FA8_PIG
ID FA8_PIG Reviewed; 2133 AA.
AC P12263; Q95243;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 25-MAY-2022, entry version 144.
DE RecName: Full=Coagulation factor VIII;
DE AltName: Full=Procoagulant component;
DE Flags: Precursor;
GN Name=F8; Synonyms=CF8;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Healey J.F., Lubin I.M., Lollar P.;
RL Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 705-1573.
RX PubMed=3016730; DOI=10.1073/pnas.83.16.5939;
RA Toole J.J., Pittman D.D., Orr E.C., Murtha P., Wasley L.C., Kaufman R.J.;
RT "A large region (approximately equal to 95 kDa) of human factor VIII is
RT dispensable for in vitro procoagulant activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:5939-5942(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 392-759.
RX PubMed=7510693; DOI=10.1016/s0021-9258(17)37014-x;
RA Lubin I.M., Healey J.F., Scandella D., Runge M.S., Lollar P.;
RT "Elimination of a major inhibitor epitope in factor VIII.";
RL J. Biol. Chem. 269:8639-8641(1994).
CC -!- FUNCTION: Factor VIII, along with calcium and phospholipid, acts as a
CC cofactor for factor IXa when it converts factor X to the activated
CC form, factor Xa.
CC -!- SUBUNIT: Interacts with vWF. vWF binding is essential for the
CC stabilization of F8 in circulation (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space.
CC -!- PTM: Proteolytically cleaved by cathepsin CTSG to produce a partially
CC activated form. {ECO:0000250|UniProtKB:P00451}.
CC -!- SIMILARITY: Belongs to the multicopper oxidase family. {ECO:0000305}.
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DR EMBL; U49517; AAB06705.1; -; mRNA.
DR PIR; A25945; A25945.
DR PIR; T42763; T42763.
DR RefSeq; NP_999332.1; NM_214167.1.
DR PDB; 4MO3; X-ray; 1.70 A; M=1971-2129.
DR PDB; 6MF0; X-ray; 3.20 A; A/B=3-405, A/B=762-1820.
DR PDB; 7K66; X-ray; 3.92 A; A=3-405, A=1438-1820.
DR PDB; 7KBT; X-ray; 4.15 A; A=3-405, A=762-1820.
DR PDB; 7S0P; X-ray; 1.30 A; M=1974-2129.
DR PDBsum; 4MO3; -.
DR PDBsum; 6MF0; -.
DR PDBsum; 7K66; -.
DR PDBsum; 7KBT; -.
DR PDBsum; 7S0P; -.
DR AlphaFoldDB; P12263; -.
DR SMR; P12263; -.
DR STRING; 9823.ENSSSCP00000028556; -.
DR GlyConnect; 100; 22 N-Linked glycans.
DR PaxDb; P12263; -.
DR PRIDE; P12263; -.
DR GeneID; 397339; -.
DR KEGG; ssc:397339; -.
DR CTD; 2157; -.
DR eggNOG; ENOG502QSFZ; Eukaryota.
DR InParanoid; P12263; -.
DR OrthoDB; 454773at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0005507; F:copper ion binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:InterPro.
DR GO; GO:0006953; P:acute-phase response; IEA:UniProtKB-KW.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR CDD; cd00057; FA58C; 2.
DR Gene3D; 2.60.40.420; -; 6.
DR InterPro; IPR001117; Cu-oxidase.
DR InterPro; IPR011706; Cu-oxidase_C.
DR InterPro; IPR045087; Cu-oxidase_fam.
DR InterPro; IPR011707; Cu-oxidase_N.
DR InterPro; IPR033138; Cu_oxidase_CS.
DR InterPro; IPR008972; Cupredoxin.
DR InterPro; IPR000421; FA58C.
DR InterPro; IPR024715; Factor_5/8-like.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR PANTHER; PTHR11709; PTHR11709; 3.
