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CPA4 carboxypeptidase A4 [ Homo sapiens (human) ]

Gene ID: 51200, updated on 16-Apr-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
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_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (130293161..130324180)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (131606545..131637922)
105.20220307 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. Carboxypeptidase A4 negatively correlates with p53 expression and regulates the stemness of breast cancer cells. Wang Y, et al. Int J Med Sci, 2021. PMID 33746592, Free PMC Article
  2. Carboxypeptidase A4 promotes cell growth via activating STAT3 and ERK signaling pathways and predicts a poor prognosis in colorectal cancer. Pan H, et al. Int J Biol Macromol, 2019 Oct 1. PMID 31279884
  3. 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. He J, et al. Growth Factors, 2016 Dec. PMID 28209092
  4. Serum carboxypeptidaseA4 levels predict liver metastasis in colorectal carcinoma. Sun L, et al. Oncotarget, 2016 Nov 29. PMID 27780921, 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 (35) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. Carboxypeptidase A4 promotes cardiomyocyte hypertrophy through activating PI3K-AKT-mTOR signaling.
    Title: Carboxypeptidase A4 promotes cardiomyocyte hypertrophy through activating PI3K-AKT-mTOR signaling.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. The crystal structure of the human CPA4 carboxypeptidase in complex with SmCI, a peptide protease inhibitor.
    Title: A noncanonical mechanism of carboxypeptidase inhibition revealed by the crystal structure of the Tri-Kunitz SmCI in complex with human CPA4.
Submit: New GeneRIF Correction See all GeneRIFs (16)

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

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)

Genotypes

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 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 cellular_component ND
No biological Data available
more info
  
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_2023_10

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

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