# Synemin
**Synemin** is a large intermediate filament (rope-like protein fiber giving cells structure) protein of muscle and some glial and other non-epithelial cells, encoded by the SYNM gene, that forms heteropolymeric 10-nm filaments with desmin or vimentin and links those filaments to Z-disks, costameres, and cell membranes while also acting as a scaffold for signaling proteins such as protein kinase A.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7090255/) • [2](https://www.uniprot.org/uniprotkb/O15061/entry) It was first described in 1980 as a 230,000-dalton polypeptide that co-purified with desmin and vimentin from avian smooth muscle, and was named from the Greek for "with filament".[3](https://pubmed.ncbi.nlm.nih.gov/7006832/)
| Key fact | Detail |
|---|---|
| Gene and locus | SYNM (OMIM *606087) on chromosome 15q26.3; three isoforms produced by alternative splicing[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC8073371/) |
| Human protein | 1,565 amino acids, reviewed (Swiss-Prot) entry, evidence at protein level[2](https://www.uniprot.org/uniprotkb/O15061/entry) |
| Mammalian isoforms | α-/high (H, 180 kDa), β-/medium (M, 150 kDa), and low (L, 41 kDa)[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7090255/) |
| Domain structure | Head of 10 amino acids, central α-helical rod of about 310 amino acids, and unusually long tails of about 1,200 (α) and 900 (β) amino acids[5](https://journals.physiology.org/doi/full/10.1152/ajpcell.00303.2016) |
| Assembly | Cannot homopolymerize; requires a partner such as desmin, vimentin, or keratin to form filaments[6](https://journals.biologists.com/jcs/article/127/21/4589/54680/Synemin-acts-as-a-regulator-of-signalling) |
| Binding partners | Desmin, vimentin, α-actinin, vinculin, metavinculin, dystrophin, utrophin, α-dystrobrevin, talin, plectin, zyxin, GFAP, and keratins 5 and 6[7](https://journals.physiology.org/doi/full/10.1152/ajpcell.00485.2019) • [8](https://pubmed.ncbi.nlm.nih.gov/12845519/) |
| Signaling role | A-kinase-anchoring protein (AKAP) that anchors PKA and modulates PKA-dependent phosphorylation of cytoskeletal substrates such as desmin[7](https://journals.physiology.org/doi/full/10.1152/ajpcell.00485.2019) |
| Disease links | SYNM mutations reported in multiple cases of dilated cardiomyopathy and one case of ulnar-mammary-like syndrome with left ventricular tachycardia[9](https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00159/full) |
## Discovery and identification as an intermediate filament protein
Synemin was isolated from chicken smooth and skeletal muscle by Granger and Lazarides in 1980 as a high-molecular-weight polypeptide that co-purified through cycles of depolymerization and polymerization with the intermediate filament subunits desmin and vimentin, and shared their spatial distribution in immunofluorescence microscopy.[3](https://pubmed.ncbi.nlm.nih.gov/7006832/) Because of this association it was initially treated as an intermediate filament-associated protein (IFAP) rather than an intermediate filament protein itself.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7090255/)
Cloning of the synemin gene (SYNM) changed this classification: the protein contains the central rod domain that lets intermediate filament proteins form coiled-coil dimers assembled into 10-nm filaments, making it a bona fide member of the intermediate filament family.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7090255/) Chicken synemin, the originally characterized ortholog, is 1,604 amino acids long.[10](https://www.uniprot.org/uniprotkb/Q90662/entry) Human synemin was independently identified in 2001 as a novel gene named desmuslin, which was later found to be β-synemin; the low sequence identity between orthologs (37% overall between chicken and human α-synemin, 29% for β) explains why the mammalian protein was not recognized at first.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7090255/) • [11](https://febs.onlinelibrary.wiley.com/doi/10.1046/j.0014-2956.2001.02594.x)
## Structure
Like all cytoplasmic intermediate filament proteins, synemin has a tripartite organization: a non-helical head, a conserved central α-helical rod of roughly 310 amino acids that drives coiled-coil dimerization, and a C-terminal tail.[5](https://journals.physiology.org/doi/full/10.1152/ajpcell.00303.2016) In synemin both flanking regions are extreme: the head is only 10 amino acids, about 10 times shorter than in most intermediate filament proteins, while the tails of α- and β-synemin run to about 1,200 and 900 amino acids respectively, about 10 times larger than in most other family members.[5](https://journals.physiology.org/doi/full/10.1152/ajpcell.00303.2016)