DR Pfam; PF00394; Cu-oxidase; 1.
DR Pfam; PF07731; Cu-oxidase_2; 1.
DR Pfam; PF07732; Cu-oxidase_3; 2.
DR Pfam; PF00754; F5_F8_type_C; 2.
DR PIRSF; PIRSF000354; Factors_V_VIII; 1.
DR SMART; SM00231; FA58C; 2.
DR SUPFAM; SSF49503; SSF49503; 6.
DR SUPFAM; SSF49785; SSF49785; 2.
DR PROSITE; PS01285; FA58C_1; 2.
DR PROSITE; PS01286; FA58C_2; 2.
DR PROSITE; PS50022; FA58C_3; 2.
DR PROSITE; PS00079; MULTICOPPER_OXIDASE1; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acute phase; Blood coagulation; Calcium; Disulfide bond;
KW Glycoprotein; Hemostasis; Metal-binding; Reference proteome; Repeat;
KW Secreted; Signal; Sulfation.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..2133
FT /note="Coagulation factor VIII"
FT /id="PRO_0000002973"
FT DOMAIN 20..357
FT /note="F5/8 type A 1"
FT DOMAIN 20..199
FT /note="Plastocyanin-like 1"
FT DOMAIN 207..357
FT /note="Plastocyanin-like 2"
FT DOMAIN 399..730
FT /note="F5/8 type A 2"
FT DOMAIN 399..573
FT /note="Plastocyanin-like 3"
FT DOMAIN 583..730
FT /note="Plastocyanin-like 4"
FT DOMAIN 1495..1822
FT /note="F5/8 type A 3"
FT DOMAIN 1495..1659
FT /note="Plastocyanin-like 5"
FT DOMAIN 1669..1822
FT /note="Plastocyanin-like 6"
FT DOMAIN 1822..1970
FT /note="F5/8 type C 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DOMAIN 1975..2127
FT /note="F5/8 type C 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT REGION 760..1599
FT /note="B"
FT REGION 760..790
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 804..914
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1042..1078
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1160..1179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1200..1221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1358..1391
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1406..1441
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 760..784
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 855..881
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 882..904
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1052..1073
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 391..392
FT /note="Cleavage; by thrombin"
FT /evidence="ECO:0000250"
FT SITE 759..760
FT /note="Cleavage; by thrombin"
FT /evidence="ECO:0000250"
FT SITE 1449..1450
FT /note="Cleavage (activation)"
FT /evidence="ECO:0000250"
FT SITE 1490..1491
FT /note="Cleavage; by thrombin"
FT /evidence="ECO:0000250"
FT MOD_RES 737
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 738
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 742
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250"
FT CARBOHYD 233
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 259
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 601
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 929
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 985
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1025
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1181
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1208
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1245
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1265
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1335
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1408
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1611
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1919
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 173..199
FT /evidence="ECO:0000305"
FT DISULFID 547..573
FT /evidence="ECO:0000305"
