ID DYSF_HUMAN Reviewed; 2080 AA. AC O75923; A0FK00; B1PZ70; B1PZ71; B1PZ72; B1PZ73; B1PZ74; B1PZ75; AC B1PZ76; B1PZ77; B1PZ78; B1PZ79; B1PZ80; B1PZ81; B3KQB9; O75696; AC Q09EX5; Q0H395; Q53QY3; Q53TD2; Q8TEL8; Q9UEN7; DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 11-NOV-2015, entry version 151. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS MMD1 VAL-1298; RP ARG-1857 AND CYS-2042, AND VARIANTS LGMD2B 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 RT myopathy 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 RT transcript: dysferlin_v1."; RL Hum. Genet. 120:410-419(2006). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 2; 3; 4; 5; 6; 7; RP 8; 9; 10; 11; 12 AND 13), ALTERNATIVE PROMOTER USAGE, AND ALTERNATIVE RP 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., RA Yee W.C.; RT "Identification and characterisation of human dysferlin transcript RT variants: implications for dysferlin mutational screening and RT 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., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA 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., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA 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., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RP 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., RA Beckmann J.S., Bushby K.M.D.; RT "A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 RT is 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 RT 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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., RA Walsh J., Johnson M.A., Bashir R., Britton S., Keers S., Argov Z., RA Mahjneh I., Fougerousse F., Beckmann J.S., Bushby K.M.D.; RT "Dysferlin is a plasma membrane protein and is expressed early in RT human development."; RL Hum. Mol. Genet. 8:855-861(1999). RN [10] RP ERRATUM. RA Anderson L.V.B., Davison K., Moss J.A., Young C., Cullen M.J., RA Walsh J., Johnson M.A., Bashir R., Britton S., Keers S., Argov Z., RA Mahjneh I., 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., RA 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 LGMD2B RP 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., RA Britton S., Nylen E., Keers S., Vafiadaki E., Greenberg C.R., RA Bushby K.M.D., Wrogemann K.; RT "Identical mutation in patients with limb girdle muscular dystrophy RT type 2B or Miyoshi myopathy suggests a role for modifier gene(s)."; RL Hum. Mol. Genet. 8:871-877(1999). RN [13] RP INVOLVEMENT IN DYSTAL MYOPATHY. 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 RT new 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 RT skeletal 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 RT mutant 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., RA Locatelli F., 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; 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., RA Takizawa T., 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, TISSUE RP SPECIFICITY, MUTAGENESIS OF VAL-67, 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, RT redistributes to the cytoplasm with dysferlin during skeletal muscle RT 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 RT in early myogenesis."; RL FASEB J. 21:1768-1776(2007). RN [21] 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., RA Buerckstuemmer T., 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 [22] 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 [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-166, PHOSPHORYLATION RP [LARGE SCALE ANALYSIS] AT SER-167 AND THR-198 (ISOFORMS 11; 13 AND 8), RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166 AND THR-197 RP (ISOFORMS 2; 5 AND 7), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [24] 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 [25] RP X-RAY CRYSTALLOGRAPHY (1.76 ANGSTROMS) OF 1-124 IN COMPLEX WITH RP CALCIUM, CALCIUM-BINDING (ISOFORMS 1 AND 14), SUBCELLULAR LOCATION, RP DOMAIN, 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 RT Ca(2+)-independent binding for membrane repair."; RL Structure 22:104-115(2014). RN [26] 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 RT Miyoshi myopathy."; RL Proc. Jpn. Acad. 75B:207-212(1999). RN [27] RP VARIANT MMD1 ASP-67, AND VARIANT LGMD2B 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 RT 2B and distal myopathy."; RL Neurology 55:1931-1933(2000). RN [28] 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., RA Oeltjen J., Brown H.E.V., Marchand S., Bourg N., Beley C., RA McKenna-Yasek D., Arahata K., Bohlega S., Cupler E., Illa I., RA Majneh I., Barohn R.J., Urtizberea J.A., Fardeau M., Amato A., RA Angelini C., Bushby K., Beckmann J.S., Brown R.H. Jr.; RT "Genomic organization of the dysferlin gene and novel mutations in RT Miyoshi myopathy."; RL Neurology 57:271-278(2001). RN [29] 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., RA Nishizawa M., Kato S., Saito K., Miyachi T., Yamashita H., Kawai M., RA Matsumura T., Kuzuhara S., Ibi T., Sahashi K., Nakai H., Kohnosu T., RA Nonaka I., 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 [30] RP VARIANTS LGMD2B 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., RA Bresolin N., Comi G.P.; RT "Molecular analysis of LGMD-2B and MM patients: identification of RT novel DYSF mutations and possible founder effect in the Italian RT population."; RL Neuromuscul. Disord. 13:788-795(2003). RN [31] 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 [32] RP VARIANTS MMD1 ARG-618; CYS-1041; LYS-1335; ARG-1361 AND ARG-1662, RP VARIANTS LGMD2B LYS-1335 AND CYS-1505, AND VARIANTS GLN-1022 AND RP 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 [33] 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- RT onset Miyoshi myopathy."; RL Muscle Nerve 29:721-723(2004). RN [34] RP VARIANT MMD1 GLN-389. RX PubMed=15515206; RA Oh S.-H., Kim T.-S., Choi Y.-C.; RT "Identification of a dysferlin gene mutation in a Korean case with RT Miyoshi myopathy."; RL Yonsei Med. J. 45:927-930(2004). RN [35] RP VARIANTS GLU-170 AND TRP-253, VARIANTS LGMD2B TRP-555 AND MET-1208, RP VARIANTS MMD1 GLU-299; TRP-456; TRP-555; HIS-1046 AND GLN-1693, RP VARIANT PROXIMODISTAL MYOPATHY VAL-1276, VARIANT PSEUDOMETABOLIC RP MYOPATHY PRO-266, AND VARIANTS VAL-189; LEU-1331; SER-1351 AND RP 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., RA Urtizberea A., 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 [36] RP ERRATUM. 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., RA Urtizberea A., Eymard B., Leturcq F., Levy N.; RL Hum. Mutat. 26:592-592(2005). RN [37] RP VARIANTS MMD1 GLU-170; LEU-374; TRP-959; TRP-1693; ASN-1837 AND RP GLY-1942 AND CYS-2042, VARIANTS LGMD2B ARG-621; TRP-959; GLN-1038; RP LYS-1335 AND CYS-2042, AND VARIANT SER-1678. RX PubMed=16100712; DOI=10.1002/humu.9364; RA Cagliani R., Magri F., Toscano A., Merlini L., Fortunato F., RA Lamperti C., Rodolico C., Prelle A., Sironi M., Aguennouz M., RA Ciscato P., Uncini A., Moggio M., Bresolin N., Comi G.P.; RT "Mutation finding in patients with dysferlin deficiency and role of RT the dysferlin interacting proteins annexin A1 and A2 in muscular RT dystrophies."; RL Hum. Mutat. 26:283-283(2005). RN [38] RP VARIANTS LGMD2B 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 RT leading to mRNA decay and possible C2-domain misfolding."; RL Hum. Mutat. 27:599-600(2006). RN [39] RP VARIANTS LGMD2B 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 RT computer-based structural predictions."; RL J. Neurol. Sci. 250:71-78(2006). RN [40] 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., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). RN [41] RP VARIANTS LGMD2B 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 [42] RP VARIANT LGMD2B 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 [43] RP VARIANTS LGMD2B ARG-52; ARG-155; GLU-170; GLU-234; THR-284; TRP-555; RP ARG-618; ARG-731; CYS-930; GLN-1022; PRO-1228; THR-1526; ASP-1543; RP TRP-1768; SER-1970 AND CYS-2042, VARIANTS MMD1 GLU-299; RP 386-PHE--ASP-390 DELINS TYR; ARG-426; TRP-456; TRP-555; LEU-1029; RP HIS-1046; HIS-1046; GLN-1693; 1938-THR-ALA-1939 DEL AND CYS-2042, RP VARIANTS GLU-170; TRP-253 AND TRP-555, VARIANTS PROXIMODISTAL