Myopalladin

MYPN
Identifiers
Aliases	MYPN, CMD1DD, CMH22, MYOP, RCM4, myopalladin, NEM11
External IDs	OMIM: 608517 MGI: 1916052 HomoloGene: 23778 GeneCards: MYPN
Gene location (Human) Chr. Chromosome 10 (human) Band 10q21.3 Start 68,087,897 bp End 68,212,017 bp
Gene location (Mouse) Chr. Chromosome 10 (mouse) Band 10|10 B4 Start 62,951,574 bp End 63,039,731 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gastrocnemius muscle vastus lateralis muscle deltoid muscle tibialis anterior muscle right ventricle body of tongue synovial membrane synovial joint superior surface of tongue cancellous bone Top expressed in knee joint triceps brachii muscle extraocular muscle vastus lateralis muscle ankle temporal muscle digastric muscle sternocleidomastoid muscle tibialis anterior muscle soleus muscle More reference expression data BioGPS n/a
Gene ontology Molecular function SH3 domain binding cytoskeletal protein binding actin binding protein binding muscle alpha-actinin binding actin filament binding cell-cell adhesion mediator activity Cellular component cytoplasm sarcomere Z disc I band nucleus plasma membrane axon Biological process sarcomere organization regulation of cell migration regulation of cytoskeleton organization homophilic cell adhesion via plasma membrane adhesion molecules axon guidance dendrite self-avoidance Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 84665 68802 Ensembl ENSG00000138347 ENSMUSG00000020067 UniProt Q86TC9 Q5DTJ9 RefSeq (mRNA) NM_001256267 NM_001256268 NM_032578 NM_182992 RefSeq (protein) NP_001243196 NP_001243197 NP_115967 NP_892037 Location (UCSC) Chr 10: 68.09 – 68.21 Mb Chr 10: 62.95 – 63.04 Mb PubMed search
Wikidata
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Myopalladin is a protein that in humans is encoded by the MYPN gene. Myopalladin is a muscle protein responsible for tethering proteins at the Z-disc and for communicating between the sarcomere and the nucleus in cardiac and skeletal muscle

Structure

Myopalladin is a 145.2 kDa protein composed of 1320 amino acids. Myopalladin has five Ig-like repeats within the protein, and a proline-rich domain. Myopalladin binds the Src homology domain of nebulette and nebulin and tethers it to alpha-actinin via its C-terminal domain binding to the EF hand domains of alpha-actinin. The N-terminal region of myopalladin binds to the nuclear protein CARP, known to regulate gene expression in muscle. It also has been shown to bind ANKRD23.

Function

Myopalladin has dual subcellular localization, residing in both the nucleus and sarcomere/I-bands in muscle. Accordingly, myopalladin has functions in both sarcomere assembly and in control of gene expression. Specifics of these functions were gleaned from studies involving MYPN mutants associated with various cardiomyopathies. The Q529X myopalladin mutant demonstrated incompetence in recruiting key binding partners such as desmin, alpha-actinin and CARP to the Z-disc during myofibrilogenesis. In contrast, the Y20C mutant resulted in decreased expression of binding partners.

Clinical significance

Mutations in MYPN have been linked to nemaline myopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy and restrictive cardiomyopathy.

Further reading