                         SEQUENCE LISTING

<110>  Mount Sinai School of Medicine
 
<120>  INHIBITORS AND AGONISTS OF THE LOW DENSITY LIPOPROTEIN
	RECEPTOR RELATED DOMAIN OF LRP6 AND/OR LRP5 AND USES THEREOF

<130>  27527-0106WO1

<150>  61/602,853
<151>  2012-02-24

<160>  16    

<170>  PatentIn version 3.5

<210>  1
<211>  4909
<212>  DNA
<213>  Homo sapiens

<400>  1
tcgccggtga gagaagagaa cgcgagaagg gaagatgggg gccgtcctga ggagcctcct       60

ggcctgcagc ttctgtgtgc tcctgagagc ggcccctttg ttgctttatg caaacagacg      120

ggacttgcga ttggttgatg ctacaaatgg caaagagaat gctacgattg tagttggagg      180

cttggaggat gcagctgcgg tggactttgt gtttagtcat ggcttgatat actggagtga      240

tgtcagcgaa gaagccatta aacgaacaga atttaacaaa actgagagtg tgcagaatgt      300

tgttgtttct ggattattgt cccccgatgg gctggcatgt gattggcttg gagaaaaatt      360

gtactggaca gattctgaaa ctaatcggat tgaagtttct aatttagatg gatctttacg      420

aaaagtttta ttttggcaag agttggatca acccagagct attgccttag atccttcaag      480

tgggttcatg tactggacag actggggaga agtgccaaag atagaacgtg ctggaatgga      540

tggttcaagt cgcttcatta taataaacag tgaaatttac tggccaaatg gactgacttt      600

ggattatgaa gaacaaaagc tttattgggc agatgcaaaa cttaatttca tccacaaatc      660

aaatctggat ggaacaaatc ggcaggcagt ggttaaaggt tcccttccac atccttttgc      720

cttgacgtta tttgaggaca tattgtactg gactgactgg agcacacact ccattttggc      780

ttgcaacaag tatactggtg agggtctgcg tgaaatccat tctgacatct tctctcccat      840

ggatatacat gccttcagcc aacagaggca gccaaatgcc acaaatccat gtggaattga      900

caatgggggt tgttcccatt tgtgtttgat gtctccagtc aagccttttt atcagtgtgc      960

ttgccccact ggggtcaaac tcctggagaa tggaaaaacc tgcaaagatg gtgccacaga     1020

attattgctt ttagctcgaa ggacagactt gagacgcatt tctttggata caccagattt     1080

tacagacatt gttctgcagt tagaagacat ccgtcatgcc attgccatag attacgatcc     1140

tgtggaaggc tacatctact ggactgatga tgaagtgagg gccatacgcc gttcatttat     1200

agatggatct ggcagtcagt ttgtggtcac tgctcaaatt gcccatcctg atggtattgc     1260

tgtggactgg gttgcacgaa atctttattg gacagacact ggcactgatc gaatagaagt     1320

gacaaggctc aatgggacca tgaggaagat cttgatttca gaggacttag aggaaccccg     1380

ggctattgtg ttagatccca tggttgggta catgtattgg actgactggg gagaaattcc     1440

gaaaattgag cgagcagctc tggatggttc tgaccgtgta gtattggtta acacttctct     1500

tggttggcca aatggtttag ccttggatta tgatgaaggc aaaatatact ggggagatgc     1560

caaaacagac aagattgagg ttatgaatac tgatggcact gggagacgag tactagtgga     1620

agacaaaatt cctcacatat ttggatttac tttgttgggt gactatgttt actggactga     1680

ctggcagagg cgtagcattg aaagagttca taaacgaagt gcagagaggg aagtgatcat     1740

agatcagctg cctgacctca tgggcctaaa ggctacaaat gttcatcgag tgattggttc     1800

caacccctgt gctgaggaaa acgggggatg tagccatctc tgcctctata gacctcaggg     1860

ccttcgctgt gcttgcccta ttggctttga actcatcagt gacatgaaga cctgcattgt     1920

cccagaggct ttccttttgt tttcacggag agcagatatc agacgaattt ctctggaaac     1980

aaacaataat aatgtggcta ttccactcac tggtgtcaaa gaagcttctg ctttggattt     2040

tgatgtgaca gacaaccgaa tttattggac tgatatatca ctcaagacca tcagcagagc     2100

ctttatgaat ggcagtgcac tggaacatgt ggtagaattc ggcttagatt atccagaagg     2160

catggcagta gactggcttg ggaagaactt gtactgggca gacacaggaa cgaatcgaat     2220

tgaggtgtca aagttggatg ggcagcaccg acaagttttg gtgtggaaag acctagatag     2280

tcccagagct ctcgcgttgg accctgccga aggatttatg tattggactg aatggggtgg     2340

aaaacctaag atagacagag ctgcaatgga tggaagtgaa cgtactacct tagttccaaa     2400

tgtggggcgg gcaaacggcc taactattga ttatgctaaa aggaggcttt attggacaga     2460

cctggacacc aacttaatag aatcttcaaa tatgcttggg ctcaaccgtg aagttatagc     2520

agatgacttg cctcatcctt ttggcttaac tcagtaccaa gattatatct actggacgga     2580

ctggagccga cgcagcattg agcgtgccaa caaaaccagt ggccaaaacc gcaccatcat     2640

tcagggccat ttggattatg tgatggacat cctcgtcttt cactcatctc gacagtcagg     2700

gtggaatgaa tgtgcttcca gcaatgggca ctgctcccac ctctgcttgg ctgtgccagt     2760

tgggggtttt gtttgtggat gccctgccca ctactctctt aatgctgaca acaggacttg     2820

tagtgctcct acgactttcc tgctcttcag tcaaaagagt gccatcaacc gcatggtgat     2880

tgatgaacaa cagagccccg acatcatcct tcccatccac agccttcgga atgtccgggc     2940

cattgactat gacccactgg acaagcaact ctattggatt gactcacgac aaaacatgat     3000

ccgaaaggca caagaagatg gcagccaggg ctttactgtg gttgtgagct cagttccgag     3060

tcagaacctg gaaatacaac cctatgacct cagcattgat atttacagcc gctacatcta     3120

ctggacttgt gaggctacca atgtcattaa tgtgacaaga ttagatggga gatcagttgg     3180

agtggtgctg aaaggcgagc aggacagacc tcgagccgtt gtggtaaacc cagagaaagg     3240

gtatatgtat tttaccaatc ttcaggaaag gtctcctaaa attgaacggg ctgctttgga     3300

tgggacagaa cgggaggtcc tctttttcag tggcttaagt aaaccaattg ctttagccct     3360

tgatagcagg ctgggcaagc tcttttgggc tgattcagat ctccggcgaa ttgaaagcag     3420

tgatctctca ggtgctaacc ggatagtatt agaagactcc aatatcttgc agcctgtggg     3480

acttactgtg tttgaaaact ggctctattg gattgataaa cagcagcaaa tgattgaaaa     3540

aattgacatg acaggtcgag agggtagaac caaagtccaa gctcgaattg cccagcttag     3600

tgacattcat gcagtaaagg agctgaacct tcaagaatac agacagcacc cttgtgctca     3660

ggataatggt ggctgttcac atatttgtct tgtaaagggg gatggtacta caaggtgttc     3720

ttgccccatg cacctggttc tacttcaaga tgagctatca tgtggagaac ctccaacatg     3780

ttctcctcag cagtttactt gtttcacggg ggaaattgac tgtatccctg tggcttggcg     3840

gtgcgatggg tttactgaat gtgaagacca cagtgatgaa ctcaattgtc ctgtatgctc     3900

agagtcccag ttccagtgtg ccagtgggca gtgtattgat ggtgccctcc gatgcaatgg     3960

agatgcaaac tgccaggaca aatcagatga gaagaactgt gaagtgcttt gtttaattga     4020

tcagttccgc tgtgccaatg gtcagtgcat tggaaagcac aagaagtgtg atcataatgt     4080

ggattgcagt gacaagtcag atgaactgga ttgttatccg actgaagaac cagcaccaca     4140

ggccaccaat acagttggtt ctgttattgg cgtaattgtc accatttttg tgtctggaac     4200

tgtatacttt atctgccaga ggatgttgtg tccacgtatg aagggagatg gggaaactat     4260

gactaatgac tatgtagttc atggaccagc ttctgtgcct cttggttatg tgccacaccc     4320

aagttctttg tcaggatctc ttccaggaat gtctcgaggt aaatcaatga tcagctccct     4380

cagtatcatg gggggaagca gtggaccccc ctatgaccga gcccatgtta caggagcatc     4440

atcaagtagt tcttcaagca ccaaaggcac ttacttccct gcaattttga accctccacc     4500

atccccagcc acagagcgat cacattacac tatggaattt ggatattctt caaacagtcc     4560

ttccactcat aggtcataca gctacaggcc atatagctac cggcactttg caccccccac     4620

cacaccctgc agcacagatg tttgtgacag tgactatgct cctagtcgga gaatgacctc     4680

agtggcaaca gccaagggct ataccagtga cttgaactat gattcagaac ctgtgccccc     4740

acctcccaca ccccgaagcc aatacttgtc agcagaggag aactatgaaa gctgcccacc     4800

