CAPN2 calpain 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CAPN2provided by HGNC
Official Full Name: calpain 2provided by HGNC
Primary source: HGNC:HGNC:1479
See related: Ensembl:ENSG00000162909 MIM:114230; AllianceGenome:HGNC:1479
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: CANP2; mCANP; CANPL2; CANPml
Summary: The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes the large subunit of the ubiquitous enzyme, calpain 2. Multiple heterogeneous transcriptional start sites in the 5' UTR have been reported. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
Expression: Ubiquitous expression in lung (RPKM 90.0), gall bladder (RPKM 66.0) and 25 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 1q41

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (223701597..223776018)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (222891307..222965751)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (223889299..223963720)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

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

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Rare variants in CAPN2 increase risk for isolated hypoplastic left heart syndrome.
Title: Rare variants in CAPN2 increase risk for isolated hypoplastic left heart syndrome.
Variants in Genes of Calpain System as Modifiers of Spinocerebellar Ataxia Type 3 Phenotype.
Title: Variants in Genes of Calpain System as Modifiers of Spinocerebellar Ataxia Type 3 Phenotype.
Cleavage and activation of LIM kinase 1 as a novel mechanism for calpain 2-mediated regulation of nuclear dynamics.
Title: Cleavage and activation of LIM kinase 1 as a novel mechanism for calpain 2-mediated regulation of nuclear dynamics.
CAPN2 acts as an indicator of hepatitis B virus to induce hepatic fibrosis.
Title: CAPN2 acts as an indicator of hepatitis B virus to induce hepatic fibrosis.
Calpain-2 participates in the process of calpain-1 inactivation.
Title: Calpain-2 participates in the process of calpain-1 inactivation.
Heat stress reduces calpain-2 expression, which then activates p38, leading to cardiomyocyte apoptosis and heart dysfunction.
Title: Calpain-2 protects against heat stress-induced cardiomyocyte apoptosis and heart dysfunction by blocking p38 mitogen-activated protein kinase activation.
protein levels of CAPN2 are regulated by miR-223, acting directly on the 3'-untranslated region as well as by miR-145, which acts via an increase in HDAC2
Title: Regulation of calpain 2 expression by miR-223 and miR-145.
Isoform-specific hyperactivation of calpain-2, but not calpain-1 occurs at the synapse early in the pathogenesis of Alzheimer's disease potentially contributing to the deregulation of synaptic signaling in humans and mice models.
Title: Isoform-specific hyperactivation of calpain-2 occurs presymptomatically at the synapse in Alzheimer's disease mice and correlates with memory deficits in human subjects.
The mechanisms that drove both mechanosensitive cell adhesion and motility converged on calpain 2, an intracellular protease important for talin cleavage and focal adhesion turnover.
Title: Integrin α(6) and EGFR signaling converge at mechanosensitive calpain 2.
Rab5 as a novel regulator of calpain2 activity and focal adhesion proteolysis leading to cell migration
Title: Calpain2 mediates Rab5-driven focal adhesion disassembly and cell migration.

Submit: New GeneRIF Correction See all GeneRIFs (93)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Common variants associated with general and MMR vaccine-related febrile seizures. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Activation of the Ca(2+)-dependent protease, calpain, is involved in cytotoxic effects mediated by HIV-1 gp120 in neuroblastoma cultures	PubMed
Tat	tat	HIV-1 Tat increases plasma membrane (PM) dopamine transporter (DAT) activity and calpain protease activity at the PM	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

