F2 coagulation factor II, thrombin [Homo sapiens (human)] - Gene

Summary

Official Symbol: F2provided by HGNC
Official Full Name: coagulation factor II, thrombinprovided by HGNC
Primary source: HGNC:HGNC:3535
See related: Ensembl:ENSG00000180210 MIM:176930; AllianceGenome:HGNC:3535
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: PT; THPH1; RPRGL2
Summary: This gene encodes the prothrombin protein (also known as coagulation factor II). This protein is proteolytically cleaved in multiple steps to form the activated serine protease thrombin. The activated thrombin enzyme plays an important role in thrombosis and hemostasis by converting fibrinogen to fibrin during blood clot formation, by stimulating platelet aggregation, and by activating additional coagulation factors. Thrombin also plays a role in cell proliferation, tissue repair, and angiogenesis as well as maintaining vascular integrity during development and postnatal life. Peptides derived from the C-terminus of this protein have antimicrobial activity against E. coli and P. aeruginosa. Mutations in this gene lead to various forms of thrombosis and dysprothrombinemia. Rapid increases in cytokine levels following coronavirus infections can dysregulate the coagulation cascade and produce thrombosis, compromised blood supply, and organ failure. [provided by RefSeq, May 2020]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is relevant for disease process.
Expression: Restricted expression toward liver (RPKM 385.8) See more
Orthologs: mouse all
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Genomic context

Location:: 11p11.2

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (46719213..46739506)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (46875235..46896332)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (46740763..46761056)

Chromosome 11 - NC_000011.10 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
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?

Effect of prothrombin Belgrade mutation, causing antithrombin resistance, on fibrin clot properties.
Title: Effect of prothrombin Belgrade mutation, causing antithrombin resistance, on fibrin clot properties.
The Complex Role of Thrombin in Cancer and Metastasis: Focus on Interactions with the Immune System.
Title: The Complex Role of Thrombin in Cancer and Metastasis: Focus on Interactions with the Immune System.
Comprehensive Analysis of the Role of Fibrinogen and Thrombin in Clot Formation and Structure for Plasma and Purified Fibrinogen.
Title: Comprehensive Analysis of the Role of Fibrinogen and Thrombin in Clot Formation and Structure for Plasma and Purified Fibrinogen.
Thrombomodulin Switches Signaling and Protease-Activated Receptor 1 Cleavage Specificity of Thrombin.
Title: Thrombomodulin Switches Signaling and Protease-Activated Receptor 1 Cleavage Specificity of Thrombin.
Thrombin Priming Promotes the Neuroprotective Effects of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Via the HGF/AKT/STAT3 Signaling Pathway.
Title: Thrombin Priming Promotes the Neuroprotective Effects of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Via the HGF/AKT/STAT3 Signaling Pathway.
Low alpha-thrombin/GPIb-alpha interaction may contribute to platelet hyperreactivity in COVID-19 patients
Title: Geringe α-Thrombin/GPIbα-Interaktion trägt möglicherweise zur Hyperreaktivität der Thrombozyten bei COVID-19-Patienten bei.
Activated protein C, protein S, and tissue factor pathway inhibitor cooperate to inhibit thrombin activation.
Title: Activated protein C, protein S, and tissue factor pathway inhibitor cooperate to inhibit thrombin activation.
Impact of Fibrinogen, Fibrin Thrombi, and Thrombin on Cancer Cell Extravasation Using In Vitro Microvascular Networks.
Title: Impact of Fibrinogen, Fibrin Thrombi, and Thrombin on Cancer Cell Extravasation Using In Vitro Microvascular Networks.
Low alpha-Thrombin/GPIbalpha Interaction Is a Potential Contributor to Platelet Hyper-reactivity in COVID-19 Patients.
Title: Low α-Thrombin/GPIbα Interaction Is a Potential Contributor to Platelet Hyper-reactivity in COVID-19 Patients.
Thrombogenic potential of picomolar coagulation factor XIa is mediated by thrombin wave propagation.
Title: Thrombogenic potential of picomolar coagulation factor XIa is mediated by thrombin wave propagation.