ttctccatac acagagagga gctattctca tcacctctac ccaccgccac cctctccctg     4860

tacagactcc tcctgaggag gggccctcct cctctgactg cctccaacg                 4909


<210>  2
<211>  1613
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Gly Ala Val Leu Arg Ser Leu Leu Ala Cys Ser Phe Cys Val Leu 
1               5                   10                  15      


Leu Arg Ala Ala Pro Leu Leu Leu Tyr Ala Asn Arg Arg Asp Leu Arg 
            20                  25                  30          


Leu Val Asp Ala Thr Asn Gly Lys Glu Asn Ala Thr Ile Val Val Gly 
        35                  40                  45              


Gly Leu Glu Asp Ala Ala Ala Val Asp Phe Val Phe Ser His Gly Leu 
    50                  55                  60                  


Ile Tyr Trp Ser Asp Val Ser Glu Glu Ala Ile Lys Arg Thr Glu Phe 
65                  70                  75                  80  


Asn Lys Thr Glu Ser Val Gln Asn Val Val Val Ser Gly Leu Leu Ser 
                85                  90                  95      


Pro Asp Gly Leu Ala Cys Asp Trp Leu Gly Glu Lys Leu Tyr Trp Thr 
            100                 105                 110         


Asp Ser Glu Thr Asn Arg Ile Glu Val Ser Asn Leu Asp Gly Ser Leu 
        115                 120                 125             


Arg Lys Val Leu Phe Trp Gln Glu Leu Asp Gln Pro Arg Ala Ile Ala 
    130                 135                 140                 


Leu Asp Pro Ser Ser Gly Phe Met Tyr Trp Thr Asp Trp Gly Glu Val 
145                 150                 155                 160 


Pro Lys Ile Glu Arg Ala Gly Met Asp Gly Ser Ser Arg Phe Ile Ile 
                165                 170                 175     


Ile Asn Ser Glu Ile Tyr Trp Pro Asn Gly Leu Thr Leu Asp Tyr Glu 
            180                 185                 190         


Glu Gln Lys Leu Tyr Trp Ala Asp Ala Lys Leu Asn Phe Ile His Lys 
        195                 200                 205             


Ser Asn Leu Asp Gly Thr Asn Arg Gln Ala Val Val Lys Gly Ser Leu 
    210                 215                 220                 


Pro His Pro Phe Ala Leu Thr Leu Phe Glu Asp Ile Leu Tyr Trp Thr 
225                 230                 235                 240 


Asp Trp Ser Thr His Ser Ile Leu Ala Cys Asn Lys Tyr Thr Gly Glu 
                245                 250                 255     


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


Ala Phe Ser Gln Gln Arg Gln Pro Asn Ala Thr Asn Pro Cys Gly Ile 
        275                 280                 285             


Asp Asn Gly Gly Cys Ser His Leu Cys Leu Met Ser Pro Val Lys Pro 
    290                 295                 300                 


Phe Tyr Gln Cys Ala Cys Pro Thr Gly Val Lys Leu Leu Glu Asn Gly 
305                 310                 315                 320 


Lys Thr Cys Lys Asp Gly Ala Thr Glu Leu Leu Leu Leu Ala Arg Arg 
                325                 330                 335     


Thr Asp Leu Arg Arg Ile Ser Leu Asp Thr Pro Asp Phe Thr Asp Ile 
            340                 345                 350         


Val Leu Gln Leu Glu Asp Ile Arg His Ala Ile Ala Ile Asp Tyr Asp 
        355                 360                 365             


Pro Val Glu Gly Tyr Ile Tyr Trp Thr Asp Asp Glu Val Arg Ala Ile 
    370                 375                 380                 


Arg Arg Ser Phe Ile Asp Gly Ser Gly Ser Gln Phe Val Val Thr Ala 
385                 390                 395                 400 


Gln Ile Ala His Pro Asp Gly Ile Ala Val Asp Trp Val Ala Arg Asn 
                405                 410                 415     


Leu Tyr Trp Thr Asp Thr Gly Thr Asp Arg Ile Glu Val Thr Arg Leu 
            420                 425                 430         


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


Arg Ala Ile Val Leu Asp Pro Met Val Gly Tyr Met Tyr Trp Thr Asp 
    450                 455                 460                 


Trp Gly Glu Ile Pro Lys Ile Glu Arg Ala Ala Leu Asp Gly Ser Asp 
465                 470                 475                 480 


Arg Val Val Leu Val Asn Thr Ser Leu Gly Trp Pro Asn Gly Leu Ala 
                485                 490                 495     


Leu Asp Tyr Asp Glu Gly Lys Ile Tyr Trp Gly Asp Ala Lys Thr Asp 
            500                 505                 510         


Lys Ile Glu Val Met Asn Thr Asp Gly Thr Gly Arg Arg Val Leu Val 
        515                 520                 525             


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


Val Tyr Trp Thr Asp Trp Gln Arg Arg Ser Ile Glu Arg Val His Lys 
545                 550                 555                 560 


Arg Ser Ala Glu Arg Glu Val Ile Ile Asp Gln Leu Pro Asp Leu Met 
                565                 570                 575     


Gly Leu Lys Ala Thr Asn Val His Arg Val Ile Gly Ser Asn Pro Cys 
            580                 585                 590         


Ala Glu Glu Asn Gly Gly Cys Ser His Leu Cys Leu Tyr Arg Pro Gln 
        595                 600                 605             


Gly Leu Arg Cys Ala Cys Pro Ile Gly Phe Glu Leu Ile Ser Asp Met 
    610                 615                 620                 


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


Asp Ile Arg Arg Ile Ser Leu Glu Thr Asn Asn Asn Asn Val Ala Ile 
                645                 650                 655     


Pro Leu Thr Gly Val Lys Glu Ala Ser Ala Leu Asp Phe Asp Val Thr 
            660                 665                 670         


Asp Asn Arg Ile Tyr Trp Thr Asp Ile Ser Leu Lys Thr Ile Ser Arg 
        675                 680                 685             


Ala Phe Met Asn Gly Ser Ala Leu Glu His Val Val Glu Phe Gly Leu 
    690                 695                 700                 


Asp Tyr Pro Glu Gly Met Ala Val Asp Trp Leu Gly Lys Asn Leu Tyr 
705                 710                 715                 720 


Trp Ala Asp Thr Gly Thr Asn Arg Ile Glu Val Ser Lys Leu Asp Gly 
                725                 730                 735     


Gln His Arg Gln Val Leu Val Trp Lys Asp Leu Asp Ser Pro Arg Ala 
            740                 745                 750         


Leu Ala Leu Asp Pro Ala Glu Gly Phe Met Tyr Trp Thr Glu Trp Gly 
        755                 760                 765             


Gly Lys Pro Lys Ile Asp Arg Ala Ala Met Asp Gly Ser Glu Arg Thr 
    770                 775                 780                 


