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Validated All-in-One™ qPCR Primer for PROC(NM_000312.3) Search again
Product ID:
HQP015041
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
APC, PC, PROC1, THPH3, THPH4
Gene Description:
protein C, inactivator of coagulation factors Va and VIIIa
Target Gene Accession:
NM_000312.3(click here to view gene page)
Estimated Delivery:
Approximately 1-3 weeks, but may vary. Please email sales@genecopoeia.com or call 301-762-0888 to confirm ETA.
Important Note:
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Validated result:
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| A | B |
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Each All-in-One™ qPCR Primer is experimentally validated to yield a single dissociation curve peak and to generate a single amplification of the correct size for the targeted gene. A cDNA Pool, containing reverse transcript products of 8 different human tissue total RNA(Liver, Testis,Muscle,Thyroid,Brain,Spleen,Stomach,Small Intestine)),was used as the qPCR validation template. qPCR was performed using 0.2 µM primer with 2XAll-in-One™ qPCR Mix (Catalog#: QP001,QP002,QP004,QP005). Reactions were incubated for 10min. at 95°C, followed by 40 cycles of 95°C for 10 sec.; 60°C, 20 sec. and 72°C, 15sec. using Bio-Rad iQ5™ Instrument. At the end of the last cycle, temperature was increased from 72 to 95°C to produce a melting curve. Panel A: Validated Result for Amplification Curve; Panel B: Validated Result for Melting Curve. |
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Summary
The PROC gene encodes protein C (EC 3.4.21.69), a vitamin K-dependent plasma glycoprotein that is a key component of the anticoagulant system. Protein C is cleaved to its activated form, 'activated protein C' (APC) on endothelial cells by the thrombin-thrombomodulin complex (MIM 176930; MIM 188040) and then acts as a serine protease to degrade the activated forms of coagulation factors V (F5; MIM 612309) and VIII (F8; see MIM 306700). Protein S (PROS1; MIM 176880), also a vitamin K-dependent plasma protein, functions as a cofactor to activated protein C.[supplied by OMIM].
Gene References into function
- A heterozygous G-->T transversion at position 1388 of the protein C (PC) gene which predicted the substitution of Arg(-1) to a Leu (PC(R-1L)) was identified in a thrombophilic patient. This shifts the propeptidase cleavage site by one amino acid.
- The combined effect of aprotinin and extracorporeal circulation resulted in lowered APC ratios for Factor V Leiden blood. Increased risk of perioperative thrombosis in cardiac surgical patients heterozygous for the F5L mutation is predicted.
- Contribution of basic residues of the 70-80-loop to heparin binding and anticoagulant function of activated protein C.
- X-ray crystallography of Activated Protein C
- protease activated receptor 1 (PAR1) is the target for endothelial cell protein C receptor (EPCR)-dependent activated protein C (APC) signaling, suggesting a role for this receptor cascade in protection from sepsis
- identifies FVa binding site in the positive exosite of APC that is primarily involved in binding and cleaving at Arg(506) on FVa
- In this population-based study, a low protein C level has been determined to be associated with an increased incidence of venous thromboembolism.
- APC is able to cleave at Arg506 and at Arg679 in FVa Cambridge and FVa Hong Kong.
- Activated protein C cleaves factor Va more efficiently on endothelium than on platelet surfaces.
- Molecular biological basis and diagnosis of hereditary defects (review)
- APC inhibited both the binding of NF-kB to target sites and the degradation of I kappa B alpha, and inhibited both the binding of activator protein-1 (AP-1) to target sites and the activation of mitogen-activated protein kinase pathways.
- activation of protein C by thrombin and inactivation of plasma FVa by APC are not impaired in human volunteers with acute hyperhomocysteinemia.
- thrombomodulin-dependent activation of protein C is regulated by Smad6 and Smad7
- Smoking-induced vascular endothelium injury reduces activated protein C in a cigarette smoke dose-dependent manner, leading to activated protein C deficiency hypercoagulability.
