Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9ESF1 (OTOF_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Otoferlin
Alternative name(s):
Fer-1-like protein 2
Gene names
Name:Otof
Synonyms:Fer1l2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1997 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Key calcium ion sensor involved in the Ca2+-triggered synaptic vesicle-plasma membrane fusion and in the control of neurotransmitter release at these output synapses. Interacts in a calcium-dependent manner to the presynaptic SNARE proteins at ribbon synapses of cochlear inner hair cells (IHCs) to trigger exocytosis of neurotransmitter. Also essential to synaptic exocytosis in immature outer hair cells (OHCs). May also play a role within the recycling of endosomes. Ref.2 Ref.7 Ref.8

Cofactor

Binds calcium ions. The ions are bound to the C2 1 domain.

Subunit structure

Interacts with SNAP25; the interaction is direct. Interacts with STX1; the interaction is direct. Interacts with RAB8B. Ref.2 Ref.7

Subcellular location

Cytoplasmic vesiclesecretory vesiclesynaptic vesicle membrane; Single-pass type II membrane protein. Basolateral cell membrane; Single-pass type II membrane protein. Endoplasmic reticulum membrane; Single-pass type II membrane protein. Cell membrane; Single-pass type II membrane protein. Note: Detected at basolateral cell membrane with synaptic vesicles surrounding the ribbon and at the presynaptic plasma membrane in the inner hair cells (IHCs) at postnatal day 30 (P30). Colocalizes with GPR25 and RAB8B in inner hair cells. Ref.2 Ref.7 Ref.8

Tissue specificity

Isoform 1 is expressed in cochlea and brain. Expressed in the cochlear and vestibular hair cells. Expressed in both inner and outer hair cells (IHCs and OHCs) and cochlear ganglions neurons at postnatal day 2 (P2) and 6 (P6). Expressed only in IHCs at postnatal day 60 (P60) (at protein level). Strongly expressed in brain and inner ear. In the inner ear, it is mainly expressed in the cochlear IHC and vestibular type I sensory hair cells. Weakly expressed in eye, heart, skeletal muscle, liver, kidney, lung and testis. Ref.2 Ref.5 Ref.6 Ref.7

Developmental stage

Expressed in the organ of Corti in the inner hair cells (IHCs), but not in the outer hair cells (OHCs) at 16 dpc. Expressed strongly in the IHCs and faintly in the OHCs at 18 dpc (at protein level). Ref.2

Domain

The N-terminal first 124 residues can be classified as C2 domain, based on their 3D-structure. They are not sufficient for calcium ion or phospholipid binding By similarity.

Miscellaneous

Mice lacking Otof display hearing loss. Both outer hair cells (OHCs) and the afferent auditory pathway are functional. Despite normal inner hair cells (IHCs) and ribbon synapse ultrastructures, these mice exhibit an almost complete abolition of IHC synaptic exocytosis in response to cell depolarization.

Sequence similarities

Belongs to the ferlin family.

Contains 4 C2 domains.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q9ESF1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q9ESF1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     169-169: R → SKGREETKGGRDGEHK
     1244-1263: Missing.
     1943-1997: SFIWFLNPLK...GYLAKKILGA → AFVWFLNPLK...GYMVKKLLGA
Isoform 3 (identifier: Q9ESF1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1244-1263: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 19971997Otoferlin
PRO_0000057882

Regions

Topological domain1 – 19631963Cytoplasmic Potential
Transmembrane1964 – 198421Helical; Potential
Topological domain1985 – 199713Extracellular Potential
Domain240 – 33798C2 1
Domain403 – 513111C2 2
Domain946 – 1051106C2 3
Domain1479 – 157799C2 4
Coiled coil791 – 82030 Potential
Compositional bias1305 – 13106Poly-Lys
Compositional bias1314 – 13207Poly-Glu
Compositional bias1970 – 19789Poly-Leu

