
                                SEQUENCE LISTING

<110> Fava, Maurizio
      Papakostas, George
      Koch Jr., Harold O.
      Kronlage, David

<120> ASSAYS AND METHODS FOR SELECTING A
  TREATMENT REGIMEN FOR A SUBJECT WITH DEPRESSION
  

<130> 95768-902958-000520TW

<150> US 61/914,338       
<151> 2013-12-10  

<150> US 61/777,650       
<151> 2013-03-12  

<150> US 13/796,362       
<151> 2013-03-12  

<160> 28

<170> FastSEQ for Windows Version 4.0

<210> 1
<211> 1983
<212> DNA
<213> Homo sapiens

<220>
<223> human MTHFR (NM_005957.4) C677T and A1298C

<400> 1
aggaacccag ccatggtgaa cgaagccaga ggaaacagca gcctcaaccc ctgcttggag 60
ggcagtgcca gcagtggcag tgagagctcc aaagatagtt cgagatgttc caccccgggc 120
ctggaccccg agcggcatga gagactccgg gagaagatga ggcggcgatt ggaatctggt 180
gacaagtggt tctccctgga attcttccct cctcgaactg ctgagggagc tgtcaatctc 240
atctcaaggt ttgaccggat ggcagcaggt ggccccctct acatagacgt gacctggcac 300
ccagcaggtg accctggctc agacaaggag acctcctcca tgatgatcgc cagcaccgcc 360
gtgaactact gtggcctgga gaccatcctg cacatgacct gctgccgtca gcgcctggag 420
gagatcacgg gccatctgca caaagctaag cagctgggcc tgaagaacat catggcgctg 480
cggggagacc caataggtga ccagtgggaa gaggaggagg gaggcttcaa ctacgcagtg 540
gacctggtga agcacatccg aagtgagttt ggtgactact ttgacatctg tgtggcaggt 600
taccccaaag gccaccccga agcagggagc tttgaggctg acctgaagca cttgaaggag 660
aaggtgtctg cgggagycga tttcatcatc acgcagcttt tctttgaggc tgacacattc 720
ttccgctttg tgaaggcatg caccgacatg ggcatcactt gccccatcgt ccccgggatc 780
tttcccatcc agggctacca ctcccttcgg cagcttgtga agctgtccaa gctggaggtg 840
ccacaggaga tcaaggacgt gattgagcca atcaaagaca acgatgctgc catccgcaac 900
tatggcatcg agctggccgt gagcctgtgc caggagcttc tggccagtgg cttggtgcca 960
ggcctccact tctacaccct caaccgcgag atggctacca cagaggtgct gaagcgcctg 1020
gggatgtgga ctgaggaccc caggcgtccc ctaccctggg ctctcagcgc ccaccccaag 1080
cgccgagagg aagatgtacg tcccatcttc tgggcctcca gaccaaagag ttacatctac 1140
cgtacccagg agtgggacga gttccctaac ggccgctggg gcaattcctc ttcccctgcc 1200
tttggggagc tgaaggacta ctacctcttc tacctgaaga gcaagtcccc caaggaggag 1260
ctgctgaaga tgtgggggga ggagctgacc agtgaagmaa gtgtctttga agtcttcgtt 1320
ctttacctct cgggagaacc aaaccggaat ggtcacaaag tgacttgcct gccctggaac 1380
gatgagcccc tggcggctga gaccagcctg ctgaaggagg agctgctgcg ggtgaaccgc 1440
cagggcatcc tcaccatcaa ctcacagccc aacatcaacg ggaagccgtc ctccgacccc 1500
atcgtgggct ggggccccag cgggggctat gtcttccaga aggcctactt agagtttttc 1560
acttcccgcg agacagcgga agcacttctg caagtgctga agaagtacga gctccgggtt 1620
aattaccacc ttgtcaatgt gaagggtgaa aacatcacca atgcccctga actgcagccg 1680
aatgctgtca cttggggcat cttccctggg cgagagatca tccagcccac cgtagtggat 1740
cccgtcagct tcatgttctg gaaggacgag gcctttgccc tgtggattga gcggtgggga 1800
aagctgtatg aggaggagtc cccgtcccgc accatcatcc agtacatcca cgacaactac 1860
ttcctggtca acctggtgga caatgacttc ccactggaca actgcctctg gcaggtggtg 1920
gaagacacat tggagcttct caacaggccc acccagaatg cgagagaaac ggaggctcca 1980
tga                                                               1983

