtcaactgaacacgaaaaatag               cggtgtcaaagcttctatttatgacaaaacagcaaaagatgcatccaaat               gggcaggtcaaacttataaaattactaaaacagcttctgccaataacgaa               gactatgtattactgcaaaatagtacaggaggcacgccactcggttggtt               caatgttaaagacgtcacaacacgcaacttaggtgctgaaacagctgtta               aagggcggtacactgttaatagtaaaacatctggactctacgctatgcct               tggggtacaacgaagcaacgtgtcgatacattaaaaaatgccacaagtcg               tttatttacagcttcaaaatcagttaaagtcggtaatgatacattcttat               tcggtacagtgaatcaaaaattgggctggattaatcaaaaagacttaaca               gctgtagcagcaaaagttgcaaacatgaaaactgcatcgaatagcgcagt               caaaggtgccgcaatcacaactttgaaaaaagtagaagattatgtgatta               cgaataaaaatggttattattacactaaagttggagattcaaaaacagct               ggtgctttaaaaggtttttatcaacaaatttttaaagtcgaaaaaacatc               tttactgaacggcattacttggtactatggcgcattccaaaacgggacga               aaggatggattaaagcagctgacatacgttcatcattcattcaacatact               gcggtcagtagcacattgaaagcagcactcgataaacaaatggcgctgac               ttacccgcctcaagttcaacgtgtagccggtaaatgggtcaatgcgaatc               gtgcagaaactgaaaaagcaatgaataccgcagcaattgaaaaagatccg               actctcatttaccaatttttaaaacttgataaataccaaggtcttggcgt               agaagaacttaataaattgttaagaggcaaaggcattttagaaggtcaag               gtgccgcatttaaagaagccgcacaaaaacacaatattaatgaggtttac               ttaatgtctcacgcatttttagaaacaggtaacgggacttctcaattagc               caatggcggtcacgtagataaaaataataaagtcgtaacaaacggtaaac               cgaagtattacaacatgttcggtatcggggcaattgatacagacgcttta               cgcaatggctttaaaactgctgaaaaatatggttggaatacggtcagcaa               agcgattatcggtggcgcaaaattcatccgtgatcagtacatcggttcag               gacaaaacacattgtatcgtatgcgttggaatccagaacaccctgccaca               catcagtatgcgactgatattaattgggcaaatgtaaacgcacaacgcat               gaaatatttctatgatcaaattggtgaaacaggtaaatatttcgacgtcg               atgtatataagaagtag            
The protein sequence translated from SEQ ID NO 25 is designated SEQ ID NO: 26 and is shown below:
 
         [0000]                                      SEQ ID NO: 26            MVKKFGYKTP TIVALTLAGT AFSAHQANAA EQVAPEKTPT               NVLDDQYALK QADDAKQTTQ GTTLAGSKEY KDPSQIDTTQ               VDTAAQTETP VEGGQQDAQQ PTTTDEATST DHTVSKGTNE               SASPATASID EGTLNAQVNS DETATNRTQD VTENVTKYPY               HSSEIDTHED ATVSPDTYHA LDTHAQQPSA MDVSDSTSAQ               TEATQVNTST NVNDKEAVST TEDAPTTQLQ AAVQSEANKE               AKATTETAQN KTPQVEKKAT ATQNTAQLAT GHQDITDKVS               KRVAVTNETK ADATTAKTQA PTSVTHQADT QAKTITDKKA               TTYSAQTATD QDINANPDGP TPPRVGGKGG PPASLSLQST               GQTAFRSAVA SKPSAYQPKV KSSINDYIRK QNYKVPVYEE               DYSSYFPKYG YRNGVGKPEG IIVHDTANDN STIDGEISYM               KRNYQNAFVH GFINGQRIVE TQPTDYLAWG AGAIANERFI               HIELVHVHSK EDFARQMNNM ADYAATNLQY YGLSPDSAEY               DGRGTVWTHD AVSRFLGGTD HTDPHGYLKQ HGYSFDALYD               LINEKYQVKM GYASPANSSS KPSTNTGLTV KNTTGFGRIN               TTNSGLYTTV YDQKGKATNQ TNQTLKVTKE ATLNGNKFYL               MSDAKSNQTL GWVKSNDATY QAAQAEKKVT KTYTVKPGTT               VYQVPWGASS QTVGKAPGTS NQSFKSTKEQ TVAKTKWLYG               TVGKVTGWIN ASSVVANDQK PSTNTALKVT TDTGLGRIKD               KNSGLYATVY DKTGKSTSAT NQTLKVTKKA SVNGQSFYLV               SDYAKGTNVG WVKQSDVEYQ TSKAPSKVNQ NYTIKSGAKL               YQVPWGTSKQ VAGTVTGAAT QTFKATQSQT VGKATYLYGT               VGKLSGWINS TALAAQKTTT NVTKTISQIG QLNTKNSGVK               ASIYDKTAKD ASKWAGQTYK ITKTASANNE DYVLLQNSTG               GTPLGWFNVK DVTTRNLGAE TAVKGRYTVN SKTSGLYAMP               WGTTKQRVDT LKNATSRLFT ASKSVKVGND TFLFGTVNQK               LGWINQKDLT AVAAKVANMK TASNSAVKGA AITTLKKVED               YVITNKNGYY YTKVGDSKTA GALKGFYQQI FKVEKTSLLN               GITWYYGAFQ NGTKGWIKAA DIRSSFIQHT AVSSTLKAAL               DKQMALTYPP QVQRVAGKWV NANRAETEKA MNTAAIEKDP               TLIYQFLKLD KYQGLGVEEL NKLLRGKGIL EGQGAAFKEA               AQKHNINEVY LMSHAFLETG NGTSQLANGG HVDKNNKVVT               NGKPKYYNMF GIGAIDTDAL RNGFKTAEKY GWNTVSKAII               GGAKFIRDQY IGSGQNTLYR MRWNPEHPAT HQYATDINWA               NVNAQRMKYF YDQIGETGKY FDVDVYKK                    SEQ ID NO: 27            gtgtcgacagaaaaacaagatgatacacaagcaaaagcgaatgcactttc               tacagatgattcaacacctacaacagaacaatcaaaaagtgataccgaac               caacgcaaaatcaagaagtgaatgaaaaagaagcaacacaagttgagcaa               actccagataatgcatcatcagaatttaaagacagtgcagcacaagatga               aacaacatcgaaagacgctgacattgctcaaacaaaagaagcaaaaaatg               aagcattgcaaagtgactcatcagcaaacctatcaaatcaagaagcagaa               aaagaaaacacaactaacagtgaatctcaagtaaatgaacaacctaaagc               agatacaacttctgattcacaagtttcaaatacacctcaacaagatccta               catcgacagtaccttcaccagaaacatcagaagacaatcgaccttcaaca               gaattaaaaaatagtgaaacaactgcttctcaaacaactttaaacgaaca               acctactgaatcaacatccaatcaaactgaaacgacaaaagcaccaacaa               atacaacagtcgcaaacaaaaaagcacctgcacaattaaaagacattaaa               ggtacaactcaacttcgcgcagtcagtgcaagtcaacctactgctgttgc               agctggtgggacaaacgtaaatgacaaagtaacagcatcaaatatgaaaa               taactgaatcttatatcgagccaaacaactcaggaaacttttatttaaaa               agtaactttaacgtaaacgggactgttaaagaaggtgactactttactgt               aaaaatgcctgacactgtcaatacttttggtgacacgcgccattcacctg               actttagagaaaaaattacaaatcaaaaaggtgaagttgtggctttaggt               gaatatgatgttgccaaccatactatgacatacacgttcactaatgtcgt               taataatttagaaaatgtgtccggttcgtttaacttgactcaatttatgg               atcgtaaagtggcaacagattctcaaacatatccattaaaatacgacatt               gcaggcgaatctttagatacacaaattaaagtgaattacggtcaatatta               cagtgaaggtgattctaacttaaaatcaatgatcacttcagaagatccta               aaactggggaatatgatcaatacatttatgtcaacccattacaaaaaacg               gcaaacggtacagttgtaagagttcaagggttccaagttgatccaactaa               gagtaatgggcaagtgaaaccagatacaacgcagatcaagattttaaaag               ttgctgatggtcaaccacttaatagtagtttcggtgtgaatgacagtgaa               tatgaagatgtcacaaaacaatttaatattgtttatcgtgataataattt               ggcagatatttactttggaaacttaaatgggcaacgctatatcgttaaag               tgacgagcaaagaaaatttggattctaaagaggatttaaacttgcgtgct               attatggccactcaaaaccgatatggtcaatataactatattacttggga               taacgatattgtgaaaagctcttctggtggtacagccgacggaaatgaag               catcatatcaattaggcgacaaagtttggaatgatgtgaataaaaatggt               atccaagatcaaggtgaaactggtattgctgatgtaaaggttactttaaa               agatcttgatggcaacattttggatacaacttatacaaacacgaatggta               aatatatctttgataatttaaaaaatggtaattatcaagtgggttttgaa               acaccggaaggctatgctgcaagtccatccaaccaaggtaatgacgccct               tgactctgatggtcctacaaatgtacaagctgtcattagtgatgggaaca               acttaactatcgaccaaggtttttaccaaactgaaacaccaacacacaac               gtcggcgacaaagtttgggaagacttaaataaagatggcatccaagacca               aaatgaaccaggtatcgctaacgttaaggtcactttaaaagacgcggatg               gtaacgttgtggatacacgtacgactgatgataaagggaattacttattc               gaaaaagttaaagaaggcgaatatacaattgaatttgaaacgcctgaagg               ttatacaccgacacaaacaggccaaggcagagtcagcactgactctaatg               ggacatcttcccttattttagtcgaaggtaacgatgacttaacaatcgat               agcggtttctacaaagaacctgttacacacaaagttggcgacaaagtttg               ggatgacttaaataaagacggtatccaagatgacaatgaaccaggcatct               ctgacgttaaagtcactttaaaagatgcggatggtaacgtcgtagataca               cgtacaactgatgctaacggtaactatttatttgaaaacgtgaaagaagg               cgactatacgattgaatttgaaacgcctgaaggttacacaccgactgtta               caggtcaaggtacagctgataatgactctaacggtacatctacaaaagtt               acagttaaagatggcgatgacttaacaattgacagtggtttcactcaagt               tacacctgagccaccgacacataatgttggcgacaaagtttgggatgact               taaataaagacggtatccaagatgacaatgaaccaggcatctctgacgtt               aaagtcactttaaaagatgcggatggtaacgtcgtagatacacgtacaac               tgatgctaacggtaactatttatttgaaaacgtgaaagaaggcgactata               cgattgaatttgaaacgcctgaaggttacacaccgactgttacaggtcaa               ggtacagctgataatgactctaacggtacatctacaaaagttacagttaa               agatggcgatgacttaacaattgacagtggtttcactcaagttacacctg               agccaccgactgaacctgaaaaccctagtccagagcaaccttctgaaccg               ggtcaacctgaaaatcctagtccagagcaaccttctgaaccaggtcaacc               tgaaaatcctagtccagagcaaccttctgaaccaggtcaacctgaaaatc               ctagtccagaacaaccttctgaaccgggtcaacctgaaaatcctagtcca               gaacagccttctgagccaggacaacctaaaaatcctagtccagaacagcc               aaataatccaagtgtgccaggtgttcaaaatcctgaaaaaccaagcttaa               ctccagtcacacaaccggttcattcaaacggcaataaagcaaaaccatct               caacaacaaaaagctttacctgaaacaggtgaaactgaatcacatcaagg               tacattattcggtggtattttagctgctttaggcgcattactctttgcac               gtaaaaaacgccacgataaaaaacaatcacactaa            
The protein sequence translated from SEQ ID NO 27 is designated SEQ ID NO: 28 and is shown below:
 
         [0000]                                      SEQ ID NO: 28            VSTEKQDDTQ AKANALSTDD STPTTEQSKS DTEPTQNQEV               NEKEATQVEQ TPDNASSEFK DSAAQDETTS KDADIAQTKE               AKNEALQSDS SANLSNQEAE KENTTNSESQ VNEQPKADTT               SDSQVSNTPQ QDPTSTVPSP ETSEDNRPST ELKNSETTAS               QTTLNEQPTE STSNQTETTK APTNTTVANK KAPAQLKDIK               GTTQLRAVSA SQPTAVAAGG TNVNDKVTAS NMKITESYIE               PNNSGNFYLK SNFNVNGTVK EGDYFTVKMP DTVNTFGDTR               HSPDFREKIT NQKGEVVALG EYDVANHTMT YTFTNVVNNL               ENVSGSFNLT QFMDRKVATD SQTYPLKYDI AGESLDTQIK               VNYGQYYSEG DSNLKSMITS EDPKTGEYDQ YIYVNPLQKT               ANGTVVRVQG FQVDPTKSNG QVKPDTTQIK ILKVADGQPL               NSSFGVNDSE YEDVTKQFNI VYRDNNLADI YFGNLNGQRY               IVKVTSKENL DSKEDLNLRA IMATQNRYGQ YNYITWDNDI               VKSSSGGTAD GNEASYQLGD KVWNDVNKNG IQDQGETGIA               DVKVTLKDLD GNILDTTYTN TNGKYIFDNL KNGNYQVGFE               TPEGYAASPS NQGNDALDSD GPTNVQAVIS DGNNLTIDQG               FYQTETPTHN VGDKVWEDLN KDGIQDQNEP GIANVKVTLK               DADGNVVDTR TTDDKGNYLF EKVKEGEYTI EFETPEGYTP               TQTGQGRVST DSNGTSSLIL VEGNDDLTID SGFYKEPVTH               KVGDKVWDDL NKDGIQDDNE PGISDVKVTL KDADGNVVDT               RTTDANGNYL FENVKEGDYT IEFETPEGYT PTVTGQGTAD               NDSNGTSTKV TVKDGDDLTI DSGFTQVTPE PPTHNVGDKV               WDDLNKDGIQ DDNEPGISDV KVTLKDADGN VVDTRTTDAN               GNYLFENVKE GDYTIEFETP EGYTPTVTGQ GTADNDSNGT               STKVTVKDGD DLTIDSGFTQ VTPEPPTEPE NPSPEQPSEP               GQPENPSPEQ PSEPGQPENP SPEQPSEPGQ PENPSPEQPS               EPGQPENPSP EQPSEPGQPK NPSPEQPNNP SVPGVQNPEK               PSLTPVTQPV HSNGNKAKPS QQQKALPETG ETESHQGTLF               GGILAALGAL LFARKKRHDK KQSH                    SEQ ID NO: 29            atgaagaaaacaatttcagtacttggtctagggctattagcaacattttt               tgtaagtaacgaatcatatgccgcagaaacgattcaaaacaatacgtcat               caagtgaaacgaatcaaaattcagatcagacgccgttagatcattatatt               cgaaaagcagatggcacactggttgaaccgaacgtgtacccacataaaga               ttatgtagagaatgaaggacctttaccagagtttaaatttcaagttgact               ctaagaaagattcatctgatccaaatcaagcaccgttagatcattatatt               cgaaaagcggatggcacgttggttgaaccgaatgtatatccacacaaaga               ttatgtcgaaaatgaagggcctttaccagagtttaaatttatgtatgctg               acaaacaaaatcatcatgaccaacagagtaaaaacaacaaggataagcag               cgtgcaaattacagtgacaaaaagcataatgatcagccgggtcatccaaa               agcagtcacgccagctgtacaacatgataaagcagtcacttcaaacgcta               ctgtaaaagcattgccaaacacaggtgaatctgataaaacaacacaatta               ccaatcgtattatcattgttatctgtggggattttagttttattaaaatt               gagaaaataa            
The protein sequence translated from SEQ ID NO 29 is designated SEQ ID NO: 30 and is shown below:
 