FT DISULFID 1633..1659
FT /evidence="ECO:0000305"
FT DISULFID 1822..1970
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DISULFID 1975..2127
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT CONFLICT 713
FT /note="N -> M (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 734
FT /note="I -> T (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 792
FT /note="G -> Q (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 1133
FT /note="E -> F (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 1191
FT /note="I -> L (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 1209
FT /note="R -> F (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 1437
FT /note="C -> G (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 1456
FT /note="F -> R (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 1539
FT /note="F -> R (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 1546
FT /note="Q -> N (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT STRAND 21..24
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 27..33
FT /evidence="ECO:0007829|PDB:6MF0"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 66..72
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:6MF0"
FT TURN 87..91
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 93..99
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 103..107
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 119..123
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:6MF0"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:6MF0"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 172..179
FT /evidence="ECO:0007829|PDB:6MF0"
FT HELIX 184..188
FT /evidence="ECO:0007829|PDB:6MF0"
FT TURN 189..191
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 193..199
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 211..223
FT /evidence="ECO:0007829|PDB:6MF0"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 250..252
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 271..280
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 287..291
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 296..298
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 301..308
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 313..319
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 324..330
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 341..347
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 400..405
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1496..1508
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1531..1543
FT /evidence="ECO:0007829|PDB:6MF0"
FT HELIX 1555..1557
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1564..1566
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1568..1578
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1580..1582
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1613..1619
FT /evidence="ECO:0007829|PDB:6MF0"
FT HELIX 1622..1624
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1632..1639
FT /evidence="ECO:0007829|PDB:6MF0"
FT HELIX 1646..1650
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1653..1659
FT /evidence="ECO:0007829|PDB:6MF0"
FT TURN 1666..1669
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1673..1685
FT /evidence="ECO:0007829|PDB:6MF0"
FT TURN 1686..1688
FT /evidence="ECO:0007829|PDB:6MF0"
FT HELIX 1690..1696
FT /evidence="ECO:0007829|PDB:6MF0"
FT HELIX 1714..1716
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1717..1722
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1734..1738
