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    PRCP prolylcarboxypeptidase [ Homo sapiens (human) ]

    Gene ID: 5547, updated on 2-Nov-2024

    Summary

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    Official Symbol
    PRCPprovided by HGNC
    Official Full Name
    prolylcarboxypeptidaseprovided by HGNC
    Primary source
    HGNC:HGNC:9344
    See related
    Ensembl:ENSG00000137509 MIM:176785; AllianceGenome:HGNC:9344
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    PCP; HUMPCP
    Summary
    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]
    Expression
    Ubiquitous expression in placenta (RPKM 42.6), urinary bladder (RPKM 37.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PRCP in Genome Data Viewer
    Location:
    11q14.1
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (82822936..82901644, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (82759396..82838151, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (82533978..82612686, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene family with sequence similarity 181 member B Neighboring gene long intergenic non-protein coding RNA 2734 Neighboring gene RBMX pseudogene 3 Neighboring gene small nucleolar RNA U13 Neighboring gene eukaryotic translation initiation factor 2 subunit 2 beta pseudogene 6 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr11:82569102-82570301 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5332 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5334 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5335 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5333 Neighboring gene MIR3 retrotransposon enhancer-blocking element Neighboring gene uncharacterized LOC124902602 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3816 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3817 Neighboring gene DNA damage induced apoptosis suppressor Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3818 Neighboring gene ribosomal protein L7a pseudogene 54

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Haplotype-based association study between PRCP gene polymorphisms and essential hypertension in Hani minority group from a remote region of China. Wu Y, et al. J Renin Angiotensin Aldosterone Syst, 2020 Oct-Dec. PMID 33319614, Free PMC Article
    2. Prolyl carboxypeptidase activity decline correlates with severity and short-term outcome in acute ischemic stroke. Kehoe K, et al. Neurochem Res, 2015 Jan. PMID 25370794
    3. Prolylcarboxypeptidase regulates proliferation, autophagy, and resistance to 4-hydroxytamoxifen-induced cytotoxicity in estrogen receptor-positive breast cancer cells. Duan L, et al. J Biol Chem, 2011 Jan 28. PMID 21087932, Free PMC Article
    4. Expression, purification and crystallization of human prolylcarboxypeptidase. Abeywickrema PD, et al. Acta Crystallogr Sect F Struct Biol Cryst Commun, 2010 Jun 1. PMID 20516604, Free PMC Article
    5. Genetic association study of prolylcarboxypeptidase polymorphisms with susceptibility to essential hypertension in the Yi minority of China: A case-control study based on an isolated population. Wu Y, et al. J Renin Angiotensin Aldosterone Syst, 2020 Apr-Jun. PMID 32448049, Free PMC Article

    See all (61) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Haplotype-based association study between PRCP gene polymorphisms and essential hypertension in Hani minority group from a remote region of China.
      Title: Haplotype-based association study between PRCP gene polymorphisms and essential hypertension in Hani minority group from a remote region of China.
    2. Genetic association study of prolylcarboxypeptidase polymorphisms with susceptibility to essential hypertension in the Yi minority of China: A case-control study based on an isolated population.
      Title: Genetic association study of prolylcarboxypeptidase polymorphisms with susceptibility to essential hypertension in the Yi minority of China: A case-control study based on an isolated population.
    3. Fast oxidation of alpha-melanocyte-stimulating hormone and derived peptides under laboratory conditions causes irreproducible results-Insights from studies of prolylcarboxypeptidase in human cell types.
      Title: Fast oxidation of α-melanocyte-stimulating hormone and derived peptides under laboratory conditions causes irreproducible results-Insights from studies of prolylcarboxypeptidase in human cell types.
    4. Using multiple -omics approach, study validated key molecules, such as CAP1, SHC1 and PRCP, that might play a significant role in IgA nephropathy pathogenesis.
      Title: Identification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis.
    5. For the first time, PRCP is identified as an apelin-cleaving enzyme.
      Title: Prolyl carboxypeptidase purified from human placenta: its characterization and identification as an apelin-cleaving enzyme.
    6. The decrease in PRCP levels in the first 24 h after stroke onset is associated with stroke severity and an unfavourable short-term stroke outcome
      Title: Prolyl carboxypeptidase activity decline correlates with severity and short-term outcome in acute ischemic stroke.
    7. PRCP1 interacts with plasma kallikrein (PK) at multiple sites for PK activation.
      Title: Prolylcarboxypeptidase independently activates plasma prekallikrein (fletcher factor).
    8. The present results indicated PRCP rs7104980 can be considered as a marker for EH and Hap3 GAGCACTAACA (PRCP) and Hap16 TTTA (CMA1) might be associated with essential hypertension in Chinese Han population.
      Title: Association of polymorphisms in prolylcarboxypeptidase and chymase genes with essential hypertension in the Chinese Han population.
    9. PRCP regulates cell growth, angiogenesis, and the response to vascular injury
      Title: Prolylcarboxypeptidase promotes angiogenesis and vascular repair.
    10. analysis of non-benzimidazole and brain-penetrant prolylcarboxypeptidase inhibitors
      Title: The discovery of non-benzimidazole and brain-penetrant prolylcarboxypeptidase inhibitors.
    Submit: New GeneRIF Correction See all GeneRIFs (25)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC2202

