Group:MUZIC:Tritopodin: Difference between revisions

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<Structure load='Trit_pdz_pred.pdb' size='400' frame='true' align='right' caption='Prediction of the PDZ binding domain of Tritopodin . Lambert et al. ESyPred3D:Prediction of Proteins 3D structures. Bioinformatics 2002)' scene='Insert optional scene name here' />
===Synaptopodin 2-like protein / Tritopodin===


==TRITOPODIN==
==Introduction==
Tritopodin is the third member and less researched of the podin family proteins and is codified by the gene ''SYNPO2L''. Tritopodin also known under the names synaptopodin 2-like, Myopodin-like and CHAP (cytoskeletal heart-enriched actin-associated protein), is found in heart (Claeys et al. 2009) <ref> PMID:19151983 </ref> and skeletal muscle tissue (Beqqali et al. 2010) <ref> PMID:20215401 </ref>. Tritopodin share with Myopodin 33% of homology in the Aminoacid sequence, which makes believe similar functions for both proteins. Tritopodin gene it is form by 5 exons and 2 isoforms are postulated: mCHAPa from exon 1,2,3 and 5, as well as mCHAPb that result from a start-codon in exon 4 and the two derives proteins are of 140kDa (mCHAPa) und 110kDa (mCHAPb).  
The synaptopodin 2-like protein or '''tritopodin''' is the third member (besides [http://www.proteopedia.org/wiki/index.php/Group:MUZIC:Myopodin myopodin] and [http://www.proteopedia.org/wiki/index.php/Group:MUZIC:Synaptopodin synaptopodin]) of the podin protein family and is encoded by the gene ''SYNPO2L''[http://www.uniprot.org/uniprot/Q9H987]. Tritopodin has been revealed by database searches, and since it is the third member  of the podin family of proteins with extended sequence similarity, was named ‘‘tritopodin’’. Tritopodin is also known under the names synaptopodin 2-like, myopodin-like and CHAP (cytoskeletal heart-enriched actin-associated protein) and is found in heart and skeletal muscle tissue <ref> PMID:19151983 </ref>.
 
==Sequence Annotation==
Tritopodin shares 33% homology at the aminoacid level with myopodin and 30% with Synaptopodin <ref> PMID:9314539 </ref>, which predicts similar functions for both proteins. The human gene SYNPO2L, that encodes tritopodin exists of 5 exons, which are separated by different large introns. Database analysis (UCSC Genome Browser, EMBL) predicted 2 putative differential isoforms. Splicing isoforms: Tritopodin a (in human 102.5kDa and in mouse 103.3kDa and Tritopodin b (in both human and mouse 79kDa) (see figure). After done biochemicals experiments, Beqqali et al. postulated 2 isoforms: mCHAPa from exon 1,2,3 and 5, as well as mCHAPb that result from a start-codon in exon 4, from which derives two proteins variants of 140kDa (mCHAPa) and 110kDa (mCHAPb) <ref> PMID:20215401 </ref>.
 
 
 
[[Image:TritopodinProteopedia.jpg|800px]]


==Function==
==Function==
Tritopodin is expressed in vivo and in vitro in differentiated skeletal- and heart muscle cells (Linnemann 2010; Beqqali et al. 2010).  
Tritopodin is expressed in vivo and in vitro in differentiated skeletal- and heart muscle cells, and is conserved amongst vertebrates, indicating an essential role in muscle function. Furthermore Tritopodin is able to translocate to the nucleus, and plays an important role in skeletal and cardiac muscle development. <ref> PMID:20554076 </ref> <ref> PMID:20215401 </ref>.  


==Tritopodin interactions==
==Tritopodin Interactions==
Tritopodin as Synaptopodin and Myopodin localizes in the sarcomeric Z-disc, where they interact with α-actinin and Filamin C, verify by CoIPs and yeast two-hybrid assays <ref> PMID:20554076 </ref> (Linnemann et al. 2010) Adult skeletal and heart tissue shows the colocalization from mCHAP with α-actinin in the sarcomeric Z-disc and in the nucleus in embrional Cardiomyocytes (Beqqali et al. 2010).  
Tritopodin localize in the sarcomeric Z-disc, where interact with α-actinin, which was verified by CoIPs and yeast two-hybrid assays <ref> PMID:20554076 </ref>. In adult skeletal and cardiac muscle tissue from mCHAP was demonstrated the colocalization with α-actinin in the sarcomeric Z-disc and in the nucleus in embryonal cardiomyocytes <ref> PMID:20215401 </ref>.  


[[Image:Tritopodin.jpg|500x]]
==Pathology==
Knockdown of CHAP in zebrafish, results in aberrant heart and skeletal muscle development, disorganized sarcomeres and ultimately lead to diminished cardiac contractility.  


==References==
==References==
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