Synemin

SYNM
Identifiers
Aliases	SYNM, DMN, SYN, synemin
External IDs	OMIM: 606087 MGI: 2661187 HomoloGene: 9081 GeneCards: SYNM
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q26.3 Start 99,098,217 bp[1] End 99,135,593 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 C Start 67,379,908 bp[2] End 67,409,490 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in seminal vesicula saphenous vein vastus lateralis muscle optic nerve right ventricle deltoid muscle thoracic diaphragm triceps brachii muscle inferior olivary nucleus urethra Top expressed in triceps brachii muscle knee joint vastus lateralis muscle temporal muscle sternocleidomastoid muscle tibialis anterior muscle digastric muscle ankle skeletal muscle tissue intercostal muscle More reference expression data BioGPS n/a
Gene ontology Molecular function vinculin binding protein binding structural molecule activity intermediate filament binding structural constituent of cytoskeleton structural constituent of muscle Cellular component cytoplasm cell junction costamere membrane cytoskeleton intermediate filament adherens junction neurofilament cytoskeleton sarcolemma Biological process intermediate filament cytoskeleton organization fast-twitch skeletal muscle fiber contraction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23336 233335 Ensembl ENSG00000182253 ENSMUSG00000030554 UniProt O15061 Q70IV5 RefSeq (mRNA) NM_145728 NM_015286 NM_183312 NM_201639 NM_207663 RefSeq (protein) NP_056101 NP_663780 NP_899135 NP_964001 NP_997546 Location (UCSC) Chr 15: 99.1 – 99.14 Mb Chr 7: 67.38 – 67.41 Mb PubMed search [3] [4]
Wikidata
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Synemin, also known as desmuslin, is a protein that in humans is encoded by the SYNM gene.^[5] Synemin is an intermediate filament (IF) family member. IF proteins are cytoskeletal proteins that confer resistance to mechanical stress and are encoded by a dispersed multigene family. This protein has been found to form a linkage between desmin, which is a subunit of the IF network, and the extracellular matrix, and provides an important structural support in muscle.

Function

Synemin is an intermediate filament (IF) and, like other IFs, primarily functions to integrate mechanical stress and maintain structural integrity in eukaryotic cells. While it has been observed in a variety of cell types, it has been best studied in the sarcomere of skeletal myocytes. It localizes at the Z-disk and has been shown to bind to α-dystrobrevin, α-actinin, and desmin to act as a mechanical linker in transmitting force laterally throughout the tissue, especially between the contractile myofibrils and extracellular matrix. Synemin contributes to linkage between costameres and the contractile apparatus in skeletal muscle of synemin null animals.^[6] Synemin plays an important regulatory role in the heart and the consequences of its absence are profound.^[7]

Properties

Synemin has properties very similar to the intermediate filament syncoilin. In particular, it binds to α-dystrobrevin in the dystrophin-associated protein complex to act as a mechanical "linker" between the myofibrillar network and the cell membrane.^[8]

Splice variants

Three splice variant isoforms of synemin exist, α and β and L. Both isoforms have a very short N-terminal domain of 10 amino acids and a long C-terminal domain consisting of 1243 amino acids for the α isoform and 931 amino acids for the β isoform.^[9] An intronic sequence of the synemin β isoform is used as a coding sequence for synemin α.^[9][10]

Cancer

SYNM gene has been observed progressively downregulated in Human papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy.^[11] For this reason, SYNM is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical preneoplastic lesions progression.^[11]

History

The origin of the synemin/desmuslin naming convention is quite complex. In 1980, synemin was first identified in avian smooth muscle and was initially described as an IF-associated protein due to its colocalization and copurification with desmin and vimentin.^[12] Subsequent to the cloning of chicken synemin, Mizuno and colleagues reported the cloning of a novel IF protein, human desmuslin, as an α-dystrobrevin-interacting protein.^[8] Sequence analysis showed that human desmuslin was 32% identical and 11% similar to the amino acid sequence of chicken synemin, while the IF proteins vimentin and desmin are more than 80% identical across the same species. Although several parts were very similar between human desmuslin and chicken synemin, the low degree of conservation between these two proteins compared to other cloned IF proteins suggested that synemin was not the human desmuslin orthologue.^[8] In addition, unlike chicken synemin, in vitro coimmunoprecipitation assays could not detect an interaction between human desmuslin and α-actinin.^[8] In 2001, Titeux and colleagues reported the cloning of the α and β splice-varying isoforms of human synemin and showed that β-synemin was identical to desmuslin.^[9] In 2014 was reported the first synemin -/- null animal.^[6]

References

External links

• Synemin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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