OTOF_MOUSE
ID OTOF_MOUSE Reviewed; 1997 AA.
AC Q9ESF1; A3KLM3; B2RWU0; Q8CCE7; Q9ESF2;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Otoferlin;
DE AltName: Full=Fer-1-like protein 2;
DE AltName: Full=Protein pachanga {ECO:0000303|PubMed:17329413};
GN Name=Otof; Synonyms=Fer1l2;
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] (ISOFORMS 1 AND 2), AND ALTERNATIVE SPLICING.
RC TISSUE=Brain, and Cochlea;
RX PubMed=10903124; DOI=10.1086/303049;
RA Yasunaga S., Grati M., Chardenoux S., Smith T.N., Friedman T.B.,
RA Lalwani A.K., Wilcox E.R., Petit C.;
RT "OTOF encodes multiple long and short isoforms: genetic evidence that the
RT long ones underlie recessive deafness DFNB9.";
RL Am. J. Hum. Genet. 67:591-600(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, DISRUPTION PHENOTYPE,
RP INTERACTION WITH SNAP25 AND STX1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND DEVELOPMENTAL STAGE.
RC STRAIN=BALB/cJ; TISSUE=Cochlea;
RX PubMed=17055430; DOI=10.1016/j.cell.2006.08.040;
RA Roux I., Safieddine S., Nouvian R., Grati M., Simmler M.-C., Bahloul A.,
RA Perfettini I., Le Gall M., Rostaing P., Hamard G., Triller A., Avan P.,
RA Moser T., Petit C.;
RT "Otoferlin, defective in a human deafness form, is essential for exocytosis
RT at the auditory ribbon synapse.";
RL Cell 127:277-289(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 954-1997 (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=17329413; DOI=10.1523/jneurosci.4975-06.2007;
RA Schwander M., Sczaniecka A., Grillet N., Bailey J.S., Avenarius M.,
RA Najmabadi H., Steffy B.M., Federe G.C., Lagler E.A., Banan R., Hice R.,
RA Grabowski-Boase L., Keithley E.M., Ryan A.F., Housley G.D., Wiltshire T.,
RA Smith R.J., Tarantino L.M., Mueller U.;
RT "A forward genetics screen in mice identifies recessive deafness traits and
RT reveals that pejvakin is essential for outer hair cell function.";
RL J. Neurosci. 27:2163-2175(2007).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=10192385; DOI=10.1038/7693;
RA Yasunaga S., Grati M., Cohen-Salmon M., El-Amraoui A., Mustapha M.,
RA Salem N., El-Zir E., Loiselet J., Petit C.;
RT "A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes
RT DFNB9, a nonsyndromic form of deafness.";
RL Nat. Genet. 21:363-369(1999).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=17229086; DOI=10.1111/j.1460-9568.2006.05225.x;
RA Schug N., Braig C., Zimmermann U., Engel J., Winter H., Ruth P., Blin N.,
RA Pfister M., Kalbacher H., Knipper M.;
RT "Differential expression of otoferlin in brain, vestibular system, immature
RT and mature cochlea of the rat.";
RL Eur. J. Neurosci. 24:3372-3380(2006).
RN [8]
RP FUNCTION, INTERACTION WITH RAB8B, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=18772196; DOI=10.1093/hmg/ddn279;
RA Heidrych P., Zimmermann U., Bress A., Pusch C.M., Ruth P., Pfister M.,
RA Knipper M., Blin N.;
RT "Rab8b GTPase, a protein transport regulator, is an interacting partner of
RT otoferlin, defective in a human autosomal recessive deafness form.";
RL Hum. Mol. Genet. 17:3814-3821(2008).
RN [9]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18287496; DOI=10.1523/jneurosci.4653-07.2008;
RA Beurg M., Safieddine S., Roux I., Bouleau Y., Petit C., Dulon D.;
RT "Calcium- and otoferlin-dependent exocytosis by immature outer hair
RT cells.";
RL J. Neurosci. 28:1798-1803(2008).
CC -!- FUNCTION: Key calcium ion sensor involved in the Ca(2+)-triggered
CC synaptic vesicle-plasma membrane fusion and in the control of
CC neurotransmitter release at these output synapses. Interacts in a
CC calcium-dependent manner to the presynaptic SNARE proteins at ribbon
CC synapses of cochlear inner hair cells (IHCs) to trigger exocytosis of
CC neurotransmitter. Also essential to synaptic exocytosis in immature
CC outer hair cells (OHCs). May also play a role within the recycling of
CC endosomes. {ECO:0000269|PubMed:17055430, ECO:0000269|PubMed:18287496,
CC ECO:0000269|PubMed:18772196}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC Note=Binds Ca(2+). The ions are bound to the C2 1 domain.;
CC -!- SUBUNIT: Interacts with SNAP25; the interaction is direct. Interacts
CC with STX1; the interaction is direct. Interacts with RAB8B.
