DESM_HUMAN
ID DESM_HUMAN Reviewed; 470 AA.
AC P17661; Q15787; Q549R7; Q549R8; Q549R9; Q8IZR1; Q8IZR6; Q8NES2; Q8NEU6;
AC Q8TAC4; Q8TCX2; Q8TD99; Q9UHN5; Q9UJ80;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=Desmin;
GN Name=DES;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2673923; DOI=10.1016/0378-1119(89)90227-8;
RA Li Z., Lilienbaum A., Butler-Browne G., Paulin D.;
RT "Human desmin-coding gene: complete nucleotide sequence, characterization
RT and regulation of expression during myogenesis and development.";
RL Gene 78:243-254(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2007603; DOI=10.1016/s0021-9258(18)38154-7;
RA Li Z., Paulin D.;
RT "High level desmin expression depends on a muscle-specific enhancer.";
RL J. Biol. Chem. 266:6562-6570(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Muscle;
RX PubMed=8792816; DOI=10.1007/s004390050233;
RA Vicart P., Dupret J.-M., Hazan J., Li Z., Gyapay G., Krishnamoorthy R.,
RA Weissenbach J., Fardeau M., Paulin D.;
RT "Human desmin gene: cDNA sequence, regional localization and exclusion of
RT the locus in a familial desmin-related myopathy.";
RL Hum. Genet. 98:422-429(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS MFM1 PRO-337; PRO-360 AND ILE-393.
RX PubMed=9697706; DOI=10.1038/1300;
RA Goldfarb L.G., Park K.-Y., Cervenakova L., Gorokhova S., Lee H.-S.,
RA Vasconcelos O., Nagle J.W., Semino-Mora C., Sivakumar K., Dalakas M.C.;
RT "Missense mutations in desmin associated with familial cardiac and skeletal
RT myopathy.";
RL Nat. Genet. 19:402-403(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT CMD1I MET-451, AND INVOLVEMENT IN
RP CMD1I.
RX PubMed=10430757; DOI=10.1161/01.cir.100.5.461;
RA Li D., Tapscoft T., Gonzalez O., Burch P.E., Quinones M.A., Zoghbi W.A.,
RA Hill R., Bachinski L.L., Mann D.L., Roberts R.;
RT "Desmin mutation responsible for idiopathic dilated cardiomyopathy.";
RL Circulation 100:461-464(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT MFM1 PRO-389.
RX PubMed=11668632; DOI=10.1002/humu.1210;
RA Goudeau B., Dagvadorj A., Rodrigues-Lima F., Nedellec P.,
RA Casteras-Simon M., Perret E., Langlois S., Goldfarb L., Vicart P.;
RT "Structural and functional analysis of a new desmin variant causing desmin-
RT related myopathy.";
RL Hum. Mutat. 18:388-396(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS MFM1 ASP-342; PRO-357;
RP 359-GLU--SER-361 DEL; ASN-366 DEL AND PRO-370, AND VARIANT VAL-213.
RX PubMed=14648196; DOI=10.1007/s00439-003-1057-7;
RA Kaminska A., Strelkov S.V., Goudeau B., Olive M., Dagvadorj A.,
RA Fidzianska A., Simon-Casteras M., Shatunov A., Dalakas M.C., Ferrer I.,
RA Kwiecinski H., Vicart P., Goldfarb L.G.;
RT "Small deletions disturb desmin architecture leading to breakdown of muscle
RT cells and development of skeletal or cardioskeletal myopathy.";
RL Hum. Genet. 114:306-313(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 337-353, VARIANT MFM1 PRO-345, AND
RP CHARACTERIZATION OF VARIANT MFM1 PRO-345.
RC TISSUE=Skeletal muscle;
RX PubMed=10545598; DOI=10.1093/hmg/8.12.2191;
RA Sjoeberg G., Saavedra-Matiz C.A., Rosen D.R., Wijsman E.M., Borg K.,
RA Horowitz S.H., Sejersen T.;
RT "A missense mutation in the desmin rod domain is associated with autosomal
RT dominant distal myopathy, and exerts a dominant negative effect on filament
RT formation.";
RL Hum. Mol. Genet. 8:2191-2198(1999).
RN [10]
RP PHOSPHORYLATION AT THR-17; THR-76 AND THR-77.
RX PubMed=9875213; DOI=10.1006/bbrc.1998.9732;
RA Inada H., Goto H., Tanabe K., Nishi Y., Kaibuchi K., Inagaki M.;
RT "Rho-associated kinase phosphorylates desmin, the myogenic intermediate
RT filament protein, at unique amino-terminal sites.";
RL Biochem. Biophys. Res. Commun. 253:21-25(1998).
RN [11]
RP PHOSPHORYLATION AT SER-12; THR-17 AND SER-60.
RX PubMed=12686604; DOI=10.1091/mbc.e02-09-0612;
RA Kawajiri A., Yasui Y., Goto H., Tatsuka M., Takahashi M., Nagata K.,
RA Inagaki M.;
RT "Functional significance of the specific sites phosphorylated in desmin at
RT cleavage furrow: Aurora-B may phosphorylate and regulate type III
RT intermediate filaments during cytokinesis coordinatedly with Rho-kinase.";
RL Mol. Biol. Cell 14:1489-1500(2003).
RN [12]
RP INTERACTION WITH EPPK1.
RX PubMed=16923132; DOI=10.1111/j.1346-8138.2006.00127.x;
RA Wang W., Sumiyoshi H., Yoshioka H., Fujiwara S.;
RT "Interactions between epiplakin and intermediate filaments.";
RL J. Dermatol. 33:518-527(2006).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP INTERACTION WITH MTM1, CHARACTERIZATION OF VARIANTS ASP-342; PRO-357;
RP PRO-360 AND PRO-370, AND SUBUNIT.
RX PubMed=21135508; DOI=10.1172/jci44021;
RA Hnia K., Tronchere H., Tomczak K.K., Amoasii L., Schultz P., Beggs A.H.,
RA Payrastre B., Mandel J.L., Laporte J.;
RT "Myotubularin controls desmin intermediate filament architecture and
RT mitochondrial dynamics in human and mouse skeletal muscle.";
RL J. Clin. Invest. 121:70-85(2011).
RN [15]
RP REVIEW ON VARIANTS MFM1.
RX PubMed=14724127; DOI=10.1093/brain/awh033;
RA Goldfarb L.G., Vicart P., Goebel H.H., Dalakas M.C.;
RT "Desmin myopathy.";
RL Brain 127:723-734(2004).
RN [16]
RP REVIEW ON VARIANTS MFM1.
RX PubMed=15495235; DOI=10.1002/path.1639;
RA Paulin D., Huet A., Khanamyrian L., Xue Z.;
RT "Desminopathies in muscle disease.";
RL J. Pathol. 204:418-427(2004).
RN [17]
RP INVOLVEMENT IN MFM1.
RX PubMed=23687351; DOI=10.1136/jmedgenet-2012-101487;
RA Cetin N., Balci-Hayta B., Gundesli H., Korkusuz P., Purali N., Talim B.,
RA Tan E., Selcen D., Erdem-Ozdamar S., Dincer P.;
RT "A novel desmin mutation leading to autosomal recessive limb-girdle
RT muscular dystrophy: distinct histopathological outcomes compared with
RT desminopathies.";
RL J. Med. Genet. 50:437-443(2013).
RN [18]
RP PHOSPHORYLATION AT SER-28 AND SER-32, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=24413773; DOI=10.1093/cvr/cvu003;
RA Agnetti G., Halperin V.L., Kirk J.A., Chakir K., Guo Y., Lund L.,
RA Nicolini F., Gherli T., Guarnieri C., Caldarera C.M., Tomaselli G.F.,
RA Kass D.A., Van Eyk J.E.;
RT "Desmin modifications associate with amyloid-like oligomers deposition in
RT heart failure.";
RL Cardiovasc. Res. 102:24-34(2014).