MYOPATHY RP ARG-299; ARG-340; VAL-1748; TRP-1768 AND CYS-2042, VARIANT RP PSEUDOMETABOLIC MYOPATHY PRO-266, AND VARIANTS VAL-84; VAL-189; RP ALA-335; LEU-374; ASN-390; GLN-819; 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., RA Urtizberea J.A., Eymard B., Leturcq F., Levy N.; RT "Analysis of the DYSF mutational spectrum in a large cohort of RT 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 CC sarcolemma repair mechanism of both skeletal muscle and CC cardiomyocytes that permits rapid resealing of membranes disrupted CC by mechanical stress (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Interacts with CACNA1S. Interacts with ANXA1; the CC interaction is Ca(2+)- and injury state-dependent. Interacts with CC ANXA2; the interaction is Ca(2+)- and injury state-dependent. CC Interacts with CACNA1S and PARVB. Interacts with TRIM72/MG53; CC interaction is required for transport to sites of cell injury CC during repair patch formation (By similarity). Interacts with CAV3 CC and PARVB. Interacts with AHNAK; the interaction is direct and CC Ca(2+)-independent. Interacts with AHNAK2; the interaction is CC direct and Ca(2+)-independent. {ECO:0000250, CC ECO:0000269|PubMed:11532985, ECO:0000269|PubMed:15835269, CC ECO:0000269|PubMed:17185750, ECO:0000269|PubMed:24239457}. CC -!- INTERACTION: CC P35609:ACTN2; NbExp=2; IntAct=EBI-2799016, EBI-77797; CC Q8TCU4:ALMS1; NbExp=3; IntAct=EBI-2799016, EBI-308651; CC Q9UKG1:APPL1; NbExp=2; IntAct=EBI-2799016, EBI-741243; CC Q8N3K9:CMYA5; NbExp=3; IntAct=EBI-2799016, EBI-2323272; CC P17661:DES; NbExp=3; IntAct=EBI-2799016, EBI-1055572; CC Q16760:DGKD; NbExp=3; IntAct=EBI-2799016, EBI-719333; CC O75190:DNAJB6; NbExp=2; IntAct=EBI-2799016, EBI-1053164; CC Q14315:FLNC; NbExp=3; IntAct=EBI-2799016, EBI-489954; CC Q00872:MYBPC1; NbExp=4; IntAct=EBI-2799016, EBI-5652924; CC P52179:MYOM1; NbExp=3; IntAct=EBI-2799016, EBI-5353249; CC P54296:MYOM2; NbExp=3; IntAct=EBI-2799016, EBI-5357134; CC P20929:NEB; NbExp=6; IntAct=EBI-2799016, EBI-1049657; CC Q96CV9:OPTN; NbExp=3; IntAct=EBI-2799016, EBI-748974; CC Q9Y3Z3:SAMHD1; NbExp=2; IntAct=EBI-2799016, EBI-1054601; CC Q13326:SGCG; NbExp=3; IntAct=EBI-2799016, EBI-5357343; CC O95295:SNAPIN; NbExp=3; IntAct=EBI-2799016, EBI-296723; CC Q8WZ42:TTN; NbExp=17; IntAct=EBI-2799016, EBI-681210; CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma; Single-pass type CC II membrane protein. Cytoplasmic vesicle membrane {ECO:0000250}; CC Single-pass type II membrane protein {ECO:0000250}. Cell membrane. CC Note=Colocalizes, during muscle differentiation, with BIN1 in the CC T-tubule system of myotubules and at the site of contact between CC two myotubes or a myoblast and a myotube. Wounding of myotubes led CC to its focal enrichment to the site of injury and to its CC relocalization in a Ca(2+)-dependent manner toward the plasma CC membrane. Colocalizes with AHNAK, AHNAK2 and PARVB at the CC sarcolemma of skeletal muscle. Detected on the apical plasma CC membrane of the syncytiotrophoblast. Reaches the plasmma membrane CC through a caveolin-independent mechanism. Retained by caveolin at CC the plasmma membrane (By similarity). Colocalizes, during muscle CC differentiation, with CACNA1S in the T-tubule system of myotubules CC (By similarity). Accumulates and colocalizes with fusion vesicles CC at the sarcolemma disruption sites (By similarity). {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 Note=Contains a phosphoserine at position 166. Contains a CC phosphothreonine at position 197. {ECO:0000244|PubMed:24275569}; 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 Note=Contains a phosphoserine at position 166. Contains a CC phosphothreonine at position 197. {ECO:0000244|PubMed:24275569}; 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 Note=Contains a phosphoserine at position 166. Contains a CC phosphothreonine at position 197. {ECO:0000244|PubMed:24275569}; CC Name=8; CC IsoId=O75923-8; Sequence=VSP_035924, VSP_035925; CC Note=Contains a phosphoserine at position 167. Contains a CC phosphothreonine at position 198. {ECO:0000244|PubMed:24275569}; 