ID DYSF_MOUSE Reviewed; 2090 AA. AC Q9ESD7; Q6KAR3; Q80VT0; Q9QXC0; DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 16-DEC-2008, sequence version 3. DT 24-JAN-2024, entry version 183. 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 Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, AND INVOLVEMENT RP IN PROGRESSIVE MUSCULAR DYSTROPHY. RC STRAIN=BALB/cJ, C57BL/10, and SJL/J; TISSUE=Skeletal muscle; RX PubMed=11234777; DOI=10.1097/00001756-200103050-00039; RA Vafiadaki E., Reis A., Keers S., Harrison R., Anderson L.V.B., RA Raffelsberger T., Ivanova S., Hoeger H., Bittner R.E., Bushby K.M.D., RA Bashir R.; RT "Cloning of the mouse dysferlin gene and genomic characterization of the RT SJL-Dysf mutation."; RL NeuroReport 12:625-629(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Thymus; RX PubMed=15449545; DOI=10.1093/dnares/11.2.127; RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., RA Saga Y., Kitamura H., Nakagawa T., Nagase T., Ohara O., Koga H.; RT "Prediction of the coding sequences of mouse homologues of FLJ genes: the RT complete nucleotide sequences of 110 mouse FLJ-homologous cDNAs identified RT by screening of terminal sequences of cDNA clones randomly sampled from RT size-fractionated libraries."; RL DNA Res. 11:127-135(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 467-1854 (ISOFORMS 1/2), AND INVOLVEMENT IN RP PROGRESSIVE MUSCULAR DYSTROPHY. RC STRAIN=B6C3FE, BALB/cJ, C3H/HeJ, C57BL/10, and C57BL/6J; RC TISSUE=Muscle; RX PubMed=10508505; DOI=10.1038/13770; RA Bittner R.E., Anderson L.V.B., Burkhardt E., Bashir R., Vafiadaki E., RA Ivanova S., Raffelsberger T., Maerk I., Hoeger H., Jung M., Karbasiyan M., RA Storch M., Lassmann H., Moss J.A., Davison K., Harrison R., Bushby K.M.D., RA Reis A.; RT "Dysferlin deletion in SJL mice (SJL-Dysf) defines a natural model for limb RT girdle muscular dystrophy 2B."; RL Nat. Genet. 23:141-142(1999). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1490-2090 (ISOFORMS 1/2/3). RC TISSUE=Mammary tumor; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION, INTERACTION WITH ANXA1 AND ANXA2, AND SUBCELLULAR LOCATION. RX PubMed=14506282; DOI=10.1074/jbc.m307247200; RA Lennon N.J., Kho A., Bacskai B.J., Perlmutter S.L., Hyman B.T., RA Brown R.H. Jr.; RT "Dysferlin interacts with annexins A1 and A2 and mediates sarcolemmal RT wound-healing."; RL J. Biol. Chem. 278:50466-50473(2003). RN [7] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=12736685; DOI=10.1038/nature01573; RA Bansal D., Miyake K., Vogel S.S., Groh S., Chen C.C., Williamson R., RA McNeil P.L., Campbell K.P.; RT "Defective membrane repair in dysferlin-deficient muscular dystrophy."; RL Nature 423:168-172(2003). RN [8] RP INTERACTION WITH CACNA1S, AND SUBCELLULAR LOCATION. RX PubMed=16550931; RA Ampong B.N., Imamura M., Matsumiya T., Yoshida M., Takeda S.; RT "Intracellular localization of dysferlin and its association with the RT dihydropyridine receptor."; RL Acta Myol. 24:134-144(2005). RN [9] RP INTERACTION WITH PARVB. 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 [10] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=17607357; DOI=10.1172/jci30848; RA Han R., Bansal D., Miyake K., Muniz V.P., Weiss R.M., McNeil P.L., RA Campbell K.P.; RT "Dysferlin-mediated membrane repair protects the heart from stress-induced RT left ventricular injury."; RL J. Clin. Invest. 