Natural variations

Alternative sequence1691R → SKGREETKGGRDGEHK in isoform 2.
VSP_001512
Alternative sequence1244 – 126320Missing in isoform 2 and isoform 3.
VSP_001513
Alternative sequence1943 – 199755SFIWF…KILGA → AFVWFLNPLKSIKYLICTRY KWLIIKIVLALLGLLMLALF LYSLPGYMVKKLLGA in isoform 2.
VSP_001514

Experimental info

Sequence conflict8261L → S in AAT40586. Ref.2
Sequence conflict9551K → E in BAC28229. Ref.4
Sequence conflict18531R → Q in AAI50703. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 7B9CCA918F79D4D1

FASTA1,997227,033
        10         20         30         40         50         60 
MALIVHLKTV SELRGKGDRI AKVTFRGQSF YSRVLENCEG VADFDETFRW PVASSIDRNE 

        70         80         90        100        110        120 
VLEIQIFNYS KVFSNKLIGT FCMVLQKVVE ENRVEVTDTL MDDSNAIIKT SLSMEVRYQA 

       130        140        150        160        170        180 
TDGTVGPWDD GDFLGDESLQ EEKDSQETDG LLPGSRPSTR ISGEKSFRRA GRSVFSAMKL 

       190        200        210        220        230        240 
GKTRSHKEEP QRQDEPAVLE MEDLDHLAIQ LGDGLDPDSV SLASVTALTS NVSNKRSKPD 

       250        260        270        280        290        300 
IKMEPSAGRP MDYQVSITVI EARQLVGLNM DPVVCVEVGD DKKYTSMKES TNCPYYNEYF 

       310        320        330        340        350        360 
VFDFHVSPDV MFDKIIKISV IHSKNLLRSG TLVGSFKMDV GTVYSQPEHQ FHHKWAILSD 

       370        380        390        400        410        420 
PDDISAGLKG YVKCDVAVVG KGDNIKTPHK ANETDEDDIE GNLLLPEGVP PERQWARFYV 

       430        440        450        460        470        480 
KIYRAEGLPR MNTSLMANVK KAFIGENKDL VDPYVQVFFA GQKGKTSVQK SSYEPLWNEQ 

       490        500        510        520        530        540 
VVFTDLFPPL CKRMKVQIRD SDKVNDVAIG THFIDLRKIS NDGDKGFLPT LGPAWVNMYG 

       550        560        570        580        590        600 
STRNYTLLDE HQDLNEGLGE GVSFRARLML GLAVEILDTS NPELTSSTEV QVEQATPVSE 

       610        620        630        640        650        660 
SCTGRMEEFF LFGAFLEASM IDRKNGDKPI TFEVTIGNYG NEVDGMSRPL RPRPRKEPGD 

       670        680        690        700        710        720 
EEEVDLIQNS SDDEGDEAGD LASVSSTPPM RPQITDRNYF HLPYLERKPC IYIKSWWPDQ 

       730        740        750        760        770        780 
RRRLYNANIM DHIADKLEEG LNDVQEMIKT EKSYPERRLR GVLEELSCGC HRFLSLSDKD 

       790        800        810        820        830        840 
QGRSSRTRLD RERLKSCMRE LESMGQQAKS LRAQVKRHTV RDKLRLCQNF LQKLRFLADE 

       850        860        870        880        890        900 
PQHSIPDVFI WMMSNNKRIA YARVPSKDLL FSIVEEELGK DCAKVKTLFL KLPGKRGFGS 

       910        920        930        940        950        960 
AGWTVQAKLE LYLWLGLSKQ RKDFLCGLPC GFEEVKAAQG LGLHSFPPIS LVYTKKQAFQ 

       970        980        990       1000       1010       1020 
LRAHMYQARS LFAADSSGLS DPFARVFFIN QSQCTEVLNE TLCPTWDQML VFDNLELYGE 

      1030       1040       1050       1060       1070       1080 
AHELRDDPPI IVIEIYDQDS MGKADFMGRT FAKPLVKMAD EAYCPPRFPP QLEYYQIYRG 