CC {ECO:0000269|PubMed:17055430, ECO:0000269|PubMed:18772196}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000269|PubMed:17055430}; Single-pass type II
CC membrane protein. Basolateral cell membrane
CC {ECO:0000269|PubMed:17055430}; Single-pass type II membrane protein.
CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:18772196}; Single-
CC pass type II membrane protein. Golgi apparatus membrane
CC {ECO:0000269|PubMed:18772196}; Single-pass type II membrane protein
CC {ECO:0000305}. Presynaptic cell membrane {ECO:0000269|PubMed:17055430};
CC Single-pass type II membrane protein {ECO:0000305}. Cell membrane;
CC Single-pass type II membrane protein. Note=Detected at basolateral cell
CC membrane with synaptic vesicles surrounding the ribbon and at the
CC presynaptic plasma membrane in the inner hair cells (IHCs) at postnatal
CC day 30 (P30). Colocalizes with GPR25 and RAB8B in inner hair cells.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=Q9ESF1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9ESF1-2; Sequence=VSP_001512, VSP_001513, VSP_001514;
CC Name=3;
CC IsoId=Q9ESF1-3; Sequence=VSP_001513;
CC -!- TISSUE SPECIFICITY: Isoform 1 is expressed in cochlea and brain.
CC Expressed in the cochlear and vestibular hair cells. Expressed in both
CC inner and outer hair cells (IHCs and OHCs) and cochlear ganglions
CC neurons at postnatal day 2 (P2) and 6 (P6). Expressed only in IHCs at
CC postnatal day 60 (P60) (at protein level). Strongly expressed in brain
CC and inner ear. In the inner ear, it is mainly expressed in the cochlear
CC IHC and vestibular type I sensory hair cells. Weakly expressed in eye,
CC heart, skeletal muscle, liver, kidney, lung and testis.
CC {ECO:0000269|PubMed:10192385, ECO:0000269|PubMed:17055430,
CC ECO:0000269|PubMed:17229086, ECO:0000269|PubMed:18772196}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the organ of Corti in the inner hair
CC cells (IHCs), but not in the outer hair cells (OHCs) at 16 dpc.
CC Expressed strongly in the IHCs and faintly in the OHCs at 18 dpc (at
CC protein level). {ECO:0000269|PubMed:17055430}.
CC -!- DOMAIN: The N-terminal first 124 residues can be classified as C2
CC domain, based on their 3D-structure. They are not sufficient for
CC calcium ion or phospholipid binding (By similarity).
CC {ECO:0000250|UniProtKB:Q9ERC5}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking Otof display hearing loss
CC (PubMed:17055430, PubMed:17329413). Both outer hair cells (OHCs) and
CC the afferent auditory pathway are functional (PubMed:17055430). Despite
CC normal inner hair cells (IHCs) and ribbon synapse ultrastructures,
CC these mice exhibit an almost complete abolition of IHC synaptic
CC exocytosis in response to cell depolarization (PubMed:17055430).
CC {ECO:0000269|PubMed:17055430, ECO:0000269|PubMed:17329413}.
CC -!- SIMILARITY: Belongs to the ferlin family. {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; AF183183; AAG12989.1; -; mRNA.
DR EMBL; AF183184; AAG12990.1; -; mRNA.
DR EMBL; AY586513; AAT40586.1; -; mRNA.
DR EMBL; BC150702; AAI50703.1; -; mRNA.
DR EMBL; AK033317; BAC28229.1; -; mRNA.
DR CCDS; CCDS19157.1; -. [Q9ESF1-1]
DR CCDS; CCDS51452.1; -. [Q9ESF1-2]
DR RefSeq; NP_001093865.1; NM_001100395.1.
DR RefSeq; NP_001273350.1; NM_001286421.1.
DR RefSeq; NP_114081.2; NM_031875.2.
DR AlphaFoldDB; Q9ESF1; -.
DR SMR; Q9ESF1; -.
DR BioGRID; 219969; 1.
DR IntAct; Q9ESF1; 1.
DR STRING; 10090.ENSMUSP00000073803; -.
DR iPTMnet; Q9ESF1; -.
DR PhosphoSitePlus; Q9ESF1; -.
DR PaxDb; Q9ESF1; -.
DR PRIDE; Q9ESF1; -.
DR ProteomicsDB; 294125; -. [Q9ESF1-1]
DR ProteomicsDB; 294126; -. [Q9ESF1-2]
DR ProteomicsDB; 294127; -. [Q9ESF1-3]
DR DNASU; 83762; -.
DR GeneID; 83762; -.
