DYSF_HUMAN
ID DYSF_HUMAN Reviewed; 2080 AA.
AC O75923; A0FK00; B1PZ70; B1PZ71; B1PZ72; B1PZ73; B1PZ74; B1PZ75; B1PZ76;
AC B1PZ77; B1PZ78; B1PZ79; B1PZ80; B1PZ81; B3KQB9; O75696; Q09EX5; Q0H395;
AC Q53QY3; Q53TD2; Q8TEL8; Q9UEN7;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Dysferlin;
DE AltName: Full=Dystrophy-associated fer-1-like protein;
DE AltName: Full=Fer-1-like protein 1;
GN Name=DYSF; Synonyms=FER1L1;
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 [MRNA] (ISOFORM 1), VARIANTS MMD1 VAL-1298; ARG-1857
RP AND CYS-2042, AND VARIANTS LGMDR2 VAL-1298 AND CYS-2042.
RC TISSUE=Skeletal muscle;
RX PubMed=9731526; DOI=10.1038/1682;
RA Liu J., Aoki M., Illa I., Wu C., Fardeau M., Angelini C., Serrano C.,
RA Urtizberea J.A., Hentati F., Hamida M.B., Bohlega S., Culper E.J.,
RA Amato A.A., Bossie K., Oeltjen J., Bejaoui K., McKenna-Yasek D.,
RA Hosler B.A., Schurr E., Arahata K., de Jong P.J., Brown R.H. Jr.;
RT "Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy
RT and limb girdle muscular dystrophy.";
RL Nat. Genet. 20:31-36(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 14), AND TISSUE SPECIFICITY.
RX PubMed=16896923; DOI=10.1007/s00439-006-0230-1;
RA Pramono Z.A.D., Lai P.S., Tan C.L., Takeda S., Yee W.C.;
RT "Identification and characterization of a novel human dysferlin transcript:
RT dysferlin_v1.";
RL Hum. Genet. 120:410-419(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 2; 3; 4; 5; 6; 7; 8; 9;
RP 10; 11; 12 AND 13), ALTERNATIVE PROMOTER USAGE, AND ALTERNATIVE SPLICING.
RX PubMed=19221801; DOI=10.1007/s00439-009-0632-y;
RA Pramono Z.A., Tan C.L., Seah I.A., See J.S., Kam S.Y., Lai P.S., Yee W.C.;
RT "Identification and characterisation of human dysferlin transcript
RT variants: implications for dysferlin mutational screening and isoforms.";
RL Hum. Genet. 125:413-420(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 569-2080 (ISOFORMS 1/2/3/5/8/9/11), AND
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1471-1628 (ISOFORMS 1/2/3/5/8/9/11).
RC TISSUE=Placenta, and Skeletal muscle;
RX PubMed=9731527; DOI=10.1038/1689;
RA Bashir R., Britton S., Strachan T., Keers S., Vafiadaki E., Lako M.,
RA Richard I., Marchand S., Bourg N., Argov Z., Sadeh M., Mahjneh I.,
RA Marconi G., Passos-Bueno M.R., de Sa Moreira E., Zatz M., Beckmann J.S.,
RA Bushby K.M.D.;
RT "A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is
RT mutated in limb-girdle muscular dystrophy type 2B.";
RL Nat. Genet. 20:37-42(1998).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 439-2080 (ISOFORM 15).
RC TISSUE=Spleen;
RA Jikuya H., Takano J., Nomura N., Kikuno R., Nagase T., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human spleen.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1497-2080 (ISOFORMS
RP 1/2/3/4/5/6/7/8/9/10/11/12/13/14).
RC TISSUE=Mammary gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [9]
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=10196375; DOI=10.1093/hmg/8.5.855;
RA Anderson L.V.B., Davison K., Moss J.A., Young C., Cullen M.J., Walsh J.,
RA Johnson M.A., Bashir R., Britton S., Keers S., Argov Z., Mahjneh I.,
RA Fougerousse F., Beckmann J.S., Bushby K.M.D.;
RT "Dysferlin is a plasma membrane protein and is expressed early in human
RT development.";
RL Hum. Mol. Genet. 8:855-861(1999).
RN [10]
RP ERRATUM OF PUBMED:10196375.
RA Anderson L.V.B., Davison K., Moss J.A., Young C., Cullen M.J., Walsh J.,
RA Johnson M.A., Bashir R., Britton S., Keers S., Argov Z., Mahjneh I.,
RA Fougerousse F., Beckmann J.S., Bushby K.M.D.;
RL Hum. Mol. Genet. 8:1141-1141(1999).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=10496277; DOI=10.1212/wnl.53.5.1119;
RA Matsuda C., Aoki M., Hayashi Y.K., Ho M.F., Arahata K., Brown R.H. Jr.;
RT "Dysferlin is a surface membrane-associated protein that is absent in
RT Miyoshi myopathy.";
RL Neurology 53:1119-1122(1999).
RN [12]
RP SUBCELLULAR LOCATION, VARIANT MMD1 ARG-791, AND VARIANT LGMDR2 ARG-791.
RX PubMed=10196377; DOI=10.1093/hmg/8.5.871;
RA Weiler T., Bashir R., Anderson L.V.B., Davison K., Moss J.A., Britton S.,
RA Nylen E., Keers S., Vafiadaki E., Greenberg C.R., Bushby K.M.D.,
RA Wrogemann K.;
RT "Identical mutation in patients with limb girdle muscular dystrophy type 2B
RT or Miyoshi myopathy suggests a role for modifier gene(s).";
RL Hum. Mol. Genet. 8:871-877(1999).
RN [13]
RP INVOLVEMENT IN DMAT.
RX PubMed=11198284;
RX DOI=10.1002/1531-8249(200101)49:1<130::aid-ana22>3.0.co;2-0;
RA Illa I., Serrano-Munuera C., Gallardo E., Lasa A., Rojas-Garcia R.,
RA Palmer J., Gallano P., Baiget M., Matsuda C., Brown R.H.;
RT "Distal anterior compartment myopathy: a dysferlin mutation causing a new
RT muscular dystrophy phenotype.";
RL Ann. Neurol. 49:130-134(2001).
RN [14]
RP INTERACTION WITH CAV3, AND TISSUE SPECIFICITY.
RX PubMed=11532985; DOI=10.1093/hmg/10.17.1761;
RA Matsuda C., Hayashi Y.K., Ogawa M., Aoki M., Murayama K., Nishino I.,
RA Nonaka I., Arahata K., Brown R.H. Jr.;
RT "The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal
RT muscle.";
RL Hum. Mol. Genet. 10:1761-1766(2001).
RN [15]
RP TISSUE SPECIFICITY, AND CHARACTERIZATION OF VARIANT MMD1 ASP-67.
RX PubMed=11959863; DOI=10.1074/jbc.m201858200;
RA Davis D.B., Doherty K.R., Delmonte A.J., McNally E.M.;
RT "Calcium-sensitive phospholipid binding properties of normal and mutant
RT ferlin C2 domains.";
RL J. Biol. Chem. 277:22883-22888(2002).
RN [16]
RP TISSUE SPECIFICITY.
RX PubMed=15318348; DOI=10.1002/mus.20106;
RA Salani S., Lucchiari S., Fortunato F., Crimi M., Corti S., Locatelli F.,
RA Bossolasco P., Bresolin N., Comi G.P.;
RT "Developmental and tissue-specific regulation of a novel dysferlin
RT isoform.";
RL Muscle Nerve 30:366-374(2004).
RN [17]
RP INTERACTION WITH PARVB, AND SUBCELLULAR LOCATION.
RX PubMed=15835269; DOI=10.1093/jnen/64.4.334;
RA Matsuda C., Kameyama K., Tagawa K., Ogawa M., Suzuki A., Yamaji S.,
RA Okamoto H., Nishino I., Hayashi Y.K.;
RT "Dysferlin interacts with affixin (beta-parvin) at the sarcolemma.";
RL J. Neuropathol. Exp. Neurol. 64:334-340(2005).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=17554076; DOI=10.1095/biolreprod.107.062190;
RA Vandre D.D., Ackerman W.E., Kniss D.A., Tewari A.K., Mori M., Takizawa T.,
RA Robinson J.M.;
RT "Dysferlin is expressed in human placenta but does not associate with
RT caveolin.";
RL Biol. Reprod. 77:533-542(2007).
RN [19]
RP INTERACTION WITH AHNAK AND AHNAK2, SUBCELLULAR LOCATION, CHARACTERIZATION
RP OF VARIANT LGMDR2 ASP-67, TISSUE SPECIFICITY, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=17185750; DOI=10.1096/fj.06-6628com;
RA Huang Y., Laval S.H., van Remoortere A., Baudier J., Benaud C.,
RA Anderson L.V., Straub V., Deelder A., Frants R.R., den Dunnen J.T.,
RA Bushby K., van der Maarel S.M.;
RT "AHNAK, a novel component of the dysferlin protein complex, redistributes
RT to the cytoplasm with dysferlin during skeletal muscle regeneration.";
RL FASEB J. 21:732-742(2007).