**Isoforms.** Mammals express three splice variants: α-synemin (also called synemin H, 180 kDa), β-synemin (synemin M, 150 kDa), and the smaller L isoform (41 kDa).[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7090255/) α- and β-synemin differ by the inclusion of one exon in α-synemin, which encodes a 312-amino-acid insert near the end of the C-terminal tail; the L isoform shares the head and rod domains but uses a different open reading frame produced by fusion of exon 3 to exon 5, giving a distinctive smaller tail.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7090255/) The human gene yields isoform A (the longer product) and isoform B, which lacks an internal coding segment while maintaining the reading frame.[12](https://www.ncbi.nlm.nih.gov/gene/23336/) Sources classify synemin differently within the intermediate filament family: the Journal of Cell Science hypertrophy study calls it a type IV intermediate filament, while UniProt and a smooth-muscle review place it in type VI.[6](https://journals.biologists.com/jcs/article/127/21/4589/54680/Synemin-acts-as-a-regulator-of-signalling) • [2](https://www.uniprot.org/uniprotkb/O15061/entry) • [13](https://pmc.ncbi.nlm.nih.gov/articles/PMC2398705/)
## Binding partners and crosslinking function
Synemin is a minor component of intermediate filaments, at ratios of roughly 50:1 with vimentin and 25:1 with desmin, and it cannot assemble into filaments on its own; it copolymerizes with desmin or vimentin to form heteropolymers in striated and smooth muscle.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7090255/) • [7](https://journals.physiology.org/doi/full/10.1152/ajpcell.00485.2019) In coassembly experiments, purified synemin mixed with desmin at 1:25, the ratio typically found in vivo, produced filaments comparable in length to desmin filaments, whereas molar ratios of 3:25 and 6:25 generated much shorter and irregularly shaped polymers.[8](https://pubmed.ncbi.nlm.nih.gov/12845519/)
Its large tail carries binding sites for cytoskeletal and membrane-associated proteins, which is what makes synemin a crosslinker. Yeast two-hybrid and blot-overlay assays demonstrated interactions with desmin and vimentin and defined subdomains for binding to α-actinin, the Z-line protein, and to the costameric protein vinculin.[14](https://pubmed.ncbi.nlm.nih.gov/11418616/) Synemin also binds dystrophin, utrophin, and α-dystrobrevin, components of the dystrophin-associated protein complex, as well as talin, plectin, and zyxin.[7](https://journals.physiology.org/doi/full/10.1152/ajpcell.00485.2019) • [6](https://journals.biologists.com/jcs/article/127/21/4589/54680/Synemin-acts-as-a-regulator-of-signalling) Some interactions are isoform-specific: α-synemin, but not β-synemin, interacts with vinculin, metavinculin, and talin, with the vinculin and talin binding regions mapped to the α-specific segment around amino acids 1151 to 1464.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7090255/) Other studies, however, co-immunoprecipitated β-synemin with vinculin from rat skeletal muscle and neonatal cardiac myocytes, a discrepancy attributed to differences in methodology, cell type, and development.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7090255/)
Through this web of interactions synemin links intermediate filament networks to costameres, the subsarcolemmal complexes that transmit force across the membrane, and to sarcomeres via α-actinin at the Z-disk.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7090255/) In the heart it interconnects Z-disks to desmosomes and participates in mitochondria positioning, a process probably involving plectin.[7](https://journals.physiology.org/doi/full/10.1152/ajpcell.00485.2019)
## Role in signaling
Synemin is an A-kinase-anchoring protein (AKAP): it anchors protein kinase A (PKA) and modulates PKA-dependent phosphorylation of cytoskeletal substrates such as desmin, which may influence muscle growth and repair by regulating phosphorylation of Z-disk and sarcolemma proteins.[7](https://journals.physiology.org/doi/full/10.1152/ajpcell.00485.2019) It also binds protein phosphatase 2A (PP2A) and Akt, participating in the PI3K-Akt pathway; in astrocytoma cells synemin regulates proliferation by interacting with PP2A to modulate Akt phosphorylation.[9](https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00159/full) • [15](https://pubmed.ncbi.nlm.nih.gov/26795483/)
**Knockout evidence.** Synemin-deficient (Synm−/−) mice develop and breed normally but show mild degeneration and regeneration of myofibers and defects in the sarcolemma. After mechanical overload their muscles show a higher hypertrophic capacity, with increased maximal force and fatigue resistance, accompanied by decreased myostatin (GDF8) and atrogin ([FBXO32](https://www.edgepedia.org/fbxo32)) expression, increased follistatin expression, and increased activity of the PKA RIIα subunit, p70S6K, and CREB1.[6](https://journals.biologists.com/jcs/article/127/21/4589/54680/Synemin-acts-as-a-regulator-of-signalling) Loss of synemin binding to dystrophin or α-dystrobrevin at the sarcolemma is thought to underlie membrane "wrinkles" in soleus fibers, weaker costameres, and increased susceptibility to injury and necrosis in tibialis anterior muscle.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7090255/)
## Tissue distribution
Synemin is present in all four classes of muscle cells: skeletal, cardiac, and smooth muscle, and myoepithelial cells, which have keratin filaments instead of desmin.