| Primary Identifier | IPR042736 | Type | Domain |
| Short Name | EFh_PEF_CAPN2 |
| description | This entry represents the Ca2 -binding penta-EF-hand (PEF) domain found in CAPN2 (also known as Calpain 2). CAPN2 is a ubiquitously expressed Ca2 -dependent intracellular cysteine protease that contains a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2 -binding penta-EF-hand (PEF) domain []. The catalytic subunit CAPN2 in complex with a regulatory subunit encoded by CAPNS1 forms an m-calpain heterodimer[]. CAPN2 acts as the key protease responsible for N-methyl-d-aspartic acid (NMDA)-induced cytoplasmic polyadenylation element-binding protein 3 (CPEB3) degradation in neurons []. It cleaves several components of the focal adhesion complex, such as FAK and talin, triggering disassembly of the complex at the rear of the cell []. The stimulation of CAPN2 activity is required for Golgi antiapoptotic proteins (GAAPs) to promote cleavage of FA kinase (FAK), cell spreading, and enhanced migration. calpain 2 is also involved in the onset of glial differentiation []. It regulates proliferation, survival, migration, and tumorigenesis of breast cancer cells through a PP2A-Akt-FoxO-p27(Kip1) signalling cascade []. Its expression is associated with response to platinum based chemotherapy, progression-free and overall survival in ovarian cancer []. Moreover, CAPN2 may play a role in fundamental mitotic functions, such as the maintenance of sister chromatid cohesion []. The activation of CAPN2 plays an essential role in hippocampal synaptic plasticity and in learning and memory []. In the eye, CAPN2, together with a lens-specific variant of CAPN3, is responsible for proteolytic cleavages of alpha and beta-crystallin. Overactivated alpha and beta-crystallin can lead to cataract formation []. Sometimes, CAPN2 compensates for loss of CAPN1, and both calpain isoforms are involved in AngII-induced aortic aneurysm formation []. The main phosphorylation sites in m-calpain are Ser50 and Ser369/Thr370. |