RN [20]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17363620; DOI=10.1096/fj.06-7659com;
RA Klinge L., Laval S., Keers S., Haldane F., Straub V., Barresi R.,
RA Bushby K.;
RT "From T-tubule to sarcolemma: damage-induced dysferlin translocation in
RT early myogenesis.";
RL FASEB J. 21:1768-1776(2007).
RN [21]
RP INVOLVEMENT IN LGMDR2.
RX PubMed=19084402; DOI=10.1016/j.nmd.2008.09.015;
RA Paradas C., Gonzalez-Quereda L., De Luna N., Gallardo E.,
RA Garcia-Consuegra I., Gomez H., Cabello A., Illa I., Gallano P.;
RT "A new phenotype of dysferlinopathy with congenital onset.";
RL Neuromuscul. Disord. 19:21-25(2009).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [23]
RP DOMAIN C2, CALCIUM-BINDING, AND MUTAGENESIS OF ASP-16; ASP-21; ASP-71;
RP ARG-79 AND PHE-80.
RX PubMed=24461013; DOI=10.1016/j.bpj.2013.11.4492;
RA Abdullah N., Padmanarayana M., Marty N.J., Johnson C.P.;
RT "Quantitation of the calcium and membrane binding properties of the c2
RT domains of dysferlin.";
RL Biophys. J. 106:382-389(2014).
RN [24]
RP INTERACTION WITH RIPOR2.
RX PubMed=24687993; DOI=10.1096/fj.13-246470;
RA Balasubramanian A., Kawahara G., Gupta V.A., Rozkalne A., Beauvais A.,
RA Kunkel L.M., Gussoni E.;
RT "Fam65b is important for formation of the HDAC6-dysferlin protein complex
RT during myogenic cell differentiation.";
RL FASEB J. 28:2955-2969(2014).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-166, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-167 AND THR-198 (ISOFORMS 11; 13 AND 8),
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166 AND THR-197 (ISOFORMS 2;
RP 5 AND 7), AND IDENTIFICATION BY 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 [26]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 942-1052.
RX PubMed=24438169; DOI=10.1186/1472-6807-14-3;
RA Sula A., Cole A.R., Yeats C., Orengo C., Keep N.H.;
RT "Crystal structures of the human Dysferlin inner DysF domain.";
RL BMC Struct. Biol. 14:3-3(2014).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (1.76 ANGSTROMS) OF 1-124 IN COMPLEX WITH CALCIUM,
RP CALCIUM-BINDING (ISOFORMS 1 AND 14), SUBCELLULAR LOCATION, DOMAIN,
RP LIPID-BINDING, AND TISSUE SPECIFICITY.
RX PubMed=24239457; DOI=10.1016/j.str.2013.10.001;
RA Fuson K., Rice A., Mahling R., Snow A., Nayak K., Shanbhogue P.,
RA Meyer A.G., Redpath G.M., Hinderliter A., Cooper S.T., Sutton R.B.;
RT "Alternate splicing of dysferlin C2A confers Ca(2+)-dependent and Ca(2+)-
RT independent binding for membrane repair.";
RL Structure 22:104-115(2014).
RN [28]
RP VARIANT MMD1 CYS-999.
RA Matsumura T., Aoki M., Nagano A., Hayashi Y.K., Asada C., Ogawa M.,
RA Yamanaka G., Goto K., Nakagawa M., Oka H., Sahashi K., Kouhara N.,
RA Saito Y., Brown R.H. Jr., Nonaka I., Arahata K.;
RT "Molecular genetic analysis of dysferlin in Japanese patients with Miyoshi
RT myopathy.";
RL Proc. Jpn. Acad. 75B:207-212(1999).
RN [29]
RP VARIANT MMD1 ASP-67, AND VARIANT LGMDR2 ASP-67.
RX PubMed=11134403; DOI=10.1212/wnl.55.12.1931;
RA Illarioshkin S.N., Ivanova-Smolenskaya I.A., Greenberg C.R., Nylen E.,
RA Sukhorukov V.S., Poleshchuk V.V., Markova E.D., Wrogemann K.;
RT "Identical dysferlin mutation in limb-girdle muscular dystrophy type 2B and
RT distal myopathy.";
RL Neurology 55:1931-1933(2000).
RN [30]
RP VARIANTS MMD1 HIS-1046 AND GLN-2000.
RX PubMed=11468312; DOI=10.1212/wnl.57.2.271;
RA Aoki M., Liu J., Richard I., Bashir R., Britton S., Keers S.M., Oeltjen J.,
RA Brown H.E.V., Marchand S., Bourg N., Beley C., McKenna-Yasek D.,
RA Arahata K., Bohlega S., Cupler E., Illa I., Majneh I., Barohn R.J.,
RA Urtizberea J.A., Fardeau M., Amato A., Angelini C., Bushby K.,
RA Beckmann J.S., Brown R.H. Jr.;
RT "Genomic organization of the dysferlin gene and novel mutations in Miyoshi
RT myopathy.";
RL Neurology 57:271-278(2001).
RN [31]
RP VARIANTS MMD1 CYS-999 AND GLU-1679, AND VARIANT HIS-1581.
RX PubMed=12796534; DOI=10.1212/01.wnl.0000068333.43005.12;
RA Takahashi T., Aoki M., Tateyama M., Kondo E., Mizuno T., Onodera Y.,
RA Takano R., Kawai H., Kamakura K., Mochizuki H., Shizuka-Ikeda M.,
RA Nakagawa M., Yoshida Y., Akanuma J., Hoshino K., Saito H., Nishizawa M.,
RA Kato S., Saito K., Miyachi T., Yamashita H., Kawai M., Matsumura T.,
RA Kuzuhara S., Ibi T., Sahashi K., Nakai H., Kohnosu T., Nonaka I.,
RA Arahata K., Brown R.H. Jr., Saito H., Itoyama Y.;
RT "Dysferlin mutations in Japanese Miyoshi myopathy: relationship to
RT phenotype.";
RL Neurology 60:1799-1804(2003).
RN [32]
RP VARIANTS LGMDR2 TRP-959; GLN-1038 AND LYS-1335, AND VARIANTS GLN-1022;
RP ALA-GLU-1065 INS AND LEU-1331.
RX PubMed=14678801; DOI=10.1016/s0960-8966(03)00133-0;
RA Cagliani R., Fortunato F., Giorda R., Rodolico C., Bonaglia M.C.,
RA Sironi M., D'Angelo M.G., Prelle A., Locatelli F., Toscano A., Bresolin N.,
RA Comi G.P.;
RT "Molecular analysis of LGMD-2B and MM patients: identification of novel
RT DYSF mutations and possible founder effect in the Italian population.";
RL Neuromuscul. Disord. 13:788-795(2003).
RN [33]
RP VARIANTS MMD1 VAL-426 AND LEU-2068.
RX PubMed=15477515; DOI=10.1001/archneur.61.10.1594;
RA Ro L.-S., Lee-Chen G.-J., Lin T.-C., Wu Y.-R., Chen C.-M., Lin C.-Y.,
RA Chen S.-T.;
RT "Phenotypic features and genetic findings in 2 Chinese families with
RT Miyoshi distal myopathy.";
RL Arch. Neurol. 61:1594-1599(2004).
RN [34]
RP VARIANTS MMD1 ARG-618; CYS-1041; LYS-1335; ARG-1361 AND ARG-1662, VARIANTS
RP LGMDR2 LYS-1335 AND CYS-1505, AND VARIANTS GLN-1022 AND ALA-GLU-1065 INS.
RX PubMed=15469449; DOI=10.1111/j.1468-1331.2004.00755.x;
RA Kawabe K., Goto K., Nishino I., Angelini C., Hayashi Y.K.;
RT "Dysferlin mutation analysis in a group of Italian patients with limb-
RT girdle muscular dystrophy and Miyoshi myopathy.";
RL Eur. J. Neurol. 11:657-661(2004).
RN [35]
RP VARIANTS MMD1 ASP-1842 AND PRO-1922.
RX PubMed=15116377; DOI=10.1002/mus.20025;
RA Suzuki N., Aoki M., Takahashi T., Takano D., Asano M., Shiga Y.,
RA Onodera Y., Tateyama M., Itoyama Y.;
RT "Novel dysferlin mutations and characteristic muscle atrophy in late-onset
RT Miyoshi myopathy.";
RL Muscle Nerve 29:721-723(2004).
RN [36]
RP VARIANT MMD1 GLN-389.
RX PubMed=15515206; DOI=10.3349/ymj.2004.45.5.927;
RA Oh S.-H., Kim T.-S., Choi Y.-C.;
RT "Identification of a dysferlin gene mutation in a Korean case with Miyoshi
RT myopathy.";
RL Yonsei Med. J. 45:927-930(2004).
