Details for: CPA3

Gene ID: 1359

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CPA3

Ensembl ID: ENSG00000163751

Description: carboxypeptidase A3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • common myeloid progenitor CL0000049
    CSI 16.12
    rCSI 13.03%
    PRS 99.82
  • hematopoietic precursor cell CL0008001
    CSI 16.05
    rCSI 16.51%
    PRS 99.74
  • basophil CL0000767
    CSI 15.82
    rCSI 33.47%
    PRS 99.63
  • promyelocyte CL0000836
    CSI 11.2
    rCSI 16.16%
    PRS 99.49
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 10.44
    rCSI 9.43%
    PRS 99.62
  • mast cell CL0000097
    CSI 10.31
    rCSI 22.27%
    PRS 96.5
  • granulocyte CL0000094
    CSI 8.74
    rCSI 13.35%
    PRS 99.61
  • basal cell of epidermis CL0002187
    CSI 5.87
    rCSI 10.4%
    PRS 92.58
  • granulocyte monocyte progenitor cell CL0000557
    CSI 5.07
    rCSI 4.39%
    PRS 99.78
  • eosinophil CL0000771
    CSI 4.85
    rCSI 31.81%
    PRS 99.73
  • hematopoietic multipotent progenitor cell CL0000837
    CSI 4.77
    rCSI 11.47%
    PRS 99.78
  • basophil mast progenitor cell CL0002028
    CSI 2.85
    rCSI 15.22%
    PRS 99.64
  • megakaryocyte CL0000556
    CSI 1.46
    rCSI 6.32%
    PRS 98.98
  • myeloid lineage restricted progenitor cell CL0000839
    CSI 1.45
    rCSI 7.51%
    PRS 99.73
  • cord blood hematopoietic stem cell CL2000095
    CSI 0.95
    rCSI 18.19%
    PRS 97.42
  • megakaryocyte progenitor cell CL0000553
    CSI 0.82
    rCSI 14.98%
    PRS 99.93
  • erythroid progenitor cell CL0000038
    CSI 0.68
    rCSI 3.91%
    PRS 99.61

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CPA3](/details-gene/1359), or carboxypeptidase A3, is a protein-coding gene located on chromosome 3 that encodes a zinc-dependent metallocarboxypeptidase. It is primarily known as mast cell carboxypeptidase A, a key enzyme stored in the [secretory granule](/details-cell/GO:0030141)s of specific immune cells [Link](https://doi.org/10.1172/jci114061). Expression data indicates that [CPA3](/details-gene/1359) is a highly specific marker for cells of the myeloid lineage, with particularly high significance in [common myeloid progenitor](/details-cell/CL0000049)s, [basophil](/details-cell/CL0000767)s, and [mast cell](/details-cell/CL0000097)s. Functionally, it is involved in proteolysis and peptide hormone metabolism, including the processing of angiotensins, suggesting a role in linking allergic or inflammatory responses to local vascular regulation. A clinical association with this gene has been recorded ([114851](https://omim.org/entry/114851)). ## Cellular Roles and Expression Landscape The expression profile of [CPA3](/details-gene/1359) firmly establishes it as a specialized enzyme within the hematopoietic system, with a distinct role in the myeloid and granulocytic compartments. **Overall**, the gene shows the highest significance in hematopoietic precursors, including [common myeloid progenitor](/details-cell/CL0000049)s (CSI: 16.12) and [hematopoietic precursor cell](/details-cell/CL0008001)s (CSI: 16.05), suggesting its expression is initiated early during myeloid differentiation. Its role as a key functional protein in mature effector cells is highlighted by its high significance in [basophil](/details-cell/CL0000767)s (CSI: 15.82) and [mast cell](/details-cell/CL0000097)s (CSI: 10.31). This is consistent with early research that first cloned and characterized the protein from human mast cells [Link](https://doi.org/10.1172/jci115571), [Link](https://doi.org/10.1073/pnas.86.23.9480). The significant expression in other granulocytes and their progenitors, such as [promyelocyte](/details-cell/CL0000836)s and [granulocyte](/details-cell/CL0000094)s, further underscores its specific function in this lineage. The narrow expression pattern, largely restricted to these cell types, suggests a highly specialized function related to inflammation and innate immunity, rather than a broad homeostatic role. ## Pathways and Molecular Function The molecular function of [CPA3](/details-gene/1359) is centered on its [metallocarboxypeptidase activity](/details-go/GO:0004181), which involves [zinc ion binding](/details-go/GO:0008270) to catalyze the cleavage of C-terminal amino acids from proteins and peptides ([proteolysis](/details-go/GO:0006508)). Its localization within the [secretory granule](/details-go/GO:0030141) is a critical aspect of its function, allowing it to be stored in an active form and rapidly released into the [extracellular space](/details-go/GO:0005615) upon cellular activation, a hallmark of [mast cell](/details-cell/CL0000097) and [basophil](/details-cell/CL0000767) degranulation. Functionally, [CPA3](/details-gene/1359) is implicated in the broad process of [peptide hormone metabolism](/details-reactome/R-HSA-2980736). More specifically, it participates in the [Metabolism of angiotensinogen to angiotensins](/details-reactome/R-HSA-2022377), which is directly linked to the [regulation of angiotensin levels in blood](/details-go/GO:0002002). This pathway involvement suggests that when [mast cell](/details-cell/CL0000097)s degranulate in tissues, the released [CPA3](/details-gene/1359) could locally process angiotensin peptides, thereby modulating vascular tone and contributing to the physiological hallmarks of an allergic or inflammatory reaction. ## Research Directions The specific expression of [CPA3](/details-gene/1359) in mast cells and basophils, coupled with its role in processing vasoactive peptides, presents several avenues for future research. **Proposed Hypotheses:** 1. Given its enzymatic role in angiotensin processing, [CPA3](/details-gene/1359) released during allergic degranulation in tissues like the skin or lungs directly contributes to local vascular permeability and edema by generating specific angiotensin fragments that act on local endothelial and smooth muscle cells. 2. The high-level expression of [CPA3](/details-gene/1359) in early hematopoietic progenitors, such as [common myeloid progenitor](/details-cell/CL0000049)s, may play an active role in lineage commitment toward the mast cell/basophil fate by processing signaling peptides within the bone marrow microenvironment. **Experimental Approach:** To test the first hypothesis, a combination of *in vivo* and *ex vivo* models could be employed. A CRISPR/Cas9-based knockout of [CPA3](/details-gene/1359) could be generated in a human mast cell line (e.g., HMC-1). The secretome of activated wild-type versus knockout cells could then be analyzed using mass spectrometry to identify differences in angiotensin peptide profiles. Furthermore, these conditioned media could be applied to primary human endothelial cell cultures to measure changes in barrier function and tight junction protein expression, directly linking CPA3 activity to a physiological outcome. **Therapeutic Potential:** As a secreted enzyme highly restricted to [mast cell](/details-cell/CL0000097)s and [basophil](/details-cell/CL0000767)s, [CPA3](/details-gene/1359) represents an attractive therapeutic target. In diseases characterized by excessive mast cell activation, such as mastocytosis or severe allergic asthma, inhibiting CPA3 activity could mitigate tissue-specific pathology without requiring cytotoxic depletion of the cells themselves. A highly specific small molecule inhibitor could be developed to block its enzymatic activity in the extracellular space, thereby reducing the downstream effects of degranulation, such as local inflammation and vascular leakage. Therefore, **inhibition** of [CPA3](/details-gene/1359) activity is the most promising therapeutic strategy.