117:1805-1813(2007). RN [11] RP SUBCELLULAR LOCATION. RX PubMed=18096699; DOI=10.1074/jbc.m708776200; RA Hernandez-Deviez D.J., Howes M.T., Laval S.H., Bushby K., Hancock J.F., RA Parton R.G.; RT "Caveolin regulates endocytosis of the muscle repair protein, dysferlin."; RL J. Biol. Chem. 283:6476-6488(2008). RN [12] RP INTERACTION WITH TRIM72. RX PubMed=19380584; DOI=10.1074/jbc.m109.009589; RA Cai C., Weisleder N., Ko J.-K., Komazaki S., Sunada Y., Nishi M., RA Takeshima H., Ma J.; RT "Membrane repair defects in muscular dystrophy are linked to altered RT interaction between MG53, caveolin-3, and dysferlin."; RL J. Biol. Chem. 284:15894-15902(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164; SER-167; SER-209 AND RP THR-219 (ISOFORM 2), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, and Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). 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. CC {ECO:0000269|PubMed:12736685, ECO:0000269|PubMed:14506282, CC ECO:0000269|PubMed:17607357}. CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00041}; CC -!- SUBUNIT: Interacts with CAV3. Interacts with AHNAK; the interaction is CC direct and Ca(2+)-independent. Interacts with AHNAK2; the interaction CC is direct and Ca(2+)-independent (By similarity). Interacts with ANXA1; CC the interaction is Ca(2+)- and injury state-dependent. Interacts with CC ANXA2; the interaction is Ca(2+)- and injury state-dependent. Interacts CC with CACNA1S and PARVB. Interacts with TRIM72/MG53; interaction is CC required for transport to sites of cell injury during repair patch CC formation. Interacts with RIPOR2; this interaction occurs during early CC myogenic differentiation (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:O75923, ECO:0000269|PubMed:14506282, CC ECO:0000269|PubMed:15835269, ECO:0000269|PubMed:16550931, CC ECO:0000269|PubMed:19380584}. CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma; Single-pass type II CC membrane protein. Cytoplasmic vesicle membrane; Single-pass type II CC membrane protein. Cell membrane {ECO:0000250}. Note=Colocalizes, during CC muscle differentiation, with BIN1 in the T-tubule system of myotubules CC and at the site of contact between two myotubes or a myoblast and a CC myotube (By similarity). Accumulates and colocalizes with fusion CC vesicles at the sarcolemma disruption sites. Wounding of myotubes led CC to its focal enrichment to the site of injury and to its relocalization CC in a Ca(2+)-dependent manner toward the plasma membrane (By CC similarity). Colocalizes with ANXA1 and ANXA2 at the sarcolemma in CC skeletal muscle. Colocalizes with PARVB at the sarcolemma of skeletal CC muscle (By similarity). Retained by caveolin at the plasmma membrane. CC Reaches the plasmma membrane through a caveolin-independent mechanism. CC Colocalizes, during muscle differentiation, with CACNA1S in the T- CC tubule system of myotubules. Detected on the apical plasma membrane of CC the syncytiotrophoblast (By similarity). {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9ESD7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9ESD7-2; Sequence=VSP_035930, VSP_035931, VSP_035932, CC VSP_035933; CC Name=3; CC IsoId=Q9ESD7-3; Sequence=VSP_035930, VSP_035932, VSP_035933; CC -!