<210> 2
<211> 3798
<212> DNA
<213> Homo sapiens

<220>
<223> human MTR (NM_000254.2) A2756G

<400> 2
atgtcacccg cgctccaaga cctgtcgcaa cccgaaggtc tgaagaaaac cctgcgggat 60
gagatcaatg ccattctgca gaagaggatt atggtgctgg atggagggat ggggaccatg 120
atccagcggg agaagctaaa cgaagaacac ttccgaggtc aggaatttaa agatcatgcc 180
aggccgctga aaggcaacaa tgacatttta agtataactc agcctgatgt catttaccaa 240
atccataagg aatacttgct ggctggggca gatatcattg aaacaaatac ttttagcagc 300
actagtattg cccaagctga ctatggcctt gaacacttgg cctaccggat gaacatgtgc 360
tctgcaggag tggccagaaa agctgccgag gaggtaactc tccagacagg aattaagagg 420
tttgtggcag gggctctggg tccgactaat aagacactct ctgtgtcccc atctgtggaa 480
aggccggatt ataggaacat cacatttgat gagcttgttg aagcatacca agagcaggcc 540
aaaggacttc tggatggcgg ggttgatatc ttactcattg aaactatttt tgatactgcc 600
aatgccaagg cagccttgtt tgcactccaa aatctttttg aggagaaata tgctccccgg 660
cctatcttta tttcagggac gatcgttgat aaaagtgggc ggactctttc cggacagaca 720
ggagagggat ttgtcatcag cgtgtctcat ggagaaccac tctgcattgg attaaattgt 780
gctttgggtg cagctgaaat gagacctttt attgaaataa ttggaaaatg tacaacagcc 840
tatgtcctct gttatcccaa tgcaggtctt cccaacacct ttggtgacta tgatgaaacg 900
ccttctatga tggccaagca cctaaaggat tttgctatgg atggcttggt caatatagtt 960
ggaggatgct gtgggtcaac accagatcat atcagggaaa ttgctgaagc tgtgaaaaat 1020
tgtaagccta gagttccacc tgccactgct tttgaaggac atatgttact gtctggtcta 1080
gagcccttca ggattggacc gtacaccaac tttgttaaca ttggagagcg ctgtaatgtt 1140
gcaggatcaa ggaagtttgc taaactcatc atggcaggaa actatgaaga agccttgtgt 1200
gttgccaaag tgcaggtgga aatgggagcc caggtgttgg atgtcaacat ggatgatggc 1260
atgctagatg gtccaagtgc aatgaccaga ttttgcaact taattgcttc cgagccagac 1320
atcgcaaagg tacctttgtg catcgactcc tccaattttg ctgtgattga agctgggtta 1380
aagtgctgcc aagggaagtg cattgtcaat agcattagtc tgaaggaagg agaggacgac 1440
ttcttggaga aggccaggaa gattaaaaag tatggagctg ctatggtggt catggctttt 1500
gatgaagaag gacaggcaac agaaacagac acaaaaatca gagtgtgcac ccgggcctac 1560
catctgcttg tgaaaaaact gggctttaat ccaaatgaca ttatttttga ccctaatatc 1620
ctaaccattg ggactggaat ggaggaacac aacttgtatg ccattaattt tatccatgca 1680
acaaaagtca ttaaagaaac attacctgga gccagaataa gtggaggtct ttccaacttg 1740
tccttctcct tccgaggaat ggaagccatt cgagaagcaa tgcatggggt tttcctttac 1800
catgcaatca agtctggcat ggacatgggg atagtgaatg ctggaaacct ccctgtgtat 1860
gatgatatcc ataaggaact tctgcagctc tgtgaagatc tcatctggaa taaagaccct 1920
gaggccactg agaagctctt acgttatgcc cagactcaag gcacaggagg gaagaaagtc 1980
attcagactg atgagtggag aaatggccct gtcgaagaac gccttgagta tgcccttgtg 2040
aagggcattg aaaaacatat tattgaggat actgaggaag ccaggttaaa ccaaaaaaaa 2100
tatccccgac ctctcaatat aattgaagga cccctgatga atggaatgaa aattgttggt 2160
gatctttttg gagctggaaa aatgtttcta cctcaggtta taaagtcagc ccgggttatg 2220
aagaaggctg ttggccacct tatccctttc atggaaaaag aaagagaaga aaccagagtg 2280
cttaacggca cagtagaaga agaggaccct taccagggca ccatcgtgct ggccactgtt 2340
aaaggcgacg tgcacgacat aggcaagaac atagttggag tagtccttgg ctgcaataat 2400
ttccgagtta ttgatttagg agtcatgact ccatgtgata agatactgaa agctgctctt 2460
gaccacaaag cagatataat tggcctgtca ggactcatca ctccttccct ggatgaaatg 2520
atttttgttg ccaaggaaat ggagagatta gctataagga ttccattgtt gattggagga 2580
gcaaccactt caaaaaccca cacagcagtt aaaatagctc cgagatacag tgcacctgta 2640
atccatgtcc tggacgcgtc caagagtgtg gtggtgtgtt cccagctgtt agatgaaaat 2700
ctaaaggatg aatactttga ggaaatcatg gaagaatatg aagatattag acaggrccat 2760
tatgagtctc tcaaggagag gagatactta cccttaagtc aagccagaaa aagtggtttc 2820
caaatggatt ggctgtctga acctcaccca gtgaagccca cgtttattgg gacccaggtc 2880
tttgaagact atgacctgca gaagctggtg gactacattg actggaagcc tttctttgat 2940
gtctggcagc tccggggcaa gtacccgaat cgaggctttc ccaagatatt taacgacaaa 3000
acagtaggtg gagaggccag gaaggtctac gatgatgccc acaatatgct gaacacactg 3060
attagtcaaa agaaactccg ggcccggggt gtggttgggt tctggccagc acagagtatc 3120
caagacgaca ttcacctgta cgcagaggct gctgtgcccc aggctgcaga gcccatagcc 3180
accttctatg ggttaaggca acaggctgag aaggactctg ccagcacgga gccatactac 3240
tgcctctcag acttcatcgc tcccttgcat tctggcatcc gtgactacct gggcctgttt 3300
gccgttgcct gctttggggt agaagagctg agcaaggcct atgaggatga tggtgacgac 3360
tacagcagca tcatggtcaa ggcgctgggg gaccggctgg cagaggcctt tgcagaagag 3420
ctccatgaaa gagttcgccg agaactgtgg gcctactgtg gcagtgagca gctggacgtc 3480
gcagacctgc gcaggctgcg gtacaagggc atccgcccgg ctcctggcta ccccagccag 3540
cccgaccaca ccgagaagct caccatgtgg agactcgcag acatcgagca gtctacaggc 3600
attaggttaa cagaatcatt agcaatggca cctgcttcag cagtctcagg cctctacttc 3660
tccaatttga agtccaaata ttttgctgtg gggaagattt ccaaggatca ggttgaggat 3720
tatgcattga ggaagaacat atctgtggct gaggttgaga aatggcttgg acccattttg 3780
ggatatgata cagactaa                                               3798

