Reviewed,
UniProtKB/Swiss-Prot P17661 (DESM_HUMAN)
Last modified
November 3, 2009.
Version 106.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Desmin | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) [Complete proteome] | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 470 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Desmin are class-III intermediate filaments found in muscle cells. In adult striated muscle they form a fibrous network connecting myofibrils to each other and to the plasma membrane from the periphery of the Z-line structures. |
| Subunit structure | Homopolymer. |
| Subcellular location | |
| Involvement in disease | Defects in DES are the cause of desmin-related cardio-skeletal myopathy (CSM) [MIM:601419]; also known as desmin-related myopathy (DRM). CSM is characterized by skeletal muscle weakness associated with cardiac conduction blocks, arrhythmias, restrictive heart failure, and by intracytoplasmic accumulation of desmin-reactive deposits in cardiac and skeletal muscle cells. A desmin-related myopathy can have a distal onset, it is then known as hereditary distal myopathy (HDM). Ref.4 Ref.6 Ref.7 Ref.9 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21 Defects in DES are the cause of cardiomyopathy dilated type 1I (CMD1I) [MIM:604765]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. Ref.5 Defects in DES are the cause of neurogenic scapuloperoneal syndrome Kaeser type (Kaeser syndrome) [MIM:181400]. Kaeser syndrome is an autosomal dominant disorder with a peculiar scapuloperoneal distribution of weakness and atrophy. A large clinical variability is observed ranging from scapuloperoneal, limb grindle and distal phenotypes with variable cardiac or respiratory involvement. Facial weakness, dysphagia and gynaecomastia are frequent additional symptoms. Affected men seemingly bear a higher risk of sudden, cardiac death as compared to affected women. Histological and immunohistochemical examination of muscle biopsy specimens reveal a wide spectrum of findings ranging from near normal or unspecific pathology to typical, myofibrillar changes with accumulation of desmin. |
| Sequence similarities | Belongs to the intermediate filament family. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Cytoplasm Intermediate filament |
| Disease | Cardiomyopathy Desmin-related myopathy Disease mutation |
| Domain | Coiled coil |
| Molecular function | Muscle protein |
| Technical term | Complete proteome |
| Gene Ontology (GO) | |
| Biological process | cytoskeleton organization Ref.12 Traceable author statement. Source: ProtInc muscle contraction Ref.4Traceable author statement. Source: ProtInc regulation of heart contraction Ref.4Traceable author statement. Source: ProtInc |
| Cellular component | Z disc Inferred from direct assay. Source: MGI |
| Molecular function | protein binding Inferred from physical interaction. Source: UniProtKB structural constituent of cytoskeleton Ref.12Traceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Initiator methionine | 1 | 1 | Removed | ||||||
| Chain | 2 – 470 | 469 | Desmin | PRO_0000063771 | |||||
Regions | |||||||||
| Region | 2 – 108 | 107 | Head | ||||||
| Region | 109 – 412 | 304 | Rod | ||||||
| Region | 109 – 141 | 33 | Coil 1A | ||||||
| Region | 142 – 151 | 10 | Linker 1 | ||||||
| Region | 152 – 252 | 101 | Coil 1B | ||||||
| Region | 253 – 268 | 16 | Linker 12 | ||||||
| Region | 269 – 287 | 19 | Coil 2A | ||||||
| Region | 288 – 295 | 8 | Linker 2 | ||||||