RN [19]
RP INTERACTION WITH PLEC.
RX PubMed=24940650; DOI=10.1038/jid.2014.255;
RA Bouameur J.E., Favre B., Fontao L., Lingasamy P., Begre N., Borradori L.;
RT "Interaction of plectin with keratins 5 and 14: dependence on several
RT plectin domains and keratin quaternary structure.";
RL J. Invest. Dermatol. 134:2776-2783(2014).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP REVIEW.
RX PubMed=25358400; DOI=10.1007/s00441-014-2016-4;
RA Hnia K., Ramspacher C., Vermot J., Laporte J.;
RT "Desmin in muscle and associated diseases: beyond the structural
RT function.";
RL Cell Tissue Res. 360:591-608(2015).
RN [22]
RP PHOSPHORYLATION AT SER-32.
RX PubMed=27565725; DOI=10.1016/j.bbrc.2016.08.122;
RA Makihara H., Inaba H., Enomoto A., Tanaka H., Tomono Y., Ushida K.,
RA Goto M., Kurita K., Nishida Y., Kasahara K., Goto H., Inagaki M.;
RT "Desmin phosphorylation by Cdk1 is required for efficient separation of
RT desmin intermediate filaments in mitosis and detected in murine
RT embryonic/newborn muscle and human rhabdomyosarcoma tissues.";
RL Biochem. Biophys. Res. Commun. 478:1323-1329(2016).
RN [23]
RP VARIANT MFM1 173-ARG--GLU-179 DEL.
RX PubMed=9736733; DOI=10.1073/pnas.95.19.11312;
RA Munoz-Marmol A.M., Strasser G., Isamat M., Coulombe P.A., Yang Y., Roca X.,
RA Vela E., Mate J.L., Coll J., Fernandez-Figueras M.T., Navas-Palacios J.J.,
RA Ariza A., Fuchs E.;
RT "A dysfunctional desmin mutation in a patient with severe generalized
RT myopathy.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:11312-11317(1998).
RN [24]
RP VARIANT MFM1 TRP-406.
RX PubMed=10905661; DOI=10.1034/j.1399-0004.2000.570604.x;
RA Park K.-Y., Dalakas M.C., Semino-Mora C., Lee H.-S., Litvak S., Takeda K.,
RA Ferrans V.J., Goldfarb L.G.;
RT "Sporadic cardiac and skeletal myopathy caused by a de novo desmin
RT mutation.";
RL Clin. Genet. 57:423-429(2000).
RN [25]
RP VARIANT MFM1 PRO-385.
RX PubMed=11061256; DOI=10.1212/wnl.55.7.986;
RA Sugawara M., Kato K., Komatsu M., Wada C., Kawamura K., Shindo P.S.,
RA Yoshioka P.N., Tanaka K., Watanabe S., Toyoshima I.;
RT "A novel de novo mutation in the desmin gene causes desmin myopathy with
RT toxic aggregates.";
RL Neurology 55:986-990(2000).
RN [26]
RP VARIANTS MFM1 PRO-337; ASP-342; PRO-360; ILE-393; TRP-406 AND MET-451, AND
RP CHARACTERIZATION OF VARIANTS MFM1 PRO-337; ASP-342; PRO-360; ILE-393;
RP TRP-406 AND MET-451.
RX PubMed=10717012; DOI=10.1056/nejm200003163421104;
RA Dalakas M.C., Park K.-Y., Semino-Mora C., Lee H.S., Sivakumar K.,
RA Goldfarb L.G.;
RT "Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by
RT mutations in the desmin gene.";
RL N. Engl. J. Med. 342:770-780(2000).
RN [27]
RP VARIANT MFM1 LYS-240 DEL, AND CHARACTERIZATION OF VARIANT MFM1 LYS-240 DEL.
RX PubMed=12620971; DOI=10.1093/hmg/ddg060;
RA Schroeder R., Goudeau B., Simon M.C., Fischer D., Eggermann T.,
RA Clemen C.S., Li Z., Reimann J., Xue Z., Rudnik-Schoeneborn S., Zerres K.,
RA van der Ven P.F., Fuerst D.O., Kunz W.S., Vicart P.;
RT "On noxious desmin: functional effects of a novel heterozygous desmin
RT insertion mutation on the extrasarcomeric desmin cytoskeleton and
RT mitochondria.";
RL Hum. Mol. Genet. 12:657-669(2003).
RN [28]
RP ERRATUM OF PUBMED:12620971.
RA Schroeder R., Goudeau B., Simon M.C., Fischer D., Eggermann T.,
RA Clemen C.S., Li Z., Reimann J., Xue Z., Rudnik-Schoeneborn S., Zerres K.,
RA van der Ven P.F., Fuerst D.O., Kunz W.S., Vicart P.;
RL Hum. Mol. Genet. 16:2989-2990(2003).
RN [29]
RP VARIANTS MFM1 PRO-357 AND PRO-370, AND CHARACTERIZATION OF VARIANTS MFM1
RP PRO-357 AND PRO-370.
RX PubMed=12766977; DOI=10.1002/mus.10370;
RA Dagvadorj A., Goudeau B., Hilton-Jones D., Blancato J.K., Shatunov A.,
RA Simon-Casteras M., Squier W., Nagle J.W., Goldfarb L.G., Vicart P.;
RT "Respiratory insufficiency in desminopathy patients caused by introduction
RT of proline residues in desmin C-terminal alpha-helical segment.";
RL Muscle Nerve 27:669-675(2003).
RN [30]
RP VARIANTS MFM1 ILE-2; TYR-46; PHE-46 AND THR-449.
RX PubMed=14711882; DOI=10.1093/brain/awh052;
RA Selcen D., Ohno K., Engel A.G.;
RT "Myofibrillar myopathy: clinical, morphological and genetic studies in 63
RT patients.";
RL Brain 127:439-451(2004).
RN [31]
RP VARIANT MFM1 PRO-350, AND CHARACTERIZATION OF VARIANT MFM1 PRO-350.
RX PubMed=15800015; DOI=10.1093/hmg/ddi136;
RA Baer H., Fischer D., Goudeau B., Kley R.A., Clemen C.S., Vicart P.,
RA Herrmann H., Vorgerd M., Schroeder R.;
RT "Pathogenic effects of a novel heterozygous R350P desmin mutation on the
RT assembly of desmin intermediate filaments in vivo and in vitro.";
RL Hum. Mol. Genet. 14:1251-1260(2005).
RN [32]
RP VARIANT MFM1 PRO-355.
RX PubMed=16009553; DOI=10.1016/j.nmd.2005.05.006;
RA Fidzianska A., Kotowicz J., Sadowska M., Goudeau B., Walczak E., Vicart P.,
RA Hausmanowa-Petrusewicz I.;
RT "A novel desmin R355P mutation causes cardiac and skeletal myopathy.";
RL Neuromuscul. Disord. 15:525-531(2005).
RN [33]
RP VARIANTS MFM1 CYS-16; TRP-406 AND ILE-453.
RX PubMed=16376610; DOI=10.1016/j.ejheart.2005.11.003;
RA Arbustini E., Pasotti M., Pilotto A., Pellegrini C., Grasso M.,
RA Previtali S., Repetto A., Bellini O., Azan G., Scaffino M., Campana C.,
RA Piccolo G., Vigano M., Tavazzi L.;
RT "Desmin accumulation restrictive cardiomyopathy and atrioventricular block
RT associated with desmin gene defects.";
RL Eur. J. Heart Fail. 8:477-483(2006).