<210> 3
<211> 2097
<212> DNA
<213> Homo sapiens

<220>
<223> human MTRR (NM_002454.2) A66G

<400> 3
atgaggaggt ttctgttact atatgctaca cagcagggac aggcaaaggc catcgcagaa 60
gaaatrtgtg agcaagctgt ggtacatgga ttttctgcag atcttcactg tattagtgaa 120
tccgataagt atgacctaaa aaccgaaaca gctcctcttg ttgttgtggt ttctaccacg 180
ggcaccggag acccacccga cacagcccgc aagtttgtta aggaaataca gaaccaaaca 240
ctgccggttg atttctttgc tcacctgcgg tatgggttac tgggtctcgg tgattcagaa 300
tacacctact tttgcaatgg ggggaagata attgataaac gacttcaaga gcttggagcc 360
cggcatttct atgacactgg acatgcagat gactgtgtag gtttagaact tgtggttgag 420
ccgtggattg ctggactctg gccagccctc agaaagcatt ttaggtcaag cagaggacaa 480
gaggagataa gtggcgcact cccggtggca tcacctgcat cctcgaggac agaccttgtg 540
aagtcagagc tgctacacat tgaatctcaa gtcgagcttc tgagattcga tgattcagga 600
agaaaggatt ctgaggtttt gaagcaaaat gcagtgaaca gcaaccaatc caatgttgta 660
attgaagact ttgagtcctc acttacccgt tcggtacccc cactctcaca agcctctctg 720
aatattcctg gtttaccccc agaatattta caggtacatc tgcaggagtc tcttggccag 780
gaggaaagcc aagtatctgt gacttcagca gatccagttt ttcaagtgcc aatttcaaag 840
gcagttcaac ttactacgaa tgatgccata aaaaccactc tgctggtaga attggacatt 900
tcaaatacag acttttccta tcagcctgga gatgccttca gcgtgatctg ccctaacagt 960
gattctgagg tacaaagcct actccaaaga ctgcagcttg aagataaaag agagcactgc 1020
gtccttttga aaataaaggc agacacaaag aagaaaggag ctaccttacc ccagcatata 1080
cctgcgggat gttctctcca gttcattttt acctggtgtc ttgaaatccg agcaattcct 1140
aaaaaggcat ttttgcgagc ccttgtggac tataccagtg acagtgctga aaagcgcagg 1200
ctacaggagc tgtgcagtaa acaaggggca gccgattata gccgctttgt acgagatgcc 1260
tgtgcctgct tgttggatct cctcctcgct ttcccttctt gccagccacc actcagtctc 1320
ctgctcgaac atcttcctaa acttcaaccc agaccatatt cgtgtgcaag ctcaagttta 1380
tttcacccag gaaagctcca ttttgtcttc aacattgtgg aatttctgtc tactgccaca 1440
acagaggttc tgcggaaggg agtatgtaca ggctggctgg ccttgttggt tgcttcagtt 1500
cttcagccaa acatacatgc atcccatgaa gacagcggga aagccctggc tcctaagata 1560
tccatctctc ctcgaacaac aaattctttc cacttaccag atgacccctc aatccccatc 1620
ataatggtgg gtccaggaac cggcatagcc ccgtttattg ggttcctaca acatagagag 1680
aaactccaag aacaacaccc agatggaaat tttggagcaa tgtggttgtt ttttggctgc 1740
aggcataagg atagggatta tctattcaga aaagagctca gacatttcct taagcatggg 1800
atcttaactc atctaaaggt ttccttctca agagatgctc ctgttgggga ggaggaagcc 1860
ccagcaaagt atgtgcaaga caacatccag cttcatggcc agcaggtggc gagaatcctc 1920
ctccaggaga acggccatat ttatgtgtgt ggagatgcaa agaatatggc caaggatgta 1980
catgatgccc ttgtgcaaat aataagcaaa gaggttggag ttgaaaaact agaagcaatg 2040
aaaaccctgg ccactttaaa agaagaaaaa cgctaccttc aggatatttg gtcataa    2097