Thr Leu Val Pro Asn Val Gly Arg Ala Asn Gly Leu Thr Ile Asp Tyr 
785                 790                 795                 800 


Ala Lys Arg Arg Leu Tyr Trp Thr Asp Leu Asp Thr Asn Leu Ile Glu 
                805                 810                 815     


Ser Ser Asn Met Leu Gly Leu Asn Arg Glu Val Ile Ala Asp Asp Leu 
            820                 825                 830         


Pro His Pro Phe Gly Leu Thr Gln Tyr Gln Asp Tyr Ile Tyr Trp Thr 
        835                 840                 845             


Asp Trp Ser Arg Arg Ser Ile Glu Arg Ala Asn Lys Thr Ser Gly Gln 
    850                 855                 860                 


Asn Arg Thr Ile Ile Gln Gly His Leu Asp Tyr Val Met Asp Ile Leu 
865                 870                 875                 880 


Val Phe His Ser Ser Arg Gln Ser Gly Trp Asn Glu Cys Ala Ser Ser 
                885                 890                 895     


Asn Gly His Cys Ser His Leu Cys Leu Ala Val Pro Val Gly Gly Phe 
            900                 905                 910         


Val Cys Gly Cys Pro Ala His Tyr Ser Leu Asn Ala Asp Asn Arg Thr 
        915                 920                 925             


Cys Ser Ala Pro Thr Thr Phe Leu Leu Phe Ser Gln Lys Ser Ala Ile 
    930                 935                 940                 


Asn Arg Met Val Ile Asp Glu Gln Gln Ser Pro Asp Ile Ile Leu Pro 
945                 950                 955                 960 


Ile His Ser Leu Arg Asn Val Arg Ala Ile Asp Tyr Asp Pro Leu Asp 
                965                 970                 975     


Lys Gln Leu Tyr Trp Ile Asp Ser Arg Gln Asn Met Ile Arg Lys Ala 
            980                 985                 990         


Gln Glu Asp Gly Ser Gln Gly Phe  Thr Val Val Val Ser  Ser Val Pro 
        995                 1000                 1005             


Ser Gln  Asn Leu Glu Ile Gln  Pro Tyr Asp Leu Ser  Ile Asp Ile 
    1010                 1015                 1020             


Tyr Ser  Arg Tyr Ile Tyr Trp  Thr Cys Glu Ala Thr  Asn Val Ile 
    1025                 1030                 1035             


Asn Val  Thr Arg Leu Asp Gly  Arg Ser Val Gly Val  Val Leu Lys 
    1040                 1045                 1050             


Gly Glu  Gln Asp Arg Pro Arg  Ala Val Val Val Asn  Pro Glu Lys 
    1055                 1060                 1065             


Gly Tyr  Met Tyr Phe Thr Asn  Leu Gln Glu Arg Ser  Pro Lys Ile 
    1070                 1075                 1080             


Glu Arg  Ala Ala Leu Asp Gly  Thr Glu Arg Glu Val  Leu Phe Phe 
    1085                 1090                 1095             


Ser Gly  Leu Ser Lys Pro Ile  Ala Leu Ala Leu Asp  Ser Arg Leu 
    1100                 1105                 1110             


Gly Lys  Leu Phe Trp Ala Asp  Ser Asp Leu Arg Arg  Ile Glu Ser 
    1115                 1120                 1125             


Ser Asp  Leu Ser Gly Ala Asn  Arg Ile Val Leu Glu  Asp Ser Asn 
    1130                 1135                 1140             


Ile Leu  Gln Pro Val Gly Leu  Thr Val Phe Glu Asn  Trp Leu Tyr 
    1145                 1150                 1155             


Trp Ile  Asp Lys Gln Gln Gln  Met Ile Glu Lys Ile  Asp Met Thr 
    1160                 1165                 1170             


Gly Arg  Glu Gly Arg Thr Lys  Val Gln Ala Arg Ile  Ala Gln Leu 
    1175                 1180                 1185             


Ser Asp  Ile His Ala Val Lys  Glu Leu Asn Leu Gln  Glu Tyr Arg 
    1190                 1195                 1200             


Gln His  Pro Cys Ala Gln Asp  Asn Gly Gly Cys Ser  His Ile Cys 
    1205                 1210                 1215             


Leu Val  Lys Gly Asp Gly Thr  Thr Arg Cys Ser Cys  Pro Met His 
    1220                 1225                 1230             


Leu Val  Leu Leu Gln Asp Glu  Leu Ser Cys Gly Glu  Pro Pro Thr 
    1235                 1240                 1245             


Cys Ser  Pro Gln Gln Phe Thr  Cys Phe Thr Gly Glu  Ile Asp Cys 
    1250                 1255                 1260             


Ile Pro  Val Ala Trp Arg Cys  Asp Gly Phe Thr Glu  Cys Glu Asp 
    1265                 1270                 1275             


His Ser  Asp Glu Leu Asn Cys  Pro Val Cys Ser Glu  Ser Gln Phe 
    1280                 1285                 1290             


Gln Cys  Ala Ser Gly Gln Cys  Ile Asp Gly Ala Leu  Arg Cys Asn 
    1295                 1300                 1305             


Gly Asp  Ala Asn Cys Gln Asp  Lys Ser Asp Glu Lys  Asn Cys Glu 
    1310                 1315                 1320             


Val Leu  Cys Leu Ile Asp Gln  Phe Arg Cys Ala Asn  Gly Gln Cys 
    1325                 1330                 1335             


Ile Gly  Lys His Lys Lys Cys  Asp His Asn Val Asp  Cys Ser Asp 
    1340                 1345                 1350             


Lys Ser  Asp Glu Leu Asp Cys  Tyr Pro Thr Glu Glu  Pro Ala Pro 
    1355                 1360                 1365             


Gln Ala  Thr Asn Thr Val Gly  Ser Val Ile Gly Val  Ile Val Thr 
    1370                 1375                 1380             


Ile Phe  Val Ser Gly Thr Val  Tyr Phe Ile Cys Gln  Arg Met Leu 
    1385                 1390                 1395             


Cys Pro  Arg Met Lys Gly Asp  Gly Glu Thr Met Thr  Asn Asp Tyr 
    1400                 1405                 1410             


Val Val  His Gly Pro Ala Ser  Val Pro Leu Gly Tyr  Val Pro His 
    1415                 1420                 1425             


Pro Ser  Ser Leu Ser Gly Ser  Leu Pro Gly Met Ser  Arg Gly Lys 
    1430                 1435                 1440             


Ser Met  Ile Ser Ser Leu Ser  Ile Met Gly Gly Ser  Ser Gly Pro 
    1445                 1450                 1455             


Pro Tyr  Asp Arg Ala His Val  Thr Gly Ala Ser Ser  Ser Ser Ser 
    1460                 1465                 1470             


Ser Ser  Thr Lys Gly Thr Tyr  Phe Pro Ala Ile Leu  Asn Pro Pro 
    1475                 1480                 1485             


Pro Ser  Pro Ala Thr Glu Arg  Ser His Tyr Thr Met  Glu Phe Gly 
    1490                 1495                 1500             


Tyr Ser  Ser Asn Ser Pro Ser  Thr His Arg Ser Tyr  Ser Tyr Arg 
    1505                 1510                 1515             


Pro Tyr  Ser Tyr Arg His Phe  Ala Pro Pro Thr Thr  Pro Cys Ser 
    1520                 1525                 1530             


Thr Asp  Val Cys Asp Ser Asp  Tyr Ala Pro Ser Arg  Arg Met Thr 
    1535                 1540                 1545             


Ser Val  Ala Thr Ala Lys Gly  Tyr Thr Ser Asp Leu  Asn Tyr Asp 
    1550                 1555                 1560             


Ser Glu  Pro Val Pro Pro Pro  Pro Thr Pro Arg Ser  Gln Tyr Leu 
    1565                 1570                 1575             


Ser Ala  Glu Glu Asn Tyr Glu  Ser Cys Pro Pro Ser  Pro Tyr Thr 
    1580                 1585                 1590             