- TISSUE SPECIFICITY: Expressed in skeletal and cardiac muscles (at CC protein level). Expressed in skeletal muscle and heart. Also found in CC brain, liver and kidney. {ECO:0000269|PubMed:11234777, CC ECO:0000269|PubMed:12736685}. 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 (By similarity). {ECO:0000250}. CC -!- DISEASE: Note=Defects in Dysf are the cause of a slowly progressive CC muscular dystrophy observed in SJL mice. It affects primarily the CC proximal muscles and it is inherited as autosomal recessive trait. CC {ECO:0000269|PubMed:10508505, ECO:0000269|PubMed:11234777}. CC -!- MISCELLANEOUS: Mice lacking Dysf maintain a functional dystrophin CC glycoprotein complex (DGC) but their muscle cells are defective in CC repairing the plasma membrane disruptions and accumulates vesicles at CC the sarcolemma. They develop a progressive muscular dystrophy and CC cardiomyopathy. CC -!- SIMILARITY: Belongs to the ferlin family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAD21394.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=CAB63111.1; Type=Miscellaneous discrepancy; Note=The sequence differs significantly from amino acid position 1855.; Evidence={ECO:0000305}; 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; AF188290; AAG17046.2; -; mRNA. DR EMBL; AK131144; BAD21394.1; ALT_INIT; mRNA. DR EMBL; AC153607; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC153608; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AJ242954; CAB63111.1; ALT_SEQ; mRNA. DR EMBL; BC043692; AAH43692.1; -; mRNA. DR CCDS; CCDS39536.1; -. [Q9ESD7-2] DR CCDS; CCDS85081.1; -. [Q9ESD7-3] DR RefSeq; NP_001071162.1; NM_001077694.2. DR RefSeq; NP_001297081.1; NM_001310152.1. [Q9ESD7-3] DR RefSeq; NP_067444.2; NM_021469.3. [Q9ESD7-2] DR AlphaFoldDB; Q9ESD7; -. DR SMR; Q9ESD7; -. DR BioGRID; 205052; 4. DR IntAct; Q9ESD7; 1. DR MINT; Q9ESD7; -. DR STRING; 10090.ENSMUSP00000080579; -. DR iPTMnet; Q9ESD7; -. DR PhosphoSitePlus; Q9ESD7; -. DR SwissPalm; Q9ESD7; -. DR jPOST; Q9ESD7; -. DR MaxQB; Q9ESD7; -. DR PaxDb; 10090-ENSMUSP00000080579; -. DR PeptideAtlas; Q9ESD7; -. DR ProteomicsDB; 277534; -. [Q9ESD7-1] DR ProteomicsDB; 277535; -. [Q9ESD7-2] DR ProteomicsDB; 277536; -. [Q9ESD7-3] DR Pumba; Q9ESD7; -. DR Antibodypedia; 2461; 359 antibodies from 34 providers. DR DNASU; 26903; -. DR Ensembl; ENSMUST00000081904.7; ENSMUSP00000080579.7; ENSMUSG00000033788.16. [Q9ESD7-2] DR Ensembl; ENSMUST00000113818.8; ENSMUSP00000109449.2; ENSMUSG00000033788.16. [Q9ESD7-3] DR Ensembl; ENSMUST00000168387.8; ENSMUSP00000132297.2; ENSMUSG00000033788.16. [Q9ESD7-1] DR GeneID; 26903; -. DR KEGG; mmu:26903; -. DR UCSC; uc009cos.3; mouse. [Q9ESD7-3] DR UCSC; uc009cot.2; mouse. [Q9ESD7-2] DR AGR; MGI:1349385; -. DR CTD; 8291; -. DR MGI; MGI:1349385; Dysf. DR VEuPathDB; HostDB:ENSMUSG00000033788; -. DR eggNOG; KOG1326; Eukaryota. DR GeneTree; ENSGT00940000156187; -. DR HOGENOM; CLU_001183_2_1_1; -. DR InParanoid; Q9ESD7; -. DR TreeFam; TF316871; -. DR BioGRID-ORCS; 26903; 2 hits in 77 CRISPR screens. DR ChiTaRS; Dysf; mouse. DR PRO; PR:Q9ESD7; -. DR Proteomes; UP000000589; Chromosome 6. DR RNAct; Q9ESD7; Protein. DR Bgee; ENSMUSG00000033788; Expressed in hindlimb stylopod muscle and 156 other cell types or tissues. DR ExpressionAtlas; Q9ESD7; baseline and differential. DR GO; GO:0034451; C:centriolar satellite; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB. DR GO; GO:0030659; C:cytoplasmic vesicle membrane; TAS:Reactome. DR GO; GO:0005769; C:early endosome; ISO:MGI. DR GO; GO:0030139; C:endocytic vesicle; ISO:MGI. DR GO; GO:0005768; C:endosome; ISO:MGI. DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI. DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB. DR GO; GO:0005770; C:late endosome; ISO:MGI. DR GO; GO:0098857; C:membrane microdomain; IDA:MGI. DR GO; GO:0005874; C:microtubule; IDA:MGI. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0042383; C:sarcolemma; IDA:UniProtKB. DR GO; GO:0030315; C:T-tubule; IDA:MGI. DR GO; GO:0043014; F:alpha-tubulin binding; IDA:MGI. DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB. DR GO; GO:0005544; F:calcium-dependent phospholipid binding; ISO:MGI. DR GO; GO:0008017; F:microtubule binding; IDA:MGI. DR GO; GO:0005543; F:phospholipid binding; ISS:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IMP:MGI. DR GO; GO:0071470; P:cellular response to osmotic stress; IMP:MGI. DR GO; GO:0045444; P:fat cell differentiation; IMP:MGI. DR GO; GO:0006071; P:glycerol metabolic process; IMP:MGI. DR GO; GO:0019915; P:lipid storage; IMP:MGI. DR GO; GO:0002281; P:macrophage activation involved in immune response; IMP:MGI. DR GO; GO:0002280; P:monocyte activation involved in immune response; IMP:MGI. DR GO; GO:0055001; P:muscle cell development; IMP:MGI. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:MGI. DR GO; GO:0050765; P:negative regulation of phagocytosis; IMP:MGI. DR GO; GO:0042177; P:negative regulation of protein catabolic process; IMP:MGI. DR GO; GO:1902915; P:negative regulation of protein polyubiquitination; IMP:MGI. DR GO; GO:0001778; P:plasma membrane repair; IDA:MGI. DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:MGI. DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:MGI. DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IMP:MGI. DR GO; GO:0030163; P:protein catabolic process; IMP:MGI. DR GO; GO:0000209; P:protein polyubiquitination; IMP:MGI. DR GO; GO:0090279; P:regulation of calcium ion import; IMP:MGI. DR GO; GO:0043403; P:skeletal muscle tissue regeneration; IMP:MGI. DR GO; GO:0033292; P:T-tubule organization; IMP:MGI. DR GO; GO:0006906; P:vesicle fusion; IMP:UniProtKB. 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; C2 domain; 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; 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:SF44; DYSFERLIN; 1. DR PANTHER; PTHR12546; FER-1-LIKE; 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; C2 domain (Calcium/lipid-binding domain, CaLB); 7. DR PROSITE; PS50004; C2; 7. DR Genevisible; Q9ESD7; MM. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Cell membrane; Cytoplasmic vesicle; KW Lipid-binding; Membrane; Metal-binding; Phosphoprotein; Reference proteome; KW Repeat; Signal-anchor; Transmembrane; Transmembrane helix. FT CHAIN 1..2090 FT /note="Dysferlin" FT /id="PRO_0000057880" FT TOPO_DOM 1..2056 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 2057..2077 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 2078..2090 FT /note="Extracellular" FT /evidence="ECO:0000255" FT DOMAIN 1..101 FT /note="C2 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT DOMAIN 206..323 FT /note="C2 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT DOMAIN 362..498 FT /note="C2 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT DOMAIN 1146..1272 FT /note="C2 