Submit: New GeneRIF Correction See all GeneRIFs (780)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Congenital prothrombin deficiency MedGen: C0272317 OMIM: 613679 GeneReviews: Not available	Compare labs
Ischemic stroke MedGen: C0948008 OMIM: 601367 GeneReviews: Not available	Compare labs
Pregnancy loss, recurrent, susceptibility to, 2 MedGen: C3280672 OMIM: 614390 GeneReviews: Not available	Compare labs
Thrombophilia due to thrombin defect MedGen: C3160733 OMIM: 188050 GeneReviews: Prothrombin Thrombophilia	Compare labs

EBI GWAS Catalog

Description
Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency. EBI GWAS Catalog EBI GWAS CatalogPubMed
Biological, clinical and population relevance of 95 loci for blood lipids. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery and refinement of loci associated with lipid levels. 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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Replication interactions

Interaction	Pubs
Knockdown of coagulation factor II (prothrombin; F2) by siRNA has both activating and inhibiting activities on HIV-1 replication in HeLa P4/R5 cells, suggesting a regulatory role in HIV replication	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Thrombin activates HIV-1 gp120/gp41 and enhances virus-cell fusion	PubMed
	env	Cleavage at amino acid position R315 of HIV-1 gp120 by thrombin is enhanced by soluble CD4 binding	PubMed
Envelope surface glycoprotein gp160, precursor	env	Thrombin enhances the fusion mediated by two R5-tropic HIV-1 gp160	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

STS-W73782 (e-PCR)
- UniSTS:40758

RH80273 (e-PCR)
- UniSTS:89656

STS-H75495 (e-PCR)
- UniSTS:32672

GDB:196314 (e-PCR)
- UniSTS:155825

GDB:196315 (e-PCR)
- UniSTS:155826

RH17520 (e-PCR)
- UniSTS:479

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables growth factor activity	TAS Traceable Author Statement more info	PubMed
enables heparin binding	IDA Inferred from Direct Assay more info	PubMed
enables lipopolysaccharide binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables serine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables serine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables signaling receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables thrombospondin receptor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in acute-phase response	IEA Inferred from Electronic Annotation more info
involved_in antimicrobial humoral immune response mediated by antimicrobial peptide	IDA Inferred from Direct Assay more info	PubMed
involved_in blood coagulation	TAS Traceable Author Statement more info	PubMed
involved_in cell surface receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in cytolysis by host of symbiont cells	IDA Inferred from Direct Assay more info	PubMed
involved_in fibrinolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in ligand-gated ion channel signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of astrocyte differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cytokine production involved in inflammatory response	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of fibrinolysis	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of platelet activation	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in neutrophil-mediated killing of gram-negative bacterium	IDA Inferred from Direct Assay more info	PubMed
involved_in platelet activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in platelet activation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of blood coagulation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of blood coagulation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell growth	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of collagen biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of insulin secretion	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of lipid kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein localization to nucleus	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of reactive oxygen species metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of receptor signaling pathway via JAK-STAT	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of release of sequestered calcium ion into cytosol	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
involved_in regulation of blood coagulation	TAS Traceable Author Statement more info	PubMed
involved_in regulation of cell shape	IEA Inferred from Electronic Annotation more info
involved_in regulation of cytosolic calcium ion concentration	IDA Inferred from Direct Assay more info	PubMed
involved_in response to wounding	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi lumen	TAS Traceable Author Statement more info
located_in blood microparticle	HDA more info	PubMed
colocalizes_with collagen-containing extracellular matrix	HDA more info	PubMed
is_active_in collagen-containing extracellular matrix	IBA Inferred from Biological aspect of Ancestor more info
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
colocalizes_with external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	PubMed
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: prothrombin

Names: prepro-coagulation factor II; prothrombin B-chain; thrombin factor II

NP_000497.1

EC 3.4.21.5

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_008953.1 RefSeqGene

Range

4974..25316

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_551

mRNA and Protein(s)

NM_000506.5 → NP_000497.1 prothrombin preproprotein

See identical proteins and their annotated locations for NP_000497.1

Status: REVIEWED

Source sequence(s)

AK303747, AK312965, BC051332

Consensus CDS

CCDS31476.1

UniProtKB/Swiss-Prot

B2R7F7, B4E1A7, P00734, Q4QZ40, Q53H04, Q53H06, Q69EZ7, Q7Z7P3, Q9UCA1

UniProtKB/TrEMBL

E9PIT3

Related

ENSP00000308541.5, ENST00000311907.10

Conserved Domains (6) summary

smart00020
Location:363 → 613

Tryp_SPc; Trypsin-like serine protease

smart00069
Location:25 → 88

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

smart00130
Location:211 → 293

KR; Kringle domain

cd00108
Location:105 → 186

KR; Kringle domain; Kringle domains are believed to play a role in binding mediators, such as peptides, other proteins, membranes, or phospholipids. They are autonomous structural domains, found in a varying number of copies, in blood clotting and ...

cd00190
Location:364 → 616

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

pfam09396
Location:317 → 363

Thrombin_light; Thrombin light chain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

46719213..46739506

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

46875235..46896332

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001311257.2: Suppressed sequence

Description

NM_001311257.2: This RefSeq was removed because currently there is insufficient support for the transcript and the protein.