RN [34]
RP VARIANTS MFM1 ARG-338; TYR-399 AND LYS-401, VARIANT VAL-213,
RP CHARACTERIZATION OF VARIANTS MFM1 ARG-338; PRO-360; ILE-393; TYR-399 AND
RP LYS-401, AND CHARACTERIZATION OF VARIANT VAL-213.
RX PubMed=16865695; DOI=10.1002/humu.20351;
RA Goudeau B., Rodrigues-Lima F., Fischer D., Casteras-Simon M.,
RA Sambuughin N., de Visser M., Laforet P., Ferrer X., Chapon F., Sjoberg G.,
RA Kostareva A., Sejersen T., Dalakas M.C., Goldfarb L.G., Vicart P.;
RT "Variable pathogenic potentials of mutations located in the desmin alpha-
RT helical domain.";
RL Hum. Mutat. 27:906-913(2006).
RN [35]
RP VARIANT KAESER SYNDROME PRO-350.
RX PubMed=17439987; DOI=10.1093/brain/awm039;
RA Walter M.C., Reilich P., Huebner A., Fischer D., Schroeder R., Vorgerd M.,
RA Kress W., Born C., Schoser B.G., Krause K.H., Klutzny U., Bulst S.,
RA Frey J.R., Lochmueller H.;
RT "Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of
RT adult-onset, dominant myopathies are associated with the desmin mutation
RT R350P.";
RL Brain 130:1485-1496(2007).
RN [36]
RP VARIANTS MFM1 ILE-442; TRP-454 AND ILE-460, AND CHARACTERIZATION OF
RP VARIANTS MFM1 ILE-442; MET-451; TRP-454 AND ILE-460.
RX PubMed=17221859; DOI=10.1002/humu.20459;
RA Baer H., Goudeau B., Waelde S., Casteras-Simon M., Muecke N., Shatunov A.,
RA Goldberg Y.P., Clarke C., Holton J.L., Eymard B., Katus H.A., Fardeau M.,
RA Goldfarb L., Vicart P., Herrmann H.;
RT "Conspicuous involvement of desmin tail mutations in diverse cardiac and
RT skeletal myopathies.";
RL Hum. Mutat. 28:374-386(2007).
RN [37]
RP VARIANT MFM1 PHE-13.
RX PubMed=18061454; DOI=10.1016/j.nmd.2007.09.011;
RA Pica E.C., Kathirvel P., Pramono Z.A., Lai P.S., Yee W.C.;
RT "Characterization of a novel S13F desmin mutation associated with desmin
RT myopathy and heart block in a Chinese family.";
RL Neuromuscul. Disord. 18:178-182(2008).
RN [38]
RP VARIANT MFM1 PHE-13, AND PHENOTYPIC VARIABILITY IN MFM1 PATIENTS.
RX PubMed=19879535; DOI=10.1016/j.hrthm.2009.07.041;
RA van Tintelen J.P., Van Gelder I.C., Asimaki A., Suurmeijer A.J.,
RA Wiesfeld A.C., Jongbloed J.D., van den Wijngaard A., Kuks J.B.,
RA van Spaendonck-Zwarts K.Y., Notermans N., Boven L., van den Heuvel F.,
RA Veenstra-Knol H.E., Saffitz J.E., Hofstra R.M., van den Berg M.P.;
RT "Severe cardiac phenotype with right ventricular predominance in a large
RT cohort of patients with a single missense mutation in the DES gene.";
RL Heart Rhythm 6:1574-1583(2009).
RN [39]
RP VARIANT MFM1 SER-116, AND CHARACTERIZATION OF VARIANT MFM1 SER-116.
RX PubMed=20829228; DOI=10.1093/hmg/ddq387;
RA Klauke B., Kossmann S., Gaertner A., Brand K., Stork I., Brodehl A.,
RA Dieding M., Walhorn V., Anselmetti D., Gerdes D., Bohms B., Schulz U.,
RA Zu Knyphausen E., Vorgerd M., Gummert J., Milting H.;
RT "De novo desmin-mutation N116S is associated with arrhythmogenic right
RT ventricular cardiomyopathy.";
RL Hum. Mol. Genet. 19:4595-4607(2010).
RN [40]
RP VARIANT VAL-213.
RX PubMed=21842594;
RA Kostareva A., Sjoberg G., Gudkova A., Smolina N., Semernin E.,
RA Shlyakhto E., Sejersen T.;
RT "Desmin A213V substitution represents a rare polymorphism but not a
RT mutation and is more prevalent in patients with heart dilation of various
RT origins.";
RL Acta Myol. 30:42-45(2011).
RN [41]
RP VARIANTS MFM1 PHE-7 AND TRP-454.
RX PubMed=22106715;
RA Vattemi G., Neri M., Piffer S., Vicart P., Gualandi F., Marini M.,
RA Guglielmi V., Filosto M., Tonin P., Ferlini A., Tomelleri G.;
RT "Clinical, morphological and genetic studies in a cohort of 21 patients
RT with myofibrillar myopathy.";
RL Acta Myol. 30:121-126(2011).
RN [42]
RP VARIANT MFM1 SER-419.
RX PubMed=22395865; DOI=10.1038/ejhg.2012.39;
RA Hedberg C., Melberg A., Kuhl A., Jenne D., Oldfors A.;
RT "Autosomal dominant myofibrillar myopathy with arrhythmogenic right
RT ventricular cardiomyopathy 7 is caused by a DES mutation.";
RL Eur. J. Hum. Genet. 20:984-985(2012).
RN [43]
RP VARIANTS VAL-213 AND GLU-241.
RX PubMed=23168288; DOI=10.1016/j.amjcard.2012.10.017;
RA Lorenzon A., Beffagna G., Bauce B., De Bortoli M., Li Mura I.E., Calore M.,
RA Dazzo E., Basso C., Nava A., Thiene G., Rampazzo A.;
RT "Desmin mutations and arrhythmogenic right ventricular cardiomyopathy.";
RL Am. J. Cardiol. 111:400-405(2013).
RN [44]
RP VARIANTS CMD1I ASP-120 AND ARG-326, CHARACTERIZATION OF VARIANTS CMD1I
RP ASP-120 AND ARG-326, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP ALA-120.
RX PubMed=24200904; DOI=10.1161/circgenetics.113.000103;
RA Brodehl A., Dieding M., Klauke B., Dec E., Madaan S., Huang T., Gargus J.,
RA Fatima A., Saric T., Cakar H., Walhorn V., Toensing K., Skrzipczyk T.,
RA Cebulla R., Gerdes D., Schulz U., Gummert J., Svendsen J.H., Olesen M.S.,
RA Anselmetti D., Christensen A.H., Kimonis V., Milting H.;
RT "The novel desmin mutant p.A120D impairs filament formation, prevents
RT intercalated disk localization, and causes sudden cardiac death.";
RL Circ. Cardiovasc. Genet. 6:615-623(2013).
RN [45]
RP CHARACTERIZATION OF VARIANTS MFM1 PHE-46; ASP-245 AND ILE-453, AND
RP INTERACTION WITH NEB.
RX PubMed=23615443; DOI=10.1091/mbc.e12-11-0840;
RA Baker L.K., Gillis D.C., Sharma S., Ambrus A., Herrmann H., Conover G.M.;
RT "Nebulin binding impedes mutant desmin filament assembly.";
RL Mol. Biol. Cell 24:1918-1932(2013).
