Details for: CELA2A

Gene ID: 63036

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: CELA2A

Ensembl ID: ENSG00000142615

Description: chymotrypsin like elastase 2A

Cell Significance Landscape

Associated with

Significant Cells

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

  • pancreatic acinar cell CL0002064
    CSI 3.63
    rCSI 4.82%
    PRS 99.85

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

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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 [CELA2A](/details-gene/63036) (Chymotrypsin Like Elastase 2A) is a protein-coding gene located on chromosome 1p36.21. It encodes Elastase-2A, a serine-type endopeptidase primarily known for its role in proteolysis. Expression data reveals that [CELA2A](/details-gene/63036) is a highly specific and abundant marker for [pancreatic acinar cells](/details-cell/CL0002064), consistent with its function as a digestive enzyme secreted by the pancreas. Beyond its canonical digestive role, functional annotations and recent research link [CELA2A](/details-gene/63036) to metabolic processes, including insulin regulation and platelet aggregation, with specific mutations predisposing individuals to early-onset atherosclerosis and metabolic syndrome ([Link](https://doi.org/10.1038/s41588-019-0470-3)). ## Cellular Roles and Expression Landscape The expression profile of [CELA2A](/details-gene/63036) is remarkably specific, establishing it as a definitive molecular signature for a single cell type. **Overall**, the gene's significance is overwhelmingly concentrated in the [pancreatic acinar cell](/details-cell/CL0002064) (CSI: 3.63). This high Cell Significance Index underscores its role as a crucial workhorse in this cell, responsible for synthesizing and secreting digestive enzymes. Its localization to the extracellular space ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615)) is consistent with its function as a secreted protease that acts within the digestive tract. The highly restricted expression pattern suggests that its primary physiological function is tightly controlled and executed by this specialized exocrine cell. While some evidence suggests potential expression in other tissues like the skin ([Link](https://doi.org/10.1046/j.1523-1747.2000.00825.x)), its dominant role is unequivocally tied to pancreatic function. ## Pathways and Molecular Function The molecular functions of [CELA2A](/details-gene/63036) are centered on its enzymatic activity as a protease. Gene Ontology (GO) annotations confirm its role in [proteolysis](/details-go/GO:0006508) through its [serine-type endopeptidase activity](/details-go/GO:0004252) and [serine hydrolase activity](/details-go/GO:0017171). Beyond general protein degradation, [CELA2A](/details-gene/63036) is implicated in specific, systemic biological processes. These include the [insulin catabolic process](/details-go/GO:1901143), [regulation of insulin secretion](/details-go/GO:0050796), and [response to insulin](/details-go/GO:0032868). This suggests that the secreted elastase has endocrine-modulating functions that extend beyond digestion. Furthermore, its involvement in the [regulation of platelet aggregation](/details-go/GO:0090330) directly links its activity to hemostasis and thrombosis. Reactome pathway analysis also points to roles in [keratinization](/details-pathway/R-HSA-6805567) and the [formation of the cornified envelope](/details-pathway/R-HSA-6809371), which may reflect its documented ancillary expression in skin. ## Research Directions The discovery of [CELA2A](/details-gene/63036)'s involvement in metabolic syndrome and atherosclerosis has shifted its perception from a simple digestive enzyme to a systemic modulator of cardiovascular and endocrine health ([Link](https://doi.org/10.1038/s41588-019-0470-3)). This opens several new avenues for investigation. ### Proposed Hypotheses 1. **Pathogenic mutations in [CELA2A](/details-gene/63036) alter its enzymatic activity or substrate specificity, leading to aberrant processing of key metabolic and coagulation factors in circulation. This results in dysregulated plasma insulin levels and heightened platelet activation, thereby creating a pro-atherogenic state.** 2. **The expression of [CELA2A](/details-gene/63036) in non-pancreatic tissues, such as the skin, contributes to local tissue homeostasis, and its dysregulation could be involved in inflammatory skin disorders. This function is likely distinct from the systemic metabolic effects of the pancreatic-secreted enzyme.** ### Experimental Approach To test the first hypothesis, a CRISPR-Cas9 knock-in mouse model could be generated to carry the specific human mutations linked to atherosclerosis. These mice and their wild-type littermates would be subjected to a high-fat, pro-atherogenic diet. The subsequent investigation would involve: * **Metabolic Phenotyping:** Regular monitoring of blood glucose, plasma insulin levels via ELISA, and glucose/insulin tolerance tests to assess metabolic dysregulation. * **Cardiovascular Analysis:** Quantification of atherosclerotic plaque formation in the aortic root using histological staining. * **Hematological Assays:** In vitro platelet aggregation assays using plasma from the mice to determine if the mutations lead to a hypercoagulable state. ### Therapeutic Potential As a secreted serine protease with a newly identified role in pathology, [CELA2A](/details-gene/63036) presents a plausible therapeutic target. Given that pathogenic variants are associated with a gain-of-function or altered activity contributing to atherosclerosis, **inhibition** of its enzymatic activity is the most likely therapeutic strategy. A small molecule inhibitor or a neutralizing monoclonal antibody designed to specifically target circulating Elastase-2A could potentially normalize insulin metabolism and reduce platelet activation. The high tissue specificity of its expression to the pancreas is advantageous, as it may limit on-target side effects in other organs, though targeting a secreted protein requires careful design to avoid disrupting its necessary digestive functions.