<210> 4
<211> 656
<212> PRT
<213> Homo sapiens

<220> 
<221> VARIANT        
<222> (222)...(222)
<223> Xaa = Ala or Val

<220>
<221> VARIANT        
<222> (429)...(429)
<223> Xaa = Glu or Ala


<400> 4
Met Val Asn Glu Ala Arg Gly Asn Ser Ser Leu Asn Pro Cys Leu Glu
 1               5                  10                  15      
Gly Ser Ala Ser Ser Gly Ser Glu Ser Ser Lys Asp Ser Ser Arg Cys
            20                  25                  30          
Ser Thr Pro Gly Leu Asp Pro Glu Arg His Glu Arg Leu Arg Glu Lys
        35                  40                  45              
Met Arg Arg Arg Leu Glu Ser Gly Asp Lys Trp Phe Ser Leu Glu Phe
    50                  55                  60                  
Phe Pro Pro Arg Thr Ala Glu Gly Ala Val Asn Leu Ile Ser Arg Phe
65                  70                  75                  80  
Asp Arg Met Ala Ala Gly Gly Pro Leu Tyr Ile Asp Val Thr Trp His
                85                  90                  95      
Pro Ala Gly Asp Pro Gly Ser Asp Lys Glu Thr Ser Ser Met Met Ile
            100                 105                 110         
Ala Ser Thr Ala Val Asn Tyr Cys Gly Leu Glu Thr Ile Leu His Met
        115                 120                 125             
Thr Cys Cys Arg Gln Arg Leu Glu Glu Ile Thr Gly His Leu His Lys
    130                 135                 140                 
Ala Lys Gln Leu Gly Leu Lys Asn Ile Met Ala Leu Arg Gly Asp Pro
145                 150                 155                 160 
Ile Gly Asp Gln Trp Glu Glu Glu Glu Gly Gly Phe Asn Tyr Ala Val
                165                 170                 175     
Asp Leu Val Lys His Ile Arg Ser Glu Phe Gly Asp Tyr Phe Asp Ile
            180                 185                 190         
Cys Val Ala Gly Tyr Pro Lys Gly His Pro Glu Ala Gly Ser Phe Glu
        195                 200                 205             
Ala Asp Leu Lys His Leu Lys Glu Lys Val Ser Ala Gly Xaa Asp Phe
    210                 215                 220                 
Ile Ile Thr Gln Leu Phe Phe Glu Ala Asp Thr Phe Phe Arg Phe Val
225                 230                 235                 240 
Lys Ala Cys Thr Asp Met Gly Ile Thr Cys Pro Ile Val Pro Gly Ile
                245                 250                 255     
Phe Pro Ile Gln Gly Tyr His Ser Leu Arg Gln Leu Val Lys Leu Ser
            260                 265                 270         
Lys Leu Glu Val Pro Gln Glu Ile Lys Asp Val Ile Glu Pro Ile Lys
        275                 280                 285             
Asp Asn Asp Ala Ala Ile Arg Asn Tyr Gly Ile Glu Leu Ala Val Ser
    290                 295                 300                 
Leu Cys Gln Glu Leu Leu Ala Ser Gly Leu Val Pro Gly Leu His Phe
305                 310                 315                 320 
Tyr Thr Leu Asn Arg Glu Met Ala Thr Thr Glu Val Leu Lys Arg Leu
                325                 330                 335     
Gly Met Trp Thr Glu Asp Pro Arg Arg Pro Leu Pro Trp Ala Leu Ser
            340                 345                 350         
Ala His Pro Lys Arg Arg Glu Glu Asp Val Arg Pro Ile Phe Trp Ala
        355                 360                 365             
Ser Arg Pro Lys Ser Tyr Ile Tyr Arg Thr Gln Glu Trp Asp Glu Phe
    370                 375                 380                 
Pro Asn Gly Arg Trp Gly Asn Ser Ser Ser Pro Ala Phe Gly Glu Leu
385                 390                 395                 400 
Lys Asp Tyr Tyr Leu Phe Tyr Leu Lys Ser Lys Ser Pro Lys Glu Glu
                405                 410                 415     
Leu Leu Lys Met Trp Gly Glu Glu Leu Thr Ser Glu Xaa Ser Val Phe
            420                 425                 430         
Glu Val Phe Val Leu Tyr Leu Ser Gly Glu Pro Asn Arg Asn Gly His
        435                 440                 445             
Lys Val Thr Cys Leu Pro Trp Asn Asp Glu Pro Leu Ala Ala Glu Thr
    450                 455                 460                 
Ser Leu Leu Lys Glu Glu Leu Leu Arg Val Asn Arg Gln Gly Ile Leu
465                 470                 475                 480 
Thr Ile Asn Ser Gln Pro Asn Ile Asn Gly Lys Pro Ser Ser Asp Pro
                485                 490                 495     
Ile Val Gly Trp Gly Pro Ser Gly Gly Tyr Val Phe Gln Lys Ala Tyr
            500                 505                 510         
Leu Glu Phe Phe Thr Ser Arg Glu Thr Ala Glu Ala Leu Leu Gln Val
        515                 520                 525             
Leu Lys Lys Tyr Glu Leu Arg Val Asn Tyr His Leu Val Asn Val Lys
    530                 535                 540                 
Gly Glu Asn Ile Thr Asn Ala Pro Glu Leu Gln Pro Asn Ala Val Thr
545                 550                 555                 560 
Trp Gly Ile Phe Pro Gly Arg Glu Ile Ile Gln Pro Thr Val Val Asp
                565                 570                 575     
Pro Val Ser Phe Met Phe Trp Lys Asp Glu Ala Phe Ala Leu Trp Ile
            580                 585                 590         
Glu Arg Trp Gly Lys Leu Tyr Glu Glu Glu Ser Pro Ser Arg Thr Ile
        595                 600                 605             
Ile Gln Tyr Ile His Asp Asn Tyr Phe Leu Val Asn Leu Val Asp Asn
    610                 615                 620                 
Asp Phe Pro Leu Asp Asn Cys Leu Trp Gln Val Val Glu Asp Thr Leu
625                 630                 635                 640 
Glu Leu Leu Asn Arg Pro Thr Gln Asn Ala Arg Glu Thr Glu Ala Pro
                645                 650                 655     