RN [46]
RP CHARACTERIZATION OF VARIANT KAESER SYNDROME PRO-350, CHARACTERIZATION OF
RP VARIANT MFM1 PRO-350, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25394388; DOI=10.1007/s00401-014-1363-2;
RA Clemen C.S., Stoeckigt F., Strucksberg K.H., Chevessier F., Winter L.,
RA Schuetz J., Bauer R., Thorweihe J.M., Wenzel D., Schloetzer-Schrehardt U.,
RA Rasche V., Krsmanovic P., Katus H.A., Rottbauer W., Just S., Mueller O.J.,
RA Friedrich O., Meyer R., Herrmann H., Schrickel J.W., Schroeder R.;
RT "The toxic effect of R350P mutant desmin in striated muscle of man and
RT mouse.";
RL Acta Neuropathol. 129:297-315(2015).
RN [47]
RP VARIANT CMD1I PRO-136, CHARACTERIZATION OF VARIANT CMD1I PRO-136, FUNCTION,
RP AND SUBCELLULAR LOCATION.
RX PubMed=26724190; DOI=10.1016/j.yjmcc.2015.12.015;
RA Brodehl A., Dieding M., Biere N., Unger A., Klauke B., Walhorn V.,
RA Gummert J., Schulz U., Linke W.A., Gerull B., Vorgert M., Anselmetti D.,
RA Milting H.;
RT "Functional characterization of the novel DES mutation p.L136P associated
RT with dilated cardiomyopathy reveals a dominant filament assembly defect.";
RL J. Mol. Cell. Cardiol. 91:207-214(2016).
RN [48]
RP CHARACTERIZATION OF VARIANTS MFM1 ASP-245 AND ILE-453, AND INTERACTION WITH
RP NEBL.
RX PubMed=27733623; DOI=10.1091/mbc.e16-04-0237;
RA Hernandez D.A., Bennett C.M., Dunina-Barkovskaya L., Wedig T.,
RA Capetanaki Y., Herrmann H., Conover G.M.;
RT "Nebulette is a powerful cytolinker organizing desmin and actin in mouse
RT hearts.";
RL Mol. Biol. Cell 27:3869-3882(2016).
RN [49]
RP CHARACTERIZATION OF VARIANTS MFM1 MET-451 AND TRP-454, AND INTERACTION WITH
RP CRYAB.
RX PubMed=28470624; DOI=10.1007/s12192-017-0788-7;
RA Sharma S., Conover G.M., Elliott J.L., Der Perng M., Herrmann H.,
RA Quinlan R.A.;
RT "alphaB-crystallin is a sensor for assembly intermediates and for the
RT subunit topology of desmin intermediate filaments.";
RL Cell Stress Chaperones 22:613-626(2017).
RN [50]
RP VARIANT CMD1I PRO-398, CHARACTERIZATION OF VARIANT CMD1I PRO-398, AND
RP SUBCELLULAR LOCATION.
RX PubMed=30262925; DOI=10.1038/s41436-018-0291-2;
RA Brodehl A., Ebbinghaus H., Gaertner-Rommel A., Stanasiuk C., Klauke B.,
RA Milting H.;
RT "Functional analysis of DES-p.L398P and RBM20-p.R636C.";
RL Genet. Med. 21:1246-1247(2019).
CC -!- FUNCTION: Muscle-specific type III intermediate filament essential for
CC proper muscular structure and function. Plays a crucial role in
CC maintaining the structure of sarcomeres, inter-connecting the Z-disks
CC and forming the myofibrils, linking them not only to the sarcolemmal
CC cytoskeleton, but also to the nucleus and mitochondria, thus providing
CC strength for the muscle fiber during activity (PubMed:25358400). In
CC adult striated muscle they form a fibrous network connecting myofibrils
CC to each other and to the plasma membrane from the periphery of the Z-
CC line structures (PubMed:24200904, PubMed:25394388, PubMed:26724190).
CC May act as a sarcomeric microtubule-anchoring protein: specifically
CC associates with detyrosinated tubulin-alpha chains, leading to buckled
CC microtubules and mechanical resistance to contraction. Contributes to
CC the transcriptional regulation of the NKX2-5 gene in cardiac progenitor
CC cells during a short period of cardiomyogenesis and in cardiac side
CC population stem cells in the adult. Plays a role in maintaining an
CC optimal conformation of nebulette (NEB) on heart muscle sarcomeres to
CC bind and recruit cardiac alpha-actin (By similarity).
CC {ECO:0000250|UniProtKB:P31001, ECO:0000269|PubMed:24200904,
CC ECO:0000269|PubMed:25394388, ECO:0000269|PubMed:26724190,
CC ECO:0000303|PubMed:25358400}.
CC -!- SUBUNIT: Homomer (PubMed:21135508). Interacts with DST (By similarity).
CC Interacts with MTM1 (PubMed:21135508). Interacts with EPPK1;
CC interaction is dependent of higher-order structure of intermediate
CC filament (PubMed:16923132). Interacts with CRYAB (PubMed:28470624).
CC Interacts with NEB (via nebulin repeats 160-164) (PubMed:23615443).
CC Interacts (via rod region) with NEBL (via nebulin repeats 1-5)
CC (PubMed:27733623). Interacts with ASB2 isoform 1; the interaction
CC targets DES for proteasomal degradation (By similarity). Interacts with
CC PLEC isoform 1C (PubMed:24940650). {ECO:0000250|UniProtKB:P31001,
CC ECO:0000269|PubMed:16923132, ECO:0000269|PubMed:21135508,
CC ECO:0000269|PubMed:23615443, ECO:0000269|PubMed:24940650,
CC ECO:0000269|PubMed:27733623, ECO:0000269|PubMed:28470624}.