Glu Arg  Ser Tyr Ser His His  Leu Tyr Pro Pro Pro  Pro Ser Pro 
    1595                 1600                 1605             


Cys Thr  Asp Ser Ser 
    1610             


<210>  3
<211>  115
<212>  PRT
<213>  Homo sapiens

<400>  3

Pro Thr Cys Ser Pro Gln Gln Phe Thr Cys Phe Thr Gly Glu Ile Asp 
1               5                   10                  15      


Cys Ile Pro Val Ala Trp Arg Cys Asp Gly Phe Thr Glu Cys Glu Asp 
            20                  25                  30          


His Ser Asp Glu Leu Asn Cys Pro Val Cys Ser Glu Ser Gln Phe Gln 
        35                  40                  45              


Cys Ala Ser Gly Gln Cys Ile Asp Gly Ala Leu Arg Cys Asn Gly Asp 
    50                  55                  60                  


Ala Asn Cys Gln Asp Lys Ser Asp Glu Lys Asn Cys Glu Val Leu Cys 
65                  70                  75                  80  


Leu Ile Asp Gln Phe Arg Cys Ala Asn Gly Gln Cys Ile Gly Lys His 
                85                  90                  95      


Lys Lys Cys Asp His Asn Val Asp Cys Ser Asp Lys Ser Asp Glu Leu 
            100                 105                 110         


Asp Cys Tyr 
        115 


<210>  4
<211>  40
<212>  PRT
<213>  Homo sapiens

<400>  4

Pro Thr Cys Ser Pro Gln Gln Phe Thr Cys Phe Thr Gly Glu Ile Asp 
1               5                   10                  15      


Cys Ile Pro Val Ala Trp Arg Cys Asp Gly Phe Thr Glu Cys Glu Asp 
            20                  25                  30          


His Ser Asp Glu Leu Asn Cys Pro 
        35                  40  


<210>  5
<211>  37
<212>  PRT
<213>  Homo sapiens

<400>  5

Val Cys Ser Glu Ser Gln Phe Gln Cys Ala Ser Gly Gln Cys Ile Asp 
1               5                   10                  15      


Gly Ala Leu Arg Cys Asn Gly Asp Ala Asn Cys Gln Asp Lys Ser Asp 
            20                  25                  30          


Glu Lys Asn Cys Glu 
        35          


<210>  6
<211>  37
<212>  PRT
<213>  Homo sapiens

<400>  6

Leu Cys Leu Ile Asp Gln Phe Arg Cys Ala Asn Gly Gln Cys Ile Gly 
1               5                   10                  15      


Lys His Lys Lys Cys Asp His Asn Val Asp Cys Ser Asp Lys Ser Asp 
            20                  25                  30          


Glu Leu Asp Cys Tyr 
        35          


<210>  7
<211>  5161
<212>  DNA
<213>  Homo sapiens

<400>  7
cgcgcgagga gccgccgccg ccgcgccatg gagcccgagt gagcgcggcg cgggcccgtc       60