| Region | 296 – 412 | 117 | Coil 2B | ||||||
| Region | 413 – 470 | 58 | Tail | ||||||
Natural variations | |||||||||
| Natural variant | 2 | 1 | S → I in CSM; entirely similar expression patterns as the wild-type. Ref.17 | VAR_042448 | |||||
| Natural variant | 46 | 1 | S → F in CSM; entirely similar expression patterns as the wild-type. Ref.17 | VAR_042449 | |||||
| Natural variant | 46 | 1 | S → Y in CSM; entirely similar expression patterns as the wild-type. Ref.17 | VAR_042450 | |||||
| Natural variant | 173 – 179 | 7 | Missing in CSM; severe form. | VAR_009188 | |||||
| Natural variant | 213 | 1 | A → V in CSM. Ref.7 | VAR_042451 | |||||
| Natural variant | 245 | 1 | E → D in CSM. | VAR_042452 | |||||
| Natural variant | 337 | 1 | A → P in CSM; mild adult-onset; unable to form a filamentous network. Ref.4 Ref.15 | VAR_007900 | |||||
| Natural variant | 342 | 1 | N → D in CSM; unable to form a filamentous network. Ref.7 Ref.15 | VAR_042453 | |||||
| Natural variant | 345 | 1 | L → P in CSM; distal onset; incapable of forming filamentous networks. Ref.9 | VAR_009189 | |||||
| Natural variant | 350 | 1 | R → P in Kaeser syndrome and CSM; incapable of de novo formation of a desmin intermediate filaments network; exerts a dominant negative effect on the ordered lateral arrangement of desmin subunits. Ref.18 Ref.20 | VAR_042454 | |||||
| Natural variant | 355 | 1 | R → P in CSM. Ref.19 | VAR_042455 | |||||
| Natural variant | 357 | 1 | A → P in CSM; unable to polymerize and form an intracellular filamentous network. Ref.7 Ref.16 | VAR_042456 | |||||
| Natural variant | 359 – 361 | 3 | Missing in CSM. | VAR_018769 | |||||
| Natural variant | 360 | 1 | A → P in CSM; heterozygous with Ile-391 gives a severe childhood-onset; unable to form a filamentous network. Ref.4 Ref.15 | VAR_007901 | |||||
| Natural variant | 366 | 1 | Missing in CSM. | VAR_018770 | |||||
| Natural variant | 370 | 1 | L → P in CSM; unable to polymerize and form an intracellular filamentous network. Ref.7 Ref.16 | VAR_042457 | |||||
| Natural variant | 385 | 1 | L → P in CSM. Ref.14 | VAR_018771 | |||||
| Natural variant | 389 | 1 | Q → P in CSM. Ref.6 | VAR_018772 | |||||
| Natural variant | 393 | 1 | N → I in CSM; heterozygous with Pro-358 gives a severe childhood-onset; unable to form a filamentous network. Ref.4 Ref.15 | VAR_007902 | |||||
| Natural variant | 406 | 1 | R → W in CSM; unable to form a filamentous network. Ref.13 Ref.15 | VAR_042458 | |||||
| Natural variant | 442 | 1 | T → I in CSM; reveals a severe disturbance of filament-formation competence and filament-filament interactions, indicating an inherent incompaibility of mutant and wild-type protein to form mixed filaments. Ref.21 | VAR_042459 | |||||
| Natural variant | 449 | 1 | K → M in CSM. | VAR_042460 | |||||
| Natural variant | 449 | 1 | K → T in CSM; entirely similar expression patterns as the wild-type. Ref.17 | VAR_042461 | |||||
| Natural variant | 451 | 1 | I → M in CMD1I; reveals a severe disturbance of filament-formation competence and filament-filament interactions, indicating an inherent incompaibility of mutant and wild-type protein to form mixed filaments. Ref.15 Ref.21 Ref.5 | VAR_018773 | |||||
| Natural variant | 454 | 1 | R → W in CSM; reveals a severe disturbance of filament-formation competence and filament-filament interactions, indicating an inherent incompaibility of mutant and wild-type protein to form mixed filaments. Ref.21 | VAR_042462 | |||||