CC -!- INTERACTION:
CC P17661; Q9UL15: BAG5; NbExp=3; IntAct=EBI-1055572, EBI-356517;
CC P17661; Q8TAB5: C1orf216; NbExp=3; IntAct=EBI-1055572, EBI-747505;
CC P17661; Q8WUE5: CT55; NbExp=6; IntAct=EBI-1055572, EBI-6873363;
CC P17661; Q2TBE0: CWF19L2; NbExp=3; IntAct=EBI-1055572, EBI-5453285;
CC P17661; P26196: DDX6; NbExp=3; IntAct=EBI-1055572, EBI-351257;
CC P17661; P17661: DES; NbExp=7; IntAct=EBI-1055572, EBI-1055572;
CC P17661; O43812: DUX1; NbExp=4; IntAct=EBI-1055572, EBI-11599346;
CC P17661; Q9UBX2: DUX4; NbExp=3; IntAct=EBI-1055572, EBI-11600078;
CC P17661; Q08426: EHHADH; NbExp=6; IntAct=EBI-1055572, EBI-2339219;
CC P17661; P14136: GFAP; NbExp=6; IntAct=EBI-1055572, EBI-744302;
CC P17661; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-1055572, EBI-5916454;
CC P17661; P42858: HTT; NbExp=9; IntAct=EBI-1055572, EBI-466029;
CC P17661; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-1055572, EBI-1055254;
CC P17661; P13646: KRT13; NbExp=3; IntAct=EBI-1055572, EBI-1223876;
CC P17661; P19012: KRT15; NbExp=3; IntAct=EBI-1055572, EBI-739566;
CC P17661; P35900: KRT20; NbExp=3; IntAct=EBI-1055572, EBI-742094;
CC P17661; Q14525: KRT33B; NbExp=3; IntAct=EBI-1055572, EBI-1049638;
CC P17661; O76014: KRT37; NbExp=3; IntAct=EBI-1055572, EBI-1045716;
CC P17661; O95678: KRT75; NbExp=3; IntAct=EBI-1055572, EBI-2949715;
CC P17661; P52954: LBX1; NbExp=3; IntAct=EBI-1055572, EBI-20141748;
CC P17661; Q96BZ8: LENG1; NbExp=3; IntAct=EBI-1055572, EBI-726510;
CC P17661; P61968: LMO4; NbExp=3; IntAct=EBI-1055572, EBI-2798728;
CC P17661; Q496Y0: LONRF3; NbExp=3; IntAct=EBI-1055572, EBI-2690768;
CC P17661; Q8TC57: M1AP; NbExp=3; IntAct=EBI-1055572, EBI-748182;
CC P17661; P40692: MLH1; NbExp=7; IntAct=EBI-1055572, EBI-744248;
CC P17661; Q13496: MTM1; NbExp=13; IntAct=EBI-1055572, EBI-2864109;
CC P17661; P07196: NEFL; NbExp=7; IntAct=EBI-1055572, EBI-475646;
CC P17661; Q9HC98-4: NEK6; NbExp=3; IntAct=EBI-1055572, EBI-11750983;
CC P17661; O75928-2: PIAS2; NbExp=3; IntAct=EBI-1055572, EBI-348567;
CC P17661; Q8WWB5: PIH1D2; NbExp=3; IntAct=EBI-1055572, EBI-10232538;
CC P17661; P62487: POLR2G; NbExp=3; IntAct=EBI-1055572, EBI-347928;
CC P17661; O60437: PPL; NbExp=3; IntAct=EBI-1055572, EBI-368321;
CC P17661; Q6NYC8: PPP1R18; NbExp=6; IntAct=EBI-1055572, EBI-2557469;
CC P17661; P41219: PRPH; NbExp=6; IntAct=EBI-1055572, EBI-752074;
CC P17661; P78317: RNF4; NbExp=3; IntAct=EBI-1055572, EBI-2340927;
CC P17661; Q15560: TCEA2; NbExp=3; IntAct=EBI-1055572, EBI-710310;
CC P17661; Q9UBB9: TFIP11; NbExp=3; IntAct=EBI-1055572, EBI-1105213;
CC P17661; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-1055572, EBI-10180829;
CC P17661; P08670: VIM; NbExp=6; IntAct=EBI-1055572, EBI-353844;
CC P17661; P07947: YES1; NbExp=3; IntAct=EBI-1055572, EBI-515331;
CC P17661; Q9UJ78-2: ZMYM5; NbExp=3; IntAct=EBI-1055572, EBI-17634549;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, myofibril, sarcomere, Z line
CC {ECO:0000269|PubMed:24200904, ECO:0000269|PubMed:26724190,
CC ECO:0000269|PubMed:30262925}. Cytoplasm {ECO:0000269|PubMed:25394388}.
CC Cell membrane, sarcolemma {ECO:0000269|PubMed:25394388}. Nucleus
CC {ECO:0000250|UniProtKB:P31001}. Note=Localizes in the intercalated
CC disks which occur at the Z line of cardiomyocytes (PubMed:24200904,
CC PubMed:26724190). Localizes in the nucleus exclusively in
CC differentiating cardiac progenitor cells and premature cardiomyocytes
CC (By similarity). {ECO:0000250|UniProtKB:P31001,
CC ECO:0000269|PubMed:24200904, ECO:0000269|PubMed:26724190}.
CC -!- PTM: ADP-ribosylation prevents ability to form intermediate filaments.
CC {ECO:0000250|UniProtKB:P48675}.
CC -!- PTM: Phosphorylation at Ser-7, Ser-28 and Ser-32 by CDK1,
CC phosphorylation at Ser-60 by AURKB and phosphorylation at Thr-76 by
CC ROCK1 contribute to efficient separation of desmin intermediate
CC filaments during mitosis. {ECO:0000250|UniProtKB:P31001}.
CC -!- PTM: Ubiquitination by a SCF-like complex containing ASB2 isoform 1
CC leads to proteasomal degradation. {ECO:0000250|UniProtKB:P31001}.
CC -!- DISEASE: Myopathy, myofibrillar, 1 (MFM1) [MIM:601419]: A form of
CC myofibrillar myopathy, a group of chronic neuromuscular disorders
CC characterized at ultrastructural level by disintegration of the
CC sarcomeric Z disk and myofibrils, and replacement of the normal
CC myofibrillar markings by small dense granules, or larger hyaline
CC masses, or amorphous material. MFM1 is characterized by skeletal muscle
CC weakness associated with cardiac conduction blocks, arrhythmias,
CC restrictive heart failure, and accumulation of desmin-reactive deposits
CC in cardiac and skeletal muscle cells. {ECO:0000269|PubMed:10545598,
CC ECO:0000269|PubMed:10717012, ECO:0000269|PubMed:10905661,
CC ECO:0000269|PubMed:11061256, ECO:0000269|PubMed:11668632,
CC ECO:0000269|PubMed:12620971, ECO:0000269|PubMed:12766977,
CC ECO:0000269|PubMed:14648196, ECO:0000269|PubMed:14711882,
CC ECO:0000269|PubMed:14724127, ECO:0000269|PubMed:15495235,
CC ECO:0000269|PubMed:15800015, ECO:0000269|PubMed:16009553,
CC ECO:0000269|PubMed:16376610, ECO:0000269|PubMed:16865695,
CC ECO:0000269|PubMed:17221859, ECO:0000269|PubMed:18061454,
CC ECO:0000269|PubMed:19879535, ECO:0000269|PubMed:20829228,
CC ECO:0000269|PubMed:22106715, ECO:0000269|PubMed:22395865,
CC ECO:0000269|PubMed:23615443, ECO:0000269|PubMed:23687351,
CC ECO:0000269|PubMed:25394388, ECO:0000269|PubMed:27733623,
CC ECO:0000269|PubMed:28470624, ECO:0000269|PubMed:9697706,
CC ECO:0000269|PubMed:9736733}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. Mutations in the DES gene
CC are associated with a variable clinical phenotype which encompasses
CC isolated myopathies, pure cardiac phenotypes (including dilated
CC cardiomyopathy, restrictive cardiomyopathy and arrhythmogenic right
CC ventricular cardiomyopathy), cardiac conduction disease, and
CC combinations of these disorders. If both cardiologic and neurologic
CC features occur, they can manifest in any order, as cardiologic features
CC can precede, occur simultaneously with, or follow manifestation of
CC generalized neuromuscular disease (PubMed:19879535).
CC {ECO:0000269|PubMed:19879535}.
CC -!- DISEASE: Cardiomyopathy, dilated 1I (CMD1I) [MIM:604765]: A disorder
CC characterized by ventricular dilation and impaired systolic function,
CC resulting in congestive heart failure and arrhythmia. Patients are at
CC risk of premature death. {ECO:0000269|PubMed:10430757,
CC ECO:0000269|PubMed:24200904, ECO:0000269|PubMed:26724190,
CC ECO:0000269|PubMed:30262925}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Neurogenic scapuloperoneal syndrome Kaeser type (Kaeser
CC syndrome) [MIM:181400]: Autosomal dominant disorder with a peculiar
CC scapuloperoneal distribution of weakness and atrophy. A large clinical
CC variability is observed ranging from scapuloperoneal, limb grindle and
CC distal phenotypes with variable cardiac or respiratory involvement.
CC Facial weakness, dysphagia and gynaecomastia are frequent additional
CC symptoms. Affected men seemingly bear a higher risk of sudden, cardiac
CC death as compared to affected women. Histological and
CC immunohistochemical examination of muscle biopsy specimens reveal a
CC wide spectrum of findings ranging from near normal or unspecific
CC pathology to typical, myofibrillar changes with accumulation of desmin.
CC {ECO:0000269|PubMed:17439987, ECO:0000269|PubMed:25394388}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC {ECO:0000255|PROSITE-ProRule:PRU01188}.
