Actinin, alpha 2

1H8B, 1HCI, 1QUU, 4D1E, 5A37, 5A36, 5A38, 5A4B8811472ENSG00000077522ENSMUSG00000052374P35609Q9JI91NM_001103NM_001278343NM_001278344NM_033268NP_001094NP_001265272NP_001265273NP_150371Alpha-actinin 2 is a protein which in humans is encoded by the ACTN2 gene. This gene encodes an alpha-actinin isoform that is expressed in both skeletal and cardiac muscles and functions to anchor myofibrillar actin thin filaments and titin to Z-discs.1h8b: EF-HANDS 3,4 FROM ALPHA-ACTININ / Z-REPEAT 7 FROM TITIN1hci: CRYSTAL STRUCTURE OF THE ROD DOMAIN OF ALPHA-ACTININ1quu: CRYSTAL STRUCTURE OF TWO CENTRAL SPECTRIN-LIKE REPEATS FROM ALPHA-ACTININ1tjt: X-ray structure of the human alpha-actinin isoform 3 at 2.2A resolution1wku: High resolution structure of the human alpha-actinin isoform 3 Alpha-actinin 2 is a protein which in humans is encoded by the ACTN2 gene. This gene encodes an alpha-actinin isoform that is expressed in both skeletal and cardiac muscles and functions to anchor myofibrillar actin thin filaments and titin to Z-discs. Alpha-actinin 2 is a 103.8 kDa protein composed of 894 amino acids. Each molecule is rod-shaped (35 nm in length) and it homodimerizes in an anti-parallel fashion. Each monomer has an N-terminal actin-binding region composed of two calponin homology domains,two C-terminal EF hand domains, and four tandem spectrin-like repeats form the rod domain in the central region of the molecule. The high-resolution crystal structure of human alpha-actinin 2 at 3.5 Å was recently resolved. Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of actin-binding cytoskeletal proteins, including spectrin, dystrophin, utrophin and fimbrin. Skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments. Alpha-actinin 2 has been shown to interact with KCNA5, DLG1, DISC1, MYOZ1, GRIN2B, ADAM12, ACTN3, MYPN, PDLIM3, PKN, MYOT, TTN, NMDAR, SYNPO2, LDB3, and FATZ. The primary function of alpha-actinin 2 is to crosslink filamentous actin molecules and titin molecules from adjoining sarcomeres at Z-discs, a function that is modulated by phospholipids. It is clear from studies by Hampton et al. that this crosslinking can assume a variety of conformations, with preferences for 60° and 120° angles. Alpha-actinin 2 also functions in docking signalling molecules at Z-discs, and additional studies have also implicated alpha-actinin 2 in the binding of cardiac ion channels, Kv1.5 in particular. Mutations in ACTN2 are associated with hypertrophic cardiomyopathy, as well as dilated cardiomyopathy and endocardial fibroelastosis. The diverse functions of alpha-actinin 2 are reflected in the diverse clinical presentation of patients carrying ACTN2 mutations.