F3 coagulation factor III, tissue factor [Homo sapiens (human)] - Gene

Summary

Official Symbol: F3provided by HGNC
Official Full Name: coagulation factor III, tissue factorprovided by HGNC
Primary source: HGNC:HGNC:3541
See related: Ensembl:ENSG00000117525 MIM:134390; AllianceGenome:HGNC:3541
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TF; TFA; CD142
Summary: 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]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is relevant for disease process.
Expression: Ubiquitous expression in placenta (RPKM 54.0), gall bladder (RPKM 41.2) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p21.3

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (94529173..94541759, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (94377216..94389797, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (94994729..95007315, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Human Genetic Variation in F3 and Its Impact on Tissue Factor-Dependent Disease.
Title: Human Genetic Variation in F3 and Its Impact on Tissue Factor-Dependent Disease.
Tissue factor overexpression promotes resistance to KRAS-G12C inhibition in non-small cell lung cancer.
Title: Tissue factor overexpression promotes resistance to KRAS-G12C inhibition in non-small cell lung cancer.
Expression of Tissue Factor and Platelet/Leukocyte Markers on Extracellular Vesicles Reflect Platelet-Leukocyte Interaction in Severe COVID-19.
Title: Expression of Tissue Factor and Platelet/Leukocyte Markers on Extracellular Vesicles Reflect Platelet-Leukocyte Interaction in Severe COVID-19.
Cell Surface Platelet Tissue Factor Expression: Regulation by P2Y12 and Link to Residual Platelet Reactivity.
Title: Cell Surface Platelet Tissue Factor Expression: Regulation by P2Y(12) and Link to Residual Platelet Reactivity.
High CD142 Level Marks Tumor-Promoting Fibroblasts with Targeting Potential in Colorectal Cancer.
Title: High CD142 Level Marks Tumor-Promoting Fibroblasts with Targeting Potential in Colorectal Cancer.
Tissue factor as a potential coagulative/vascular marker in relapsing-remitting multiple sclerosis.
Title: Tissue factor as a potential coagulative/vascular marker in relapsing-remitting multiple sclerosis.
Tissue factor expression in monocyte subsets during human immunothrombosis, endotoxemia and sepsis.
Title: Tissue factor expression in monocyte subsets during human immunothrombosis, endotoxemia and sepsis.
CD142 Identifies Neoplastic Desmoid Tumor Cells, Uncovering Interactions Between Neoplastic and Stromal Cells That Drive Proliferation.
Title: CD142 Identifies Neoplastic Desmoid Tumor Cells, Uncovering Interactions Between Neoplastic and Stromal Cells That Drive Proliferation.
The Heparan Sulfate Proteoglycan Syndecan-1 Triggers Breast Cancer Cell-Induced Coagulability by Induced Expression of Tissue Factor.
Title: The Heparan Sulfate Proteoglycan Syndecan-1 Triggers Breast Cancer Cell-Induced Coagulability by Induced Expression of Tissue Factor.
Peripheral blood mononuclear cell tissue factor (F3 gene) transcript levels and circulating extracellular vesicles are elevated in severe coronavirus 2019 (COVID-19) disease.
Title: Peripheral blood mononuclear cell tissue factor (F3 gene) transcript levels and circulating extracellular vesicles are elevated in severe coronavirus 2019 (COVID-19) disease.

Submit: New GeneRIF Correction See all GeneRIFs (573)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association search for type 2 diabetes genes in African Americans. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic predictors of fibrin D-dimer levels in healthy adults. EBI GWAS Catalog EBI GWAS CatalogPubMed
Ischemic stroke is associated with the ABO locus: the EuroCLOT study. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope transmembrane glycoprotein gp41	env	A synthetic peptide corresponding to the immunosuppressive domain (amino acids 574-592) of HIV-1 gp41 upregulates the expression of coagulation factor III (F3; thromboplastin, tissue factor) in peptide-treated PBMCs	PubMed
Vif	vif	HIV-1 Vif upregulates the expression of coagulation factor III (F3, thromboplastin, tissue factor) in Vif-expression T cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

F3_45.3 (e-PCR)
- UniSTS:280663

SHGC-75172 (e-PCR)
- UniSTS:57732

SHGC-31493 (e-PCR)
- UniSTS:12173

GDB:583385 (e-PCR)
- UniSTS:157885

PMC311069P5 (e-PCR)
- UniSTS:272886

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cytokine receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables phospholipid binding	IDA Inferred from Direct Assay more info	PubMed
enables protease binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to serine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in activation of blood coagulation via clotting cascade	IC Inferred by Curator more info	PubMed
involved_in activation of plasma proteins involved in acute inflammatory response	IDA Inferred from Direct Assay more info	PubMed
involved_in blood coagulation	IDA Inferred from Direct Assay more info	PubMed
involved_in cytokine-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of TOR signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of angiogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell migration	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of endothelial cell apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of endothelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of interleukin-8 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of platelet-derived growth factor receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of positive chemotaxis	IC Inferred by Curator more info	PubMed
involved_in protein processing	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in cell surface	HDA more info	PubMed
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in collagen-containing extracellular matrix	IDA Inferred from Direct Assay more info	PubMed
located_in external side of plasma membrane	IC Inferred by Curator more info	PubMed
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	TAS Traceable Author Statement more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info
part_of serine-type peptidase complex	IPI Inferred from Physical Interaction more info	PubMed

General protein information

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Preferred Names: tissue factor

Names: coagulation factor III (thromboplastin, tissue factor)

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029366.1 RefSeqGene

Range

5099..17685

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_552

mRNA and Protein(s)

NM_001178096.2 → NP_001171567.1 tissue factor isoform 2 precursor

See identical proteins and their annotated locations for NP_001171567.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the coding region, which results in a frameshift and an early stop codon, compared to variant 1. The encoded isoform (2) is shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AC093117, AF487337, DB499288

Consensus CDS

CCDS53345.1

UniProtKB/TrEMBL

Q86SE7

Related

ENSP00000359226.4, ENST00000370207.4

Conserved Domains (2) summary

pfam01108
Location:34 → 114

Tissue_fac; Tissue factor

cl21522
Location:138 → 190

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...
NM_001993.5 → NP_001984.1 tissue factor isoform 1 precursor

See identical proteins and their annotated locations for NP_001984.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC093117, DB499288, M27436

Consensus CDS

CCDS750.1

UniProtKB/Swiss-Prot

D3DT47, P13726, Q6FHG2, Q86WH4

UniProtKB/TrEMBL

B2R6M5

Related

ENSP00000334145.7, ENST00000334047.12

Conserved Domains (2) summary

pfam01108
Location:34 → 118

Tissue_fac; Tissue factor

pfam09294
Location:138 → 242

Interfer-bind; Interferon-alpha/beta receptor, fibronectin type III