<210> 5
<211> 1265
<212> PRT
<213> Homo sapiens

<220> 
<221> VARIANT        
<222> (919)...(919)
<223> Xaa = Asp or Gly


<400> 5
Met Ser Pro Ala Leu Gln Asp Leu Ser Gln Pro Glu Gly Leu Lys Lys
 1               5                  10                  15      
Thr Leu Arg Asp Glu Ile Asn Ala Ile Leu Gln Lys Arg Ile Met Val
            20                  25                  30          
Leu Asp Gly Gly Met Gly Thr Met Ile Gln Arg Glu Lys Leu Asn Glu
        35                  40                  45              
Glu His Phe Arg Gly Gln Glu Phe Lys Asp His Ala Arg Pro Leu Lys
    50                  55                  60                  
Gly Asn Asn Asp Ile Leu Ser Ile Thr Gln Pro Asp Val Ile Tyr Gln
65                  70                  75                  80  
Ile His Lys Glu Tyr Leu Leu Ala Gly Ala Asp Ile Ile Glu Thr Asn
                85                  90                  95      
Thr Phe Ser Ser Thr Ser Ile Ala Gln Ala Asp Tyr Gly Leu Glu His
            100                 105                 110         
Leu Ala Tyr Arg Met Asn Met Cys Ser Ala Gly Val Ala Arg Lys Ala
        115                 120                 125             
Ala Glu Glu Val Thr Leu Gln Thr Gly Ile Lys Arg Phe Val Ala Gly
    130                 135                 140                 
Ala Leu Gly Pro Thr Asn Lys Thr Leu Ser Val Ser Pro Ser Val Glu
145                 150                 155                 160 
Arg Pro Asp Tyr Arg Asn Ile Thr Phe Asp Glu Leu Val Glu Ala Tyr
                165                 170                 175     
Gln Glu Gln Ala Lys Gly Leu Leu Asp Gly Gly Val Asp Ile Leu Leu
            180                 185                 190         
Ile Glu Thr Ile Phe Asp Thr Ala Asn Ala Lys Ala Ala Leu Phe Ala
        195                 200                 205             
Leu Gln Asn Leu Phe Glu Glu Lys Tyr Ala Pro Arg Pro Ile Phe Ile
    210                 215                 220                 
Ser Gly Thr Ile Val Asp Lys Ser Gly Arg Thr Leu Ser Gly Gln Thr
225                 230                 235                 240 
Gly Glu Gly Phe Val Ile Ser Val Ser His Gly Glu Pro Leu Cys Ile
                245                 250                 255     
Gly Leu Asn Cys Ala Leu Gly Ala Ala Glu Met Arg Pro Phe Ile Glu
            260                 265                 270         
Ile Ile Gly Lys Cys Thr Thr Ala Tyr Val Leu Cys Tyr Pro Asn Ala
        275                 280                 285             
Gly Leu Pro Asn Thr Phe Gly Asp Tyr Asp Glu Thr Pro Ser Met Met
    290                 295                 300                 
Ala Lys His Leu Lys Asp Phe Ala Met Asp Gly Leu Val Asn Ile Val
305                 310                 315                 320 
Gly Gly Cys Cys Gly Ser Thr Pro Asp His Ile Arg Glu Ile Ala Glu
                325                 330                 335     
Ala Val Lys Asn Cys Lys Pro Arg Val Pro Pro Ala Thr Ala Phe Glu
            340                 345                 350         
Gly His Met Leu Leu Ser Gly Leu Glu Pro Phe Arg Ile Gly Pro Tyr
        355                 360                 365             
Thr Asn Phe Val Asn Ile Gly Glu Arg Cys Asn Val Ala Gly Ser Arg
    370                 375                 380                 
Lys Phe Ala Lys Leu Ile Met Ala Gly Asn Tyr Glu Glu Ala Leu Cys
385                 390                 395                 400 
Val Ala Lys Val Gln Val Glu Met Gly Ala Gln Val Leu Asp Val Asn
                405                 410                 415     
Met Asp Asp Gly Met Leu Asp Gly Pro Ser Ala Met Thr Arg Phe Cys
            420                 425                 430         
Asn Leu Ile Ala Ser Glu Pro Asp Ile Ala Lys Val Pro Leu Cys Ile
        435                 440                 445             
Asp Ser Ser Asn Phe Ala Val Ile Glu Ala Gly Leu Lys Cys Cys Gln
    450                 455                 460                 
Gly Lys Cys Ile Val Asn Ser Ile Ser Leu Lys Glu Gly Glu Asp Asp
465                 470                 475                 480 
Phe Leu Glu Lys Ala Arg Lys Ile Lys Lys Tyr Gly Ala Ala Met Val
                485                 490                 495     
Val Met Ala Phe Asp Glu Glu Gly Gln Ala Thr Glu Thr Asp Thr Lys
            500                 505                 510         
Ile Arg Val Cys Thr Arg Ala Tyr His Leu Leu Val Lys Lys Leu Gly
        515                 520                 525             
Phe Asn Pro Asn Asp Ile Ile Phe Asp Pro Asn Ile Leu Thr Ile Gly
    530                 535                 540                 
Thr Gly Met Glu Glu His Asn Leu Tyr Ala Ile Asn Phe Ile His Ala
545                 550                 555                 560 
Thr Lys Val Ile Lys Glu Thr Leu Pro Gly Ala Arg Ile Ser Gly Gly
                565                 570                 575     
Leu Ser Asn Leu Ser Phe Ser Phe Arg Gly Met Glu Ala Ile Arg Glu
            580                 585                 590         
Ala Met His Gly Val Phe Leu Tyr His Ala Ile Lys Ser Gly Met Asp
        595                 600                 605             
Met Gly Ile Val Asn Ala Gly Asn Leu Pro Val Tyr Asp Asp Ile His
    610                 615                 620                 
