Group:MUZIC:ZASP

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	==Sequence annotation and domain topology==		==Sequence annotation and domain topology==
-	[[Image:ZASP.png|leftt|600px|thumb| Domain organization in ZASP]]	+	[[Image:ZASP.png|left|500px|thumb| Domain organization in ZASP]]
	==Structure==		==Structure==

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Revision as of 11:51, 12 July 2011

Contents 1 ZASP (Z-disk Alternatively Spliced PDZ domain protein) 2 Sequence annotation and domain topology 3 Structure 4 Function and Interactions 5 Pathology 6 References

ZASP (Z-disk Alternatively Spliced PDZ domain protein)

ZASP also referred to as LIM domain-binding protein 3 (LDB-3), is the 78 kDa, 727-amino-acid human ortholog of cypher, independently identified in heart and skeletal muscle ^[1]. ZASP is a component protein of the striated muscle Z-disk and a member of the enigma family of proteins. Like most enigma family members, it possess an N-terminal PDZ domain and three C-terminal LIM domains. The PDZ domain has recently been characterized to bind a very C-terminal class III motif in myotilin and myozenin. Apart from the PDZ domain, ZASP possess an internal motif (ZASP-like motif) which confers the ability to interact with the spectrin repeats of α-actinin-2 ^[2], suggesting it plays an important role during myofibrillogenesis.

Sequence annotation and domain topology

Structure

spinqualitylabelsall models NMR solution structure of the PDZ domain of ZASP (PDB code: 1RGW)[1] Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Function and Interactions

PDZ domains are known to target proteins to sites of complex formation, as such ZASP functions most probably as the oracle of Z-disk multi-protein complexes. This is suggested by the experimental evidences which show the PDZ domain interacts with alpha-actinin-2, myotilin, and FATZ protein family.

Pathology

Mutations in the ZASP gene have been associated with dilated cardiomyopathy (DCM) and DCM associated with isolated left ventricular noncompaction of the myocardium (INLVM) in humans ^[3]. The presence of multiple mutations in the ZASP gene in patients with DCM and INLVM suggests that disruption of this gene is a common cause of left ventricular dysfunction and dilation. Recently, mutations in ZASP have been linked to a novel form of muscular dystrophy in humans^[4].

References

1. ↑ Faulkner G, Pallavicini A, Formentin E, Comelli A, Ievolella C, Trevisan S, Bortoletto G, Scannapieco P, Salamon M, Mouly V, Valle G, Lanfranchi G. ZASP: a new Z-band alternatively spliced PDZ-motif protein. J Cell Biol. 1999 Jul 26;146(2):465-75. PMID:10427098
2. ↑ Klaavuniemi T, Ylanne J. Zasp/Cypher internal ZM-motif containing fragments are sufficient to co-localize with alpha-actinin--analysis of patient mutations. Exp Cell Res. 2006 May 1;312(8):1299-311. Epub 2006 Feb 14. PMID:16476425 doi:10.1016/j.yexcr.2005.12.036
3. ↑ 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. Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction. J Am Coll Cardiol. 2003 Dec 3;42(11):2014-27. PMID:14662268
4. ↑ Selcen D, Engel AG. Mutations in ZASP define a novel form of muscular dystrophy in humans. Ann Neurol. 2005 Feb;57(2):269-76. PMID:15668942 doi:10.1002/ana.20376