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FLASH GENE
Symbol PROC contributors: mct/pgu - updated : 09-09-2014
HGNC name protein C (inactivator of coagulation factors Va and VIIIa)
HGNC id 9451
Corresponding disease
PROC thrombophilia , hereditary, due to protein C deficiency
Location 2q14.3      Physical location : 128.175.995 - 128.186.821
Synonym name
  • anticoagulant protein C
  • blood coagulation factor XIV
  • autoprothrombin IIA
  • protein C
  • vitamin K-dependent protein C
  • activated protein C
  • Synonym symbol(s) PC, PROC1, APC, PC1, THPH3, THPH4
    EC.number 3.4.21.69
    DNA
    TYPE functioning gene
    STRUCTURE 10.80 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site   enhancer   silencer
    motif repetitive sequence   other
    text structure
  • hepatocyte nuclear factor binding sites
  • a strong silencer upstream of the promoter
  • two liver-specific enhancer regions
  • a regulator region in intron 1
  • MAPPING cloned Y linked N status confirmed
    Physical map
    LOC150554 2q21.1 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta pseudogene GYPC 2q14-q21 glycophorin C (Gerbich blood group) LOC339760 2q21.1 hypothetical LOC339760 BIN1 2q14 bridging integrator 1 LOC389029 2 LOC389029 LOC339761 2q21.1 similar to 25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial precursor (Calcidiol 1-monooxygenase) (25-OHD-1 alpha-hydroxylase) (25-hydroxyvitamin D(3) 1-alpha-hydroxylase) (VD3 1A hydroxylase) (P450C1 alpha) (P450VD1-alpha) ERCC3 2q21 excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing) MAP3K2 2q14.3 mitogen-activated protein kinase kinase kinase 2 LOC389030 2 LOC389030 PROC 2q13-q14 protein C (inactivator of coagulation factors Va and VIIIa) FLJ10006 2q21.1 hypothetical protein FLJ10006 LOC389031 2 similar to myosin-VIIb MYO7B 2q21.1 myosin VIIB LIMS2 2q14.2 LIM and senescent cell antigen-like domains 2 GPR17 2q21 G protein-coupled receptor 17 MGC5391 2q21.1 hypothetical protein MGC5391 FLJ11294 2q21.1 hypothetical protein FLJ11294 POLR2D 2q21 polymerase (RNA) II (DNA directed) polypeptide D MGC4268 2q21 hypothetical protein MGC4268 SAP130 2q21.1 mSin3A-associated protein 130 UGCGL1 2q14.2 UDP-glucose ceramide glucosyltransferase-like 1 HS6ST1 2q21 heparan sulfate 6-O-sulfotransferase 1 LOC391432 2 similar to hypothetical protein LOC389032 2 LOC389032 LOC391433 2 similar to peptidyl-Pro cis trans isomerase
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 1790 - 461 - 2007 17646160
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
    Lymphoid/Immunespleen    
    Reproductivefemale systembreastmammary gland  
    Urinarykidney    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two EGF-like domains
  • one Gla (gamma-carboxy-glutamate) domain
  • one peptidase S1 domain
  • conjugated GlycoP
    isoforms Precursor precursor cleaved into a light and a heavy chains held together by a disulfide bond and then activated by thrombin at the surface of endothelial cells
    HOMOLOGY
    Homologene
    FAMILY
  • peptidase S1 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    text plasma
    basic FUNCTION
  • vitamin K-dependent serine protease regulating blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids
  • negative regulation of apoptosis and blood coagulation
  • has an important role in governing intestinal microvascular inflammation
  • may protect macro and microcirculation from endotoxic shock
  • inhibits LPS-stimulated complement factor B promoter activity and protein expression, and thus have beneficial effect in therapy in sepsis
  • attenuating both hepatic and renal injury caused by hepatic ischemia and reperfusion injury
  • procoagulant role of PROC pathway may have important implications for the regulation of F3- and TFPI-dependent biologic responses and for fine tuning of the hemostatic balance in the vascular system
  • vitamin K-dependent serine protease zymogen in plasma which upon activation to activated protein C (PROC) by thrombin down-regulates the clotting cascade by limited proteolysis of the procoagulant cofactors Va and VIIIa
  • cytoprotective anticoagulant that can promote cutaneous healing
  • may influence bone cells and has potential to be a therapeutic drug for bone regeneration
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS coagulation/hemostasis
    PATHWAY
    metabolism
    signaling
  • PROC pathway is a unique system involved in controlling intestinal homeostasis and inflammation by regulating epithelial barrier function
  • a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
  • Zinc ions bind to and inhibit activated protein C
  • protein
  • FVa
  • FVIIIa
  • using the endothelial cell protein C receptor as a coreceptor for cleavage of PAR1
  • ligation of LRP8 causes Dab1-dependent signaling thereby contributing to PROC's beneficial effects on cells
  • induces F2R phosphorylation and desensitizes endothelial cells to thrombin signaling but promotes limited receptor cleavage and negligible internalization and degradation even after prolonged PROC exposure
  • induced endoplasmic reticulum stress and attenuated lipopolysaccharide-induced umbilical vein endothelial cell apoptosis mediated by GSK3B
  • F7 and PROC are phosphatidic acid-binding proteins
  • cell & other
    REGULATION
    activated by thrombin, PROS1
    Other vitamin K-dependent
    ASSOCIATED DISORDERS
    corresponding disease(s) PROC
    related resource Database of Mutations Protein C
    Susceptibility
  • to meningococcal disease in young children
  • to variation of bone mineral density in Caucasian men and women
  • Variant & Polymorphism other
  • promoter genotype might significantly influence susceptibility for meningococcal disease in young children
  • CNV significantly associated with bone mineral density in Caucasian men and women
  • Candidate gene
  • PROC pathway is defective in patients with inflammatory Bowel disease
  • Marker
  • decreased PROC levels in patients with type 2 diabetes may serve as a biomarker to indicate the early development of diabetic nephropathy
  • Therapy target
    SystemTypeDisorderPubmed
    bloodcoagulation 
    Zn2+ supports a physiological role in the regulation of anticoagulant activity of PROC and for treatments of thrombotic diseases
    ANIMAL & CELL MODELS