CC -!- WEB RESOURCE: Name=Human Intermediate Filament Mutation Database;
CC URL="http://www.interfil.org";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Desmin entry;
CC URL="https://en.wikipedia.org/wiki/Desmin";
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DR EMBL; M63391; AAA99221.1; -; Genomic_DNA.
DR EMBL; U59167; AAC50680.1; -; mRNA.
DR EMBL; AF055081; AAC39938.1; -; mRNA.
DR EMBL; AF055082; AAC39939.1; -; mRNA.
DR EMBL; AF055083; AAC39940.1; -; mRNA.
DR EMBL; AF137053; AAF15400.1; -; mRNA.
DR EMBL; AF486807; AAL93205.1; -; mRNA.
DR EMBL; AF487828; AAL99078.1; -; mRNA.
DR EMBL; AF521879; AAN15036.1; -; mRNA.
DR EMBL; AF527578; AAN37810.1; -; mRNA.
DR EMBL; AY083345; AAL99215.1; -; mRNA.
DR EMBL; AY114212; AAM47026.1; -; Genomic_DNA.
DR EMBL; AY125465; AAM95238.1; -; mRNA.
DR EMBL; BC032116; AAH32116.1; -; mRNA.
DR EMBL; AJ132926; CAB62389.1; -; mRNA.
DR CCDS; CCDS33383.1; -.
DR PIR; JE0063; DMHU.
DR RefSeq; NP_001918.3; NM_001927.3.
DR AlphaFoldDB; P17661; -.
DR SMR; P17661; -.
DR BioGRID; 108038; 131.
DR IntAct; P17661; 64.
DR MINT; P17661; -.
DR STRING; 9606.ENSP00000363071; -.
DR GlyGen; P17661; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P17661; -.
DR PhosphoSitePlus; P17661; -.
DR SwissPalm; P17661; -.
DR BioMuta; DES; -.
DR DMDM; 6686280; -.
DR REPRODUCTION-2DPAGE; IPI00465084; -.
DR REPRODUCTION-2DPAGE; P17661; -.
DR SWISS-2DPAGE; P17661; -.
DR UCD-2DPAGE; P17661; -.
DR EPD; P17661; -.
DR jPOST; P17661; -.
DR MassIVE; P17661; -.
DR PaxDb; P17661; -.
DR PeptideAtlas; P17661; -.
DR PRIDE; P17661; -.
DR ProteomicsDB; 53502; -.
DR ABCD; P17661; 1 sequenced antibody.
DR Antibodypedia; 3503; 1513 antibodies from 53 providers.
DR DNASU; 1674; -.
DR Ensembl; ENST00000373960.4; ENSP00000363071.3; ENSG00000175084.13.
DR GeneID; 1674; -.
DR KEGG; hsa:1674; -.
DR MANE-Select; ENST00000373960.4; ENSP00000363071.3; NM_001927.4; NP_001918.3.
DR CTD; 1674; -.
DR DisGeNET; 1674; -.
DR GeneCards; DES; -.
DR GeneReviews; DES; -.
DR HGNC; HGNC:2770; DES.
DR HPA; ENSG00000175084; Tissue enhanced (heart muscle, skeletal muscle).
DR MalaCards; DES; -.
DR MIM; 125660; gene.
DR MIM; 181400; phenotype.
DR MIM; 601419; phenotype.
DR MIM; 604765; phenotype.
DR neXtProt; NX_P17661; -.
DR OpenTargets; ENSG00000175084; -.
DR Orphanet; 98909; Desminopathy.
DR Orphanet; 154; Familial isolated dilated cardiomyopathy.
DR Orphanet; 85146; Neurogenic scapuloperoneal syndrome, Kaeser type.
DR PharmGKB; PA27253; -.
DR VEuPathDB; HostDB:ENSG00000175084; -.
DR eggNOG; KOG0977; Eukaryota.
DR GeneTree; ENSGT00940000155522; -.
DR HOGENOM; CLU_012560_7_4_1; -.
DR InParanoid; P17661; -.
DR OMA; TMSQSYS; -.
DR OrthoDB; 655109at2759; -.
DR PhylomeDB; P17661; -.
DR TreeFam; TF330122; -.
DR PathwayCommons; P17661; -.
DR Reactome; R-HSA-390522; Striated Muscle Contraction.
DR SignaLink; P17661; -.
DR SIGNOR; P17661; -.
DR BioGRID-ORCS; 1674; 7 hits in 1078 CRISPR screens.
DR ChiTaRS; DES; human.
DR GeneWiki; Desmin; -.
DR GenomeRNAi; 1674; -.
DR Pharos; P17661; Tbio.
DR PRO; PR:P17661; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P17661; protein.
DR Bgee; ENSG00000175084; Expressed in saphenous vein and 194 other tissues.
DR ExpressionAtlas; P17661; baseline and differential.
DR Genevisible; P17661; HS.
DR GO; GO:0097512; C:cardiac myofibril; IDA:CAFA.
DR GO; GO:0005911; C:cell-cell junction; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005916; C:fascia adherens; IEA:Ensembl.
DR GO; GO:0014704; C:intercalated disc; IDA:UniProtKB.
DR GO; GO:0005882; C:intermediate filament; IBA:GO_Central.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; IDA:UniProtKB.
DR GO; GO:0030018; C:Z disc; IDA:UniProtKB.
DR GO; GO:0008092; F:cytoskeletal protein binding; IPI:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; IBA:GO_Central.
DR GO; GO:0007010; P:cytoskeleton organization; TAS:ProtInc.
DR GO; GO:0045109; P:intermediate filament organization; IMP:UniProtKB.
DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc.
DR GO; GO:0008016; P:regulation of heart contraction; TAS:ProtInc.
DR GO; GO:0060538; P:skeletal muscle organ development; IBA:GO_Central.
DR InterPro; IPR018039; IF_conserved.
DR InterPro; IPR039008; IF_rod_dom.
DR InterPro; IPR006821; Intermed_filament_DNA-bd.
DR Pfam; PF00038; Filament; 1.
DR Pfam; PF04732; Filament_head; 1.
DR SMART; SM01391; Filament; 1.
DR PROSITE; PS00226; IF_ROD_1; 1.
DR PROSITE; PS51842; IF_ROD_2; 1.
PE 1: Evidence at protein level;
KW ADP-ribosylation; Cardiomyopathy; Cell membrane; Coiled coil; Cytoplasm;
KW Desmin-related myopathy; Disease variant; Intermediate filament;
KW Limb-girdle muscular dystrophy; Membrane; Methylation; Muscle protein;
KW Myofibrillar myopathy; Nucleus; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P02542"
FT CHAIN 2..470
FT /note="Desmin"
FT /id="PRO_0000063771"
FT DOMAIN 108..416
FT /note="IF rod"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01188"
FT REGION 2..108
FT /note="Head"
FT REGION 109..141
FT /note="Coil 1A"
FT REGION 142..151
FT /note="Linker 1"
FT REGION 152..252
FT /note="Coil 1B"
FT REGION 253..268
FT /note="Linker 12"
FT REGION 268..415
FT /note="Interaction with NEB"
FT /evidence="ECO:0000269|PubMed:23615443"
FT REGION 269..287
FT /note="Coil 2A"
FT REGION 288..295
FT /note="Linker 2"
FT REGION 296..412
FT /note="Coil 2B"
FT REGION 413..470
FT /note="Tail"
FT REGION 438..453
FT /note="Interaction with CRYAB"
FT /evidence="ECO:0000269|PubMed:28470624"
FT MOD_RES 7
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:P31001"
FT MOD_RES 12
FT /note="Phosphoserine; by AURKB"
FT /evidence="ECO:0000269|PubMed:12686604"
FT MOD_RES 16
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P31001"
FT MOD_RES 17
FT /note="Phosphothreonine; by AURKB and ROCK1"
FT /evidence="ECO:0000269|PubMed:12686604,
FT ECO:0000269|PubMed:9875213"
FT MOD_RES 28
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:24413773,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 31
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31001"
FT MOD_RES 32
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000269|PubMed:24413773,
FT ECO:0000269|PubMed:27565725"
FT MOD_RES 37
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P31001"
FT MOD_RES 37
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P31001"
FT MOD_RES 45
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48675"
FT MOD_RES 58
FT /note="ADP-ribosylarginine"
FT /evidence="ECO:0000250|UniProtKB:P48675"
FT MOD_RES 60
FT /note="Phosphoserine; by AURKB"
FT /evidence="ECO:0000269|PubMed:12686604"
FT MOD_RES 68
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31001"
FT MOD_RES 70
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P31001"
FT MOD_RES 76
FT /note="Phosphothreonine; by ROCK1"
FT /evidence="ECO:0000269|PubMed:9875213"
FT MOD_RES 77
FT /note="Phosphothreonine; by ROCK1"
FT /evidence="ECO:0000269|PubMed:9875213"
FT MOD_RES 81
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48675"
FT MOD_RES 290
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48675"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48675"
FT MOD_RES 361
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48675"
FT MOD_RES 424
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31001"
FT VARIANT 2
FT /note="S -> I (in MFM1; dbSNP:rs58999456)"
FT /evidence="ECO:0000269|PubMed:14711882"
FT /id="VAR_042448"
FT VARIANT 7
FT /note="S -> F (in MFM1; dbSNP:rs903985237)"
FT /evidence="ECO:0000269|PubMed:22106715"
FT /id="VAR_067207"
FT VARIANT 13
FT /note="S -> F (in MFM1; some patients manifest a severe
FT cardiac phenotype with right ventricular predominance;
FT dbSNP:rs62636495)"
FT /evidence="ECO:0000269|PubMed:18061454,
FT ECO:0000269|PubMed:19879535"
FT /id="VAR_067208"
FT VARIANT 16
FT /note="R -> C (in MFM1; dbSNP:rs60798368)"
FT /evidence="ECO:0000269|PubMed:16376610"
FT /id="VAR_079048"
FT VARIANT 46
FT /note="S -> F (in MFM1; exhibits significantly delayed
FT filament assembly kinetics when bound to NEB; enhanced
FT binding affinity towards NEB; dbSNP:rs60794845)"
FT /evidence="ECO:0000269|PubMed:14711882,
FT ECO:0000269|PubMed:23615443"
FT /id="VAR_042449"
FT VARIANT 46
FT /note="S -> Y (in MFM1; dbSNP:rs60794845)"
FT /evidence="ECO:0000269|PubMed:14711882"
FT /id="VAR_042450"
FT VARIANT 116
FT /note="N -> S (in MFM1; the clinical picture is dominated
FT by arrhythmogenic right ventricular cardiomyopathy and
FT terminal heart failure; results in impaired filaments
FT formation; dbSNP:rs267607499)"
FT /evidence="ECO:0000269|PubMed:20829228"
FT /id="VAR_069191"
FT VARIANT 120
FT /note="A -> D (in CMD1I; results in impaired filaments
FT formation, does not localize at intercalated disks)"
FT /evidence="ECO:0000269|PubMed:24200904"
FT /id="VAR_075228"
FT VARIANT 136
FT /note="L -> P (in CMD1I; results in impaired filaments
FT formation, does not localize at intercalated disks;
FT dbSNP:rs397516695)"
FT /evidence="ECO:0000269|PubMed:26724190"
FT /id="VAR_075229"
FT VARIANT 173..179
FT /note="Missing (in MFM1; severe form)"
FT /evidence="ECO:0000269|PubMed:9736733"
FT /id="VAR_009188"
FT VARIANT 213
FT /note="A -> V (may play a role in cardiomyopathies and
FT distal myopathies if combined with other DES mutations or
FT mutations in other genes; does not affect the formation of
FT a normal complete filamentous network; dbSNP:rs41272699)"
FT /evidence="ECO:0000269|PubMed:14648196,
FT ECO:0000269|PubMed:16865695, ECO:0000269|PubMed:21842594,
FT ECO:0000269|PubMed:23168288"
FT /id="VAR_042451"
FT VARIANT 240
FT /note="Missing (in MFM1; the mutant cannot form de novo
FT desmin intermediate filaments causing disruption of the
FT endogenous intermediate filament network and formation of
FT pathologic aggregates)"
FT /evidence="ECO:0000269|PubMed:12620971"
FT /id="VAR_070101"
FT VARIANT 241
FT /note="K -> E (found in a patient with severe
FT arrhythmogenic right ventricular cardiomyopathy also
FT carrying a pathogenic frameshift mutation in PKP2;
FT dbSNP:rs201945924)"
FT /evidence="ECO:0000269|PubMed:23168288"
FT /id="VAR_069192"
FT VARIANT 245
FT /note="E -> D (in MFM1; exhibits significantly delayed
FT filament assembly kinetics when bound to NEB and NEBL;
FT enhanced binding affinity towards NEB and NEBL;
FT dbSNP:rs267607486)"
FT /evidence="ECO:0000269|PubMed:23615443"
FT /id="VAR_042452"
FT VARIANT 326
FT /note="H -> R (in CMD1I; unknown pathological significance;
FT does not affect filaments formation)"
FT /evidence="ECO:0000269|PubMed:24200904"
FT /id="VAR_075230"
FT VARIANT 337
FT /note="A -> P (in MFM1; mild adult-onset; unable to form a
FT functional filamentous network; dbSNP:rs59962885)"
FT /evidence="ECO:0000269|PubMed:10717012,
FT ECO:0000269|PubMed:9697706"
FT /id="VAR_007900"
FT VARIANT 338
FT /note="L -> R (in MFM1; results in the formation of a
FT filamentous network disrupted by multiple breaks and clumps
FT or large aggregates; dbSNP:rs57496341)"
FT /evidence="ECO:0000269|PubMed:16865695"
FT /id="VAR_067209"
FT VARIANT 342
FT /note="N -> D (in MFM1; unable to form a filamentous
FT network; abolishes binding to MTM1; dbSNP:rs267607482)"
