PROCR
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Official Full Name
protein C receptor, endothelial
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Overview
The protein encoded by this gene is a receptor for activated protein C, a serine protease activated by and involved in the blood coagulation pathway. The encoded protein is an N-glycosylated type I membrane protein that enhances the activation of protein C. Mutations in this gene have been associated with venous thromboembolism and myocardial infarction, as well as with late fetal loss during pregnancy. The encoded protein may also play a role in malarial infection and has been associated with cancer. [provided by RefSeq, Jul 2013] -
Synonyms
PROCR; protein C receptor, endothelial; CCCA; EPCR; CCD41; endothelial protein C receptor; APC receptor; centrocyclin; CD201 antigen; activated protein C receptor; cell cycle, centrosome-associated protein;
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What is PROCR Protein?
PROCR gene (protein C receptor) is a protein coding gene which situated on the long arm of chromosome 20 at locus 20q11. The protein encoded by this gene is a receptor for activated protein C, a serine protease activated by and involved in the blood coagulation pathway. The encoded protein is an N-glycosylated type I membrane protein that enhances the activation of protein C. The encoded protein may also play a role in malarial infection and has been associated with cancer. The PROCR protein is consisted of 238 amino acids and PROCR molecular weight is approximately26.7 kDa.
What is the Function of PROCR Protein?
The PROCR protein, the protein C receptor, is an important molecule that plays a role in a variety of physiological and pathological processes. PROCR plays a key role in dry maintenance and self-renewal of breast stem cells. Studies have found that Procr acts as a receptor to transmit signals to the intracellular pathway, regulating the function of mammary stem cells. Specifically, Procr is able to use its intracellular segment to bind to Hsp90aa1 and recruit Src and IGF1R to form protein complexes that further activate Akt and ERK signaling pathways downstream of IGF1R. In the blood clotting pathway, PROCR acts as a receptor for activating protein C, enhancing the activation of protein C, which is accomplished by the thrombine-thromboregulatory complex. This function is essential for controlling blood clotting and preventing blood clots from forming.
PROCR Related Signaling Pathway
After stimulated by ligand protein C (PC), PROCR can use its intracellular segment to bind to Hsp90aa1, recruit Src and IGF1R to form protein complex, and further activate Akt and ERK signaling pathways downstream of IGF1R, thus promoting the specific activation and importance of mammary stem cells. In the Wnt signaling pathway, PROCR, as a novel target gene of the Wnt signaling pathway, encodes a membrane protein that labels a variety of adult stem cells, including breast stem cells and vascular endothelial stem cells. Wnt signaling pathway plays a crucial role in the function maintenance and play of stem cells, and is closely related to breast development and breast cancer formation.
Fig1. The model of PROCR signaling mechanisms in breast cancer cells. (Daisong Wang, 2018)
PROCR Related Diseases
As a receptor for activated protein C, PROCR is involved in regulating blood clotting and anticoagulation. The mutation of PROCR gene may be related to the occurrence of venous thromboembolism, myocardial infarction and other diseases. The abnormality of PROCR may be related to pregnancy related complications such as fetal loss in the third trimester, which may affect the normal progression of pregnancy. In some types of cancer, such as breast cancer, the expression level or functional status of PROCR may be related to the occurrence and development of the disease. PROCR may influence the development of tumors by affecting the dry maintenance and self-renewal of breast stem cells. The role of PROCR in islet adult stem cells may be related to the occurrence and development of diabetes and other diseases. By regulating the function of PROCR, it may contribute to the regeneration of islets and the treatment of diabetes. The role of PROCR in ovarian epithelial stem cells may be related to ovarian dysfunction, affecting ovulation and damage repair of ovarian epithelium.
Bioapplications of PROCR
Due to changes in the expression level or functional status of PROCR in a variety of diseases, it can be used as a biomarker to diagnose certain diseases, such as thrombotic diseases and pregnancy complications. Based on the mechanism of action of PROCR in diseases, small molecule drugs or biologics targeting PROCR can be developed for the treatment of related diseases. In cancer and other diseases, PROCR may act as a therapeutic target to influence disease progression by modulating its activity or expression levels. The role of PROCR in the dry maintenance and self-renewal of adult stem cells provides new strategies for tissue regeneration and repair, especially in islet regeneration and diabetes treatment. In the field of blood clotting and anticoagulant therapy, PROCR, as a receptor for activated protein C, may contribute to the development of new anticoagulant therapeutic strategies.
High Purity
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Fig1. SDS-PAGE (PROCR-589H)
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Fig2. SDS-PAGE (PROCR-8575H)
Case Study 1: Panpan Zhang, 2022
Metastasis and recurrence account for 95% of deaths from nasopharyngeal carcinoma (NPC). Cancer stem cells (CSCs) are regarded as one of the main reasons for tumor cell resistance to clinical therapy, and cancer metastasis or recurrence, while little is known about CSCs in NPC. The present study uncovers a subpopulation of cells labeled as CD45-EPCAM+PROCR+ in NPC biopsy samples that exhibit stem cell-like characteristics. A relatively low number of these cells initiate xenograft tumors in mice. Functional analysis reveals that protein C receptor (PROCR) not only serves as a stem cell marker in NPC, but also maintains tumor cells' stemness potential through regulating lipid metabolism and mitochondrial fission. Epistatic studies reveal that cAMP-protein kinase A stimulates Ca2+ release to manipulate lipid metabolism related genes' expression. Finally, in a cohort of 207 NPC samples, PROCR expression is correlated with tumor metastasis or recurrence, and predicts poor prognosis.
Fig1. Immunofluorescence staining of CD31 and PROCR in sectioned paraffin embedded NPC biopsy samples.
Fig2. Sphere forming assay of the sorted CD45-EPCAM+PROCR+ cells treated with different drugs.
Case Study 2: Hao Wang, 2020
Preeclampsia is a severe pregnancy-related disease that is found in 3%-5% of pregnancies worldwide and is primarily related to the decreased proliferation and invasion of trophoblast cells and abnormal uterine spiral artery remodelling. However, studies on the pathogenesis of placental trophoblasts are insufficient, and the aetiology of PE remains unclear. Here, researchers report that endothelial protein C receptor (EPCR), a transmembrane glycoprotein, was down-regulated in placentas from preeclamptic patients. Moreover, lack of EPCR significantly reduced the trophoblast cell proliferation, invasion and tube formation capabilities. Microscale thermophoresis analysis showed that EPCR directly bound to protease-activated receptor 1 (PAR-1), a G protein-coupled receptor. This change resulted in a substantial reduction in active Rac1 and caused excessive actin rearrangement.
Fig3. The expression of EPCR in placental tissues was determined by WB analysis.
Fig4. Validation of EPCR-KO by WB analysis.
PROCR involved in several pathways and played different roles in them. We selected most pathways PROCR participated on our site, such as Cell surface interactions at the vascular wall, Common Pathway of Fibrin Clot Formation, Formation of Fibrin Clot (Clotting Cascade), which may be useful for your reference. Also, other proteins which involved in the same pathway with PROCR were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.
| Pathway Name | Pathway Related Protein |
|---|---|
| Cell surface interactions at the vascular wall | CD84;ITGB1B.1;CD177;BSG;GRB7;SLC16A8;CEACAM1;TREM1;DOK2 |
| Common Pathway of Fibrin Clot Formation | CFHL1;PROCR;LOC100514666;CFHL3;SERPINE2;CFHL4;SERPINA1L;F13A1B;PROCA |
| Formation of Fibrin Clot (Clotting Cascade) | F3B;PRTN3;CFHL3;CFHL1;F13A1A.1;LOC100514666;SERPINA1L;F3A;CFHL4 |
| Hemostasis | ANGPT2A;NADL1.1;AKAP1;APOBB.1;TRPC6A;PDPN;DGKG;ABHD12;MFN2 |
PROCR has several biochemical functions, for example, protein binding, receptor activity. Some of the functions are cooperated with other proteins, some of the functions could acted by PROCR itself. We selected most functions PROCR had, and list some proteins which have the same functions with PROCR. You can find most of the proteins on our site.
| Function | Related Protein |
|---|---|
| protein binding | MCCC2;NCLN;FAIM;MED31;CD99L2;XBP1;SPCS1;CDC25A;STIP1 |
| receptor activity | P2RY11;CUBN;AMHR2;APLNR;NPY2R;GRIA3A;KRT1;PVR;NPC1 |
PROCR has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with PROCR here. Most of them are supplied by our site. Hope this information will be useful for your research of PROCR.
F2R; ganglioside_gm1; DMTN; CAV1
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