| Natural variant | 460 | 1 | S → I in CSM; reveals a severe disturbance of filament-formation competence and filament-filament interactions, indicating an inherent incompaibility of mutant and wild-type protein to form mixed filaments. Ref.21 | VAR_042463 | |||||
Experimental info | |||||||||
| Sequence conflict | 23 – 25 | 3 | GFP → VFS Ref.1 | ||||||
| Sequence conflict | 23 – 25 | 3 | GFP → VFS Ref.2 | ||||||
| Sequence conflict | 39 | 1 | G → P Ref.1 | ||||||
| Sequence conflict | 39 | 1 | G → P Ref.2 | ||||||
| Sequence conflict | 119 – 123 | 5 | FANYI → SPIYM Ref.1 | ||||||
| Sequence conflict | 119 – 123 | 5 | FANYI → SPIYM Ref.2 | ||||||
| Sequence conflict | 135 | 1 | Missing Ref.1 | ||||||
| Sequence conflict | 135 | 1 | Missing Ref.2 | ||||||
| Sequence conflict | 135 | 1 | Missing Ref.3 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Human desmin-coding gene: complete nucleotide sequence, characterization and regulation of expression during myogenesis and development." Li Z., Lilienbaum A., Butler-Browne G., Paulin D. Gene 78:243-254(1989) [PubMed: 2673923] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [2] | "High level desmin expression depends on a muscle-specific enhancer." Li Z., Paulin D. J. Biol. Chem. 266:6562-6570(1991) [PubMed: 2007603] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [3] | "Human desmin gene: cDNA sequence, regional localization and exclusion of the locus in a familial desmin-related myopathy." Vicart P., Dupret J.-M., Hazan J., Li Z., Gyapay G., Krishnamoorthy R., Weissenbach J., Fardeau M., Paulin D. Hum. Genet. 98:422-429(1996) [PubMed: 8792816] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Muscle. |
| [4] | "Missense mutations in desmin associated with familial cardiac and skeletal myopathy." Goldfarb L.G., Park K.-Y., Cervenakova L., Gorokhova S., Lee H.-S., Vasconcelos O., Nagle J.W., Semino-Mora C., Sivakumar K., Dalakas M.C. Nat. Genet. 19:402-403(1998) [PubMed: 9697706] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS CSM PRO-337; PRO-360 AND ILE-393. |
| [5] | "Desmin mutation responsible for idiopathic dilated cardiomyopathy." Li D., Tapscoft T., Gonzalez O., Burch P.E., Quinones M.A., Zoghbi W.A., Hill R., Bachinski L.L., Mann D.L., Roberts R. Circulation 100:461-464(1999) [PubMed: 10430757] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CMD1I MET-451. |
| [6] | "Structural and functional analysis of a new desmin variant causing desmin-related myopathy." Goudeau B., Dagvadorj A., Rodrigues-Lima F., Nedellec P., Casteras-Simon M., Perret E., Langlois S., Goldfarb L., Vicart P. Hum. Mutat. 18:388-396(2001) [PubMed: 11668632] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT CSM PRO-389. |
| [7] | "Small deletions disturb desmin architecture leading to breakdown of muscle cells and development of skeletal or cardioskeletal myopathy." Kaminska A., Strelkov S.V., Goudeau B., Olive M., Dagvadorj A., Fidzianska A., Simon-Casteras M., Shatunov A., Dalakas M.C., Ferrer I., Kwiecinski H., Vicart P., Goldfarb L.G. Hum. Genet. 114:306-313(2004) [PubMed: 14648196] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CSM VAL-213; 359-GLU--SER-361 DEL; ASP-342; PRO-357; ASN-366 DEL AND PRO-370. |
| [8] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Muscle. |
| [9] | "A missense mutation in the desmin rod domain is associated with autosomal dominant distal myopathy, and exerts a dominant negative effect on filament formation." Sjoeberg G., Saavedra-Matiz C.A., Rosen D.R., Wijsman E.M., Borg K., Horowitz S.H., Sejersen T. Hum. Mol. Genet. 8:2191-2198(1999) [PubMed: 10545598] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 337-353, VARIANT CSM PRO-345, CHARACTERIZATION OF VARIANT CSM PRO-345. Tissue: Skeletal muscle. |
| [10] | "Desmin myopathy." Goldfarb L.G., Vicart P., Goebel H.H., Dalakas M.C. Brain 127:723-734(2004) [PubMed: 14724127] [Abstract] Cited for: REVIEW ON VARIANTS CSM. |
| [11] | "Desminopathies in muscle disease." Paulin D., Huet A., Khanamyrian L., Xue Z. J. Pathol. 204:418-427(2004) [PubMed: 15495235] [Abstract] Cited for: REVIEW ON VARIANTS CSM. |
| [12] | "A dysfunctional desmin mutation in a patient with severe generalized myopathy." Munoz-Marmol A.M., Strasser G., Isamat M., Coulombe P.A., Yang Y., Roca X., Vela E., Mate J.L., Coll J., Fernandez-Figueras M.T., Navas-Palacios J.J., Ariza A., Fuchs E. Proc. Natl. Acad. Sci. U.S.A. 95:11312-11317(1998) [PubMed: 9736733] [Abstract] Cited for: VARIANT CSM 173-ARG--GLU-179 DEL. |
| [13] | "Sporadic cardiac and skeletal myopathy caused by a de novo desmin mutation." Park K.-Y., Dalakas M.C., Semino-Mora C., Lee H.-S., Litvak S., Takeda K., Ferrans V.J., Goldfarb L.G. Clin. Genet. 57:423-429(2000) [PubMed: 10905661] [Abstract] Cited for: VARIANT CSM TRP-406. |
| [14] | "A novel de novo mutation in the desmin gene causes desmin myopathy with toxic aggregates." Sugawara M., Kato K., Komatsu M., Wada C., Kawamura K., Shindo P.S., Yoshioka P.N., Tanaka K., Watanabe S., Toyoshima I. Neurology 55:986-990(2000) [PubMed: 11061256] [Abstract] Cited for: VARIANT CSM PRO-385. |
| [15] | "Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene." Dalakas M.C., Park K.-Y., Semino-Mora C., Lee H.S., Sivakumar K., Goldfarb L.G. N. Engl. J. Med. 342:770-780(2000) [PubMed: 10717012] [Abstract] Cited for: VARIANTS CSM PRO-337; ASP-342; PRO-360; ILE-393; TRP-406 AND MET-451, CHARACTERIZATION OF VARIANTS CSM PRO-337; ASP-342; PRO-360; ILE-393; TRP-406 AND MET-451. |
| [16] | "Respiratory insufficiency in desminopathy patients caused by introduction of proline residues in desmin C-terminal alpha-helical segment." Dagvadorj A., Goudeau B., Hilton-Jones D., Blancato J.K., Shatunov A., Simon-Casteras M., Squier W., Nagle J.W., Goldfarb L.G., Vicart P. Muscle Nerve 27:669-675(2003) [PubMed: 12766977] [Abstract] Cited for: VARIANTS CSM PRO-357 AND PRO-370, CHARACTERIZATION OF VARIANTS CSM PRO-357 AND PRO-370. |
| [17] | "Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients." Selcen D., Ohno K., Engel A.G. Brain 127:439-451(2004) [PubMed: 14711882] [Abstract] Cited for: VARIANTS CSM ILE-2; TYR-46; PHE-46 AND THR-449, CHARACTERIZATION OF VARIANTS CSM ILE-2; TYR-46; PHE-46 AND THR-449. |
| [18] | "Pathogenic effects of a novel heterozygous R350P desmin mutation on the assembly of desmin intermediate filaments in vivo and in vitro." Baer H., Fischer D., Goudeau B., Kley R.A., Clemen C.S., Vicart P., Herrmann H., Vorgerd M., Schroeder R. Hum. Mol. Genet. 14:1251-1260(2005) [PubMed: 15800015] [Abstract] Cited for: VARIANT CSM PRO-350, CHARACTERIZATION OF VARIANT CSM PRO-350. |
| [19] | "A novel desmin R355P mutation causes cardiac and skeletal myopathy." Fidzianska A., Kotowicz J., Sadowska M., Goudeau B., Walczak E., Vicart P., Hausmanowa-Petrusewicz I. Neuromuscul. Disord. 15:525-531(2005) [PubMed: 16009553] [Abstract] Cited for: VARIANT CSM PRO-355. |