         [0000]                                      SEQ ID NO: 30            MKKTISVLGL GLLATFFVSN ESYAAETIQN NTSSSETNQN               SDQTPLDHYI RKADGTLVEP NVYPHKDYVE NEGPLPEFKF               QVDSKKDSSD PNQAPLDHYI RKADGTLVEP NVYPHKDYVE               NEGPLPEFKF MYADKQNHHD QQSKNNKDKQ RANYSDKKHN               DQPGHPKAVT PAVQHDKAVT SNATVKALPN TGESDKTTQL               PIVLSLLSVG ILVLLKLRK                    SEQ ID NO: 31            atgaaaagtaaatatgattttttacctaatagacttaataaattttctat               acgaaaatttactgttggtagtgtatcagtgctaataggagccactttat               tattcgggtttgtagaaggagaagcatcagcatcagtaaaagaaggtcaa               caaagtataaattctagtgagaaagaaagcgccgatcctacagtagttga               tttaattagtaagaaagaaacaaatttagatggactagatgtatcaagag               aagaaacgaccaaagtaccaataaatgaaaacaaaagaggtgaggaacaa               agtatttctgataaagctataacagaaaaagctgatacaccagtaagcaa               tttatcaagtaaggaagttgaggagcaaggtgtttctgataaagctataa               cagaaaaagctgatacaccagtaaccaatttatcaagtaaggaagctaag               gagcaaggtgcttctgatagagttataacagaaaaagctgatacaccagt               aagcaatttatcaagtaaggaagctaaggagcaaggtgcttctgatagag               ttataacagaaaaagctgatacaccagtaagcaatttatcaagtaaggaa               gttgaggagcaaggtgtttctgataaagctatagagaaaatagctgatgc               atcagctactgatttgtcaagtaaggaagaagtagaacaagatatatcta               cacaaggtaaagtaaaatcaaaggaagcagtacaagtagaaagtagtcag               ttacaaaatttaaatagtgaaataaatgctgaacctaatgaaattaaggc               aatagatagaagttcaatattacctttaaatttaaatgatgaagaaaata               acaaaaaagttaataaagggactcgggttccagaagctacattaagaaat               gcctctaataaccaactcaatacacgaatgagatcagtgagtttatttag               agttgctagactaacagaaatcaatagaaatgttaatgataaagtaaagg               tttcggatatcgacatcgcaatagccccaccgcatactaaccctaaaact               ggaaaagaagaattttgggcgacatcttcttcagttttaaagttaaaggc               aagctatgaattggataatagcatttctaaaggggatcaatttactattc               aatttggtcaaaatattcgtccaggtggattaaatttaccaagaccttat               aattttttatatgataaggataaaaaattagttgcaactggccgttacaa               taaagaatcaaatacaatcacatatacatttacggattatgtagataaac               atcaaaacattaaaggtagttttgagatgaatgcattttctagaaaggaa               aatgctactactgacaaaacagcatatccaatggatgttactattgcgaa               tcaaaaatatagtgaaaatattattgtagactatggtaataaaaagaatg               ctgctattatttcaagtacagaatatattgatttagatggtagtagaaaa               atgacaacatatattaatcaaaatggtagtaaaaattccatctatcgtgc               tgatatgcaaattgatttgaacggttataaatttgatccatccaaaaaca               attttaaaatttatgaagtggaaaatagcagtgactttgtggatagcttt               tcaccagatgtgagcaagttaagggatgttacgagtcaatttaatattca               atatacaaataataatacaatggcaaaagtggattttggtactaaccttt               ggaggggtaaaaaatatattattcagcaagtggcgaatatagacgacagt               aaattagtgaaaaatgcttcaatcaattatacattgaataaaatggattt               taataataaaagaacggtagaaacacataacaatacttattctacagtga               aagataaatcaacagcactaggtgacgtacaggaaagtcaatctattagt               gagagccaatcagttagtgaaagcgagtcactaagtgagagccaatcaat               cagtgaaagcgaatcattaagtgagagccaatcaatcagtgaaagcgaat               cattaagtgaaagtcaatcaatctcagagagcgaatcactaagtgaaagt               cagtcaatttcagaaagcgaatcattaagtgaaagccaatcaatctcaga               gagtgaatcattaagtgaaagtcagtcaatttcagagagtgaatcactaa               gtgaaagtcagtcaatttcagaaagcgaatcattaagcgagagtcagtca               atttcagaaagcgaatcattaagcgagagtcagtcaatttcagaaagcga               atcattaagtgaaagccaatcaatcagtgaaagcgaatcactaagcgaga               gccaatcaatctcagagagtgaatcattaagcgagagtcaatcaatctca               gagagcgaatcattaagtgagagtcaatcaatcagtgaaagcgagtcact               aagtgagagtcaatcaatttcagagagcgaatcattaagtgaaagccaat               caatctcagagagtgaatcactaagtgagagccaatcaatctcagagagt               gaatcattaagtgagagccaatcaatctcagagagcgagtcactaagcga               gagccaatcaatttcagagagtgaatcactaagtgaaagtcaatcaattt               cagagagcgaatcactaagtgagagccaatcaatctcagagagcgaatca               ctaagtgaaagtcaatcaatttcagagagtgaatcactaagcgagagcca               atcaatctcagagagtgaatcattaagtgaaagtcagtcaatttcagaga               gtgaatcactaagtgaaagtcagtcaatttcagaaagcgaatcattaagt               gaaagccaatcaatcagtgaaagcgaatcactaagcgagagtcaatcaat               ctcagagagcgaatcattaagtgaaagtcaatcaatttcagaaagcgagt               cattaagcgagagtcagtcaatctcagagagcgaatcactaagcgagagt               caatcaatctcagagagtgaatcattaagtgagagccaatcagttagtga               aagcgaatcactaagtgaaagtcagtcaatttcagaaagcgaatcattaa               gtgagagtcaatcaatttcagaaagcgaatcattaagtgaaagccaatca               atcagtgaaagcgaatcactaagcgagagccaatcaatcagtgaaagcga               atcattaagtgagagtcaatcaatctcagaaagcgaatcattaagtgaga               gtcaatcaatcagtgaaagcgaatcactaagcgagagccaatcaatctca               gagagcgaatcactaagcgagagccaatcaatctcagagagcgagtcact               aagcgagagccaatcaatcagtgaaagcgaatcattaagtgagagtcaat               caatcagtgaaagcgagtcactaagtgagagccaatcaatctcagagagt               gaatcattgagtgagagccaatcaatctcagagagcgagtcactaagtga               gagtcaatcaatttcagagagcgaatcattaagtgaaagccaatcaatct               cagagagtgaatcattgagtgagagccaatcagttagtgaaagcgagtca               ctaagtgagagtcaatcaatcagtgaaagcgagtcactaagtgagagtca               atcaatttcagagagcgaatcattaagcgagagtcagtcaatctcagaga               gtgaatcactaagtgagagccaatcaatctcagagagtgaatcattaagt               gagagccaatcaatctcagagagtgaatcactaagtgagagtcaatcaat               cagtgaaagcgaatcactaagcgagagccaatcaatttcagagagtgaat               cattaagtgagagccaatcagttagtgaaagcgaatcactaagcgagagc               caatcaatctcagagagcgaatcattgagtgagagccaatcaatctcaga               gagtgaatcattgagtgagagtcaatcaatcagtgaaagcgaatcactaa               gcgaaagtcaatcaatttcagagagtgaatcattgagtgagagccaatca               atttcagagagtgaatcactaagtgaaagtcagtcaatttcagaaagcga               atcactaagcgagagccaatcaatctcagagagcgaatcactaagtgaaa               gtcagtcaatttcagaaagcgaatcattaagtgaaagccaatcaatctca               gagagtgaatcattaagtgaaagtcagtcaatttcagagagtgaatcact               aagtgaaagtcagtcaatttcagaaagcgaatcattaagcgagagtcagt               caatttcagaaagcgaatcattaagtgaaagccaatcaatcagtgaaagc               gaatcactaagcgagagccaatcaatctcagagagcgaatcactaagcga               gagccaatcaatctcagagagcgaatcactaagtgaaagtcaatcaattt               cagagagtgaatcattgagtgagagtcaatcaatttcagagagtgaatca               ctaagtgaaagtcaatcaatttcagagagtgaatcactaagcgagagcca               atcaatctcagagagtgaatcattaagtgaaagtcagtcaatttcagaga               gggaatcactaagtgaaagtcagtcaatttcagaaagcgaatcattaagt               gaaagccaatcaatcagtgaaagcgaatcactaagtgaaagtcaatcaat               ctcagagagtgaatcactaagtgagagccaatcaatctcagagagtgaat               cattgagtgagagccaatcaatctcagagagcgaatcactaagtgaaagt               caatcaatttcagaaagcgagtcattaagcgagagtcagtcaatctcaga               gagtgaatcactaagtgagagccaatcaatctcagagagtgaatcactaa               gtgagagtcaatcaatcagtgaaagcgaatcactaagcgagagccaatca               atttcagagagtgaatcattaagtgagagccaatcagttagtgaaagcga               atcactaagcgagagccaatcaatctcagagagcgagtcactaagcgaga               gtcaatcaatctcagagagtgaatcactaagtgaaagtcagtcaatttca               gaaagcgagtcactaagcgagagtcaatcaatctcagagagtgaatcatt               gagtgagagccaatcaatctcagagagcgaatcattgagtgagagccaat               caatctcagagagtgaatcattgagtgagagccaatcaatttcagagagc               gaatcactaagcgagagccaatcaatcagtgaaagcgaatcattaagtga               gagtcagtcaattagcgaaagcgaatcactaagtgagagtcaatcaatct               cagagagtgaatcactaagtgaaagtcagtcaatcagcgaaagcgaatct               aaatctttacctaataccggtactggagaaaagatttctaattatccagg               tattttaggaggattattaagcatattaggtataagtttgcttaaaagaa               aagacagagagaaaaaattaggacaaaaatctaataagtag            
The protein sequence translated from SEQ ID NO 31 is designated SEQ ID NO: 32 and is shown below:
 
         [0000]                                      SEQ ID NO: 32            MKSKYDFLPN RLNKFSIRKF TVGSVSVLIG ATLLFGFVEG               EASASVKEGQ QSINSSEKES ADPTVVDLIS KKETNLDGLD               VSREETTKVP INENKRGEEQ SISDKAITEK ADTPVSNLSS               KEVEEQGVSD KAITEKADTP VTNLSSKEAK EQGASDRVIT               EKADTPVSNL SSKEAKEQGA SDRVITEKAD TPVSNLSSKE               VEEQGVSDKA IEKIADASAT DLSSKEEVEQ DISTQGKVKS               KEAVQVESSQ LQNLNSEINA EPNEIKAIDR SSILPLNLND               EENNKKVNKG TRVPEATLRN ASNNQLNTRM RSVSLFRVAR               LTEINRNVND KVKVSDIDIA IAPPHTNPKT GKEEFWATSS               SVLKLKASYE LDNSISKGDQ FTIQFGQNIR PGGLNLPRPY               NFLYDKDKKL VATGRYNKES NTITYTFTDY VDKHQNIKGS               FEMNAFSRKE NATTDKTAYP MDVTIANQKY SENIIVDYGN               KKNAAIISST EYIDLDGSRK MTTYINQNGS KNSIYRADMQ               IDLNGYKFDP SKNNFKIYEV ENSSDFVDSF SPDVSKLRDV               TSQFNIQYTN NNTMAKVDFG TNLWRGKKYI IQQVANIDDS               KLVKNASINY TLNKMDFNNK RTVETHNNTY STVKDKSTAL               GDVQESQSIS ESQSVSESES LSESQSISES ESLSESQSIS               ESESLSESQS ISESESLSES QSISESESLS ESQSISESES               LSESQSISES ESLSESQSIS ESESLSESQS ISESESLSES               QSISESESLS ESQSISESES LSESQSISES ESLSESQSIS               ESESLSESQS ISESESLSES QSISESESLS ESQSISESES               LSESQSISES ESLSESQSIS ESESLSESQS ISESESLSES               QSISESESLS ESQSISESES LSESQSISES ESLSESQSIS               ESESLSESQS ISESESLSES QSISESESLS ESQSISESES               LSESQSISES ESLSESQSIS ESESLSESQS ISESESLSES               QSISESESLS ESQSVSESES LSESQSISES ESLSESQSIS               ESESLSESQS ISESESLSES QSISESESLS ESQSISESES               LSESQSISES ESLSESQSIS ESESLSESQS ISESESLSES               QSISESESLS ESQSISESES LSESQSISES ESLSESQSIS               ESESLSESQS ISESESLSES QSISESESLS ESQSVSESES               LSESQSISES ESLSESQSIS ESESLSESQS ISESESLSES               QSISESESLS ESQSISESES LSESQSISES ESLSESQSIS               ESESLSESQS VSESESLSES QSISESESLS ESQSISESES               LSESQSISES ESLSESQSIS ESESLSESQS ISESESLSES               QSISESESLS ESQSISESES LSESQSISES ESLSESQSIS               ESESLSESQS ISESESLSES QSISESESLS ESQSISESES               LSESQSISES ESLSESQSIS ESESLSESQS ISESESLSES               QSISESESLS ESQSISESES LSESQSISES ESLSESQSIS               ESESLSESQS ISERESLSES QSISESESLS ESQSISESES               LSESQSISES ESLSESQSIS ESESLSESQS ISESESLSES               QSISESESLS ESQSISESES LSESQSISES ESLSESQSIS               ESESLSESQS ISESESLSES QSVSESESLS ESQSISESES               LSESQSISES ESLSESQSIS ESESLSESQS ISESESLSES               QSISESESLS ESQSISESES LSESQSISES ESLSESQSIS               ESESLSESQS ISESESLSES QSISESESLS ESQSISESES               KSLPNTGTGE KISNYPGILG GLLSILGISL LKRKDREKKL GQKSNK                    SEQ ID NO: 33            atgttaagaacaaattataaactaagaaagcttaaagtaggtttagtatc               gacaggtgtggcgttgacttttgtgatggcaagtgggaatgcagaggcgt               cggagaacgagcagactgaagtaaaaggggaggcgcaagttgcttctgtg               aatgaaaaagagagtgaagcagaattacctgtagcgcaacaagaagcatc               tattcaactagacaaagtacaaccaggcgatgcacagctttcaggctata               cacagccaaacaaagcgatttctgtaaagatcgacaataaagatattgtg               tctgtagatgatggctatgaagaggtattatcggatgatacaggtaaatt               tgtatatgatttgaaagggcgtcaaattgtttacaatcaaaaagttgatg               ttgaagcgatgacgccatttaattttgaagattttgatgaatcagcactt               gagagcgaagaggcattggaggcgttaggtcaattggaagacgaagaaac               agcgacagcttctgtgacgacgcctagatatgaaggtgcgtatacagttc               ctgaagaacgcttgacacccattcaaggccaacagcaagtattcatcgaa               cctattttagaaggggcaagtaaaatcaaaggacatacatctgtacaagg               taaagtcgcgttagcaatcaatcaagaacatgtgcacctaggtgatacgt               tagaagaacaagcagcactcactgatcaagagtggcaaggtcgttatgac               gggatttggcgccatattgatgatcaagggtttttcgagtttgacttgaa               ccgtctttacaataaatcttacccattgaagtctggcgatttagtgactt               tatcttttaaatctaatgacgaagtaggcccattattcaatgtgaacgtt               gagcctttcgaacgtgtggcacaagctaaaacaaagtatgagcagaatga               cagtccagtagtcaacaaattggatgatactaaaagtgacttggaggttc               aacctatctatggagaccttacacaagcagcagtacatggcgagtcgaaa               gtgttgataccggggacgtcaaaagttgaaggacgtacgaattatgcaca               tgcatggatagagatggcatctaatttaggggaatatcgtagtttcccta               aattacaagctgatgcgacaggtgcgtttatatttgatttaaaagcggca               gacatacaattgttaaacggagaacgtttgacattcagagccgttgaccc               acatacaaaacaacagttagctgaaactacatcagaagtacgcccagtag               atatgcaagatgaagagtcagaggttgtgcagacttcaagcactgagaaa               tcagcacttgcggatgaaattcttcgttctatgacaattgacaaatcatt               taatcctgaagttaccgagataccgggtcatgtatatcctaagaaaacag               aggataaaggtgctgaaaatacagaacaagcctcagagaattctgagaag               ccatctcagactacagaatctcaaaatgatgccgtacaagatgtagagaa               atcctctgttaatgaggaggttacgccaccttcaacagaatctgctcaag               ttgaaaaggggcaaaatacagaaggggctttgcttccaaaaaatgtagaa               caacatgtagagagtataccataccaaaaacgtaaagcgttgataggact               gacaaaacatcaaggatcagggcacatgccgccattttctttaagcttta               ataataaagaagatgacgtatccacaaaggttaacgaagcaaacgagcat               gaacgtaagcagggtacagtttatccagagcaaatagaacaattacctca               aacaggtttaactgaaaaatcgccattctgggcattgttatttgttgtat               caggcacaggtttattattattcaaacgttctagacgacaacgccaatct               taa            
The protein sequence translated from SEQ ID NO 33 is designated SEQ ID NO: 34 and is shown below:
 