FT /evidence="ECO:0000269|PubMed:10717012,
FT ECO:0000269|PubMed:14648196, ECO:0000269|PubMed:21135508"
FT /id="VAR_042453"
FT VARIANT 345
FT /note="L -> P (in MFM1; distal onset; incapable of forming
FT filamentous networks; dbSNP:rs57639980)"
FT /evidence="ECO:0000269|PubMed:10545598"
FT /id="VAR_009189"
FT VARIANT 350
FT /note="R -> P (in Kaeser syndrome and MFM1; incapable of de
FT novo formation of a desmin intermediate filaments network;
FT exerts a dominant negative effect on the ordered lateral
FT arrangement of desmin subunits; may produce structural
FT changes; forms subsarcolemmal aggregates;
FT dbSNP:rs57965306)"
FT /evidence="ECO:0000269|PubMed:15800015,
FT ECO:0000269|PubMed:17439987, ECO:0000269|PubMed:25394388"
FT /id="VAR_042454"
FT VARIANT 355
FT /note="R -> P (in MFM1; dbSNP:rs61368398)"
FT /evidence="ECO:0000269|PubMed:16009553"
FT /id="VAR_042455"
FT VARIANT 357
FT /note="A -> P (in MFM1; unable to polymerize and form an
FT intracellular filamentous network; abolishes binding to
FT MTM1; dbSNP:rs58898021)"
FT /evidence="ECO:0000269|PubMed:12766977,
FT ECO:0000269|PubMed:14648196, ECO:0000269|PubMed:21135508"
FT /id="VAR_042456"
FT VARIANT 359..361
FT /note="Missing (in MFM1)"
FT /evidence="ECO:0000269|PubMed:14648196"
FT /id="VAR_018769"
FT VARIANT 360
FT /note="A -> P (in MFM1; heterozygous with I-393 gives a
FT severe childhood-onset; unable to form a functional
FT filamentous network in the presence of I-393; abolishes
FT binding to MTM1; dbSNP:rs121913000)"
FT /evidence="ECO:0000269|PubMed:10717012,
FT ECO:0000269|PubMed:16865695, ECO:0000269|PubMed:21135508,
FT ECO:0000269|PubMed:9697706"
FT /id="VAR_007901"
FT VARIANT 366
FT /note="Missing (in MFM1)"
FT /evidence="ECO:0000269|PubMed:14648196"
FT /id="VAR_018770"
FT VARIANT 370
FT /note="L -> P (in MFM1; unable to polymerize and form an
FT intracellular filamentous network; does not affect binding
FT to MTM1; dbSNP:rs59308628)"
FT /evidence="ECO:0000269|PubMed:12766977,
FT ECO:0000269|PubMed:14648196, ECO:0000269|PubMed:21135508"
FT /id="VAR_042457"
FT VARIANT 385
FT /note="L -> P (in MFM1; dbSNP:rs57955682)"
FT /evidence="ECO:0000269|PubMed:11061256"
FT /id="VAR_018771"
FT VARIANT 389
FT /note="Q -> P (in MFM1; dbSNP:rs121913004)"
FT /evidence="ECO:0000269|PubMed:11668632"
FT /id="VAR_018772"
FT VARIANT 393
FT /note="N -> I (in MFM1; heterozygous with P-360 gives a
FT severe childhood-onset; filamentous network is not affected
FT however several spots indicate focal disorganization;
FT dbSNP:rs121913001)"
FT /evidence="ECO:0000269|PubMed:10717012,
FT ECO:0000269|PubMed:16865695, ECO:0000269|PubMed:9697706"
FT /id="VAR_007902"
FT VARIANT 398
FT /note="L -> P (in CMD1I; unknown pathological significance;
FT impaired subcellular localization)"
FT /evidence="ECO:0000269|PubMed:30262925"
FT /id="VAR_086534"
FT VARIANT 399
FT /note="D -> Y (in MFM1; results in the formation of a
FT filamentous network disrupted by multiple breaks and clumps
FT or large aggregates; dbSNP:rs61130669)"
FT /evidence="ECO:0000269|PubMed:16865695"
FT /id="VAR_067210"
FT VARIANT 401
FT /note="E -> K (in MFM1; results in the formation of a
FT filamentous network disrupted by multiple breaks and clumps
FT or large aggregates; dbSNP:rs57694264)"
FT /evidence="ECO:0000269|PubMed:16865695"
FT /id="VAR_067211"
FT VARIANT 406
FT /note="R -> W (in MFM1; unable to form a filamentous
FT network; dbSNP:rs121913003)"
FT /evidence="ECO:0000269|PubMed:10717012,
FT ECO:0000269|PubMed:10905661, ECO:0000269|PubMed:16376610"
FT /id="VAR_042458"
FT VARIANT 419
FT /note="P -> S (in MFM1; found in a family with myofibrillar
FT myopathy and arrhythmogenic right ventricular
FT cardiomyopathy; dbSNP:rs62635763)"
FT /evidence="ECO:0000269|PubMed:22395865"
FT /id="VAR_069074"
FT VARIANT 442
FT /note="T -> I (in MFM1; reveals a severe disturbance of
FT filament-formation competence and filament-filament
FT interactions; dbSNP:rs121913005)"
FT /evidence="ECO:0000269|PubMed:17221859"
FT /id="VAR_042459"
FT VARIANT 449
FT /note="K -> M (in MFM1)"
FT /id="VAR_042460"
FT VARIANT 449
FT /note="K -> T (in MFM1; dbSNP:rs267607485)"
FT /evidence="ECO:0000269|PubMed:14711882"
FT /id="VAR_042461"
FT VARIANT 451
FT /note="I -> M (in CMD1I and MFM1; reveals a severe
FT disturbance of filament-formation competence and filament-
FT filament interactions; reduced interaction with CRYAB;
FT dbSNP:rs121913002)"
FT /evidence="ECO:0000269|PubMed:10430757,
FT ECO:0000269|PubMed:10717012, ECO:0000269|PubMed:17221859,
FT ECO:0000269|PubMed:28470624"
FT /id="VAR_018773"
FT VARIANT 453
FT /note="T -> I (in MFM1; exhibits significantly delayed
FT filament assembly kinetics when bound to NEB and NEBL;
FT enhanced binding affinity towards NEB and NEBL;
FT dbSNP:rs267607488)"
FT /evidence="ECO:0000269|PubMed:16376610,
FT ECO:0000269|PubMed:23615443"
FT /id="VAR_079049"
FT VARIANT 454
FT /note="R -> W (in MFM1; reveals a severe disturbance of
FT filament-formation competence and filament-filament
FT interactions; increased interaction with CRYAB;
FT dbSNP:rs267607490)"
FT /evidence="ECO:0000269|PubMed:17221859,
FT ECO:0000269|PubMed:22106715, ECO:0000269|PubMed:28470624"
FT /id="VAR_042462"
FT VARIANT 460
FT /note="S -> I (in MFM1; reveals a severe disturbance of
FT filament-formation competence and filament-filament
FT interactions; dbSNP:rs267607491)"
FT /evidence="ECO:0000269|PubMed:17221859"
FT /id="VAR_042463"
FT MUTAGEN 120
FT /note="A->E,R: Results in impaired filaments formation."
FT /evidence="ECO:0000269|PubMed:24200904"
FT MUTAGEN 120
FT /note="A->K,L,V: Does not result in impaired filaments
FT formation."
FT /evidence="ECO:0000269|PubMed:24200904"
FT CONFLICT 23..25
FT /note="GFP -> VFS (in Ref. 1 and 2; AAA99221)"
FT /evidence="ECO:0000305"
FT CONFLICT 39
FT /note="G -> P (in Ref. 1 and 2; AAA99221)"
FT /evidence="ECO:0000305"
FT CONFLICT 119..123
FT /note="FANYI -> SPIYM (in Ref. 1 and 2; AAA99221)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="Missing (in Ref. 1, 2; AAA99221 and 3; AAC50680)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 470 AA; 53536 MW; 1B5D9EA93C3BB319 CRC64;
MSQAYSSSQR VSSYRRTFGG APGFPLGSPL SSPVFPRAGF GSKGSSSSVT SRVYQVSRTS
GGAGGLGSLR ASRLGTTRTP SSYGAGELLD FSLADAVNQE FLTTRTNEKV ELQELNDRFA
NYIEKVRFLE QQNAALAAEV NRLKGREPTR VAELYEEELR ELRRQVEVLT NQRARVDVER
DNLLDDLQRL KAKLQEEIQL KEEAENNLAA FRADVDAATL ARIDLERRIE SLNEEIAFLK
KVHEEEIREL QAQLQEQQVQ VEMDMSKPDL TAALRDIRAQ YETIAAKNIS EAEEWYKSKV
SDLTQAANKN NDALRQAKQE MMEYRHQIQS YTCEIDALKG TNDSLMRQMR ELEDRFASEA
SGYQDNIARL EEEIRHLKDE MARHLREYQD LLNVKMALDV EIATYRKLLE GEESRINLPI
QTYSALNFRE TSPEQRGSEV HTKKTVMIKT IETRDGEVVS EATQQQHEVL
