Protein C (PROC)

PRO-C; VKDPC; PC; Vitamin K Dependent Protein C; Inactivator Of Coagulation Factors Va And VIIIa; Autoprothrombin IIA; Blood coagulation factor XIV; Activation peptide

SPN	W078
HGNC	9451
MGI	97771
PubMed	1317308
RGD	3411
UniProt	P04070
Wiki	Protein_C

Protein C is a major physiological anticoagulant. It is a vitamin K-dependent serine protease enzyme (EC 3.4.21.69) that is activated by thrombin into activated protein C (APC). The activated form (with protein S and phospholipid as a cofactor) degrades Factor Va and Factor VIIIa. It should not be confused with C peptide or c-reactive protein or protein kinase C.The protein C pathway’s key enzyme, activated protein C, provides physiologic antithrombotic activity and exhibits both anti-inflammatory and anti-apoptotic activities. Its actions are related to development of thrombosis and ischemic stroke. The protein C pathway of the coagulation of the blood involves the influences of lipids and lipoproteins and the study of the strong epidemiologic association between hyperlipidemia and hypercoagulability.

Reference

"The structure and evolution of a 461 amino acid human protein C precursor and its messenger RNA, based upon the DNA sequence of cloned human liver cDNAs."
Nucleic Acids Res. 13:5233-5247(1985) [PubMed] [Europe PMC] [Abstract]

"The nucleotide sequence of the gene for human protein C."
Proc. Natl. Acad. Sci. U.S.A. 82:4673-4677(1985) [PubMed] [Europe PMC] [Abstract]

"Evolution and organization of the human protein C gene."
Proc. Natl. Acad. Sci. U.S.A. 83:546-550(1986) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Protein C Osaka 10 with aberrant propeptide processing: loss of anticoagulant activity due to an amino acid substitution in the protein C precursor."
Thromb. Haemost. 74:1003-1008(1995) [PubMed] [Europe PMC] [Abstract]

"An abnormal protein C (protein C Yonago) with an amino acid substitution of Gly for Arg-15 caused by a single base mutation of C to G in codon 57 (CGG-->GGG). Deteriorated calcium-dependent conformation of the gamma-carboxyglutamic acid domain relevant to a thrombotic tendency."
Int. J. Hematol. 57:9-14(1993) [PubMed] [Europe PMC] [Abstract]

"Characterization of a cDNA coding for human protein C."
Proc. Natl. Acad. Sci. U.S.A. 81:4766-4770(1984) [PubMed] [Europe PMC] [Abstract]

"Homozygous type I protein C deficiency in two unrelated families exhibiting thrombophilia related to Ala136-->Pro or Arg286-->His mutations."
Thromb. Haemost. 72:526-533(1994) [PubMed] [Europe PMC] [Abstract]

"Beta protein C is not glycosylated at asparagine 329. The rate of translation may influence the frequency of usage at asparagine-X-cysteine sites."
J. Biol. Chem. 265:11397-11404(1990) [PubMed] [Europe PMC] [Abstract]

"O-linked fucose is present in the first epidermal growth factor domain of factor XII but not protein C."
J. Biol. Chem. 267:5102-5107(1992) [PubMed] [Europe PMC] [Abstract]

"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]

"Human urinary glycoproteomics; attachment site specific analysis of N-and O-linked glycosylations by CID and ECD."
Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Models of the serine protease domain of the human antithrombotic plasma factor activated protein C and its zymogen."
Protein Sci. 3:588-599(1994) [PubMed] [Europe PMC] [Abstract]

"The 2.8 A crystal structure of Gla-domainless activated protein C."
EMBO J. 15:6822-6831(1996) [PubMed] [Europe PMC] [Abstract]

"Protein C deficiency: a database of mutations."
Thromb. Haemost. 69:77-84(1993) [PubMed] [Europe PMC] [Abstract]

"Hereditary thrombophilia: identification of nonsense and missense mutations in the protein C gene."
Proc. Natl. Acad. Sci. U.S.A. 84:2829-2832(1987) [PubMed] [Europe PMC] [Abstract]

"Protein C London 1: recurrent mutation at Arg-169 (CGG-->TGG) in the protein C gene causing thrombosis."
Nucleic Acids Res. 17:10513-10513(1989) [PubMed] [Europe PMC] [Abstract]

"The spectrum of genetic defects in a panel of 40 Dutch families with symptomatic protein C deficiency type I: heterogeneity and founder effects."
Blood 78:890-894(1991) [PubMed] [Europe PMC] [Abstract]

"Protein CVermont: symptomatic type II protein C deficiency associated with two GLA domain mutations."
Blood 79:1456-1465(1992) [PubMed] [Europe PMC] [Abstract]

"Protein C deficiency Hong Kong 1 and 2: hereditary protein C deficiency caused by two mutant alleles, a 5-nucleotide deletion and a missense mutation."
Blood 80:126-133(1992) [PubMed] [Europe PMC] [Abstract]

"A novel homozygous missense mutation in the protein C (PROC) gene causing recurrent venous thrombosis."
Hum. Genet. 89:683-684(1992) [PubMed] [Europe PMC] [Abstract]

"Two different missense mutations at Arg 178 of the protein C (PROC) gene causing recurrent venous thrombosis."
Hum. Genet. 89:685-686(1992) [PubMed] [Europe PMC] [Abstract]

"Two novel mutations responsible for hereditary type I protein C deficiency: characterization by denaturing gradient gel electrophoresis."
Hum. Mutat. 1:491-500(1992) [PubMed] [Europe PMC] [Abstract]

"Homozygous protein C deficiency: identification of a novel missense mutation that causes impaired secretion of the mutant protein C."
J. Lab. Clin. Med. 119:682-689(1992) [PubMed] [Europe PMC] [Abstract]

"Five novel mutations located in exons III and IX of the protein C gene in patients presenting with defective protein C anticoagulant activity."
Blood 82:159-168(1993) [PubMed] [Europe PMC] [Abstract]

"Twelve novel and two recurrent mutations in 14 Austrian families with hereditary protein C deficiency."
Blood Coagul. Fibrinolysis 4:273-280(1993) [PubMed] [Europe PMC] [Abstract]

"A Gla domain mutation (Arg 15-->Trp) in the protein C (PROC) gene causing type 2 protein C deficiency and recurrent venous thrombosis."
Blood Coagul. Fibrinolysis 4:345-347(1993) [PubMed] [Europe PMC] [Abstract]

"Genetic mutations in ten unrelated American patients with symptomatic type 1 protein C deficiency."
Blood Coagul. Fibrinolysis 4:791-796(1993) [PubMed] [Europe PMC] [Abstract]

"Symptomatic type II protein C deficiency caused by a missense mutation (Gly 381-->Ser) in the substrate-binding pocket."
Br. J. Haematol. 84:285-289(1993) [PubMed] [Europe PMC] [Abstract]

"First de novo mutations in the protein C gene of two patients with type I deficiency: a missense mutation and a splice site deletion."
Blood 84:2566-2570(1994) [PubMed] [Europe PMC] [Abstract]

"A homozygous deletion/insertion mutation in the protein C (PROC) gene causing neonatal Purpura fulminans: prenatal diagnosis in an at-risk pregnancy."
Blood Coagul. Fibrinolysis 5:647-649(1994) [PubMed] [Europe PMC] [Abstract]

"A novel homozygous missense mutation (Val 325-->Ala) in the protein C gene causing neonatal purpura fulminans."
Blood Coagul. Fibrinolysis 5:651-653(1994) [PubMed] [Europe PMC] [Abstract]

"Six missense mutations associated with type I and type II protein C deficiency and implications obtained from molecular modelling."
Blood Coagul. Fibrinolysis 5:687-696(1994) [PubMed] [Europe PMC] [Abstract]

"Influence of six mutations of the protein C gene on the Gla domain conformation and calcium affinity."
Thromb. Haemost. 71:748-754(1994) [PubMed] [Europe PMC] [Abstract]

"Three novel mutations in the protein C (PROC) gene causing venous thrombosis."
Blood Coagul. Fibrinolysis 6:138-140(1995) [PubMed] [Europe PMC] [Abstract]

"Six different point mutations in seven Danish families with symptomatic protein C deficiency."
Thromb. Haemost. 73:186-193(1995) [PubMed] [Europe PMC] [Abstract]

"Two novel (R(-11)C; T394D) and two repeat missense mutations in the protein C gene associated with venous thrombosis in six kindreds."
Hum. Mutat. 7:176-179(1996) [PubMed] [Europe PMC] [Abstract]

"Type I protein C deficiency in French Canadians: evidence of a founder effect and association of specific protein C gene mutations with plasma protein C levels."
Thromb. Haemost. 80:551-556(1998) [PubMed] [Europe PMC] [Abstract]

"Molecular characterization of p.Asp77Gly and the novel p.Ala163Val and p.Ala163Glu mutations causing protein C deficiency."
Thromb. Res. 135:718-726(2015) [PubMed] [Europe PMC] [Abstract]