RN [37]
RP VARIANTS GLU-170 AND TRP-253, VARIANTS LGMDR2 TRP-555 AND MET-1208,
RP VARIANTS MMD1 GLU-299; TRP-456; TRP-555; HIS-1046 AND GLN-1693, VARIANT
RP PROXIMODISTAL MYOPATHY VAL-1276, VARIANT PSEUDOMETABOLIC MYOPATHY PRO-266,
RP AND VARIANTS VAL-189; LEU-1331; SER-1351 AND VAL-1748.
RX PubMed=16010686; DOI=10.1002/humu.9355;
RA Nguyen K., Bassez G., Bernard R., Krahn M., Labelle V.,
RA Figarella-Branger D., Pouget J., Hammouda el H., Beroud C., Urtizberea A.,
RA Eymard B., Leturcq F., Ben-Yaou R., Levy N.;
RT "Dysferlin mutations in LGMD2B, Miyoshi myopathy, and atypical
RT dysferlinopathies.";
RL Hum. Mutat. 26:165-165(2005).
RN [38]
RP ERRATUM OF PUBMED:16010686.
RX DOI=10.1002/humu.9388;
RA Nguyen K., Bassez G., Bernard R., Krahn M., Labelle V.,
RA Figarella-Branger D., Pouget J., Hammouda el H., Beroud C., Urtizberea A.,
RA Eymard B., Leturcq F., Levy N.;
RL Hum. Mutat. 26:592-592(2005).
RN [39]
RP VARIANTS MMD1 TRP-959; TRP-1693; ASN-1837 AND GLY-1942 AND CYS-2042,
RP VARIANTS LGMDR2 ARG-621; TRP-959; GLN-1038; LYS-1335 AND CYS-2042, AND
RP VARIANTS GLU-170; LEU-374 AND SER-1678.
RX PubMed=16100712; DOI=10.1002/humu.9364;
RA Cagliani R., Magri F., Toscano A., Merlini L., Fortunato F., Lamperti C.,
RA Rodolico C., Prelle A., Sironi M., Aguennouz M., Ciscato P., Uncini A.,
RA Moggio M., Bresolin N., Comi G.P.;
RT "Mutation finding in patients with dysferlin deficiency and role of the
RT dysferlin interacting proteins annexin A1 and A2 in muscular dystrophies.";
RL Hum. Mutat. 26:283-283(2005).
RN [40]
RP VARIANTS LGMDR2 ARG-299 AND PRO-1341.
RX PubMed=16705711; DOI=10.1002/humu.9424;
RA Wenzel K., Carl M., Perrot A., Zabojszcza J., Assadi M., Ebeling M.,
RA Geier C., Robinson P.N., Kress W., Osterziel K.-J., Spuler S.;
RT "Novel sequence variants in dysferlin-deficient muscular dystrophy leading
RT to mRNA decay and possible C2-domain misfolding.";
RL Hum. Mutat. 27:599-600(2006).
RN [41]
RP VARIANTS LGMDR2 ARG-791; CYS-930; TRP-1768 AND CYS-2042, AND VARIANT
RP ALA-GLU-1065 INS.
RX PubMed=16996541; DOI=10.1016/j.jns.2006.07.004;
RA Therrien C., Dodig D., Karpati G., Sinnreich M.;
RT "Mutation impact on dysferlin inferred from database analysis and computer-
RT based structural predictions.";
RL J. Neurol. Sci. 250:71-78(2006).
RN [42]
RP VARIANTS [LARGE SCALE ANALYSIS] MET-1325 AND VAL-1349.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [43]
RP VARIANTS LGMDR2 TYR-625 AND GLY-1734, AND VARIANT MMD1 ARG-519.
RX PubMed=17287450; DOI=10.1212/01.wnl.0000256768.79353.60;
RA Illa I., De Luna N., Dominguez-Perles R., Rojas-Garcia R., Paradas C.,
RA Palmer J., Marquez C., Gallano P., Gallardo E.;
RT "Symptomatic dysferlin gene mutation carriers: characterization of two
RT cases.";
RL Neurology 68:1284-1289(2007).
RN [44]
RP VARIANT LGMDR2 ARG-299, AND VARIANT MMD1 TRP-299.
RX PubMed=18306167; DOI=10.1002/ana.21309;
RA Spuler S., Carl M., Zabojszcza J., Straub V., Bushby K., Moore S.A.,
RA Baehring S., Wenzel K., Vinkemeier U., Rocken C.;
RT "Dysferlin-deficient muscular dystrophy features amyloidosis.";
RL Ann. Neurol. 63:323-328(2008).
RN [45]
RP VARIANTS LGMDR2 ARG-52; ARG-155; GLU-234; THR-284; TRP-555; ARG-618;
RP ARG-731; CYS-930; PRO-1228; THR-1526; ASP-1543; TRP-1768; SER-1970 AND
RP CYS-2042, VARIANTS MMD1 GLU-299; 386-PHE--ASP-390 DELINS TYR; ARG-426;
RP TRP-456; TRP-555; LEU-1029; HIS-1046; HIS-1046; GLN-1693; 1938-THR-ALA-1939
RP DEL AND CYS-2042, VARIANTS GLU-170; TRP-253 AND TRP-555, VARIANTS
RP PROXIMODISTAL MYOPATHY ARG-299; ARG-340; VAL-1748; TRP-1768 AND CYS-2042,
RP VARIANT PSEUDOMETABOLIC MYOPATHY PRO-266, AND VARIANTS VAL-84; VAL-189;
RP ALA-335; LEU-374; ASN-390; GLN-819; GLN-1022; GLN-1038; VAL-1276; VAL-1325;
RP ASN-1837 AND SER-1967.
RX PubMed=18853459; DOI=10.1002/humu.20910;
RA Krahn M., Beroud C., Labelle V., Nguyen K., Bernard R., Bassez G.,
RA Figarella-Branger D., Fernandez C., Bouvenot J., Richard I.,
RA Ollagnon-Roman E., Bevilacqua J.A., Salvo E., Attarian S., Chapon F.,
RA Pellissier J.-F., Pouget J., Hammouda el H., Laforet P., Urtizberea J.A.,
RA Eymard B., Leturcq F., Levy N.;
RT "Analysis of the DYSF mutational spectrum in a large cohort of patients.";
RL Hum. Mutat. 30:E345-E375(2009).
CC -!- FUNCTION: Key calcium ion sensor involved in the Ca(2+)-triggered
CC synaptic vesicle-plasma membrane fusion. Plays a role in the sarcolemma
CC repair mechanism of both skeletal muscle and cardiomyocytes that
CC permits rapid resealing of membranes disrupted by mechanical stress (By
CC similarity). {ECO:0000250}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBUNIT: Interacts with CACNA1S. Interacts with ANXA1; the interaction
CC is Ca(2+)- and injury state-dependent. Interacts with ANXA2; the
CC interaction is Ca(2+)- and injury state-dependent. Interacts with
CC CACNA1S and PARVB. Interacts with TRIM72/MG53; interaction is required
CC for transport to sites of cell injury during repair patch formation (By
CC similarity). Interacts with RIPOR2; this interaction occurs during
CC early myogenic differentiation (PubMed:24687993). Interacts with CAV3
CC and PARVB. Interacts with AHNAK; the interaction is direct and Ca(2+)-
CC independent. Interacts with AHNAK2; the interaction is direct and
CC Ca(2+)-independent. {ECO:0000250, ECO:0000269|PubMed:11532985,
CC ECO:0000269|PubMed:15835269, ECO:0000269|PubMed:17185750,
CC ECO:0000269|PubMed:24239457, ECO:0000269|PubMed:24687993}.
CC -!- INTERACTION:
CC O75923; Q00872: MYBPC1; NbExp=4; IntAct=EBI-2799016, EBI-5652924;
CC O75923; P52179: MYOM1; NbExp=3; IntAct=EBI-2799016, EBI-5353249;
CC O75923; P54296: MYOM2; NbExp=3; IntAct=EBI-2799016, EBI-5357134;
CC O75923; P20929: NEB; NbExp=6; IntAct=EBI-2799016, EBI-1049657;
CC O75923; Q13326: SGCG; NbExp=3; IntAct=EBI-2799016, EBI-5357343;
CC O75923; Q8WZ42: TTN; NbExp=17; IntAct=EBI-2799016, EBI-681210;
CC O75923-13; P60201-2: PLP1; NbExp=3; IntAct=EBI-19949386, EBI-12188331;
CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma; Single-pass type II
CC membrane protein. Cytoplasmic vesicle membrane {ECO:0000250}; Single-
CC pass type II membrane protein {ECO:0000250}. Cell membrane.
