                         SEQUENCE LISTING

<110>  ALBIREO AB
 
<120>  BENZOTHIA(DI)AZEPINE COMPOUNDS AND THEIR USE AS BILE ACID 
       MODULATORS

<130>  NP0500WO

<150>  IN 201911049982
<151>  2019-12-04

<160>  4     

<170>  PatentIn version 3.5

<210>  1
<211>  1251
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Ser Thr Glu Arg Asp Ser Glu Thr Thr Phe Asp Glu Asp Ser Gln 
1               5                   10                  15      


Pro Asn Asp Glu Val Val Pro Tyr Ser Asp Asp Glu Thr Glu Asp Glu 
            20                  25                  30          


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


Arg Glu Ala Glu Glu Asn Arg Glu Pro Phe Arg Lys Glu Cys Thr Trp 
    50                  55                  60                  


Gln Val Lys Ala Asn Asp Arg Lys Tyr His Glu Gln Pro His Phe Met 
65                  70                  75                  80  


Asn Thr Lys Phe Leu Cys Ile Lys Glu Ser Lys Tyr Ala Asn Asn Ala 
                85                  90                  95      


Ile Lys Thr Tyr Lys Tyr Asn Ala Phe Thr Phe Ile Pro Met Asn Leu 
            100                 105                 110         


Phe Glu Gln Phe Lys Arg Ala Ala Asn Leu Tyr Phe Leu Ala Leu Leu 
        115                 120                 125             


Ile Leu Gln Ala Val Pro Gln Ile Ser Thr Leu Ala Trp Tyr Thr Thr 
    130                 135                 140                 


Leu Val Pro Leu Leu Val Val Leu Gly Val Thr Ala Ile Lys Asp Leu 
145                 150                 155                 160 


Val Asp Asp Val Ala Arg His Lys Met Asp Lys Glu Ile Asn Asn Arg 
                165                 170                 175     


Thr Cys Glu Val Ile Lys Asp Gly Arg Phe Lys Val Ala Lys Trp Lys 
            180                 185                 190         


Glu Ile Gln Val Gly Asp Val Ile Arg Leu Lys Lys Asn Asp Phe Val 
        195                 200                 205             


Pro Ala Asp Ile Leu Leu Leu Ser Ser Ser Glu Pro Asn Ser Leu Cys 
    210                 215                 220                 


Tyr Val Glu Thr Ala Glu Leu Asp Gly Glu Thr Asn Leu Lys Phe Lys 
225                 230                 235                 240 


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


Ala Thr Phe Asp Gly Phe Ile Glu Cys Glu Glu Pro Asn Asn Arg Leu 
            260                 265                 270         


Asp Lys Phe Thr Gly Thr Leu Phe Trp Arg Asn Thr Ser Phe Pro Leu 
        275                 280                 285             


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


Phe Cys His Gly Leu Val Ile Phe Ala Gly Ala Asp Thr Lys Ile Met 
305                 310                 315                 320 


Lys Asn Ser Gly Lys Thr Arg Phe Lys Arg Thr Lys Ile Asp Tyr Leu 
                325                 330                 335     


Met Asn Tyr Met Val Tyr Thr Ile Phe Val Val Leu Ile Leu Leu Ser 
            340                 345                 350         


Ala Gly Leu Ala Ile Gly His Ala Tyr Trp Glu Ala Gln Val Gly Asn 
        355                 360                 365             


Ser Ser Trp Tyr Leu Tyr Asp Gly Glu Asp Asp Thr Pro Ser Tyr Arg 
    370                 375                 380                 


Gly Phe Leu Ile Phe Trp Gly Tyr Ile Ile Val Leu Asn Thr Met Val 
385                 390                 395                 400 


Pro Ile Ser Leu Tyr Val Ser Val Glu Val Ile Arg Leu Gly Gln Ser 
                405                 410                 415     


His Phe Ile Asn Trp Asp Leu Gln Met Tyr Tyr Ala Glu Lys Asp Thr 
            420                 425                 430         


Pro Ala Lys Ala Arg Thr Thr Thr Leu Asn Glu Gln Leu Gly Gln Ile 
        435                 440                 445             


His Tyr Ile Phe Ser Asp Lys Thr Gly Thr Leu Thr Gln Asn Ile Met 
    450                 455                 460                 


Thr Phe Lys Lys Cys Cys Ile Asn Gly Gln Ile Tyr Gly Asp His Arg 
465                 470                 475                 480 


Asp Ala Ser Gln His Asn His Asn Lys Ile Glu Gln Val Asp Phe Ser 
                485                 490                 495     


Trp Asn Thr Tyr Ala Asp Gly Lys Leu Ala Phe Tyr Asp His Tyr Leu 
            500                 505                 510         


Ile Glu Gln Ile Gln Ser Gly Lys Glu Pro Glu Val Arg Gln Phe Phe 
        515                 520                 525             