         [0000]                                      SEQ ID NO: 34            MLRTNYKLRKLKVGLVSTGVALTFVMASGNAEASENEQTEVKGEAQVASV               NEKESEAELPVAQQEASIQLDKVQPGDAQLSGYTQPNKAISVKIDNKDIV               SVDDGYEEVLSDDTGKFVYDLKGRQIVYNQKVDVEAMTPFNFEDFDESAL               ESEEALEALGQLEDEETATASVTTPRYEGAYTVPEERLTPIQGQQQVFIE               PILEGASKIKGHTSVQGKVALAINQEHVHLGDTLEEQAALTDQEWQGRYD               GIWRHIDDQGFFEFDLNRLYNKSYPLKSGDLVTLSFKSNDEVGPLFNVNV               EPFERVAQAKTKYEQNDSPVVNKLDDTKSDLEVQPIYGDLTQAAVHGESK               VLIPGTSKVEGRTNYAHAWIEMASNLGEYRSFPKLQADATGAFIFDLKAA               DIQLLNGERLTFRAVDPHTKQQLAETTSEVRPVDMQDEESEVVQTSSTEK               SALADEILRSMTIDKSFNPEVTEIPGHVYPKKTEDKGAENTEQASENSEK               PSQTTESQNDAVQDVEKSSVNEEVTPPSTESAQVEKGQNTEGALLPKNVE               QHVESIPYQKRKALIGLTKHQGSGHMPPFSLSFNNKEDDVSTKVNEANEH               ERKQGTVYPEQIEQLPQTGLTEKSPFWALLFVVSGTGLLLFKRSRRQRQS                    SEQ ID NO: 35            atgaaaactaaatacacagcaaaattattaattggggcagcaacaatatc               tttagcaacatttatttcacaagggaacgcacatgcgagcgaacaaacta               caggactcgcaccggcacaacctgtcaactttgattcaatcaatgtaacg               ccagaccaaaaaacattctatcaagtcttacatatggaaggcatttcaga               agaccaacgtgaacaatatttgaaacaattgcacgaagacccaagtagcg               cacaaaatgttttttcagaatcaattaaagatgccatccacccggaacgt               cgtgttgcgcaacaaaatgcgttttacagcgtattacacaacgatgactt               atccgaagagcaacgtgatgcatacattggtagaattaaagaagatccag               atcaaagccaagaagtatttgttgagtctttaaatgtggcacctaaagca               gaatcacatgaagatcgcctcattgaattacaaaacaaaaatttaatgga               agcgaatgaagcacttaaagcgttacaacaagaagacagcattcagaata               gacgtgcggctcaacgtgctgtcaacaaattgacgccggatagcgcgaac               gcattccaaaaagaattagatcaaatcaatgccccacgcgacgctaaaat               taaagctgacgctgaagcaaaaaaacaagcacctgaagtaagcgcaccac               aaattgaagatgcacctactactgaagttgcaccatctccaaaacaagat               atgccaaaagtagataaaaaagaagaagataaagtagaaagtgatactga               ggtcaaagaagtacctaaagctgatacagagaaaaaccctcaatctaaag               acacttctaaaactgaacaagctaaagaaacacctaaagtagagcaatca               cctaaaacagaaaaggctgaagaagcacctaaagcagaaacacctcaaaa               tggaaataaagcacaaactgaagaagctaaaccagaagtaaaagacaatg               tgaaaaacactccatctgcacctgtgttacctgaaacaggaaaagcaaca               acttcaacacttgaaagctactggaattctttcaaagacagtgtgaataa               aggttatacttacattaaacaaagcttagaaagtggttatcaatatttaa               aaggtcaatacgactatatcactaaaaaatacaatgatgcgaaatactat               acaaaaatgtattcaaatcataagtctacaattgatcagtctgtattagc               tatattaggtaaaactggatctagcgcatatatcaagccattaaatatcg               aagaaaattcaaacgtattttacaaagcttatgcaaaaacaagaaacttt               gctacagaaagcattaacacaggaaaagtattatacacattatatcaaaa               ccctactgtagttaaatctgctttcactgcaattgaaacagcaaatacag               taaaaaatgcaataagcaatcttttctctctcttcaaataa            
The protein sequence translated from SEQ ID NO 35 is designated SEQ ID NO: 36 and is shown below:
 
         [0000]                          SEQ ID NO: 36            MKTKYTAKLLIGAATISLATFISQGNAHASEQTTGLAPAQPVNFDSINVT               PDQKTFYQVLHMEGISEDQREQYLKQLHEDPSSAQNVFSESIKDAIHPER               RVAQQNAFYSVLHNDDLSEEQRDAYIGRIKEDPDQSQEVFVESLNVAPKA               ESHEDRLIELQNKNLMEANEALKALQQEDSIQNRRAAQRAVNKLTPDSAN               AFQKELDQINAPRDAKIKADAEAKKQAPEVSAPQIEDAPTTEVAPSPKQD               MPKVDKKEEDKVESDTEVKEVPKADTEKNPQSKDTSKTEQAKETPKVEQS               PKTEKAEEAPKAETPQNGNKAQTEEAKPEVKDNVKNTPSAPVLPETGKAT               TSTLESYWNSFKDSVNKGYTYIKQSLESGYQYLKGQYDYITKKYNDAKYY               TKMYSNHKSTIDQSVLAILGKTGSSAYIKPLNIEENSNVFYKAYAKTRNF               ATESINTGKVLYTLYQNPTVVKSAFTAIETANTVKNAISNLFSLFK            
An active domain from the protein of SEQ ID NO: 6 is designated SEQ ID NO: 37
 
         [0000]                          SEQ ID NO: 37            NEDVTETTGRNSVTTQASEQHLQVEAVPQEGNNVNVSSVKVPTNTATQAQ               EDVASVSDVKAHADDALQVQESSHTDGVSSEFKQETAYANPQTAETVKPN               SEAVHQSEYEDKQKPVSSSRKEDETMLQQQQVEAKNVVSAEEVSKEENTQ               VMQSPQDVEQHVGGKDISNEVVVDRSDIKGFNSETTIRPHQGQGGRLNYQ               LKFPSNVKPGDQFTIKLSDNINTHGVSVERTAPRIMAKNTEGATDVIAEG               LVLEDGKTIVYTFKDYVNGKQNLTAELSVSYFVSPEKVLTTGTQTFTTMI               GNHSTQSNIDVYYDNSHYVDGRISQVNKKEAKFQQIAYINPNGYLNGRGT               IAVNGEVVSGTTKDLMQPTVRVYQYKGQGVPPESITIDPNMWEEISINDT               MVRKYDGGYSLNLDTSKNQKYAIYYEGAYDAQADTLLYRTYIDSLNSYYP               FSYQKMNGVKFYENSASGSGELKPKPPEQPKPEPEIQADVVDIIEDSHVI               DIGW            
An spsl gene fragment corresponding to A domain is designated SEQ ID NO: 38, which encodes the protein of SEQ ID NO: 37
 
         [0000]    
       
         
               
             
               
             
           
               
                 SEQ ID NO: 38 
               
             
          
           
               
                 AATGAAGATGTCACTGAAACAACTGGGAGAAATTCAGTGACAACGCAAGC 
               
               
                   
               
               
                 TTCTGAGCAACATTTGCAAGTGGAAGCAGTACCTCAAGAAGGCAATAATG 
               
               
                   
               
               
                 TAAATGTATCCTCTGTAAAAGTACCTACGAATACGGCAACGCAAGCACAA 
               
               
                   
               
               
                 GAAGATGTTGCAAGTGTATCCGATGTTAAAGCACATGCTGATGATGCATT 
               
               
                   
               
               
                 ACAAGTACAAGAAAGTAGTCATACTGATGGTGTTTCTTCAGAATTCAAGC 
               
               
                   
               
               
                 AGGAGACAGCTTATGCGAATCCTCAAACAGCTGAGACAGTTAAACCTAAT 
               
               
                   
               
               
                 AGTGAAGCAGTGCATCAGTCTGAATACGAGGATAAGCAAAAACCCGTATC 
               
               
                   
               
               
                 ATCTAGCCGCAAAGAAGATGAGACTATGCTTCAGCAGCAACAAGTTGAAG 
               
               
                   
               
               
                 CCAAAAATGTTGTGAGTGCGGAGGAAGTGTCTAAAGAAGAAAATACTCAA 
               
               
                   
               
               
                 GTGATGCAATCCCCTCAAGACGTTGAACAACATGTAGGTGGTAAAGATAT 
               
               
                   
               
               
                 CTCTAATGAGGTTGTAGTGGATAGGAGTGATATCAAAGGATTTAACAGCG 
               
               
                   
               
               
                 AAACTACTATTCGACCTCATCAGGGACAAGGTGGTAGGTTGAATTATCAA 
               
               
                   
               
               
                 TTAAAGTTTCCTAGCAATGTAAAGCCAGGCGATCAGTTTACTATAAAATT 
               
               
                   
               
               
                 ATCTGACAATATCAATACACATGGTGTTTCTGTTGAAAGAACCGCACCGA 
               
               
                   
               
               
                 GAATCATGGCTAAAAATACTGAAGGTGCGACGGATGTAATTGCTGAAGGT 
               
               
                   
               
               
                 CTAGTGTTGGAAGATGGTAAAACCATCGTATATACATTTAAAGACTATGT 
               
               
                   
               
               
                 AAATGGCAAGCAAAATTTGACTGCTGAGTTATCAGTGAGCTATTTCGTAA 
               
               
                   
               
               
                 GTCCGGAAAAAGTCTTGACTACTGGGACACAAACATTCACGACGATGATC 
               
               
                   
               
               
                 GGTAATCATTCAACGCAATCCAATATTGACGTTTATTATGATAATAGTCA 
               
               
                   
               
               
                 TTATGTAGATGGACGTATTTCGCAAGTGAACAAAAAAGAAGCTAAATTTC 
               
               
                   
               
               
                 AACAAATAGCATACATTAACCCTAATGGCTATTTAAATGGCAGGGGGACA 
               
               
                   
               
               
                 ATTGCAGTTAATGGTGAAGTGGTCAGTGGTACGACTAAAGACTTAATGCA 
               
               
                   
               
               
                 ACCTACAGTGCGTGTATATCAATATAAAGGACAAGGTGTTCCTCCTGAAA 
               
               
                   
               
               
                 GTATTACTATAGACCCTAATATGTGGGAAGAAATCAGCATAAACGATACT 
               
               
                   
               
               
                 ATGGTAAGAAAATATGATGGTGGCTATAGCTTGAATCTGGATACCAGCAA 
               
               
                   
               
               
                 GAATCAAAAATATGCCATCTATTATGAAGGGGCATATGATGCGCAAGCTG 
               
               
                   
               
               
                 ACACACTGTTGTATAGAACATATATACAGTCATTAAACAGTTACTATCCG 
               
               
                   
               
               
                 TTCAGTTACCAAAAAATGAACGGTGTGAAGTTTTACGAAAACAGTGCGAG 
               
               
                   
               
               
                 TGGAAGCGGTGAGTTGAAACCGAAACCACCTGAACAACCAAAACCAGAAC 
               
               
                   
               
               
                 CTGAAATTCAAGCTGATGTAGTAGATATTATTGAAGATAGCCATGTGATT 
               
               
                   
               
               
                 GATATAGGATGG 
               
             
          
         
       