      1090       1100       1110       1120       1130       1140 
SATAGDLLAA FELLQIGPSG KADLPPINGP VDMDRGPIMP VPVGIRPVLS KYRVEVLFWG 

      1150       1160       1170       1180       1190       1200 
LRDLKRVNLA QVDRPRVDIE CAGKGVQSSL IHNYKKNPNF NTLVKWFEVD LPENELLHPP 

      1210       1220       1230       1240       1250       1260 
LNIRVVDCRA FGRYTLVGSH AVSSLRRFIY RPPDRSAPNW NTTVRLLRGC HRLRNGGPSS 

      1270       1280       1290       1300       1310       1320 
RPTGEVVVSM EPEEPVKKLE TMVKLDATSD AVVKVDVAED EKERKKKKKK GPSEEPEEEE 

      1330       1340       1350       1360       1370       1380 
PDESMLDWWS KYFASIDTMK EQLRQHETSG TDLEEKEEME SAEGLKGPMK SKEKSRAAKE 

      1390       1400       1410       1420       1430       1440 
EKKKKNQSPG PGQGSEAPEK KKAKIDELKV YPKELESEFD SFEDWLHTFN LLRGKTGDDE 

      1450       1460       1470       1480       1490       1500 
DGSTEEERIV GRFKGSLCVY KVPLPEDVSR EAGYDPTYGM FQGIPSNDPI NVLVRIYVVR 

      1510       1520       1530       1540       1550       1560 
ATDLHPADIN GKADPYIAIK LGKTDIRDKE NYISKQLNPV FGKSFDIEAS FPMESMLTVA 

      1570       1580       1590       1600       1610       1620 
VYDWDLVGTD DLIGETKIDL ENRFYSKHRA TCGIAQTYSI HGYNIWRDPM KPSQILTRLC 

      1630       1640       1650       1660       1670       1680 
KEGKVDGPHF GPHGRVRVAN RVFTGPSEIE DENGQRKPTD EHVALSALRH WEDIPRVGCR 

      1690       1700       1710       1720       1730       1740 
LVPEHVETRP LLNPDKPGIE QGRLELWVDM FPMDMPAPGT PLDISPRKPK KYELRVIVWN 

      1750       1760       1770       1780       1790       1800 
TDEVVLEDDD FFTGEKSSDI FVRGWLKGQQ EDKQDTDVHY HSLTGEGNFN WRYLFPFDYL 

      1810       1820       1830       1840       1850       1860 
AAEEKIVMSK KESMFSWDET EYKIPARLTL QIWDADHFSA DDFLGAIELD LNRFPRGAKT 

      1870       1880       1890       1900       1910       1920 
AKQCTMEMAT GEVDVPLVSI FKQKRVKGWW PLLARNENDE FELTGKVEAE LHLLTAEEAE 

      1930       1940       1950       1960       1970       1980 
KNPVGLARNE PDPLEKPNRP DTSFIWFLNP LKSARYFLWH TYRWLLLKFL LLFLLLLLFA 

      1990 
LFLYSLPGYL AKKILGA 

« Hide

Isoform 2 [UniParc].

Checksum: AE487C8E9652B1F6
Show »

FASTA1,992226,123
Isoform 3 [UniParc].

Checksum: A8E2C6737567EEF7
Show »