[8](https://pubmed.ncbi.nlm.nih.gov/12845519/) Immunoblotting detected a 180-kDa polypeptide in skeletal muscle and 180- and 200-kDa polypeptides in cardiac and smooth muscle.[8](https://pubmed.ncbi.nlm.nih.gov/12845519/) Synemin is also found in optic nerve astrocytes and in Schwann cells that do not form myelin, where it coexists with glial fibrillary acidic protein (GFAP) and vimentin; the protein has additionally been detected in the nervous system, endothelial cells, retinal cells, and hepatic stellate cells.[8](https://pubmed.ncbi.nlm.nih.gov/12845519/) • [6](https://journals.biologists.com/jcs/article/127/21/4589/54680/Synemin-acts-as-a-regulator-of-signalling) Expression is regulated, sometimes isoform-specifically, during nervous system development, in brain and breast cancer cells, and after brain and liver injury; loss of synemin expression is associated with aggressive forms of breast cancer.[15](https://pubmed.ncbi.nlm.nih.gov/26795483/) • [6](https://journals.biologists.com/jcs/article/127/21/4589/54680/Synemin-acts-as-a-regulator-of-signalling)
## Synemin in disease
Synemin mutations have been linked to heart disease: clinical reports describe multiple cases of dilated cardiomyopathy caused by SYNM mutations, and a single case of the rare ulnar-mammary-like syndrome with left ventricular tachycardia due to a SYNM mutation.[9](https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00159/full) In desmin-related myopathies, synemin associates with cytoplasmic desmin aggregates in skeletal muscle, although in desmin mutations within the conserved helix 2B motif (E401K, R406W, E413K) synemin is excluded from the aggregates.[7](https://journals.physiology.org/doi/full/10.1152/ajpcell.00485.2019) Synemin is also upregulated in pathological conditions such as neurotrauma and [Alexander disease](https://www.edgepedia.org/alexander-disease), a neurodegenerative disorder.[6](https://journals.biologists.com/jcs/article/127/21/4589/54680/Synemin-acts-as-a-regulator-of-signalling) Whether protein aggregates formed by GFAP and synemin contribute to disease pathology remains unknown.[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC7090255/)
## References
1. [Russell MA (2020). Synemin Redefined: Multiple Binding Partners Results in Multifunctionality. Frontiers in Cell and Developmental Biology 8:159.](https://pmc.ncbi.nlm.nih.gov/articles/PMC7090255/)
2. [SYNM - Synemin - Homo sapiens, UniProtKB O15061](https://www.uniprot.org/uniprotkb/O15061/entry)
3. [Granger BL, Lazarides E (1980). Synemin: a new high molecular weight protein associated with desmin and vimentin filaments in muscle. Cell 22(3):727-738.](https://pubmed.ncbi.nlm.nih.gov/7006832/)
4. [Skeletal and Cardiac Muscle Disorders Caused by Mutations in Genes Encoding Intermediate Filament Proteins (PMC8073371)](https://pmc.ncbi.nlm.nih.gov/articles/PMC8073371/)
5. [The cytoskeleton meets the skeleton. Focus on "Deficiency of the intermediate filament synemin reduces bone mass in vivo". Am J Physiol Cell Physiol.](https://journals.physiology.org/doi/full/10.1152/ajpcell.00303.2016)
6. [Li Z et al. (2014). Synemin acts as a regulator of signalling molecules during skeletal muscle hypertrophy. Journal of Cell Science 127(21):4589-4601.](https://journals.biologists.com/jcs/article/127/21/4589/54680/Synemin-acts-as-a-regulator-of-signalling)
7. [Synemin-related skeletal and cardiac myopathies: an overview of pathogenic variants. Am J Physiol Cell Physiol.](https://journals.physiology.org/doi/full/10.1152/ajpcell.00485.2019)
8. [Characterization of mammalian synemin, an intermediate filament protein present in all four classes of muscle cells and some neuroglial cells (PMID 12845519)](https://pubmed.ncbi.nlm.nih.gov/12845519/)
9. [Synemin Redefined: Multiple Binding Partners Results in Multifunctionality, Frontiers full text](https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00159/full)
10. [Synemin - Gallus gallus (Chicken), UniProtKB Q90662](https://www.uniprot.org/uniprotkb/Q90662/entry)
11. [Titeux M et al. (2001). Human synemin gene generates splice variants encoding two distinct intermediate filament proteins. European Journal of Biochemistry.](https://febs.onlinelibrary.wiley.com/doi/10.1046/j.0014-2956.2001.02594.x)
12. [SYNM synemin [Homo sapiens (human)] - Gene - NCBI, Gene ID 23336](https://www.ncbi.nlm.nih.gov/gene/23336/)
13. [Intermediate filaments in smooth muscle (PMC2398705)](https://pmc.ncbi.nlm.nih.gov/articles/PMC2398705/)
14. [Bellin RM et al. (2001). Synemin may function to directly link muscle cell intermediate filaments to both myofibrillar Z-lines and costameres. J Biol Chem (PMID 11418616)](https://pubmed.ncbi.nlm.nih.gov/11418616/)
15. [Synemin: Molecular Features and the Use of Proximity Ligation Assay to Study Its Interactions (PMID 26795483)](https://pubmed.ncbi.nlm.nih.gov/26795483/)
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*Topic: Encyclopedia › Life and health › Biological foundations › Genetics and genomic reference › Human gene and locus records › Cytoskeleton and motor protein genes*
*Initially written Oct 21, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license