CC Note=Colocalizes, during muscle differentiation, with BIN1 in the T-
CC tubule system of myotubules and at the site of contact between two
CC myotubes or a myoblast and a myotube. Wounding of myotubes led to its
CC focal enrichment to the site of injury and to its relocalization in a
CC Ca(2+)-dependent manner toward the plasma membrane. Colocalizes with
CC AHNAK, AHNAK2 and PARVB at the sarcolemma of skeletal muscle. Detected
CC on the apical plasma membrane of the syncytiotrophoblast. Reaches the
CC plasmma membrane through a caveolin-independent mechanism. Retained by
CC caveolin at the plasmma membrane (By similarity). Colocalizes, during
CC muscle differentiation, with CACNA1S in the T-tubule system of
CC myotubules (By similarity). Accumulates and colocalizes with fusion
CC vesicles at the sarcolemma disruption sites (By similarity).
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=15;
CC Comment=Approximately 23% of the transcripts in skeletal muscle
CC incorporate exon 1a from an alternative promoter and missing the
CC calcium-binding sites of domain C2 1.;
CC Name=1;
CC IsoId=O75923-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75923-2; Sequence=VSP_035925;
CC Name=3;
CC IsoId=O75923-3; Sequence=VSP_035926;
CC Name=4;
CC IsoId=O75923-4; Sequence=VSP_035927;
CC Name=5;
CC IsoId=O75923-5; Sequence=VSP_035925, VSP_035926;
CC Name=6;
CC IsoId=O75923-6; Sequence=VSP_035926, VSP_035927;
CC Name=7;
CC IsoId=O75923-7; Sequence=VSP_035925, VSP_035926, VSP_035927;
CC Name=8;
CC IsoId=O75923-8; Sequence=VSP_035924, VSP_035925;
CC Name=9;
CC IsoId=O75923-9; Sequence=VSP_035924, VSP_035926;
CC Name=10;
CC IsoId=O75923-10; Sequence=VSP_035924, VSP_035927;
CC Name=11;
CC IsoId=O75923-11; Sequence=VSP_035924, VSP_035925, VSP_035926;
CC Name=12;
CC IsoId=O75923-12; Sequence=VSP_035924, VSP_035926, VSP_035927;
CC Name=13;
CC IsoId=O75923-13; Sequence=VSP_035924, VSP_035925, VSP_035926,
CC VSP_035927;
CC Name=14; Synonyms=Dysferlin_v1, DYSF_v1;
CC IsoId=O75923-14; Sequence=VSP_035924;
CC Name=15;
CC IsoId=O75923-15; Sequence=VSP_035926, VSP_035928, VSP_035929;
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle, myoblast, myotube and
CC in the syncytiotrophoblast (STB) of the placenta (at protein level).
CC Ubiquitous. Highly expressed in skeletal muscle. Also found in heart,
CC brain, spleen, intestine, placenta and at lower levels in liver, lung,
CC kidney and pancreas. {ECO:0000269|PubMed:10196375,
CC ECO:0000269|PubMed:11532985, ECO:0000269|PubMed:11959863,
CC ECO:0000269|PubMed:15318348, ECO:0000269|PubMed:16896923,
CC ECO:0000269|PubMed:17185750, ECO:0000269|PubMed:17363620,
CC ECO:0000269|PubMed:17554076, ECO:0000269|PubMed:24239457}.
CC -!- DEVELOPMENTAL STAGE: Expression in limb tissue from 5-6 weeks embryos;
CC persists throughout development. {ECO:0000269|PubMed:10196375}.
CC -!- DOMAIN: All seven C2 domains associate with lipid membranes in a
CC calcium-dependent manner. Domains C2 1 and 3 have the highest affinity
CC for calcium, the C2 domain 1 seems to be largely unstructured in the
CC absence of bound ligands. The C2 domain 1 from isoform 14 does not bind
CC calcium in the absence of bound phospholipid (PubMed:24239457,
CC PubMed:24461013). {ECO:0000269|PubMed:24239457,
CC ECO:0000269|PubMed:24461013}.
CC -!- DISEASE: Muscular dystrophy, limb-girdle, autosomal recessive 2
CC (LGMDR2) [MIM:253601]: An autosomal recessive degenerative myopathy
CC characterized by weakness and atrophy starting in the proximal
CC pelvifemoral muscles, with onset in the late teens or later, massive
CC elevation of serum creatine kinase levels and slow progression.
CC Scapular muscle involvement is minor and not present at onset. Upper
CC limb girdle involvement follows some years after the onset in lower
CC limbs. {ECO:0000269|PubMed:10196377, ECO:0000269|PubMed:11134403,
CC ECO:0000269|PubMed:14678801, ECO:0000269|PubMed:15469449,
CC ECO:0000269|PubMed:16010686, ECO:0000269|PubMed:16100712,
CC ECO:0000269|PubMed:16705711, ECO:0000269|PubMed:16996541,
CC ECO:0000269|PubMed:17185750, ECO:0000269|PubMed:17287450,
CC ECO:0000269|PubMed:18306167, ECO:0000269|PubMed:18853459,
CC ECO:0000269|PubMed:19084402, ECO:0000269|PubMed:9731526}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Miyoshi muscular dystrophy 1 (MMD1) [MIM:254130]: A late-onset
CC muscular dystrophy involving the distal lower limb musculature. It is
CC characterized by weakness that initially affects the gastrocnemius
CC muscle during early adulthood. {ECO:0000269|PubMed:10196377,
CC ECO:0000269|PubMed:11134403, ECO:0000269|PubMed:11468312,
CC ECO:0000269|PubMed:11959863, ECO:0000269|PubMed:12796534,
CC ECO:0000269|PubMed:15116377, ECO:0000269|PubMed:15469449,
CC ECO:0000269|PubMed:15477515, ECO:0000269|PubMed:15515206,
CC ECO:0000269|PubMed:16010686, ECO:0000269|PubMed:16100712,
CC ECO:0000269|PubMed:17287450, ECO:0000269|PubMed:18306167,
CC ECO:0000269|PubMed:18853459, ECO:0000269|PubMed:9731526,
CC ECO:0000269|Ref.28}. Note=The disease is caused by variants affecting
CC the gene represented in this entry.
CC -!- DISEASE: Distal myopathy with anterior tibial onset (DMAT)
CC [MIM:606768]: Onset of the disorder is between 14 and 28 years of age
CC and the anterior tibial muscles are the first muscle group to be
CC involved. Inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:11198284}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 14]: Produced by alternative promoter usage.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the ferlin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAG51981.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAA07603.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA07603.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Leiden Muscular Dystrophy pages; Note=Dysferlin;
CC URL="https://www.dmd.nl/dysf_home.html";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Dysferlin entry;
CC URL="https://en.wikipedia.org/wiki/Dysferlin";
CC ---------------------------------------------------------------------------
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DR EMBL; AF075575; AAC63519.1; -; mRNA.
DR EMBL; DQ267935; ABB89736.1; -; mRNA.
DR EMBL; DQ976379; ABI75150.1; -; Genomic_DNA.
DR EMBL; EF015906; ABK20181.1; -; Genomic_DNA.
DR EMBL; EU515155; ACB12752.1; -; mRNA.
DR EMBL; EU515156; ACB12753.1; -; mRNA.
DR EMBL; EU515157; ACB12754.1; -; mRNA.
DR EMBL; EU515158; ACB12755.1; -; mRNA.
DR EMBL; EU515159; ACB12756.1; -; mRNA.
DR EMBL; EU515160; ACB12757.1; -; mRNA.
DR EMBL; EU515161; ACB12758.1; -; mRNA.
DR EMBL; EU515162; ACB12759.1; -; mRNA.
DR EMBL; EU515163; ACB12760.1; -; mRNA.
DR EMBL; EU515164; ACB12761.1; -; mRNA.
DR EMBL; EU515165; ACB12762.1; -; mRNA.
DR EMBL; EU515166; ACB12763.1; -; mRNA.
DR EMBL; AC010147; AAY14954.1; -; Genomic_DNA.
DR EMBL; AC104084; AAY24199.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99763.1; -; Genomic_DNA.
DR EMBL; AJ007670; CAA07603.1; ALT_SEQ; mRNA.
DR EMBL; AJ007973; CAA07800.1; -; Genomic_DNA.
DR EMBL; AK074104; BAB84930.1; -; mRNA.
DR EMBL; AK074649; BAG51981.1; ALT_INIT; mRNA.
