F10

Protein identityUniProt · HPA

UniProt accession

P00742

Gene

F10

Ensembl

ENSG00000126218

Chromosome

13

Canonical length

488 aa

Protein class

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

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes the vitamin K-dependent coagulation factor X of the blood coagulation cascade. This factor undergoes multiple processing steps before its preproprotein is converted to a mature two-chain form by the excision of the tripeptide RKR. Two chains of the factor are held together by 1 or more disulfide bonds; the light chain contains 2 EGF-like domains, while the heavy chain contains the catalytic domain which is structurally homologous to those of the other hemostatic serine proteases. The mature factor is activated by the cleavage of the activation peptide by factor IXa (in the intrisic pathway), or by factor VIIa (in the extrinsic pathway). The activated factor then converts prothrombin to thrombin in the presence of factor Va, Ca+2, and phospholipid during blood clotting. Mutations of this gene result in factor X deficiency, a hemorrhagic condition of variable severity. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing to generate mature polypeptides. [provided by RefSeq, Aug 2015]

Canonical amino-acid sequenceUniProt

488 residues, UniProt reviewed canonical sequence.

>P00742|F10
     1  MGRPLHLVLL SASLAGLLLL GESLFIRREQ ANNILARVTR ANSFLEEMKK GHLERECMEE
    61  TCSYEEAREV FEDSDKTNEF WNKYKDGDQC ETSPCQNQGK CKDGLGEYTC TCLEGFEGKN
   121  CELFTRKLCS LDNGDCDQFC HEEQNSVVCS CARGYTLADN GKACIPTGPY PCGKQTLERR
   181  KRSVAQATSS SGEAPDSITW KPYDAADLDP TENPFDLLDF NQTQPERGDN NLTRIVGGQE
   241  CKDGECPWQA LLINEENEGF CGGTILSEFY ILTAAHCLYQ AKRFKVRVGD RNTEQEEGGE
   301  AVHEVEVVIK HNRFTKETYD FDIAVLRLKT PITFRMNVAP ACLPERDWAE STLMTQKTGI
   361  VSGFGRTHEK GRQSTRLKML EVPYVDRNSC KLSSSFIITQ NMFCAGYDTK QEDACQGDSG
   421  GPHVTRFKDT YFVTGIVSWG EGCARKGKYG IYTKVTAFLK WIDRSMKTRG LPKAKSHAPE
   481  VITSSPLK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against F10 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)

0.37

Highest tissue expression

150 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about F10.

Disease | AllUniProt

Conditions F10 is implicated in, by any mechanism.

• Factor X deficiency (FA10D) MIM:227600

Disease | GeneticClinVar

44 pathogenic / likely-pathogenic of 167 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hereditary factor X deficiency disease
• Factor X deficiency
• F10-related disorder
• Factor x deficiency, autosomal dominant
• Abnormal bleeding

ReferencesPubMed · IEDB

Publications for F10 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. 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)

0.97

gnomAD pLI

0

gnomAD missense Z

1.2

DepMap mean gene effect

0.14

DepMap dependency class

none

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 coagulation
• positive regulation of cell migration
• positive regulation of TOR signaling
• proteolysis

Molecular functions

• calcium ion binding
• phospholipid binding
• serine-type endopeptidase activity

Cellular components

• endoplasmic reticulum lumen
• external side of plasma membrane
• extracellular region
• extracellular space
• Golgi lumen
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• EGF-type aspartate/asparagine hydroxylation site
• Gamma-carboxyglutamic acid-rich (GLA) domain
• EGF-like domain
• Serine proteases, trypsin domain
• Peptidase S1A, chymotrypsin family
• EGF-like calcium-binding domain
• Peptidase S1, PA clan
• Peptidase S1A, coagulation factor VII/IX/X/C/Z
• Coagulation factor-like, Gla domain superfamily
• EGF-like calcium-binding, conserved site
• Serine proteases, trypsin family, histidine active site
• Serine proteases, trypsin family, serine active site
• Gamma-carboxyglutamic acid-rich (GLA) domain superfamily
• Peptidase S1 family, coagulation factors
• EGF-like domain
• Trypsin
• Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain
• Coagulation Factor Xa inhibitory site

KeywordsUniProt

• Blood coagulation
• Calcium
• Cleavage on pair of basic residues
• Disulfide bond
• EGF-like domain
• Gamma-carboxyglutamic acid
• Glycoprotein
• Hemostasis
• Hydrolase
• Hydroxylation
• Protease
• Repeat
• Secreted
• Serine protease
• Signal
• Zymogen