FA8_MOUSE
ID FA8_MOUSE Reviewed; 2319 AA.
AC Q06194; A2AN88;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Coagulation factor VIII;
DE AltName: Full=Procoagulant component;
DE Flags: Precursor;
GN Name=F8; Synonyms=Cf8, F8c;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6 X CBA; TISSUE=Liver;
RX PubMed=8314577; DOI=10.1006/geno.1993.1200;
RA Elder B., Lakich D., Gitschier J.;
RT "Sequence of the murine factor VIII cDNA.";
RL Genomics 16:374-379(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
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 -!- TISSUE SPECIFICITY: Found in most tissues.
CC -!- PTM: The binding of vWF and activation depend on the sulfation of Tyr-
CC 1669.
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; L05573; AAA37385.1; -; mRNA.
DR EMBL; AL731844; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL808110; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466576; EDL29229.1; -; Genomic_DNA.
DR CCDS; CCDS30238.1; -.
DR PIR; A47004; A47004.
DR RefSeq; NP_032003.2; NM_007977.2.
DR AlphaFoldDB; Q06194; -.
DR SMR; Q06194; -.
DR STRING; 10090.ENSMUSP00000033539; -.
DR GlyGen; Q06194; 26 sites.
DR iPTMnet; Q06194; -.
DR PhosphoSitePlus; Q06194; -.
DR MaxQB; Q06194; -.
DR PaxDb; Q06194; -.
DR PRIDE; Q06194; -.
DR ProteomicsDB; 271544; -.
DR Antibodypedia; 393; 1120 antibodies from 41 providers.
DR DNASU; 14069; -.
DR Ensembl; ENSMUST00000033539; ENSMUSP00000033539; ENSMUSG00000031196.
DR GeneID; 14069; -.
DR KEGG; mmu:14069; -.
DR UCSC; uc009tpt.3; mouse.
DR CTD; 2157; -.
DR MGI; MGI:88383; F8.
DR VEuPathDB; HostDB:ENSMUSG00000031196; -.
DR eggNOG; ENOG502QSFZ; Eukaryota.
DR GeneTree; ENSGT00940000160294; -.
DR HOGENOM; CLU_000948_1_0_1; -.
DR InParanoid; Q06194; -.
DR OMA; FPMTAVT; -.
DR OrthoDB; 454773at2759; -.
DR PhylomeDB; Q06194; -.
DR TreeFam; TF329807; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR Reactome; R-MMU-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR Reactome; R-MMU-140875; Common Pathway of Fibrin Clot Formation.
DR Reactome; R-MMU-163841; Gamma carboxylation, hypusine formation and arylsulfatase activation.
DR Reactome; R-MMU-204005; COPII-mediated vesicle transport.
DR Reactome; R-MMU-5694530; Cargo concentration in the ER.
DR BioGRID-ORCS; 14069; 3 hits in 73 CRISPR screens.
DR ChiTaRS; F8; mouse.
DR PRO; PR:Q06194; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q06194; protein.
DR Bgee; ENSMUSG00000031196; Expressed in mesenteric lymph node and 70 other tissues.
DR ExpressionAtlas; Q06194; baseline and differential.
DR Genevisible; Q06194; MM.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0007597; P:blood coagulation, intrinsic pathway; ISO:MGI.
DR GO; GO:0006508; P:proteolysis; ISO:MGI.
DR CDD; cd00057; FA58C; 2.
DR Gene3D; 2.60.40.420; -; 6.
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; 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 2: Evidence at transcript level;
KW Acute phase; Blood coagulation; Calcium; Disulfide bond; Glycoprotein;
KW Hemostasis; Metal-binding; Reference proteome; Repeat; Secreted; Signal;
KW Sulfation.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..2319
FT /note="Coagulation factor VIII"
FT /id="PRO_0000002972"
FT DOMAIN 20..349
FT /note="F5/8 type A 1"
FT DOMAIN 20..199
FT /note="Plastocyanin-like 1"
FT DOMAIN 207..349
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 1683..2008
FT /note="F5/8 type A 3"
FT DOMAIN 1683..1845
FT /note="Plastocyanin-like 5"
FT DOMAIN 1855..2008
FT /note="Plastocyanin-like 6"
FT DOMAIN 2008..2156
FT /note="F5/8 type C 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DOMAIN 2161..2313
FT /note="F5/8 type C 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT REGION 760..1640
FT /note="B"
FT REGION 1530..1549
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1531..1549
FT /note="Basic and acidic 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 1324..1325
FT /note="Cleavage (activation)"
FT /evidence="ECO:0000250"
FT SITE 1640..1641
FT /note="Cleavage (activation)"
FT /evidence="ECO:0000250"
FT SITE 1678..1679
FT /note="Cleavage; by thrombin"
FT /evidence="ECO:0000250"
FT MOD_RES 367
FT /note="Sulfotyrosine"
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 MOD_RES 1669
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250"