cggccgccgg acaacatgga ggcagcgccg cccgggccgc cgtggccgct gctgctgctg      120

ctgctgctgc tgctggcgct gtgcggctgc ccggcccccg ccgcggcctc gccgctcctg      180

ctatttgcca accgccggga cgtacggctg gtggacgccg gcggagtcaa gctggagtcc      240

accatcgtgg tcagcggcct ggaggatgcg gccgcagtgg acttccagtt ttccaaggga      300

gccgtgtact ggacagacgt gagcgaggag gccatcaagc agacctacct gaaccagacg      360

ggggccgccg tgcagaacgt ggtcatctcc ggcctggtct ctcccgacgg cctcgcctgc      420

gactgggtgg gcaagaagct gtactggacg gactcagaga ccaaccgcat cgaggtggcc      480

aacctcaatg gcacatcccg gaaggtgctc ttctggcagg accttgacca gccgagggcc      540

atcgccttgg accccgctca cgggtacatg tactggacag actggggtga gacgccccgg      600

attgagcggg cagggatgga tggcagcacc cggaagatca ttgtggactc ggacatttac      660

tggcccaatg gactgaccat cgacctggag gagcagaagc tctactgggc tgacgccaag      720

ctcagcttca tccaccgtgc caacctggac ggctcgttcc ggcagaaggt ggtggagggc      780

agcctgacgc accccttcgc cctgacgctc tccggggaca ctctgtactg gacagactgg      840

cagacccgct ccatccatgc ctgcaacaag cgcactgggg ggaagaggaa ggagatcctg      900

agtgccctct actcacccat ggacatccag gtgctgagcc aggagcggca gcctttcttc      960

cacactcgct gtgaggagga caatggcggc tgctcccacc tgtgcctgct gtccccaagc     1020

gagcctttct acacatgcgc ctgccccacg ggtgtgcagc tgcaggacaa cggcaggacg     1080

tgtaaggcag gagccgagga ggtgctgctg ctggcccggc ggacggacct acggaggatc     1140

tcgctggaca cgccggactt caccgacatc gtgctgcagg tggacgacat ccggcacgcc     1200

attgccatcg actacgaccc gctagagggc tatgtctact ggacagatga cgaggtgcgg     1260

gccatccgca gggcgtacct ggacgggtct ggggcgcaga cgctggtcaa caccgagatc     1320

aacgaccccg atggcatcgc ggtcgactgg gtggcccgaa acctctactg gaccgacacg     1380

ggcacggacc gcatcgaggt gacgcgcctc aacggcacct cccgcaagat cctggtgtcg     1440

gaggacctgg acgagccccg agccatcgca ctgcaccccg tgatgggcct catgtactgg     1500

acagactggg gagagaaccc taaaatcgag tgtgccaact tggatgggca ggagcggcgt     1560

gtgctggtca atgcctccct cgggtggccc aacggcctgg ccctggacct gcaggagggg     1620

aagctctact ggggagacgc caagacagac aagatcgagg tgatcaatgt tgatgggacg     1680

aagaggcgga ccctcctgga ggacaagctc ccgcacattt ttgggttcac gctgctgggg     1740

gacttcatct actggactga ctggcagcgc cgcagcatcg agcgggtgca caaggtcaag     1800

gccagccggg acgtcatcat tgaccagctg cccgacctga tggggctcaa agctgtgaat     1860

gtggccaagg tcgtcggaac caacccgtgt gcggacagga acggggggtg cagccacctg     1920

tgcttcttca caccccacgc aacccggtgt ggctgcccca tcggcctgga gctgctgagt     1980

gacatgaaga cctgcatcgt gcctgaggcc ttcttggtct tcaccagcag agccgccatc     2040

cacaggatct ccctcgagac caataacaac gacgtggcca tcccgctcac gggcgtcaag     2100

gaggcctcag ccctggactt tgatgtgtcc aacaaccaca tctactggac agacgtcagc     2160

ctgaagacca tcagccgcgc cttcatgaac gggagctcgg tggagcacgt ggtggagttt     2220

ggccttgact accccgaggg catggccgtt gactggatgg gcaagaacct ctactgggcc     2280

gacactggga ccaacagaat cgaagtggcg cggctggacg ggcagttccg gcaagtcctc     2340

gtgtggaggg acttggacaa cccgaggtcg ctggccctgg atcccaccaa gggctacatc     2400

tactggaccg agtggggcgg caagccgagg atcgtgcggg ccttcatgga cgggaccaac     2460

tgcatgacgc tggtggacaa ggtgggccgg gccaacgacc tcaccattga ctacgctgac     2520

cagcgcctct actggaccga cctggacacc aacatgatcg agtcgtccaa catgctgggt     2580

caggagcggg tcgtgattgc cgacgatctc ccgcacccgt tcggtctgac gcagtacagc     2640

gattatatct actggacaga ctggaatctg cacagcattg agcgggccga caagactagc     2700

ggccggaacc gcaccctcat ccagggccac ctggacttcg tgatggacat cctggtgttc     2760

cactcctccc gccaggatgg cctcaatgac tgtatgcaca acaacgggca gtgtgggcag     2820

ctgtgccttg ccatccccgg cggccaccgc tgcggctgcg cctcacacta caccctggac     2880

cccagcagcc gcaactgcag cccgcccacc accttcttgc tgttcagcca gaaatctgcc     2940

atcagtcgga tgatcccgga cgaccagcac agcccggatc tcatcctgcc cctgcatgga     3000

ctgaggaacg tcaaagccat cgactatgac ccactggaca agttcatcta ctgggtggat     3060

gggcgccaga acatcaagcg agccaaggac gacgggaccc agccctttgt tttgacctct     3120

ctgagccaag gccaaaaccc agacaggcag ccccacgacc tcagcatcga catctacagc     3180

cggacactgt tctggacgtg cgaggccacc aataccatca acgtccacag gctgagcggg     3240

gaagccatgg gggtggtgct gcgtggggac cgcgacaagc ccagggccat cgtcgtcaac     3300

gcggagcgag ggtacctgta cttcaccaac atgcaggacc gggcagccaa gatcgaacgc     3360

gcagccctgg acggcaccga gcgcgaggtc ctcttcacca ccggcctcat ccgccctgtg     3420

gccctggtgg tggacaacac actgggcaag ctgttctggg tggacgcgga cctgaagcgc     3480

attgagagct gtgacctgtc aggggccaac cgcctgaccc tggaggacgc caacatcgtg     3540

cagcctctgg gcctgaccat ccttggcaag catctctact ggatcgaccg ccagcagcag     3600

atgatcgagc gtgtggagaa gaccaccggg gacaagcgga ctcgcatcca gggccgtgtc     3660

gcccacctca ctggcatcca tgcagtggag gaagtcagcc tggaggagtt ctcagcccac     3720

ccatgtgccc gtgacaatgg tggctgctcc cacatctgta ttgccaaggg tgatgggaca     3780

ccacggtgct catgcccagt ccacctcgtg ctcctgcaga acctgctgac ctgtggagag     3840

ccgcccacct gctccccgga ccagtttgca tgtgccacag gggagatcga ctgtatcccc     3900

ggggcctggc gctgtgacgg ctttcccgag tgcgatgacc agagcgacga ggagggctgc     3960

cccgtgtgct ccgccgccca gttcccctgc gcgcggggtc agtgtgtgga cctgcgcctg     4020

cgctgcgacg gcgaggcaga ctgtcaggac cgctcagacg aggcggactg tgacgccatc     4080

tgcctgccca accagttccg gtgtgcgagc ggccagtgtg tcctcatcaa acagcagtgc     4140

gactccttcc ccgactgtat cgacggctcc gacgagctca tgtgtgaaat caccaagccg     4200

ccctcagacg acagcccggc ccacagcagt gccatcgggc ccgtcattgg catcatcctc     4260

tctctcttcg tcatgggtgg tgtctatttt gtgtgccagc gcgtggtgtg ccagcgctat     4320

gcgggggcca acgggccctt cccgcacgag tatgtcagcg ggaccccgca cgtgcccctc     4380

aatttcatag ccccgggcgg ttcccagcat ggccccttca caggcatcgc atgcggaaag     4440

tccatgatga gctccgtgag cctgatgggg ggccggggcg gggtgcccct ctacgaccgg     4500

aaccacgtca caggggcctc gtccagcagc tcgtccagca cgaaggccac gctgtacccg     4560

ccgatcctga acccgccgcc ctccccggcc acggacccct ccctgtacaa catggacatg     4620

ttctactctt caaacattcc ggccactgcg agaccgtaca ggccctacat cattcgagga     4680

atggcgcccc cgacgacgcc ctgcagcacc gacgtgtgtg acagcgacta cagcgccagc     4740

cgctggaagg ccagcaagta ctacctggat ttgaactcgg actcagaccc ctatccaccc     4800

ccacccacgc cccacagcca gtacctgtcg gcggaggaca gctgcccgcc ctcgcccgcc     4860

accgagagga gctacttcca tctcttcccg ccccctccgt ccccctgcac ggactcatcc     4920

tgacctcggc cgggccactc tggcttctct gtgcccctgt aaatagtttt aaatatgaac     4980

aaagaaaaaa atatatttta tgatttaaaa aataaatata attgggattt taaaaacatg     5040

agaaatgtga actgtgatgg ggtgggcagg gctgggagaa ctttgtacag tggagaaata     5100

tttataaact taattttgta aaacagaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa     5160

a                                                                     5161


<210>  8
<211>  1615
<212>  PRT
<213>  Homo sapiens

<400>  8

Met Glu Ala Ala Pro Pro Gly Pro Pro Trp Pro Leu Leu Leu Leu Leu 
1               5                   10                  15      


Leu Leu Leu Leu Ala Leu Cys Gly Cys Pro Ala Pro Ala Ala Ala Ser 
            20                  25                  30          


Pro Leu Leu Leu Phe Ala Asn Arg Arg Asp Val Arg Leu Val Asp Ala 
        35                  40                  45              


Gly Gly Val Lys Leu Glu Ser Thr Ile Val Val Ser Gly Leu Glu Asp 
    50                  55                  60                  


Ala Ala Ala Val Asp Phe Gln Phe Ser Lys Gly Ala Val Tyr Trp Thr 
65                  70                  75                  80  


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


Ala Ala Val Gln Asn Val Val Ile Ser Gly Leu Val Ser Pro Asp Gly 
            100                 105                 110         


Leu Ala Cys Asp Trp Val Gly Lys Lys Leu Tyr Trp Thr Asp Ser Glu 
        115                 120                 125             


Thr Asn Arg Ile Glu Val Ala Asn Leu Asn Gly Thr Ser Arg Lys Val 
    130                 135                 140                 


Leu Phe Trp Gln Asp Leu Asp Gln Pro Arg Ala Ile Ala Leu Asp Pro 
145                 150                 155                 160 


Ala His Gly Tyr Met Tyr Trp Thr Asp Trp Gly Glu Thr Pro Arg Ile 
                165                 170                 175     


Glu Arg Ala Gly Met Asp Gly Ser Thr Arg Lys Ile Ile Val Asp Ser 
            180                 185                 190         


Asp Ile Tyr Trp Pro Asn Gly Leu Thr Ile Asp Leu Glu Glu Gln Lys 
        195                 200                 205             


Leu Tyr Trp Ala Asp Ala Lys Leu Ser Phe Ile His Arg Ala Asn Leu 
    210                 215                 220                 


Asp Gly Ser Phe Arg Gln Lys Val Val Glu Gly Ser Leu Thr His Pro 
225                 230                 235                 240 


Phe Ala Leu Thr Leu Ser Gly Asp Thr Leu Tyr Trp Thr Asp Trp Gln 
                245                 250                 255     


Thr Arg Ser Ile His Ala Cys Asn Lys Arg Thr Gly Gly Lys Arg Lys 
            260                 265                 270         


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


Gln Glu Arg Gln Pro Phe Phe His Thr Arg Cys Glu Glu Asp Asn Gly 
    290                 295                 300                 


Gly Cys Ser His Leu Cys Leu Leu Ser Pro Ser Glu Pro Phe Tyr Thr 
305                 310                 315                 320 


Cys Ala Cys Pro Thr Gly Val Gln Leu Gln Asp Asn Gly Arg Thr Cys 
                325                 330                 335     


Lys Ala Gly Ala Glu Glu Val Leu Leu Leu Ala Arg Arg Thr Asp Leu 
            340                 345                 350         


Arg Arg Ile Ser Leu Asp Thr Pro Asp Phe Thr Asp Ile Val Leu Gln 
        355                 360                 365             


Val Asp Asp Ile Arg His Ala Ile Ala Ile Asp Tyr Asp Pro Leu Glu 
    370                 375                 380                 


Gly Tyr Val Tyr Trp Thr Asp Asp Glu Val Arg Ala Ile Arg Arg Ala 
385                 390                 395                 400 


