UniProtKB - P17661 (DESM_HUMAN)
Protein
Desmin
Gene
DES
Organism
Homo sapiens (Human)
Status
Functioni
Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and forming the myofibrils, linking them not only to the sarcolemmal cytoskeleton, but also to the nucleus and mitochondria, thus providing strength for the muscle fiber during activity (PubMed:25358400). 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 (PubMed:24200904, PubMed:25394388, PubMed:26724190). May act as a sarcomeric microtubule-anchoring protein: specifically associates with detyrosinated tubulin-alpha chains, leading to buckled microtubules and mechanical resistance to contraction. Contributes to the transcriptional regulation of the NKX2-5 gene in cardiac progenitor cells during a short period of cardiomyogenesis and in cardiac side population stem cells in the adult. Plays a role in maintaining an optimal conformation of nebulette (NEB) on heart muscle sarcomeres to bind and recruit cardiac alpha-actin (By similarity).1 PublicationBy similarity3 Publications
GO - Molecular functioni
- cytoskeletal protein binding Source: BHF-UCL
- identical protein binding Source: IntAct
- structural constituent of cytoskeleton Source: ProtInc
GO - Biological processi
- cytoskeleton organization Source: ProtInc
- intermediate filament organization Source: UniProtKB
- muscle contraction Source: ProtInc
- muscle filament sliding Source: Reactome
- regulation of heart contraction Source: ProtInc
Keywordsi
Molecular function | Muscle protein |
Enzyme and pathway databases
PathwayCommonsi | P17661 |
Reactomei | R-HSA-390522, Striated Muscle Contraction |
SIGNORi | P17661 |
Names & Taxonomyi
Protein namesi | Recommended name: Desmin |
Gene namesi | Name:DES |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:2770, DES |
MIMi | 125660, gene |
neXtProti | NX_P17661 |
VEuPathDBi | HostDB:ENSG00000175084.11 |
Subcellular locationi
Plasma membrane
- sarcolemma 1 Publication
Nucleus
- Nucleus By similarity
Other locations
Note: Localizes in the intercalated disks which occur at the Z line of cardiomyocytes (PubMed:24200904, PubMed:26724190). Localizes in the nucleus exclusively in differentiating cardiac progenitor cells and premature cardiomyocytes (By similarity).By similarity2 Publications
Cytoskeleton
- intermediate filament Source: ProtInc
- intermediate filament cytoskeleton Source: HPA
Cytosol
- cytosol Source: Reactome
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- sarcolemma Source: UniProtKB
Other locations
- cardiac myofibril Source: CAFA
- fascia adherens Source: Ensembl
- intercalated disc Source: UniProtKB
- neuromuscular junction Source: Ensembl
- Z disc Source: UniProtKB
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Intermediate filament, Membrane, NucleusPathology & Biotechi
Involvement in diseasei
Myopathy, myofibrillar, 1 (MFM1)28 Publications
The disease is caused by variants affecting the gene represented in this entry. Mutations in the DES gene are associated with a variable clinical phenotype which encompasses isolated myopathies, pure cardiac phenotypes (including dilated cardiomyopathy, restrictive cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy), cardiac conduction disease, and combinations of these disorders. If both cardiologic and neurologic features occur, they can manifest in any order, as cardiologic features can precede, occur simultaneously with, or follow manifestation of generalized neuromuscular disease (PubMed:19879535).1 Publication
Disease descriptionA form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM1 is characterized by skeletal muscle weakness associated with cardiac conduction blocks, arrhythmias, restrictive heart failure, and accumulation of desmin-reactive deposits in cardiac and skeletal muscle cells.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_042448 | 2 | S → I in MFM1. 1 PublicationCorresponds to variant dbSNP:rs58999456EnsemblClinVar. | 1 | |