DR CCDS; CCDS1918.1; -. [O75923-1]
DR CCDS; CCDS46323.1; -. [O75923-2]
DR CCDS; CCDS46324.1; -. [O75923-7]
DR CCDS; CCDS46325.1; -. [O75923-5]
DR CCDS; CCDS46326.1; -. [O75923-4]
DR CCDS; CCDS46327.1; -. [O75923-8]
DR CCDS; CCDS46328.1; -. [O75923-13]
DR CCDS; CCDS46329.1; -. [O75923-11]
DR CCDS; CCDS46330.1; -. [O75923-10]
DR CCDS; CCDS46331.1; -. [O75923-14]
DR CCDS; CCDS46332.1; -. [O75923-12]
DR RefSeq; NP_001123927.1; NM_001130455.1. [O75923-14]
DR RefSeq; NP_001124448.1; NM_001130976.1. [O75923-3]
DR RefSeq; NP_001124449.1; NM_001130977.1. [O75923-6]
DR RefSeq; NP_001124450.1; NM_001130978.1. [O75923-4]
DR RefSeq; NP_001124451.1; NM_001130979.1. [O75923-2]
DR RefSeq; NP_001124452.1; NM_001130980.1. [O75923-5]
DR RefSeq; NP_001124453.1; NM_001130981.1. [O75923-7]
DR RefSeq; NP_001124454.1; NM_001130982.1. [O75923-8]
DR RefSeq; NP_001124455.1; NM_001130983.1. [O75923-10]
DR RefSeq; NP_001124456.1; NM_001130984.1. [O75923-12]
DR RefSeq; NP_001124457.1; NM_001130985.1. [O75923-11]
DR RefSeq; NP_001124458.1; NM_001130986.1. [O75923-9]
DR RefSeq; NP_001124459.1; NM_001130987.1. [O75923-13]
DR RefSeq; NP_003485.1; NM_003494.3. [O75923-1]
DR PDB; 4CAH; X-ray; 1.90 A; B=942-1052.
DR PDB; 4CAI; X-ray; 2.20 A; A/B/C=942-1052.
DR PDB; 4IHB; X-ray; 2.04 A; A/B/C/D/E/F=1-124.
DR PDB; 4IQH; X-ray; 1.76 A; A/B/C=30-124.
DR PDB; 7JOF; X-ray; 2.00 A; A/B/C/D=1-130.
DR PDB; 7K6B; NMR; -; A=1-130.
DR PDB; 7KRB; NMR; -; A=1-130.
DR PDBsum; 4CAH; -.
DR PDBsum; 4CAI; -.
DR PDBsum; 4IHB; -.
DR PDBsum; 4IQH; -.
DR PDBsum; 7JOF; -.
DR PDBsum; 7K6B; -.
DR PDBsum; 7KRB; -.
DR AlphaFoldDB; O75923; -.
DR SMR; O75923; -.
DR BioGRID; 113896; 58.
DR CORUM; O75923; -.
DR IntAct; O75923; 52.
DR STRING; 9606.ENSP00000386881; -.
DR TCDB; 1.F.1.2.1; the synaptosomal vesicle fusion pore (svf-pore) family.
DR iPTMnet; O75923; -.
DR PhosphoSitePlus; O75923; -.
DR BioMuta; DYSF; -.
DR EPD; O75923; -.
DR jPOST; O75923; -.
DR MassIVE; O75923; -.
DR MaxQB; O75923; -.
DR PaxDb; O75923; -.
DR PeptideAtlas; O75923; -.
DR PRIDE; O75923; -.
DR ProteomicsDB; 50278; -. [O75923-1]
DR ProteomicsDB; 50279; -. [O75923-10]
DR ProteomicsDB; 50280; -. [O75923-11]
DR ProteomicsDB; 50281; -. [O75923-12]
DR ProteomicsDB; 50282; -. [O75923-13]
DR ProteomicsDB; 50283; -. [O75923-14]
DR ProteomicsDB; 50284; -. [O75923-15]
DR ProteomicsDB; 50285; -. [O75923-2]
DR ProteomicsDB; 50286; -. [O75923-3]
DR ProteomicsDB; 50287; -. [O75923-4]
DR ProteomicsDB; 50288; -. [O75923-5]
DR ProteomicsDB; 50289; -. [O75923-6]
DR ProteomicsDB; 50290; -. [O75923-7]
DR ProteomicsDB; 50291; -. [O75923-8]
DR ProteomicsDB; 50292; -. [O75923-9]
DR Antibodypedia; 2461; 301 antibodies from 34 providers.
DR DNASU; 8291; -.
DR Ensembl; ENST00000258104.8; ENSP00000258104.3; ENSG00000135636.15. [O75923-1]
DR Ensembl; ENST00000394120.6; ENSP00000377678.2; ENSG00000135636.15. [O75923-14]
DR Ensembl; ENST00000409366.5; ENSP00000386512.1; ENSG00000135636.15. [O75923-10]
DR Ensembl; ENST00000409582.7; ENSP00000386547.3; ENSG00000135636.15. [O75923-7]
DR Ensembl; ENST00000409651.5; ENSP00000386683.1; ENSG00000135636.15. [O75923-8]
DR Ensembl; ENST00000409744.5; ENSP00000386285.1; ENSG00000135636.15. [O75923-12]
DR Ensembl; ENST00000409762.5; ENSP00000387137.1; ENSG00000135636.15. [O75923-5]
DR Ensembl; ENST00000410020.8; ENSP00000386881.3; ENSG00000135636.15. [O75923-13]
DR Ensembl; ENST00000410041.1; ENSP00000386617.1; ENSG00000135636.15. [O75923-11]
DR Ensembl; ENST00000413539.6; ENSP00000407046.2; ENSG00000135636.15. [O75923-2]
DR Ensembl; ENST00000429174.6; ENSP00000398305.2; ENSG00000135636.15. [O75923-4]
DR GeneID; 8291; -.
DR KEGG; hsa:8291; -.
DR MANE-Select; ENST00000410020.8; ENSP00000386881.3; NM_001130987.2; NP_001124459.1. [O75923-13]
DR UCSC; uc002sie.4; human. [O75923-1]
DR CTD; 8291; -.
DR DisGeNET; 8291; -.
DR GeneCards; DYSF; -.
DR GeneReviews; DYSF; -.
DR HGNC; HGNC:3097; DYSF.
DR HPA; ENSG00000135636; Tissue enhanced (skeletal).
DR MalaCards; DYSF; -.
DR MIM; 253601; phenotype.
DR MIM; 254130; phenotype.
DR MIM; 603009; gene.
DR MIM; 606768; phenotype.
DR neXtProt; NX_O75923; -.
DR OpenTargets; ENSG00000135636; -.
DR Orphanet; 199329; Congenital myopathy, Paradas type.
DR Orphanet; 178400; Distal myopathy with anterior tibial onset.
DR Orphanet; 268; Dysferlin-related limb-girdle muscular dystrophy R2.
DR Orphanet; 45448; Miyoshi myopathy.
DR PharmGKB; PA27554; -.
DR VEuPathDB; HostDB:ENSG00000135636; -.
DR eggNOG; KOG1326; Eukaryota.
DR GeneTree; ENSGT00940000156187; -.
DR HOGENOM; CLU_001183_2_1_1; -.
DR InParanoid; O75923; -.
DR OMA; DAYCSVT; -.
DR OrthoDB; 20162at2759; -.
DR PhylomeDB; O75923; -.
DR TreeFam; TF316871; -.
DR PathwayCommons; O75923; -.
DR Reactome; R-HSA-445355; Smooth Muscle Contraction.
DR SignaLink; O75923; -.
DR SIGNOR; O75923; -.
DR BioGRID-ORCS; 8291; 18 hits in 1072 CRISPR screens.
DR ChiTaRS; DYSF; human.
DR GeneWiki; Dysferlin; -.
DR GenomeRNAi; 8291; -.
DR Pharos; O75923; Tbio.
DR PRO; PR:O75923; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O75923; protein.
DR Bgee; ENSG00000135636; Expressed in blood and 190 other tissues.
DR Genevisible; O75923; HS.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; IDA:UniProtKB.
DR GO; GO:0030315; C:T-tubule; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IMP:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; IDA:UniProtKB.
DR GO; GO:0002281; P:macrophage activation involved in immune response; IMP:MGI.
DR GO; GO:0061025; P:membrane fusion; IBA:GO_Central.
DR GO; GO:0002280; P:monocyte activation involved in immune response; IMP:MGI.
DR GO; GO:0050765; P:negative regulation of phagocytosis; IMP:MGI.
DR GO; GO:0007009; P:plasma membrane organization; IBA:GO_Central.
DR GO; GO:0001778; P:plasma membrane repair; IBA:GO_Central.
DR GO; GO:0033292; P:T-tubule organization; IBA:GO_Central.
DR GO; GO:0006906; P:vesicle fusion; IBA:GO_Central.
DR CDD; cd08373; C2A_Ferlin; 1.
DR CDD; cd04011; C2B_Ferlin; 1.
DR CDD; cd04018; C2C_Ferlin; 1.
DR CDD; cd04017; C2D_Ferlin; 1.
DR CDD; cd04037; C2E_Ferlin; 1.
DR CDD; cd08374; C2F_Ferlin; 1.
DR Gene3D; 2.60.40.150; -; 6.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR037726; C2A_Ferlin.
DR InterPro; IPR037720; C2B_Ferlin.
DR InterPro; IPR037722; C2C_Ferlin.
DR InterPro; IPR037723; C2D_Ferlin.
DR InterPro; IPR037724; C2E_Ferlin.
DR InterPro; IPR037725; C2F_Ferlin.