     
         [0009]    Since each of the abovementioned proteins/nucleic acid sequences is derived from  Staphylococcus pseudintermedius , the inventors have designated these (and the corresponding protein sequences)  Staphylococcus pseudintermedius  surface genes/nucleic acids/proteins (Sps). For simplicity, the bulk of this specification will use the term “Sps” or “Sps genes” or “Sps nucleic acids” which are intended to encompass all of the nucleic acid sequences described above (i.e. SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33 and 35. 
         [0010]    Furthermore, in addition to encompassing the entire or complete gene/nucleic sequences listed above, it is to be understood that the designation “Sps” also encompasses fragments, portions, mutants, derivatives and/or homologoues/orthologues of any of these genes. 
         [0011]    In addition, the term “Sps” or “Sps proteins” encompasses the proteinaceous products of the Sps genes/nucleic acids or fragments, portions, analogues, variants or derivatives thereof (for example short peptide fragments). In particular, the term “Sps proteins” encompasses the sequences given as SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36 and 37 above. 
         [0012]    Typically, the gene/nucleic acid fragments, portions, mutants, variants, derivatives and/or homologues/orthologues of the invention are functional or active—that is, they retain the function and/or activity of the wild type or native Sps genes/nucleic acids. Advantageously, fragments, portions, mutants, variants, derivatives and/or homologues/orthologues of any of the Sps genes/nucleic acids provided by this invention, encode proteins (or peptides, peptide fragments) retaining the ability to bind to or associate with extracellular matrix proteins such as, for example, fibrinogen, fibronectin and/or collagen. In other embodiments, the proteins and/or peptides encoded by the nucleic acid sequences described herein are immunogenic or antigenic. Furthermore, fragments, portions, variants or derivatives of any of the proteins encoded by the nucleic acid sequences described herein may also retain the immunogenicity and/or antigenicity of a corresponding wild type Sps protein (for example the proteins listed above). Where the invention relates to immunogenic compositions and/or vaccines, the use of proteins and/or peptides which are immunogenic (or antigenic) is important. 
         [0013]    The term “mutants” may encompass naturally occurring mutants or those artificially created by the introduction of one or more nucleic acid additions, deletions, substitutions or inversions. 
         [0014]    Homologous or identical genes, nucleic acid or protein sequences may exhibit as little as approximately 20 or 30% sequence homology or identity to certain reference sequences, however, in other cases, homologous or identical genes/nucleic acids and/or proteins may exhibit at least 40, 50, 60, 65, 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99% homology or identity to the various sequences given above as SEQ ID NOS: 1-36 or 37-38. It should be understood that mutant, variant, derivative and/or orthologuous sequences may exhibit similar levels of homology/identity to each other and/or to the Sps genes/nucleic acids shown as SEQ ID NOS 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35 and/or 38 above. 
         [0015]    One of skill in this field will readily understand that genes/nucleic acids homologous/identical to the Sps genes detailed herein may be found in other bacterial species. As such, homologous genes from other species may be included within the scope of this invention. Using the various nucleic acid and amino acid sequences described herein, one of skill in the art could readily identify related sequences in other microbial (particularly bacterial) species. For example, nucleic acid obtained from a particular bacterial species may be probed using the probes derived from the sequences of this invention, to identify homologous or closely related sequences. 
         [0016]    It should be understood that Sps nucleic acid sequences of this invention may be single-stranded or double-stranded and a single-stranded nucleic acid molecule may include a polynucleotide fragment having a nucleotide sequence that is complementary to a nucleotide sequence that encodes a Sps protein or fragment thereof. As used herein, the term “complementary” refers to the ability of two single stranded polynucleotide fragments to base pair with each other. 
         [0017]    A single-stranded nucleic acid molecule of the invention may further include a polynucleotide fragment having a nucleotide sequence that is substantially complementary to a nucleotide sequence that encodes a Sps protein or fragment thereof according to the invention, or to the complement of the nucleotide sequence that encodes said Sps protein or fragment thereof. Substantially complementary polynucleotide fragments can include at least one base pair mismatch, such that at least one nucleotide present on a first polynucleotide fragment will not base pair to at least one nucleotide present on a second polynucleotide fragment, however the two polynucleotide fragments will still have the capacity to hybridize. The present invention therefore encompasses polynucleotide fragments which are substantially complementary. Two polynucleotide fragments are substantially complementary if they hybridize under hybridization conditions exemplified by 2×SSC(SSC: 150 mM NaCl, 15 mM trisodium citrate, pH 7.6) at 55° C. Substantially complementary polynucleotide fragments for purposes of the present invention may preferably share at least about 60, 65, 70, 75, 80 or 85% nucleotide identity, preferably at least about 90%, 95% or 99% nucleotide identity. Locations and levels of nucleotide sequence identity between two nucleotide sequences can be readily determined using, for example, CLUSTALW multiple sequence alignment software. 
         [0018]    In addition, it should be understood that the present invention also relates to the products of the genes/nucleic acids encompassed by this invention and in particular to proteins or peptides homologous/identical to those having sequences provided by SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36 and 37. Furthermore, fragments, portions, analogues, variants, derivatives of any of these or homologous and/or identical or modified proteins are also within the scope of this invention. Typically, fragments, portions, derivatives, variants and/or homologous or modified proteins or peptides of the invention are functional or active—that is they retain the function of a wild type Sps protein. In certain embodiments fragments, portions, derivatives or variants of, and/or modified sequences or sequences with homology or identity to, the amino acid sequences provided by this invention, retain the ability to bind to or associate with extracellular matrix proteins such as, for example, fibrinogen, fibronectin and/or collagen. 
         [0019]    Additionally or alternatively, fragments, portions, mutants, variants, derivatives and/or homologues/orthologues of the Sps genes provided by this invention, may encode proteins (or peptide fragments) that are antigenically similar or identical to the proteins encoded by the genes described herein. Similarly, fragments, portions, derivatives and/or variants of and/or modified sequences or sequences with homology or identity to, the amino acid sequences provided by this invention are also antigenically similar or identical to the proteins encoded by the genes described herein. It should be understood that the term “antigenically similar or identical” may encompass proteins or peptides eliciting an immune response similar or identical to the immune response elicited by any of the Sps proteins described herein. In certain embodiments fragments, portions, derivatives and/or variants of and/or modified sequences or sequences with homology or identity to, the amino acid sequences described herein, elicit immune responses which protect against  Staphylococcus pseudinrermedius  infection and/or prevent, reduce or neutralise  Staphylococcus pseudintermedius  cell/tissue adhesion and/or colonisation. One of skill will readily understand that the antigenicity of a polypeptide can be evaluated in vitro by, for example, performing a Western blot on the purified polypeptide (for example, an affinity purified polypeptide) using polyclonal antisera from an animal, such as a rabbit that was vaccinated with at least an antigenic portion of an Sps protein of the present invention. 
         [0020]    One of skill in this field will readily understand that for the various nucleic acid sequences and polypeptides described herein, natural variations due to, for example, polymorphisms, may exist between Sps genes and proteins isolated from different microbial species and even different strains of the same species. Gene or protein variants may manifest as proteins and/or genes that exhibit one or more amino acid/nucleic acid substitutions, additions, deletions and/or inversions relative to a reference sequence (for example any of the sequences described above). As such, it is to be understood that all such natural variants, especially those that are functional or display the desired activity, are to be included within the scope of this invention. 
         [0021]    In another embodiment, the invention relates to derivatives of any of the Sps sequences described herein. The term “derivatives” may encompass Sps genes or peptide sequences which, relative to those described herein, comprise one or more amino acid substitutions, deletions, additions and/or inversions. 
         [0022]    Additionally, or alternatively, analogues of the various peptides described herein may be produced by introducing one or more conservative amino acid substitutions into the primary sequence. One of skill in this field will understand that the term “conservative substitution” is intended to embrace the act of replacing one or more amino acids of a protein or peptide with an alternate amino acid with similar properties and which does not substantially alter the physcio-chemical properties and/or structure or function of the native (or wild type) protein. Analogues of this type are also encompassed with the scope of this invention. In one embodiment, substitute amino acids may be selected from other members of the class to which the amino acid belongs. For example, nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, praline, phenylalanine, tryptophan, and tyrosine. Polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine and glutamine. The positively charged (basic) amino acids include arginine, lysine and histidine. The negatively charged (acidic) amino acids include aspartic acid and glutamic acid. Examples of preferred conservative substitutions include Lys for Arg and vice versa to maintain a positive charge; Glu for Asp and vice versa to maintain a negative charge; Ser for Thr so that a free —OH is maintained; and Gln for Asn to maintain a free NH 2 . 
         [0023]    As is well known in the art, the degeneracy of the genetic code permits substitution of one or more bases in a codon without changing the primary amino acid sequence. Consequently, although the sequences described in this application are known to encode the Sps proteins described herein, the degeneracy of the code may be exploited to yield variant nucleic acid sequences which encode the same primary amino acid sequences. 
         [0024]    The present invention may further provide modified Sps proteins. For example, a “modified” Sps protein may be chemically and/or enzymatically derivatised at one or more constituent amino acids, including side chain modifications, backbone modifications, and N- and C-terminal modifications including acetylation, hydroxylation, methylation, amidation, phosphorylation and the attachment of carbohydrate or lipid moieties, cofactors, and the like. 
         [0025]    One of skill in this field will appreciate that the amino acid and/or nucleic acid sequences described herein may be used to generate recombinant Sps genes/proteins and as such, the present invention further contemplates methods of generating and/or expressing recombinant Sps genes and/or proteins, and products for use in such methods. Accordingly, in addition to providing substantially purified or isolated recombinant Sps sequences, a second aspect of this invention provides DNA constructs comprising a replicable expression vector and nucleic acid encoding one or more of the Sps protein(s) described herein. 
         [0026]    Expression vectors for the production of the molecules of the invention include plasmids, phagemids, viruses, bacteriophages, integratable DNA fragments, and other vehicles, which enable the integration of DNA fragments into the genome of the host. Expression vectors are typically self-replicating DNA or RNA constructs containing the desired gene or its fragments, and operably linked genetic control elements that are recognised in a suitable host cell to effect expression of the desired genes. 
         [0027]    Generally, the genetic control elements can include a prokaryotic promoter system or a eukaryotic promoter expression control system. Such systems typically include a transcriptional promoter, an optional operator to control the onset of transcription, transcription enhancers to elevate the level of RNA expression, a sequence that encodes a suitable ribosome binding site, RNA splice junctions, sequences that terminate transcription and translation and so forth. Expression vectors usually contain an origin of replication that allows the vector to replicate independently of the host cell. 
         [0028]    A vector may additionally include appropriate restriction sites, antibiotic resistance or other markers for selection of vector containing cells. 
         [0029]    Plasmids are the most commonly used form of vector but other forms of vectors which serve an equivalent function and which are, or become, known in the art are suitable for use herein. See, e.g., Pouwels et al. Cloning Vectors: a Laboratory Manual (1985 and supplements), Elsevier, N.Y.; and Rodriquez, et al. (ads.) Vectors: a Survey of Molecular Cloning Vectors and their Uses, Buttersworth, Boston, Mass. (1988). 
         [0030]    In general, such vectors may contain specific genes, which are capable of providing phenotypic selection in transformed cells. The use of prokaryotic and eukaryotic viral expression vectors to express the nucleic acid sequences coding for the recombinant proteins of the present invention are also contemplated. 
         [0031]    The vector is introduced into a host cell by methods known to those of skill in the art. Introduction of the vector into the host cell can be accomplished by any method that introduces the construct into the cell, including, for example, electroporation, heat shock, chemical compounds such, for example, calcium phosphate, stronitium phosphate, microinjection techniques and/or gene guns. See, e.g., Current Protocols in Molecular Biology, Ausuble, F. M., ea., John Wiley &amp; Sons, N.Y. (1989). 
         [0032]    Another aspect relates to a host cell transformed with any one of the nucleic acid constructs of the present invention. Suitable host cells include prokaryote cells, lower eukaryotic and higher eukaryotic cells. Prokaryotes include Gram negative and Gram positive organisms, e.g.,  E. coli  and  B. subtilis . Lower eukaryotes include yeast,  S. cerevisiae  and  Pichia , and species of the genus  Diclyostelium.    
         [0033]    “Host cell” as used herein refers to cell which can be recombinantly transformed with vectors constructed using recombinant DNA techniques. 
         [0034]    A drug resistance or other selectable marker is intended in part to facilitate the selection of the transformants. Additionally, the presence of a selectable marker, such as a drug resistance marker may be of use in keeping contaminating microorganisms from multiplying in the culture medium. Such a pure culture of the transformed host cells would be obtained by culturing the cells under conditions which require the induced phenotype for survival. 
         [0035]    PCR techniques may be exploited to selectively obtain Sps gene sequences from samples of Staphylococcal DNA. These amplified sequences may be introduced into any of the vectors described above. In one embodiment, the vector may further comprise a nucleotide sequence of a tag or label to assist in protein purification procedures. 
         [0036]    Techniques used to purify recombinant proteins generated in this way are known and, where the recombinant protein is tagged or labelled, these may include the use of, for example, affinity chromatography techniques. 
         [0037]    In view of the above, a fourth aspect of this invention provides a process for the production of recombinant Sps protein(s) or peptide(s) of the invention, said process comprising the steps of (a) transforming a host cell with the nucleotide sequence of the invention or transfecting a host cell with a nucleic acid construct of the invention; (b) culturing the cells obtained in (a) under conditions in which expression of the protein takes place; and (c) isolating the expressed recombinant protein or peptide from the cell culture or/and the culture supernatant. 
         [0038]    The polypeptide may be partially purified from the host and where the polypeptide is secreted from the host cell, the cells may be separated from the media by centrifugation, the cells being pelleted. Alternatively, the polypeptide may be partially purified from this supernatant, for example using affinity chromatography. 
         [0039]    A fifth aspect of this invention provides monoclonal or polyclonal antibodies, whether derived from rodents, mammals, avians, ungulates, or other organisms, that bind to the Sps proteins described herein. Production and isolation of monoclonal and polyclonal antibodies to a selected polypeptide sequence is routine in the art see for example “Basic methods in Antibody production and characterisation” Howard &amp; Bethell, 2000, Taylor &amp; Francis Ltd. Such antibodies may be used in diagnostic procedures, as well as for passive immunisation. 
         [0040]      Staphylococcus pseudintermedius  is known to cause cutaneous inflammatory diseases in a variety of animals. One such cutaneous inflammatory disease is canine pyoderma which is a major cause or morbidity in dogs. Pydoderma associated with  Staphylococcus pseudintermedius  infection is common among dogs and is often associated with puritis, alopecia, erythema and swelling. At present, the treatment of this infection is difficult, requiring the use of aggressive, systemically administered antibiotics. The present inventors have discovered that Sps genes (and their protein products) play a role in  Staphylococcus pseudintermedius  colonisation and pathogenesis. As such, the Sps genes and proteins described herein may find application in the treatment and/or prevention of cutaneous disorders such as canine pyoderma. 
         [0041]    Accordingly, a sixth aspect of this invention provides an Sps protein or gene as substantially defined above, for use in raising an immune response in an organism. The proteins and genes described herein may find particular application as a vaccine, but could also be used to obtain an immune serum potentially useful in passive vaccination techniques. 
         [0042]    Advantageously, the invention may provide a vaccine for use in preventing or controlling disease in canine species caused or contributed to by  Staphylococcus  pseudintermedius. In other embodiments, the vaccines provided by this invention may be used to protect against the development of infections caused or contributed to by  Staphylococcus pseudintermedius . In other embodiments, the vaccines may be used to protect against instances of canine pyoderma. 
         [0043]    In one embodiment, the vaccine may be a polypeptide and/or polynucleotide vaccine. 
         [0044]    A polynucleotide vaccine may comprise a polynucleotide fragment, preferably a DNA fragment, having a nucleotide sequence encoding an antigenic polypeptide comprising at least an antigenic portion any one or more of the Sps proteins described herein. Vaccines of this type may otherwise be referred to as “DNA vaccines”—such vaccines may be introduced to host cells (such as mammalian, for example, canine cells) where they express antigens which elicit immune responses. 
         [0045]    A polypeptide or protein vaccine may comprises one or more of the Sps proteins (or antigentic fragments or portions) described herein. One of skill will appreciate that the one or more Sps protein(s) may be naturally occurring and isolated from  Staphylococcus  pseudintermedius, or recombinant. 
         [0046]    A protein vaccine may be administered by any suitable route. Advantageously, a protein vaccine may be administered orally (by ingestion), topically or by direct injection—preferably intraperitoneal or intramuscular injection. A protein subunit vaccine formulated for oral administration can contain the polypeptide encapsulated in for example, a biodegradable polymer as described hereinafter. 
         [0047]    In view of the above, the invention further provides a method of immunising a dog against  Staphylococcus pseudintermedius , said method comprising administering to the dog a DNA or protein vaccine of the invention. 
         [0048]    Conveniently, the protein vaccines described herein may further include or comprise one or more adjuvant(s). Further, one or more booster vaccinations are preferably administered at time periods subsequent to the initial administration to create a higher level of immune response in the animal. 
         [0049]    In yet another aspect, the vaccine of the invention may comprise a fusion protein comprising a carrier polypeptide and one or more Sps protein(s) of the invention. The Sps protein(s) for use in this aspect of the invention can itself be antigenic or non-antigenic; in embodiments wherein the protein is non-antigenic, the carrier polypeptide is antigenic, stimulating the immune system to react to the fusion protein thereby generating an immune response in an organism—such as, for example a canine immune response to  Staphylococcus pseudintermedius . A non-antigenic protein thus functions as a hapten. An example of an antigenic carrier polypeptide is keyhole limpet hemocyanim (KLH). Conventional fusion constructs between carriers such as glutathione sulfotransferase (GST) and said Sps protein(s) of the invention are also included as protein vaccines according to the invention, as are fusions of the Sps protein(s) and an affinity tag such as a polyhistidine sequence. A fusion construct may be preferred for use as a protein vaccine when the antigenic Sps analog, fragment, or modification thereof is small. 
         [0050]    In a seventh aspect, the present invention provides a method for immunising dogs against  Staphylococcus pseudintermedius , said method comprising administering to the dog a vaccine of the invention. 
         [0051]    A polynucleotide vaccine may further comprises a promoter, such as the CMV promoter, operably linked to the coding sequence for the Sps polypeptide or antigenic fragment thereof (e.g., U.S. Pat. No. 5,780,44, Davis). The polynucleotide may be cloned within a vector such as a plasmid. There are numerous plasmids known to those of ordinary skill in the art useful for the production of polynucleotide vaccines. 
         [0052]    Other possible additions to the polynucleotide vaccine constructs include nucleotide sequences encoding cytokines, such as granulocyte macrophage colony stimulating factor (GM-CSF), interleukin-12 (IL-12) and co-stimulatory molecules such B7-1, B7-2, CD40. The cytokines can be used in various combinations to fine-tune the response of the animal&#39;s immune system, including both antibody and cytotoxic T lymphocyte responses, to bring out the specific level of response needed to affect the animal&#39;s reproductive system. A polynucleotide vaccine of the invention can also encode a fusion product containing the antigenic polypeptide and a molecule, such as CTLA-4, that directs the fusion product to antigen-presenting cells inside the host. 
         [0053]    Plasmid DNA can also be delivered using attenuated bacteria as delivery system, a method that is suitable for DNA vaccines that are administered orally. Bacteria are transformed with an independently replicating plasmid, which becomes released into the host cell cytoplasm following the death of the attenuated bacterium in the host cell. An alternative approach to delivering the polynucleotide to an animal involves the use of a viral or bacterial vector. Examples of suitable viral vectors include adenovirus, polio virus, pox viruses such as vaccinia, canary pox, and fowl pox, herpes viruses, including catfish herpes virus, adenovirus-associated vector, retroviruses and bacteriophage. Exemplary bacterial vectors include attenuated forms of  Salmonella, Shigella, Edwardsiella ictaluri,  and  Yersinia ruckeri . Preferably, the polynucleotide is a vector, such as a plasmid, that is capable of autologous expression of the nucleotide sequence encoding said Sps protein or fragment thereof. 
         [0054]    In one embodiment, the vaccine may be a DNA vaccine comprising a DNA fragment having a nucleotide sequence that encodes a polypeptide having an amino acid sequence homologous or identic to a sequence selected from the group consisting of SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36 or 37 or an antigenic analog, fragment, or modified version thereof. 
         [0055]    Polynucleotide-based immunisation induces an immune response to an antigen expressed in vivo from a heterologous polynucleotide fragment introduced into a cell. DNA vaccine may be particularly useful as the heterologous nucleic acid expression may continue for a length of time sufficient to induce a relatively strong and sustained immune response without the need for subsequent “booster” vaccinations, as may be required when using protein based vaccines. A polynucleotide vaccine comprising a polynucleotide fragment having a nucleotide sequence encoding said Sps can be administered to dog (or rather to a particular tissue or cells thereof) using biolistic bombardment, ingestion or direct injection, as described for example, in U.S. Pat. No. 5,780,448 (Davis), preferably intraperitoneal or intramuscular injection. A preferred method of administration is biolistic bombardment, as with a “gene gun”. A polynucleotide vaccine formulated for oral administration preferably contains DNA encapsulated in a biodegradable polymer. Examples of a suitable biodegradable polymer include chitosan and homo- or co-polyers of polylactic acid and polyglycolic acid. Accordingly, the present invention further provides a method for immunising dogs against  Staphylococcus pseudintermedius  by administering to the dog a polynucleotide vaccine of the invention, preferably a DNA vaccine. 
         [0056]    Other methods of administering nucleic acid vaccines of the type described herein may include, for example, use of the technology described in WO02/076498. 
         [0057]    The amount of protein/polynucleotide vaccine to be administered to an animal depends on the type and size of animal, the condition being treated, and the nature of the protein/polynucleotide, and can be readily determined by one of skill in the art. In some applications, one or more booster administrations of the protein/polynucleotide vaccine at time periods subsequent to the initial administration are useful to create a higher level of immune response in the animal. 
         [0058]    In one embodiment of the vaccine of the invention and/or Sps proteins described herein (including antigenic fragments, analogs or modified version thereof) may be linked, for example, at its carboxy-terminus, to a further component. The further component may serve to facilitate uptake of the Sps protein, or enhance its immunogenicity/processing. 
         [0059]    The immune-stimulating compositions of the invention may be optionally mixed with excipients or diluents that are pharmaceutically acceptable as carriers and compatible with the active component(s). The term “pharmaceutically acceptable carrier” refers to a carder(s) that is “acceptable” in the sense of being compatible with the other ingredients of a composition and not deleterious to the recipient thereof. Suitable excipients are well known to the person skilled in the art. Examples include; water, saline (e.g. 0.85% sodium chloride; see Ph.Eur. monograph 2001:0062), buffered saline, fish oil with an emulsifier (e.g. a lecithin, Bolec MT), inactivant (e.g. formaldehyde; see Ph.Eur. monograph 1997:0193), mineral oils, such as light mineral oils, alhydrogel, aluminium hydroxide. Where used herein, the term “oil adjuvant” to embraces both mineral oils and synthetic oils. A preferred adjuvant is Montanide ISA 711 (SeppicQuai D&#39;Orsay, 75321 Paris, France) which is a manide oleate in an oil suspension. In addition, if desired, the immune-stimulating composition (including vaccine) may contain minor amounts of auxiliary substances such as wetting or emulsifying agents, pH buffering agents, and/or adjuvants which enhance the effectiveness of the immune-stimulating composition. 
         [0060]    A vaccine composition may be administered as a course of a number of discrete doses over a period of time. For example it may be administered over a period of around 2-21 days. 
         [0061]    Vaccination may be repeated at daily, twice-weekly, weekly or monthly intervals. For example a boost vaccination may be administered after the initial dose. For example a boost may be administered at around 4-14 weeks after the vaccination. The initial vaccination and any boost may be carried out using the same or different modes of administration. For example, the initial may be by injection and the boost may be by oral administration. An example regime includes a first vaccination by injection, followed by a course of orally administered boost vaccine, or a booster prior to an expected outbreak. However, it will be appreciated that any suitable route of administration(s) and/or regime(s) may be employed. 
         [0062]    Additionally, knowledge of the Sps protein nucleotide and amino acid sequences set forth herein opens up new possibilities for detecting, diagnosing and characterising  Staphylococcus pseudintermedius  in canine populations. For example, an oligonucleotide probe or primer based on a conserved region of one or more of the Sps proteins described herein, may be used to detect the presence of the Sps protein in or on a canine host. 
         [0063]    Vaccines may contain one or more of the Sps proteins/nucleic acids/genes described herein (i.e. those shown as SEQ ID NOS: 1-38). In one embodiment, the vaccine may comprise a cocktail of Sps proteins/peptides and or nucleic acids. Typically, a cocktail may comprise 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 or 38 Sps nucleic acid and/or protein/peptide components (for example (2 or more) components having sequences homologous or identical to any of SEQ ID NOS: 1-38). 
         [0064]    Furthermore, the vaccines may contain bacterial antigens used to control other diseases, for example diseases caused by other Staphylococcal species and/or antigens to treat, prevent or control diseases and/or conditions with other aetiologies or caused or contributed to by other pathogens. As such, the vaccine compositions described herein may find application in multivalent vaccines including antigens against other canine diseases. 
         [0065]    In addition to vaccines and/or immunogenic compositions comprising one or more of the Sps proteins described herein, the present invention further provides compounds for treating infections caused or contributed to by  Staphylococcus  pseudintermedius or compounds for the preparation of medicaments for treating the same. 
         [0066]    In one embodiment, the compound may be a small organic molecule, antibody, peptide or carbohydrate which antagonises the interaction between the Sps protein and its ligand (an extracellular matrix (ECM) protein). For example, the compound may be a synthetic peptide comprising or based on, the sequence of an ECM protein known to interact with a particular Sps protein, or the sequence of a protein given above which may interfere with binding between the wild type  S. psedintermedius  protein and its ligand. Additionally or alternatively, binding agents, such as for example, antibodies with specificity or affinity for one or more Sps protein ligands, may also be used to antagonise the Sps/ligand interaction. Therapeutic approaches of this type may prevent  Staphylococcus pseudintermedius  colonising or binding/adhering to cells. 
         [0067]    In view of the above, the invention may relate to methods of treating infections caused or contributed to by  Staphylococcus pseudintermedius , said method comprising administering to an animal a therapeutically effective amount of a compound which antagonises Sps/ligand interactions. 
         [0068]    In a further aspect, the present invention provides pharmaceutical compositions comprising a compound which antagonises Sps/ligand interactions together with a pharmaceutical excipient, carrier or diluent. 
         [0069]    One of skill will appreciate that the vaccines, methods, uses or medicaments comprising any of the Sps genes/nucleic acids and/or proteins and/or antagonistic compounds (for example Sps protein/nucleic acid fragments and/or antibodies) described herein may be combined with one or more other compounds for treating one or more other conditions—in particular one or more other skin conditions. Said other skin condition may be, for example, atopic dermatitis. 
         [0070]    In a further aspect, the present invention provides methods of diagnosing infections, diseases and/or conditions caused or contributed to by  S. pseudintermedius , said methods comprising the steps of identifying in a sample provided by a subject suspected of suffering from an infection, disease and/or conditions  S. pseudintermedius  caused or contributed to by  S. pseudintermedius , a level of a protein, peptide or nucleic acid (for example a gene) encoded by a sequence provided by SEQ ID NOS: 1-38 or a fragment, portion, mutant, derivative and/or homologoue/orthologue thereof. 
         [0071]    It should be understood that all methods of diagnosis or detection described herein, may include an optional step in which the results are compared with the results of a control sample, which does not comprise sequences derived from  S. pseudintermedius , in particular sequences corresponding to those provided as SEQ ID NOS: 1-38 disclosed herein. 
         [0072]    The term “sample” may be taken to mean any sample comprising protein and/or nucleic acid. For example, a “sample” may comprise a bodily fluids such as whole blood, plasma, serum, saliva, sweat and/or semen. In other instances “samples” such as tissue biopsies and/or scrapings may be used. In particular, cutaneous (i.e. skin) tissue biopsies and/or scrapings may be used. Advantageously such biopsies may comprise cells obtained from lesions suspected of resulting from or being associated with a  S. pseudintermedius . Specifically, a biopsy, tissue sample or scraping may comprise cells derived from lesions exhibiting pathology characteristic of the  S. pseudintermedius  disease, pyoderma (particularly caninine pyoderma). 
         [0073]    In addition, a sample may comprise a tissue or gland secretion and washing protocols may be used to obtain samples of fluid secreted into or onto various tissues, including, for example, the skin. One of skill in this field will appreciate that the samples described above may yield or comprise quantities of nucleic acid (i.e. DNA or RNA) encoding all or part of the various proteins described herein as well as quantities of proteins or peptides (or fragments thereof) encoded thereby. In one embodiment, the sample may comprise quantities of nucleic acid/peptide having or comprising the sequences given as SEQ ID NOS: 1-38. 
         [0074]    One of skill in the art will be familiar with the techniques that may be used to identify levels of certain nucleic acid sequences and/or proteins, such as, for example, levels of the sequences given as SEQ ID NOS: 1-38 described herein (or a fragment, portion, mutant, derivative and/or homologoue/orthologue thereof). 
         [0075]    For example, PCR based techniques may be used to detect levels of gene expression or gene quantity in a sample. Useful techniques may include, for example, polymerase chain reaction (PCR) or reverse transcriptase (RT)-PCR based techniques in combination with real-time PCR (otherwise known as quantitative PCR). 
         [0076]    Additionally, or alternatively, a level of gene/protein expression may be identified by way of microarray analysis. Such a method would involve the use of a DNA micro-array which comprises nucleic acid derived from one or more of the nucleic acid sequences described herein (for example SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 38). To identify a level of gene expression, one of skill in the art may extract nucleic acid, preferably mRNA, from a sample and subject it to an amplification protocol such as, for example RT-PCR to generate cDNA. Preferably, primers specific for a certain mRNA sequence—in this case a  S. pseudintermedius  sequence comprised with any of, for example, SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 38. 
         [0077]    The amplified cDNA may be subjected to a further amplification step, optionally in the presence of labelled nucleotides (as described above). Thereafter, the optionally labelled amplified cDNA may be contacted with the microarray under conditions which permit binding with the DNA of the microarray. In this way, it may be possible to identify a level of  S. pseudintermedius  gene expression. 
         [0078]    Further information regarding the PCR based techniques described herein may be found in, for example, PCR Primer: A Laboratory Manual, Second Edition Edited by Carl W. Dieffenbach &amp; Gabriela S. Dveksler: Cold Spring Harbour Laboratory Press and Molecular Cloning: A Laboratory Manual by Joseph Sambrook &amp; David Russell: Cold Spring Harbour Laboratory Press. 
         [0079]    In addition, other techniques such as deep sequencing and/or pyrosequencing may be used to detect cSCC sequences in any of the samples described above. Further information on these techniques may be found in “Applications of next-generation sequencing technologies in functional genomics”, Olena Morozovaa and Marco A. Marra, Genomics Volume 92, Issue 5, November 2008, Pages 255-264 and “Pyrosequencing sheds light on DNA sequencing”, Ronaghi, Genome Research, Vol. 11, 2001, pages 3-11. 
         [0080]    In addition to the molecular detection methods described above, one of skill will also appreciate that immunological detection techniques such as, for example, enzyme-linked immunosorbent assays (ELISAs) may be used to identify levels of  S. pseudintermedius  proteins in samples. In other embodiments, ELISPOT, dot blot and/or Western blot techniques may also be used. In this way, samples provided by subjects suffering from  S. pseudintermedius  related diseases and/or infections (for example canine subjects suffereing from canine pyoderma), may be probed for levels of one or more  S. pseudintermedius  proteins, particularly those encoded by SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, or 37 so as to detect the presence of such proteins in a sample which may indicate a  S. pseudintermedius  infection. 
         [0081]    Immunological detection techniques, may require the use of a substrate to which an antibody and/or antigen may be bound, conjugated or otherwise immobilised. 
         [0082]    Suitable substrates may comprise, for example, glass, nitrocellulose, paper, agarose and/or plastic. A substrate which comprises, for example, a plastic material, may take the form of a microtitre plate. 
         [0083]    Further information regarding ELISA procedures and protocols relating to the other immunological techniques described herein may be found in Using Antibodies: A Laboratory Manual by Harlow &amp; Lane (CSHLP: 1999) and Antibodies: A Laboratory Manual by Harlow &amp; Lane (CSHLP: 1988). 
         [0084]    The present invention also extends to kits comprising reagents and compositions suitable for diagnosing, detecting or evaluating possible  S. pseudintermedius  infections, diseases and/or conditions. Kits according to this invention may be used to identify and/or detect levels of  S. pseudintermedius  gene(s)/ S. pseudintermedius  protein(s) in samples. Depending on whether or not the kits are intended to be used to identify levels of  S. pseudintermedius  genes and/or  S. pseudintermedius  proteins in samples, the kits may comprise substrates having  S. pseudintermedius  proteins or agents capable of binding  S. pseudintermedius  proteins, bound thereto. In addition, the kits may comprise agents capable of binding  S. pseudintermedius  proteins—particularly where the kit is to be used to identify levels of one or more  S. pseudintermedius  proteins in samples. In other embodiments, the kit may comprise polyclonal antibodies or monoclonal antibodies which exhibit specificity and/or selectivity for one or more  S. pseudintermedius  proteins. Antibodies for inclusion in the kits provided by this invention may be conjugated to detectable moieties. Kits for use in detecting the expression of genes encoding  S. pseudintermedius  proteins may comprise one or more oligonucleotides/primers for detecting/amplifying/probing samples for  S. pseudintermedius  protein encoding sequences. The kits may also comprise other reagents to facilitate, for example, sequencing, PCR and/or RFLP analysis. In one embodiment, the kits may comprise one or more oligonucleotides/primers for detecting/amplifying/probing nucleic acid samples (for example nucleic acid derived from canine skin) for levels of sequences corresponding to all or part of those described as SEQ ID NOS: 1-38 herein. 
     
    
     
       DETAILED DESCRIPTION 
         [0085]    The invention will now be described in more detail with reference to the following Figures which show: 
           [0086]      FIG. 1 . Genomic location of the 17 genes encoding putative CWA proteins in  S. pseudintermedius  strain ED99. Eight genes are situated in the oriC environ, indicated in orange, and nine are located in the core genome. sps ═ S. pseudintermedius  surface protein. 
           [0087]      FIG. 2 . Distribution of the genes encoding putative CWA proteins among 20  S. pseudintermedius  strains, representatives of the closely related  S. delphini  and  S. intermedius , and other staphylococcal species associated with animal skin disease. The diversity of strains is represented a phylogenetic tree; grey squares indicate that the gene is present, blank squares that the gene is absent based on Southern blot analysis (for spsA to spsO), or PCR amplification (for spsP and spsQ). 
           [0088]      FIG. 3 . Western blot analysis of cell wall-associated proteins of  S. pseudintermedius  ED99 and  L. lactis  expressing SpsD, SpsL, and SpsO with sera from dogs diagnosed with pyoderma. (A) SDS PAGE analysis and (B) Western blot analysis of protein fractions from  S. pseudintermedius  ED99 in exponential phase of growth (lane 1);  L. lactis  expressing SpsL (lane 2);  L. lactis  expressing SpsD (lane 3);  L. lactis  expressing SpsO (lane 4); and  L. lactis  with pOri23 alone (lane 5). 
           [0089]      FIG. 4 . Adherence of  L. lactis  expressing specified MSCRAMMs to human Fn. Plates were coated with 1 μg of human Fn or 1 μg of BSA per well. Absorbance was measured at 590 nm and results are expressed as mean values of triplicate samples. Error bars indicate standard deviation.  L. lactis  expressing FnbpA from  S. aureus  and PBS were included as controls. 
           [0090]      FIG. 5 . Adherence of  L. lactis  expressing specified MSCRAMMs to Fg from different animal sources. Plates were coated with 1 μg of Fg or 1 μg of BSA per well. Absorbance was measured at 590 nm and results are expressed as mean values of triplicate samples. Error bars indicate standard deviation.  L. lactis  expressing FnbpA from  S. aureus  and PBS were included as controls. 
           [0091]      FIG. 6 . Adherence of  L. lactis  expressing specified MSCRAMMs to CK10. Plates were coated with 1 μg of recombinant CK10 or 1 μg of BSA per well. Absorbance was measured at 590 nm and results are expressed as mean values of triplicate samples. Error bars indicate standard deviation.  S. aureus  strain SH1000 in exponential and stationary phases of growth and PBS were included as controls. 
           [0092]      FIG. 7 . Adherence of  L. lactis  expressing different MSCRAMMs to canine corneocytes of five dogs. Bacterial adherence is calculated as percentage area covered with bacterial cells per field of corneocytes (ROI=500 μm 2 ). Results are based on the arithmetic mean of duplicate experiments. The bottom of each box represents the first quartile (Q1), the top of the box the third quartile (Q3), the bold lines the median, and the black circles the mean values. The whiskers define the range of the data. 
           [0093]      FIG. 8 : Reactivity of canine convalescent serum from pyoderma cases to Sps D, Sps L and Sps 0 recombinant A domain. 1 ug aliquots of rSps D and rSps L, and 10 μl volumes of purified rSps O were subjected to SDS-PAGE under standard conditions and Coomassie stained (A) or Western blot transferred onto a nitrocellulose membrane. Membranes were probed with a 1:1000 dilution of canine serum, followed by a 1:3000 dilution of HRP— conjugated sheep anti-canine IgG. Reactive bands were visualized on Chemi-luminescent Film (B). 5 μl aliquots of recombinant CIfB and the superantigen SEI from  S. aureus  were included in the terminal lanes of each gel as negative controls. 
           [0094]      FIG. 9 : Inhibition of adherence of  L. lactis  expressing SpsD (A) and SpsL (B) to fibrinogen (2 μg per well) by canine convalescent serum from pyoderma cases. Bacterial cultures, normalised to an OD600 of 1 in PBS were pre-incubated for 2 h with doubling dilutions of serum ranging from 2% to ˜0.01% (v/v), prior to inoculation into fibrinogen coated wells. Results (n=3, ±SD) are expressed as absorbance readings at 590 nm minus background levels of fluorescence. Background fluorescence was measured by inoculating control cultures, incubated for 2 h in the absence of serum, into wells coated with BSA (2 μg per well). Incubations of  S. aureus  Newman (C) were included as a negative control. 
       
    
    
