DYSF_MOUSE
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 03-AUG-2022, entry version 175.
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; 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, Pancreas,
RC 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;
CC Evidence={ECO:0000255|PROSITE-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};
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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; Q9ESD7; -.
DR PeptideAtlas; Q9ESD7; -.
DR PRIDE; Q9ESD7; -.
DR ProteomicsDB; 277534; -. [Q9ESD7-1]
DR ProteomicsDB; 277535; -. [Q9ESD7-2]
DR ProteomicsDB; 277536; -. [Q9ESD7-3]
DR Antibodypedia; 2461; 301 antibodies from 34 providers.
DR DNASU; 26903; -.
DR Ensembl; ENSMUST00000081904; ENSMUSP00000080579; ENSMUSG00000033788. [Q9ESD7-2]
DR Ensembl; ENSMUST00000113818; ENSMUSP00000109449; ENSMUSG00000033788. [Q9ESD7-3]
DR Ensembl; ENSMUST00000168387; ENSMUSP00000132297; ENSMUSG00000033788. [Q9ESD7-1]
DR GeneID; 26903; -.
DR KEGG; mmu:26903; -.
DR UCSC; uc009cos.3; mouse. [Q9ESD7-3]
DR UCSC; uc009cot.2; mouse. [Q9ESD7-2]
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 Reactome; R-MMU-445355; Smooth Muscle Contraction.
DR BioGRID-ORCS; 26903; 2 hits in 72 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 153 other tissues.
DR ExpressionAtlas; Q9ESD7; baseline and differential.
DR Genevisible; Q9ESD7; MM.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0061025; P:membrane fusion; IBA:GO_Central.
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:1901842; P:negative regulation of high voltage-gated calcium channel activity; 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:0007009; P:plasma membrane organization; IBA:GO_Central.
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; -; 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 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
