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.

Human ZASP can exist in cardiac and skeletal cells as six distinct isoforms, based on alternative splicing of 16 exons.{{cite journal | vauthors = Sheikh F, Bang ML, Lange S, Chen J | title = "Z"eroing in on the role of Cypher in striated muscle function, signaling, and human disease | journal = Trends in Cardiovascular Medicine | volume = 17 | issue = 8 | pages = 258–62 | date = Nov 2007 | pmid = 18021935 | doi = 10.1016/j.tcm.2007.09.002 | pmc=2134983}} There are 2 ZASP short forms (Uniprot ID: O75112-6, 31.0 kDa, 283 amino acids;{{cite web |url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=O75112-6 |title=O75112-6 |access-date=2015-06-11 |archive-date=2015-06-13 |archive-url=https://web.archive.org/web/20150613073747/http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=O75112-6 |url-status=dead }} and Uniprot ID: O75112-5, 35.6 kDa, 330 amino acids);{{cite web |url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=O75112-5 |title=O75112-5 |access-date=2015-06-11 |archive-date=2015-06-13 |archive-url=https://web.archive.org/web/20150613120022/http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=O75112-5 |url-status=dead }} and 4 ZASP long forms (Uniprot ID: O75112-4, 42.8 kDa, 398 amino acids;{{cite web |url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=O75112-4 |title=O75112-4 |access-date=2015-06-11 |archive-date=2015-06-13 |archive-url=https://web.archive.org/web/20150613070404/http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=O75112-4 |url-status=dead }} Uniprot ID: O75112-3, 50.6 kDa, 470 amino acids;{{cite web |url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=O75112-3 |title=O75112-3 |access-date=2015-06-11 |archive-date=2015-06-13 |archive-url=https://web.archive.org/web/20150613073153/http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=O75112-3 |url-status=dead }} Uniprot ID: O75112-2, 66.6 kDa, 617 amino acids;{{cite web |url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=O75112-2 |title=O75112-2 |access-date=2015-06-11 |archive-date=2015-06-13 |archive-url=https://web.archive.org/web/20150613103726/http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=O75112-2 |url-status=dead }} and Uniprot ID: O75112, 77.1 kDa, 727 amino acids).{{cite web |url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=O75112 |title=O75112 |access-date=2015-06-11 |archive-date=2015-06-13 |archive-url=https://web.archive.org/web/20150613071704/http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=O75112 |url-status=dead }}{{cite journal | vauthors = Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P|display-authors = 6 | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = Oct 2013 | pmid = 23965338 | doi = 10.1161/CIRCRESAHA.113.301151 | pmc=4076475}} 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.

ZASP functions to maintain structural integrity of sarcomeres during contraction, and has been shown to be involved in protein kinase A signaling.{{cite journal | vauthors = Lin C, Guo X, Lange S, Liu J, Ouyang K, Yin X, Jiang L, Cai Y, Mu Y, Sheikh F, Ye S, Chen J, Ke Y, Cheng H |display-authors = 6| title = Cypher/ZASP is a novel A-kinase anchoring protein | journal = The Journal of Biological Chemistry | volume = 288 | issue = 41 | pages = 29403–13 | date = Oct 2013 | pmid = 23996002 | doi = 10.1074/jbc.M113.470708 | pmc=3795241|doi-access = free}} ZASP has also been shown to co-activate α5β1 integrins along with the protein TLN1.{{cite journal | vauthors = Bouaouina M, Jani K, Long JY, Czerniecki S, Morse EM, Ellis SJ, Tanentzapf G, Schöck F, Calderwood DA|display-authors = 6 | title = Zasp regulates integrin activation | journal = Journal of Cell Science | volume = 125 | issue = Pt 23 | pages = 5647–57 | date = Dec 2012 | pmid = 22992465 | doi = 10.1242/jcs.103291 | pmc=3575701}}

Mutations in ZASP have been associated with myofibrillar myopathy,{{cite journal | vauthors = Selcen D, Engel AG | title = Mutations in ZASP define a novel form of muscular dystrophy in humans | journal = Annals of Neurology | volume = 57 | issue = 2 | pages = 269–76 | date = Feb 2005 | pmid = 15668942 | doi = 10.1002/ana.20376 | s2cid = 25733755 }} dilated cardiomyopathy,{{cite journal | vauthors = Vatta M, Mohapatra B, Jimenez S, Sanchez X, Faulkner G, Perles Z, Sinagra G, Lin JH, Vu TM, Zhou Q, Bowles KR, Di Lenarda A, Schimmenti L, Fox M, Chrisco MA, Murphy RT, McKenna W, Elliott P, Bowles NE, Chen J, Valle G, Towbin JA|display-authors = 6 | title = Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction | journal = Journal of the American College of Cardiology | volume = 42 | issue = 11 | pages = 2014–27 | date = Dec 2003 | pmid = 14662268 | doi = 10.1016/j.jacc.2003.10.021 | doi-access = free }}{{cite journal | vauthors = Arimura T, Hayashi T, Terada H, Lee SY, Zhou Q, Takahashi M, Ueda K, Nouchi T, Hohda S, Shibutani M, Hirose M, Chen J, Park JE, Yasunami M, Hayashi H, Kimura A | title = A Cypher/ZASP mutation associated with dilated cardiomyopathy alters the binding affinity to protein kinase C | journal = The Journal of Biological Chemistry | volume = 279 | issue = 8 | pages = 6746–52 | date = Feb 2004 | pmid = 14660611 | doi = 10.1074/jbc.M311849200 | doi-access = free }} arrhythmogenic right ventricular cardiomyopathy,{{cite journal | vauthors = Lopez-Ayala JM, Ortiz-Genga M, Gomez-Milanes I, Lopez-Cuenca D, Ruiz-Espejo F, Sanchez-Munoz JJ, Oliva-Sandoval MJ, Monserrat L, Gimeno JR|display-authors = 6 | title = A mutation in the Z-line Cypher/ZASP protein is associated with arrhythmogenic right ventricular cardiomyopathy | journal = Clinical Genetics | date = Jul 2014 | pmid = 25041374 | doi = 10.1111/cge.12458 | volume=88 | issue = 2 | pages=172–6| s2cid = 21822009 }} noncompaction cardiomyopathy,{{cite journal | vauthors = Xi Y, Ai T, De Lange E, Li Z, Wu G, Brunelli L, Kyle WB, Turker I, Cheng J, Ackerman MJ, Kimura A, Weiss JN, Qu Z, Kim JJ, Faulkner G, Vatta M|display-authors = 6 | title = Loss of function of hNav1.5 by a ZASP1 mutation associated with intraventricular conduction disturbances in left ventricular noncompaction | journal = Circulation: Arrhythmia and Electrophysiology | volume = 5 | issue = 5 | pages = 1017–26 | date = Oct 2012 | pmid = 22929165 | doi = 10.1161/CIRCEP.111.969220 | pmc=4331025}} and muscular dystrophy.

The PDZ domain of ZASP binds the C-terminus of alpha actinin-2{{cite journal | vauthors = Zhou Q, Ruiz-Lozano P, Martone ME, Chen J | title = Cypher, a striated muscle-restricted PDZ and LIM domain-containing protein, binds to alpha-actinin-2 and protein kinase C | journal = The Journal of Biological Chemistry | volume = 274 | issue = 28 | pages = 19807–13 | date = Jul 1999 | pmid = 10391924 | doi=10.1074/jbc.274.28.19807| doi-access = free }} and ZMs bind the rod domain of alpha actinin-2.{{cite journal | vauthors = Klaavuniemi T, Ylänne J | title = Zasp/Cypher internal ZM-motif containing fragments are sufficient to co-localize with alpha-actinin--analysis of patient mutations | journal = Experimental Cell Research | volume = 312 | issue = 8 | pages = 1299–311 | date = May 2006 | pmid = 16476425 | doi = 10.1016/j.yexcr.2005.12.036 }} The LIM domains have been shown to interact with protein kinase C.{{cite journal | vauthors = Kuroda S, Tokunaga C, Kiyohara Y, Higuchi O, Konishi H, Mizuno K, Gill GN, Kikkawa U|display-authors = 6 | title = Protein-protein interaction of zinc finger LIM domains with protein kinase C | journal = The Journal of Biological Chemistry | volume = 271 | issue = 49 | pages = 31029–32 | date = Dec 1996 | pmid = 8940095 | doi=10.1074/jbc.271.49.31029| doi-access = free }} The cardiac-specific region of ZASP encoded by exon 4 includes a ZP motif and binds a regulatory subunit of protein kinase A.

• Dilated cardiomyopathy
• Noncompaction cardiomyopathy

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• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=mfm GeneReviews/NIH/NCBI/UW entry on Myofibrillar Myopathy]
• {{PDBe-KB2|O75112|Human LIM domain-binding protein 3}}
• {{PDBe-KB2|Q9JKS4|Mouse LIM domain-binding protein 3}}

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{{Signal transducing adaptor proteins}}

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