Phe Leu Leu Ala Val Cys His Thr Val Met Val Asp Arg Thr Asp Gly 
    530                 535                 540                 


Gln Leu Asn Tyr Gln Ala Ala Ser Pro Asp Glu Gly Ala Leu Val Asn 
545                 550                 555                 560 


Ala Ala Arg Asn Phe Gly Phe Ala Phe Leu Ala Arg Thr Gln Asn Thr 
                565                 570                 575     


Ile Thr Ile Ser Glu Leu Gly Thr Glu Arg Thr Tyr Asn Val Leu Ala 
            580                 585                 590         


Ile Leu Asp Phe Asn Ser Asp Arg Lys Arg Met Ser Ile Ile Val Arg 
        595                 600                 605             


Thr Pro Glu Gly Asn Ile Lys Leu Tyr Cys Lys Gly Ala Asp Thr Val 
    610                 615                 620                 


Ile Tyr Glu Arg Leu His Arg Met Asn Pro Thr Lys Gln Glu Thr Gln 
625                 630                 635                 640 


Asp Ala Leu Asp Ile Phe Ala Asn Glu Thr Leu Arg Thr Leu Cys Leu 
                645                 650                 655     


Cys Tyr Lys Glu Ile Glu Glu Lys Glu Phe Thr Glu Trp Asn Lys Lys 
            660                 665                 670         


Phe Met Ala Ala Ser Val Ala Ser Thr Asn Arg Asp Glu Ala Leu Asp 
        675                 680                 685             


Lys Val Tyr Glu Glu Ile Glu Lys Asp Leu Ile Leu Leu Gly Ala Thr 
    690                 695                 700                 


Ala Ile Glu Asp Lys Leu Gln Asp Gly Val Pro Glu Thr Ile Ser Lys 
705                 710                 715                 720 


Leu Ala Lys Ala Asp Ile Lys Ile Trp Val Leu Thr Gly Asp Lys Lys 
                725                 730                 735     


Glu Thr Ala Glu Asn Ile Gly Phe Ala Cys Glu Leu Leu Thr Glu Asp 
            740                 745                 750         


Thr Thr Ile Cys Tyr Gly Glu Asp Ile Asn Ser Leu Leu His Ala Arg 
        755                 760                 765             


Met Glu Asn Gln Arg Asn Arg Gly Gly Val Tyr Ala Lys Phe Ala Pro 
    770                 775                 780                 


Pro Val Gln Glu Ser Phe Phe Pro Pro Gly Gly Asn Arg Ala Leu Ile 
785                 790                 795                 800 


Ile Thr Gly Ser Trp Leu Asn Glu Ile Leu Leu Glu Lys Lys Thr Lys 
                805                 810                 815     


Arg Asn Lys Ile Leu Lys Leu Lys Phe Pro Arg Thr Glu Glu Glu Arg 
            820                 825                 830         


Arg Met Arg Thr Gln Ser Lys Arg Arg Leu Glu Ala Lys Lys Glu Gln 
        835                 840                 845             


Arg Gln Lys Asn Phe Val Asp Leu Ala Cys Glu Cys Ser Ala Val Ile 
    850                 855                 860                 


Cys Cys Arg Val Thr Pro Lys Gln Lys Ala Met Val Val Asp Leu Val 
865                 870                 875                 880 


Lys Arg Tyr Lys Lys Ala Ile Thr Leu Ala Ile Gly Asp Gly Ala Asn 
                885                 890                 895     


Asp Val Asn Met Ile Lys Thr Ala His Ile Gly Val Gly Ile Ser Gly 
            900                 905                 910         


Gln Glu Gly Met Gln Ala Val Met Ser Ser Asp Tyr Ser Phe Ala Gln 
        915                 920                 925             


Phe Arg Tyr Leu Gln Arg Leu Leu Leu Val His Gly Arg Trp Ser Tyr 
    930                 935                 940                 


Ile Arg Met Cys Lys Phe Leu Arg Tyr Phe Phe Tyr Lys Asn Phe Ala 
945                 950                 955                 960 


Phe Thr Leu Val His Phe Trp Tyr Ser Phe Phe Asn Gly Tyr Ser Ala 
                965                 970                 975     


Gln Thr Ala Tyr Glu Asp Trp Phe Ile Thr Leu Tyr Asn Val Leu Tyr 
            980                 985                 990         


Thr Ser Leu Pro Val Leu Leu Met  Gly Leu Leu Asp Gln  Asp Val Ser 
        995                 1000                 1005             


Asp Lys  Leu Ser Leu Arg Phe  Pro Gly Leu Tyr Ile  Val Gly Gln 
    1010                 1015                 1020             


Arg Asp  Leu Leu Phe Asn Tyr  Lys Arg Phe Phe Val  Ser Leu Leu 
    1025                 1030                 1035             