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables dipeptidyl-peptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables serine-type carboxypeptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in angiogenesis involved in wound healing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in energy homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in glucose homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of systemic arterial blood pressure IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in plasma kallikrein-kinin cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of blood vessel endothelial cell migration IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of reactive oxygen species metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of thyroid hormone receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in azurophil granule membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in basal part of cell IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in ficolin-1-rich granule membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    lysosomal Pro-X carboxypeptidase
    Names
    angiotensinase C
    lysosomal carboxypeptidase C
    proline carboxypeptidase
    NP_001306143.1
    NP_005031.1
    NP_955450.2
    XP_005274150.1
    XP_054225298.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001319214.2 → NP_001306143.1  lysosomal Pro-X carboxypeptidase isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the the 5' UTR, lacks a portion of the 5' coding region and initiates translation at a downstream start codon compared to variant 1. The encoded isoform (3) has a shorter N-terminus and lacks a predicted signal peptide compared to isoform 1.
      Source sequence(s)
      AA477618, AK302386, AP001646, AW627417, BC001500, BE154586, CB154314
      Consensus CDS
      CCDS91553.1
      UniProtKB/TrEMBL
      B7Z7Q6, E9PIG4, E9PNF7, E9PR42
      Related
      ENSP00000436095.2, ENST00000534264.2
      Conserved Domains (1) summary
      cl21494
      Location:1 → 372
      Abhydrolase; alpha/beta hydrolases

    2. NM_005040.4 → NP_005031.1  lysosomal Pro-X carboxypeptidase isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_005031.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes isoform 1.
      Source sequence(s)
      AA477618, AP001646, AW627417, BC001500, BE154586, BI827978, CB154314
      Consensus CDS
      CCDS8262.1
      UniProtKB/Swiss-Prot
      A8MU24, B2R7B7, B3KRK5, B5BU34, P42785
      UniProtKB/TrEMBL
      E9PNF7
      Related
      ENSP00000317362.3, ENST00000313010.8
      Conserved Domains (2) summary
      COG0596
      Location:104 → 214
      MhpC; Pimeloyl-ACP methyl ester carboxylesterase [Coenzyme transport and metabolism, General function prediction only]
      cl21494
      Location:55 → 477
      Abhydrolase; alpha/beta hydrolases

    3. NM_199418.4 → NP_955450.2  lysosomal Pro-X carboxypeptidase isoform 2 precursor

      See identical proteins and their annotated locations for NP_955450.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) includes an alternate in-frame exon in the 5' coding region compared to variant 1. The encoded isoform (2) is longer than isoform 1. This isoform (2) may undergo proteolytic processing similar to isoform 1.
      Source sequence(s)
      AA477618, AK091786, AP001646, AW627417, BC001500, BE154586, CB154314
      Consensus CDS
      CCDS41695.1
      UniProtKB/TrEMBL
      E9PNF7
      Related
      ENSP00000377055.2, ENST00000393399.6
      Conserved Domains (2) summary
      COG0596
      Location:125 → 235
      MhpC; Pimeloyl-ACP methyl ester carboxylesterase [Coenzyme transport and metabolism, General function prediction only]
      cl21494
      Location:78 → 498
      Abhydrolase; alpha/beta hydrolases

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      82822936..82901644 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005274093.2 → XP_005274150.1  lysosomal Pro-X carboxypeptidase isoform X1

      See identical proteins and their annotated locations for XP_005274150.1

      UniProtKB/TrEMBL
      B7Z7Q6, E9PIG4, E9PNF7, E9PR42
      Related
      ENSP00000505064.1, ENST00000680566.1
      Conserved Domains (1) summary
      cl21494
      Location:1 → 372
      Abhydrolase; alpha/beta hydrolases

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      82759396..82838151 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054369323.1 → XP_054225298.1  lysosomal Pro-X carboxypeptidase isoform X1

      UniProtKB/TrEMBL
      B7Z7Q6, E9PIG4, E9PR42
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P42785.1 GenPept UniProtKB/Swiss-Prot:P42785

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