Lys Glu Leu Leu Gln Leu Cys Glu Asp Leu Ile Trp Asn Lys Asp Pro
625                 630                 635                 640 
Glu Ala Thr Glu Lys Leu Leu Arg Tyr Ala Gln Thr Gln Gly Thr Gly
                645                 650                 655     
Gly Lys Lys Val Ile Gln Thr Asp Glu Trp Arg Asn Gly Pro Val Glu
            660                 665                 670         
Glu Arg Leu Glu Tyr Ala Leu Val Lys Gly Ile Glu Lys His Ile Ile
        675                 680                 685             
Glu Asp Thr Glu Glu Ala Arg Leu Asn Gln Lys Lys Tyr Pro Arg Pro
    690                 695                 700                 
Leu Asn Ile Ile Glu Gly Pro Leu Met Asn Gly Met Lys Ile Val Gly
705                 710                 715                 720 
Asp Leu Phe Gly Ala Gly Lys Met Phe Leu Pro Gln Val Ile Lys Ser
                725                 730                 735     
Ala Arg Val Met Lys Lys Ala Val Gly His Leu Ile Pro Phe Met Glu
            740                 745                 750         
Lys Glu Arg Glu Glu Thr Arg Val Leu Asn Gly Thr Val Glu Glu Glu
        755                 760                 765             
Asp Pro Tyr Gln Gly Thr Ile Val Leu Ala Thr Val Lys Gly Asp Val
    770                 775                 780                 
His Asp Ile Gly Lys Asn Ile Val Gly Val Val Leu Gly Cys Asn Asn
785                 790                 795                 800 
Phe Arg Val Ile Asp Leu Gly Val Met Thr Pro Cys Asp Lys Ile Leu
                805                 810                 815     
Lys Ala Ala Leu Asp His Lys Ala Asp Ile Ile Gly Leu Ser Gly Leu
            820                 825                 830         
Ile Thr Pro Ser Leu Asp Glu Met Ile Phe Val Ala Lys Glu Met Glu
        835                 840                 845             
Arg Leu Ala Ile Arg Ile Pro Leu Leu Ile Gly Gly Ala Thr Thr Ser
    850                 855                 860                 
Lys Thr His Thr Ala Val Lys Ile Ala Pro Arg Tyr Ser Ala Pro Val
865                 870                 875                 880 
Ile His Val Leu Asp Ala Ser Lys Ser Val Val Val Cys Ser Gln Leu
                885                 890                 895     
Leu Asp Glu Asn Leu Lys Asp Glu Tyr Phe Glu Glu Ile Met Glu Glu
            900                 905                 910         
Tyr Glu Asp Ile Arg Gln Xaa His Tyr Glu Ser Leu Lys Glu Arg Arg
        915                 920                 925             
Tyr Leu Pro Leu Ser Gln Ala Arg Lys Ser Gly Phe Gln Met Asp Trp
    930                 935                 940                 
Leu Ser Glu Pro His Pro Val Lys Pro Thr Phe Ile Gly Thr Gln Val
945                 950                 955                 960 
Phe Glu Asp Tyr Asp Leu Gln Lys Leu Val Asp Tyr Ile Asp Trp Lys
                965                 970                 975     
Pro Phe Phe Asp Val Trp Gln Leu Arg Gly Lys Tyr Pro Asn Arg Gly
            980                 985                 990         
Phe Pro Lys Ile Phe Asn Asp Lys Thr Val Gly Gly Glu Ala Arg Lys
        995                 1000                1005            
Val Tyr Asp Asp Ala His Asn Met Leu Asn Thr Leu Ile Ser Gln Lys
    1010                1015                1020                
Lys Leu Arg Ala Arg Gly Val Val Gly Phe Trp Pro Ala Gln Ser Ile
1025                1030                1035                1040
Gln Asp Asp Ile His Leu Tyr Ala Glu Ala Ala Val Pro Gln Ala Ala
                1045                1050                1055    
Glu Pro Ile Ala Thr Phe Tyr Gly Leu Arg Gln Gln Ala Glu Lys Asp
            1060                1065                1070        
Ser Ala Ser Thr Glu Pro Tyr Tyr Cys Leu Ser Asp Phe Ile Ala Pro
        1075                1080                1085            
Leu His Ser Gly Ile Arg Asp Tyr Leu Gly Leu Phe Ala Val Ala Cys
    1090                1095                1100                
Phe Gly Val Glu Glu Leu Ser Lys Ala Tyr Glu Asp Asp Gly Asp Asp
1105                1110                1115                1120
Tyr Ser Ser Ile Met Val Lys Ala Leu Gly Asp Arg Leu Ala Glu Ala
                1125                1130                1135    
Phe Ala Glu Glu Leu His Glu Arg Val Arg Arg Glu Leu Trp Ala Tyr
            1140                1145                1150        
Cys Gly Ser Glu Gln Leu Asp Val Ala Asp Leu Arg Arg Leu Arg Tyr
        1155                1160                1165            
Lys Gly Ile Arg Pro Ala Pro Gly Tyr Pro Ser Gln Pro Asp His Thr
    1170                1175                1180                
Glu Lys Leu Thr Met Trp Arg Leu Ala Asp Ile Glu Gln Ser Thr Gly
1185                1190                1195                1200
Ile Arg Leu Thr Glu Ser Leu Ala Met Ala Pro Ala Ser Ala Val Ser
                1205                1210                1215    
Gly Leu Tyr Phe Ser Asn Leu Lys Ser Lys Tyr Phe Ala Val Gly Lys
            1220                1225                1230        
Ile Ser Lys Asp Gln Val Glu Asp Tyr Ala Leu Arg Lys Asn Ile Ser
        1235                1240                1245            
Val Ala Glu Val Glu Lys Trp Leu Gly Pro Ile Leu Gly Tyr Asp Thr
    1250                1255                1260                
Asp
1265