     EXAMPLES 
     Example 1 
     Materials and Methods 
     Genome-Wide Screen for Genes Encoding for Cell-Wall Anchored Proteins 
       [0095]    The  S. pseudintermedius  strain ED99 draft genome was interrogated for homologous sequences using position specific iterative basic local alignment search tool (PSI-BLAST), available from the National Center for Biotechnology Information (NCBD, USA (http://blast.ncbi.nlm.nih.gov/Blast.cgi), and for the presence of a LPX[TSA](GANS) motif pattern by pattern hit initiated basic local alignment search tool (PHI-BLAST), available from NCBI (http://blast.ncbi.nlm.nih.gov/Blast.cgi). Signal sequences were predicted by employing the SignalP server (http://www.cbs.dtu.dk/services/SignalP/), provided by the Center for Biological Sequence Analysis (CBS), Technical University of Denmark. 
       In Silica Structural Analysis of Cell-Wall Anchored Proteins 
       [0096]    The predicted CWA proteins were searched for functional domains using EMBL-EBI InterPro Scan (http://www.ebi.ac.uk/interpro). Structural analysis was carried out with the PHYRE (Protein Homology/analogY Recognition Engine) fold recognition server, available from the Structural Bioinformatics Group, Imperial College London, UK (http://www.sbg.bio.ic.ac.uk/phyre/). Repeat sequences were predicted by generating nucleic acid dot plots, using software available from Colorado State University, USA (http://www.vivo.colostate.edu/molkit/dnadot/), applying tandem repeats finder software from Boston University, USA (http://tandem.bu.edu/trf/trf.html), and variable sequence tandem repeats extraction and architecture modelling (XSTREAM), available from the University of California, USA (http://jimcooperlab.mcdb.ucsb.edu/xstream/). Sequence alignments and pair-wise sequence comparisons were generated with ClustalW2 (http://www.ebi.ac.uk/Tools/clustalw2). Amino acid composition and molecular weight predictions were generated using ProtParam on the ExPASy Proteomics Server (http://www.expasy.ch/tools/protparam.html). 
         [0000]    Cloning of selected genes encoding putative MSCRAMMs of  S. pseudintermedius  ED99 into  L. lactis  MG1363 
         [0097]    Oligonucleotides were designed for PCR amplification of the full-length spsD, spsL and spsO genes and either PstI, SalI or BamHI specific restriction sites were inserted on both sides of the DNA fragments. 50 μl PCR reactions contained 2 μl (approximately 100 ng) genomic DNA template, 0.25 μM forward primer, 0.25 μM reverse primer, 1×PfuUltra™ II reaction buffer (Stratagene, USA), 0.25 mM dNTP&#39;s (Promega, USA) and 1 μl PfuUltra™ II Fusion HS DNA polymerase (Stratagene, USA). The thermocycler programme included an initial denaturation step at 95° C. for 2 min, followed by 30 cycles of denaturation at 95° C. for 20 s, annealing at 50° C. for 20 s and extension at 72° C. for 2 min, followed by a final extension step at 72° C. for 3 min. PCR products were visualised on 0.8% (w/v) agarose gels, gel extracted under avoidance of UV light exposure and purified using QIAquick Gel Extraction Kit (Qiagen, UK) according to the manufacturer&#39;s instructions. Purified DNA fragments were cloned into the StrataClone™ Blunt PCR cloning vector pSC-B (Stratagene, USA) using the StrataClone Ultra™ Blunt PCR Cloning Kit (Stratagene, USA) according to the manufacturer&#39;s instructions. Each cloning reaction consisted of 3 μl Strataclone Buffer Blunt (Stratagene, USA), 2 μl purified PCR product and 1 μl Strataclone™ Blunt Vector Mix (Stratagene, USA). StrataClone™ SoloPack® competent cells (Stratagene, USA) were transformed according to the manufacturer&#39;s instructions and colonies selected using blue-white screening on LB-ampicillin (100 μg/ml)-X-gal plates. White colonies were transferred into 5 ml LB-ampicillin (100 μg/ml) broth and grown overnight at 37° C. with shaking at 200 rpm. Plasmid was isolated using QIAprep Spin Miniprep Kit (Qiagen, UK) according to the manufacturer&#39;s instructions. Purified plasmids were digested using appropriate restriction endonucleases (New England Biolabs, UK), and diagnostic digests were analysed on 0.8% (w/v) agarose gels. For generating DNA constructs, the  E. coli - L. lactis  shuttle vector pOri23 (kindly provided by P. Moreillon, University of Lausanne, Switzerland) was used. The pOri23 vector carries the ermAM gene for erythromycin resistance, the high-copy-number oriColE1 replicon for autonomous replication in  E. coli  and the constitutive lactococcal promoter P23 (Que et al., 2000). The multiple cloning site of pOri23 consists of restriction sites for endonucleases PstI, SalI and BamHI (Que et al., 2000). 
         [0098]    StrataClone™ plasmids containing the DNA inserts of interest and the  E. coli - L. lactis  shuttle vector pOri23 were each digested in a 100 μl total reaction volume containing 10 μl plasmid (approximately 2.5 μg), 20 units appropriate restriction endonucleases (New England Biolabs, UK), and suitable buffers (New England Biolabs, UK) according to the manufacturer&#39;s instructions. Restriction digestions were performed at 37° C. for 16 h. The restriction fragments to be cloned were extracted from 0.8% (w/v) agarose gels without UV exposure as described in the general Material and Methods and purified using QIAquick Gel Extraction Kit (Qiagen, UK) according to the manufacturer&#39;s instructions. DNA inserts and restriction-digested pOri23 plasmid were quantified using spectrophotometry (NanoDrop ND-1000, Thermo Scientific, USA) and ligation reactions were carried out with a plasmid to insert ratio of 1:3 in a 10 μl total ligation reaction volume, consisting of 1 μl vector (approximately 10 ng), 400 units T4 DNA ligase (New England Biolabs, UK), 1× T4 DNA ligase reaction buffer (New England Biolabs, UK), x μl DNA insert (depending on DNA concentration), and x μl sterile water (depending on the volume of DNA insert). Ligations were incubated at 16° C. for 16 h. 
         [0099]    One 50 μl aliquot of electrocompetent  L. lactis  cells was thawed on ice and 2 μl (˜20 ng) pOri23 plasmid carrying the DNA insert of interest was added. Electroporation cuvettes (Sigma-Aldrich, UK) were pre-chilled and  L. lactis  cells plus plasmid were transferred into the cuvettes. Electroporation was performed at standard settings (25 μF, 23 kV, 200 Ohm) and 1 ml GM17 was added immediately. Cells were incubated at 30° C. in a static incubator for 2 h prior to spreading 250 μl of cell suspension per plate onto GM17 plates containing 5 μg/ml erythromycin. Plates were incubated overnight at 30° C. 
         [0100]    For screening of  L. lactis  transformants, plasmid was isolated using the Qiagen MiniPrep Kit (Qiagen, UK) with addition of 100 U/ml mutanolysin (Sigma-Aldrich, UK) and 100 μg/ml lysozyme (Sigma-Aldrich, UK) to buffer P1. Diagnostic digests of purified plasmids were carried out with appropriate restriction enzymes and analysed on 0.8% (w/v) agarose gels. 
         [0101]    Additionally, colony PCR was performed for pOri23 carrying spsD and spsO using gene-specific oligonucleotides (Table 5.3).  L. lactis  colonies were resuspended in 10 μl 10% (v/v) IGEPAL (Sigma-Aldrich, UK) and incubated for 10 min at 95° C. in a thermocycler machine. 40 μl master mix containing 0.3 μM forward primer, 0.3 μM reverse primer, 0.2 mM dNTP&#39;s (Promega, USA), 1× reaction buffer (Promega, USA), 1.5 mM MgCl 2  (Promega, USA) and 0.025 u/μl taq polymerase (Promega, USA) was added. The thermocycler programme included an initial denaturation step at 95° C. for 2 min, followed by 30 cycles of denaturation at 95° C. for 1 min, annealing at 50° C. for 1 min and extension at 72° C. for 1 min, followed by a final extension step at 72° C. for 7 min. PCR products were visualised on 0.8% (w/v) agarose gels. 
       Western Blot Analysis of  L. Lactis  Constructs 
       [0102]    Samples were dissolved in 1× Laemmli sample buffer (Sigma-Aldrich, UK), boiled for 10 min and resolved by SDS-PAGE in 10% polyacrylamide gels by standard procedures, and Western blot analysis was carried out as described in the general Materials and Methods. Three canine sera samples from pyoderma cases (obtained from patients at the Hospital for Small Animals, The Royal (Dick) School of Veterinary Studies, The University of Edinburgh) were pooled and used as primary antibody in a 1:1000 dilution. HRP-conjugated sheep anti-dog antibody was used as a secondary antibody in a 1:5000 dilution (Bethyl Laboratories Inc., USA). 
       Canine Corneocyte Adherence Assay 
       [0103]    For preliminary experiments to confirm adherence of  S. pseudintermedius  ED99 and non-adherence of  L. lactis , corneocytes were obtained from a seven-year-old male neutered Border collie cross-breed with no history or physical signs of systemic or cutaneous disease. Corneocytes for the  L. lactis  adherence study were obtained from five dogs of different breeds (one Labrador retriever, two Border collies and two cross-breeds). Three dogs were ovariohysterectomised females and two were entire males. The median age was seven years (range one to twelve years). The dogs showed no abnormalities on general physical examination and had no history or physical signs of skin disease at the time of corneocyte collection. All dogs were privately owned by staff or students of the Royal (Dick) School of Veterinary Studies, The University of Edinburgh. None of the dogs had received topical or systemic drug treatments for at least three weeks prior to the day of corneocyte collection. 
         [0104]    Samples were taken from the ventral abdomen and inner thigh. If necessary, sample sites were clipped with Oster clippers (Oster Cryotech, USA) using a number 40 blade. For collection of corneocytes, the method described by Forsythe et al. (2002) was used. Briefly, the area was cleaned of surface debris and commensal bacteria by applying four strips of single sided adhesive tape (Cellux, Henkel Consumer Adhesives, UK), using each strip once. To collect corneocytes, double-sided, clear, adhesive wig tape (Tropical Tape Super Grip, USA) was mounted onto a microscope slide in 1 cm 2  pieces and applied to the same area of skin surface 10 times with gentle force. Slides were investigated by microscopic examination and only slides with at least 75% corneocyte coverage were used in the study. 
         [0105]    The corneocyte slides were positioned in moisture chambers (Nunc™, Thermo Fisher Scientific, Denmark) as described by Forsythe et al. (2002). The moisture chambers consisted of 30 cm×30 cm plastic trays with lids and were prepared by lining the trays with moistened paper towels.  S. pseudintermedius  ED99 stationary or exponential (OD 600  of 0.5) phase cultures and  L. lactis  exponential phase cultures (OD 600  0.6 to 0.8) were centrifuged at 4000 rpm for 5 min, washed with PBS and resuspended in PBS to a final OD 600  of 0.5. The moisture chambers were placed in a static incubator and 250 μl of bacterial suspension was added to each 1 cm 2  of tape, forming a meniscus on the tape. Slides incubated with 250 μl of sterile PBS were included as a control. The slides were incubated at 37° C. for 90 min and washed in PBS. Each slide was stained with 0.5% (w/v) crystal violet (Sigma-Aldrich, UK) for 90 s before rinsing off with PBS. The slides were air-dried and a drop of immersion oil (Cargille Laboratories Inc., USA) and a cover slip (Scientific Laboratory Supplies, UK) were added before microscopic quantification. All slides were prepared in duplicate on the same day and incubated at the same time. Prior to incubation with bacterial suspensions or PBS, each slide was labelled with a letter code to allow identification after the microscopic analysis. The identification code on each slide was hidden by a third party for subsequent image acquisition so that the investigator was blinded to the origin of the slide. For quantification of adherent bacteria, computerised image analysis was used as described previously by Forsythe et al. (2002) with minor modifications. For each slide, bright field images of 1000× oil-immersion fields were acquired with a Sony DXC-390P 3CCD colour video camera (Scion Corporation, USA) connected to a Leica Laborlux S microscope (Leica Microsystems UK Ltd., UK). The ROB video signal from the camera was digitised using Scion Image (Scion Corporation, USA) installed in a G4 Macintosh computer (Apple Computer, USA) fitted with a CG-7 frame grabber (Scion Corporation, USA). For image acquisition, fields equivalent to 14.4 mm 2  were selected randomly by starting in the bottom left corner of each slide and moving through the slide in a defined way using the scale on the microscope stage. A field was discarded if the corneocyte layer was not confluent, the bacteria were poorly stained against the background or the field could not be focused properly. The software used for quantification of bacterial adherence was set to calculate the percentage area that was covered by bacteria per confluent layer of corneocytes in a defined region of interest (ROI) of 500 μm 2  within each image field acquired. Previous studies by Forsythe et al. (2002) using the same technique and software have demonstrated that 15 replicates of each duplicate slide resulted in acceptable coefficients of variation of approximately 10%. In this study, 25 replicates of each slide were acquired and the overall mean percentage area of adherence was determined by calculating the mean of all replicates. 
       Results 
     Identification of Genes Encoding 17 Putative Cell-Wall-Anchored Proteins in the  S. Pseudintermedius  Ed99 Genome 
       [0106]    The initial search for putative CWA proteins identified 34 sequences that fulfilled at least one of the search criteria (homology to characterised MSCRAMMs in the database, predicted LPXTG motif or variant near the C terminus, predicted signal peptide at the N terminus). After gap closure and combination of incomplete sequences, a total of 17 ORFs encoding putative CWA proteins with a predicted minimum length of approximately 250 amino acids was determined. The 17 predicted CWA proteins were designated ‘Sps’ for ‘ Staphylococcus pseudintermedius  surface proteins’, followed by a capital letter (SpsA to SpsQ). Their position in the  S. pseudintermedius  ED99 genome is indicated in  FIG. 1 . Of note, eight genes encoding putative CWA proteins are located near the oriC environ ( FIG. 1 ). Homology searches in the database resulted in sequence identities with known staphylococcal proteins ranging from ˜30% to ˜80% (Table 1). Signal sequences, necessary for Sec-dependent protein secretion (Foster and Hook, 1998), were predicted for 14 putative Sps proteins, consisting of 29 aa for SpsC and SpsK, 33 aa for SpsN, SpsP, and SpsQ, 36 aa for SpsD, 37 for SpsG, 38 aa for SpsA, SpsB, and SpsL, 39 aa for SpsH, 44 aa for SpsO, and 48 aa for SpsF and SpsM. No signal sequence was predicted for SpsE, Sps1, and SpsJ ( FIG. 4.3 ). 
         [0000]    The Putative CWA Proteins SpsD, SpsL, and SpsO have Several MSCRAMM Features. 
         [0107]    Out of the 17 putative CWA proteins of  S. pseudintermedius  ED99, SpsD, SpsL, and SpsO contained each of the MSCRAMM features screened for, including a signal sequence at the N-terminus, followed by a non-repeated A domain with two IgG-like folds, dividing the A domain into N1, N2, and N3 subdomains, a tandemly repeated domain at the C-terminus (and at the N-terminus for SpsO), and a C-terminal LPXTG-anchor motif. The main characteristics of SpsD, SpsL, and SpsO are summarised in Table 2. Of interest, a TYTFTDYVD motif or variant, important for the ‘dock, lock and latch’ ligand-binding mechanism (Ponnuraj et al., 2003), was found in SpsD, SpsL, and SpsO, and putative latching sequences were identified (Table 2). Further, putative Fn-binding motifs with weak homology to FnbpA-10 of FnbpA in  S. aureus  were detected in the repeat region of SpsL (24% identity in pair-wise alignments for SpsLi-SpsL6, and 21% for SpsL-7). No homology to Fn-binding motifs of FnbpA was detected in the repeat regions of SpsD and SpsO. Of note, the genes encoding for SpsD, SpsL, and SpsO in the  S. pseudintermedius  ED99 genome are situated in different genomic contexts. While spsD is located in a well-conserved region of the core genome, spsL is part of the oriC environ (Takeuchi et al., 2005) ( FIG. 1 ). The spsO gene appears to be species-specific as it is not present in the genomes of other staphylococcal species. The region contains two putative transposases, suggesting that the whole region might be subjected to horizontal gene transfer. 
       Distribution of the 17 Genes Encoding Putative Cell-Wall-Anchored Proteins Among the  S. Intermedius  Group 
       [0108]    In order to investigate the distribution of the 17 genes encoding putative CWA proteins identified in the  S. pseudintermedius  ED99 genome among other members of the SIG and closely related staphylococcal species, Southern blot analysis and PCR amplification were performed. A total of 20  S. pseudintermedius  strains representing the breadth of diversity within the species, representatives of the closely related  S. delphini  and  S. intermedius  species, and other staphylococcal species associated with animal hosts ( FIG. 2 ) were screened for the presence of the putative CWA encoding genes by Southern blot analysis (spsA to spsO). For the  S. aureus  spa orthologues spsP and spsQ, PCR amplification was employed, as the genes share 70% nucleotide identity which precluded design of gene-specific probes for Southern blot analysis. For similar reasons, the primers designed for PCR amplification were located upstream of spsP (spsP-F), in the non-repeated region of spsP (spsP-R), in the unique region between spsP and spsQ (spsQ-F), and in a region unique for spsQ (spsQ-R). 
         [0109]    Of the 17 genes examined, 13 were found in all  S. pseudintermedius  strains investigated. The remaining 4 (spsF, spsO, and the  S. aureus  spa orthologues spsP and spsQ) were present in 11, 6, 7, and 11 of the 20  S. pseudintermedius  strains, respectively. Furthermore, 8 of the 17 genes were detected in  S. delphini  and 6 in  S. intermedius , and 9 genes were exclusive to  S. pseudintermedius . None of the genes encoding putative CWA proteins was detected in the non-SIG staphylococcal species examined. Results are summarised in  FIG. 2 . Of note, it cannot be excluded at this point that DNA sequence variation in PCR primer annealing sites for spsP and spsQ, and weak homology (less than approximate 70%) for spsA to spsO among different strains have influenced the results. 
       Expression of CWA Proteins on the  S. Pseudintermedius  Bacterial Cell Surface. 
       [0110]    The in silico identification of 17 putative CWA proteins in  S. pseudintermedius  ED99 raises questions about the expression of these proteins and their role in colonisation and disease. Surface proteome analysis of early-, mid-, and late exponential phase  S. pseudintermedius  ED99 was performed in collaboration with the Moredun Research Institute, Penicuik, Scotland, UK, using liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS-MS). Six out of the 17 putative CWA proteins predicted in the  S. pseudintermedius  ED99 genome were detected on the bacterial surface, including SpsD, SpsK, SpsL, SpsN, SpsO, and SpsQ. The putative CWA proteins SpsL, SpsN, and SpsQ were identified in all three phases of growth; SpsK was lacking in early-, SpsO in mid-, and SpsD in late exponential phase. The 11 undetected CWA proteins might not have been expressed under the conditions tested, or the expression level might have been below the detection threshold of the LC-ESI-MS-MS method used. 
         [0000]    Cloning and Expression of SpsD, SpsL, and SpsO in  L. lactis.    
         [0111]    In order to examine the role of putative selected MSCRAMMs independently on the bacterial cell surface, the full-length spsD (3096 bp), spsL (2793 bp) and spsO (5538 bp) genes were cloned into  L. lactis  using the shuttle vector pOri23 (Que et al., 2000). Positive clones were identified by restriction digestion of purified pOri23 plasmids from single colonies of transformed  L. lactis  cells (data not shown). The pOri23 construct inserts were verified by DNA sequencing for spsL and spsD. For spsO, DNA sequence was generated for approximately 3000 bp of the total length of 5538 bp. A segment of the repeat region corresponding to ˜2500 bp could not be determined due to the existence of identical tandem repeats which did not allow directed sequencing. As a negative control for subsequent MSCRAMM characterisation studies,  L. lactis  was transformed with the empty vector pOri23, confirmed by restriction digestion analysis. The predicted molecular weights were 115 kDa for SpsD, 103 kDa for SpsL, and 198 kDa for SpsO. 
         [0112]      L. lactis  expressing SpsD and SpsL Demonstrated Seroreactivity with Canine Sera from Pyoderma Cases. 
         [0113]    The potential antibody response to SpsD, SpsL, and SpsO in vivo was investigated by Western blot analysis employing canine sera from staphylococcal pyoderma cases. The pyoderma was clinically manifested at the time of blood sampling and the dogs were also diagnosed with AD (Neuber et at., 2008). Cell wall-associated protein fractions of the  L. lactis  constructs and of  S. pseudintermedius  ED99 were subjected to SDS-PAGE, transferred to nitrocellulose membrane and incubated with pooled canine sera from three pyoderma cases as described in Materials and Methods. An array of immunoreactive bands was detected for  S. pseudintermedius  ED99, ranging from 24 kDa to 102 kDa in molecular weight ( FIG. 3 ). For  L. lactis  expressing SpsD and  L. lactis  expressing SpsL, multiple seroreactive bands in the range of 38 kDa to 225 kDa for SpsD, and 38 kDa and 52 kDa for SpsL were detected, which were absent in the protein fractions of  L. lactis  carrying pOri23 alone ( FIG. 3 ). In contrast,  L. lactis  expressing SpsO did not demonstrate seroreactivity with sera from dogs diagnosed with pyoderma ( FIG. 3 ). 
       Adherence of  L. Lactis  Constructs to Extracellular Matrix Proteins. 
       [0114]      L. lactis  expressing SpsO, SpsD, SpsL, and  L. lactis  carrying the vector pOri23 alone were tested for their ability to adhere to human Fn, human, canine, feline, and bovine Fg, and to recombinant mouse CK10 in solid phase assays. 
         [0000]    The putative MSCRAMMs SpsD and SpsL mediate binding of  L. lactis  to fibronectin. 
         [0115]      L. lactis  expressing SpsD and SpsL demonstrated adherence to human Fn, whereas  L. lactis  expressing SpsO demonstrated increased binding to Fn, but also to BSA, indicative of a non-specific interaction ( FIG. 4 ). 
         [0000]    The Putative MSCRAMMs SpsD and SpsL Mediate Binding of  L. lactis  to Fibrinogen, and SpsL Demonstrates Canine Host-Specificity. 
         [0116]      L. lactis  expressing SpsD strongly adhered to Fg from several animal sources ( FIG. 5 ). In contrast,  L. lactis  expressing SpsL adhered to canine and feline Fg only, and did not bind to human and bovine Fg ( FIG. 5 ), indicating a host-specific interaction.  L. lactis  expressing SpsO did not bind to Fg from any source compared to  L. lactis  with the pOri23 vector alone ( FIG. 5 ). 
         [0000]    The Putative MSCRAMM SpsD Mediates Binding of  L. lactis  to Cytokeratin 10. 
         [0117]      L. lactis  expressing SpsD demonstrated strong adherence to CK10, whereas  L. lactis  expressing SpsO and SpsL did not show increased binding compared to  L. lactis  with the vector pOri23 alone ( FIG. 6 ). 
         [0000]    The Putative MSCRAMMs SpsD and SpsO, but not SpsL, Mediate Adherence of  L. lactis  to Ex Vivo Canine Corneocytes. 
         [0118]      L. lactis  expressing SpsD, SpsL, and SpsO were tested for their ability to adhere to ex vivo canine corneocytes in comparison to  L. lactis  with the empty vector pOri23 and  S. pseudintermedius  ED99 . L. lactis  carrying the empty vector pOri23 adhered poorly to canine corneocytes ( FIG. 7 ). For  S. pseudintermedius  ED99, the mean percentage adherence to canine corneocytes was 4.24% which was significantly different to  L. lactis  carrying pOri23 alone (P=0.001) ( FIG. 7 ).  L. lactis  expressing SpsD and  L. lactis  expressing SpsO adhered to ex vivo canine corneocytes ( FIG. 7 ). The increase in adherence was approaching significance for SpsD (P=0.050), and was significant for SpsO when expressed in  L. lactis  compared to  L. lactis  carrying pOri23 alone (P=0.004). Binding of  L. lactis  expressing SpsL was not significantly different to  L. lactis  carrying pOri23 alone (P=0.108), indicating that SpsL does not promote adherence to canine corneocytes ( FIG. 7 ). 
         [0000]    Purified Recombinant Sps D, Sys L, and Sps O Demonstrate Reactivity with Canine Convalescent Serum. 
         [0119]    Reactivity of recombinant A domain from Sps D, Sps L and Sps 0 with canine convalescent serum from pyoderma cases was examined by Western affinity blot analysis ( FIG. 8 ). rSpsD, rSpsL and rSpsO all crossreacted with IgG present in the canine serum ( FIG. 8 ). 
         [0000]    Pre-Incubation with Canine Convalescent Serum Inhibits SpsL-Mediated Binding to fibrinogen. 
         [0120]    The ability of the reactive antibody present in convalescent serum to inhibit SpsD and SpsL ligand binding was investigated using a modified solid phase adherence assay. Prior to inoculation into fibrinogen coated wells, PBS normalised cultures of  L. lactis  expressing SpsD and SpsL were incubated for 2 h with doubling dilutions of convalescent serum at 28° C. ( FIG. 9 ). Convalescent serum inhibited binding of  L. lactis  expressing SpsL, but not SpsD to canine fibrinogen, with complete inhibition at a final concentration of 2% v/v ( FIG. 9 ). 
       Discussion 
       [0121]    In summary, genome-wide analysis of  S. pseudintermedius  ED99 revealed the presence of 17 genes encoding putative CWA proteins based on typical MSCRAMM features. All MSCRAMM characteristics searched for were identified for SpsD, SpsL, and SpsO, including a signal sequence, a non-repeated A domain with two IgG-like folds, tandemly repeated regions, and a C-terminal LPX′TG-anchor motif. Interestingly, SpsD, SpsL, and SpsO belong to different groups based on Southern blot analysis, with SpsD being present in all SIG members, SpsL in  S. pseudintermedius  only, and SpsO in only six of the  S. pseudintermedius  strains investigated, and not in the other SIG species tested. Based on in silico analysis and in vitro expression data, SpsD, SpsL, and SpsO were selected for functional characterisation. 
         [0122]    All CWA proteins and in particular, SpsD, SpsL, and SpsO could be employed in passive and active immunisation studies to test their antigenic properties, either singular or in combination, in a similar fashion as proposed for  S. aureus  C1fA (Josefsson et al., 2001; Hall et al., 2003; Patti, 2004; Nanra et al., 2009). Further, a combinatory vaccine of  S. aureus  surface proteins IsdA, iron-regulated surface determinant protein B (IsdB), SdrD, and SdrE has proven to be highly protective in a mouse infection model (Stranger-Jones et al., 2006), demonstrating the promising potential of vaccine preparations containing multiple staphylococcal CWA proteins. 
         [0123]    In addition, MSCRAMMs with known ligands could be targets of anti-staphylococcal drug development, e.g. by generating synthetic peptides based on the interacting ECM proteins, which antagonise the MSCRAMM-host protein interaction, but do not interfere profoundly with physiological processes in the host. An excellent example is provided by Ganesh et al. (2008) who demonstrated that synthetic peptides, based on the Fg-binding site for C1fA, hinder the C1fA interaction, but do not block binding of the platelet integrin α 11b β 3  to Fg. Recently, Stranger-Jones et al screened the genome of the human pathogen  S. aureus  for all genes predicted to encode CWA proteins, and immunized mice with each protein to determine their capacity to protect against lethal or invasive infection (Stranger-Jones et al, 2006). Four of the proteins were combined into a multiple protein vaccine which induced high levels of protection against  S. aureus  invasive disease of mice. These data have stimulated renewed optimism in a vaccine for the prevention of human  S. aureus  infections. A similar approach could be used to design an effective vaccine for the prevention of  S. pseudintermedius  canine pyoderma. 
       Example 2 
       Staphylococcus Pseudintermedius  Surface Protein Vaccination Experiment 
       [0124]      S. pseudintermedius  surface antigens were divided into 2 pools of 3 and 4 antigens, respectively. Vaccine pool 1 contained antigens SpsC, IsaA, and SpsN and vaccine pool 2 contained SpsD A domain, N2,N3 subdomains, SpsL A domain (SEQ ID NO: 37), and SpsA. 
         [0125]    Groups of 8 or 9 BalbC mice were vaccinated subcutaneously with pool 1 or pool 2 or PBS, each with complete Freund&#39;s adjuvant, followed by additional vaccinations at day 8 and day 23 with incomplete Freund&#39;s adjuvant. On day 32, mice were challenged through a subcutaneous route with 10 7  cfu  S. pseudintermedius  ED99. Mice were then examined for abscess formation, and weight loss. 
         [0126]    Mice vaccinated with pool 2 (comprising the protein having amino acid sequence provided in SEQ ID NO: 37) had significantly reduced lesion size (−50% reduction), and significantly reduced weight loss (−50%) compared to PBS control mock vaccinated animals. 
       REFERENCES 
       [0000]    
       
