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.[5]

Human ZASP can exist in cardiac and skeletal cells as six distinct isoforms, based on alternative splicing of 16 exons.[7] There are 2 ZASP short forms (Uniprot ID: O75112-6, 31.0 kDa, 283 amino acids;[8] and Uniprot ID: O75112-5, 35.6 kDa, 330 amino acids);[9] and 4 ZASP long forms (Uniprot ID: O75112-4, 42.8 kDa, 398 amino acids;[10] Uniprot ID: O75112-3, 50.6 kDa, 470 amino acids;[11] Uniprot ID: O75112-2, 66.6 kDa, 617 amino acids;[12] and Uniprot ID: O75112, 77.1 kDa, 727 amino acids).[13][14] 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.[7]

ZASP functions to maintain structural integrity of sarcomeres during contraction, and has been shown to be involved in protein kinase A signaling.[15] ZASP has also been shown to co-activate α5β1 integrins along with the protein TLN1.[16]

Mutations in ZASP have been associated with myofibrillar myopathy,[17] dilated cardiomyopathy,[18][19][18] arrhythmogenic right ventricular cardiomyopathy,[20] noncompaction cardiomyopathy,[18][21] and muscular dystrophy.[17]

The PDZ domain of ZASP binds the C-terminus of alpha actinin-2[6][22] and ZMs bind the rod domain of alpha actinin-2.[23] The LIM domains have been shown to interact with protein kinase C.[22][24] The cardiac-specific region of ZASP encoded by exon 4 includes a ZP motif and binds a regulatory subunit of protein kinase A.[15]

• Dilated cardiomyopathy
• Noncompaction cardiomyopathy

• GeneReviews/NIH/NCBI/UW entry on Myofibrillar Myopathy
• Overview of all the structural information available in the PDB for UniProt: O75112 (Human LIM domain-binding protein 3) at the PDBe-KB.
• Overview of all the structural information available in the PDB for UniProt: Q9JKS4 (Mouse LIM domain-binding protein 3) at the PDBe-KB.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.