Proc protein C [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Procprovided by MGI
Official Full Name: protein Cprovided by MGI
Primary source: MGI:MGI:97771
See related: Ensembl:ENSMUSG00000024386 AllianceGenome:MGI:97771
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: PC
Summary: This gene encodes the vitamin K-dependent protein C, which plays a vital role in the anticoagulation pathway. The encoded protein undergoes proteolytic processing including activation by thrombin-thrombomodulin complex to form the anticoagulant serine protease that degrades activated coagulation factors. A complete lack of the encoded protein in mice results in severe perinatal consumptive coagulopathy in the brain and liver, resulting in death within 24 hours after birth. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate the mature protein. [provided by RefSeq, Sep 2015]
Expression: Biased expression in liver adult (RPKM 230.9), liver E18 (RPKM 159.9) and 4 other tissues See more
Orthologs: human all
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Genomic context

Location:: 18 B1; 18 17.94 cM

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	18	NC_000084.7 (32256179..32272623, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	18	NC_000084.6 (32123126..32139570, complement)

Chromosome 18 - NC_000084.7 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: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Activated Protein C Strengthens Cardiac Tolerance to Ischemic Insults in Aging.
Title: Activated Protein C Strengthens Cardiac Tolerance to Ischemic Insults in Aging.
Activated Protein C Protects against Murine Contact Dermatitis by Suppressing Protease-Activated Receptor 2.
Title: Activated Protein C Protects against Murine Contact Dermatitis by Suppressing Protease-Activated Receptor 2.
APC inhibits LPS-mediated cytoplasmic translocation and secretion of HMGB1 in endothelial cells by epigenetic mechanisms
Title: Activated protein C inhibits lipopolysaccharide-mediated acetylation and secretion of high-mobility group box 1 in endothelial cells.
there is a predilection of low protein C-induced spontaneous atherothrombosis in Apoe(-/-) mice for the right coronary sinus.
Title: Predilection of Low Protein C-induced Spontaneous Atherothrombosis for the Right Coronary Sinus in Apolipoprotein E deficient mice.
These results support the concept that APC-induced, PAR1-dependent biased signaling following R46 cleavage is central to the in vivo benefits of APC.
Title: PAR1 biased signaling is required for activated protein C in vivo benefits in sepsis and stroke.
Data show that activated protein C signals via protease activated receptors PAR2/PAR3 to expand Treg cells, mitigating the disease in mice.
Title: Activated protein C protects from GvHD via PAR2/PAR3 signalling in regulatory T-cells.
insulin and aPC converge on a common spliced-X-box binding protein-1 (sXBP1) signaling pathway to maintain endoplasmic reticulum (ER) homeostasis.
Title: Signal integration at the PI3K-p85-XBP1 hub endows coagulation protease activated protein C with insulin-like function.
loss of the convertase furin or PC5/6 in hepatocytes results in a approximately 30% decrease in APC levels, with no significant contribution from PACE4. We conclude that prior convertase cleavage of protein C in hepatocytes is critical for its thrombin activation.
Title: Thrombin activation of protein C requires prior processing by a liver proprotein convertase.
APC modifies pulmonary fibrosis by limiting thrombin-dependent macrophage recruitment.
Title: High endogenous activated protein C levels attenuates bleomycin-induced pulmonary fibrosis.
Small interfering RNA-mediated silencing of protein C in apolipoprotein E-deficient mice creates a condition that allows the occurrence of spontaneous atherothrombosis.
Title: Silencing of Anticoagulant Protein C Evokes Low-Incident but Spontaneous Atherothrombosis in Apolipoprotein E-Deficient Mice-Brief Report.

Submit: New GeneRIF Correction See all GeneRIFs (38)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (4)
Targeted (1) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Proc (e-PCR), detects polymorphism
- UniSTS:525935

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables oligopeptidase activity	ISO Inferred from Sequence Orthology more info
enables peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables serine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables serine-type endopeptidase activity	ISO Inferred from Sequence Orthology more info
enables serine-type endopeptidase activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in blood coagulation	IBA Inferred from Biological aspect of Ancestor more info
involved_in blood coagulation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within liver development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of apoptotic process	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of blood coagulation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within negative regulation of blood coagulation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of blood coagulation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of blood coagulation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of coagulation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of coagulation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of inflammatory response	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of establishment of endothelial barrier	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of establishment of endothelial barrier	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of circulating fibrinogen levels	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in Golgi apparatus	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
located_in endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
located_in extracellular region	IEA Inferred from Electronic Annotation more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: vitamin K-dependent protein C

Names: anticoagulant protein C; autoprothrombin IIA; blood coagulation factor XIV; inactivator of coagulation factors Va, VIII

NP_001036232.1

EC 3.4.21.69

NP_001036233.2

EC 3.4.21.69

NP_001300867.1

EC 3.4.21.69

NP_032960.3

EC 3.4.21.69

XP_006525784.1

EC 3.4.21.69

XP_006525785.1

EC 3.4.21.69

XP_011245159.1

EC 3.4.21.69

XP_030106222.1

EC 3.4.21.69

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_001042767.3 → NP_001036232.1 vitamin K-dependent protein C isoform 2 preproprotein

See identical proteins and their annotated locations for NP_001036232.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and uses an in-frame downstream start codon, compared to variant 1. The encoded isoform (2) is shorter at the N-terminus, compared to isoform 1.