His Gly  Val Leu Thr Ser Met  Ile Leu Phe Phe Ile  Pro Leu Gly 
    1040                 1045                 1050             


Ala Tyr  Leu Gln Thr Val Gly  Gln Asp Gly Glu Ala  Pro Ser Asp 
    1055                 1060                 1065             


Tyr Gln  Ser Phe Ala Val Thr  Ile Ala Ser Ala Leu  Val Ile Thr 
    1070                 1075                 1080             


Val Asn  Phe Gln Ile Gly Leu  Asp Thr Ser Tyr Trp  Thr Phe Val 
    1085                 1090                 1095             


Asn Ala  Phe Ser Ile Phe Gly  Ser Ile Ala Leu Tyr  Phe Gly Ile 
    1100                 1105                 1110             


Met Phe  Asp Phe His Ser Ala  Gly Ile His Val Leu  Phe Pro Ser 
    1115                 1120                 1125             


Ala Phe  Gln Phe Thr Gly Thr  Ala Ser Asn Ala Leu  Arg Gln Pro 
    1130                 1135                 1140             


Tyr Ile  Trp Leu Thr Ile Ile  Leu Ala Val Ala Val  Cys Leu Leu 
    1145                 1150                 1155             


Pro Val  Val Ala Ile Arg Phe  Leu Ser Met Thr Ile  Trp Pro Ser 
    1160                 1165                 1170             


Glu Ser  Asp Lys Ile Gln Lys  His Arg Lys Arg Leu  Lys Ala Glu 
    1175                 1180                 1185             


Glu Gln  Trp Gln Arg Arg Gln  Gln Val Phe Arg Arg  Gly Val Ser 
    1190                 1195                 1200             


Thr Arg  Arg Ser Ala Tyr Ala  Phe Ser His Gln Arg  Gly Tyr Ala 
    1205                 1210                 1215             


Asp Leu  Ile Ser Ser Gly Arg  Ser Ile Arg Lys Lys  Arg Ser Pro 
    1220                 1225                 1230             


Leu Asp  Ala Ile Val Ala Asp  Gly Thr Ala Glu Tyr  Arg Arg Thr 
    1235                 1240                 1245             


Gly Asp  Ser 
    1250     


<210>  2
<211>  3756
<212>  DNA
<213>  Homo sapiens

<400>  2
atgagtacag aaagagactc agaaacgaca tttgacgagg attctcagcc taatgacgaa       60

