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protein C; vitamin K-dependent protein C; anticoagulant protein C; autoprothrombin IIA; blood coagulation factor XIV; contains: vitamin K-dependent protein C light chain; vitamin K-dependent protein C heavy chain; activation peptide (PROC)

Function: - vitamin K-dependent serine protease - regulates blood coagulation by inactivating factor Va & factor VIIIa in the presence of Ca+2 & phospholipids - the vitamin K-dependent, enzymatic carboxylation of some Glu residues allows the modified protein to bind Ca+2 - iron & 2-oxoglutarate dependent 3-hydroxylation of aspartate & asparagine is (R) stereospecific within EGF domains - may be phosphorylated on a Ser or Thr in a region (AA 25-30) of the propeptide - synthesized as a single chain precursor, which is cleaved into a light chain & a heavy chain held together by a disulfide bond - the molecular complex is then activated by thrombin, which cleaves a tetradecapeptide from the amino end of the heavy chain at the surface of endothelial cells - activation of protein C is strongly promoted by thrombomodulin - thrombin/thrombomodulin complex preferentially activates protein C, whereas free thrombin primarily converts fibrinogen to fibrin - Ca+2 also binds, with stronger affinity to another site, beyond the GLA domain - this GLA-independent binding site is necessary for the recognition of the thrombin-thrombomodulin complex - procoagulant inhibitor Structure: - N-glycosylated & O-glycosylated - partial (70%) N-glycosylation of Asn- 371 with an atypical N-X-C site produces a higher molecular weight form referred to as protein C-alpha - the lower molecular weight form, not N- glycosylated at Asn-371, is protein C-beta - O-glycosylated with core 1 glycan or possibly core 8 glycan - belongs to the peptidase S1 family - contains 2 EGF-like domains - contains 1 Gla (gamma-carboxy-glutamate) domain - contains 1 peptidase S1 domain Compartment: - secreted, plasma Expression: - expressed & secreted by liver Pathology: - defects in PROC are the cause of protein C deficiency a) autosomal dominant (heterozygous protein C deficiency) - often develop thromoembolic disease before age 30 b) autosomal recessive homoygous protein C deficiency) - severe neonatal disease to late-onset thrombophilia

Interactions

molecular events

Related

coagulation cascade protein C deficiency protein C in plasma (protein C assay) protein C inhibitor; plasma serine protease inhibitor; acrosomal serine protease inhibitor; plasminogen activator inhibitor 3; PAI-3; PAI3; PCI; Serpin A5 (SERPINA5, PCI, PLANH3, PROCI) protein C, activated thrombin; coagulation factor IIa thrombomodulin; TM; fetomodulin; CD141 (THBD, THRM) vitamin K

Specific

protein C parenteral; protein C concentrate

General

coagulation factor enzyme precursor (zymogen)

Properties

SIZE: entity length = 461 aa MW = 52 kD COMPARTMENT: plasma MOTIF: signal sequence {1-18} Thr glycosylation site {T19} Gla {43-88} MOTIF: cysteine residue {C59} MODIFICATION: cysteine residue {C64} cysteine residue {C64} MODIFICATION: cysteine residue {C59} cysteine residue {C92} MODIFICATION: cysteine residue {C111} EGF domain {97-132} MOTIF: cysteine residue {C101} MODIFICATION: cysteine residue {C106} cysteine residue {C105} MODIFICATION: cysteine residue {C120} cysteine residue {C106} MODIFICATION: cysteine residue {C101} cysteine residue {C111} MODIFICATION: cysteine residue {C92} cysteine residue {C120} MODIFICATION: cysteine residue {C105} cysteine residue {C122} MODIFICATION: cysteine residue {C131} cysteine residue {C131} MODIFICATION: cysteine residue {C122} EGF domain {136-176} MOTIF: N-glycosylation site {N139} cysteine residue {C140} MODIFICATION: cysteine residue {C151} cysteine residue {C147} MODIFICATION: cysteine residue {C160} cysteine residue {C151} MODIFICATION: cysteine residue {C140} cysteine residue {C160} MODIFICATION: cysteine residue {C147} cysteine residue {C162} MODIFICATION: cysteine residue {C175} cysteine residue {C175} MODIFICATION: cysteine residue {C162} cysteine residue {C183} MODIFICATION: cysteine residue {C-INTERCHAIN} proteolytic site {211-212} S1 domain {212-450} MOTIF: cysteine residue {C238} MODIFICATION: cysteine residue {C254} histidine residue {H253} cysteine residue {C254} MODIFICATION: cysteine residue {C238} N-glycosylation site {N290} aspartate residue {D299} N-glycosylation site {N355} N-glycosylation site {N371} cysteine residue {C373} MODIFICATION: cysteine residue {C387} cysteine residue {C387} MODIFICATION: cysteine residue {C373} cysteine residue {C398} MODIFICATION: cysteine residue {C426} serine residue {S402} cysteine residue {C426} MODIFICATION: cysteine residue {C398} PRECURSOR-FOR: protein C, activated

Database Correlations

OMIM correlations MORBIDMAP 612283 UniProt P04070 PFAM correlations Entrez Gene 5624 Kegg hsa:5624 ENZYME 3.4.21.69

References

  1. Baron M, Norman DG, Campbell ID. Protein modules. Trends Biochem Sci. 1991 Jan;16(1):13-7. Review. PMID: 2053133
  2. Suttie JW. Synthesis of vitamin K-dependent proteins. FASEB J. 1993 Mar;7(5):445-52. Review. PMID: 8462786
  3. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
  4. UniProt :accession P04070
  5. Wikipedia; Note: protein C entry http://en.wikipedia.org/wiki/protein_C
  6. GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/PROC
  7. SeattleSNPs http://pga.gs.washington.edu/data/proc/

Component-of

factor ix/factor vii/factor x/protein c/protein s/prothrombin/prothrombin complex concentrate prothrombin complex concentrate (Autoplex-T, Kcentra)