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 Note=Contains a phosphoserine at position 167. Contains a CC phosphothreonine at position 198. {ECO:0000244|PubMed:24275569}; 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 Note=Contains a phosphoserine at position 167. Contains a CC phosphothreonine at position 198. {ECO:0000244|PubMed:24275569}; CC Name=14; Synonyms=Dysferlin_v1, DYSF_v1; CC IsoId=O75923-14; Sequence=VSP_035924; CC Note=Produced by alternative promoter usage.; CC Name=15; CC IsoId=O75923-15; Sequence=VSP_035926, VSP_035928, VSP_035929; CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle, myoblast, CC myotube and in the syncytiotrophoblast (STB) of the placenta (at CC protein level). Ubiquitous. Highly expressed in skeletal muscle. CC Also found in heart, brain, spleen, intestine, placenta and at CC lower levels in liver, lung, kidney and pancreas. CC {ECO:0000269|PubMed:10196375, ECO:0000269|PubMed:11532985, CC ECO:0000269|PubMed:11959863, ECO:0000269|PubMed:15318348, CC ECO:0000269|PubMed:16896923, ECO:0000269|PubMed:17185750, CC ECO:0000269|PubMed:17363620, ECO:0000269|PubMed:17554076, CC ECO:0000269|PubMed:24239457}. CC -!- DEVELOPMENTAL STAGE: Expression in limb tissue from 5-6 weeks CC embryos; persists throughout development. CC {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 CC affinity for calcium, the C2 domain 1 seems to be largely CC unstructured in the absence of bound ligands. The C2 domain 1 from CC isoform 14 does not bind calcium in the absence of bound CC phospholipid (PubMed:24239457, PubMed:24461013). CC {ECO:0000269|PubMed:24239457, ECO:0000269|PubMed:24461013}. CC -!- DISEASE: Limb-girdle muscular dystrophy 2B (LGMD2B) [MIM:253601]: CC An autosomal recessive degenerative myopathy characterized by CC weakness and atrophy starting in the proximal pelvifemoral CC muscles, with onset in the late teens or later, massive elevation CC of serum creatine kinase levels and slow progression. Scapular CC muscle involvement is minor and not present at onset. Upper limb CC 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:17287450, ECO:0000269|PubMed:18306167, CC ECO:0000269|PubMed:18853459, ECO:0000269|PubMed:9731526}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC -!- DISEASE: Miyoshi muscular dystrophy 1 (MMD1) [MIM:254130]: A late- CC onset muscular dystrophy involving the distal lower limb CC musculature. It is characterized by weakness that initially CC affects the gastrocnemius muscle during early adulthood. CC {ECO:0000269|PubMed:10196377, ECO:0000269|PubMed:11134403, CC ECO:0000269|PubMed:11468312, 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.26}. Note=The disease is caused by mutations CC affecting 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 CC age and the anterior tibial muscles are the first muscle group to CC be involved. Inheritance is autosomal recessive. Note=The disease CC is caused by mutations affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the ferlin family. {ECO:0000305}. CC -!- SIMILARITY: Contains 7 C2 domains. {ECO:0000255|PROSITE- CC ProRule:PRU00041}. CC -!- SEQUENCE CAUTION: CC Sequence=BAG51981.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=CAA07603.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC Sequence=CAA07603.1; Type=Frameshift; Positions=1972; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Leiden Muscular Dystrophy pages; CC Note=Dysferlin; CC URL="http://www.dmd.nl/dysf_home.html"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Dysferlin entry; CC URL="https://en.wikipedia.org/wiki/Dysferlin"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 UniGene; Hs.252180; -. 