OTOF_DANRE
ID OTOF_DANRE Reviewed; 1992 AA.
AC Q5SPC5;
DT 16-DEC-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Otoferlin;
DE AltName: Full=Fer-1-like protein 2;
GN Name=otof; Synonyms=fer1l2; ORFNames=si:dkey-181f18.3;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
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.
CC {ECO:0000250|UniProtKB:Q9ESF1}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II
CC membrane protein {ECO:0000250|UniProtKB:Q9ESF1}. Basolateral cell
CC membrane {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II membrane
CC protein {ECO:0000250|UniProtKB:Q9ESF1}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q9ESF1}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q9ESF1}. Presynaptic cell membrane
CC {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q9ESF1}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q9ESF1}. 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 {ECO:0000250|UniProtKB:Q9ESF1}.
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 -!- SIMILARITY: Belongs to the ferlin family. {ECO:0000305}.
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DR EMBL; AL929014; CAI11718.1; -; Genomic_DNA.
DR EMBL; BX000361; CAI11718.1; JOINED; Genomic_DNA.
DR EMBL; BX000361; CAI20764.1; -; Genomic_DNA.
DR EMBL; AL929014; CAI20764.1; JOINED; Genomic_DNA.
DR RefSeq; NP_001025283.1; NM_001030112.2.
DR AlphaFoldDB; Q5SPC5; -.
DR SMR; Q5SPC5; -.
DR STRING; 7955.ENSDARP00000118166; -.
DR PaxDb; Q5SPC5; -.
DR PRIDE; Q5SPC5; -.
DR Ensembl; ENSDART00000008840; ENSDARP00000007932; ENSDARG00000030832.
DR GeneID; 557476; -.
DR KEGG; dre:557476; -.
DR CTD; 557476; -.
DR ZFIN; ZDB-GENE-030131-7778; otofa.
DR eggNOG; KOG1326; Eukaryota.
DR GeneTree; ENSGT00940000155086; -.
DR HOGENOM; CLU_001183_3_1_1; -.
DR InParanoid; Q5SPC5; -.
DR OrthoDB; 20162at2759; -.
DR PhylomeDB; Q5SPC5; -.
DR TreeFam; TF316871; -.
DR Reactome; R-DRE-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
DR PRO; PR:Q5SPC5; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 20.
DR Bgee; ENSDARG00000030832; Expressed in brain and 25 other tissues.
DR ExpressionAtlas; Q5SPC5; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
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:0048787; C:presynaptic active zone membrane; IBA:GO_Central.
DR GO; GO:0030672; C:synaptic vesicle membrane; ISS:UniProtKB.
DR GO; GO:0035612; F:AP-2 adaptor complex binding; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IGI:ZFIN.
DR GO; GO:0007009; P:plasma membrane organization; IBA:GO_Central.
DR GO; GO:0010996; P:response to auditory stimulus; IGI:ZFIN.
DR GO; GO:0007605; P:sensory perception of sound; IDA:MGI.
DR GO; GO:0001964; P:startle response; IDA:MGI.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; ISS:UniProtKB.
DR GO; GO:0016082; P:synaptic vesicle priming; IBA:GO_Central.
DR CDD; cd08373; C2A_Ferlin; 1.
DR CDD; cd04011; C2B_Ferlin; 1.
DR CDD; cd04018; C2C_Ferlin; 1.
DR CDD; cd04017; C2D_Ferlin; 1.
DR CDD; cd04037; C2E_Ferlin; 1.
DR CDD; cd08374; C2F_Ferlin; 1.
DR Gene3D; 2.60.40.150; -; 6.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR037726; C2A_Ferlin.
DR InterPro; IPR037720; C2B_Ferlin.
DR InterPro; IPR037722; C2C_Ferlin.
DR InterPro; IPR037723; C2D_Ferlin.
DR InterPro; IPR037724; C2E_Ferlin.
DR InterPro; IPR037725; C2F_Ferlin.