FASTA1,977224,819

References

« Hide 'large scale' references
[1]"OTOF encodes multiple long and short isoforms: genetic evidence that the long ones underlie recessive deafness DFNB9."
Yasunaga S., Grati M., Chardenoux S., Smith T.N., Friedman T.B., Lalwani A.K., Wilcox E.R., Petit C.
Am. J. Hum. Genet. 67:591-600(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING.
Tissue: Brain and Cochlea.
[2]"Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse."
Roux I., Safieddine S., Nouvian R., Grati M., Simmler M.-C., Bahloul A., Perfettini I., Le Gall M., Rostaing P., Hamard G., Triller A., Avan P., Moser T., Petit C.
Cell 127:277-289(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH SNAP25 AND STX1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
Strain: BALB/c.
Tissue: Cochlea.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Brain.
[4]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 954-1997 (ISOFORM 2).
Strain: C57BL/6J.
Tissue: Testis.
[5]"A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness."
Yasunaga S., Grati M., Cohen-Salmon M., El-Amraoui A., Mustapha M., Salem N., El-Zir E., Loiselet J., Petit C.
Nat. Genet. 21:363-369(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[6]"Differential expression of otoferlin in brain, vestibular system, immature and mature cochlea of the rat."
Schug N., Braig C., Zimmermann U., Engel J., Winter H., Ruth P., Blin N., Pfister M., Kalbacher H., Knipper M.
Eur. J. Neurosci. 24:3372-3380(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[7]"Rab8b GTPase, a protein transport regulator, is an interacting partner of otoferlin, defective in a human autosomal recessive deafness form."
Heidrych P., Zimmermann U., Bress A., Pusch C.M., Ruth P., Pfister M., Knipper M., Blin N.
Hum. Mol. Genet. 17:3814-3821(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RAB8B, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[8]"Calcium- and otoferlin-dependent exocytosis by immature outer hair cells."
Beurg M., Safieddine S., Roux I., Bouleau Y., Petit C., Dulon D.
J. Neurosci. 28:1798-1803(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF183183 mRNA. Translation: AAG12989.1.
AF183184 mRNA. Translation: AAG12990.1.
AY586513 mRNA. Translation: AAT40586.1.
BC150702 mRNA. Translation: AAI50703.1.
AK033317 mRNA. Translation: BAC28229.1.
RefSeqNP_001093865.1. NM_001100395.1.
NP_001273350.1. NM_001286421.1.
NP_114081.2. NM_031875.2.
UniGeneMm.244502.

3D structure databases

ProteinModelPortalQ9ESF1.
SMRQ9ESF1. Positions 1-124.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9ESF1. 1 interaction.
STRING10090.ENSMUSP00000073803.

PTM databases

PhosphoSiteQ9ESF1.

Proteomic databases

PaxDbQ9ESF1.
PRIDEQ9ESF1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000114747; ENSMUSP00000110395; ENSMUSG00000062372.
GeneID83762.
KEGGmmu:83762.
UCSCuc008wvl.1. mouse. [Q9ESF1-2]
uc012dud.1. mouse. [Q9ESF1-3]

Organism-specific databases

CTD9381.
MGIMGI:1891247. Otof.

Phylogenomic databases

eggNOGCOG5038.
GeneTreeENSGT00550000074414.
HOGENOMHOG000006770.
HOVERGENHBG108221.
InParanoidQ9ESF1.
OrthoDBEOG7J9VNQ.
PhylomeDBQ9ESF1.

Gene expression databases

BgeeQ9ESF1.
CleanExMM_OTOF.
GenevestigatorQ9ESF1.

Family and domain databases

Gene3D2.60.40.150. 8 hits.
InterProIPR000008. C2_dom.
IPR012968. FerIin-domain.
IPR012561. Ferlin_B-domain.
[Graphical view]
PfamPF00168. C2. 7 hits.
PF08150. FerB. 1 hit.
PF08151. FerI. 1 hit.
[Graphical view]
PRINTSPR00360. C2DOMAIN.
SMARTSM00239. C2. 6 hits.
[Graphical view]
SUPFAMSSF49562. SSF49562. 8 hits.
PROSITEPS50004. C2. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio350750.
PROQ9ESF1.
SOURCESearch...

Entry information

Entry nameOTOF_MOUSE
AccessionPrimary (citable) accession number: Q9ESF1
Secondary accession number(s): A3KLM3 expand/collapse secondary AC list , B2RWU0, Q8CCE7, Q9ESF2
Entry history
Integrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: March 1, 2001
Last modified: April 16, 2014
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot