[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. DOI=10.1016/0378-1119(89)90227-8; PubMed=2673923 [NCBI, ExPASy, EBI, Israel, Japan] Li Z., Lilienbaum A., Butler-Browne G., Paulin D.; "Human desmin-coding gene: complete nucleotide sequence, characterization and regulation of expression during myogenesis and development."; Gene 78:243-254(1989).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. PubMed=2007603 [NCBI, ExPASy, EBI, Israel, Japan] Li Z., Paulin D.; "High level desmin expression depends on a muscle-specific enhancer."; J. Biol. Chem. 266:6562-6570(1991).
[3]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Muscle; DOI=10.1007/s004390050233; PubMed=8792816 [NCBI, ExPASy, EBI, Israel, Japan] Vicart P., Dupret J.-M., Hazan J., Li Z., Gyapay G., Krishnamoorthy R., Weissenbach J., Fardeau M., Paulin D.; "Human desmin gene: cDNA sequence, regional localization and exclusion of the locus in a familial desmin-related myopathy."; Hum. Genet. 98:422-429(1996).
[4]	NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS CSM PRO-337; PRO-360 AND ILE-393. DOI=10.1038/1300; PubMed=9697706 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Missense mutations in desmin associated with familial cardiac and skeletal myopathy."; Nat. Genet. 19:402-403(1998).
[5]	NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT CMD1I MET-451. PubMed=10430757 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Desmin mutation responsible for idiopathic dilated cardiomyopathy."; Circulation 100:461-464(1999).
[6]	NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT CSM PRO-389. DOI=10.1002/humu.1210; PubMed=11668632 [NCBI, ExPASy, EBI, Israel, Japan] Goudeau B., Dagvadorj A., Rodrigues-Lima F., Nedellec P., Casteras-Simon M., Perret E., Langlois S., Goldfarb L., Vicart P.; "Structural and functional analysis of a new desmin variant causing desmin-related myopathy."; Hum. Mutat. 18:388-396(2001).
[7]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CSM VAL-213; 359-GLU--SER-361 DEL; ASP-342; PRO-357; ASN-366 DEL AND PRO-370. DOI=10.1007/s00439-003-1057-7; PubMed=14648196 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Small deletions disturb desmin architecture leading to breakdown of muscle cells and development of skeletal or cardioskeletal myopathy."; Hum. Genet. 114:306-313(2004).
[8]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. TISSUE=Muscle; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[9]	NUCLEOTIDE SEQUENCE [MRNA] OF 337-353, VARIANT CSM PRO-345, AND CHARACTERIZATION OF VARIANT CSM PRO-345. TISSUE=Skeletal muscle; DOI=10.1093/hmg/8.12.2191; PubMed=10545598 [NCBI, ExPASy, EBI, Israel, Japan] Sjoeberg G., Saavedra-Matiz C.A., Rosen D.R., Wijsman E.M., Borg K., Horowitz S.H., Sejersen T.; "A missense mutation in the desmin rod domain is associated with autosomal dominant distal myopathy, and exerts a dominant negative effect on filament formation."; Hum. Mol. Genet. 8:2191-2198(1999).
[10]	REVIEW ON VARIANTS CSM. DOI=10.1093/brain/awh033; PubMed=14724127 [NCBI, ExPASy, EBI, Israel, Japan] Goldfarb L.G., Vicart P., Goebel H.H., Dalakas M.C.; "Desmin myopathy."; Brain 127:723-734(2004).
[11]	REVIEW ON VARIANTS CSM. DOI=10.1002/path.1639; PubMed=15495235 [NCBI, ExPASy, EBI, Israel, Japan] Paulin D., Huet A., Khanamyrian L., Xue Z.; "Desminopathies in muscle disease."; J. Pathol. 204:418-427(2004).
[12]	VARIANT CSM 173-ARG--GLU-179 DEL. DOI=10.1073/pnas.95.19.11312; PubMed=9736733 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "A dysfunctional desmin mutation in a patient with severe generalized myopathy."; Proc. Natl. Acad. Sci. U.S.A. 95:11312-11317(1998).
[13]	VARIANT CSM TRP-406. DOI=10.1034/j.1399-0004.2000.570604.x; PubMed=10905661 [NCBI, ExPASy, EBI, Israel, Japan] Park K.-Y., Dalakas M.C., Semino-Mora C., Lee H.-S., Litvak S., Takeda K., Ferrans V.J., Goldfarb L.G.; "Sporadic cardiac and skeletal myopathy caused by a de novo desmin mutation."; Clin. Genet. 57:423-429(2000).
[14]	VARIANT CSM PRO-385. PubMed=11061256 [NCBI, ExPASy, EBI, Israel, Japan] Sugawara M., Kato K., Komatsu M., Wada C., Kawamura K., Shindo P.S., Yoshioka P.N., Tanaka K., Watanabe S., Toyoshima I.; "A novel de novo mutation in the desmin gene causes desmin myopathy with toxic aggregates."; Neurology 55:986-990(2000).
[15]	VARIANTS CSM PRO-337; ASP-342; PRO-360; ILE-393; TRP-406 AND MET-451, AND CHARACTERIZATION OF VARIANTS CSM PRO-337; ASP-342; PRO-360; ILE-393; TRP-406 AND MET-451. DOI=10.1056/NEJM200003163421104; PubMed=10717012 [NCBI, ExPASy, EBI, Israel, Japan] Dalakas M.C., Park K.-Y., Semino-Mora C., Lee H.S., Sivakumar K., Goldfarb L.G.; "Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene."; N. Engl. J. Med. 342:770-780(2000).
[16]	VARIANTS CSM PRO-357 AND PRO-370, AND CHARACTERIZATION OF VARIANTS CSM PRO-357 AND PRO-370. DOI=10.1002/mus.10370; PubMed=12766977 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Respiratory insufficiency in desminopathy patients caused by introduction of proline residues in desmin C-terminal alpha-helical segment."; Muscle Nerve 27:669-675(2003).
[17]	VARIANTS CSM ILE-2; TYR-46; PHE-46 AND THR-449, AND CHARACTERIZATION OF VARIANTS CSM ILE-2; TYR-46; PHE-46 AND THR-449. DOI=10.1093/brain/awh052; PubMed=14711882 [NCBI, ExPASy, EBI, Israel, Japan] Selcen D., Ohno K., Engel A.G.; "Myofibrillar myopathy: clinical, morphological and genetic studies in 63 patients."; Brain 127:439-451(2004).
[18]	VARIANT CSM PRO-350, AND CHARACTERIZATION OF VARIANT CSM PRO-350. DOI=10.1093/hmg/ddi136; PubMed=15800015 [NCBI, ExPASy, EBI, Israel, Japan] Baer H., Fischer D., Goudeau B., Kley R.A., Clemen C.S., Vicart P., Herrmann H., Vorgerd M., Schroeder R.; "Pathogenic effects of a novel heterozygous R350P desmin mutation on the assembly of desmin intermediate filaments in vivo and in vitro."; Hum. Mol. Genet. 14:1251-1260(2005).
[19]	VARIANT CSM PRO-355. DOI=10.1016/j.nmd.2005.05.006; PubMed=16009553 [NCBI, ExPASy, EBI, Israel, Japan] Fidzianska A., Kotowicz J., Sadowska M., Goudeau B., Walczak E., Vicart P., Hausmanowa-Petrusewicz I.; "A novel desmin R355P mutation causes cardiac and skeletal myopathy."; Neuromuscul. Disord. 15:525-531(2005).
[20]	VARIANT KAESER SYNDROME PRO-350. DOI=10.1093/brain/awm039; PubMed=17439987 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult-onset, dominant myopathies are associated with the desmin mutation R350P."; Brain 130:1485-1496(2007).
[21]	VARIANTS CSM ILE-442; TRP-454 AND ILE-460, AND CHARACTERIZATION OF VARIANTS CSM ILE-442; MET-451; TRP-454 AND ILE-460. DOI=10.1002/humu.20459; PubMed=17221859 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Conspicuous involvement of desmin tail mutations in diverse cardiac and skeletal myopathies."; Hum. Mutat. 28:374-386(2007).

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: Homopolymer.
SUBCELLULAR LOCATION: Cytoplasm.
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).
DISEASE: 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.
DISEASE: 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.
SIMILARITY: Belongs to the intermediate filament family.
WEB RESOURCE: Name=Human Intermediate Filament Mutation Database; URL="http://www.interfil.org";.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=DES";.
WEB RESOURCE: Name=Wikipedia; Note=Desmin entry; URL="http://en.wikipedia.org/wiki/Desmin";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M63391; AAA99221.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U59167; AAC50680.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF137053; AAF15400.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF486807; AAL93205.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF487828; AAL99078.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF521879; AAN15036.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF527578; AAN37810.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY083345; AAL99215.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY114212; AAM47026.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY125465; AAM95238.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC032116; AAH32116.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AJ132926; CAB62389.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI00465084; -.

JE0063; DMHU.

NP_001918.3; -.

3D structure databases

HSSP

P08670; 1GK7. [HSSP ENTRY / PDB]

SMR

P17661; 333-411.

ModBase

P17661.

Protein-protein interaction databases

IntAct

P17661; 1.

PTM databases

PhosphoSite

P17661; -.

Enzyme and pathway databases

Pathway_Interaction_DB

aurora_b_pathway; Aurora B signaling.

2D gel databases

SWISS-2DPAGE

P17661; -.

HSC-2DPAGE

P17661; -.

REPRODUCTION-2DPAGE

IPI00465084; -.
P17661; -.

Organism-specific databases

GC02P219991; -.

HIX0002862; -.

HGNC:2770; DES.

DES.

CAB000034; -.
HPA018803; -.

MIM

125660; gene. [NCBI / EBI]
181400; phenotype. [NCBI / EBI]
601419; phenotype. [NCBI / EBI]
604765; phenotype. [NCBI / EBI]

Orphanet

154; Cardiomyopathy, familial dilated.
593; Myofibrillary myopathy.

PharmGKB

PA27253; -.

Gene expression databases

ArrayExpress

P17661; -.

Bgee

P17661; -.

GermOnline

ENSG00000175084; Homo sapiens.

Ontologies

GO:0030018;	Cellular component: Z disc (inferred from direct assay from MGI).
GO:0005515;	Molecular function: protein binding (inferred from physical interaction from UniProtKB).
GO:0005200;	Molecular function: structural constituent of cytoskeleton (traceable author statement from ProtInc).
GO:0007010;	Biological process: cytoskeleton organization (traceable author statement from ProtInc).
GO:0006936;	Biological process: muscle contraction (traceable author statement from ProtInc).
GO:0008016;	Biological process: regulation of heart contraction (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR016044; F.
IPR001664; IF.
IPR006821; Intermed_filament_DNA_bd.
IPR018039; Intermediate_filament_CS.
Graphical view of domain structure.

PANTHER

PTHR23239; IF; 1.

Pfam

PF00038; Filament; 1.
PF04732; Filament_head; 1.
Pfam graphical view of domain structure.

PROSITE

PS00226; IF; 1.

Proteomic databases

PRIDE

P17661; -.

Genome annotation databases

Ensembl

ENSG00000175084; Homo sapiens. [Contig view]

GeneID

1674; -.

KEGG

hsa:1674; -.

Phylogenomic databases

HOVERGEN

P17661; -.

OMA

P17661; RAPSSYG.

Other

6888; -.

DES; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Cardiomyopathy; Coiled coil; Cytoplasm; Desmin-related myopathy; Disease mutation; Intermediate filament; Muscle protein.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`INIT_MET`	`1 1`		`Removed.`
`CHAIN`	`2 470`	`469`	`Desmin.`	`PRO_0000063771`
`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.`
`VARIANT`	`2 2`	`1`	`S -> I (in CSM; entirely similar expression patterns as the wild-type).`	`VAR_042448`
`VARIANT`	`46 46`	`1`	`S -> F (in CSM; entirely similar expression patterns as the wild-type).`	`VAR_042449`
`VARIANT`	`46 46`	`1`	`S -> Y (in CSM; entirely similar expression patterns as the wild-type).`	`VAR_042450`
`VARIANT`	`173 179`	`7`	`Missing (in CSM; severe form).`	`VAR_009188`
`VARIANT`	`213 213`	`1`	`A -> V (in CSM).`	`VAR_042451`
`VARIANT`	`245 245`	`1`	`E -> D (in CSM).`	`VAR_042452`
`VARIANT`	`337 337`	`1`	`A -> P (in CSM; mild adult-onset; unable to form a filamentous network).`	`VAR_007900`
`VARIANT`	`342 342`	`1`	`N -> D (in CSM; unable to form a filamentous network).`	`VAR_042453`
`VARIANT`	`345 345`	`1`	`L -> P (in CSM; distal onset; incapable of forming filamentous networks).`	`VAR_009189`
`VARIANT`	`350 350`	`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).`	`VAR_042454`
`VARIANT`	`355 355`	`1`	`R -> P (in CSM).`	`VAR_042455`
`VARIANT`	`357 357`	`1`	`A -> P (in CSM; unable to polymerize and form an intracellular filamentous network).`	`VAR_042456`
`VARIANT`	`359 361`	`3`	`Missing (in CSM).`	`VAR_018769`
`VARIANT`	`360 360`	`1`	`A -> P (in CSM; heterozygous with Ile-391 gives a severe childhood-onset; unable to form a filamentous network).`	`VAR_007901`
`VARIANT`	`366 366`	`1`	`Missing (in CSM).`	`VAR_018770`
`VARIANT`	`370 370`	`1`	`L -> P (in CSM; unable to polymerize and form an intracellular filamentous network).`	`VAR_042457`
`VARIANT`	`385 385`	`1`	`L -> P (in CSM).`	`VAR_018771`
`VARIANT`	`389 389`	`1`	`Q -> P (in CSM).`	`VAR_018772`
`VARIANT`	`393 393`	`1`	`N -> I (in CSM; heterozygous with Pro-358 gives a severe childhood-onset; unable to form a filamentous network).`	`VAR_007902`
`VARIANT`	`406 406`	`1`	`R -> W (in CSM; unable to form a filamentous network).`	`VAR_042458`
`VARIANT`	`442 442`	`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).`	`VAR_042459`
`VARIANT`	`449 449`	`1`	`K -> M (in CSM).`	`VAR_042460`
`VARIANT`	`449 449`	`1`	`K -> T (in CSM; entirely similar expression patterns as the wild-type).`	`VAR_042461`
`VARIANT`	`451 451`	`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).`	`VAR_018773`
`VARIANT`	`454 454`	`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).`	`VAR_042462`
`VARIANT`	`460 460`	`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).`	`VAR_042463`
`CONFLICT`	`23 25`		`GFP -> VFS (in Ref. 1 and 2).`
`CONFLICT`	`39 39`		`G -> P (in Ref. 1 and 2).`
`CONFLICT`	`119 123`		`FANYI -> SPIYM (in Ref. 1 and 2).`
`CONFLICT`	`135 135`		`Missing (in Ref. 1, 2 and 3).`

Sequence information

Length: 470 AA [This is the length of the unprocessed precursor]

Molecular weight: 53536 Da [This is the MW of the unprocessed precursor]

CRC64: 1B5D9EA93C3BB319 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MSQAYSSSQR VSSYRRTFGG APGFPLGSPL SSPVFPRAGF GSKGSSSSVT SRVYQVSRTS 

        70         80         90        100        110        120 
GGAGGLGSLR ASRLGTTRTP SSYGAGELLD FSLADAVNQE FLTTRTNEKV ELQELNDRFA 

       130        140        150        160        170        180 
NYIEKVRFLE QQNAALAAEV NRLKGREPTR VAELYEEELR ELRRQVEVLT NQRARVDVER 

       190        200        210        220        230        240 
DNLLDDLQRL KAKLQEEIQL KEEAENNLAA FRADVDAATL ARIDLERRIE SLNEEIAFLK 

       250        260        270        280        290        300 
KVHEEEIREL QAQLQEQQVQ VEMDMSKPDL TAALRDIRAQ YETIAAKNIS EAEEWYKSKV 

       310        320        330        340        350        360 
SDLTQAANKN NDALRQAKQE MMEYRHQIQS YTCEIDALKG TNDSLMRQMR ELEDRFASEA 

       370        380        390        400        410        420 
SGYQDNIARL EEEIRHLKDE MARHLREYQD LLNVKMALDV EIATYRKLLE GEESRINLPI 

       430        440        450        460        470 
QTYSALNFRE TSPEQRGSEV HTKKTVMIKT IETRDGEVVS EATQQQHEVL

P17661 in FASTA format

View entry in raw text format (no links)
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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools