CPA4 carboxypeptidase A4 [Homo sapiens (human)] - Gene

Summary

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

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_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
Carboxypeptidase A4 promotes cardiomyocyte hypertrophy through activating PI3K-AKT-mTOR signaling.
Title: Carboxypeptidase A4 promotes cardiomyocyte hypertrophy through activating PI3K-AKT-mTOR signaling.
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.
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.
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.
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.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2560 (e-PCR)
- UniSTS:37928

CPA4_7257 (e-PCR)
- UniSTS:471399

D7S2519 (e-PCR), detects polymorphism
- UniSTS:52077

RH122316 (e-PCR)
- UniSTS:137839

RH102846 (e-PCR)
- UniSTS:97180

SHGC-149533 (e-PCR)
- UniSTS:177061

D7S2519 (e-PCR), detects polymorphism
- UniSTS:76997

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

EC 3.4.17.15

NP_057436.2

EC 3.4.17.15

XP_047276394.1

EC 3.4.17.15

XP_054214303.1

EC 3.4.17.15

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

NG_011788.2 RefSeqGene

Range

5028..36047

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1038

mRNA and Protein(s)

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
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