gtggttccct acagtgatga tgaaacagaa gatgaacttg atgaccaggg gtctgctgtt      120

gaaccagaac aaaaccgagt caacagggaa gcagaggaga accgggagcc attcagaaaa      180

gaatgtacat ggcaagtcaa agcaaacgat cgcaagtacc acgaacaacc tcactttatg      240

aacacaaaat tcttgtgtat taaggagagt aaatatgcga ataatgcaat taaaacatac      300

aagtacaacg catttacctt tataccaatg aatctgtttg agcagtttaa gagagcagcc      360

aatttatatt tcctggctct tcttatctta caggcagttc ctcaaatctc taccctggct      420

tggtacacca cactagtgcc cctgcttgtg gtgctgggcg tcactgcaat caaagacctg      480

gtggacgatg tggctcgcca taaaatggat aaggaaatca acaataggac gtgtgaagtc      540

attaaggatg gcaggttcaa agttgctaag tggaaagaaa ttcaagttgg agacgtcatt      600

cgtctgaaaa aaaatgattt tgttccagct gacattctcc tgctgtctag ctctgagcct      660

aacagcctct gctatgtgga aacagcagaa ctggatggag aaaccaattt aaaatttaag      720

atgtcacttg aaatcacaga ccagtacctc caaagagaag atacattggc tacatttgat      780

ggttttattg aatgtgaaga acccaataac agactagata agtttacagg aacactattt      840

tggagaaaca caagttttcc tttggatgct gataaaattt tgttacgtgg ctgtgtaatt      900

aggaacaccg atttctgcca cggcttagtc atttttgcag gtgctgacac taaaataatg      960

aagaatagtg ggaaaaccag atttaaaaga actaaaattg attacttgat gaactacatg     1020

gtttacacga tctttgttgt tcttattctg ctttctgctg gtcttgccat cggccatgct     1080

tattgggaag cacaggtggg caattcctct tggtacctct atgatggaga agacgataca     1140

ccctcctacc gtggattcct cattttctgg ggctatatca ttgttctcaa caccatggta     1200

cccatctctc tctatgtcag cgtggaagtg attcgtcttg gacagagtca cttcatcaac     1260

tgggacctgc aaatgtacta tgctgagaag gacacacccg caaaagctag aaccaccaca     1320

ctcaatgaac agctcgggca gatccattat atcttctctg ataagacggg gacactcaca     1380

caaaatatca tgacctttaa aaagtgctgt atcaacgggc agatatatgg ggaccatcgg     1440

gatgcctctc aacacaacca caacaaaata gagcaagttg attttagctg gaatacatat     1500

gctgatggga agcttgcatt ttatgaccac tatcttattg agcaaatcca gtcagggaaa     1560

gagccagaag tacgacagtt cttcttcttg ctcgcagttt gccacacagt catggtggat     1620

aggactgatg gtcagctcaa ctaccaggca gcctctcccg atgaaggtgc cctggtaaac     1680

gctgccagga actttggctt tgccttcctc gccaggaccc agaacaccat caccatcagt     1740

gaactgggca ctgaaaggac ttacaatgtt cttgccattt tggacttcaa cagtgaccgg     1800

aagcgaatgt ctatcattgt aagaacccca gaaggcaata tcaagcttta ctgtaaaggt     1860

gctgacactg ttatttatga acggttacat cgaatgaatc ctactaagca agaaacacag     1920

gatgccctgg atatctttgc aaatgaaact cttagaaccc tatgcctttg ctacaaggaa     1980

attgaagaaa aagaatttac agaatggaat aaaaagttta tggctgccag tgtggcctcc     2040

accaaccggg acgaagctct ggataaagta tatgaggaga ttgaaaaaga cttaattctc     2100

ctgggagcta cagctattga agacaagcta caggatggag ttccagaaac catttcaaaa     2160

cttgcaaaag ctgacattaa gatctgggtg cttactggag acaaaaagga aactgctgaa     2220

aatataggat ttgcttgtga acttctgact gaagacacca ccatctgcta tggggaggat     2280

attaattctc ttcttcatgc aaggatggaa aaccagagga atagaggtgg cgtctacgca     2340

aagtttgcac ctcctgtgca ggaatctttt tttccacccg gtggaaaccg tgccttaatc     2400

atcactggtt cttggttgaa tgaaattctt ctcgagaaaa agaccaagag aaataagatt     2460

ctgaagctga agttcccaag aacagaagaa gaaagacgga tgcggaccca aagtaaaagg     2520

aggctagaag ctaagaaaga gcagcggcag aaaaactttg tggacctggc ctgcgagtgc     2580

agcgcagtca tctgctgccg cgtcaccccc aagcagaagg ccatggtggt ggacctggtg     2640

aagaggtaca agaaagccat cacgctggcc atcggagatg gggccaatga cgtgaacatg     2700

atcaaaactg cccacattgg cgttggaata agtggacaag aaggaatgca agctgtcatg     2760

tcgagtgact attcctttgc tcagttccga tatctgcaga ggctactgct ggtgcatggc     2820

cgatggtctt acataaggat gtgcaagttc ctacgatact tcttttacaa aaactttgcc     2880

tttactttgg ttcatttctg gtactccttc ttcaatggct actctgcgca gactgcatac     2940

gaggattggt tcatcaccct ctacaacgtg ctgtacacca gcctgcccgt gctcctcatg     3000

gggctgctcg accaggatgt gagtgacaaa ctgagcctcc gattccctgg gttatacata     3060

gtgggacaaa gagacttact attcaactat aagagattct ttgtaagctt gttgcatggg     3120

gtcctaacat cgatgatcct cttcttcata cctcttggag cttatctgca aaccgtaggg     3180

caggatggag aggcaccttc cgactaccag tcttttgccg tcaccattgc ctctgctctt     3240

gtaataacag tcaatttcca gattggcttg gatacttctt attggacttt tgtgaatgct     3300

ttttcaattt ttggaagcat tgcactttat tttggcatca tgtttgactt tcatagtgct     3360

ggaatacatg ttctctttcc atctgcattt caatttacag gcacagcttc aaacgctctg     3420

agacagccat acatttggtt aactatcatc ctggctgttg ctgtgtgctt actacccgtc     3480

gttgccattc gattcctgtc aatgaccatc tggccatcag aaagtgataa gatccagaag     3540

catcgcaagc ggttgaaggc ggaggagcag tggcagcgac ggcagcaggt gttccgccgg     3600

ggcgtgtcaa cgcggcgctc ggcctacgcc ttctcgcacc agcggggcta cgcggacctc     3660

atctcctccg ggcgcagcat ccgcaagaag cgctcgccgc ttgatgccat cgtggcggat     3720

ggcaccgcgg agtacaggcg caccggggac agctga                               3756


<210>  3
<211>  1321
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Ser Asp Ser Val Ile Leu Arg Ser Ile Lys Lys Phe Gly Glu Glu 
1               5                   10                  15      


Asn Asp Gly Phe Glu Ser Asp Lys Ser Tyr Asn Asn Asp Lys Lys Ser 
            20                  25                  30          


