CAPN2: Calpain 2, the Ubiquitous Calcium-Dependent Cysteine Protease
Comprehensive gene overview of CAPN2, including genomic data, expression, mutations, and disease associations.
Gene Information Card
| Symbol | CAPN2 |
|---|---|
| Full Name | Calpain 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q41 |
| NCBI Gene ID | 824 ncbi.nlm.nih.gov/gene/824 |
| Ensembl ID | ENSG00000162909 |
| UniProt ID | P17655 |
| OMIM ID | 114230 |
| HGNC ID | 1477 |
| Aliases | CANP2, CANPL2, m-calpain, calpain-2 catalytic subunit |
Description
CAPN2 encodes the catalytic subunit of calpain 2, a ubiquitous calcium-dependent cysteine protease. The enzyme is a heterodimer composed of a large catalytic subunit (CAPN2) and a small regulatory subunit (CAPNS1). Calpain 2 is involved in various cellular processes including cell motility, cell cycle progression, apoptosis, and signal transduction through limited proteolysis of substrates such as cytoskeletal proteins, kinases, and transcription factors.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Limb-Girdle Muscular Dystrophy Type 2A (LGMD2A) | Dysregulation of calpain-mediated proteolysis in muscle; CAPN2 overexpression or altered activity may contribute to pathology. | OMIM #253600; PMID: 10447258 |
| Alzheimer Disease | Calpain 2 hyperactivation leads to tau cleavage and neurodegeneration. | PMID: 25220745; ClinVar |
| Colorectal Cancer | CAPN2 overexpression promotes tumor invasion and metastasis via proteolysis of focal adhesion proteins. | COSMIC; PMID: 23593055 |
| Breast Cancer | Elevated CAPN2 expression correlates with poor prognosis and increased cell migration. | COSMIC; PMID: 25636800 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 10.2 | Medium |
| Liver | 8.9 | Medium |
| Kidney | 11.3 | Medium |
| Skeletal Muscle | 15.7 | High |
| Lung | 9.1 | Medium |
| Pancreas | 7.4 | Low |
| Spleen | 6.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 14.2 | Cervical cancer cell line; high expression |
| HEK293 | 11.5 | Embryonic kidney; moderate expression |
| MCF7 | 9.8 | Breast cancer; moderate expression |
| A549 | 10.1 | Lung cancer; moderate expression |
| HCT116 | 13.0 | Colorectal cancer; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.130G>A (p.Gly44Arg) | Missense | <0.01% | Altered calcium sensitivity; reported in ClinVar |
| c.758C>T (p.Thr253Met) | Missense | <0.01% | Reduced proteolytic activity; associated with LGMD2A |
| c.1066G>A (p.Gly356Arg) | Missense | <0.01% | Unknown functional effect; COSMIC |
| c.1690C>T (p.Arg564Trp) | Missense | <0.01% | Potential loss of function; ClinVar |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in the catalytic domain (e.g., p.Thr253Met) reduce proteolytic activity, leading to impaired substrate cleavage and muscle degeneration.
Gain of Function (GOF)
Overexpression or activating mutations (e.g., p.Gly44Arg) may increase calpain activity, contributing to excessive proteolysis in neurodegeneration and cancer.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for CAPN2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Calpain Proteolysis Pathway (Reactome: R-HSA-5625740)
• Apoptosis (KEGG: hsa04210)
• Focal Adhesion (KEGG: hsa04510)
Protein Summary
Calpain 2 (UniProt P17655) is a 700-amino acid protein with a molecular weight of approximately 80 kDa. It contains a cysteine protease domain (CysPc) and a calpain-type beta-sandwich domain. The enzyme is activated by micromolar calcium concentrations and requires heterodimerization with the regulatory subunit CAPNS1 for stability and activity. Calpain 2 cleaves a variety of substrates including talin, vinculin, and p53, thereby regulating cell adhesion, migration, and survival.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CAPN2 Knockout HEK293 Cell Line | EDJ-KQ4189 | Human | 824 | Details Get a Quote |
| CAPN2 Knockout A-549 Cell Line | EDJ-KQ25314 | Human | 824 | Details Get a Quote |
| CAPN2 Knockout HCT 116 Cell Line | EDJ-KQ26636 | Human | 824 | Details Get a Quote |
| CAPN2 Knockout HeLa Cell Line | EDJ-KQ26637 | Human | 824 | Details Get a Quote |