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


Asp Pro Asp Gly Ile Ala Val Asp Trp Val Ala Arg Asn Leu Tyr Trp 
            420                 425                 430         


Thr Asp Thr Gly Thr Asp Arg Ile Glu Val Thr Arg Leu Asn Gly Thr 
        435                 440                 445             


Ser Arg Lys Ile Leu Val Ser Glu Asp Leu Asp Glu Pro Arg Ala Ile 
    450                 455                 460                 


Ala Leu His Pro Val Met Gly Leu Met Tyr Trp Thr Asp Trp Gly Glu 
465                 470                 475                 480 


Asn Pro Lys Ile Glu Cys Ala Asn Leu Asp Gly Gln Glu Arg Arg Val 
                485                 490                 495     


Leu Val Asn Ala Ser Leu Gly Trp Pro Asn Gly Leu Ala Leu Asp Leu 
            500                 505                 510         


Gln Glu Gly Lys Leu Tyr Trp Gly Asp Ala Lys Thr Asp Lys Ile Glu 
        515                 520                 525             


Val Ile Asn Val Asp Gly Thr Lys Arg Arg Thr Leu Leu Glu Asp Lys 
    530                 535                 540                 


Leu Pro His Ile Phe Gly Phe Thr Leu Leu Gly Asp Phe Ile Tyr Trp 
545                 550                 555                 560 


Thr Asp Trp Gln Arg Arg Ser Ile Glu Arg Val His Lys Val Lys Ala 
                565                 570                 575     


Ser Arg Asp Val Ile Ile Asp Gln Leu Pro Asp Leu Met Gly Leu Lys 
            580                 585                 590         


Ala Val Asn Val Ala Lys Val Val Gly Thr Asn Pro Cys Ala Asp Arg 
        595                 600                 605             


Asn Gly Gly Cys Ser His Leu Cys Phe Phe Thr Pro His Ala Thr Arg 
    610                 615                 620                 


Cys Gly Cys Pro Ile Gly Leu Glu Leu Leu Ser Asp Met Lys Thr Cys 
625                 630                 635                 640 


Ile Val Pro Glu Ala Phe Leu Val Phe Thr Ser Arg Ala Ala Ile His 
                645                 650                 655     


Arg Ile Ser Leu Glu Thr Asn Asn Asn Asp Val Ala Ile Pro Leu Thr 
            660                 665                 670         


Gly Val Lys Glu Ala Ser Ala Leu Asp Phe Asp Val Ser Asn Asn His 
        675                 680                 685             


Ile Tyr Trp Thr Asp Val Ser Leu Lys Thr Ile Ser Arg Ala Phe Met 
    690                 695                 700                 


Asn Gly Ser Ser Val Glu His Val Val Glu Phe Gly Leu Asp Tyr Pro 
705                 710                 715                 720 


Glu Gly Met Ala Val Asp Trp Met Gly Lys Asn Leu Tyr Trp Ala Asp 
                725                 730                 735     


Thr Gly Thr Asn Arg Ile Glu Val Ala Arg Leu Asp Gly Gln Phe Arg 
            740                 745                 750         


Gln Val Leu Val Trp Arg Asp Leu Asp Asn Pro Arg Ser Leu Ala Leu 
        755                 760                 765             


Asp Pro Thr Lys Gly Tyr Ile Tyr Trp Thr Glu Trp Gly Gly Lys Pro 
    770                 775                 780                 


Arg Ile Val Arg Ala Phe Met Asp Gly Thr Asn Cys Met Thr Leu Val 
785                 790                 795                 800 


Asp Lys Val Gly Arg Ala Asn Asp Leu Thr Ile Asp Tyr Ala Asp Gln 
                805                 810                 815     


Arg Leu Tyr Trp Thr Asp Leu Asp Thr Asn Met Ile Glu Ser Ser Asn 
            820                 825                 830         


Met Leu Gly Gln Glu Arg Val Val Ile Ala Asp Asp Leu Pro His Pro 
        835                 840                 845             


Phe Gly Leu Thr Gln Tyr Ser Asp Tyr Ile Tyr Trp Thr Asp Trp Asn 
    850                 855                 860                 


Leu His Ser Ile Glu Arg Ala Asp Lys Thr Ser Gly Arg Asn Arg Thr 
865                 870                 875                 880 


Leu Ile Gln Gly His Leu Asp Phe Val Met Asp Ile Leu Val Phe His 
                885                 890                 895     


Ser Ser Arg Gln Asp Gly Leu Asn Asp Cys Met His Asn Asn Gly Gln 
            900                 905                 910         


Cys Gly Gln Leu Cys Leu Ala Ile Pro Gly Gly His Arg Cys Gly Cys 
        915                 920                 925             


Ala Ser His Tyr Thr Leu Asp Pro Ser Ser Arg Asn Cys Ser Pro Pro 
    930                 935                 940                 


Thr Thr Phe Leu Leu Phe Ser Gln Lys Ser Ala Ile Ser Arg Met Ile 
945                 950                 955                 960 


Pro Asp Asp Gln His Ser Pro Asp Leu Ile Leu Pro Leu His Gly Leu 
                965                 970                 975     


Arg Asn Val Lys Ala Ile Asp Tyr Asp Pro Leu Asp Lys Phe Ile Tyr 
            980                 985                 990         


Trp Val Asp Gly Arg Gln Asn Ile  Lys Arg Ala Lys Asp  Asp Gly Thr 
        995                 1000                 1005             


Gln Pro  Phe Val Leu Thr Ser  Leu Ser Gln Gly Gln  Asn Pro Asp 
    1010                 1015                 1020             


Arg Gln  Pro His Asp Leu Ser  Ile Asp Ile Tyr Ser  Arg Thr Leu 
    1025                 1030                 1035             


Phe Trp  Thr Cys Glu Ala Thr  Asn Thr Ile Asn Val  His Arg Leu 
    1040                 1045                 1050             


Ser Gly  Glu Ala Met Gly Val  Val Leu Arg Gly Asp  Arg Asp Lys 
    1055                 1060                 1065             


Pro Arg  Ala Ile Val Val Asn  Ala Glu Arg Gly Tyr  Leu Tyr Phe 
    1070                 1075                 1080             


Thr Asn  Met Gln Asp Arg Ala  Ala Lys Ile Glu Arg  Ala Ala Leu 
    1085                 1090                 1095             


Asp Gly  Thr Glu Arg Glu Val  Leu Phe Thr Thr Gly  Leu Ile Arg 
    1100                 1105                 1110             


Pro Val  Ala Leu Val Val Asp  Asn Thr Leu Gly Lys  Leu Phe Trp 
    1115                 1120                 1125             


Val Asp  Ala Asp Leu Lys Arg  Ile Glu Ser Cys Asp  Leu Ser Gly 
    1130                 1135                 1140             


Ala Asn  Arg Leu Thr Leu Glu  Asp Ala Asn Ile Val  Gln Pro Leu 
    1145                 1150                 1155             


Gly Leu  Thr Ile Leu Gly Lys  His Leu Tyr Trp Ile  Asp Arg Gln 
    1160                 1165                 1170             


Gln Gln  Met Ile Glu Arg Val  Glu Lys Thr Thr Gly  Asp Lys Arg 
    1175                 1180                 1185             


Thr Arg  Ile Gln Gly Arg Val  Ala His Leu Thr Gly  Ile His Ala 
    1190                 1195                 1200             


Val Glu  Glu Val Ser Leu Glu  Glu Phe Ser Ala His  Pro Cys Ala 
    1205                 1210                 1215             


Arg Asp  Asn Gly Gly Cys Ser  His Ile Cys Ile Ala  Lys Gly Asp 
    1220                 1225                 1230             


Gly Thr  Pro Arg Cys Ser Cys  Pro Val His Leu Val  Leu Leu Gln 
    1235                 1240                 1245             


Asn Leu  Leu Thr Cys Gly Glu  Pro Pro Thr Cys Ser  Pro Asp Gln 
    1250                 1255                 1260             


Phe Ala  Cys Ala Thr Gly Glu  Ile Asp Cys Ile Pro  Gly Ala Trp 
    1265                 1270                 1275             