Natural variantiVAR_067207 | 7 | S → F in MFM1. 1 PublicationCorresponds to variant dbSNP:rs903985237EnsemblClinVar. | 1 | |
Natural variantiVAR_067208 | 13 | S → F in MFM1; some patients manifest a severe cardiac phenotype with right ventricular predominance. 2 PublicationsCorresponds to variant dbSNP:rs62636495EnsemblClinVar. | 1 | |
Natural variantiVAR_079048 | 16 | R → C in MFM1. 1 PublicationCorresponds to variant dbSNP:rs60798368EnsemblClinVar. | 1 | |
Natural variantiVAR_042449 | 46 | S → F in MFM1; exhibits significantly delayed filament assembly kinetics when bound to NEB; enhanced binding affinity towards NEB. 2 PublicationsCorresponds to variant dbSNP:rs60794845EnsemblClinVar. | 1 | |
Natural variantiVAR_042450 | 46 | S → Y in MFM1. 1 PublicationCorresponds to variant dbSNP:rs60794845EnsemblClinVar. | 1 | |
Natural variantiVAR_069191 | 116 | N → S in MFM1; the clinical picture is dominated by arrhythmogenic right ventricular cardiomyopathy and terminal heart failure; results in impaired filaments formation. 1 PublicationCorresponds to variant dbSNP:rs267607499EnsemblClinVar. | 1 | |
Natural variantiVAR_009188 | 173 – 179 | Missing in MFM1; severe form. 1 Publication | 7 | |
Natural variantiVAR_070101 | 240 | Missing in MFM1; the mutant cannot form de novo desmin intermediate filaments causing disruption of the endogenous intermediate filament network and formation of pathologic aggregates. 1 Publication | 1 | |
Natural variantiVAR_042452 | 245 | E → D in MFM1; exhibits significantly delayed filament assembly kinetics when bound to NEB and NEBL; enhanced binding affinity towards NEB and NEBL. 1 PublicationCorresponds to variant dbSNP:rs267607486EnsemblClinVar. | 1 | |
Natural variantiVAR_007900 | 337 | A → P in MFM1; mild adult-onset; unable to form a functional filamentous network. 2 PublicationsCorresponds to variant dbSNP:rs59962885EnsemblClinVar. | 1 | |
Natural variantiVAR_067209 | 338 | L → R in MFM1; results in the formation of a filamentous network disrupted by multiple breaks and clumps or large aggregates. 1 PublicationCorresponds to variant dbSNP:rs57496341EnsemblClinVar. | 1 | |
Natural variantiVAR_042453 | 342 | N → D in MFM1; unable to form a filamentous network; abolishes binding to MTM1. 3 PublicationsCorresponds to variant dbSNP:rs267607482EnsemblClinVar. | 1 | |
Natural variantiVAR_009189 | 345 | L → P in MFM1; distal onset; incapable of forming filamentous networks. 1 PublicationCorresponds to variant dbSNP:rs57639980EnsemblClinVar. | 1 | |
Natural variantiVAR_042454 | 350 | R → P in Kaeser syndrome and MFM1; incapable of de novo formation of a desmin intermediate filaments network; exerts a dominant negative effect on the ordered lateral arrangement of desmin subunits; may produce structural changes; forms subsarcolemmal aggregates. 3 PublicationsCorresponds to variant dbSNP:rs57965306EnsemblClinVar. | 1 | |
Natural variantiVAR_042455 | 355 | R → P in MFM1. 1 PublicationCorresponds to variant dbSNP:rs61368398EnsemblClinVar. | 1 | |
Natural variantiVAR_042456 | 357 | A → P in MFM1; unable to polymerize and form an intracellular filamentous network; abolishes binding to MTM1. 3 PublicationsCorresponds to variant dbSNP:rs58898021EnsemblClinVar. | 1 | |
Natural variantiVAR_018769 | 359 – 361 | Missing in MFM1. 1 Publication | 3 | |
Natural variantiVAR_007901 | 360 | A → P in MFM1; heterozygous with I-393 gives a severe childhood-onset; unable to form a functional filamentous network in the presence of I-393; abolishes binding to MTM1. 4 PublicationsCorresponds to variant dbSNP:rs121913000EnsemblClinVar. | 1 | |
Natural variantiVAR_018770 | 366 | Missing in MFM1. 1 Publication | 1 | |
Natural variantiVAR_042457 | 370 | L → P in MFM1; unable to polymerize and form an intracellular filamentous network; does not affect binding to MTM1. 3 PublicationsCorresponds to variant dbSNP:rs59308628EnsemblClinVar. | 1 | |
Natural variantiVAR_018771 | 385 | L → P in MFM1. 1 PublicationCorresponds to variant dbSNP:rs57955682EnsemblClinVar. | 1 | |
Natural variantiVAR_018772 | 389 | Q → P in MFM1. 1 PublicationCorresponds to variant dbSNP:rs121913004EnsemblClinVar. | 1 | |
Natural variantiVAR_007902 | 393 | N → I in MFM1; heterozygous with P-360 gives a severe childhood-onset; filamentous network is not affected however several spots indicate focal disorganization. 3 PublicationsCorresponds to variant dbSNP:rs121913001EnsemblClinVar. | 1 | |
Natural variantiVAR_067210 | 399 | D → Y in MFM1; results in the formation of a filamentous network disrupted by multiple breaks and clumps or large aggregates. 1 PublicationCorresponds to variant dbSNP:rs61130669EnsemblClinVar. | 1 | |
Natural variantiVAR_067211 | 401 | E → K in MFM1; results in the formation of a filamentous network disrupted by multiple breaks and clumps or large aggregates. 1 PublicationCorresponds to variant dbSNP:rs57694264EnsemblClinVar. | 1 | |
Natural variantiVAR_042458 | 406 | R → W in MFM1; unable to form a filamentous network. 3 PublicationsCorresponds to variant dbSNP:rs121913003EnsemblClinVar. | 1 | |
Natural variantiVAR_069074 | 419 | P → S in MFM1; found in a family with myofibrillar myopathy and arrhythmogenic right ventricular cardiomyopathy. 1 PublicationCorresponds to variant dbSNP:rs62635763EnsemblClinVar. | 1 | |
Natural variantiVAR_042459 | 442 | T → I in MFM1; reveals a severe disturbance of filament-formation competence and filament-filament interactions. 1 PublicationCorresponds to variant dbSNP:rs121913005EnsemblClinVar. | 1 | |
Natural variantiVAR_042460 | 449 | K → M in MFM1. | 1 | |
Natural variantiVAR_042461 | 449 | K → T in MFM1. 1 PublicationCorresponds to variant dbSNP:rs267607485EnsemblClinVar. | 1 | |
Natural variantiVAR_018773 | 451 | I → M in CMD1I and MFM1; reveals a severe disturbance of filament-formation competence and filament-filament interactions; reduced interaction with CRYAB. 4 PublicationsCorresponds to variant dbSNP:rs121913002EnsemblClinVar. | 1 | |
Natural variantiVAR_079049 | 453 | T → I in MFM1; exhibits significantly delayed filament assembly kinetics when bound to NEB and NEBL; enhanced binding affinity towards NEB and NEBL. 2 PublicationsCorresponds to variant dbSNP:rs267607488EnsemblClinVar. | 1 | |
Natural variantiVAR_042462 | 454 | R → W in MFM1; reveals a severe disturbance of filament-formation competence and filament-filament interactions; increased interaction with CRYAB. 3 PublicationsCorresponds to variant dbSNP:rs267607490EnsemblClinVar. | 1 | |
Natural variantiVAR_042463 | 460 | S → I in MFM1; reveals a severe disturbance of filament-formation competence and filament-filament interactions. 1 PublicationCorresponds to variant dbSNP:rs267607491EnsemblClinVar. | 1 |
Cardiomyopathy, dilated 1I (CMD1I)3 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_075228 | 120 | A → D in CMD1I; results in impaired filaments formation, does not localize at intercalated disks. 1 Publication | 1 | |
Natural variantiVAR_075229 | 136 | L → P in CMD1I; results in impaired filaments formation, does not localize at intercalated disks. 1 PublicationCorresponds to variant dbSNP:rs397516695EnsemblClinVar. | 1 | |
Natural variantiVAR_075230 | 326 | H → R in CMD1I; unknown pathological significance; does not affect filaments formation. 1 Publication | 1 | |
Natural variantiVAR_018773 | 451 | I → M in CMD1I and MFM1; reveals a severe disturbance of filament-formation competence and filament-filament interactions; reduced interaction with CRYAB. 4 PublicationsCorresponds to variant dbSNP:rs121913002EnsemblClinVar. | 1 |
Neurogenic scapuloperoneal syndrome Kaeser type (Kaeser syndrome)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAutosomal 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_042454 | 350 | R → P in Kaeser syndrome and MFM1; incapable of de novo formation of a desmin intermediate filaments network; exerts a dominant negative effect on the ordered lateral arrangement of desmin subunits; may produce structural changes; forms subsarcolemmal aggregates. 3 PublicationsCorresponds to variant dbSNP:rs57965306EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 120 | A → E or R: Results in impaired filaments formation. 1 Publication | 1 | |
Mutagenesisi | 120 | A → K, L or V: Does not result in impaired filaments formation. 1 Publication | 1 |
Keywords - Diseasei
Cardiomyopathy, Desmin-related myopathy, Disease variant, Limb-girdle muscular dystrophy, Myofibrillar myopathyOrganism-specific databases
DisGeNETi | 1674 |
GeneReviewsi | DES |
MalaCardsi | DES |
MIMi | 181400, phenotype 601419, phenotype 604765, phenotype |
OpenTargetsi | ENSG00000175084 |
Orphaneti | 98909, Desminopathy 154, Familial isolated dilated cardiomyopathy 85146, Neurogenic scapuloperoneal syndrome, Kaeser type |
PharmGKBi | PA27253 |
Miscellaneous databases
Pharosi | P17661, Tbio |
Genetic variation databases
BioMutai | DES |
DMDMi | 6686280 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedBy similarity | |||
ChainiPRO_0000063771 | 2 – 470 | DesminAdd BLAST | 469 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 7 | Phosphoserine; by CDK1By similarity | 1 | |
Modified residuei | 12 | Phosphoserine; by AURKB1 Publication | 1 | |
Modified residuei | 16 | Omega-N-methylarginineBy similarity | 1 | |
Modified residuei | 17 | Phosphothreonine; by AURKB and ROCK12 Publications | 1 | |
Modified residuei | 28 | Phosphoserine; by CDK1Combined sources1 Publication | 1 | |
Modified residuei | 31 | PhosphoserineBy similarity | 1 | |
Modified residuei | 32 | Phosphoserine; by CDK12 Publications | 1 | |
Modified residuei | 37 | Asymmetric dimethylarginine; alternateBy similarity | 1 | |
Modified residuei | 37 | Omega-N-methylarginine; alternateBy similarity | 1 | |
Modified residuei | 45 | PhosphoserineBy similarity | 1 | |
Modified residuei | 58 | ADP-ribosylarginineBy similarity | 1 | |
Modified residuei | 60 | Phosphoserine; by AURKB1 Publication | 1 | |
Modified residuei | 68 | PhosphoserineBy similarity | 1 | |
Modified residuei | 70 | Omega-N-methylarginineBy similarity | 1 | |
Modified residuei | 76 | Phosphothreonine; by ROCK11 Publication | 1 | |
Modified residuei | 77 | Phosphothreonine; by ROCK11 Publication | 1 | |
Modified residuei | 81 | PhosphoserineBy similarity | 1 | |
Modified residuei | 290 | PhosphoserineBy similarity | 1 | |
Modified residuei | 358 | PhosphoserineBy similarity | 1 | |
Modified residuei | 361 | PhosphoserineBy similarity | 1 | |
Modified residuei | 424 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
ADP-ribosylation prevents ability to form intermediate filaments.By similarity
Phosphorylation at Ser-7, Ser-28 and Ser-32 by CDK1, phosphorylation at Ser-60 by AURKB and phosphorylation at Thr-76 by ROCK1 contribute to efficient separation of desmin intermediate filaments during mitosis.By similarity
Keywords - PTMi
ADP-ribosylation, Methylation, PhosphoproteinProteomic databases
EPDi | P17661 |
jPOSTi | P17661 |
MassIVEi | P17661 |
PaxDbi | P17661 |
PeptideAtlasi | P17661 |
PRIDEi | P17661 |
ProteomicsDBi | 53502 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00465084 P17661 |
SWISS-2DPAGEi | P17661 |
UCD-2DPAGEi | P17661 |
PTM databases
iPTMneti | P17661 |
PhosphoSitePlusi | P17661 |
SwissPalmi | P17661 |
Expressioni
Gene expression databases
Bgeei | ENSG00000175084, Expressed in esophagogastric junction muscularis propria and 232 other tissues |
ExpressionAtlasi | P17661, baseline and differential |
Genevisiblei | P17661, HS |
Organism-specific databases
HPAi | ENSG00000175084, Tissue enhanced (heart muscle, skeletal muscle, smooth muscle) |
Interactioni
Subunit structurei
Homopolymer (PubMed:21135508).
Interacts with DST (By similarity).
Interacts with MTM1 (PubMed:21135508).
Interacts with EPPK1; interaction is dependent of higher-order structure of intermediate filament (PubMed:16923132).
Interacts with CRYAB (PubMed:28470624).
Interacts with NEB (via nebulin repeats 160-164) (PubMed:23615443).
Interacts (via rod region) with NEBL (via nebulin repeats 1-5) (PubMed:27733623).
By similarity5 PublicationsBinary interactionsi
Hide detailsP17661
GO - Molecular functioni
- cytoskeletal protein binding Source: BHF-UCL
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 108038, 78 interactors |
IntActi | P17661, 62 interactors |
MINTi | P17661 |
STRINGi | 9606.ENSP00000363071 |
Miscellaneous databases
RNActi | P17661, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 108 – 416 | IF rodPROSITE-ProRule annotationAdd BLAST | 309 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 2 – 108 | HeadAdd BLAST | 107 | |
Regioni | 109 – 141 | Coil 1AAdd BLAST | 33 | |
Regioni | 142 – 151 | Linker 1 | 10 | |
Regioni | 152 – 252 | Coil 1BAdd BLAST | 101 | |
Regioni | 253 – 268 | Linker 12Add BLAST | 16 | |
Regioni | 268 – 415 | Interaction with NEB1 PublicationAdd BLAST | 148 | |
Regioni | 269 – 287 | Coil 2AAdd BLAST | 19 | |
Regioni | 288 – 295 | Linker 2 | 8 | |
Regioni | 296 – 412 | Coil 2BAdd BLAST | 117 | |
Regioni | 413 – 470 | TailAdd BLAST | 58 | |
Regioni | 438 – 453 | Interaction with CRYAB1 PublicationAdd BLAST | 16 |
Sequence similaritiesi
Belongs to the intermediate filament family.PROSITE-ProRule annotation
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | KOG0977, Eukaryota |
GeneTreei | ENSGT00940000155522 |
HOGENOMi | CLU_012560_7_4_1 |
InParanoidi | P17661 |
OMAi | YSTISFR |
OrthoDBi | 655109at2759 |
PhylomeDBi | P17661 |
TreeFami | TF330122 |
Family and domain databases
Gene3Di | 1.20.5.1160, 1 hit |
InterProi | View protein in InterPro IPR018039, IF_conserved IPR039008, IF_rod_dom IPR042180, IF_rod_dom_coil1B IPR006821, Intermed_filament_DNA-bd |
Pfami | View protein in Pfam PF00038, Filament, 1 hit PF04732, Filament_head, 1 hit |
SMARTi | View protein in SMART SM01391, Filament, 1 hit |
PROSITEi | View protein in PROSITE PS00226, IF_ROD_1, 1 hit PS51842, IF_ROD_2, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P17661-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MSQAYSSSQR VSSYRRTFGG APGFPLGSPL SSPVFPRAGF GSKGSSSSVT
60 70 80 90 100
SRVYQVSRTS GGAGGLGSLR ASRLGTTRTP SSYGAGELLD FSLADAVNQE
110 120 130 140 150
FLTTRTNEKV ELQELNDRFA NYIEKVRFLE QQNAALAAEV NRLKGREPTR
160 170 180 190 200
VAELYEEELR ELRRQVEVLT NQRARVDVER DNLLDDLQRL KAKLQEEIQL
210 220 230 240 250
KEEAENNLAA FRADVDAATL ARIDLERRIE SLNEEIAFLK KVHEEEIREL
260 270 280 290 300
QAQLQEQQVQ VEMDMSKPDL TAALRDIRAQ YETIAAKNIS EAEEWYKSKV
310 320 330 340 350
SDLTQAANKN NDALRQAKQE MMEYRHQIQS YTCEIDALKG TNDSLMRQMR
360 370 380 390 400
ELEDRFASEA SGYQDNIARL EEEIRHLKDE MARHLREYQD LLNVKMALDV
410 420 430 440 450
EIATYRKLLE GEESRINLPI QTYSALNFRE TSPEQRGSEV HTKKTVMIKT
460 470
IETRDGEVVS EATQQQHEVL
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 23 – 25 | GFP → VFS (PubMed:2673923).Curated | 3 | |
Sequence conflicti | 23 – 25 | GFP → VFS in AAA99221 (PubMed:2007603).Curated | 3 | |
Sequence conflicti | 39 | G → P (PubMed:2673923).Curated | 1 | |
Sequence conflicti | 39 | G → P in AAA99221 (PubMed:2007603).Curated | 1 | |
Sequence conflicti | 119 – 123 | FANYI → SPIYM (PubMed:2673923).Curated | 5 | |
Sequence conflicti | 119 – 123 | FANYI → SPIYM in AAA99221 (PubMed:2007603).Curated | 5 | |
Sequence conflicti | 134 | Missing (PubMed:2673923).Curated | 1 | |
Sequence conflicti | 134 | Missing in AAA99221 (PubMed:2007603).Curated | 1 | |
Sequence conflicti | 134 | Missing in AAC50680 (PubMed:8792816).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_042448 | 2 | S → I in MFM1. 1 PublicationCorresponds to variant dbSNP:rs58999456EnsemblClinVar. | 1 | |
Natural variantiVAR_067207 | 7 | S → F in MFM1. 1 PublicationCorresponds to variant dbSNP:rs903985237EnsemblClinVar. | 1 | |
Natural variantiVAR_067208 | 13 | S → F in MFM1; some patients manifest a severe cardiac phenotype with right ventricular predominance. 2 PublicationsCorresponds to variant dbSNP:rs62636495EnsemblClinVar. | 1 | |
Natural variantiVAR_079048 | 16 | R → C in MFM1. 1 PublicationCorresponds to variant dbSNP:rs60798368EnsemblClinVar. | 1 | |
Natural variantiVAR_042449 | 46 | S → F in MFM1; exhibits significantly delayed filament assembly kinetics when bound to NEB; enhanced binding affinity towards NEB. 2 PublicationsCorresponds to variant dbSNP:rs60794845EnsemblClinVar. | 1 | |
Natural variantiVAR_042450 | 46 | S → Y in MFM1. 1 PublicationCorresponds to variant dbSNP:rs60794845EnsemblClinVar. | 1 | |
Natural variantiVAR_069191 | 116 | N → S in MFM1; the clinical picture is dominated by arrhythmogenic right ventricular cardiomyopathy and terminal heart failure; results in impaired filaments formation. 1 PublicationCorresponds to variant dbSNP:rs267607499EnsemblClinVar. | 1 | |
Natural variantiVAR_075228 | 120 | A → D in CMD1I; results in impaired filaments formation, does not localize at intercalated disks. 1 Publication | 1 | |
Natural variantiVAR_075229 | 136 | L → P in CMD1I; results in impaired filaments formation, does not localize at intercalated disks. 1 PublicationCorresponds to variant dbSNP:rs397516695EnsemblClinVar. | 1 | |
Natural variantiVAR_009188 | 173 – 179 | Missing in MFM1; severe form. 1 Publication | 7 | |
Natural variantiVAR_042451 | 213 | A → V May play a role in cardiomyopathies and distal myopathies if combined with other DES mutations or mutations in other genes; does not affect the formation of a normal complete filamentous network. 4 PublicationsCorresponds to variant dbSNP:rs41272699EnsemblClinVar. | 1 | |
Natural variantiVAR_070101 | 240 | Missing in MFM1; the mutant cannot form de novo desmin intermediate filaments causing disruption of the endogenous intermediate filament network and formation of pathologic aggregates. 1 Publication | 1 | |
Natural variantiVAR_069192 | 241 | K → E Found in a patient with severe arrhythmogenic right ventricular cardiomyopathy also carrying a pathogenic frameshift mutation in PKP2. 1 PublicationCorresponds to variant dbSNP:rs201945924Ensembl. | 1 | |
Natural variantiVAR_042452 | 245 | E → D in MFM1; exhibits significantly delayed filament assembly kinetics when bound to NEB and NEBL; enhanced binding affinity towards NEB and NEBL. 1 PublicationCorresponds to variant dbSNP:rs267607486EnsemblClinVar. | 1 | |
Natural variantiVAR_075230 | 326 | H → R in CMD1I; unknown pathological significance; does not affect filaments formation. 1 Publication | 1 | |
Natural variantiVAR_007900 | 337 | A → P in MFM1; mild adult-onset; unable to form a functional filamentous network. 2 PublicationsCorresponds to variant dbSNP:rs59962885EnsemblClinVar. | 1 | |
Natural variantiVAR_067209 | 338 | L → R in MFM1; results in the formation of a filamentous network disrupted by multiple breaks and clumps or large aggregates. 1 PublicationCorresponds to variant dbSNP:rs57496341EnsemblClinVar. | 1 | |
Natural variantiVAR_042453 | 342 | N → D in MFM1; unable to form a filamentous network; abolishes binding to MTM1. 3 PublicationsCorresponds to variant dbSNP:rs267607482EnsemblClinVar. | 1 | |
Natural variantiVAR_009189 | 345 | L → P in MFM1; distal onset; incapable of forming filamentous networks. 1 PublicationCorresponds to variant dbSNP:rs57639980EnsemblClinVar. | 1 | |
Natural variantiVAR_042454 | 350 | R → P in Kaeser syndrome and MFM1; incapable of de novo formation of a desmin intermediate filaments network; exerts a dominant negative effect on the ordered lateral arrangement of desmin subunits; may produce structural changes; forms subsarcolemmal aggregates. 3 PublicationsCorresponds to variant dbSNP:rs57965306EnsemblClinVar. | 1 | |
Natural variantiVAR_042455 | 355 | R → P in MFM1. 1 PublicationCorresponds to variant dbSNP:rs61368398EnsemblClinVar. | 1 | |
