LDB3

ZASP is a PDZ domain-containing protein. PDZ motifs are modular protein-protein interaction domains consisting of 80-120 amino acid residues. PDZ domain-containing proteins interact with each other in cytoskeletal assembly or with other proteins involved in targeting and clustering of membrane proteins. ZASP interacts with alpha-actinin-2 through its N-terminal PDZ domain and with protein kinase C via its C-terminal LIM domains. The LIM domain is a cysteine-rich motif defined by 50-60 amino acids containing two zinc-binding modules. This protein also interacts with all three members of the myozenin family. There are 2 ZASP short forms (Uniprot ID: O75112-6, 31.0 kDa, 283 amino acids; and Uniprot ID: O75112-5, 35.6 kDa, 330 amino acids); and 4 ZASP long forms (Uniprot ID: O75112-4, 42.8 kDa, 398 amino acids; Uniprot ID: O75112-3, 50.6 kDa, 470 amino acids; Uniprot ID: O75112-2, 66.6 kDa, 617 amino acids; and Uniprot ID: O75112, 77.1 kDa, 727 amino acids). All ZASP isoforms have an N-terminal PDZ domain; internal, conserved sequences known as ZASP-like motifs (ZMs); and the four long isoforms have three C-terminal LIM domains. == Function ==

ZASP functions to maintain structural integrity of sarcomeres during contraction, and has been shown to be involved in protein kinase A signaling. ZASP has also been shown to co-activate α5β1 integrins along with the protein TLN1. == Clinical significance ==

Mutations in ZASP have been associated with myofibrillar myopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, noncompaction cardiomyopathy, and muscular dystrophy. ==Interactions==

The PDZ domain of ZASP binds the C-terminus of alpha actinin-2 and ZMs bind the rod domain of alpha actinin-2. The LIM domains have been shown to interact with protein kinase C. The cardiac-specific region of ZASP encoded by exon 4 includes a ZP motif and binds a regulatory subunit of protein kinase A. == See also ==