Arg Cys  Asp Gly Phe Pro Glu  Cys Asp Asp Gln Ser  Asp Glu Glu 
    1280                 1285                 1290             


Gly Cys  Pro Val Cys Ser Ala  Ala Gln Phe Pro Cys  Ala Arg Gly 
    1295                 1300                 1305             


Gln Cys  Val Asp Leu Arg Leu  Arg Cys Asp Gly Glu  Ala Asp Cys 
    1310                 1315                 1320             


Gln Asp  Arg Ser Asp Glu Ala  Asp Cys Asp Ala Ile  Cys Leu Pro 
    1325                 1330                 1335             


Asn Gln  Phe Arg Cys Ala Ser  Gly Gln Cys Val Leu  Ile Lys Gln 
    1340                 1345                 1350             


Gln Cys  Asp Ser Phe Pro Asp  Cys Ile Asp Gly Ser  Asp Glu Leu 
    1355                 1360                 1365             


Met Cys  Glu Ile Thr Lys Pro  Pro Ser Asp Asp Ser  Pro Ala His 
    1370                 1375                 1380             


Ser Ser  Ala Ile Gly Pro Val  Ile Gly Ile Ile Leu  Ser Leu Phe 
    1385                 1390                 1395             


Val Met  Gly Gly Val Tyr Phe  Val Cys Gln Arg Val  Val Cys Gln 
    1400                 1405                 1410             


Arg Tyr  Ala Gly Ala Asn Gly  Pro Phe Pro His Glu  Tyr Val Ser 
    1415                 1420                 1425             


Gly Thr  Pro His Val Pro Leu  Asn Phe Ile Ala Pro  Gly Gly Ser 
    1430                 1435                 1440             


Gln His  Gly Pro Phe Thr Gly  Ile Ala Cys Gly Lys  Ser Met Met 
    1445                 1450                 1455             


Ser Ser  Val Ser Leu Met Gly  Gly Arg Gly Gly Val  Pro Leu Tyr 
    1460                 1465                 1470             


Asp Arg  Asn His Val Thr Gly  Ala Ser Ser Ser Ser  Ser Ser Ser 
    1475                 1480                 1485             


Thr Lys  Ala Thr Leu Tyr Pro  Pro Ile Leu Asn Pro  Pro Pro Ser 
    1490                 1495                 1500             


Pro Ala  Thr Asp Pro Ser Leu  Tyr Asn Met Asp Met  Phe Tyr Ser 
    1505                 1510                 1515             


Ser Asn  Ile Pro Ala Thr Ala  Arg Pro Tyr Arg Pro  Tyr Ile Ile 
    1520                 1525                 1530             


Arg Gly  Met Ala Pro Pro Thr  Thr Pro Cys Ser Thr  Asp Val Cys 
    1535                 1540                 1545             


Asp Ser  Asp Tyr Ser Ala Ser  Arg Trp Lys Ala Ser  Lys Tyr Tyr 
    1550                 1555                 1560             


Leu Asp  Leu Asn Ser Asp Ser  Asp Pro Tyr Pro Pro  Pro Pro Thr 
    1565                 1570                 1575             


Pro His  Ser Gln Tyr Leu Ser  Ala Glu Asp Ser Cys  Pro Pro Ser 
    1580                 1585                 1590             


Pro Ala  Thr Glu Arg Ser Tyr  Phe His Leu Phe Pro  Pro Pro Pro 
    1595                 1600                 1605             


Ser Pro  Cys Thr Asp Ser Ser  
    1610                 1615 


<210>  9
<211>  116
<212>  PRT
<213>  Homo sapiens

<400>  9

Pro Pro Thr Cys Ser Pro Asp Gln Phe Ala Cys Ala Thr Gly Glu Ile 
1               5                   10                  15      


Asp Cys Ile Pro Gly Ala Trp Arg Cys Asp Gly Phe Pro Glu Cys Asp 
            20                  25                  30          


Asp Gln Ser Asp Glu Glu Gly Cys Pro Val Cys Ser Ala Ala Gln Phe 
        35                  40                  45              


Pro Cys Ala Arg Gly Gln Cys Val Asp Leu Arg Leu Arg Asp Gly Glu 
    50                  55                  60                  


Ala Asp Cys Gln Asp Arg Ser Asp Glu Val Asp Cys Asp Ala Ile Cys 
65                  70                  75                  80  


Leu Pro Asn Gln Phe Arg Cys Ala Ser Gly Gln Cys Val Leu Ile Lys 
                85                  90                  95      


Gln Gln Cys Asp Ser Phe Pro Asp Cys Ile Asp Gly Ser Asp Glu Leu 
            100                 105                 110         


Met Cys Glu Ile 
        115     


<210>  10
<211>  860
<212>  PRT
<213>  Homo sapiens

<400>  10

Met Gly Pro Trp Gly Trp Lys Leu Arg Trp Thr Val Ala Leu Leu Leu 
1               5                   10                  15      


Ala Ala Ala Gly Thr Ala Val Gly Asp Arg Cys Glu Arg Asn Glu Phe 
            20                  25                  30          


Gln Cys Gln Asp Gly Lys Cys Ile Ser Tyr Lys Trp Val Cys Asp Gly 
        35                  40                  45              


Ser Ala Glu Cys Gln Asp Gly Ser Asp Glu Ser Gln Glu Thr Cys Leu 
    50                  55                  60                  


Ser Val Thr Cys Lys Ser Gly Asp Phe Ser Cys Gly Gly Arg Val Asn 
65                  70                  75                  80  


Arg Cys Ile Pro Gln Phe Trp Arg Cys Asp Gly Gln Val Asp Cys Asp 
                85                  90                  95      


Asn Gly Ser Asp Glu Gln Gly Cys Pro Pro Lys Thr Cys Ser Gln Asp 
            100                 105                 110         


Glu Phe Arg Cys His Asp Gly Lys Cys Ile Ser Arg Gln Phe Val Cys 
        115                 120                 125             


Asp Ser Asp Arg Asp Cys Leu Asp Gly Ser Asp Glu Ala Ser Cys Pro 
    130                 135                 140                 


Val Leu Thr Cys Gly Pro Ala Ser Phe Gln Cys Asn Ser Ser Thr Cys 
145                 150                 155                 160 


Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp Pro Asp Cys Glu Asp Gly 
                165                 170                 175     


Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly Leu Tyr Val Phe Gln Gly 
            180                 185                 190         


Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe His Cys Leu Ser Gly Glu 
        195                 200                 205             


Cys Ile His Ser Ser Trp Arg Cys Asp Gly Gly Pro Asp Cys Lys Asp 
    210                 215                 220                 


Lys Ser Asp Glu Glu Asn Cys Ala Val Ala Thr Cys Arg Pro Asp Glu 
225                 230                 235                 240 


Phe Gln Cys Ser Asp Gly Asn Cys Ile His Gly Ser Arg Gln Cys Asp 
                245                 250                 255     


Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp Glu Val Gly Cys Val Asn 
            260                 265                 270         


Val Thr Leu Cys Glu Gly Pro Asn Lys Phe Lys Cys His Ser Gly Glu 
        275                 280                 285             


Cys Ile Thr Leu Asp Lys Val Cys Asn Met Ala Arg Asp Cys Arg Asp 
    290                 295                 300                 


Trp Ser Asp Glu Pro Ile Lys Glu Cys Gly Thr Asn Glu Cys Leu Asp 
305                 310                 315                 320 


Asn Asn Gly Gly Cys Ser His Val Cys Asn Asp Leu Lys Ile Gly Tyr 
                325                 330                 335     


Glu Cys Leu Cys Pro Asp Gly Phe Gln Leu Val Ala Gln Arg Arg Cys 
            340                 345                 350         


Glu Asp Ile Asp Glu Cys Gln Asp Pro Asp Thr Cys Ser Gln Leu Cys 
        355                 360                 365             


Val Asn Leu Glu Gly Gly Tyr Lys Cys Gln Cys Glu Glu Gly Phe Gln 
    370                 375                 380                 