- The ability of activated protein C to upregulate the production of MCP-1 is most likely by increasing the stability of MCP-1-mRNA rather than by transcriptional activation via NF-KB
- Data show that activated protein C directly prevents apoptosis in hypoxic human brain endothelium through transcriptionally dependent inhibition of tumor suppressor protein p53.
- Interactions within thrombin that involve autolytic loop-2 and the Na(+)-binding site impair thrombin action on protein C, yet the activity of the mutant meizothrombins for protein C was increased to >10 times that of alpha-thrombin
- physiologically relevant concentrations of PF4 stimulate thrombin-dependent activated protein C generation in cultured vascular endothelial cells
- mAb identifies binding site on PROC involved in APC-mediated inactivation of factor Va; binding is phospholipid-independent and calcium-dependent.
- seven newly found mutations in PROC are described; one with 4% PROC activity is a novel mutation in the promoter region, located in the HNF-1 site and associated with the Y226H heterozygous mutation
- REVIEW OF the physiology of the protein C pathway with special emphasis on pediatric venous thromboembolism as well as acquired disturbances of protein C pathway during sepsis
- activated protein C inactivates factor Va in the absence of arginine cleavage sites
- The cleavage and inactivation of PAI-1 by generated thrombin is proposed to be responsible for the shortening of clot lysis time by Ca2+ and for coagulation-associated over-expression of fibrinolysis, which was suppressed by aPC.
- free APC, APC-PCI and APC-alpha1AT generation is reduced in newborn compared to adult plasma with or without endothelium, likely due to reduced plasma PC levels. Endothelium enhances APC generation, regardless of plasma type.
- Poor susceptibility to APC and impaired APC cofactor activity contributed equally to FV(Leiden)-associated APC resistance, whereas FV(R2)-associated APC resistance was entirely due to the reduced APC cofactor activity of FV(R2).
- R147W mutation is a significant thrombotic risk factor and is the most common defect of PROC gene in Taiwanese patients with protein C deficiency
- individuals carrying the 4600AG EPCR genotype have high sEPCR levels but do not have an increased risk of thrombosis, whereas individuals carrying the 4678CC genotype have higher APC levels and lower risk of venous thromboembolism
- Review. TM, APC, & EPCR impact coagulation, inflammation, fibrinolysis, & cell proliferation. We review the functions of this complex multimolecular system & how its components maintain homeostasis under hypercoagulable &/or proinflammatory conditions.
- Activated protein C (APC) and MMP-2 are coordinately up-regulated and tightly bound in rheumatoid arthritis (RA) synovial fluid and colocalized in synovia. APC may modulate MMP-2 activity in RA.
- face 1 was necessary for efficient phospholipid binding but face 2 residues were not strictly required for phospholipid binding and were involved in the interaction with activated protein C
- No significant differences exist between survivors and nonsurvivors of sepsis with respect to baseline protein C levels.
- Results provide insights into the importance of the activated protein C (APC)-phospholipid interaction for the APC-mediated cleavages at Arg-306 and Arg-506 in coagulation factor Va.
- Exposure of human umbilical vein endothelial cells or monocytes to activated protein C (6.25-100 nM) results in the release of endothelial protein C receptor-containing microparticles.
- A new antiinflammatory mechanism of APC-dependent gene regulation occurs in human coronary artery endothelial cells. APC downregulates genes related to inflammation, most pronounced under intermediate or mild inflammatory conditions.
- Activated Protein C blocks tissue plasminogen activator's (tPA) neurovascular toxicity and may add substantially to the effectiveness of tPA therapy for stroke.
- mechanism of thrombomodulin action is to kinetically facilitate the productive encounter of thrombin and protein C and to allosterically change the conformation of the activation peptide of protein C for optimal presentation to the thrombin active site
- protein C binding to sEPCR and phospholipids is broadly dependent on correct Gla domain folding, but can be selectively influenced by judicious mutation
- analysis of PAR1 cleavage and signaling in response to activated protein C and thrombin
- APC anticoagulant activity in plasma and factor Va inactivation as a result of cleavages at R506 and R306 by APC is markedly enhanced by cholesterol in phospholipid vesicles
- PC interactions with thrombin and thrombomodulin are likely contribute in a secondary or minor way to protein substrate affinity
- endothelial protein C receptor ligation and sphingosine 1-phosphate receptor transactivation results in endothelial cell cytoskeletal rearrangement and barrier protection through activated protein C
- by signaling through the same receptor PAR1, APC, and thrombin can exert distinct biological effects in perturbed endothelium
- induction of COX-2-expression is an important response of HUVEC to stimulation with rhAPC and may represent a new molecular mechanism, by which rhAPC promotes upregulation of prostanoid production in human endothelium
- The protein C system is physiologically important, and genetic defects affecting the system are the most common risk factors of venous thrombosis.
- APC has an anti-inflammatory role in I/R injury in clinical renal transplantation
- significant elevation of anti-protein C antibodies and anti-protein S antibodies in the thrombosis group of uremia patients
- the autolysis loop in protein C and activated protein C is critical for the Ca(2+)-dependence of activation by thrombin
- case report of a type I/II compound heterozygote newborn with protein C deficiency
- silent hereditary defects of protein C may have a role in venous thrombosis in athletes [case report]
- APC effectively modulates the complex changes that occur during multi-system activation and dysfunction in sepsis (review)
- APC remarkably suppressed the mRNA expression and secretion of MCP-1 and IL-1beta from AGS cells infected with H. pylori. APC may play a critical role in the protection against gastric mucosal inflammation
- TM functions by alleviating the Ca(2+)-dependent inhibitory interactions of Arg-67 of protein C and Arg-35 of thrombin
- Protein C pathway defects are associated with the development of multiple organ failure in acute pancreatitis.
- the prothrombin G20210A mutation affects the anticoagulant and fibrinolytic activities of APC
- analysis of the specific Gla domain residues responsible for mediating protein C/APC molecular recognition with both its cofactor and receptor
- Activated protein C to has the ability to modulate monocyte apoptosis, inflammation, phagocytosis, and adhesion in a manner that promotes monocyte antimicrobial properties while limiting tissue damage.
- annihilation of the FXa protection of the individual activated protein C-mediated Arg-506 cleavage by protein S is due to an enhanced rate of Arg-506 cleavage of FVa not bound to FXa
- Gamma-carboxyglutamic acid--> Lysine mutation in in the endothelial protein C receptor causes a significant reduction in the binding force between this protein and protein C.
- Endothelial cell protein C receptor (EPCR)-bound activated protein C might modulate protease-activated receptor-1-mediated responses of smooth muscle cells to vascular injury.
- Activated Protein C increases invasion and chemotaxis of cells by binding to the cell surface and activating specific signaling pathways through EPCR and PAR-1.
- mutations in ProC cause the loss of ability to interact with the procoagulant cofactors but not with the protective signaling molecules
- This study reveals that when f.Xa interacts with anionic phospholipids, glycosaminoglycans bind f.Xa more tightly, allosterically modulate its active site, and enhance its capacity to activate protein C.
- Roles of calcium and platelet activation factor 4 in protein C activation by thrombin-thrombomodulin complex.
- Restoring the protein C pathway may represent a new therapeutic approach to suppress intestinal inflammation in inflammatory bowel disease
- Protein C promoter polymorphisms associate with sepsis in children with systemic meningococcemia.
- study reports familial cases with 3 nucleotide substitutions: a missense mutation Arg169Trp, previously reported; the other two are C-154T promoter polymorphism (rs1799808 on dbSNP database)and Ser99Ser synonymous polymorphism (rs5936)
- peptide VP311-325 represents both an Activated protein C and fXa binding region in fVa.
- Thrombin-thrombomodulin-mediated degradation of protein C by epithelial/endothelial cell suggests a previously unrecognized mechanism, which can contribute to protein C consumption.
- Protein C levels remained unchanged during pregnancy and postpartum. A remarkable finding is the strong inverse relationship between APC-SR and protein C levels.
- Activated protein C may provide cytoprotective activity by activating the ERK pathway, which upregulates EGR-1 thereby suppressing the expression of TRAIL by PAR-1/S1p1 dependent but EPCR independent mechanism.
- A mouse model of human protein C shows that activated protein C (APC) formation is reduced in transgenic diabetic mice and causally linked to nephropathy. Maintaining high APC levels during long-term diabetes protects against diabetic nephropathy.
- Ligands interacting with alpha-helix F of PAI-1 demonstrated a potential for the protection of activated PC from inactivation by PAI-1
- The data suggest that different trafficking of activated PAR1 might explain how PAR1 signaling by APC can be relevant when thrombin is present.
- Protein C mutation incidence was higher in the pulmonary emboli group than in the deep vein thrombosis (8.33%) and cerebral vein thrombosis (16.1%) groups.
- Patients with abdominal aortic aneurysm have increased thrombin generation reflected by an increase in the activated protein C-protein C inhibitor complex, which correlates with aneurysm size.
- FVa, being part of the prothrombinase complex, is protected from APC by both FXa and prothrombin
- Protein C -1641A/-1654C haplotype is associated with organ dysfunction and the fatal outcome of severe sepsis
- autolysis loop of APC may not be a target for modulation by protein S
- analysis of the protein C gene coding sequences in two sisters with severe congenital protein C deficiency identified 2 mutations in both patients, the previously described Arg169 to Trp mutation, and a novel mutation that changes Cys17 into a stop codon
- Low activated protein C ratio, elevated tissue factor activity and increased activated factor VII in plasma may contribute to development of coronary heart disease
- factor VIIIa is inactivated by activated protein C in the presence of its cofactors, protein S and factor V
- Recombinant activated protein C attenuates endothelial injury and inhibits procoagulant microparticles release in baboon heatstroke.
- the PC pathway has an important role in governing intestinal microvascular inflammation and might provide a novel therapeutic target in the management of inflammatory bowel disease
- protein C and APC may directly promote cell signaling in other cells by binding to ApoER2 and/or GPIbalpha
- The C allele was associated with increased mortality and organ dysfunction.
- Severe protein C deficiency from compound heterozygous mutations in the PROC gene in two Korean adult patients is reported.
- discuss possible mechanisms contributing to oxidative inactivation of activated protein C by hydrogen peroxide and hypochlorite.
- The PROCR Ser219Gly variant was associated with higher levels of circulating protein C antigen; the minor alleles of PROC rs2069901 and PROS1 rs4857343 were weakly associated with lower protein C and free protein S levels, respectively.
- the occurrence of acquired APC resistance in ET and PV patients, probably because of a reduction in free PS levels. The APC-resistant phenotype is influenced by the JAK2(V617F) mutational load.
- Dissociation of activated protein C functions by elimination of protein S cofactor enhancement
- Compared with nondeficient family members, subjects with protein S or protein C deficiency but not antithrombin deficiency have a higher risk for arterial thromboembolism before 55 years of age that is independent of prior venous thromboembolism
- Thus, a low level of P-APC-PCI complex may be associated with an increased risk of AVFG failure in HD patients.
- ligation of ApoER2 by APC signals via Dab1 phosphorylation and subsequent activation of PI3K and Akt and inactivation of GSK3beta, thereby contributing to APC's beneficial effects on cells.
- There is no clear synergistic effect of the protein C CC/GG genotype with factor V Leiden or oral contraceptive use on thrombotic risk.
- Case Report: Activated protein C concentrate treatment for skin necrosis under warfarin treatment in severe genetic protein C deficiency combined with prothrombin mutation and factor V Leiden.