SHGC-76403 (e-PCR)
- UniSTS:42019

NoName (e-PCR)
- UniSTS:56629

D1S3584 (e-PCR)
- UniSTS:5231

AL009595 (e-PCR)
- UniSTS:24432

D1S1423 (e-PCR)
- UniSTS:149619

D1S2550 (e-PCR)
- UniSTS:35788

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables calcium-dependent cysteine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables calcium-dependent cysteine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables calcium-dependent cysteine-type endopeptidase activity	ISS Inferred from Sequence or Structural Similarity more info
enables cysteine-type peptidase activity	TAS Traceable Author Statement more info	PubMed
enables cytoskeletal protein binding	NAS Non-traceable Author Statement more info	PubMed
enables enzyme binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in behavioral response to pain	IEA Inferred from Electronic Annotation more info
involved_in blastocyst development	IEA Inferred from Electronic Annotation more info
involved_in cellular response to amino acid stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to interferon-beta	IEA Inferred from Electronic Annotation more info
involved_in cellular response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in female pregnancy	IEA Inferred from Electronic Annotation more info
involved_in myoblast fusion	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cardiac muscle cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of myoblast fusion	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of phosphatidylcholine biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in protein autoprocessing	IEA Inferred from Electronic Annotation more info
involved_in proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis	ISS Inferred from Sequence or Structural Similarity more info
involved_in proteolysis	NAS Non-traceable Author Statement more info	PubMed
involved_in proteolysis involved in protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cytoskeleton organization	TAS Traceable Author Statement more info	PubMed
involved_in regulation of interleukin-6 production	IEA Inferred from Electronic Annotation more info
involved_in response to hydrogen peroxide	IEA Inferred from Electronic Annotation more info
involved_in response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in response to mechanical stimulus	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
part_of calpain complex	IPI Inferred from Physical Interaction more info	PubMed
part_of chromatin	IEA Inferred from Electronic Annotation more info
located_in cortical actin cytoskeleton	TAS Traceable Author Statement more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in external side of plasma membrane	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in focal adhesion	HDA more info	PubMed
located_in lysosome	IEA Inferred from Electronic Annotation more info
colocalizes_with membrane raft	IDA Inferred from Direct Assay more info	PubMed
located_in membrane raft	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in perinuclear endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in pseudopodium	IDA Inferred from Direct Assay more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: calpain-2 catalytic subunit

Names: CANP 2; M-calpain; calcium-activated neutral proteinase 2; calpain 2, (m/II) large subunit; calpain 2, large [catalytic] subunit; calpain 2, large subunit; calpain M-type; calpain, large polypeptide L2; millimolar-calpain

NP_001139540.1

EC 3.4.22.53

NP_001739.3

EC 3.4.22.53

XP_047287300.1

EC 3.4.22.53

XP_054194910.1

EC 3.4.22.53

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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.

mRNA and Protein(s)

NM_001146068.2 → NP_001139540.1 calpain-2 catalytic subunit isoform 2

See identical proteins and their annotated locations for NP_001139540.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 1.

Source sequence(s)

AC096542, AC099065

Consensus CDS

CCDS53478.1

UniProtKB/TrEMBL

B4DN77

Related

ENSP00000413158.2, ENST00000433674.6

Conserved Domains (3) summary

pfam00648
Location:2 → 264

Peptidase_C2; Calpain family cysteine protease

pfam01067
Location:285 → 429

Calpain_III; Calpain large subunit, domain III

cd16199
Location:455 → 622

EFh_PEF_CAPN2; Penta-EF hand, calcium binding motifs, found in m-type calpain (CAPN2)
NM_001748.5 → NP_001739.3 calpain-2 catalytic subunit isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC096542, AC099065

Consensus CDS

CCDS31035.1

UniProtKB/Swiss-Prot

A6NDG7, B7ZA96, E7ES58, P17655, Q16738, Q6PJT3, Q8WU26, Q9HBB1

UniProtKB/TrEMBL

B2RCM3

Related

ENSP00000295006.5, ENST00000295006.6

Conserved Domains (3) summary

pfam00648
Location:46 → 342

Peptidase_C2; Calpain family cysteine protease

pfam01067
Location:363 → 507

Calpain_III; Calpain large subunit, domain III

cd16199
Location:533 → 700

EFh_PEF_CAPN2; Penta-EF hand, calcium binding motifs, found in m-type calpain (CAPN2)