DR KEGG; mmu:83762; -.
DR UCSC; uc008wvl.1; mouse. [Q9ESF1-2]
DR UCSC; uc012dud.1; mouse. [Q9ESF1-3]
DR CTD; 9381; -.
DR MGI; MGI:1891247; Otof.
DR eggNOG; KOG1326; Eukaryota.
DR InParanoid; Q9ESF1; -.
DR OrthoDB; 20162at2759; -.
DR PhylomeDB; Q9ESF1; -.
DR Reactome; R-MMU-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
DR BioGRID-ORCS; 83762; 1 hit in 73 CRISPR screens.
DR PRO; PR:Q9ESF1; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9ESF1; protein.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0045177; C:apical part of cell; ISO:MGI.
DR GO; GO:0045178; C:basal part of cell; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0060203; C:clathrin-sculpted glutamate transport vesicle membrane; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0048787; C:presynaptic active zone membrane; IDA:MGI.
DR GO; GO:0030672; C:synaptic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0035612; F:AP-2 adaptor complex binding; IDA:MGI.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0007009; P:plasma membrane organization; IBA:GO_Central.
DR GO; GO:0007605; P:sensory perception of sound; ISO:MGI.
DR GO; GO:0001964; P:startle response; ISO:MGI.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; IDA:UniProtKB.
DR GO; GO:0016082; P:synaptic vesicle priming; IMP:CACAO.
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; IPR012968; FerIin_dom.
DR InterPro; IPR037721; Ferlin.
DR InterPro; IPR012561; Ferlin_B-domain.
DR InterPro; IPR032362; Ferlin_C.
DR InterPro; IPR029996; Otoferlin.
DR PANTHER; PTHR12546; PTHR12546; 1.
DR PANTHER; PTHR12546:SF32; PTHR12546:SF32; 1.
DR Pfam; PF00168; C2; 6.
DR Pfam; PF08150; FerB; 1.
DR Pfam; PF08151; FerI; 1.
DR Pfam; PF16165; Ferlin_C; 1.
DR PRINTS; PR00360; C2DOMAIN.
DR SMART; SM00239; C2; 6.
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; Cell projection; Coiled coil;
KW Cytoplasmic vesicle; Deafness; Endoplasmic reticulum; Golgi apparatus;
KW Hearing; Membrane; Metal-binding; Reference proteome; Repeat;
KW Signal-anchor; Synapse; Transmembrane; Transmembrane helix.
FT CHAIN 1..1997
FT /note="Otoferlin"
FT /id="PRO_0000057882"
FT TOPO_DOM 1..1963
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1964..1984
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1985..1997
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 1..98
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 235..356
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 399..530
FT /note="C2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 943..1068
FT /note="C2 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1115..1241
FT /note="C2 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1464..1593
FT /note="C2 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1714..1865
FT /note="C2 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 140..167
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 643..692
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1253..1272
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1296..1326
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1343..1402
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 791..820
FT /evidence="ECO:0000255"
FT COMPBIAS 648..663
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 664..679
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1296..1315
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1343..1387
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 975
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 975
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 981
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1037
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1037
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1039
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1039
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1045