Leu Asp Pro His Thr Lys Ala Cys Lys Ala Val Gly Ser Ile Ala Tyr 
385                 390                 395                 400 


Leu Phe Phe Thr Asn Arg His Glu Val Arg Lys Met Thr Leu Asp Arg 
                405                 410                 415     


Ser Glu Tyr Thr Ser Leu Ile Pro Asn Leu Arg Asn Val Val Ala Leu 
            420                 425                 430         


Asp Thr Glu Val Ala Ser Asn Arg Ile Tyr Trp Ser Asp Leu Ser Gln 
        435                 440                 445             


Arg Met Ile Cys Ser Thr Gln Leu Asp Arg Ala His Gly Val Ser Ser 
    450                 455                 460                 


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


Val Asp Trp Ile His Ser Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly 
                485                 490                 495     


Thr Val Ser Val Ala Asp Thr Lys Gly Val Lys Arg Lys Thr Leu Phe 
            500                 505                 510         


Arg Glu Asn Gly Ser Lys Pro Arg Ala Ile Val Val Asp Pro Val His 
        515                 520                 525             


Gly Phe Met Tyr Trp Thr Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys 
    530                 535                 540                 


Gly Gly Leu Asn Gly Val Asp Ile Tyr Ser Leu Val Thr Glu Asn Ile 
545                 550                 555                 560 


Gln Trp Pro Asn Gly Ile Thr Leu Asp Leu Leu Ser Gly Arg Leu Tyr 
                565                 570                 575     


Trp Val Asp Ser Lys Leu His Ser Ile Ser Ser Ile Asp Val Asn Gly 
            580                 585                 590         


Gly Asn Arg Lys Thr Ile Leu Glu Asp Glu Lys Arg Leu Ala His Pro 
        595                 600                 605             


Phe Ser Leu Ala Val Phe Glu Asp Lys Val Phe Trp Thr Asp Ile Ile 
    610                 615                 620                 


Asn Glu Ala Ile Phe Ser Ala Asn Arg Leu Thr Gly Ser Asp Val Asn 
625                 630                 635                 640 


Leu Leu Ala Glu Asn Leu Leu Ser Pro Glu Asp Met Val Leu Phe His 
                645                 650                 655     


Asn Leu Thr Gln Pro Arg Gly Val Asn Trp Cys Glu Arg Thr Thr Leu 
            660                 665                 670         


Ser Asn Gly Gly Cys Gln Tyr Leu Cys Leu Pro Ala Pro Gln Ile Asn 
        675                 680                 685             


Pro His Ser Pro Lys Phe Thr Cys Ala Cys Pro Asp Gly Met Leu Leu 
    690                 695                 700                 


Ala Arg Asp Met Arg Ser Cys Leu Thr Glu Ala Glu Ala Ala Val Ala 
705                 710                 715                 720 


Thr Gln Glu Thr Ser Thr Val Arg Leu Lys Val Ser Ser Thr Ala Val 
                725                 730                 735     


Arg Thr Gln His Thr Thr Thr Arg Pro Val Pro Asp Thr Ser Arg Leu 
            740                 745                 750         


Pro Gly Ala Thr Pro Gly Leu Thr Thr Val Glu Ile Val Thr Met Ser 
        755                 760                 765             


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


Ser Ser Val Arg Ala Leu Ser Ile Val Leu Pro Ile Val Leu Leu Val 
785                 790                 795                 800 


Phe Leu Cys Leu Gly Val Phe Leu Leu Trp Lys Asn Trp Arg Leu Lys 
                805                 810                 815     


Asn Ile Asn Ser Ile Asn Phe Asp Asn Pro Val Tyr Gln Lys Thr Thr 
            820                 825                 830         


Glu Asp Glu Val His Ile Cys His Asn Gln Asp Gly Tyr Ser Tyr Pro 
        835                 840                 845             


Ser Arg Gln Met Val Ser Leu Glu Asp Asp Val Ala 
    850                 855                 860 


<210>  11
<211>  122
<212>  PRT
<213>  Homo sapiens

<400>  11

Asp Glu Leu Ser Cys Gly Glu Pro Pro Thr Cys Ser Pro Gln Gln Phe 
1               5                   10                  15      


Thr Cys Phe Thr Gly Glu Ile Asp Cys Ile Pro Val Ala Trp Arg Cys 
            20                  25                  30          


Asp Gly Phe Thr Glu Cys Glu Asp His Ser Asp Glu Leu Asn Cys Pro 
        35                  40                  45              


Val Cys Ser Glu Ser Gln Phe Gln Cys Ala Ser Gly Gln Cys Ile Asp 
    50                  55                  60                  


Gly Ala Leu Arg Cys Asn Gly Asp Ala Asn Cys Gln Asp Lys Ser Asp 
65                  70                  75                  80  


Glu Lys Asn Cys Glu Val Leu Cys Leu Ile Asp Gln Phe Arg Cys Ala 
                85                  90                  95      


Asn Gly Gln Cys Ile Gly Lys His Lys Lys Cys Asp His Asn Val Asp 
            100                 105                 110         


Cys Ser Asp Lys Ser Asp Glu Leu Asp Cys 
        115                 120         


<210>  12
<211>  132
<212>  PRT
<213>  Homo sapiens

<400>  12

Asp Glu Ala Ser Cys Pro Val Leu Thr Cys Gly Pro Ala Ser Phe Gln 
1               5                   10                  15      


Cys Asn Ser Ser Thr Cys Ile Pro Gln Leu Trp Ala Cys Asp Asn Asp 
            20                  25                  30          


Pro Asp Cys Glu Asp Gly Ser Asp Glu Trp Pro Gln Arg Cys Arg Gly 
        35                  40                  45              


Leu Tyr Val Phe Gln Gly Asp Ser Ser Pro Cys Ser Ala Phe Glu Phe 
    50                  55                  60                  


His Cys Leu Ser Gly Glu Cys Ile His Ser Ser Trp Arg Cys Asp Gly 
65                  70                  75                  80  


Gly Pro Asp Cys Lys Asp Lys Ser Asp Glu Glu Asn Cys Ala Val Ala 
                85                  90                  95      


Thr Cys Arg Pro Asp Glu Phe Gln Cys Ser Asp Gly Asn Cys Ile His 
            100                 105                 110         


Gly Ser Arg Gln Cys Asp Arg Glu Tyr Asp Cys Lys Asp Met Ser Asp 
        115                 120                 125             


Glu Val Gly Cys 
    130         


<210>  13
<211>  39
<212>  PRT
<213>  Homo sapiens

<400>  13

Pro Pro Thr Cys Ser Pro Asp Gln Phe Ala Cys Ala Thr Gly Glu Ile 
1               5                   10                  15      


Asp Cys Ile Pro Gly Ala Trp Arg Cys Asp Gly Phe Pro Glu Cys Asp 
            20                  25                  30          


Asp Gln Ser Asp Glu Glu Gly 
        35                  


<210>  14
<211>  35
<212>  PRT
<213>  Homo sapiens

<400>  14

Cys Ser Ala Ala Gln Phe Pro Cys Ala Arg Gly Gln Cys Val Asp Leu 
1               5                   10                  15      


Arg Leu Arg Asp Gly Glu Ala Asp Cys Gln Asp Arg Ser Asp Glu Val 
            20                  25                  30          


Asp Cys Asp 
        35  


<210>  15
<211>  36
<212>  PRT
<213>  Homo sapiens

<400>  15

Cys Leu Pro Asn Gln Phe Arg Cys Ala Ser Gly Gln Cys Val Leu Ile 
1               5                   10                  15      


Lys Gln Gln Cys Asp Ser Phe Pro Asp Cys Ile Asp Gly Ser Asp Glu 
            20                  25                  30          


Leu Met Cys Glu 
        35      


<210>  16
<211>  5
<212>  PRT
<213>  Artificial

<220>
<223>  synthetic (linker peptide for linking heavy and light chains in 
       an scFv)

<400>  16

Gly Gly Gly Gly Ser 
1               5   