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=28-124. DR PDBsum; 4CAH; -. DR PDBsum; 4CAI; -. DR PDBsum; 4IHB; -. DR PDBsum; 4IQH; -. DR ProteinModelPortal; O75923; -. DR SMR; O75923; 1-124, 943-1051. DR BioGrid; 113896; 4. DR IntAct; O75923; 44. DR STRING; 9606.ENSP00000386881; -. DR TCDB; 1.F.1.2.1; the synaptosomal vesicle fusion pore (svf-pore) family. DR PhosphoSite; O75923; -. DR BioMuta; DYSF; -. DR MaxQB; O75923; -. DR PaxDb; O75923; -. DR PRIDE; O75923; -. DR Ensembl; ENST00000258104; ENSP00000258104; ENSG00000135636. [O75923-1] DR Ensembl; ENST00000394120; ENSP00000377678; ENSG00000135636. [O75923-14] DR Ensembl; ENST00000409366; ENSP00000386512; ENSG00000135636. [O75923-10] DR Ensembl; ENST00000409582; ENSP00000386547; ENSG00000135636. [O75923-7] DR Ensembl; ENST00000409651; ENSP00000386683; ENSG00000135636. [O75923-8] DR Ensembl; ENST00000409744; ENSP00000386285; ENSG00000135636. [O75923-12] DR Ensembl; ENST00000409762; ENSP00000387137; ENSG00000135636. [O75923-5] DR Ensembl; ENST00000410020; ENSP00000386881; ENSG00000135636. [O75923-13] DR Ensembl; ENST00000410041; ENSP00000386617; ENSG00000135636. [O75923-11] DR Ensembl; ENST00000413539; ENSP00000407046; ENSG00000135636. [O75923-2] DR Ensembl; ENST00000429174; ENSP00000398305; ENSG00000135636. [O75923-4] DR GeneID; 8291; -. DR KEGG; hsa:8291; -. DR UCSC; uc002sie.3; human. [O75923-1] DR UCSC; uc002sif.3; human. [O75923-14] DR UCSC; uc002sig.4; human. [O75923-3] DR UCSC; uc010fee.3; human. [O75923-4] DR UCSC; uc010fef.3; human. [O75923-7] DR UCSC; uc010feg.3; human. [O75923-2] DR UCSC; uc010feh.3; human. [O75923-6] DR UCSC; uc010fei.3; human. [O75923-5] DR UCSC; uc010fej.3; human. [O75923-12] DR UCSC; uc010fek.3; human. [O75923-11] DR UCSC; uc010fel.3; human. [O75923-9] DR UCSC; uc010fem.3; human. [O75923-10] DR UCSC; uc010fen.3; human. [O75923-13] DR UCSC; uc010feo.3; human. [O75923-8] DR CTD; 8291; -. DR GeneCards; DYSF; -. DR GeneReviews; DYSF; -. DR HGNC; HGNC:3097; DYSF. DR HPA; CAB002510; -. DR HPA; HPA017071; -. DR HPA; HPA021945; -. DR MIM; 253601; phenotype. DR MIM; 254130; phenotype. DR MIM; 603009; gene. DR MIM; 606768; phenotype. DR neXtProt; NX_O75923; -. DR Orphanet; 268; Autosomal recessive limb-girdle muscular dystrophy type 2B. DR Orphanet; 199329; Congenital myopathy, Paradas type. DR Orphanet; 178400; Distal myopathy with anterior tibial onset. DR Orphanet; 45448; Miyoshi myopathy. DR PharmGKB; PA27554; -. DR eggNOG; KOG1326; Eukaryota. DR eggNOG; ENOG410XPT2; LUCA. DR GeneTree; ENSGT00550000074414; -. DR HOVERGEN; HBG018972; -. DR InParanoid; O75923; -. DR KO; K18261; -. DR OMA; EPLIPIQ; -. DR OrthoDB; EOG7CVPWR; -. DR PhylomeDB; O75923; -. DR TreeFam; TF316871; -. DR Reactome; R-HSA-397014; Muscle contraction. DR ChiTaRS; DYSF; human. DR GeneWiki; Dysferlin; -. DR GenomeRNAi; 8291; -. DR NextBio; 31071; -. DR PRO; PR:O75923; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; O75923; -. DR Genevisible; O75923; HS. 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; IDA:UniProtKB. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0030027; C:lamellipodium; IEA:Ensembl. 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:0001778; P:plasma membrane repair; IEA:Ensembl. DR GO; GO:0006906; P:vesicle fusion; IEA:Ensembl. DR Gene3D; 2.60.40.150; -; 8. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR012968; FerIin-domain. DR InterPro; IPR012560; Ferlin_A-domain. DR InterPro; IPR012561; Ferlin_B-domain. DR InterPro; IPR032362; Ferlin_C. DR InterPro; IPR006614; Peroxin/Ferlin. 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 SUPFAM; SSF49562; SSF49562; 8. DR PROSITE; PS50004; C2; 5. PE 1: Evidence at protein level; KW 3D-structure; Alternative promoter usage; Alternative splicing; KW Calcium; Cell membrane; Complete proteome; Cytoplasmic vesicle; KW Disease mutation; Limb-girdle muscular dystrophy; Lipid-binding; KW Membrane; Metal-binding; Phosphoprotein; Polymorphism; KW Reference proteome; Repeat; Signal-anchor; Transmembrane; KW Transmembrane helix. FT CHAIN 1 2080 Dysferlin. FT /FTId=PRO_0000057879. FT TOPO_DOM 1 2046 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 2047 2067 Helical. {ECO:0000255}. FT TOPO_DOM 2068 2080 Extracellular. {ECO:0000255}. FT DOMAIN 1 85 C2 1. {ECO:0000255|PROSITE- FT ProRule:PRU00041}. FT DOMAIN 207 302 C2 2. {ECO:0000255|PROSITE- FT ProRule:PRU00041}. FT DOMAIN 366 479 C2 3. {ECO:0000255|PROSITE- FT ProRule:PRU00041}. FT DOMAIN 1139 1244 C2 4. {ECO:0000255|PROSITE- FT ProRule:PRU00041}. FT DOMAIN 1336 1423 C2 5. {ECO:0000255|PROSITE- FT ProRule:PRU00041}. FT