DR InterPro; IPR029998; Dysferlin.
DR InterPro; IPR012968; FerIin_dom.
DR InterPro; IPR037721; Ferlin.
DR InterPro; IPR012560; Ferlin_A-domain.
DR InterPro; IPR012561; Ferlin_B-domain.
DR InterPro; IPR032362; Ferlin_C.
DR InterPro; IPR006614; Peroxin/Ferlin.
DR PANTHER; PTHR12546; PTHR12546; 1.
DR PANTHER; PTHR12546:SF44; PTHR12546:SF44; 1.
DR Pfam; PF00168; C2; 7.
DR Pfam; PF08165; FerA; 1.
DR Pfam; PF08150; FerB; 1.
DR Pfam; PF08151; FerI; 1.
DR Pfam; PF16165; Ferlin_C; 1.
DR SMART; SM00239; C2; 7.
DR SMART; SM00694; DysFC; 2.
DR SMART; SM00693; DysFN; 2.
DR SMART; SM01200; FerA; 1.
DR SMART; SM01201; FerB; 1.
DR SMART; SM01202; FerI; 1.
DR SUPFAM; SSF49562; SSF49562; 7.
DR PROSITE; PS50004; C2; 7.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative promoter usage; Alternative splicing; Calcium;
KW Cell membrane; Cytoplasmic vesicle; Disease variant;
KW Limb-girdle muscular dystrophy; Lipid-binding; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Signal-anchor; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..2080
FT /note="Dysferlin"
FT /id="PRO_0000057879"
FT TOPO_DOM 1..2046
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 2047..2067
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 2068..2080
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 1..101
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 203..321
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 360..496
FT /note="C2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1136..1262
FT /note="C2 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1310..1438
FT /note="C2 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1561..1679
FT /note="C2 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1795..1943
FT /note="C2 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 132..215
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1995..2017
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 152..168
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 18
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24239457"
FT BINDING 19
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24239457"
FT BINDING 21
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24239457"
FT BINDING 40
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24239457"
FT BINDING 1168
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1174
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1230
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1232
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1594
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1600
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1649
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1651
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1914
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1917
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1920
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT MOD_RES 166
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..29
FT /note="MLRVFILYAENVHTPDTDISDAYCSAVFA -> MLCCLLVRASNLPSAKKDR
FT RSDPVASLTFR (in isoform 8, isoform 9, isoform 10, isoform
FT 11, isoform 12, isoform 13 and isoform 14)"
FT /evidence="ECO:0000303|PubMed:16896923,
FT ECO:0000303|PubMed:19221801"
FT /id="VSP_035924"
FT VAR_SEQ 152
FT /note="A -> AGGGQSRAETWSLLSDSTMDTRYSGKKWPAPT (in isoform 2,
FT isoform 5, isoform 7, isoform 8, isoform 11 and isoform
FT 13)"
FT /evidence="ECO:0000303|PubMed:19221801"
FT /id="VSP_035925"
FT VAR_SEQ 494..508
FT /note="EEPAGAVKPSKASDL -> V (in isoform 3, isoform 5,
FT isoform 6, isoform 7, isoform 9, isoform 11, isoform 12,
FT isoform 13 and isoform 15)"
FT /evidence="ECO:0000303|PubMed:19221801, ECO:0000303|Ref.7"
FT /id="VSP_035926"
FT VAR_SEQ 1470
FT /note="Q -> QLADGLSSLAPTNTASPPSSPH (in isoform 4, isoform
FT 6, isoform 7, isoform 10, isoform 12 and isoform 13)"
FT /evidence="ECO:0000303|PubMed:19221801"
FT /id="VSP_035927"
FT VAR_SEQ 1934..1968
FT /note="KPAKTAKKCSLDQLDDAFHPEWFVSLFEQKTVKGW -> SSASSSRPPRPDC
FT PARVGRQTDGPAHTPRVANMEL (in isoform 15)"
FT /evidence="ECO:0000303|Ref.7"
FT /id="VSP_035928"
FT VAR_SEQ 1969..2080
FT /note="Missing (in isoform 15)"
FT /evidence="ECO:0000303|Ref.7"
FT /id="VSP_035929"
FT VARIANT 52
FT /note="W -> R (in LGMDR2; dbSNP:rs1553508863)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057834"
FT VARIANT 67
FT /note="V -> D (in MMD1 and LGMDR2; Reduces calcium-
FT sensitive phospholipid binding and interaction with AHNAK
FT and AHNAK2; dbSNP:rs121908957)"
FT /evidence="ECO:0000269|PubMed:11134403,
FT ECO:0000269|PubMed:11959863, ECO:0000269|PubMed:17185750"
FT /id="VAR_057835"
FT VARIANT 84
FT /note="A -> V (in dbSNP:rs772008300)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057836"
FT VARIANT 155
FT /note="G -> R (in LGMDR2; dbSNP:rs200970855)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057837"
FT VARIANT 170
FT /note="A -> E (in dbSNP:rs34999029)"
FT /evidence="ECO:0000269|PubMed:16010686,
FT ECO:0000269|PubMed:16100712, ECO:0000269|PubMed:18853459"
FT /id="VAR_024853"
FT VARIANT 189
FT /note="L -> V (in dbSNP:rs13407355)"
FT /evidence="ECO:0000269|PubMed:16010686,
FT ECO:0000269|PubMed:18853459"
FT /id="VAR_024854"
FT VARIANT 234
FT /note="G -> E (in LGMDR2; dbSNP:rs141497053)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057838"
FT VARIANT 253
FT /note="R -> W (found in patients with isolated hyperCKemia;
FT dbSNP:rs149827237)"
FT /evidence="ECO:0000269|PubMed:16010686,
FT ECO:0000269|PubMed:18853459"
FT /id="VAR_024855"
FT VARIANT 266
FT /note="L -> P (in pseudometabolic myopathy)"
FT /evidence="ECO:0000269|PubMed:16010686,
FT ECO:0000269|PubMed:18853459"
FT /id="VAR_024856"
FT VARIANT 284
FT /note="I -> T (in LGMDR2; dbSNP:rs1553522164)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057839"
FT VARIANT 299
FT /note="G -> E (in MMD1; dbSNP:rs1258728780)"
FT /evidence="ECO:0000269|PubMed:16010686,
FT ECO:0000269|PubMed:18853459"
FT /id="VAR_024857"
FT VARIANT 299
FT /note="G -> R (in LGMDR2 and proximodistal myopathy;
FT dbSNP:rs121908963)"
FT /evidence="ECO:0000269|PubMed:16705711,
FT ECO:0000269|PubMed:18306167, ECO:0000269|PubMed:18853459"
FT /id="VAR_057840"
FT VARIANT 299
FT /note="G -> W (in MMD1; dbSNP:rs121908963)"
FT /evidence="ECO:0000269|PubMed:18306167"
FT /id="VAR_057841"
FT VARIANT 335
FT /note="G -> A"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057842"
FT VARIANT 340
FT /note="S -> R (in proximodistal myopathy;
FT dbSNP:rs766891289)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057843"
FT VARIANT 374
FT /note="V -> L (in dbSNP:rs150724610)"
FT /evidence="ECO:0000269|PubMed:16100712,
FT ECO:0000269|PubMed:18853459"
FT /id="VAR_057844"
FT VARIANT 386..390
FT /note="FRAED -> Y (in MMD1)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057845"
FT VARIANT 389
FT /note="E -> Q (in MMD1)"
FT /evidence="ECO:0000269|PubMed:15515206"
FT /id="VAR_057846"
FT VARIANT 390
FT /note="D -> N (in dbSNP:rs886042389)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057847"
FT VARIANT 426
FT /note="G -> R (in MMD1; dbSNP:rs886042093)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057848"
FT VARIANT 426
FT /note="G -> V (in MMD1)"
FT /evidence="ECO:0000269|PubMed:15477515"
FT /id="VAR_057849"
FT VARIANT 456
FT /note="C -> W (in MMD1)"
FT /evidence="ECO:0000269|PubMed:16010686,
FT ECO:0000269|PubMed:18853459"
FT /id="VAR_024858"
FT VARIANT 519
FT /note="G -> R (in MMD1; dbSNP:rs121908962)"
FT /evidence="ECO:0000269|PubMed:17287450"
FT /id="VAR_057850"
