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    CPA4 carboxypeptidase A4 [ Homo sapiens (human) ]

    Gene ID: 51200, updated on 9-Dec-2024

    Summary

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    Official Symbol
    CPA4provided by HGNC
    Official Full Name
    carboxypeptidase A4provided by HGNC
    Primary source
    HGNC:HGNC:15740
    See related
    Ensembl:ENSG00000128510 MIM:607635; AllianceGenome:HGNC:15740
    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
    CPA3
    Summary
    This gene is a member of the carboxypeptidase A/B subfamily, and it is located in a cluster with three other family members on chromosome 7. Carboxypeptidases are zinc-containing exopeptidases that catalyze the release of carboxy-terminal amino acids, and are synthesized as zymogens that are activated by proteolytic cleavage. This gene could be involved in the histone hyperacetylation pathway. It is imprinted and may be a strong candidate gene for prostate cancer aggressiveness. [provided by RefSeq, Jul 2008]
    Expression
    Biased expression in skin (RPKM 24.3) and esophagus (RPKM 4.3) See more
    Orthologs
    mouse all
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    Genomic context

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    See CPA4 in Genome Data Viewer
    Location:
    7q32.2
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (130293161..130324180)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (131606545..131637922)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (129933001..129964020)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:129844685-129845484 Neighboring gene serine rich single-pass membrane protein 1 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:129912168-129912820 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:129912821-129913472 Neighboring gene Sharpr-MPRA regulatory region 5425 Neighboring gene carboxypeptidase A2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26652 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:129937306-129937806 Neighboring gene uncharacterized LOC105375503 Neighboring gene small nucleolar RNA U13 Neighboring gene small nucleolar RNA U13 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:129985848-129986818 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26653 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26654 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:129992089-129992735 Neighboring gene carboxypeptidase A5 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:130005327-130005828 Neighboring gene uncharacterized LOC105375504 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18645

    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. Macrophage-Induced Carboxypeptidase A4 Promotes the Progression of Anaplastic Thyroid Cancer. Choi YS, et al. Thyroid, 2024 Sep. PMID 38666696
    2. Detailed molecular comparison between the inhibition mode of A/B-type carboxypeptidases in the zymogen state and by the endogenous inhibitor latexin. García-Castellanos R, et al. Cell Mol Life Sci, 2005 Sep. PMID 16091843, Free PMC Article
    3. Carboxypeptidase 4 gene variants and early-onset intermediate-to-high risk prostate cancer. Ross PL, et al. BMC Cancer, 2009 Feb 26. PMID 19245716, Free PMC Article
    4. Crystal structure of novel metallocarboxypeptidase inhibitor from marine mollusk Nerita versicolor in complex with human carboxypeptidase A4. Covaleda G, et al. J Biol Chem, 2012 Mar 16. PMID 22294694, Free PMC Article
    5. A noncanonical mechanism of carboxypeptidase inhibition revealed by the crystal structure of the Tri-Kunitz SmCI in complex with human CPA4. Alonso del Rivero M, et al. Structure, 2013 Jul 2. PMID 23746805

    See all (39) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Macrophage-Induced Carboxypeptidase A4 Promotes the Progression of Anaplastic Thyroid Cancer.
      Title: Macrophage-Induced Carboxypeptidase A4 Promotes the Progression of Anaplastic Thyroid Cancer.
    2. CircCPA4 induces ASCT2 expression to promote tumor property of non-small cell lung cancer cells in a miR-145-5p-dependent manner.
      Title: CircCPA4 induces ASCT2 expression to promote tumor property of non-small cell lung cancer cells in a miR-145-5p-dependent manner.
    3. circCPA4 induces malignant behaviors of prostate cancer via miR-491-5p/SHOC2 feedback loop.
      Title: circCPA4 induces malignant behaviors of prostate cancer via miR-491-5p/SHOC2 feedback loop.
    4. Carboxypeptidase A4 negatively correlates with p53 expression and regulates the stemness of breast cancer cells.
      Title: Carboxypeptidase A4 negatively correlates with p53 expression and regulates the stemness of breast cancer cells.
    5. Carboxypeptidase A4 promotes cardiomyocyte hypertrophy through activating PI3K-AKT-mTOR signaling.
      Title: Carboxypeptidase A4 promotes cardiomyocyte hypertrophy through activating PI3K-AKT-mTOR signaling.
    6. Findings suggest that the angiotensin II (Ang II) generation from hAng-(1-12) is primarily mediated by chymase rather than carboxypeptidase A (CPA).
      Title: Mast cell peptidases (carboxypeptidase A and chymase)-mediated hydrolysis of human angiotensin-(1-12) substrate.
    7. CPA4 promotes CRC cell growth via activating the STAT3 and ERK pathways and may be a prognostic factor or therapeutic target for CRC
      Title: Carboxypeptidase A4 promotes cell growth via activating STAT3 and ERK signaling pathways and predicts a poor prognosis in colorectal cancer.
    8. we revealed that CPA4 downregulation may induce apoptosis and G1-S arrest by suppressing the protein kinase B/c-MYC pathway. These results suggest that CPA4 has an oncogenic effect on lung cancer growth. Taken together, we identified a novel gene in lung cancer that might provide a basis for new therapeutic targets.
      Title: Downregulation of CPA4 inhibits non small-cell lung cancer growth by suppressing the AKT/c-MYC pathway.
    9. Serum CPA4 concentration combined with lymph node involvement may be used as accurate predictors of liver metastasis in colorectal cancer.
      Title: Serum carboxypeptidaseA4 levels predict liver metastasis in colorectal carcinoma.
    10. CPA4 as a negative regulator of adipogenesis that is down-regulated by FGF-1. Expression of CPA4 in subcutaneous adipose tissue correlated negatively with insulin sensitivity.
      Title: Fibroblast growth factor-1 (FGF-1) promotes adipogenesis by downregulation of carboxypeptidase A4 (CPA4) - a negative regulator of adipogenesis implicated in the modulation of local and systemic insulin sensitivity.
    Submit: New GeneRIF Correction See all GeneRIFs (17)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    No evidence available (Last evaluated 2012-07-25)

    ClinGen Genome Curation Page
    Triplosensitivity

    No evidence available (Last evaluated 2012-07-25)

    ClinGen Genome Curation Page

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metallocarboxypeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables metallocarboxypeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables metallocarboxypeptidase activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in hormone catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in peptide catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in proteolysis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in extracellular space IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    carboxypeptidase A4
    Names
    carboxypeptidase A3
    NP_001156918.1
    NP_057436.2
    XP_047276394.1
    XP_054214303.1

    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.

    Genomic

    1. NG_011788.2 RefSeqGene

      Range
      5028..36047
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1038

    mRNA and Protein(s)

    1. NM_001163446.2 → NP_001156918.1  carboxypeptidase A4 isoform 2 precursor

      See identical proteins and their annotated locations for NP_001156918.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon in the coding region, compared to variant 1, resulting in an isoform (2) that is shorter than isoform 1. The encoded isoform (2) lacks a portion of the activation peptide and the carboxypeptidase A4 chain, and lacks the intervening cleavage site compared to isoform 1.
      Source sequence(s)
      AC024085
      Consensus CDS
      CCDS55163.1
      UniProtKB/Swiss-Prot
      Q9UI42
      Related
      ENSP00000412947.2, ENST00000445470.6
      Conserved Domains (3) summary
      COG2866
      Location:1 → 370
      MpaA; Murein tripeptide amidase MpaA [Cell wall/membrane/envelope biogenesis]
      pfam02244
      Location:28 → 95
      Propep_M14; Carboxypeptidase activation peptide
      cl11393
      Location:95 → 386
      Peptidase_M14_like; M14 family of metallocarboxypeptidases and related proteins

    2. NM_016352.4 → NP_057436.2  carboxypeptidase A4 isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_057436.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AC024085
      Consensus CDS
      CCDS5818.1
      UniProtKB/Swiss-Prot
      B7Z576, Q86UY9, Q9UI42
      UniProtKB/TrEMBL
      A4D1M3
      Related
      ENSP00000222482.4, ENST00000222482.10
      Conserved Domains (2) summary
      cd03870
      Location:118 → 419
      M14_CPA; Peptidase M14 carboxypeptidase subfamily A/B-like; Carboxypeptidase A subgroup
      pfam02244
      Location:27 → 101
      Propep_M14; Carboxypeptidase activation peptide

    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_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      130293161..130324180
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047420438.1 → XP_047276394.1  carboxypeptidase A4 isoform X1

      UniProtKB/TrEMBL
      B7Z5J4
      Related
      ENSP00000419660.1, ENST00000493259.5

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      131606545..131637922
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054358328.1 → XP_054214303.1  carboxypeptidase A4 isoform X1

      UniProtKB/TrEMBL
      B7Z5J4
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UI42.2 GenPept UniProtKB/Swiss-Prot:Q9UI42

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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