DOMAIN 1565 1663 C2 6. {ECO:0000255|PROSITE- FT ProRule:PRU00041}. FT DOMAIN 1813 1926 C2 7. {ECO:0000255|PROSITE- FT ProRule:PRU00041}. FT COMPBIAS 1038 1097 Arg-rich. FT METAL 18 18 Calcium. {ECO:0000269|PubMed:24239457}. FT METAL 19 19 Calcium; via carbonyl oxygen. FT {ECO:0000269|PubMed:24239457}. FT METAL 21 21 Calcium. {ECO:0000269|PubMed:24239457}. FT METAL 40 40 Calcium. {ECO:0000269|PubMed:24239457}. FT MOD_RES 166 166 Phosphothreonine. FT {ECO:0000244|PubMed:24275569}. FT VAR_SEQ 1 29 MLRVFILYAENVHTPDTDISDAYCSAVFA -> MLCCLLVR FT ASNLPSAKKDRRSDPVASLTFR (in isoform 8, FT isoform 9, isoform 10, isoform 11, FT isoform 12, isoform 13 and isoform 14). FT {ECO:0000303|PubMed:16896923, FT ECO:0000303|PubMed:19221801}. FT /FTId=VSP_035924. FT VAR_SEQ 152 152 A -> AGGGQSRAETWSLLSDSTMDTRYSGKKWPAPT (in FT isoform 2, isoform 5, isoform 7, isoform FT 8, isoform 11 and isoform 13). FT {ECO:0000303|PubMed:19221801}. FT /FTId=VSP_035925. FT VAR_SEQ 494 508 EEPAGAVKPSKASDL -> V (in isoform 3, FT isoform 5, isoform 6, isoform 7, isoform FT 9, isoform 11, isoform 12, isoform 13 and FT isoform 15). FT {ECO:0000303|PubMed:19221801, FT ECO:0000303|Ref.7}. FT /FTId=VSP_035926. FT VAR_SEQ 1470 1470 Q -> QLADGLSSLAPTNTASPPSSPH (in isoform FT 4, isoform 6, isoform 7, isoform 10, FT isoform 12 and isoform 13). FT {ECO:0000303|PubMed:19221801}. FT /FTId=VSP_035927. FT VAR_SEQ 1934 1968 KPAKTAKKCSLDQLDDAFHPEWFVSLFEQKTVKGW -> SS FT ASSSRPPRPDCPARVGRQTDGPAHTPRVANMEL (in FT isoform 15). {ECO:0000303|Ref.7}. FT /FTId=VSP_035928. FT VAR_SEQ 1969 2080 Missing (in isoform 15). FT {ECO:0000303|Ref.7}. FT /FTId=VSP_035929. FT VARIANT 52 52 W -> R (in LGMD2B). FT {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057834. FT VARIANT 67 67 V -> D (in MMD1 and LGMD2B; Reduces FT calcium-sensitive phospholipid binding FT and interaction with AHNAK and AHNAK2). FT {ECO:0000269|PubMed:11134403, FT ECO:0000269|PubMed:11959863}. FT /FTId=VAR_057835. FT VARIANT 84 84 A -> V. {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057836. FT VARIANT 155 155 G -> R (in LGMD2B). FT {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057837. FT VARIANT 170 170 A -> E (in MMD1 and LGMD2B; also found in FT patients with isolated hyperCKemia; FT dbSNP:rs34999029). FT {ECO:0000269|PubMed:16010686, FT ECO:0000269|PubMed:16100712, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_024853. FT VARIANT 189 189 L -> V (in dbSNP:rs13407355). FT {ECO:0000269|PubMed:16010686, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_024854. FT VARIANT 234 234 G -> E (in LGMD2B). FT {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057838. FT VARIANT 253 253 R -> W (found in patients with isolated FT hyperCKemia). FT {ECO:0000269|PubMed:16010686, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_024855. FT VARIANT 266 266 L -> P (in pseudometabolic myopathy). FT {ECO:0000269|PubMed:16010686, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_024856. FT VARIANT 284 284 I -> T (in LGMD2B). FT {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057839. FT VARIANT 299 299 G -> E (in MMD1). FT {ECO:0000269|PubMed:16010686, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_024857. FT VARIANT 299 299 G -> R (in LGMD2B and proximodistal FT myopathy). {ECO:0000269|PubMed:16705711, FT ECO:0000269|PubMed:18306167, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057840. FT VARIANT 299 299 G -> W (in MMD1). FT {ECO:0000269|PubMed:18306167}. FT /FTId=VAR_057841. FT VARIANT 335 335 G -> A. {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057842. FT VARIANT 340 340 S -> R (in proximodistal myopathy). FT {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057843. FT VARIANT 374 374 V -> L (in MMD1; unknown pathological FT significance; dbSNP:rs150724610). FT {ECO:0000269|PubMed:16100712, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057844. FT VARIANT 386 390 FRAED -> Y (in MMD1). FT {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057845. FT VARIANT 389 389 E -> Q (in MMD1). FT {ECO:0000269|PubMed:15515206}. FT /FTId=VAR_057846. FT VARIANT 390 390 D -> N. {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057847. FT VARIANT 426 426 G -> R (in MMD1). FT {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057848. FT VARIANT 426 426 G -> V (in MMD1). FT {ECO:0000269|PubMed:15477515}. FT /FTId=VAR_057849. FT VARIANT 456 456 C -> W (in MMD1). FT {ECO:0000269|PubMed:16010686, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_024858. FT VARIANT 519 519 G -> R (in MMD1). FT {ECO:0000269|PubMed:17287450}. FT /FTId=VAR_057850. FT VARIANT 555 555 R -> W (in LGMD2B and MMD1; also found in FT patients with isolated hyperCKemia). FT {ECO:0000269|PubMed:16010686, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_024859. FT VARIANT 618 618 G -> R (in MMD1 and LGMD2B). FT {ECO:0000269|PubMed:15469449, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057851. FT VARIANT 621 621 G -> R (in LGMD2B). FT {ECO:0000269|PubMed:16100712}. FT /FTId=VAR_057852. FT VARIANT 625 625 D -> Y (in LGMD2B). FT {ECO:0000269|PubMed:17287450}. FT /FTId=VAR_057853. FT VARIANT 731 731 P -> R (in LGMD2B). FT {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057854. FT VARIANT 791 791 P -> R (in MMD1 and LGMD2B). FT {ECO:0000269|PubMed:10196377, FT ECO:0000269|PubMed:16996541}. FT /FTId=VAR_012308. FT VARIANT 819 819 R -> Q. {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057855. FT VARIANT 834 834 I -> V (in dbSNP:rs34671418). FT /FTId=VAR_049055. FT VARIANT 930 930 W -> C (in LGMD2B; unknown pathological FT significance). FT {ECO:0000269|PubMed:16996541, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057856. FT VARIANT 959 959 R -> W (in MMD1 and LGMD2B). FT {ECO:0000269|PubMed:14678801, FT ECO:0000269|PubMed:16100712}. FT /FTId=VAR_024860. FT VARIANT 999 999 W -> C (in MMD1; dbSNP:rs28937581). FT {ECO:0000269|PubMed:12796534, FT ECO:0000269|Ref.26}. FT /FTId=VAR_057857. FT VARIANT 1022 1022 R -> Q (in LGMD2B; unknown pathological FT significance; dbSNP:rs34211915). FT {ECO:0000269|PubMed:14678801, FT ECO:0000269|PubMed:15469449, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_024861. FT VARIANT 1029 1029 P -> L (in MMD1). FT {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057858. FT VARIANT 1038 1038 R -> Q (in LGMD2B; unknown pathological FT significance). FT {ECO:0000269|PubMed:14678801, FT ECO:0000269|PubMed:16100712, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_024862. FT VARIANT 1041 1041 R -> C (in MMD1). FT {ECO:0000269|PubMed:15469449}. FT /FTId=VAR_057859. FT VARIANT 1046 1046 R -> H (in MMD1; dbNP:28939700; FT dbSNP:rs28939700). FT {ECO:0000269|PubMed:11468312, FT ECO:0000269|PubMed:16010686, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_024863. FT VARIANT 1065 1065 E -> EAE. {ECO:0000269|PubMed:16996541}. FT /FTId=VAR_024864. FT VARIANT 1072 1072 A -> P (in dbSNP:rs34660230). FT /FTId=VAR_049056. FT VARIANT 1096 1096 R -> H (in dbSNP:rs59915619). FT /FTId=VAR_061170. FT VARIANT 1208 1208 I -> M (in LGMD2B; dbSNP:rs148858485). FT {ECO:0000269|PubMed:16010686}. FT /FTId=VAR_024865. FT VARIANT 1228 1228 L -> P (in LGMD2B). FT {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057860. FT VARIANT 1242 1242 R -> H (in dbSNP:rs2303603). FT /FTId=VAR_020308. FT VARIANT 1276 1276 L -> V (in proximodistal myopathy). FT {ECO:0000269|PubMed:16010686, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_024866. FT VARIANT 1298 1298 I -> V (in MMD1 and LGMD2B; FT dbSNP:rs121908954). FT {ECO:0000269|PubMed:9731526}. FT /FTId=VAR_012309. FT VARIANT 1325 1325 I -> M (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_035893. FT VARIANT 1325 1325 I -> V (in dbSNP:rs145401010). FT {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057861. FT VARIANT 1331 1331 R -> L (in dbSNP:rs61742872). FT {ECO:0000269|PubMed:14678801, FT ECO:0000269|PubMed:16010686}. FT /FTId=VAR_024867. FT VARIANT 1335 1335 E -> K (in MMD1 and LGMD2B). FT {ECO:0000269|PubMed:14678801, FT ECO:0000269|PubMed:15469449, FT ECO:0000269|PubMed:16100712}. FT /FTId=VAR_024868. FT VARIANT 1341 1341 L -> P (in LGMD2B). FT {ECO:0000269|PubMed:16705711}. FT /FTId=VAR_057862. FT VARIANT 1349 1349 L -> V (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_035894. FT