FT VARIANT 555
FT /note="R -> W (in LGMDR2 and MMD1; also found in patients
FT with isolated hyperCKemia; dbSNP:rs377735262)"
FT /evidence="ECO:0000269|PubMed:16010686,
FT ECO:0000269|PubMed:18853459"
FT /id="VAR_024859"
FT VARIANT 618
FT /note="G -> R (in MMD1 and LGMDR2; dbSNP:rs201049092)"
FT /evidence="ECO:0000269|PubMed:15469449,
FT ECO:0000269|PubMed:18853459"
FT /id="VAR_057851"
FT VARIANT 621
FT /note="G -> R (in LGMDR2; dbSNP:rs886043900)"
FT /evidence="ECO:0000269|PubMed:16100712"
FT /id="VAR_057852"
FT VARIANT 625
FT /note="D -> Y (in LGMDR2; dbSNP:rs121908960)"
FT /evidence="ECO:0000269|PubMed:17287450"
FT /id="VAR_057853"
FT VARIANT 731
FT /note="P -> R (in LGMDR2)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057854"
FT VARIANT 791
FT /note="P -> R (in MMD1 and LGMDR2; dbSNP:rs121908956)"
FT /evidence="ECO:0000269|PubMed:10196377,
FT ECO:0000269|PubMed:16996541"
FT /id="VAR_012308"
FT VARIANT 819
FT /note="R -> Q (in dbSNP:rs748636047)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057855"
FT VARIANT 834
FT /note="I -> V (in dbSNP:rs34671418)"
FT /id="VAR_049055"
FT VARIANT 930
FT /note="W -> C (in LGMDR2; unknown pathological
FT significance; dbSNP:rs727503910)"
FT /evidence="ECO:0000269|PubMed:16996541,
FT ECO:0000269|PubMed:18853459"
FT /id="VAR_057856"
FT VARIANT 959
FT /note="R -> W (in MMD1 and LGMDR2; dbSNP:rs202218890)"
FT /evidence="ECO:0000269|PubMed:14678801,
FT ECO:0000269|PubMed:16100712"
FT /id="VAR_024860"
FT VARIANT 999
FT /note="W -> C (in MMD1; dbSNP:rs28937581)"
FT /evidence="ECO:0000269|PubMed:12796534, ECO:0000269|Ref.28"
FT /id="VAR_057857"
FT VARIANT 1022
FT /note="R -> Q (in dbSNP:rs34211915)"
FT /evidence="ECO:0000269|PubMed:14678801,
FT ECO:0000269|PubMed:15469449, ECO:0000269|PubMed:18853459"
FT /id="VAR_024861"
FT VARIANT 1029
FT /note="P -> L (in MMD1)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057858"
FT VARIANT 1038
FT /note="R -> Q (in LGMDR2; dbSNP:rs150877497)"
FT /evidence="ECO:0000269|PubMed:14678801,
FT ECO:0000269|PubMed:16100712, ECO:0000269|PubMed:18853459"
FT /id="VAR_024862"
FT VARIANT 1041
FT /note="R -> C (in MMD1; dbSNP:rs144598063)"
FT /evidence="ECO:0000269|PubMed:15469449"
FT /id="VAR_057859"
FT VARIANT 1046
FT /note="R -> H (in MMD1; dbNP:28939700; dbSNP:rs121908958)"
FT /evidence="ECO:0000269|PubMed:11468312,
FT ECO:0000269|PubMed:16010686, ECO:0000269|PubMed:18853459"
FT /id="VAR_024863"
FT VARIANT 1065
FT /note="E -> EAE"
FT /evidence="ECO:0000269|PubMed:16996541"
FT /id="VAR_024864"
FT VARIANT 1072
FT /note="A -> P (in dbSNP:rs34660230)"
FT /id="VAR_049056"
FT VARIANT 1096
FT /note="R -> H (in dbSNP:rs59915619)"
FT /id="VAR_061170"
FT VARIANT 1208
FT /note="I -> M (in LGMDR2; unknown pathological
FT significance; dbSNP:rs148858485)"
FT /evidence="ECO:0000269|PubMed:16010686"
FT /id="VAR_024865"
FT VARIANT 1228
FT /note="L -> P (in LGMDR2)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057860"
FT VARIANT 1242
FT /note="R -> H (in dbSNP:rs2303603)"
FT /id="VAR_020308"
FT VARIANT 1276
FT /note="L -> V (in proximodistal myopathy)"
FT /evidence="ECO:0000269|PubMed:16010686,
FT ECO:0000269|PubMed:18853459"
FT /id="VAR_024866"
FT VARIANT 1298
FT /note="I -> V (in MMD1 and LGMDR2; dbSNP:rs121908954)"
FT /evidence="ECO:0000269|PubMed:9731526"
FT /id="VAR_012309"
FT VARIANT 1325
FT /note="I -> M (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035893"
FT VARIANT 1325
FT /note="I -> V (in dbSNP:rs145401010)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057861"
FT VARIANT 1331
FT /note="R -> L (in dbSNP:rs61742872)"
FT /evidence="ECO:0000269|PubMed:14678801,
FT ECO:0000269|PubMed:16010686"
FT /id="VAR_024867"
FT VARIANT 1335
FT /note="E -> K (in MMD1 and LGMDR2; dbSNP:rs758993965)"
FT /evidence="ECO:0000269|PubMed:14678801,
FT ECO:0000269|PubMed:15469449, ECO:0000269|PubMed:16100712"
FT /id="VAR_024868"
FT VARIANT 1341
FT /note="L -> P (in LGMDR2; dbSNP:rs757917335)"
FT /evidence="ECO:0000269|PubMed:16705711"
FT /id="VAR_057862"
FT VARIANT 1349
FT /note="L -> V (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035894"
FT VARIANT 1351
FT /note="N -> S (in dbSNP:rs139529811)"
FT /evidence="ECO:0000269|PubMed:16010686"
FT /id="VAR_024869"
FT VARIANT 1361
FT /note="C -> R (in MMD1; dbSNP:rs776472879)"
FT /evidence="ECO:0000269|PubMed:15469449"
FT /id="VAR_057863"
FT VARIANT 1505
FT /note="Y -> C (in LGMDR2; dbSNP:rs757820496)"
FT /evidence="ECO:0000269|PubMed:15469449"
FT /id="VAR_057864"
FT VARIANT 1526
FT /note="K -> T (in LGMDR2; dbSNP:rs76086153)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057865"
FT VARIANT 1543
FT /note="G -> D (in LGMDR2)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057866"
FT VARIANT 1581
FT /note="R -> H (in dbSNP:rs185596534)"
FT /evidence="ECO:0000269|PubMed:12796534"
FT /id="VAR_057867"
FT VARIANT 1662
FT /note="T -> R (in MMD1)"
FT /evidence="ECO:0000269|PubMed:15469449"
FT /id="VAR_057868"
FT VARIANT 1678
FT /note="C -> S (found in patients with isolated hyperCKemia;
FT dbSNP:rs753279446)"
FT /evidence="ECO:0000269|PubMed:16100712"
FT /id="VAR_057869"
FT VARIANT 1679
FT /note="G -> E (in MMD1)"
FT /evidence="ECO:0000269|PubMed:12796534"
FT /id="VAR_057870"
FT VARIANT 1693
FT /note="R -> Q (in MMD1; dbSNP:rs779987458)"
FT /evidence="ECO:0000269|PubMed:16010686,
FT ECO:0000269|PubMed:18853459"
FT /id="VAR_024870"
FT VARIANT 1693
FT /note="R -> W (in MMD1; dbSNP:rs863225021)"
FT /evidence="ECO:0000269|PubMed:16100712"
FT /id="VAR_057871"
FT VARIANT 1734
FT /note="E -> G (in LGMDR2; dbSNP:rs121908961)"
FT /evidence="ECO:0000269|PubMed:17287450"
FT /id="VAR_057872"
FT VARIANT 1748
FT /note="E -> V (in proximodistal myopathy)"
FT /evidence="ECO:0000269|PubMed:16010686,
FT ECO:0000269|PubMed:18853459"
FT /id="VAR_024871"
FT VARIANT 1768
FT /note="R -> W (in LGMDR2 and proximodistal myopathy;
FT unknown pathological significance; dbSNP:rs746243052)"
FT /evidence="ECO:0000269|PubMed:16996541,
FT ECO:0000269|PubMed:18853459"
FT /id="VAR_057873"
FT VARIANT 1837
FT /note="D -> N (in MMD1; dbSNP:rs398123794)"
FT /evidence="ECO:0000269|PubMed:16100712,
FT ECO:0000269|PubMed:18853459"
FT /id="VAR_057874"
FT VARIANT 1842
FT /note="G -> D (in MMD1; dbSNP:rs1131692158)"
FT /evidence="ECO:0000269|PubMed:15116377"
FT /id="VAR_057875"
FT VARIANT 1857
FT /note="H -> R (in MMD1; dbSNP:rs199601326)"
FT /evidence="ECO:0000269|PubMed:9731526"
FT /id="VAR_012310"
FT VARIANT 1922
FT /note="L -> P (in MMD1)"
FT /evidence="ECO:0000269|PubMed:15116377"
FT /id="VAR_057876"
FT VARIANT 1938..1939
FT /note="Missing (in MMD1)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057877"
FT VARIANT 1942
FT /note="C -> G (in MMD1)"
FT /evidence="ECO:0000269|PubMed:16100712"
FT /id="VAR_057878"
FT VARIANT 1967
FT /note="G -> S"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057879"
FT VARIANT 1970
FT /note="P -> S (in LGMDR2; dbSNP:rs1057521141)"
FT /evidence="ECO:0000269|PubMed:18853459"
FT /id="VAR_057880"
FT VARIANT 2000
FT /note="R -> Q (in MMD1; dbSNP:rs115407852)"
FT /evidence="ECO:0000269|PubMed:11468312"
FT /id="VAR_024872"
FT VARIANT 2042
FT /note="R -> C (in MMD1, LGMDR2 and proximodistal myopathy;
FT dbSNP:rs121908955)"
FT /evidence="ECO:0000269|PubMed:16100712,
FT ECO:0000269|PubMed:16996541, ECO:0000269|PubMed:18853459,
FT ECO:0000269|PubMed:9731526"
FT /id="VAR_012311"
FT VARIANT 2068
FT /note="P -> L (in MMD1; dbSNP:rs149732545)"
FT /evidence="ECO:0000269|PubMed:15477515"
FT /id="VAR_057881"
FT MUTAGEN 16
FT /note="D->A: Fails to bind calcium."
FT /evidence="ECO:0000269|PubMed:24461013"
FT MUTAGEN 21
FT /note="D->A: Fails to bind calcium."
FT /evidence="ECO:0000269|PubMed:24461013"
FT MUTAGEN 71
FT /note="D->A: Fails to bind calcium."
FT /evidence="ECO:0000269|PubMed:24461013"
FT MUTAGEN 79
FT /note="R->D: Moderately increased calcium affinity."
FT /evidence="ECO:0000269|PubMed:24461013"
FT MUTAGEN 80
FT /note="F->A: Reduced calcium affinity."
FT /evidence="ECO:0000269|PubMed:24461013"
FT STRAND 1..11
FT /evidence="ECO:0007829|PDB:4IQH"
FT STRAND 15..18
FT /evidence="ECO:0007829|PDB:7JOF"
FT STRAND 22..28
FT /evidence="ECO:0007829|PDB:4IQH"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:4IQH"
FT STRAND 45..53
FT /evidence="ECO:0007829|PDB:4IQH"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:7K6B"
FT STRAND 64..71
FT /evidence="ECO:0007829|PDB:4IQH"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:4IQH"
FT STRAND 79..87
FT /evidence="ECO:0007829|PDB:4IQH"
FT HELIX 89..92
FT /evidence="ECO:0007829|PDB:4IQH"
FT STRAND 98..106
FT /evidence="ECO:0007829|PDB:4IQH"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:7K6B"
FT STRAND 112..123
FT /evidence="ECO:0007829|PDB:4IQH"
FT STRAND 946..958
FT /evidence="ECO:0007829|PDB:4CAH"
FT STRAND 966..973
FT /evidence="ECO:0007829|PDB:4CAH"
FT HELIX 983..985
FT /evidence="ECO:0007829|PDB:4CAH"
FT STRAND 996..998
FT /evidence="ECO:0007829|PDB:4CAH"
FT STRAND 1000..1002
FT /evidence="ECO:0007829|PDB:4CAI"
FT STRAND 1011..1015
FT /evidence="ECO:0007829|PDB:4CAH"
FT STRAND 1021..1023
FT /evidence="ECO:0007829|PDB:4CAH"
FT STRAND 1028..1030
FT /evidence="ECO:0007829|PDB:4CAH"
FT STRAND 1037..1049
FT /evidence="ECO:0007829|PDB:4CAH"
FT MOD_RES O75923-2:166
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES O75923-2:197
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES O75923-5:166
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES O75923-5:197
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES O75923-7:166
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES O75923-7:197
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES O75923-8:167
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES O75923-8:198
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES O75923-11:167
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES O75923-11:198
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES O75923-13:167
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES O75923-13:198
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
SQ SEQUENCE 2080 AA; 237295 MW; 376E25A5AB9BE398 CRC64;
MLRVFILYAE NVHTPDTDIS DAYCSAVFAG VKKRTKVIKN SVNPVWNEGF EWDLKGIPLD
QGSELHVVVK DHETMGRNRF LGEAKVPLRE VLATPSLSAS FNAPLLDTKK QPTGASLVLQ
VSYTPLPGAV PLFPPPTPLE PSPTLPDLDV VADTGGEEDT EDQGLTGDEA EPFLDQSGGP
GAPTTPRKLP SRPPPHYPGI KRKRSAPTSR KLLSDKPQDF QIRVQVIEGR QLPGVNIKPV
VKVTAAGQTK RTRIHKGNSP LFNETLFFNL FDSPGELFDE PIFITVVDSR SLRTDALLGE
FRMDVGTIYR EPRHAYLRKW LLLSDPDDFS AGARGYLKTS LCVLGPGDEA PLERKDPSED
KEDIESNLLR PTGVALRGAH FCLKVFRAED LPQMDDAVMD NVKQIFGFES NKKNLVDPFV
EVSFAGKMLC SKILEKTANP QWNQNITLPA MFPSMCEKMR IRIIDWDRLT HNDIVATTYL
SMSKISAPGG EIEEEPAGAV KPSKASDLDD YLGFLPTFGP CYINLYGSPR EFTGFPDPYT
ELNTGKGEGV AYRGRLLLSL ETKLVEHSEQ KVEDLPADDI LRVEKYLRRR KYSLFAAFYS
ATMLQDVDDA IQFEVSIGNY GNKFDMTCLP LASTTQYSRA VFDGCHYYYL PWGNVKPVVV
LSSYWEDISH RIETQNQLLG IADRLEAGLE QVHLALKAQC STEDVDSLVA QLTDELIAGC
SQPLGDIHET PSATHLDQYL YQLRTHHLSQ ITEAALALKL GHSELPAALE QAEDWLLRLR
ALAEEPQNSL PDIVIWMLQG DKRVAYQRVP AHQVLFSRRG ANYCGKNCGK LQTIFLKYPM
EKVPGARMPV QIRVKLWFGL SVDEKEFNQF AEGKLSVFAE TYENETKLAL VGNWGTTGLT
YPKFSDVTGK IKLPKDSFRP SAGWTWAGDW FVCPEKTLLH DMDAGHLSFV EEVFENQTRL
PGGQWIYMSD NYTDVNGEKV LPKDDIECPL GWKWEDEEWS TDLNRAVDEQ GWEYSITIPP
ERKPKHWVPA EKMYYTHRRR RWVRLRRRDL SQMEALKRHR QAEAEGEGWE YASLFGWKFH
LEYRKTDAFR RRRWRRRMEP LEKTGPAAVF ALEGALGGVM DDKSEDSMSV STLSFGVNRP
TISCIFDYGN RYHLRCYMYQ ARDLAAMDKD SFSDPYAIVS FLHQSQKTVV VKNTLNPTWD
QTLIFYEIEI FGEPATVAEQ PPSIVVELYD HDTYGADEFM GRCICQPSLE RMPRLAWFPL
TRGSQPSGEL LASFELIQRE KPAIHHIPGF EVQETSRILD ESEDTDLPYP PPQREANIYM
VPQNIKPALQ RTAIEILAWG LRNMKSYQLA NISSPSLVVE CGGQTVQSCV IRNLRKNPNF
DICTLFMEVM LPREELYCPP ITVKVIDNRQ FGRRPVVGQC TIRSLESFLC DPYSAESPSP
QGGPDDVSLL SPGEDVLIDI DDKEPLIPIQ EEEFIDWWSK FFASIGEREK CGSYLEKDFD
TLKVYDTQLE NVEAFEGLSD FCNTFKLYRG KTQEETEDPS VIGEFKGLFK IYPLPEDPAI
PMPPRQFHQL AAQGPQECLV RIYIVRAFGL QPKDPNGKCD PYIKISIGKK SVSDQDNYIP
CTLEPVFGKM FELTCTLPLE KDLKITLYDY DLLSKDEKIG ETVVDLENRL LSKFGARCGL
PQTYCVSGPN QWRDQLRPSQ LLHLFCQQHR VKAPVYRTDR VMFQDKEYSI EEIEAGRIPN
PHLGPVEERL ALHVLQQQGL VPEHVESRPL YSPLQPDIEQ GKLQMWVDLF PKALGRPGPP
FNITPRRARR FFLRCIIWNT RDVILDDLSL TGEKMSDIYV KGWMIGFEEH KQKTDVHYRS
LGGEGNFNWR FIFPFDYLPA EQVCTIAKKD AFWRLDKTES KIPARVVFQI WDNDKFSFDD
FLGSLQLDLN RMPKPAKTAK KCSLDQLDDA FHPEWFVSLF EQKTVKGWWP CVAEEGEKKI
LAGKLEMTLE IVAESEHEER PAGQGRDEPN MNPKLEDPRR PDTSFLWFTS PYKTMKFILW
RRFRWAIILF IILFILLLFL AIFIYAFPNY AAMKLVKPFS