<210> 6
<211> 698
<212> PRT
<213> Homo sapiens

<220> 
<221> VARIANT        
<222> (22)...(22)
<223> Xaa = Ile or Met

<400> 6
Met Arg Arg Phe Leu Leu Leu Tyr Ala Thr Gln Gln Gly Gln Ala Lys
 1               5                  10                  15      
Ala Ile Ala Glu Glu Xaa Cys Glu Gln Ala Val Val His Gly Phe Ser
            20                  25                  30          
Ala Asp Leu His Cys Ile Ser Glu Ser Asp Lys Tyr Asp Leu Lys Thr
        35                  40                  45              
Glu Thr Ala Pro Leu Val Val Val Val Ser Thr Thr Gly Thr Gly Asp
    50                  55                  60                  
Pro Pro Asp Thr Ala Arg Lys Phe Val Lys Glu Ile Gln Asn Gln Thr
65                  70                  75                  80  
Leu Pro Val Asp Phe Phe Ala His Leu Arg Tyr Gly Leu Leu Gly Leu
                85                  90                  95      
Gly Asp Ser Glu Tyr Thr Tyr Phe Cys Asn Gly Gly Lys Ile Ile Asp
            100                 105                 110         
Lys Arg Leu Gln Glu Leu Gly Ala Arg His Phe Tyr Asp Thr Gly His
        115                 120                 125             
Ala Asp Asp Cys Val Gly Leu Glu Leu Val Val Glu Pro Trp Ile Ala
    130                 135                 140                 
Gly Leu Trp Pro Ala Leu Arg Lys His Phe Arg Ser Ser Arg Gly Gln
145                 150                 155                 160 
Glu Glu Ile Ser Gly Ala Leu Pro Val Ala Ser Pro Ala Ser Ser Arg
                165                 170                 175     
Thr Asp Leu Val Lys Ser Glu Leu Leu His Ile Glu Ser Gln Val Glu
            180                 185                 190         
Leu Leu Arg Phe Asp Asp Ser Gly Arg Lys Asp Ser Glu Val Leu Lys
        195                 200                 205             
Gln Asn Ala Val Asn Ser Asn Gln Ser Asn Val Val Ile Glu Asp Phe
    210                 215                 220                 
Glu Ser Ser Leu Thr Arg Ser Val Pro Pro Leu Ser Gln Ala Ser Leu
225                 230                 235                 240 
Asn Ile Pro Gly Leu Pro Pro Glu Tyr Leu Gln Val His Leu Gln Glu
                245                 250                 255     
Ser Leu Gly Gln Glu Glu Ser Gln Val Ser Val Thr Ser Ala Asp Pro
            260                 265                 270         
Val Phe Gln Val Pro Ile Ser Lys Ala Val Gln Leu Thr Thr Asn Asp
        275                 280                 285             
Ala Ile Lys Thr Thr Leu Leu Val Glu Leu Asp Ile Ser Asn Thr Asp
    290                 295                 300                 
Phe Ser Tyr Gln Pro Gly Asp Ala Phe Ser Val Ile Cys Pro Asn Ser
305                 310                 315                 320 
Asp Ser Glu Val Gln Ser Leu Leu Gln Arg Leu Gln Leu Glu Asp Lys
                325                 330                 335     
Arg Glu His Cys Val Leu Leu Lys Ile Lys Ala Asp Thr Lys Lys Lys
            340                 345                 350         
Gly Ala Thr Leu Pro Gln His Ile Pro Ala Gly Cys Ser Leu Gln Phe
        355                 360                 365             
Ile Phe Thr Trp Cys Leu Glu Ile Arg Ala Ile Pro Lys Lys Ala Phe
    370                 375                 380                 
Leu Arg Ala Leu Val Asp Tyr Thr Ser Asp Ser Ala Glu Lys Arg Arg
385                 390                 395                 400 
Leu Gln Glu Leu Cys Ser Lys Gln Gly Ala Ala Asp Tyr Ser Arg Phe
                405                 410                 415     
Val Arg Asp Ala Cys Ala Cys Leu Leu Asp Leu Leu Leu Ala Phe Pro
            420                 425                 430         
Ser Cys Gln Pro Pro Leu Ser Leu Leu Leu Glu His Leu Pro Lys Leu
        435                 440                 445             
Gln Pro Arg Pro Tyr Ser Cys Ala Ser Ser Ser Leu Phe His Pro Gly
    450                 455                 460                 
Lys Leu His Phe Val Phe Asn Ile Val Glu Phe Leu Ser Thr Ala Thr
465                 470                 475                 480 
Thr Glu Val Leu Arg Lys Gly Val Cys Thr Gly Trp Leu Ala Leu Leu
                485                 490                 495     
Val Ala Ser Val Leu Gln Pro Asn Ile His Ala Ser His Glu Asp Ser
            500                 505                 510         
Gly Lys Ala Leu Ala Pro Lys Ile Ser Ile Ser Pro Arg Thr Thr Asn
        515                 520                 525             
Ser Phe His Leu Pro Asp Asp Pro Ser Ile Pro Ile Ile Met Val Gly
    530                 535                 540                 
Pro Gly Thr Gly Ile Ala Pro Phe Ile Gly Phe Leu Gln His Arg Glu
545                 550                 555                 560 
Lys Leu Gln Glu Gln His Pro Asp Gly Asn Phe Gly Ala Met Trp Leu
                565                 570                 575     
Phe Phe Gly Cys Arg His Lys Asp Arg Asp Tyr Leu Phe Arg Lys Glu
            580                 585                 590         
Leu Arg His Phe Leu Lys His Gly Ile Leu Thr His Leu Lys Val Ser
        595                 600                 605             
Phe Ser Arg Asp Ala Pro Val Gly Glu Glu Glu Ala Pro Ala Lys Tyr
    610                 615                 620                 
Val Gln Asp Asn Ile Gln Leu His Gly Gln Gln Val Ala Arg Ile Leu
625                 630                 635                 640 
Leu Gln Glu Asn Gly His Ile Tyr Val Cys Gly Asp Ala Lys Asn Met
                645                 650                 655     
Ala Lys Asp Val His Asp Ala Leu Val Gln Ile Ile Ser Lys Glu Val
            660                 665                 670         
Gly Val Glu Lys Leu Glu Ala Met Lys Thr Leu Ala Thr Leu Lys Glu
        675                 680                 685             
Glu Lys Arg Tyr Leu Gln Asp Ile Trp Ser
    690                 695             