VARIANT 1351 1351 N -> S. {ECO:0000269|PubMed:16010686}. FT /FTId=VAR_024869. FT VARIANT 1361 1361 C -> R (in MMD1). FT {ECO:0000269|PubMed:15469449}. FT /FTId=VAR_057863. FT VARIANT 1505 1505 Y -> C (in LGMD2B). FT {ECO:0000269|PubMed:15469449}. FT /FTId=VAR_057864. FT VARIANT 1526 1526 K -> T (in LGMD2B; dbSNP:rs76086153). FT {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057865. FT VARIANT 1543 1543 G -> D (in LGMD2B). FT {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057866. FT VARIANT 1581 1581 R -> H (in dbSNP:rs185596534). FT {ECO:0000269|PubMed:12796534}. FT /FTId=VAR_057867. FT VARIANT 1662 1662 T -> R (in MMD1). FT {ECO:0000269|PubMed:15469449}. FT /FTId=VAR_057868. FT VARIANT 1678 1678 C -> S (found in patients with isolated FT hyperCKemia). FT {ECO:0000269|PubMed:16100712}. FT /FTId=VAR_057869. FT VARIANT 1679 1679 G -> E (in MMD1). FT {ECO:0000269|PubMed:12796534}. FT /FTId=VAR_057870. FT VARIANT 1693 1693 R -> Q (in MMD1). FT {ECO:0000269|PubMed:16010686, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_024870. FT VARIANT 1693 1693 R -> W (in MMD1). FT {ECO:0000269|PubMed:16100712}. FT /FTId=VAR_057871. FT VARIANT 1734 1734 E -> G (in LGMD2B). FT {ECO:0000269|PubMed:17287450}. FT /FTId=VAR_057872. FT VARIANT 1748 1748 E -> V (in proximodistal myopathy). FT {ECO:0000269|PubMed:16010686, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_024871. FT VARIANT 1768 1768 R -> W (in LGMD2B and proximodistal FT myopathy; unknown pathological FT significance). FT {ECO:0000269|PubMed:16996541, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057873. FT VARIANT 1837 1837 D -> N (in MMD1). FT {ECO:0000269|PubMed:16100712, FT ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057874. FT VARIANT 1842 1842 G -> D (in MMD1). FT {ECO:0000269|PubMed:15116377}. FT /FTId=VAR_057875. FT VARIANT 1857 1857 H -> R (in MMD1). FT {ECO:0000269|PubMed:9731526}. FT /FTId=VAR_012310. FT VARIANT 1922 1922 L -> P (in MMD1). FT {ECO:0000269|PubMed:15116377}. FT /FTId=VAR_057876. FT VARIANT 1938 1939 Missing (in MMD1). FT {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057877. FT VARIANT 1942 1942 C -> G (in MMD1). FT {ECO:0000269|PubMed:16100712}. FT /FTId=VAR_057878. FT VARIANT 1967 1967 G -> S. {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057879. FT VARIANT 1970 1970 P -> S (in LGMD2B). FT {ECO:0000269|PubMed:18853459}. FT /FTId=VAR_057880. FT VARIANT 2000 2000 R -> Q (in MMD1; dbSNP:rs115407852). FT {ECO:0000269|PubMed:11468312}. FT /FTId=VAR_024872. FT VARIANT 2042 2042 R -> C (in MMD1, LGMD2B and proximodistal FT myopathy). {ECO:0000269|PubMed:16100712, FT ECO:0000269|PubMed:16996541, FT ECO:0000269|PubMed:18853459, FT ECO:0000269|PubMed:9731526}. FT /FTId=VAR_012311. FT VARIANT 2068 2068 P -> L (in MMD1). FT {ECO:0000269|PubMed:15477515}. FT /FTId=VAR_057881. FT MUTAGEN 16 16 D->A: Fails to bind calcium. FT {ECO:0000269|PubMed:24461013}. FT MUTAGEN 21 21 D->A: Fails to bind calcium. FT {ECO:0000269|PubMed:24461013}. FT MUTAGEN 71 71 D->A: Fails to bind calcium. FT {ECO:0000269|PubMed:24461013}. FT MUTAGEN 79 79 R->D: Moderately increased calcium FT affinity. {ECO:0000269|PubMed:24461013}. FT MUTAGEN 80 80 F->A: Reduced calcium affinity. FT {ECO:0000269|PubMed:24461013}. FT STRAND 1 11 {ECO:0000244|PDB:4IHB}. FT STRAND 22 28 {ECO:0000244|PDB:4IHB}. FT STRAND 31 34 {ECO:0000244|PDB:4IQH}. FT STRAND 45 53 {ECO:0000244|PDB:4IQH}. FT STRAND 64 71 {ECO:0000244|PDB:4IQH}. FT STRAND 74 76 {ECO:0000244|PDB:4IQH}. FT STRAND 79 87 {ECO:0000244|PDB:4IQH}. FT HELIX 89 92 {ECO:0000244|PDB:4IQH}. FT STRAND 98 106 {ECO:0000244|PDB:4IQH}. FT STRAND 112 123 {ECO:0000244|PDB:4IQH}. FT STRAND 946 958 {ECO:0000244|PDB:4CAH}. FT STRAND 966 973 {ECO:0000244|PDB:4CAH}. FT HELIX 983 985 {ECO:0000244|PDB:4CAH}. FT STRAND 996 998 {ECO:0000244|PDB:4CAH}. FT STRAND 1000 1002 {ECO:0000244|PDB:4CAI}. FT STRAND 1011 1015 {ECO:0000244|PDB:4CAH}. FT STRAND 1021 1023 {ECO:0000244|PDB:4CAH}. FT STRAND 1028 1030 {ECO:0000244|PDB:4CAH}. FT STRAND 1037 1049 {ECO:0000244|PDB:4CAH}. 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 //