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1741..1747
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1756..1759
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1764..1778
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1784..1789
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1795..1801
FT /evidence="ECO:0007829|PDB:6MF0"
FT HELIX 1804..1808
FT /evidence="ECO:0007829|PDB:6MF0"
FT STRAND 1813..1818
FT /evidence="ECO:0007829|PDB:6MF0"
FT TURN 1981..1983
FT /evidence="ECO:0007829|PDB:4MO3"
FT STRAND 1984..1986
FT /evidence="ECO:0007829|PDB:4MO3"
FT HELIX 1988..1990
FT /evidence="ECO:0007829|PDB:4MO3"
FT STRAND 1991..1994
FT /evidence="ECO:0007829|PDB:4MO3"
FT HELIX 2006..2008
FT /evidence="ECO:0007829|PDB:4MO3"
FT STRAND 2031..2047
FT /evidence="ECO:0007829|PDB:4MO3"
FT STRAND 2049..2051
FT /evidence="ECO:0007829|PDB:4MO3"
FT STRAND 2054..2071
FT /evidence="ECO:0007829|PDB:4MO3"
FT STRAND 2088..2091
FT /evidence="ECO:0007829|PDB:4MO3"
FT STRAND 2094..2117
FT /evidence="ECO:0007829|PDB:4MO3"
FT STRAND 2120..2127
FT /evidence="ECO:0007829|PDB:4MO3"
SQ SEQUENCE 2133 AA; 239305 MW; 152BBA8997F570DA CRC64;
MQLELSTCVF LCLLPLGFSA IRRYYLGAVE LSWDYRQSEL LRELHVDTRF PATAPGALPL
GPSVLYKKTV FVEFTDQLFS VARPRPPWMG LLGPTIQAEV YDTVVVTLKN MASHPVSLHA
VGVSFWKSSE GAEYEDHTSQ REKEDDKVLP GKSQTYVWQV LKENGPTASD PPCLTYSYLS
HVDLVKDLNS GLIGALLVCR EGSLTRERTQ NLHEFVLLFA VFDEGKSWHS ARNDSWTRAM
DPAPARAQPA MHTVNGYVNR SLPGLIGCHK KSVYWHVIGM GTSPEVHSIF LEGHTFLVRH
HRQASLEISP LTFLTAQTFL MDLGQFLLFC HISSHHHGGM EAHVRVESCA EEPQLRRKAD
EEEDYDDNLY DSDMDVVRLD GDDVSPFIQI RSVAKKHPKT WVHYISAEEE DWDYAPAVPS
PSDRSYKSLY LNSGPQRIGR KYKKARFVAY TDVTFKTRKA IPYESGILGP LLYGEVGDTL
LIIFKNKASR PYNIYPHGIT DVSALHPGRL LKGWKHLKDM PILPGETFKY KWTVTVEDGP
TKSDPRCLTR YYSSSINLEK DLASGLIGPL LICYKESVDQ RGNQMMSDKR NVILFSVFDE
NQSWYLAENI QRFLPNPDGL QPQDPEFQAS NIMHSINGYV FDSLQLSVCL HEVAYWYILS
VGAQTDFLSV FFSGYTFKHK MVYEDTLTLF PFSGETVFMS MENPGLWVLG CHNSDLRNRG
MTALLKVYSC DRDIGDYYDN TYEDIPGFLL SGKNVIEPRS FAQNSRPPSA SQKQFQTITS
PEDDVELDPQ SGERTQALEE LSVPSGDGSM LLGQNPAPHG SSSSDLQEAR NEADDYLPGA
RERNTAPSAA ARLRPELHHS AERVLTPEPE KELKKLDSKM SSSSDLLKTS PTIPSDTLSA
ETERTHSLGP PHPQVNFRSQ LGAIVLGKNS SHFIGAGVPL GSTEEDHESS LGENVSPVES
DGIFEKERAH GPASLTKDDV LFKVNISLVK TNKARVYLKT NRKIHIDDAA LLTENRASAT
FMDKNTTASG LNHVSNWIKG PLGKNPLSSE RGPSPELLTS SGSGKSVKGQ SSGQGRIRVA
VEEEELSKGK EMMLPNSELT FLTNSADVQG NDTHSQGKKS REEMERREKL VQEKVDLPQV
YTATGTKNFL RNIFHQSTEP SVEGFDGGSH APVPQDSRSL NDSAERAETH IAHFSAIREE
APLEAPGNRT GPGPRSAVPR RVKQSLKQIR LPLEEIKPER GVVLNATSTR WSESSPILQG
AKRNNLSLPF LTLEMAGGQG KISALGKSAA GPLASGKLEK AVLSSAGLSE ASGKAEFLPK
VRVHREDLLP QKTSNVSCAH GDLGQEIFLQ KTRGPVNLNK VNRPGRTPSK LLGPPMPKEW
ESLEKSPKST ALRTKDIISL PLDRHESNHS IAAKNEGQAE TQREAAWTKQ GGPGRLCAPK
PPVLRRHQRD ISLPTFQPEE DKMDYDDIFS TETKGEDFDI YGEDENQDPR SFQKRTRHYF
IAAVEQLWDY GMSESPRALR NRAQNGEVPR FKKVVFREFA DGSFTQPSYR GELNKHLGLL
GPYIRAEVED NIMVTFKNQA SRPYSFYSSL ISYPDDQEQG AEPRHNFVQP NETRTYFWKV
QHHMAPTEDE FDCKAWAYFS DVDLEKDVHS GLIGPLLICR ANTLNAAHGR QVTVQEFALF
FTIFDETKSW YFTENVERNC RAPCHLQMED PTLKENYRFH AINGYVMDTL PGLVMAQNQR
IRWYLLSMGS NENIHSIHFS GHVFSVRKKE EYKMAVYNLY PGVFETVEML PSKVGIWRIE
CLIGEHLQAG MSTTFLVYSK ECQAPLGMAS GRIRDFQITA SGQYGQWAPK LARLHYSGSI
NAWSTKDPHS WIKVDLLAPM IIHGIMTQGA RQKFSSLYIS QFIIMYSLDG RNWQSYRGNS
TGTLMVFFGN VDASGIKHNI FNPPIVARYI RLHPTHYSIR STLRMELMGC DLNSCSMPLG
MQNKAISDSQ ITASSHLSNI FATWSPSQAR LHLQGRTNAW RPRVSSAEEW LQVDLQKTVK
VTGITTQGVK SLLSSMYVKE FLVSSSQDGR RWTLFLQDGH TKVFQGNQDS STPVVNALDP
PLFTRYLRIH PTSWAQHIAL RLEVLGCEAQ DLY