| [20] | "Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult-onset, dominant myopathies are associated with the desmin mutation R350P." Walter M.C., Reilich P., Huebner A., Fischer D., Schroeder R., Vorgerd M., Kress W., Born C., Schoser B.G., Krause K.H., Klutzny U., Bulst S., Frey J.R., Lochmueller H. Brain 130:1485-1496(2007) [PubMed: 17439987] [Abstract] Cited for: VARIANT KAESER SYNDROME PRO-350. |
| [21] | "Conspicuous involvement of desmin tail mutations in diverse cardiac and skeletal myopathies." Baer H., Goudeau B., Waelde S., Casteras-Simon M., Muecke N., Shatunov A., Goldberg Y.P., Clarke C., Holton J.L., Eymard B., Katus H.A., Fardeau M., Goldfarb L., Vicart P., Herrmann H. Hum. Mutat. 28:374-386(2007) [PubMed: 17221859] [Abstract] Cited for: VARIANTS CSM ILE-442; TRP-454 AND ILE-460, CHARACTERIZATION OF VARIANTS CSM ILE-442; MET-451; TRP-454 AND ILE-460. |
| + | Additional computationally mapped references. |
Web resources
Cross-references
Sequence databases | |
|---|---|
| M63391 Genomic DNA. Translation: AAA99221.1. U59167 mRNA. Translation: AAC50680.1. AF137053 mRNA. Translation: AAF15400.1. AF486807 mRNA. Translation: AAL93205.1. AF487828 mRNA. Translation: AAL99078.1. AF521879 mRNA. Translation: AAN15036.1. AF527578 mRNA. Translation: AAN37810.1. AY083345 mRNA. Translation: AAL99215.1. AY114212 Genomic DNA. Translation: AAM47026.1. AY125465 mRNA. Translation: AAM95238.1. BC032116 mRNA. Translation: AAH32116.1. AJ132926 mRNA. Translation: CAB62389.1. | |
| IPI | IPI00465084. |
| PIR | DMHU. JE0063. |
| RefSeq | NP_001918.3. |
| UniGene | Hs.594952 |
3D structure databases | |
| HSSP | HSSP built from PDB template 1GK7 based on UniProtKB P08670. |
| SMR | P17661. Positions 333-411. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P17661. 1 interaction. |
| STRING | P17661. |
PTM databases | |
| PhosphoSite | P17661. |
2-D gel databases | |
| SWISS-2DPAGE | P17661. |
| HSC-2DPAGE | P17661. |
| REPRODUCTION-2DPAGE | IPI00465084. P17661. |
Proteomic databases | |
| PRIDE | P17661. |
Genome annotation databases | |
| Ensembl | ENST00000373960; ENSP00000363071; ENSG00000175084; Homo sapiens. [Genome view] |
| GeneID | 1674. |
| KEGG | hsa:1674. |
| UCSC | uc002vll.1. human. |
Organism-specific databases | |
| CTD | 1674. |
| GeneCards | GC02P219991. |
| H-InvDB | HIX0002862. |
| HGNC | HGNC:2770. DES. |
| HPA | CAB000034. HPA018803. |
| MIM | 125660. gene. 181400. phenotype. 601419. phenotype. 604765. phenotype. |
| Orphanet | 154. Cardiomyopathy, familial dilated. 98909. Desminopathy. |
| PharmGKB | PA27253. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOVERGEN | P17661. |
| OMA | RAPSSYG. |
Enzyme and pathway databases | |
| Pathway_Interaction_DB | aurora_b_pathway. Aurora B signaling. |
| Reactome | REACT_17044. Muscle contraction. |
Gene expression databases | |
| ArrayExpress | P17661. |
| Bgee | P17661. |
| Genevestigator | P17661. |
| GermOnline | ENSG00000175084. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR016044. F. IPR001664. IF. IPR006821. Intermed_filament_DNA_bd. IPR018039. Intermediate_filament_CS. [Graphical view] |
| PANTHER | PTHR23239. IF. 1 hit. |
| Pfam | PF00038. Filament. 1 hit. PF04732. Filament_head. 1 hit. [Graphical view] |
| PROSITE | PS00226. IF. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 6888. |
| SOURCE | Search... |
Entry information
| Entry name | DESM_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P17661 Secondary accession number(s): Q15787 Q9UJ80 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 2 Human chromosome 2: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