Genular Protein ID: 912180868

Symbol: CEL2A_HUMAN

Name: Elastase-2A

UniProtKB Accession Codes:

P08217 B2R5I4 Q14243

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 EC 2 EMBL 8 Ensembl 1 GO 12 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MEROPS 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 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 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 3427074

Title: Primary structure of human pancreatic elastase 2 determined by sequence analysis of the cloned mRNA.

PubMed ID: 3427074

DOI: 10.1021/bi00397a010

PubMed ID: 3646943

Title: Characterization of pancreatic elastase II cDNAs: two elastase II mRNAs are expressed in human pancreas.

PubMed ID: 3646943

DOI: 10.1089/dna.1987.6.163

PubMed ID: 2834346

Title: Molecular cloning and expression in Escherichia coli of a cDNA encoding human pancreatic elastase 2.

PubMed ID: 2834346

DOI: 10.1093/oxfordjournals.jbchem.a122204

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 2307232

Title: Further studies on the human pancreatic binary complexes involving procarboxypeptidase A.

PubMed ID: 2307232

DOI: 10.1016/0014-5793(90)80665-6

PubMed ID: 10620133

Title: Human elastase 1: evidence for expression in the skin and the identification of a frequent frameshift polymorphism.

PubMed ID: 10620133

DOI: 10.1046/j.1523-1747.2000.00825.x

PubMed ID: 31358993

Title: CELA2A mutations predispose to early-onset atherosclerosis and metabolic syndrome and affect plasma insulin and platelet activation.

PubMed ID: 31358993

DOI: 10.1038/s41588-019-0470-3

Sequence Information:

  • Length: 269
  • Mass: 28888
  • Checksum: A2E05143EFF4987C
  • Sequence:
    • MIRTLLLSTL VAGALSCGDP TYPPYVTRVV GGEEARPNSW PWQVSLQYSS NGKWYHTCGG 
SLIANSWVLT AAHCISSSRT YRVGLGRHNL YVAESGSLAV SVSKIVVHKD WNSNQISKGN 
DIALLKLANP VSLTDKIQLA CLPPAGTILP NNYPCYVTGW GRLQTNGAVP DVLQQGRLLV 
VDYATCSSSA WWGSSVKTSM ICAGGDGVIS SCNGDSGGPL NCQASDGRWQ VHGIVSFGSR 
LGCNYYHKPS VFTRVSNYID WINSVIANN