F2 coagulation factor II, thrombin [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: F2provided by RGD
Official Full Name: coagulation factor II, thrombinprovided by RGD
Primary source: RGD:61996
See related: EnsemblRapid:ENSRNOG00000016325 AllianceGenome:RGD:61996
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Summary: Predicted to enable several functions, including heparin binding activity; lipopolysaccharide binding activity; and serine-type endopeptidase activity. Involved in several processes, including cellular response to mechanical stimulus; response to thyrotropin-releasing hormone; and response to thyroxine. Located in collagen-containing extracellular matrix and extracellular space. Used to study several diseases, including atherosclerosis; end stage renal disease; hyperhomocysteinemia; obesity; and thrombophilia (multiple). Biomarker of bacterial pneumonia; brain edema; calcium oxalate nephrolithiasis; and thrombosis. Human ortholog(s) of this gene implicated in several diseases, including X-linked recessive disease (multiple); appendicitis; artery disease (multiple); autoimmune disease (multiple); and thrombophilia (multiple). Orthologous to human F2 (coagulation factor II, thrombin). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Restricted expression toward (RPKM 9803.3) See more
Orthologs: human mouse all
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Genomic context

Location:: 3q24

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	3	NC_086021.1 (98051958..98065246, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	3	NC_051338.1 (77596196..77609486, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	3	NC_005102.4 (80529468..80542993, complement)

Chromosome 3 - NC_086021.1 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: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

These findings imply that a thrombin-pericyte interaction in the brain could be a significant mechanism responsible for blood-brain barrier dysfunction under obesity-associated diabetic conditions and thus could represent a therapeutic target for central nervous system complications of diabetes.
Title: Contribution of thrombin-reactive brain pericytes to blood-brain barrier dysfunction in an in vivo mouse model of obesity-associated diabetes and an in vitro rat model.
Study suggests a potent role for spinal thrombin and its activation of PAR1 in pain onset following neuropathic injury
Title: The role of spinal thrombin through protease-activated receptor 1 in hyperalgesia after neural injury.
Inflammatory bowel disease is associated with production of prothrombin in the dorsal motor nucleus of the vagus (DMV). Thrombin in the DMV causes vagal neuron apoptosis and decreased sensitivity to neurotransmitters.
Title: Thrombin mediates vagal apoptosis and dysfunction in inflammatory bowel disease.
Thrombin-induced overexpression of TGF-beta1 and activation of its downstream factors might be a mechanism of communicating hydrocephalus after subarachnoid hemorrhage.
Title: Thrombin-induced TGF-β1 pathway: a cause of communicating hydrocephalus post subarachnoid hemorrhage.
These results suggest that thrombin triggers the generation of epileptic seizures by reducing the inhibitory and increasing the excitatory tone in CA3 neurons
Title: Thrombin regulation of synaptic transmission: implications for seizure onset.
The contribution of cyclic stretch to vascular smooth muscle cell-supported thrombin generation is driven by the integrin alpha(v)beta(3) signalling pathway.
Title: Cyclic stretch-induced thrombin generation by rat vascular smooth muscle cells is mediated by the integrin αvβ3 pathway.
Thrombin positively regulates the expression of TSP-1 & TSP-2 in adjacent blood vessels after intracerebral hemorrhage. It may be involved in modulating angiogenesis in injured brains following ICH.
Title: Thrombin promotes the expression of thrombospondin-1 and -2 in a rat model of intracerebral hemorrhage.
Leukocyte-endothelial adhesion induced by thrombin was markedly attenuated in endothelial cells with creb-binding protein knockdown.
Title: Down-regulation of CREB-binding protein expression blocks thrombin-mediated endothelial activation by inhibiting acetylation of NF-κB.
These results indicate that thrombin activates autophagy in the brain
Title: Thrombin-induced autophagy: a potential role in intracerebral hemorrhage.
Clotting factor derangement leading to impaired thrombin generation is the principle etiology of acute coagulopathy of trauma.
Title: The acute coagulopathy of trauma is due to impaired initial thrombin generation but not clot formation or clot strength.

