F3

Protein identityUniProt · HPA

UniProt accession

P13726

Gene

F3

Ensembl

ENSG00000117525

Chromosome

1

Canonical length

295 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, CD markers, FDA approved drug targets, Plasma proteins, Predicted membrane proteins, Predicted secreted proteins, Transporters

Subcellular location

Vesicles

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes coagulation factor III which is a cell surface glycoprotein. This factor enables cells to initiate the blood coagulation cascades, and it functions as the high-affinity receptor for the coagulation factor VII. The resulting complex provides a catalytic event that is responsible for initiation of the coagulation protease cascades by specific limited proteolysis. Unlike the other cofactors of these protease cascades, which circulate as nonfunctional precursors, this factor is a potent initiator that is fully functional when expressed on cell surfaces, for example, on monocytes. There are 3 distinct domains of this factor: extracellular, transmembrane, and cytoplasmic. Platelets and monocytes have been shown to express this coagulation factor under procoagulatory and proinflammatory stimuli, and a major role in HIV-associated coagulopathy has been described. Platelet-dependent monocyte expression of coagulation factor III has been described to be associated with Coronavirus Disease 2019 (COVID-19) severity and mortality. This protein is the only one in the coagulation pathway for which a congenital deficiency has not been described. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Aug 2020]

Canonical amino-acid sequenceUniProt

295 residues, UniProt reviewed canonical sequence.

>P13726|F3
     1  METPAWPRVP RPETAVARTL LLGWVFAQVA GASGTTNTVA AYNLTWKSTN FKTILEWEPK
    61  PVNQVYTVQI STKSGDWKSK CFYTTDTECD LTDEIVKDVK QTYLARVFSY PAGNVESTGS
   121  AGEPLYENSP EFTPYLETNL GQPTIQSFEQ VGTKVNVTVE DERTLVRRNN TFLSLRDVFG
   181  KDLIYTLYYW KSSSSGKKTA KTNTNEFLID VDKGENYCFS VQAVIPSRTV NRKSTDSPVE
   241  CMGQEKGEFR EIFYIIGAVV FVVIILVIIL AISLHKCRKA GVGQSWKENS PLNVS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against F3 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

1

Mean surface accessibility (rSASA)

0.38

Highest tissue expression

125 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about F3.

Disease | ImmuneIEDB

Conditions an epitope on F3 was assayed in.

• lymphoid leukemia T cell

ReferencesPubMed · IEDB

Publications for F3 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)

0.8

gnomAD pLI

0.02

gnomAD missense Z

0.61

DepMap mean gene effect

-0.09

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

• activation of blood coagulation via clotting cascade
• blood coagulation
• cytokine-mediated signaling pathway
• positive regulation of angiogenesis
• positive regulation of cell migration
• positive regulation of endothelial cell apoptotic process
• positive regulation of endothelial cell proliferation
• positive regulation of gene expression
• positive regulation of interleukin-8 production
• positive regulation of platelet-derived growth factor receptor signaling pathway
• positive regulation of positive chemotaxis
• positive regulation of TOR signaling
• protein processing
• activation of plasma proteins involved in acute inflammatory response

Molecular functions

• cytokine receptor activity
• phospholipid binding
• protease binding

Cellular components

• cell surface
• external side of plasma membrane
• extracellular matrix
• extracellular space
• membrane
• plasma membrane
• serine-type peptidase complex

Protein domainsUniProt · Pfam · InterPro

• Fibronectin type III
• Immunoglobulin-like fold
• Interferon/interleukin receptor domain
• Fibronectin type III superfamily
• Tissue factor
• Interferon-alpha/beta receptor, fibronectin type III
• Tissue factor
• Tissue factor, conserved site

KeywordsUniProt

• Blood coagulation
• Disulfide bond
• Glycoprotein
• Hemostasis
• Lipoprotein
• Membrane
• Palmitate
• Secreted
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of F3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HSPE
• F7