         Bannoehr J, Ben Zakour N L, Waller A S, Guardabassi L, Thoday K L, van den Broek A H, Fitzgerald J R. (2007). Population genetic structure of the  Staphylococcus intermedius  group: insights into agr diversification and the emergence of methicillin-resistant strains. J. Bacteriol. 189:8685-92 
         Ben Zakour, N. L., Guinane, C. M. &amp; Fitzgerald, J. R. (2008) Pathogenomics of the staphylococci: insights into niche adaptation and the emergence of new virulent strains.  FEMS Microbial Lett,  289, 1-12. 
         Clarke, S. R. &amp; Foster, S. J. (2006) Surface adhesins of  Staphylococcus aureus. Adv Microb Physiol,  51, 187-224. 
         Corrigan, R. M., Miajlovic, H. &amp; Foster, T. J. (2009) Surface proteins that promote adherence of  Staphylococcus aureus  to human desquamated nasal epithelial cells.  BMC Microbial,  9, 22. 
         Clarke, S. R., Andre, G., Walsh, E. J., Dufrene, Y. F., Foster, T. J. &amp; Foster, S. J. (2009) Iron-regulated surface determinant protein A mediates adhesion of  Staphylococcus aureus  to human corneocyte envelope proteins.  Infect Immun,  77, 2408-16. 
         Curtis, C. F., et al (2006) Masked, controlled study to investigate the efficacy of a  Staphylococcus intermedius  autogenous bacterin for the control of canine idiopathic recurrent superficial pyoderma.  Vet Dermatol  17, 163-8 (2006). 
         Forsythe, P. J., Hill, P. B., Thoday, K. L. &amp; Brown, J. (2002) Use of computerized image analysis to quantify staphylococcal adhesion to canine corneocytes: does breed and body site have any relevance to the pathogenesis of pyoderma?  Vet Dermatol,  13, 29-36. 
         Foster, T. J. &amp; Hook, M. (1998) Surface protein adhesins of  Staphylococcus aureus. Trends Microbiol,  6, 484-8. 
         Ganesh, V. K., Rivera, J. J., Smeds, E., Ko, Y. P., Bowden, M. G., Wann, E. R., Gurusiddappa, S., Fitzgerald, J. R. &amp; Hook, M. (2008) A structural model of the  Staphylococcus aureus  ClfA-fibrinogen interaction opens new avenues for the design of anti-staphylococcal therapeutics.  PLoS Pathog,  4, e1000226 
         Guardabassi, L., Schwarz, S. &amp; Lloyd, D. H. (2004b) Pet animals as reservoirs of antimicrobial-resistant bacteria.  J Antimicrob Chemother,  54, 321-32. 
         Hall, A. E., Domanski, P. J., Patel, P. R., Vernachio, J. H., Syribeys, P. J., Gorovits, E. L., Johnson, M. A., Ross, J. M., Hutchins, J. T. &amp; Patti, J. M. (2003) Characterization of a protective monoclonal antibody recognizing  Staphylococcus aureus  MSCRAMM protein clumping factor A.  Infect Immun,  71, 6864-70. 
         Hill, P. B. et al. (2006) Survey of the prevalence, diagnosis and treatment of dermatological conditions in small animals in general practice  Vet Rec  158, 533-9 (2006). 
         Josefsson, E., Hartford, O., O&#39;brien, L., Patti, J. M. &amp; Foster, T. (2001) Protection against experimental  Staphylococcus aureus  arthritis by vaccination with clumping factor A, a novel virulence determinant.  J Infect Dis,  184, 1572-80. 
         Lindsay, J. A., Moore, C. E., Day, N. P., Peacock, S. J., Witney, A. A., Stabler, R. A., Husain, S. E., Butcher, P. D. &amp; Hinds, J. (2006) Microarrays reveal that each of the ten dominant lineages of  Staphylococcus aureus  has a unique combination of surface-associated and regulatory genes.  J Bacteriol,  188, 669-76. 
         Mazmanian, S. K., et al. (1999)  Staphylococcus aureus  sortase, an enzyme that anchors surface proteins to the cell wall. Science 285, 760-3 (1999). 
         Nanra, J. S., Timofeyeva, Y., Buitrago, S. M., Sellman, B. R., Dilts, D. A., Fink, P., Nunez, L., Hagen, M., Matsuka, Y. V., Mininni, T., Zhu, D., Pavliak, V., Green, B. A., 
         Jansen, K. U. &amp; Anderson, A. S. (2009) Heterogeneous in vivo expression of clumping factor A and capsular polysaccharide by  Staphylococcus aureus : implications for vaccine design.  Vaccine,  27, 3276-80. 
         Otto, M. (2008) Targeted immunotherapy for staphylococcal infections: focus on anti-MSCRAMM antibodies.  BioDrugs  22, 27-36 (2008) 
         Patti, J. M. (2004) A humanized monoclonal antibody targeting  Staphylococcus aureus. Vaccine,  22 Suppl 1, S39-43. 
         Pizza, M. et al. (2008) Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing.  Science  287, 1816-1820 
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Sequence homology of the 17 predicted cell-wall-anchored proteins against known proteins in the public domain. 
               
             
          
           
               
                 Putative CWA 
                   
                 Identity 
                 Similarity 
               
               
                 protein 
                 Best Hit (BLAST) 
                 (%) 
                 (%) 
               
               
                   
               
             
          
           
               
                 SpsA 
                 LPXTG cell-wall surface anchor family protein of  S. aureus  COL 
                 31.2 
                 56.9 
               
               
                 SpsB 
                 RodA, a rod shape determining protein of  S. epidermidis  ATCC 12228 
                 69.7 
                 87.8 
               
               
                 SpsC 
                 bifunctional autolysin precursor of  S. epidermidis  ATCC 12228 
                 50.7 
                 65.9 
               
               
                 SpsD 
                 Fnbp protein homolog of  S. aureus  Mu50 
                 40.7 
                 59.1 
               
               
                 SpsE 
                 Fibrinogen binding protein of  S. epidermidis  ATCC 12228 
                 78.6 
                 90.1 
               
               
                 SpsF 
                 hypothetical protein, similar to the putative cell-surface adhesin SdrF of  S. haemolyticus  JCSC1435 
                 52.8 
                 69.3 
               
               
                 SpsG 
                 hypothetical protein, cell-wall surface anchor family of  Streptococcus pneumoniae  D39 
                 47.7 
                 63.6 
               
               
                 SpsH 
                 Sdr-repeat family protein SdrH,  S. aureus  USA300 
                 36.0 
                 53.1 
               
               
                 SpsI 
                 serine-aspartate rich, fibrinogen-binding, bone sialoprotein-binding protein  S. epidermidis  ATCC 12228 
                 37.3 
                 55.5 
               
               
                 SpsJ 
                 precursor of a serine-rich adhesin for platelets of  S. haemolyticus  JCSC143S 
                 52.2 
                 61.2 
               
               
                 SpsK 
                 IgG-binding protein of  S. aureus  COL 
                 50.4 
                 71.1 
               
               
                 SpsL 
                 Fnbp protein homolog of  S. aureus  Mu50 
                 33.4 
                 51.7 
               
               
                 SpsM 
                 hypothetical protein, similar to the putative cell-surface adhesin SdrF,  S. haemolyticus  JCSC1435 
                 44.4 
                 61.7 
               
               
                 SpsN 
                 probable exported protein of  S. aureus  RF122 
                 38.0 
                 60.0 
               
               
                 SpsO 
                 serine-aspartate repeat-containing protein C precursor of  Staphylococcus warneri  L37603 
                 50.0 
                 68 
               
               
                 SpsP 
                 LPXTG-motif cell wall anchor domain of  S. aureus  JH9 
                 60.6 
                 74.3 
               
               
                 SpsQ 
                 IgG-binding protein A precursor of  S. aureus  MRSA252 
                 57.0 
                 71.7 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Main characteristics of the predicted CWA proteins SpsD, SpsL, 
               
               
                 and SpsO of  S. pseudintermedius  ED99. 
               
             
          
           
               
                   
                   
                   
                   
                   
                   
                   
                 Putative 
                   
                   
               
               
                   
                   
                   
                   
                   
                 Ig-like 
                 TYTFTDYVD- 
                 latching 
                 Repeat 
                 Copy 
               
               
                   
                 Amino 
                 MW 
                 Signal 
                 LPXTG 
                 fold b   
                 like motif 
                 sequence 
                 region 
                 number 
               
               
                   
                 acids 
                 (kDa) a   
                 peptide 
                 motif 
                 (position) 
                 (position) b   
                 (position) b   
                 (position) 
                 repeats 
               
               
                   
                   
               
             
          
           
               
                 SpsD 
                 1031 
                 115 
                 36 aa 
                 LPDTG 
                 167-320 aa 
                 RYRFMDYVN 
                 NNASGEG 
                  867-959 aa 
                  5 
               
               
                   
                   
                   
                   
                   
                 322-519 aa 
                 (267-275 aa) 
                 (491-497 aa) 
               
               
                   
               
               
                 SpsL 
                 930 
                 103 
                 38 aa 
                 LPKTG 
                 220-363 aa 
                 VYTFKDYVN 
                 NSASGSG 
                  543-818 aa 
                  7 
               
               
                   
                   
                   
                   
                   
                 364-531 aa 
                 (298-306 aa) 
                 (502-508 aa) 
               
               
                   
               
               
                 SpsO 
                 1846 
                 198 
                 44 aa 
                 LPNTG 
                 339-492 aa 
                 TYTFTDYVD 
                 DKSTALG 
                 661-1800 aa 
                 96 
               
               
                   
                   
                   
                   
                   
                 487-659 aa 
                 (424-432 aa) 
                 (635-641 aa) 
                   97-216 aa c   
                  4 c   
               
               
                   
               
               
                 aa = amino acids; 
               
               
                   a MW = predicted approximate molecular weight in kDa (kilo dalton); 
               
               
                   b within the A domain; 
               
               
                   c N-terminal repeats