Submit: New GeneRIF Correction See all GeneRIFs (30)

General gene information

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Markers

RH140523 (e-PCR)
- UniSTS:222592

D3Chm80 (e-PCR)
- UniSTS:265377

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables endopeptidase activity	ISO Inferred from Sequence Orthology more info
enables heparin binding	IEA Inferred from Electronic Annotation more info
enables heparin binding	ISO Inferred from Sequence Orthology more info
enables lipopolysaccharide binding	IEA Inferred from Electronic Annotation more info
enables lipopolysaccharide binding	ISO Inferred from Sequence Orthology more info
enables peptidase activity	ISO Inferred from Sequence Orthology more info
enables receptor ligand activity	IEA Inferred from Electronic Annotation more info
enables receptor ligand activity	ISO Inferred from Sequence Orthology more info
enables serine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables serine-type endopeptidase activity	IEA Inferred from Electronic Annotation more info
enables serine-type endopeptidase activity	ISO Inferred from Sequence Orthology more info
enables signaling receptor binding	ISO Inferred from Sequence Orthology more info
enables thrombospondin receptor activity	IEA Inferred from Electronic Annotation more info
enables thrombospondin receptor activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in acute-phase response	IEA Inferred from Electronic Annotation more info
involved_in antimicrobial humoral immune response mediated by antimicrobial peptide	IEA Inferred from Electronic Annotation more info
involved_in antimicrobial humoral immune response mediated by antimicrobial peptide	ISO Inferred from Sequence Orthology more info
involved_in blood coagulation	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in cellular response to mechanical stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cytolysis by host of symbiont cells	IEA Inferred from Electronic Annotation more info
involved_in fibrinolysis	IEA Inferred from Electronic Annotation more info
involved_in fibrinolysis	ISO Inferred from Sequence Orthology more info
involved_in ligand-gated ion channel signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in ligand-gated ion channel signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of astrocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of astrocyte differentiation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of blood coagulation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cytokine production involved in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cytokine production involved in inflammatory response	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of proteolysis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of proteolysis	ISO Inferred from Sequence Orthology more info
involved_in neutrophil-mediated killing of gram-negative bacterium	IEA Inferred from Electronic Annotation more info
involved_in platelet activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in platelet activation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within platelet activation	ISO Inferred from Sequence Orthology more info
involved_in platelet activation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of blood coagulation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of blood coagulation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of blood coagulation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of blood coagulation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell growth	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of cell growth	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of collagen biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of collagen biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of insulin secretion	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of insulin secretion	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein localization to nucleus	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein localization to nucleus	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of reactive oxygen species metabolic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of reactive oxygen species metabolic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of release of sequestered calcium ion into cytosol	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of release of sequestered calcium ion into cytosol	ISO Inferred from Sequence Orthology more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell shape	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of cell shape	ISO Inferred from Sequence Orthology more info
involved_in regulation of cytosolic calcium ion concentration	IEA Inferred from Electronic Annotation more info
involved_in regulation of cytosolic calcium ion concentration	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in response to Thyroglobulin triiodothyronine	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to inactivity	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to thyrotropin-releasing hormone	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to thyroxine	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to wounding	ISO Inferred from Sequence Orthology more info
involved_in thrombin-activated receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in thrombin-activated receptor signaling pathway	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in collagen-containing extracellular matrix	IBA Inferred from Biological aspect of Ancestor more info
located_in collagen-containing extracellular matrix	IDA Inferred from Direct Assay more info	PubMed
located_in external side of plasma membrane	IEA Inferred from Electronic Annotation more info
located_in external side of plasma membrane	ISO Inferred from Sequence Orthology more info
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 extracellular space	IEA Inferred from Electronic Annotation more info
located_in extracellular space	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: prothrombin

Names: coagulation factor 2; thrombin

NP_075213.2

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.

mRNA and Protein(s)

NM_022924.2 → NP_075213.2 prothrombin precursor

See identical proteins and their annotated locations for NP_075213.2

Status: VALIDATED

Source sequence(s)

CO575133, DW391550, DW392486, DY318887, EX492416

UniProtKB/Swiss-Prot

P18292

UniProtKB/TrEMBL

A6HND0, G3V843

Related

ENSRNOP00000022233.3, ENSRNOT00000022233.7

Conserved Domains (5) summary

smart00069
Location:25 → 89

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

smart00130
Location:107 → 189

KR; Kringle domain

cd00190
Location:360 → 612

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 ...

pfam00051
Location:215 → 292

Kringle; Kringle domain

pfam09396
Location:313 → 359

Thrombin_light; Thrombin light chain