Natural variantiVAR_042456 | 357 | A → P in MFM1; unable to polymerize and form an intracellular filamentous network; abolishes binding to MTM1. 3 PublicationsCorresponds to variant dbSNP:rs58898021EnsemblClinVar. | 1 | |
Natural variantiVAR_018769 | 359 – 361 | Missing in MFM1. 1 Publication | 3 | |
Natural variantiVAR_007901 | 360 | A → P in MFM1; heterozygous with I-393 gives a severe childhood-onset; unable to form a functional filamentous network in the presence of I-393; abolishes binding to MTM1. 4 PublicationsCorresponds to variant dbSNP:rs121913000EnsemblClinVar. | 1 | |
Natural variantiVAR_018770 | 366 | Missing in MFM1. 1 Publication | 1 | |
Natural variantiVAR_042457 | 370 | L → P in MFM1; unable to polymerize and form an intracellular filamentous network; does not affect binding to MTM1. 3 PublicationsCorresponds to variant dbSNP:rs59308628EnsemblClinVar. | 1 | |
Natural variantiVAR_018771 | 385 | L → P in MFM1. 1 PublicationCorresponds to variant dbSNP:rs57955682EnsemblClinVar. | 1 | |
Natural variantiVAR_018772 | 389 | Q → P in MFM1. 1 PublicationCorresponds to variant dbSNP:rs121913004EnsemblClinVar. | 1 | |
Natural variantiVAR_007902 | 393 | N → I in MFM1; heterozygous with P-360 gives a severe childhood-onset; filamentous network is not affected however several spots indicate focal disorganization. 3 PublicationsCorresponds to variant dbSNP:rs121913001EnsemblClinVar. | 1 | |
Natural variantiVAR_067210 | 399 | D → Y in MFM1; results in the formation of a filamentous network disrupted by multiple breaks and clumps or large aggregates. 1 PublicationCorresponds to variant dbSNP:rs61130669EnsemblClinVar. | 1 | |
Natural variantiVAR_067211 | 401 | E → K in MFM1; results in the formation of a filamentous network disrupted by multiple breaks and clumps or large aggregates. 1 PublicationCorresponds to variant dbSNP:rs57694264EnsemblClinVar. | 1 | |
Natural variantiVAR_042458 | 406 | R → W in MFM1; unable to form a filamentous network. 3 PublicationsCorresponds to variant dbSNP:rs121913003EnsemblClinVar. | 1 | |
Natural variantiVAR_069074 | 419 | P → S in MFM1; found in a family with myofibrillar myopathy and arrhythmogenic right ventricular cardiomyopathy. 1 PublicationCorresponds to variant dbSNP:rs62635763EnsemblClinVar. | 1 | |
Natural variantiVAR_042459 | 442 | T → I in MFM1; reveals a severe disturbance of filament-formation competence and filament-filament interactions. 1 PublicationCorresponds to variant dbSNP:rs121913005EnsemblClinVar. | 1 | |
Natural variantiVAR_042460 | 449 | K → M in MFM1. | 1 | |
Natural variantiVAR_042461 | 449 | K → T in MFM1. 1 PublicationCorresponds to variant dbSNP:rs267607485EnsemblClinVar. | 1 | |
Natural variantiVAR_018773 | 451 | I → M in CMD1I and MFM1; reveals a severe disturbance of filament-formation competence and filament-filament interactions; reduced interaction with CRYAB. 4 PublicationsCorresponds to variant dbSNP:rs121913002EnsemblClinVar. | 1 | |
Natural variantiVAR_079049 | 453 | T → I in MFM1; exhibits significantly delayed filament assembly kinetics when bound to NEB and NEBL; enhanced binding affinity towards NEB and NEBL. 2 PublicationsCorresponds to variant dbSNP:rs267607488EnsemblClinVar. | 1 | |
Natural variantiVAR_042462 | 454 | R → W in MFM1; reveals a severe disturbance of filament-formation competence and filament-filament interactions; increased interaction with CRYAB. 3 PublicationsCorresponds to variant dbSNP:rs267607490EnsemblClinVar. | 1 | |
Natural variantiVAR_042463 | 460 | S → I in MFM1; reveals a severe disturbance of filament-formation competence and filament-filament interactions. 1 PublicationCorresponds to variant dbSNP:rs267607491EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M63391 Genomic DNA Translation: AAA99221.1 U59167 mRNA Translation: AAC50680.1 AF055081 mRNA Translation: AAC39938.1 AF055082 mRNA Translation: AAC39939.1 AF055083 mRNA Translation: AAC39940.1 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 |
CCDSi | CCDS33383.1 |
PIRi | JE0063, DMHU |
RefSeqi | NP_001918.3, NM_001927.3 |
Genome annotation databases
Ensembli | ENST00000373960; ENSP00000363071; ENSG00000175084 |
GeneIDi | 1674 |
KEGGi | hsa:1674 |
Similar proteinsi
Cross-referencesi
Web resourcesi
Human Intermediate Filament Mutation Database |
Wikipedia Desmin entry |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M63391 Genomic DNA Translation: AAA99221.1 U59167 mRNA Translation: AAC50680.1 AF055081 mRNA Translation: AAC39938.1 AF055082 mRNA Translation: AAC39939.1 AF055083 mRNA Translation: AAC39940.1 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 |
CCDSi | CCDS33383.1 |
PIRi | JE0063, DMHU |
RefSeqi | NP_001918.3, NM_001927.3 |
3D structure databases
SMRi | P17661 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 108038, 78 interactors |
IntActi | P17661, 62 interactors |
MINTi | P17661 |
STRINGi | 9606.ENSP00000363071 |
PTM databases
iPTMneti | P17661 |
PhosphoSitePlusi | P17661 |
SwissPalmi | P17661 |
Genetic variation databases
BioMutai | DES |
DMDMi | 6686280 |
2D gel databases
REPRODUCTION-2DPAGEi | IPI00465084 P17661 |
SWISS-2DPAGEi | P17661 |
UCD-2DPAGEi | P17661 |
Proteomic databases
EPDi | P17661 |
jPOSTi | P17661 |
MassIVEi | P17661 |
PaxDbi | P17661 |
PeptideAtlasi | P17661 |
PRIDEi | P17661 |
ProteomicsDBi | 53502 |
Protocols and materials databases
Antibodypediai | 3503, 1436 antibodies |
DNASUi | 1674 |
Genome annotation databases
Ensembli | ENST00000373960; ENSP00000363071; ENSG00000175084 |
GeneIDi | 1674 |
KEGGi | hsa:1674 |
Organism-specific databases
CTDi | 1674 |
DisGeNETi | 1674 |
GeneCardsi | DES |
GeneReviewsi | DES |
HGNCi | HGNC:2770, DES |
HPAi | ENSG00000175084, Tissue enhanced (heart muscle, skeletal muscle, smooth muscle) |
MalaCardsi | DES |
MIMi | 125660, gene 181400, phenotype 601419, phenotype 604765, phenotype |
neXtProti | NX_P17661 |
OpenTargetsi | ENSG00000175084 |
Orphaneti | 98909, Desminopathy 154, Familial isolated dilated cardiomyopathy 85146, Neurogenic scapuloperoneal syndrome, Kaeser type |
PharmGKBi | PA27253 |
VEuPathDBi | HostDB:ENSG00000175084.11 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0977, Eukaryota |
GeneTreei | ENSGT00940000155522 |
HOGENOMi | CLU_012560_7_4_1 |
InParanoidi | P17661 |
OMAi | YSTISFR |
OrthoDBi | 655109at2759 |
PhylomeDBi | P17661 |
TreeFami | TF330122 |
Enzyme and pathway databases
PathwayCommonsi | P17661 |
Reactomei | R-HSA-390522, Striated Muscle Contraction |
SIGNORi | P17661 |
Miscellaneous databases
BioGRID-ORCSi | 1674, 6 hits in 880 CRISPR screens |
ChiTaRSi | DES, human |
GeneWikii | Desmin |
GenomeRNAii | 1674 |
Pharosi | P17661, Tbio |
PROi | PR:P17661 |
RNActi | P17661, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000175084, Expressed in esophagogastric junction muscularis propria and 232 other tissues |
ExpressionAtlasi | P17661, baseline and differential |
Genevisiblei | P17661, HS |
Family and domain databases
Gene3Di | 1.20.5.1160, 1 hit |
InterProi | View protein in InterPro IPR018039, IF_conserved IPR039008, IF_rod_dom IPR042180, IF_rod_dom_coil1B IPR006821, Intermed_filament_DNA-bd |
Pfami | View protein in Pfam PF00038, Filament, 1 hit PF04732, Filament_head, 1 hit |
SMARTi | View protein in SMART SM01391, Filament, 1 hit |
PROSITEi | View protein in PROSITE PS00226, IF_ROD_1, 1 hit PS51842, IF_ROD_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | DESM_HUMAN | |
Accessioni | P17661Primary (citable) accession number: P17661 Secondary accession number(s): Q15787 Q9UJ80 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1990 |
Last sequence update: | January 23, 2007 | |
Last modified: | February 10, 2021 | |
This is version 215 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM