F5

Protein identityUniProt · HPA

UniProt accession

P12259

Gene

F5

Ensembl

ENSG00000198734

Chromosome

1

Canonical length

2224 aa

Protein class

Candidate cardiovascular disease genes, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted secreted proteins

Subcellular location

Golgi apparatus

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes an essential cofactor of the blood coagulation cascade. This factor circulates in plasma, and is converted to the active form by the release of the activation peptide by thrombin during coagulation. This generates a heavy chain and a light chain which are held together by calcium ions. The activated protein is a cofactor that participates with activated coagulation factor X to activate prothrombin to thrombin. Defects in this gene result in either an autosomal recessive hemorrhagic diathesis or an autosomal dominant form of thrombophilia, which is known as activated protein C resistance. [provided by RefSeq, Oct 2008]

Canonical amino-acid sequenceUniProt

2224 residues, UniProt reviewed canonical sequence.

>P12259|F5
     1  MFPGCPRLWV LVVLGTSWVG WGSQGTEAAQ LRQFYVAAQG ISWSYRPEPT NSSLNLSVTS
    61  FKKIVYREYE PYFKKEKPQS TISGLLGPTL YAEVGDIIKV HFKNKADKPL SIHPQGIRYS
   121  KLSEGASYLD HTFPAEKMDD AVAPGREYTY EWSISEDSGP THDDPPCLTH IYYSHENLIE
   181  DFNSGLIGPL LICKKGTLTE GGTQKTFDKQ IVLLFAVFDE SKSWSQSSSL MYTVNGYVNG
   241  TMPDITVCAH DHISWHLLGM SSGPELFSIH FNGQVLEQNH HKVSAITLVS ATSTTANMTV
   301  GPEGKWIISS LTPKHLQAGM QAYIDIKNCP KKTRNLKKIT REQRRHMKRW EYFIAAEEVI
   361  WDYAPVIPAN MDKKYRSQHL DNFSNQIGKH YKKVMYTQYE DESFTKHTVN PNMKEDGILG
   421  PIIRAQVRDT LKIVFKNMAS RPYSIYPHGV TFSPYEDEVN SSFTSGRNNT MIRAVQPGET
   481  YTYKWNILEF DEPTENDAQC LTRPYYSDVD IMRDIASGLI GLLLICKSRS LDRRGIQRAA
   541  DIEQQAVFAV FDENKSWYLE DNINKFCENP DEVKRDDPKF YESNIMSTIN GYVPESITTL
   601  GFCFDDTVQW HFCSVGTQNE ILTIHFTGHS FIYGKRHEDT LTLFPMRGES VTVTMDNVGT
   661  WMLTSMNSSP RSKKLRLKFR DVKCIPDDDE DSYEIFEPPE STVMATRKMH DRLEPEDEES
   721  DADYDYQNRL AAALGIRSFR NSSLNQEEEE FNLTALALEN GTEFVSSNTD IIVGSNYSSP
   781  SNISKFTVNN LAEPQKAPSH QQATTAGSPL RHLIGKNSVL NSSTAEHSSP YSEDPIEDPL
   841  QPDVTGIRLL SLGAGEFKSQ EHAKHKGPKV ERDQAAKHRF SWMKLLAHKV GRHLSQDTGS
   901  PSGMRPWEDL PSQDTGSPSR MRPWKDPPSD LLLLKQSNSS KILVGRWHLA SEKGSYEIIQ
   961  DTDEDTAVNN WLISPQNASR AWGESTPLAN KPGKQSGHPK FPRVRHKSLQ VRQDGGKSRL
  1021  KKSQFLIKTR KKKKEKHTHH APLSPRTFHP LRSEAYNTFS ERRLKHSLVL HKSNETSLPT
  1081  DLNQTLPSMD FGWIASLPDH NQNSSNDTGQ ASCPPGLYQT VPPEEHYQTF PIQDPDQMHS
  1141  TSDPSHRSSS PELSEMLEYD RSHKSFPTDI SQMSPSSEHE VWQTVISPDL SQVTLSPELS
  1201  QTNLSPDLSH TTLSPELIQR NLSPALGQMP ISPDLSHTTL SPDLSHTTLS LDLSQTNLSP
  1261  ELSQTNLSPA LGQMPLSPDL SHTTLSLDFS QTNLSPELSH MTLSPELSQT NLSPALGQMP
  1321  ISPDLSHTTL SLDFSQTNLS PELSQTNLSP ALGQMPLSPD PSHTTLSLDL SQTNLSPELS
  1381  QTNLSPDLSE MPLFADLSQI PLTPDLDQMT LSPDLGETDL SPNFGQMSLS PDLSQVTLSP
  1441  DISDTTLLPD LSQISPPPDL DQIFYPSESS QSLLLQEFNE SFPYPDLGQM PSPSSPTLND
  1501  TFLSKEFNPL VIVGLSKDGT DYIEIIPKEE VQSSEDDYAE IDYVPYDDPY KTDVRTNINS
  1561  SRDPDNIAAW YLRSNNGNRR NYYIAAEEIS WDYSEFVQRE TDIEDSDDIP EDTTYKKVVF
  1621  RKYLDSTFTK RDPRGEYEEH LGILGPIIRA EVDDVIQVRF KNLASRPYSL HAHGLSYEKS
  1681  SEGKTYEDDS PEWFKEDNAV QPNSSYTYVW HATERSGPES PGSACRAWAY YSAVNPEKDI
  1741  HSGLIGPLLI CQKGILHKDS NMPMDMREFV LLFMTFDEKK SWYYEKKSRS SWRLTSSEMK
  1801  KSHEFHAING MIYSLPGLKM YEQEWVRLHL LNIGGSQDIH VVHFHGQTLL ENGNKQHQLG
  1861  VWPLLPGSFK TLEMKASKPG WWLLNTEVGE NQRAGMQTPF LIMDRDCRMP MGLSTGIISD
  1921  SQIKASEFLG YWEPRLARLN NGGSYNAWSV EKLAAEFASK PWIQVDMQKE VIITGIQTQG
  1981  AKHYLKSCYT TEFYVAYSSN QINWQIFKGN STRNVMYFNG NSDASTIKEN QFDPPIVARY
  2041  IRISPTRAYN RPTLRLELQG CEVNGCSTPL GMENGKIENK QITASSFKKS WWGDYWEPFR
  2101  ARLNAQGRVN AWQAKANNNK QWLEIDLLKI KKITAIITQG CKSLSSEMYV KSYTIHYSEQ
  2161  GVEWKPYRLK SSMVDKIFEG NTNTKGHVKN FFNPPIISRF IRVIPKTWNQ SIALRLELFG
  2221  CDIY

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against F5 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.4

Highest tissue expression

165 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about F5.

Disease | AllUniProt

Conditions F5 is implicated in, by any mechanism.

• Factor V deficiency (FA5D) MIM:227400
• Thrombophilia due to activated protein C resistance (THPH2) MIM:188055
• Budd-Chiari syndrome (BDCHS) MIM:600880
• Ischemic stroke (ISCHSTR) MIM:601367
• Pregnancy loss, recurrent, 1 (RPRGL1) MIM:614389

Disease | GeneticClinVar

111 pathogenic / likely-pathogenic of 1,459 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Congenital factor V deficiency
• Factor V deficiency
• Thrombophilia due to activated protein C resistance
• Pregnancy loss, recurrent, susceptibility to, 1
• Budd-Chiari syndrome

Disease | AutoantibodyPubMed

Conditions in which antibodies against F5 are reported. Each links to that disease's full target list.

Showing 0 of 1 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for F5 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.56

gnomAD pLI

0

gnomAD missense Z

0.46

DepMap mean gene effect

-0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• blood circulation
• blood coagulation
• response to vitamin K

Molecular functions

• copper ion binding

Cellular components

• COPII-coated ER to Golgi transport vesicle
• endoplasmic reticulum lumen
• endoplasmic reticulum-Golgi intermediate compartment membrane
• extracellular region
• extracellular space
• extracellular vesicle
• membrane
• plasma membrane
• platelet alpha granule
• platelet alpha granule lumen

Protein domainsUniProt · Pfam · InterPro

• Coagulation factor 5/8, C-terminal domain
• Cupredoxin
• Galactose-binding-like domain superfamily
• Multicopper oxidase-like, N-terminal
• Coagulation factor 5/8-like
• Multicopper oxidases, conserved site
• Neuropilin/Multicopper Oxidase/Coagulation Factor
• F5/8 type C domain
• Multicopper oxidase

KeywordsUniProt

• Blood coagulation
• Calcium
• Copper
• Disulfide bond
• Glycoprotein
• Hemostasis
• Metal-binding
• Phosphoprotein
• Repeat
• Secreted
• Signal
• Sulfation
• Thrombophilia
• Zymogen