DR InterPro; 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 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 3: Inferred from homology;
KW Calcium; Cell membrane; Cell projection; Coiled coil; Cytoplasmic vesicle;
KW Endoplasmic reticulum; Golgi apparatus; Membrane; Metal-binding;
KW Reference proteome; Repeat; Signal-anchor; Synapse; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1992
FT /note="Otoferlin"
FT /id="PRO_0000355561"
FT TOPO_DOM 1..1958
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1959..1979
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1980..1992
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 1..98
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 241..362
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 405..536
FT /note="C2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 952..1077
FT /note="C2 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1124..1250
FT /note="C2 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1470..1588
FT /note="C2 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1711..1860
FT /note="C2 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 655..699
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1288..1311
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1354..1399
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1282..1363
FT /evidence="ECO:0000255"
FT COMPBIAS 655..673
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 674..689
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1288..1307
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 984
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 990
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1046
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1048
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1503
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1503
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1509
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1558
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1558
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1560
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1560
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1566
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1831
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1834
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1837
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
SQ SEQUENCE 1992 AA; 226228 MW; 0251225768F645B7 CRC64;
MALVVHLKTV TELRGKGDRI AKVTFRGLSF FSRVLENCED EARFEQAFRW PIGSQVDGDE
MLEIQVFNYS KVFTNRLIGT FRMVLQKVVE EGHLEVSDTL IDDNNTAIQT TISIEIKYQT
MDGSVKVWSD GEFLDIPDDL DGTFQFETDS LLSGRSQSSG TSPGRSIHGI PTFRKAGKGV
FSAMKLGKTR TSKDDHKKGD DAAILDAEDL DRKAMRLGGI LDPDTISLAS VTAVTTNVSN
KRSKPDIKME PSSGRPVDYQ ISVTVIEARQ LVGLNMDPVV CVEIGEEKKY TSMKESTNCP
YYNEYFVFDF HVPPDVMFDK IIKISVIHSK NLLRSGTLVG TFKLDVGTVY TQPEHQFHHK
WAMLSDPDDI TTGCKGYVKC DIAVVGKGDN IKTPHKASEA DEDDIEGNLL LPEGVPSERQ
WARFYVKIYR AEGLPKMNTS IMANVKKAFI GENRDLVDPY VLVQFAGQKG KTSVQKSSYE
PIWNEQVIFT EMFPPLCRRL KVQIRDSDKV NDVAIGTHFI DLRKVSNDGD KGFLPTMGPA
WVNMYGSTRN YTLMDEHQDL NEGLGEGVSF RARLLISIAV EILDTTSAEI MSSTEVHMEP
VSNISESATG KMEEFFLFGS FLEATMIDRK IGDKPISFEV TIGNYGNQID GVSKPALAKK
KKEGGGESEE EESELIHNSS EEEAEDDGDL TSVPSTPPMK PVITDRNYFH LPYFEKKPCI
YIKSWWQDQR RRLYNSNIMD KIADKLEEGL NDVQEIIKTE KAYPERRLRG VLEELSTSCS
RFVTLANKDQ NLSGRTKLDR ERLKSCMREM ESMGQQAKTI RTQVKRNTVR DKLKLVLNFL
QRLRFLADEP QHSIPDVFIW MISNNKRIAY ARIPSKDILY SIVDEEMGKD CGKVKAVFLR
LPGKKGFGPA GWTVQAKLEM YLWLGLNKQR KDFLIGLPSG FEENKAVKGI GIQAVPPISL
VYNMKQVFQL RAHMYQARSL FAADTSGLSD PFARVFFSTH SQVTEVLSET LCPTWDQLLV
FDNVELYGEA GELRDDPPII VIELYDQDTV GKAEFIGRTF AKPLTKMVDE HYGPPRFPPQ
LEYYQIYRGN CAAGDLLAAF ELLQIGPAGR AALPPIDGPT DSDRGPILPV PLGIRPVLSR
YRIEVLFWGL RDLKRVNLAQ VDRPRVDIEC AGKGVQSALI QNYKKNPNFS TLVKWFEVDL
PENELLHPPL NIRVVDCRAF GRYILVGSHA VTTLRKFIYS PPDKTANNWA HTGDIVVNMS
PEPNIKKMDT VVKIEATTDA VVKVDLNEDE KEKEKKKKKK KKGEEVEEEE PDESMLDWWS
KYFASIETMM ENLRAQEAAQ AEAEEREDLE IAAESAEIKA DDFPMKGTKP KEKSKDKKST
KDKKKNNDGT EKRPPKPKVD ELMVYNKELE SEFGSFEDWL HTFNLYRGKA GDDDDHNVVD
EDRIVGRFKG SLCMYKLPLS EEITREAGFD PNMGMFQSIP HNDPINVLVR IYIIRATDLH
PADINGKADP YIVIKLGKSD IRDKENYISK QLNPVFGKSF DIEATFPMES MLTVAVYDWD
LVGTDDLIGE TKIDLENRYY SKHRATCGIA SNYSVHGYNV WRDPQKPAQI LAKLCKEGKL
DGPHYGPGGR VKVANRIFLG PTEIEDESGL KKQTEEHLAL TVLRHWEEIP RVGCKLIPEH
VETRPLLNPD KPGIEQGRIE MWVDMFPMDV PAPGPAIDIS PRKPKRYELR VIIWNTDEVI
LEDDDYFTGE KSSDIFVRGW LKGQQEDKQD TDVHYHSLTG EGNFNWRFVF PFDYLMAEEK
IVISKKESMF SWDETEYKIP ARLTLQVWDA DHFSADDFLG AIELDLNKFP RGAKTAKQCS
LDMVLKEHEL PTISIFKQKR VKGWWPFVAQ NENDEFELTG KVEAELHLLT AEEAEKSPVG
LGRNDPEPLE KPNRPDTSLM WFMNPLRSIR YFIWHNYRWL ILKALALLLL LLLVGLFLYS
IPGYLVKKLL GA