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT DOMAIN 1320..1448 FT /note="C2 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT DOMAIN 1571..1689 FT /note="C2 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT DOMAIN 1805..1953 FT /note="C2 7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT REGION 130..217 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2005..2027 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:0000250" FT BINDING 19 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 21 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 40 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 411 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 411 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 419 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 467 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 467 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 469 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 469 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 475 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 1178 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 1184 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 1240 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 1242 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 1604 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 1610 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 1659 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 1661 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 1924 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 1927 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT BINDING 1930 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT MOD_RES 166 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O75923" FT VAR_SEQ 1..29 FT /note="MLRVFILFAENVHTPDSDISDAYCSAVFA -> MLCCLLARASNLPNVKKDR FT RSDPVASLIFR (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:11234777, FT ECO:0000303|PubMed:15449545" FT /id="VSP_035930" FT VAR_SEQ 152 FT /note="P -> PGGGQSRAETWSLLSDSTMDTRYSGKKWPVPT (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:15449545" FT /id="VSP_035931" FT VAR_SEQ 496..510 FT /note="EEPAGVLKSPQATDL -> V (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:11234777, FT ECO:0000303|PubMed:15449545" FT /id="VSP_035932" FT VAR_SEQ 647..654 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:11234777, FT ECO:0000303|PubMed:15449545" FT /id="VSP_035933" FT CONFLICT 467 FT /note="D -> G (in Ref. 4; CAB63111)" FT /evidence="ECO:0000305" FT CONFLICT 476 FT /note="T -> I (in Ref. 1; AAG17046)" FT /evidence="ECO:0000305" FT CONFLICT 510 FT /note="L -> V (in Ref. 4; CAB63111)" FT /evidence="ECO:0000305" FT CONFLICT 684 FT /note="I -> T (in Ref. 1; AAG17046)" FT /evidence="ECO:0000305" FT CONFLICT 690..691 FT /note="RV -> GI (in Ref. 1; AAG17046)" FT /evidence="ECO:0000305" FT CONFLICT 698 FT /note="N -> G (in Ref. 1; AAG17046)" FT /evidence="ECO:0000305" FT CONFLICT 712 FT /note="S -> T (in Ref. 1; AAG17046)" FT /evidence="ECO:0000305" FT CONFLICT 717 FT /note="A -> S (in Ref. 1; AAG17046)" FT /evidence="ECO:0000305" FT CONFLICT 727 FT /note="L -> I (in Ref. 1; AAG17046)" FT /evidence="ECO:0000305" FT CONFLICT 885 FT /note="L -> F (in Ref. 1; AAG17046)" FT /evidence="ECO:0000305" FT CONFLICT 909..910 FT /note="LT -> FS (in Ref. 1; AAG17046)" FT /evidence="ECO:0000305" FT CONFLICT 931 FT /note="S -> T (in Ref. 1; AAG17046)" FT /evidence="ECO:0000305" FT CONFLICT 953 FT /note="D -> A (in Ref. 1; AAG17046)" FT /evidence="ECO:0000305" FT CONFLICT 1175 FT /note="P -> A (in Ref. 1; AAG17046)" FT /evidence="ECO:0000305" FT CONFLICT 1187 FT /note="A -> S (in Ref. 4; CAB63111)" FT /evidence="ECO:0000305" FT CONFLICT 1694 FT /note="Y -> C (in Ref. 1; AAG17046)" FT /evidence="ECO:0000305" FT CONFLICT 1701 FT /note="Q -> K (in Ref. 1; AAG17046)" FT /evidence="ECO:0000305" FT CONFLICT 1705 FT /note="Q -> K (in Ref. 1; AAG17046)" FT /evidence="ECO:0000305" FT CONFLICT 1806 FT /note="R -> Q (in Ref. 1; AAG17046)" FT /evidence="ECO:0000305" FT MOD_RES Q9ESD7-2:164 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES Q9ESD7-2:167 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES Q9ESD7-2:209 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES Q9ESD7-2:219 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" SQ SEQUENCE 2090 AA; 237911 MW; 0EBD1E2353946143 CRC64; MLRVFILFAE NVHTPDSDIS DAYCSAVFAG VKKRTKVIKN SVNPVWNEGF EWDLKGIPLD QSSELLVVVK DHETMGRNRF LGEAKIPLQE VLATPSLSAS FNAPLLDAKQ QPTGASLVLQ VSYTPPPGAV PLFPPPASLA PSPTLPDMDL VPDTGGEEDT EDQGLTGDEA EPFLDQSAAV GPGGPTTPRK PPSHPPPHYP GAKRKRSSAP PRKLLSDKPQ DFQIRVQVIE GRQLPGVNIK PVVKVTAAGQ TKRTRIQKGN SPLFNETLFF NVFDSPLELF DEPIFITVVD SRSLRTDALL GEFRMDVGTV YREPRHAYLR KWLLLSDPDD FSAGARGYLK ASLCVLGPGD EAPLDKKDPS EDKEDIEGNL LRPTGVALRG AHFCLKLFRA EDLPQMDDAV MDNVKQIFGF DSNKKNLVDP FVEVSFAGKM LCSKILEKTA NPQWNQNITL PAMFPSMCEK MRIRVMDWDR LTHNDTVATT YLGMSKISAT GGEIEEEPAG VLKSPQATDL DDNLGFLPTF GPCYVNLYGS PREFTGFPDP YAELNTGKGE GVAYRGRVLL SLETKLVEHS EQKVEDLPAD DILRVEKYLR RRKYSLFAAF YSATMLQDVD DAIQFEVSIG NYGNKFDTTC LPLASTTQYS RAVFDGGSLP LPVGCHYYYL PWGNVKPVVV LSSYWEDISH RIEIQNQLLR VADRLEANLE QVHLALKAQC SSEDVDALVA QLTDELLADC SQPLCDIHEI PSATHLDQYL LRLRTRHLSQ IKEAALALKL GHSELSTALE QAEDWLLHLR ALAEEPQNSL PDIIIWMLQG DKRVAYQRVP AHEVLFSRRG PSYCGRNCGK LQTIFLKYPM EGMPGARMPV QIRIKLWFGL SVDEKEFNQF AEGKLSVFAE TYENQTKLAL VGNWGTTGLT YPKFSDVTGK IKLPKDSFRP SAGWAWAGDW FVCPEKTLLH DADAGHLSFV EEVFENQTRL PGGQWIYMSD NYTDVNGEKV LPKDDIECPL GWKWEDEEWS TDLNRAVDEQ GWEYSITIPP DRKPKHWVPV EKMYYTHRRR RWVRLRRRDL SQMEALKRHR QAEAEGEGWE YASLFGWKFH LEYRKTDAFR RRRWRRRMEP LEKTGPAAVF ALEGALGGMV DDKSEDSMSV STLSFGVNRP TISCIFDYGN RYHLRCYLYQ ARDLPAMDKD SFSDPYAIVS FLHQSQKTVV EKNTLNPTWD QTLIFYEIEI FGEPASIAEH PPCIVVELYD HDTYGADEFM GRCICQPSLE RMPRLAWFPL TRGSQPAGEL LAAFELIQRE KPAIHHIPGF EMHETSRILD ETEDTDLPYP PPQREANIYM VPQNIKPALQ RTAIEILAWG LRNMKSYQMA SISSPSLVVE CGGQTVQSCV IRNLRKNPNF DVCTLFMEVM LPREDLYCPP IVVKVIDNRQ FGRRPVVGQC TIRSLENFLC DPYSAESPSP QGGPDDVSLL SPGEDVLIDI DDKEPLIPVQ EEEFIDWWSK FFASVGEREK CGSYLEKDFD TLKVYDTQLE NVEAFGGLSD FCNTFKLYRG RTQEETDDPS VIGEFKGLFK IYPLPEDPAI PMPPRQFHQL AAQGPQECLV RIYIVRAFGL QPKDPNGKCD PYIKISIGKK SVSDQDNYIP CTLEPVFGKM FELTCTLPLE KDLKITLYDY DLLSKDEKIG ETVIDLENRL LSKFGARCGL PQTYCVSGPN QWRDQLRPSQ LLHLFCQQHR IKAPVYRTDR VTFQDKDYTI EEIEAGRLPN PHLGPVEERL ALHVLQQQGL VPEHVESRPL YSPLQPDIEQ GKLQMWIDIF PKVLGRPGPP FNITPRKARR FFLRCIIWNT KDVILDDLSL TGEKMSDIYV KGWMVGFEEH KQKTDVHYRS LGGEGNFNWR FVFPFDYLPA EQVCAVAKKD AFWRLDKTES KIPARVVFQI WDNDKFSFDD FLGSLQLDLN RMPKPAKTAE KCSLDQLDDT FHPEWFVSLF EQKTVKGWWP CVTEEGEKKM LAGKLEMTLE IVAESEHEER PAGQGRDEPN MNPKLEDPRR PDTSFLWFTS PYKTMKFILW RRFRCAIILF IILFILLLFL GVFVYAFPNY AAMKLVKPFR //