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1508
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1508
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1514
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1563
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1563
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1565
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1565
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1571
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1836
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1839
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1842
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT VAR_SEQ 169
FT /note="R -> SKGREETKGGRDGEHK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10903124,
FT ECO:0000303|PubMed:16141072, ECO:0000303|PubMed:17055430"
FT /id="VSP_001512"
FT VAR_SEQ 1244..1263
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10903124,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:16141072,
FT ECO:0000303|PubMed:17055430"
FT /id="VSP_001513"
FT VAR_SEQ 1943..1997
FT /note="SFIWFLNPLKSARYFLWHTYRWLLLKFLLLFLLLLLFALFLYSLPGYLAKKI
FT LGA -> AFVWFLNPLKSIKYLICTRYKWLIIKIVLALLGLLMLALFLYSLPGYMVKKL
FT LGA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10903124,
FT ECO:0000303|PubMed:16141072, ECO:0000303|PubMed:17055430"
FT /id="VSP_001514"
FT CONFLICT 826
FT /note="L -> S (in Ref. 2; AAT40586)"
FT /evidence="ECO:0000305"
FT CONFLICT 955
FT /note="K -> E (in Ref. 4; BAC28229)"
FT /evidence="ECO:0000305"
FT CONFLICT 1853
FT /note="R -> Q (in Ref. 3; AAI50703)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1997 AA; 227033 MW; 7B9CCA918F79D4D1 CRC64;
MALIVHLKTV SELRGKGDRI AKVTFRGQSF YSRVLENCEG VADFDETFRW PVASSIDRNE
VLEIQIFNYS KVFSNKLIGT FCMVLQKVVE ENRVEVTDTL MDDSNAIIKT SLSMEVRYQA
TDGTVGPWDD GDFLGDESLQ EEKDSQETDG LLPGSRPSTR ISGEKSFRRA GRSVFSAMKL
GKTRSHKEEP QRQDEPAVLE MEDLDHLAIQ LGDGLDPDSV SLASVTALTS NVSNKRSKPD
IKMEPSAGRP MDYQVSITVI EARQLVGLNM DPVVCVEVGD DKKYTSMKES TNCPYYNEYF
VFDFHVSPDV MFDKIIKISV IHSKNLLRSG TLVGSFKMDV GTVYSQPEHQ FHHKWAILSD
PDDISAGLKG YVKCDVAVVG KGDNIKTPHK ANETDEDDIE GNLLLPEGVP PERQWARFYV
KIYRAEGLPR MNTSLMANVK KAFIGENKDL VDPYVQVFFA GQKGKTSVQK SSYEPLWNEQ
VVFTDLFPPL CKRMKVQIRD SDKVNDVAIG THFIDLRKIS NDGDKGFLPT LGPAWVNMYG
STRNYTLLDE HQDLNEGLGE GVSFRARLML GLAVEILDTS NPELTSSTEV QVEQATPVSE
SCTGRMEEFF LFGAFLEASM IDRKNGDKPI TFEVTIGNYG NEVDGMSRPL RPRPRKEPGD
EEEVDLIQNS SDDEGDEAGD LASVSSTPPM RPQITDRNYF HLPYLERKPC IYIKSWWPDQ
RRRLYNANIM DHIADKLEEG LNDVQEMIKT EKSYPERRLR GVLEELSCGC HRFLSLSDKD
QGRSSRTRLD RERLKSCMRE LESMGQQAKS LRAQVKRHTV RDKLRLCQNF LQKLRFLADE
PQHSIPDVFI WMMSNNKRIA YARVPSKDLL FSIVEEELGK DCAKVKTLFL KLPGKRGFGS
AGWTVQAKLE LYLWLGLSKQ RKDFLCGLPC GFEEVKAAQG LGLHSFPPIS LVYTKKQAFQ
LRAHMYQARS LFAADSSGLS DPFARVFFIN QSQCTEVLNE TLCPTWDQML VFDNLELYGE
AHELRDDPPI IVIEIYDQDS MGKADFMGRT FAKPLVKMAD EAYCPPRFPP QLEYYQIYRG
SATAGDLLAA FELLQIGPSG KADLPPINGP VDMDRGPIMP VPVGIRPVLS KYRVEVLFWG
LRDLKRVNLA QVDRPRVDIE CAGKGVQSSL IHNYKKNPNF NTLVKWFEVD LPENELLHPP
LNIRVVDCRA FGRYTLVGSH AVSSLRRFIY RPPDRSAPNW NTTVRLLRGC HRLRNGGPSS
RPTGEVVVSM EPEEPVKKLE TMVKLDATSD AVVKVDVAED EKERKKKKKK GPSEEPEEEE
PDESMLDWWS KYFASIDTMK EQLRQHETSG TDLEEKEEME SAEGLKGPMK SKEKSRAAKE
EKKKKNQSPG PGQGSEAPEK KKAKIDELKV YPKELESEFD SFEDWLHTFN LLRGKTGDDE
DGSTEEERIV GRFKGSLCVY KVPLPEDVSR EAGYDPTYGM FQGIPSNDPI NVLVRIYVVR
ATDLHPADIN GKADPYIAIK LGKTDIRDKE NYISKQLNPV FGKSFDIEAS FPMESMLTVA
VYDWDLVGTD DLIGETKIDL ENRFYSKHRA TCGIAQTYSI HGYNIWRDPM KPSQILTRLC
KEGKVDGPHF GPHGRVRVAN RVFTGPSEIE DENGQRKPTD EHVALSALRH WEDIPRVGCR
LVPEHVETRP LLNPDKPGIE QGRLELWVDM FPMDMPAPGT PLDISPRKPK KYELRVIVWN
TDEVVLEDDD FFTGEKSSDI FVRGWLKGQQ EDKQDTDVHY HSLTGEGNFN WRYLFPFDYL
AAEEKIVMSK KESMFSWDET EYKIPARLTL QIWDADHFSA DDFLGAIELD LNRFPRGAKT
AKQCTMEMAT GEVDVPLVSI FKQKRVKGWW PLLARNENDE FELTGKVEAE LHLLTAEEAE
KNPVGLARNE PDPLEKPNRP DTSFIWFLNP LKSARYFLWH TYRWLLLKFL LLFLLLLLFA
LFLYSLPGYL AKKILGA