Arg Leu Gln Asp Glu Lys Lys Gly Asp Gly Val Arg Val Gly Phe Phe 
        35                  40                  45              


Gln Leu Phe Arg Phe Ser Ser Ser Thr Asp Ile Trp Leu Met Phe Val 
    50                  55                  60                  


Gly Ser Leu Cys Ala Phe Leu His Gly Ile Ala Gln Pro Gly Val Leu 
65                  70                  75                  80  


Leu Ile Phe Gly Thr Met Thr Asp Val Phe Ile Asp Tyr Asp Val Glu 
                85                  90                  95      


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


Val Trp Thr Asn Ser Ser Leu Asn Gln Asn Met Thr Asn Gly Thr Arg 
        115                 120                 125             


Cys Gly Leu Leu Asn Ile Glu Ser Glu Met Ile Lys Phe Ala Ser Tyr 
    130                 135                 140                 


Tyr Ala Gly Ile Ala Val Ala Val Leu Ile Thr Gly Tyr Ile Gln Ile 
145                 150                 155                 160 


Cys Phe Trp Val Ile Ala Ala Ala Arg Gln Ile Gln Lys Met Arg Lys 
                165                 170                 175     


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


Asn Ser Val Gly Glu Leu Asn Thr Arg Phe Ser Asp Asp Ile Asn Lys 
        195                 200                 205             


Ile Asn Asp Ala Ile Ala Asp Gln Met Ala Leu Phe Ile Gln Arg Met 
    210                 215                 220                 


Thr Ser Thr Ile Cys Gly Phe Leu Leu Gly Phe Phe Arg Gly Trp Lys 
225                 230                 235                 240 


Leu Thr Leu Val Ile Ile Ser Val Ser Pro Leu Ile Gly Ile Gly Ala 
                245                 250                 255     


Ala Thr Ile Gly Leu Ser Val Ser Lys Phe Thr Asp Tyr Glu Leu Lys 
            260                 265                 270         


Ala Tyr Ala Lys Ala Gly Val Val Ala Asp Glu Val Ile Ser Ser Met 
        275                 280                 285             


Arg Thr Val Ala Ala Phe Gly Gly Glu Lys Arg Glu Val Glu Arg Tyr 
    290                 295                 300                 


Glu Lys Asn Leu Val Phe Ala Gln Arg Trp Gly Ile Arg Lys Gly Ile 
305                 310                 315                 320 


Val Met Gly Phe Phe Thr Gly Phe Val Trp Cys Leu Ile Phe Leu Cys 
                325                 330                 335     


Tyr Ala Leu Ala Phe Trp Tyr Gly Ser Thr Leu Val Leu Asp Glu Gly 
            340                 345                 350         


Glu Tyr Thr Pro Gly Thr Leu Val Gln Ile Phe Leu Ser Val Ile Val 
        355                 360                 365             


Gly Ala Leu Asn Leu Gly Asn Ala Ser Pro Cys Leu Glu Ala Phe Ala 
    370                 375                 380                 


Thr Gly Arg Ala Ala Ala Thr Ser Ile Phe Glu Thr Ile Asp Arg Lys 
385                 390                 395                 400 


Pro Ile Ile Asp Cys Met Ser Glu Asp Gly Tyr Lys Leu Asp Arg Ile 
                405                 410                 415     


Lys Gly Glu Ile Glu Phe His Asn Val Thr Phe His Tyr Pro Ser Arg 
            420                 425                 430         


Pro Glu Val Lys Ile Leu Asn Asp Leu Asn Met Val Ile Lys Pro Gly 
        435                 440                 445             


Glu Met Thr Ala Leu Val Gly Pro Ser Gly Ala Gly Lys Ser Thr Ala 
    450                 455                 460                 


Leu Gln Leu Ile Gln Arg Phe Tyr Asp Pro Cys Glu Gly Met Val Thr 
465                 470                 475                 480 


Val Asp Gly His Asp Ile Arg Ser Leu Asn Ile Gln Trp Leu Arg Asp 
                485                 490                 495     


Gln Ile Gly Ile Val Glu Gln Glu Pro Val Leu Phe Ser Thr Thr Ile 
            500                 505                 510         


Ala Glu Asn Ile Arg Tyr Gly Arg Glu Asp Ala Thr Met Glu Asp Ile 
        515                 520                 525             


Val Gln Ala Ala Lys Glu Ala Asn Ala Tyr Asn Phe Ile Met Asp Leu 
    530                 535                 540                 


Pro Gln Gln Phe Asp Thr Leu Val Gly Glu Gly Gly Gly Gln Met Ser 
545                 550                 555                 560 


Gly Gly Gln Lys Gln Arg Val Ala Ile Ala Arg Ala Leu Ile Arg Asn 
                565                 570                 575     