Source sequence(s)

AC126686, AC127347, BX639472, CJ237265, DV662175

Consensus CDS

CCDS29116.1

UniProtKB/Swiss-Prot

O35498, P33587, Q91WN8, Q99PC6

Related

ENSMUSP00000132226.2, ENSMUST00000171765.2

Conserved Domains (4) summary

smart00069
Location:26 → 86

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:87 → 131

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00190
Location:212 → 446

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 ...

pfam14670
Location:139 → 174

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_001042768.3 → NP_001036233.2 vitamin K-dependent protein C isoform 3 precursor

See identical proteins and their annotated locations for NP_001036233.2

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and 5' coding region, and uses an alternate start codon, compared to variant 1. The encoded isoform (3) has a distinct and shorter N-terminus, compared to isoform 1. This isoform (3) may undergo proteolytic processing similar to isoform 2.

Source sequence(s)

AC127347, BX639472, BY086829, BY788141, CJ237265, DV662175

Conserved Domains (4) summary

smart00069
Location:35 → 95

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:96 → 140

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00190
Location:221 → 455

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 ...

pfam14670
Location:148 → 183

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_001313938.1 → NP_001300867.1 vitamin K-dependent protein C isoform 2 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses an alternate splice site in the 5' UTR, lacks a portion of the 5' coding region and initiates translation at a downstream start codon, compared to variant 1. It encodes isoform 2, which has a shorter N-terminus compared to isoform 1.

Source sequence(s)

AC127347, BX639472, BY082597, BY086829, CJ237265, DV662175

Consensus CDS

CCDS29116.1

UniProtKB/Swiss-Prot

O35498, P33587, Q91WN8, Q99PC6

Related

ENSMUSP00000157269.2, ENSMUST00000234651.2

Conserved Domains (4) summary

smart00069
Location:26 → 86

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:87 → 131

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00190
Location:212 → 446

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 ...

pfam14670
Location:139 → 174

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_008934.4 → NP_032960.3 vitamin K-dependent protein C isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1). This isoform (1) may undergo proteolytic processing similar to isoform 2.

Source sequence(s)

AC127347, BX639472, BY086829, CJ237265, DV662175

Conserved Domains (5) summary

smart00020
Location:232 → 465

Tryp_SPc; Trypsin-like serine protease

smart00069
Location:47 → 107

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:108 → 152

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00190
Location:233 → 467

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 ...

pfam14670
Location:160 → 195

FXa_inhibition; Coagulation Factor Xa inhibitory site

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000084.7 Reference GRCm39 C57BL/6J

Range

32256179..32272623 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030250362.1 → XP_030106222.1 vitamin K-dependent protein C isoform X2

Conserved Domains (4) summary

smart00069
Location:35 → 95

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:96 → 140

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00190
Location:221 → 455

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 ...

pfam14670
Location:148 → 183

FXa_inhibition; Coagulation Factor Xa inhibitory site
XM_011246857.2 → XP_011245159.1 vitamin K-dependent protein C isoform X3

See identical proteins and their annotated locations for XP_011245159.1

UniProtKB/Swiss-Prot

O35498, P33587, Q91WN8, Q99PC6

Conserved Domains (4) summary

smart00069
Location:26 → 86

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:87 → 131

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00190
Location:212 → 446

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 ...

pfam14670
Location:139 → 174

FXa_inhibition; Coagulation Factor Xa inhibitory site
XM_006525722.4 → XP_006525785.1 vitamin K-dependent protein C isoform X2

See identical proteins and their annotated locations for XP_006525785.1

Conserved Domains (4) summary

smart00069
Location:35 → 95

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:96 → 140

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00190
Location:221 → 455

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 ...

pfam14670
Location:148 → 183

FXa_inhibition; Coagulation Factor Xa inhibitory site
XM_006525721.3 → XP_006525784.1 vitamin K-dependent protein C isoform X1

Conserved Domains (4) summary

smart00069
Location:50 → 110

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:111 → 155

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00190
Location:236 → 470

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 ...

pfam14670
Location:163 → 198

FXa_inhibition; Coagulation Factor Xa inhibitory site