Genular Protein ID: 798622465

Symbol: CBPA3_HUMAN

Name: Mast cell carboxypeptidase A

UniProtKB Accession Codes:

P15088 Q96E94

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 4 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EC 2 EMBL 9 Ensembl 1 GO 9 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OGP 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2594780

Title: Cloning of cDNAs that encode human mast cell carboxypeptidase A, and comparison of the protein with mouse mast cell carboxypeptidase A and rat pancreatic carboxypeptidases.

PubMed ID: 2594780

DOI: 10.1073/pnas.86.23.9480

PubMed ID: 1729276

Title: Cloning and characterization of the novel gene for mast cell carboxypeptidase A.

PubMed ID: 1729276

DOI: 10.1172/jci115571

PubMed ID: 16641997

Title: The DNA sequence, annotation and analysis of human chromosome 3.

PubMed ID: 16641997

DOI: 10.1038/nature04728

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 1629626

Title: Human skin mast cell carboxypeptidase: functional characterization, cDNA cloning, and genealogy.

PubMed ID: 1629626

DOI: 10.1111/1523-1747.ep12616776

PubMed ID: 2708524

Title: Human mast cell carboxypeptidase. Purification and characterization.

PubMed ID: 2708524

DOI: 10.1172/jci114061

Sequence Information:

  • Length: 417
  • Mass: 48670
  • Checksum: ACB9038758117F9A
  • Sequence:
    • MRLILPVGLI ATTLAIAPVR FDREKVFRVK PQDEKQADII KDLAKTNELD FWYPGATHHV 
AANMMVDFRV SEKESQAIQS ALDQNKMHYE ILIHDLQEEI EKQFDVKEDI PGRHSYAKYN 
NWEKIVAWTE KMMDKYPEMV SRIKIGSTVE DNPLYVLKIG EKNERRKAIF TDCGIHAREW 
VSPAFCQWFV YQATKTYGRN KIMTKLLDRM NFYILPVFNV DGYIWSWTKN RMWRKNRSKN 
QNSKCIGTDL NRNFNASWNS IPNTNDPCAD NYRGSAPESE KETKAVTNFI RSHLNEIKVY 
ITFHSYSQML LFPYGYTSKL PPNHEDLAKV AKIGTDVLST RYETRYIYGP IESTIYPISG 
SSLDWAYDLG IKHTFAFELR DKGKFGFLLP ESRIKPTCRE TMLAVKFIAK YILKHTS