CAPZB

F-actin-capping protein subunit beta, also known as CapZβ is a is_associated_with::protein that in humans is encoded by the CAPZB is_associated_with::gene. CapZβ functions to cap is_associated_with::actin filaments at barbed ends in muscle and other tissues.

Structure
CapZβ can exist as 3 unique β subunits, dependent on alternative splicing mechanisms. CapZβ1 is 31.4 kDa and 277 amino acids in length, CapZβ2 is 30.6 kDa and 272 amino acids in length, and CapZβ3 is 301 amino acids in length (N-terminal extension of 29 amino acids relative to the β2 subunit. ). In contrast, the 3 α subunits arise from distinct genes. CapZ is a heterodimer composed of an α and β subunit. In muscle, capping protein α1 subunit and β1 subunit are localized at the Z-disc, and form CapZ. CapZ interacts with α-actinin, nebulette, nebulin, is_associated_with::HSC70. at the Z-disc.

Function
CAPZB is a member of the is_associated_with::F-actin capping protein family. This gene encodes the beta subunit of the barbed-end actin binding protein. The protein regulates growth of the actin filament by capping the barbed end of growing actin filaments.

CapZβ functions to cap is_associated_with::actin filaments at barbed (+) ends, thus controlling the rate of G-actin polymerization to F-actin and corresponding filament length. CapZ works in concert with is_associated_with::tropomodulin, which caps actin at pointed ends. In muscle, the interaction of CapZ with is_associated_with::actin is critical during myofibrilogenesis, as administration of a CapZ monoclonal antibody or expression of CapZ mutant protein disrupts actin filament formation and assembly of myofibrils. Isoforms of the CapZβ (β1 and β2) have distinct functions, as CapZβ1 anchors is_associated_with::actin at Z-discs and CapZβ2 at is_associated_with::intercalated discs. Overexpression of CapZβ2 (and concomitant down-regulation of CapZβ1) in mice resulted in a diseased phenotype with stunted growth, irregular gait, labored breathing and juvenile lethality. Ultrastructural measurements showed severely disrupted myofibrillar architecture. A function of CapZβ in transducing is_associated_with::protein kinase C signaling in is_associated_with::cardiac myocytes was illuminated by a study in skinned cardiac fibers which demonstrated that partial, transgenic reduction of CapZβ attenuated the functional effect of is_associated_with::protein kinase C on contraction and disturbed normal PKC isoform translocation patterns following is_associated_with::phenylephrine or is_associated_with::endothelin-1 treatment. Interestingly, a later study showed that partial reduction of CapZβ was cardioprotective during ischemia-reperfusion injury, concomitant with altered PKC isoform translocation to is_associated_with::myofilaments. Regarding the turnover of CapZβ, it was recently demonstrated that the protein turnover of CapZβ1 is in part regulated by the Bcl-2–associated athanogene, is_associated_with::BAG3, through a mechanism involving the association between is_associated_with::HSC70 and CapZβ1.

Clinical Significance
There is currently little to no data available on the relationship between the CAPZB gene and human disease.

Model organisms
is_associated_with::Model organisms have been used in the study of CAPZB function. A conditional is_associated_with::knockout mouse line, called Capzbtm1a(EUCOMM)Wtsi was generated as part of the is_associated_with::International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.

Male and female animals underwent a standardized is_associated_with::phenotypic screen to determine the effects of deletion. Twenty three tests were carried out on is_associated_with::mutant mice and four significant abnormalities were observed. No is_associated_with::homozygous is_associated_with::mutant embryos were identified during gestation, and therefore none survived until is_associated_with::weaning. The remaining tests were carried out on is_associated_with::heterozygous mutant adult mice and decreased circulating is_associated_with::triglyceride levels were observed in female animals, while males displayed abnormal behaviour in an open field.