PROC protein C, inactivator of coagulation factors Va and VIIIa [Homo sapiens (human)] - Gene

Summary

Official Symbol: PROCprovided by HGNC
Official Full Name: protein C, inactivator of coagulation factors Va and VIIIaprovided by HGNC
Primary source: HGNC:HGNC:9451
See related: Ensembl:ENSG00000115718 MIM:612283; AllianceGenome:HGNC:9451
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: PC; APC; PROC1; THPH3; THPH4
Summary: This gene encodes a vitamin K-dependent plasma glycoprotein. The encoded protein is cleaved to its activated form by the thrombin-thrombomodulin complex. This activated form contains a serine protease domain and functions in degradation of the activated forms of coagulation factors V and VIII. Mutations in this gene have been associated with thrombophilia due to protein C deficiency, neonatal purpura fulminans, and recurrent venous thrombosis.[provided by RefSeq, Dec 2009]
Annotation information: Note: PROC (Gene ID: 5624) and APC (Gene ID: 324) loci share the APC symbol/alias in common. [08 Feb 2019]
Expression: Biased expression in liver (RPKM 55.9) and kidney (RPKM 6.8) See more
Orthologs: mouse all
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Genomic context

Location:: 2q14.3

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (127418427..127429242)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (127853697..127864511)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (128176003..128186818)

Chromosome 2 - NC_000002.12 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?

Mutation Ter462GlnextTer17 introduces a tail to C-terminus of protein C and causes venous thrombosis.
Title: Mutation Ter462GlnextTer17 introduces a tail to C-terminus of protein C and causes venous thrombosis.
Analysis of PROC mutations and clinical features in 22 unrelated families with inherited protein C deficiency.
Title: Analysis of PROC mutations and clinical features in 22 unrelated families with inherited protein C deficiency.
Computational analysis of the functional and structural impact of the most deleterious missense mutations in the human Protein C.
Title: Computational analysis of the functional and structural impact of the most deleterious missense mutations in the human Protein C.
Activated Protein C Prevents Neuronal Apoptosis via Protease Activated Receptors 1 and 3.
Title: Activated Protein C Prevents Neuronal Apoptosis via Protease Activated Receptors 1 and 3.
Design and characterization of novel activated protein C variants for the proteolysis of cytotoxic extracellular histone H3.
Title: Design and characterization of novel activated protein C variants for the proteolysis of cytotoxic extracellular histone H3.
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.
APC ameliorates idiopathic membranous nephropathy by affecting podocyte apoptosis through the ERK1/2/YB-1/PLA2R1 axis.
Title: APC ameliorates idiopathic membranous nephropathy by affecting podocyte apoptosis through the ERK1/2/YB-1/PLA2R1 axis.
Protein C and S levels in patients with Thalassemia intermedia.
Title: Protein C and S levels in patients with Thalassemia intermedia.
Pediatric Retinal Detachment in Homozygous Protein C Deficiency: Genetic and Phenotypic Description of a Single Family.
Title: Pediatric Retinal Detachment in Homozygous Protein C Deficiency: Genetic and Phenotypic Description of a Single Family.
[Clinical phenotype and gene mutation analysis of 12 patients with hereditary protein C deficiency in different families].
Title: [Clinical phenotype and gene mutation analysis of 12 patients with hereditary protein C deficiency in different families].

Submit: New GeneRIF Correction See all GeneRIFs (290)

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
Thrombophilia due to protein C deficiency, autosomal dominant MedGen: C2674321 OMIM: 176860 GeneReviews: Not available	Compare labs
Thrombophilia due to protein C deficiency, autosomal recessive MedGen: C2676759 OMIM: 612304 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study of self-rated health. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic Markers Associated With Plasma Protein C Level in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies novel loci for plasma levels of protein C: the ARIC 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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:181257 (e-PCR)
- UniSTS:155225

GDB:178362 (e-PCR)
- UniSTS:154988

GDB:186843 (e-PCR)
- UniSTS:155512

GDB:181584 (e-PCR)
- UniSTS:155295

GDB:176978 (e-PCR)
- UniSTS:154817

D2S2639 (e-PCR)
- UniSTS:60395

RH70647 (e-PCR)
- UniSTS:34047

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
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	IMP Inferred from Mutant Phenotype more info	PubMed
enables serine-type endopeptidase activity	TAS Traceable Author Statement more info	PubMed

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
involved_in negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of blood coagulation	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of blood coagulation	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of coagulation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of inflammatory response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of establishment of endothelial barrier	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteolysis	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi lumen	TAS Traceable Author Statement more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
located_in extracellular region	NAS Non-traceable Author Statement more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
is_active_in extracellular space	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: vitamin K-dependent protein C

Names: Protein C-Nagoya; activated protein C; anticoagulant protein C; autoprothrombin IIA; blood coagulation factor XIV; coagulation factor XIV; prepro-protein C; type I protein C

NP_000303.1

EC 3.4.21.69

NP_001362531.1

EC 3.4.21.69

NP_001362532.1

EC 3.4.21.69

NP_001362533.1

EC 3.4.21.69

NP_001362534.1

EC 3.4.21.69

NP_001362535.1

EC 3.4.21.69

NP_001362536.1

EC 3.4.21.69

NP_001362537.1

EC 3.4.21.69

NP_001362538.1

EC 3.4.21.69

NP_001362539.1

EC 3.4.21.69

NP_001362540.1

EC 3.4.21.69

NP_001362542.1

EC 3.4.21.69

XP_016859994.2

EC 3.4.21.69

XP_024308770.2

EC 3.4.21.69

XP_024308771.1

EC 3.4.21.69

XP_047301073.1

EC 3.4.21.69

XP_047301074.1

EC 3.4.21.69

XP_054199004.1

EC 3.4.21.69

XP_054199005.1

EC 3.4.21.69

XP_054199006.1

EC 3.4.21.69

XP_054199007.1

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.

Genomic

NG_016323.1 RefSeqGene

Range

5001..15827

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_599

mRNA and Protein(s)

NM_000312.4 → NP_000303.1 vitamin K-dependent protein C isoform 10 preproprotein

See identical proteins and their annotated locations for NP_000303.1

Status: REVIEWED

Description

Transcript Variant: This variant (10), as well as variants 11 and 12, encodes isoform 10.

Source sequence(s)

BC034377, DA642156

Consensus CDS

CCDS2145.1

UniProtKB/Swiss-Prot

B4DPQ7, P04070, Q15189, Q15190, Q16001, Q53S74, Q9UC55

Related

ENSP00000234071.4, ENST00000234071.8

Conserved Domains (4) summary

smart00069
Location:24 → 87

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:101 → 132

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:213 → 448

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:140 → 175

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_001375602.1 → NP_001362531.1 vitamin K-dependent protein C isoform 2

Status: REVIEWED

Source sequence(s)

AC068282

Conserved Domains (4) summary

smart00069
Location:85 → 148

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:162 → 193

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:274 → 509

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:201 → 236

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_001375603.1 → NP_001362532.1 vitamin K-dependent protein C isoform 4 precursor

Status: REVIEWED

Source sequence(s)

AC068282

Conserved Domains (4) summary

smart00069
Location:45 → 108

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:122 → 153

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:268 → 503

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:195 → 230

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_001375604.1 → NP_001362533.1 vitamin K-dependent protein C isoform 6 precursor

Status: REVIEWED

Source sequence(s)

AC068282

Conserved Domains (4) summary

smart00069
Location:45 → 108

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:122 → 153

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:234 → 469

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:161 → 196

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_001375605.1 → NP_001362534.1 vitamin K-dependent protein C isoform 5 preproprotein

Status: REVIEWED

Source sequence(s)

AC068282

Consensus CDS

CCDS92858.1

UniProtKB/TrEMBL

E7END6

Related

ENSP00000386679.1, ENST00000409048.1

Conserved Domains (4) summary

smart00069
Location:24 → 87

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:101 → 132

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:247 → 482

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:174 → 209

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_001375606.1 → NP_001362535.1 vitamin K-dependent protein C isoform 3 precursor

Status: REVIEWED

Source sequence(s)

AC068282

UniProtKB/TrEMBL

B4DPQ3

Conserved Domains (3) summary

smart00069
Location:45 → 108

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00190
Location:269 → 504

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:196 → 231

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_001375607.1 → NP_001362536.1 vitamin K-dependent protein C isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AC068282

Conserved Domains (4) summary

smart00069
Location:64 → 115

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:129 → 160

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:275 → 510

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:202 → 237

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_001375608.1 → NP_001362537.1 vitamin K-dependent protein C isoform 9 precursor

Status: REVIEWED

Source sequence(s)

AC068282

Conserved Domains (3) summary

smart00069
Location:24 → 87

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:101 → 132

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:194 → 429

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 ...
NM_001375609.1 → NP_001362538.1 vitamin K-dependent protein C isoform 8

Status: REVIEWED

Source sequence(s)

AC068282

Conserved Domains (4) summary

smart00069
Location:17 → 79

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:93 → 124

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:205 → 440

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:132 → 167

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_001375610.1 → NP_001362539.1 vitamin K-dependent protein C isoform 7 preproprotein

Status: REVIEWED

Source sequence(s)

AC068282

Conserved Domains (4) summary

smart00069
Location:24 → 85

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:99 → 130

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:211 → 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:138 → 173

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_001375611.1 → NP_001362540.1 vitamin K-dependent protein C isoform 10 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (11), as well as variants 10 and 12, encodes isoform 10.

Source sequence(s)

AC068282

Consensus CDS

CCDS2145.1

UniProtKB/Swiss-Prot

B4DPQ7, P04070, Q15189, Q15190, Q16001, Q53S74, Q9UC55

Conserved Domains (4) summary

smart00069
Location:24 → 87

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:101 → 132

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:213 → 448

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:140 → 175

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_001375613.1 → NP_001362542.1 vitamin K-dependent protein C isoform 10 preproprotein

Status: REVIEWED

Description

Transcript Variant: This variant (12), as well as variants 10 and 11, encodes isoform 10.

Source sequence(s)

AC068282

Consensus CDS

CCDS2145.1

UniProtKB/Swiss-Prot

B4DPQ7, P04070, Q15189, Q15190, Q16001, Q53S74, Q9UC55

Conserved Domains (4) summary

smart00069
Location:24 → 87

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:101 → 132

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:213 → 448

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:140 → 175

FXa_inhibition; Coagulation Factor Xa inhibitory site

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

127418427..127429242

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047445117.1 → XP_047301073.1 vitamin K-dependent protein C isoform X4
XM_024453003.2 → XP_024308771.1 vitamin K-dependent protein C isoform X2

Conserved Domains (4) summary

smart00069
Location:85 → 148

GLA; Domain containing Gla (gamma-carboxyglutamate) residues

cd00054
Location:162 → 193

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:308 → 543

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:235 → 270

FXa_inhibition; Coagulation Factor Xa inhibitory site
XM_024453002.2 → XP_024308770.2 vitamin K-dependent protein C isoform X1
XM_017004505.2 → XP_016859994.2 vitamin K-dependent protein C isoform X3

UniProtKB/TrEMBL

B4DPC8
XM_047445118.1 → XP_047301074.1 vitamin K-dependent protein C isoform X1

Alternate T2T-CHM13v2.0

Genomic

NC_060926.1 Alternate T2T-CHM13v2.0

Range

127853697..127864511

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054343030.1 → XP_054199005.1 vitamin K-dependent protein C isoform X2
XM_054343029.1 → XP_054199004.1 vitamin K-dependent protein C isoform X1
XM_054343031.1 → XP_054199006.1 vitamin K-dependent protein C isoform X3

UniProtKB/TrEMBL

B4DPC8
XM_054343032.1 → XP_054199007.1 vitamin K-dependent protein C isoform X4