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


Ser Glu Ala Met Val Gln Glu Val Leu Ser Lys Ile Gln His Gly His 
        595                 600                 605             


Thr Ile Ile Ser Val Ala His Arg Leu Ser Thr Val Arg Ala Ala Asp 
    610                 615                 620                 


Thr Ile Ile Gly Phe Glu His Gly Thr Ala Val Glu Arg Gly Thr His 
625                 630                 635                 640 


Glu Glu Leu Leu Glu Arg Lys Gly Val Tyr Phe Thr Leu Val Thr Leu 
                645                 650                 655     


Gln Ser Gln Gly Asn Gln Ala Leu Asn Glu Glu Asp Ile Lys Asp Ala 
            660                 665                 670         


Thr Glu Asp Asp Met Leu Ala Arg Thr Phe Ser Arg Gly Ser Tyr Gln 
        675                 680                 685             


Asp Ser Leu Arg Ala Ser Ile Arg Gln Arg Ser Lys Ser Gln Leu Ser 
    690                 695                 700                 


Tyr Leu Val His Glu Pro Pro Leu Ala Val Val Asp His Lys Ser Thr 
705                 710                 715                 720 


Tyr Glu Glu Asp Arg Lys Asp Lys Asp Ile Pro Val Gln Glu Glu Val 
                725                 730                 735     


Glu Pro Ala Pro Val Arg Arg Ile Leu Lys Phe Ser Ala Pro Glu Trp 
            740                 745                 750         


Pro Tyr Met Leu Val Gly Ser Val Gly Ala Ala Val Asn Gly Thr Val 
        755                 760                 765             


Thr Pro Leu Tyr Ala Phe Leu Phe Ser Gln Ile Leu Gly Thr Phe Ser 
    770                 775                 780                 


Ile Pro Asp Lys Glu Glu Gln Arg Ser Gln Ile Asn Gly Val Cys Leu 
785                 790                 795                 800 


Leu Phe Val Ala Met Gly Cys Val Ser Leu Phe Thr Gln Phe Leu Gln 
                805                 810                 815     


Gly Tyr Ala Phe Ala Lys Ser Gly Glu Leu Leu Thr Lys Arg Leu Arg 
            820                 825                 830         


Lys Phe Gly Phe Arg Ala Met Leu Gly Gln Asp Ile Ala Trp Phe Asp 
        835                 840                 845             


Asp Leu Arg Asn Ser Pro Gly Ala Leu Thr Thr Arg Leu Ala Thr Asp 
    850                 855                 860                 


Ala Ser Gln Val Gln Gly Ala Ala Gly Ser Gln Ile Gly Met Ile Val 
865                 870                 875                 880 


Asn Ser Phe Thr Asn Val Thr Val Ala Met Ile Ile Ala Phe Ser Phe 
                885                 890                 895     


Ser Trp Lys Leu Ser Leu Val Ile Leu Cys Phe Phe Pro Phe Leu Ala 
            900                 905                 910         


Leu Ser Gly Ala Thr Gln Thr Arg Met Leu Thr Gly Phe Ala Ser Arg 
        915                 920                 925             


Asp Lys Gln Ala Leu Glu Met Val Gly Gln Ile Thr Asn Glu Ala Leu 
    930                 935                 940                 


Ser Asn Ile Arg Thr Val Ala Gly Ile Gly Lys Glu Arg Arg Phe Ile 
945                 950                 955                 960 


Glu Ala Leu Glu Thr Glu Leu Glu Lys Pro Phe Lys Thr Ala Ile Gln 
                965                 970                 975     


Lys Ala Asn Ile Tyr Gly Phe Cys Phe Ala Phe Ala Gln Cys Ile Met 
            980                 985                 990         


Phe Ile Ala Asn Ser Ala Ser Tyr  Arg Tyr Gly Gly Tyr  Leu Ile Ser 
        995                 1000                 1005             


Asn Glu  Gly Leu His Phe Ser  Tyr Val Phe Arg Val  Ile Ser Ala 
    1010                 1015                 1020             


Val Val  Leu Ser Ala Thr Ala  Leu Gly Arg Ala Phe  Ser Tyr Thr 
    1025                 1030                 1035             


Pro Ser  Tyr Ala Lys Ala Lys  Ile Ser Ala Ala Arg  Phe Phe Gln 
    1040                 1045                 1050             


Leu Leu  Asp Arg Gln Pro Pro  Ile Ser Val Tyr Asn  Thr Ala Gly 
    1055                 1060                 1065             


Glu Lys  Trp Asp Asn Phe Gln  Gly Lys Ile Asp Phe  Val Asp Cys 
    1070                 1075                 1080             


Lys Phe  Thr Tyr Pro Ser Arg  Pro Asp Ser Gln Val  Leu Asn Gly 
    1085                 1090                 1095             