FT MOD_RES 1687
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250"
FT CARBOHYD 61
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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 423
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 880
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 958
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1015
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1022
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1026
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1044
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1076
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1087
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1136
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1255
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1268
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1273
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1274
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1302
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1316
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1378
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1797
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 2105
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 1819..1845
FT /evidence="ECO:0000305"
FT DISULFID 2008..2156
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DISULFID 2161..2313
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT CONFLICT 959
FT /note="V -> A (in Ref. 1; AAA37385)"
FT /evidence="ECO:0000305"
FT CONFLICT 988
FT /note="M -> I (in Ref. 1; AAA37385)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2319 AA; 266196 MW; 09CAC4CFBCCECA57 CRC64;
MQIALFACFF LSLFNFCSSA IRRYYLGAVE LSWNYIQSDL LSVLHTDSRF LPRMSTSFPF
NTSIMYKKTV FVEYKDQLFN IAKPRPPWMG LLGPTIWTEV HDTVVITLKN MASHPVSLHA
VGVSYWKASE GDEYEDQTSQ MEKEDDKVFP GESHTYVWQV LKENGPMASD PPCLTYSYMS
HVDLVKDLNS GLIGALLVCK EGSLSKERTQ MLYQFVLLFA VFDEGKSWHS ETNDSYTQSM
DSASARDWPK MHTVNGYVNR SLPGLIGCHR KSVYWHVIGM GTTPEIHSIF LEGHTFFVRN
HRQASLEISP ITFLTAQTLL IDLGQFLLFC HISSHKHDGM EAYVKVDSCP EESQWQKKNN
NEEMEDYDDD LYSEMDMFTL DYDSSPFIQI RSVAKKYPKT WIHYISAEEE DWDYAPSVPT
SDNGSYKSQY LSNGPHRIGR KYKKVRFIAY TDETFKTRET IQHESGLLGP LLYGEVGDTL
LIIFKNQASR PYNIYPHGIT DVSPLHARRL PRGIKHVKDL PIHPGEIFKY KWTVTVEDGP
TKSDPRCLTR YYSSFINPER DLASGLIGPL LICYKESVDQ RGNQMMSDKR NVILFSIFDE
NQSWYITENM QRFLPNAAKT QPQDPGFQAS NIMHSINGYV FDSLELTVCL HEVAYWHILS
VGAQTDFLSI FFSGYTFKHK MVYEDTLTLF PFSGETVFMS MENPGLWVLG CHNSDFRKRG
MTALLKVSSC DKSTSDYYEE IYEDIPTQLV NENNVIDPRS FFQNTNHPNT RKKKFKDSTI
PKNDMEKIEP QFEEIAEMLK VQSVSVSDML MLLGQSHPTP HGLFLSDGQE AIYEAIHDDH
SPNAIDSNEG PSKVTQLRPE SHHSEKIVFT PQPGLQLRSN KSLETTIEVK WKKLGLQVSS
LPSNLMTTTI LSDNLKATFE KTDSSGFPDM PVHSSSKLST TAFGKKAYSL VGSHVPLNVS
EENSDSNILD STLMYSQESL PRDNILSMEN DRLLREKRFH GIALLTKDNT LFKDNVSLMK
TNKTYNHSTT NEKLHTESPT SIENSTTDLQ DAILKVNSEI QEVTALIHDG TLLGKNSTYL
RLNHMLNRTT STKNKDIFHR KDEDPIPQDE ENTIMPFSKM LFLSESSNWF KKTNGNNSLN
SEQEHSPKQL VYLMFKKYVK NQSFLSEKNK VTVEQDGFTK NIGLKDMAFP HNMSIFLTTL
SNVHENGRHN QEKNIQEEIE KEALIEEKVV LPQVHEATGS KNFLKDILIL GTRQNISLYE
VHVPVLQNIT SINNSTNTVQ IHMEHFFKRR KDKETNSEGL VNKTREMVKN YPSQKNITTQ
RSKRALGQFR LSTQWLKTIN CSTQCIIKQI DHSKEMKKFI TKSSLSDSSV IKSTTQTNSS
DSHIVKTSAF PPIDLKRSPF QNKFSHVQAS SYIYDFKTKS SRIQESNNFL KETKINNPSL
AILPWNMFID QGKFTSPGKS NTNSVTYKKR ENIIFLKPTL PEESGKIELL PQVSIQEEEI
LPTETSHGSP GHLNLMKEVF LQKIQGPTKW NKAKRHGESI KGKTESSKNT RSKLLNHHAW
DYHYAAQIPK DMWKSKEKSP EIISIKQEDT ILSLRPHGNS HSIGANEKQN WPQRETTWVK
QGQTQRTCSQ IPPVLKRHQR ELSAFQSEQE ATDYDDAITI ETIEDFDIYS EDIKQGPRSF
QQKTRHYFIA AVERLWDYGM STSHVLRNRY QSDNVPQFKK VVFQEFTDGS FSQPLYRGEL
NEHLGLLGPY IRAEVEDNIM VTFKNQASRP YSFYSSLISY KEDQRGEEPR RNFVKPNETK
IYFWKVQHHM APTEDEFDCK AWAYFSDVDL ERDMHSGLIG PLLICHANTL NPAHGRQVSV
QEFALLFTIF DETKSWYFTE NVKRNCKTPC NFQMEDPTLK ENYRFHAING YVMDTLPGLV
MAQDQRIRWY LLSMGNNENI QSIHFSGHVF TVRKKEEYKM AVYNLYPGVF ETLEMIPSRA
GIWRVECLIG EHLQAGMSTL FLVYSKQCQI PLGMASGSIR DFQITASGHY GQWAPNLARL
HYSGSINAWS TKEPFSWIKV DLLAPMIVHG IKTQGARQKF SSLYISQFII MYSLDGKKWL
SYQGNSTGTL MVFFGNVDSS GIKHNSFNPP IIARYIRLHP THSSIRSTLR MELMGCDLNS
CSIPLGMESK VISDTQITAS SYFTNMFATW SPSQARLHLQ GRTNAWRPQV NDPKQWLQVD
LQKTMKVTGI ITQGVKSLFT SMFVKEFLIS SSQDGHHWTQ ILYNGKVKVF QGNQDSSTPM
MNSLDPPLLT RYLRIHPQIW EHQIALRLEI LGCEAQQQY