<210> 7
<211> 52
<212> DNA
<213> Homo sapiens

<400> 7
cttgaaggag aaggtgtctg cgggagycga tttcatcatc acgcagcttt tc         52

<210> 8
<211> 52
<212> DNA
<213> Homo sapiens

<400> 8
cgaggccttt gccctgtgga ttgagcrgtg gggaaagctg tatgaggagg ag         52

<210> 9
<211> 52
<212> DNA
<213> Homo sapiens

<400> 9
ggaagaatat gaagatatta gacaggrcca ttatgagtct ctcaaggtaa gt         52

<210> 10
<211> 52
<212> DNA
<213> Homo sapiens

<400> 10
caggcaaagg ccatcgcaga agaaatrtgt gagcaagctg tggtacatgg at         52

<210> 11
<211> 52
<212> DNA
<213> Homo sapiens

<400> 11
taagttccat tccatctcag cccgaartgt tttcagagcc ggagacctca ca         52

<210> 12
<211> 52
<212> DNA
<213> Homo sapiens

<400> 12
ctgctgctgg tatcagcctg gaggaartga gtgacatcag ttctcagcat ta         52

<210> 13
<211> 51
<212> DNA
<213> Homo sapiens

<400> 13
accaatcaca acaaggcaga taaagwagga tgagttgtca gattttgata a          51

<210> 14
<211> 52
<212> DNA
<213> Homo sapiens

<400> 14
gcttcggagc tggagcgcat gaatccyggc ccaggcggga agctgggaca cg         52

<210> 15
<211> 52
<212> DNA
<213> Homo sapiens

<400> 15
aagctgagaa catcaagaag ttcttayagt aagtacatcc tcgaaagttt at         52

<210> 16
<211> 52
<212> DNA
<213> Homo sapiens

<400> 16
gggagggcac ccgcagaggc ctgcgcrctg acactgctga gtggctctgc tc         52

<210> 17
<211> 52
<212> DNA
<213> Homo sapiens

<400> 17
tgaccccgag ctccggtcct ggcggcrcct cgtgtgctac ctttgcttct ac         52

<210> 18
<211> 52
<212> DNA
<213> Homo sapiens

<400> 18
caataggagc gtgtgtttga acagtayacg ccaaacttca gtcattcaag ta         52

<210> 19
<211> 52
<212> DNA
<213> Homo sapiens

<400> 19
ggcctaatca atccttctca tcttttrtac ccaccttttg caggaaacct gt         52

<210> 20
<211> 52
<212> DNA
<213> Homo sapiens

<400> 20
ctgactctcc ccgacccgtc ccaccayggt ctccacagca ctcccgacag cc         52

<210> 21
<211> 52
<212> DNA
<213> Homo sapiens

<400> 21
gtccctgcag tttaattatc ctcaacrtta ctgccatacc ctacattttt gg         52

<210> 22
<211> 52
<212> DNA
<213> Homo sapiens

<400> 22
ctcacagttt gtggttgaga ctaagtrtga caacagtggc actttgtggt cc         52

<210> 23
<211> 52
<212> DNA
<213> Homo sapiens

<400> 23
accaaggagc agcgcatcct gaaccaygtg ctgcagcatg cggagcccgg ga         52

<210> 24
<211> 52
<212> DNA
<213> Homo sapiens

<400> 24
cccagcggat ggtggatttc gctggcrtga aggacaaggt gtgcatgcct ga         52

<210> 25
<211> 52
<212> DNA
<213> Homo sapiens

<400> 25
taatatggcc accccaactt tcgtatsatt actgtttgtg tggtattatc tt         52

<210> 26
<211> 52
<212> DNA
<213> Homo sapiens

<400> 26
atcagcccta gatgcttgac cagctcytcg ggcctcacct cctggttctt cc         52

<210> 27
<211> 52
<212> DNA
<213> Homo sapiens

<400> 27
ctgggccaac aagcttgagt gcgatcyggt ctgcaatgat ggaggaattg cc         52

<210> 28
<211> 271
<212> PRT
<213> Homo sapiens

<220> 
<221> VARIANT        
<222> (158)...(158)
<223> Xaa = Val or Met

<400> 28
Met Pro Glu Ala Pro Pro Leu Leu Leu Ala Ala Val Leu Leu Gly Leu
 1               5                  10                  15      
Val Leu Leu Val Val Leu Leu Leu Leu Leu Arg His Trp Gly Trp Gly
            20                  25                  30          
Leu Cys Leu Ile Gly Trp Asn Glu Phe Ile Leu Gln Pro Ile His Asn
        35                  40                  45              
Leu Leu Met Gly Asp Thr Lys Glu Gln Arg Ile Leu Asn His Val Leu
    50                  55                  60                  
Gln His Ala Glu Pro Gly Asn Ala Gln Ser Val Leu Glu Ala Ile Asp
65                  70                  75                  80  
Thr Tyr Cys Glu Gln Lys Glu Trp Ala Met Asn Val Gly Asp Lys Lys
                85                  90                  95      
Gly Lys Ile Val Asp Ala Val Ile Gln Glu His Gln Pro Ser Val Leu
            100                 105                 110         
Leu Glu Leu Gly Ala Tyr Cys Gly Tyr Ser Ala Val Arg Met Ala Arg
        115                 120                 125             
Leu Leu Ser Pro Gly Ala Arg Leu Ile Thr Ile Glu Ile Asn Pro Asp
    130                 135                 140                 
Cys Ala Ala Ile Thr Gln Arg Met Val Asp Phe Ala Gly Xaa Lys Asp
145                 150                 155                 160 
Lys Val Thr Leu Val Val Gly Ala Ser Gln Asp Ile Ile Pro Gln Leu
                165                 170                 175     
Lys Lys Lys Tyr Asp Val Asp Thr Leu Asp Met Val Phe Leu Asp His
            180                 185                 190         
Trp Lys Asp Arg Tyr Leu Pro Asp Thr Leu Leu Leu Glu Glu Cys Gly
        195                 200                 205             
Leu Leu Arg Lys Gly Thr Val Leu Leu Ala Asp Asn Val Ile Cys Pro
    210                 215                 220                 
Gly Ala Pro Asp Phe Leu Ala His Val Arg Gly Ser Ser Cys Phe Glu
225                 230                 235                 240 
Cys Thr His Tyr Gln Ser Phe Leu Glu Tyr Arg Glu Val Val Asp Gly
                245                 250                 255     
Leu Glu Lys Ala Ile Tyr Lys Gly Pro Gly Ser Glu Ala Gly Pro
            260                 265                 270     