Leu Ser  Val Ser Ile Ser Pro  Gly Gln Thr Leu Ala  Phe Val Gly 
    1100                 1105                 1110             


Ser Ser  Gly Cys Gly Lys Ser  Thr Ser Ile Gln Leu  Leu Glu Arg 
    1115                 1120                 1125             


Phe Tyr  Asp Pro Asp Gln Gly  Lys Val Met Ile Asp  Gly His Asp 
    1130                 1135                 1140             


Ser Lys  Lys Val Asn Val Gln  Phe Leu Arg Ser Asn  Ile Gly Ile 
    1145                 1150                 1155             


Val Ser  Gln Glu Pro Val Leu  Phe Ala Cys Ser Ile  Met Asp Asn 
    1160                 1165                 1170             


Ile Lys  Tyr Gly Asp Asn Thr  Lys Glu Ile Pro Met  Glu Arg Val 
    1175                 1180                 1185             


Ile Ala  Ala Ala Lys Gln Ala  Gln Leu His Asp Phe  Val Met Ser 
    1190                 1195                 1200             


Leu Pro  Glu Lys Tyr Glu Thr  Asn Val Gly Ser Gln  Gly Ser Gln 
    1205                 1210                 1215             


Leu Ser  Arg Gly Glu Lys Gln  Arg Ile Ala Ile Ala  Arg Ala Ile 
    1220                 1225                 1230             


Val Arg  Asp Pro Lys Ile Leu  Leu Leu Asp Glu Ala  Thr Ser Ala 
    1235                 1240                 1245             


Leu Asp  Thr Glu Ser Glu Lys  Thr Val Gln Val Ala  Leu Asp Lys 
    1250                 1255                 1260             


Ala Arg  Glu Gly Arg Thr Cys  Ile Val Ile Ala His  Arg Leu Ser 
    1265                 1270                 1275             


Thr Ile  Gln Asn Ala Asp Ile  Ile Ala Val Met Ala  Gln Gly Val 
    1280                 1285                 1290             


Val Ile  Glu Lys Gly Thr His  Glu Glu Leu Met Ala  Gln Lys Gly 
    1295                 1300                 1305             


Ala Tyr  Tyr Lys Leu Val Thr  Thr Gly Ser Pro Ile  Ser 
    1310                 1315                 1320     


<210>  4
<211>  3966
<212>  DNA
<213>  Homo sapiens

<400>  4
atgtctgact cagtaattct tcgaagtata aagaaatttg gagaggagaa tgatggtttt       60

