PRCP Gene

HGNC Family	Minor histocompatibility antigens
Name	prolylcarboxypeptidase (angiotensinase C)
Description	This gene encodes a member of the peptidase S28 family of serine exopeptidases. The encoded preproprotein is proteolytically processed to generate the mature lysosomal prolylcarboxypeptidase. This enzyme cleaves C-terminal amino acids linked to proline in peptides such as angiotension II, III and des-Arg9-bradykinin. The cleavage occurs at acidic pH, but the enzyme activity is retained with some substrates at neutral pH. This enzyme has been shown to be an activator of the cell matrix-associated prekallikrein. The importance of angiotension II, one of the substrates of this enzyme, in regulating blood pressure and electrolyte balance suggests that this gene may be related to essential hypertension. A pseudogene of this gene has been identified on chromosome 2. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProlylcarboxypeptidase (PRCP) has been identified as a membrane‐associated serine protease expressed by endothelial cells that plays a crucial role in activating plasma prekallikrein (PK) when assembled on high–molecular weight kininogen. This enzymatic activity converts PK to kallikrein and is supported by experiments using endothelial cell lysates and recombinant PRCP, with its activity being selectively inhibited by specific serine protease inhibitors and peptides."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in kallikrein activation, PRCP is a multifunctional regulator of vascular homeostasis. By processing vasoactive peptides such as angiotensin II and angiotensin III, and by modulating bradykinin availability, PRCP influences blood flow and blood pressure. Its gene has been associated with conditions such as preeclampsia, and experimental depletion of PRCP impairs endothelial cell growth, angiogenesis, and the repair response following vascular injury."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMolecular and structural studies further reveal that PRCP belongs to the unique S28 family of proteases, whose active‐site architecture enables the specific cleavage of substrates such as angiotensin III—generating angiotensin 1–7—and mediates interactions with PK via multiple contact regions. Crystallographic analyses have provided insights into its glycosylated structure expressed in cell systems, while pharmacological inhibitor studies underscore its potential as a drug target for obesity and other metabolic disorders. Genetic investigations indicate that polymorphisms in the PRCP gene may affect blood pressure responses to treatments and are linked with essential hypertension. Moreover, altered serum activity of PRCP correlates with stroke severity and outcomes, and its expression has been detected in kidney tissues affected by IgA nephropathy, highlighting its broad clinical significance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zia Shariat-Madar, Fakhri Mahdi, Alvin H Schmaier "}, {"type": "b", "children": [{"type": "t", "text": "Identification and characterization of prolylcarboxypeptidase as an endothelial cell prekallikrein activator."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M106101200"}], "href": "https://doi.org/10.1074/jbc.M106101200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11830581"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11830581"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Claudia R Moreira, Alvin H Schmaier, Fakhri Mahdi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of prolylcarboxypeptidase as the cell matrix-associated prekallikrein activator."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0014-5793(02)02980-0"}], "href": "https://doi.org/10.1016/s0014-5793(02"}, {"type": "t", "text": "02980-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12123826"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12123826"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zia Shariat-Madar, Fakhri Mahdi, Alvin H Schmaier "}, {"type": "b", "children": [{"type": "t", "text": "Recombinant prolylcarboxypeptidase activates plasma prekallikrein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2003-07-2510"}], "href": "https://doi.org/10.1182/blood-2003-07-2510"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14996700"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14996700"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Lin Wang, Yan Feng, Yan Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prolylcarboxypeptidase gene, chronic hypertension, and risk of preeclampsia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Obstet Gynecol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajog.2006.01.079"}], "href": "https://doi.org/10.1016/j.ajog.2006.01.079"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16681991"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16681991"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "J Mallela, J Yang, Z Shariat-Madar "}, {"type": "b", "children": [{"type": "t", "text": "Prolylcarboxypeptidase: a cardioprotective enzyme."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2008.02.022"}], "href": "https://doi.org/10.1016/j.biocel.2008.02.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18396440"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18396440"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Gregory N Adams, Evi X Stavrou, Chao Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prolylcarboxypeptidase promotes angiogenesis and vascular repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2012-10-460360"}], "href": "https://doi.org/10.1182/blood-2012-10-460360"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23744584"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23744584"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yan Zhang, Xiu-mei Hong, Hou-xun Xing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "E112D polymorphism in the prolylcarboxypeptidase gene is associated with blood pressure response to benazepril in Chinese hypertensive patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Chin Med J (Engl) (2009)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20079160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20079160"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Pravien D Abeywickrema, Sangita B Patel, Noel J Byrne, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression, purification and crystallization of human prolylcarboxypeptidase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Crystallogr Sect F Struct Biol Cryst Commun (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1107/S1744309110014041"}], "href": "https://doi.org/10.1107/S1744309110014041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20516604"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20516604"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Xuemei Zhao, Katie Southwick, Helene L Cardasis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Peptidomic profiling of human cerebrospinal fluid identifies YPRPIHPA as a novel substrate for prolylcarboxypeptidase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proteomics (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pmic.201000145"}], "href": "https://doi.org/10.1002/pmic.201000145"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20517885"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20517885"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Stephen M Soisson, Sangita B Patel, Pravien D Abeywickrema, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural definition and substrate specificity of the S28 protease family: the crystal structure of human prolylcarboxypeptidase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Struct Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1472-6807-10-16"}], "href": "https://doi.org/10.1186/1472-6807-10-16"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20540760"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20540760"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Thomas H Graham, Hong C Shen, Wensheng Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The discovery of non-benzimidazole and brain-penetrant prolylcarboxypeptidase inhibitors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioorg Med Chem Lett (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bmcl.2011.10.060"}], "href": "https://doi.org/10.1016/j.bmcl.2011.10.060"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22079761"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22079761"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yanrui Wu, Hongju Yang, Benguan Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of polymorphisms in prolylcarboxypeptidase and chymase genes with essential hypertension in the Chinese Han population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Renin Angiotensin Aldosterone Syst (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/1470320312448949"}], "href": "https://doi.org/10.1177/1470320312448949"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22679278"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22679278"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "J Wang, A Matafonov, H Madkhali, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prolylcarboxypeptidase independently activates plasma prekallikrein (fletcher factor)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Mol Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2174/1566524014666141015153519"}], "href": "https://doi.org/10.2174/1566524014666141015153519"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25324000"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25324000"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Kaat Kehoe, Raf Brouns, Robert Verkerk, et al. 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Synonyms	HUMPCP
Proteins	PCP_HUMAN
NCBI Gene ID	5547
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PRCP has 6,680 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 119 datasets.

Click the + buttons to view associations for PRCP from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PRCP Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by PRCP gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PRCP gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PRCP gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of PRCP gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PRCP gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PRCP gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PRCP gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PRCP gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PRCP gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PRCP gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PRCP gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PRCP gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PRCP protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PRCP gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PRCP gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PRCP gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PRCP gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PRCP protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PRCP gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PRCP protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PRCP protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PRCP protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PRCP protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PRCP gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PRCP gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PRCP gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PRCP gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PRCP protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PRCP gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PRCP gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PRCP gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PRCP gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PRCP gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at PRCP gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PRCP gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of PRCP gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing PRCP from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with PRCP gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with PRCP gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of PRCP gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.