gagtcagata aatcatataa taatgataag aaatcaaggt tacaagatga gaagaaaggt      120

gatggcgtta gagttggctt ctttcaattg tttcggtttt cttcatcaac tgacatttgg      180

ctgatgtttg tgggaagttt gtgtgcattt ctccatggaa tagcccagcc aggcgtgcta      240

ctcatttttg gcacaatgac agatgttttt attgactacg acgttgagtt acaagaactc      300

cagattccag gaaaagcatg tgtgaataac accattgtat ggactaacag ttccctcaac      360

cagaacatga caaatggaac acgttgtggg ttgctgaaca tcgagagcga aatgatcaaa      420

tttgccagtt actatgctgg aattgctgtc gcagtactta tcacaggata tattcaaata      480

tgcttttggg tcattgccgc agctcgtcag atacagaaaa tgagaaaatt ttactttagg      540

agaataatga gaatggaaat agggtggttt gactgcaatt cagtggggga gctgaataca      600

agattctctg atgatattaa taaaatcaat gatgccatag ctgaccaaat ggcccttttc      660

attcagcgca tgacctcgac catctgtggt ttcctgttgg gatttttcag gggttggaaa      720

ctgaccttgg ttattatttc tgtcagccct ctcattggga ttggagcagc caccattggt      780

ctgagtgtgt ccaagtttac ggactatgag ctgaaggcct atgccaaagc aggggtggtg      840

gctgatgaag tcatttcatc aatgagaaca gtggctgctt ttggtggtga gaaaagagag      900

gttgaaaggt atgagaaaaa tcttgtgttc gcccagcgtt ggggaattag aaaaggaata      960

gtgatgggat tctttactgg attcgtgtgg tgtctcatct ttttgtgtta tgcactggcc     1020

ttctggtacg gctccacact tgtcctggat gaaggagaat atacaccagg aacccttgtc     1080

cagattttcc tcagtgtcat agtaggagct ttaaatcttg gcaatgcctc tccttgtttg     1140

gaagcctttg caactggacg tgcagcagcc accagcattt ttgagacaat agacaggaaa     1200

cccatcattg actgcatgtc agaagatggt tacaagttgg atcgaatcaa gggtgaaatt     1260

gaattccata atgtgacctt ccattatcct tccagaccag aggtgaagat tctaaatgac     1320

ctcaacatgg tcattaaacc aggggaaatg acagctctgg taggacccag tggagctgga     1380

aaaagtacag cactgcaact cattcagcga ttctatgacc cctgtgaagg aatggtgacc     1440

gtggatggcc atgacattcg ctctcttaac attcagtggc ttagagatca gattgggata     1500

gtggagcaag agccagttct gttctctacc accattgcag aaaatattcg ctatggcaga     1560

gaagatgcaa caatggaaga catagtccaa gctgccaagg aggccaatgc ctacaacttc     1620

atcatggacc tgccacagca atttgacacc cttgttggag aaggaggagg ccagatgagt     1680

ggtggccaga aacaaagggt agctatcgcc agagccctca tccgaaatcc caagattctg     1740

cttttggaca tggccacctc agctctggac aatgagagtg aagccatggt gcaagaagtg     1800

ctgagtaaga ttcagcatgg gcacacaatc atttcagttg ctcatcgctt gtctacggtc     1860

agagctgcag ataccatcat tggttttgaa catggcactg cagtggaaag agggacccat     1920

gaagaattac tggaaaggaa aggtgtttac ttcactctag tgactttgca aagccaggga     1980

aatcaagctc ttaatgaaga ggacataaag gatgcaactg aagatgacat gcttgcgagg     2040

acctttagca gagggagcta ccaggatagt ttaagggctt ccatccggca acgctccaag     2100

tctcagcttt cttacctggt gcacgaacct ccattagctg ttgtagatca taagtctacc     2160

tatgaagaag atagaaagga caaggacatt cctgtgcagg aagaagttga acctgcccca     2220

gttaggagga ttctgaaatt cagtgctcca gaatggccct acatgctggt agggtctgtg     2280

ggtgcagctg tgaacgggac agtcacaccc ttgtatgcct ttttattcag ccagattctt     2340

gggacttttt caattcctga taaagaggaa caaaggtcac agatcaatgg tgtgtgccta     2400

ctttttgtag caatgggctg tgtatctctt ttcacccaat ttctacaggg atatgccttt     2460

gctaaatctg gggagctcct aacaaaaagg ctacgtaaat ttggtttcag ggcaatgctg     2520

gggcaagata ttgcctggtt tgatgacctc agaaatagcc ctggagcatt gacaacaaga     2580

cttgctacag atgcttccca agttcaaggg gctgccggct ctcagatcgg gatgatagtc     2640

aattccttca ctaacgtcac tgtggccatg atcattgcct tctcctttag ctggaagctg     2700

agcctggtca tcttgtgctt cttccccttc ttggctttat caggagccac acagaccagg     2760

atgttgacag gatttgcctc tcgagataag caggccctgg agatggtggg acagattaca     2820

aatgaagccc tcagtaacat ccgcactgtt gctggaattg gaaaggagag gcggttcatt     2880

gaagcacttg agactgagct ggagaagccc ttcaagacag ccattcagaa agccaatatt     2940

tacggattct gctttgcctt tgcccagtgc atcatgttta ttgcgaattc tgcttcctac     3000

agatatggag gttacttaat ctccaatgag gggctccatt tcagctatgt gttcagggtg     3060

atctctgcag ttgtactgag tgcaacagct cttggaagag ccttctctta caccccaagt     3120

tatgcaaaag ctaaaatatc agctgcacgc ttttttcaac tgctggaccg acaaccccca     3180

atcagtgtat acaatactgc aggtgaaaaa tgggacaact tccaggggaa gattgatttt     3240

gttgattgta aatttacata tccttctcga cctgactcgc aagttctgaa tggtctctca     3300

gtgtcgatta gtccagggca gacactggcg tttgttggga gcagtggatg tggcaaaagc     3360

actagcattc agctgttgga acgtttctat gatcctgatc aagggaaggt gatgatagat     3420

ggtcatgaca gcaaaaaagt aaatgtccag ttcctccgct caaacattgg aattgtttcc     3480

caggaaccag tgttgtttgc ctgtagcata atggacaata tcaagtatgg agacaacacc     3540

aaagaaattc ccatggaaag agtcatagca gctgcaaaac aggctcagct gcatgatttt     3600

gtcatgtcac tcccagagaa atatgaaact aacgttgggt cccaggggtc tcaactctct     3660

agaggggaga aacaacgcat tgctattgct cgggccattg tacgagatcc taaaatcttg     3720

ctactagatg aagccacttc tgccttagac acagaaagtg aaaagacggt gcaggttgct     3780

ctagacaaag ccagagaggg tcggacctgc attgtcattg cccatcgctt gtccaccatc     3840

cagaacgcgg atatcattgc tgtcatggca cagggggtgg tgattgaaaa ggggacccat     3900

gaagaactga tggcccaaaa aggagcctac tacaaactag tcaccactgg atcccccatc     3960

agttga                                                                3966


