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Protein

Otoferlin

Gene

Otof

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity

Cofactori

Ca2+By similarityNote: Binds Ca2+. The ions are bound to the C2 1 domain.By similarity

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • protein complex binding Source: RGD

GO - Biological processi

  • cochlea development Source: RGD
  • sensory perception of sound Source: UniProtKB-KW
  • synaptic vesicle exocytosis Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Hearing

Keywords - Ligandi

Calcium

Names & Taxonomyi

Protein namesi
Recommended name:
Otoferlin
Alternative name(s):
Fer-1-like protein 2
Gene namesi
Name:Otof
Synonyms:Fer1l2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 6

Organism-specific databases

RGDi620646. Otof.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 1959CytoplasmicSequence analysisAdd BLAST1959
Transmembranei1960 – 1980HelicalSequence analysisAdd BLAST21
Topological domaini1981 – 1993ExtracellularSequence analysisAdd BLAST13

GO - Cellular componenti

  • apical part of cell Source: RGD
  • basal part of cell Source: RGD
  • basolateral plasma membrane Source: UniProtKB-SubCell
  • cell junction Source: UniProtKB-KW
  • cytoplasm Source: RGD
  • endoplasmic reticulum Source: RGD
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: RGD
  • synaptic vesicle membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cytoplasmic vesicle, Endoplasmic reticulum, Membrane, Synapse

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000578831 – 1993OtoferlinAdd BLAST1993

Proteomic databases

PaxDbiQ9ERC5.
PRIDEiQ9ERC5.

PTM databases

iPTMnetiQ9ERC5.
PhosphoSitePlusiQ9ERC5.

Expressioni

Tissue specificityi

Isoform 1 is expressed in the cochlea and brain. Expressed in cerebellum (Purkinje cells), hippocampus (granule cells of the dentate gyrus and in pyramidal cells of the CA1-CA3 region) and cortex (stellate and pyramidal cells). Expressed in hair cells of vestibular organs such as the saccule, utricle and crista ampullari. Expressed in the cochlear inner and outer cells (IHCs and OHCs) (at protein level). Expressed in brain: brainstem, cerebellum (granules cells and Purkinje cell layer), cortex (layers IV and V), inferior colliculus, superior colliculus and hippocampus (granule cells of the dentate gyrus and in pyramidal cells of the CA1-CA3 region).2 Publications

Gene expression databases

BgeeiENSRNOG00000009967.
ExpressionAtlasiQ9ERC5. baseline and differential.

Interactioni

Subunit structurei

Interacts with SNAP25; the interaction is direct. Interacts with STX1; the interaction is direct. Interacts with RAB8B (By similarity).By similarity

GO - Molecular functioni

  • protein complex binding Source: RGD

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000046997.

Structurei

Secondary structure

11993
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi1 – 12Combined sources12
Beta strandi17 – 25Combined sources9
Beta strandi28 – 31Combined sources4
Beta strandi35 – 38Combined sources4
Beta strandi42 – 54Combined sources13
Beta strandi61 – 69Combined sources9
Beta strandi76 – 85Combined sources10
Helixi86 – 91Combined sources6
Beta strandi92 – 101Combined sources10
Beta strandi107 – 120Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3L9BX-ray1.95A1-124[»]
ProteinModelPortaliQ9ERC5.
SMRiQ9ERC5.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9ERC5.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini256 – 353C2 1PROSITE-ProRule annotationAdd BLAST98
Domaini419 – 529C2 2PROSITE-ProRule annotationAdd BLAST111
Domaini962 – 1067C2 3PROSITE-ProRule annotationAdd BLAST106
Domaini1475 – 1573C2 4PROSITE-ProRule annotationAdd BLAST99

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili807 – 836Sequence analysisAdd BLAST30

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1301 – 1306Poly-Lys6
Compositional biasi1310 – 1316Poly-Glu7

Domaini

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.1 Publication

Sequence similaritiesi

Belongs to the ferlin family.Curated
Contains 4 C2 domains.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1326. Eukaryota.
ENOG410XPT2. LUCA.
GeneTreeiENSGT00550000074414.
HOGENOMiHOG000006770.
HOVERGENiHBG108221.
InParanoidiQ9ERC5.

Family and domain databases

Gene3Di2.60.40.150. 8 hits.
InterProiIPR000008. C2_dom.
IPR012968. FerIin_dom.
IPR012561. Ferlin_B-domain.
IPR032362. Ferlin_C.
IPR029996. Otoferlin.
[Graphical view]
PANTHERiPTHR12546:SF32. PTHR12546:SF32. 5 hits.
PfamiPF00168. C2. 6 hits.
PF08150. FerB. 1 hit.
PF08151. FerI. 1 hit.
PF16165. Ferlin_C. 1 hit.
[Graphical view]
PRINTSiPR00360. C2DOMAIN.
SMARTiSM00239. C2. 6 hits.
SM01201. FerB. 1 hit.
SM01202. FerI. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 8 hits.
PROSITEiPS50004. C2. 4 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9ERC5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MALIVHLKTV SELRGRADRI AKVTFRGQSF YSRVLENCED VADFDETFRW
60 70 80 90 100
PVASSIDRNE VLEIQIFNYS KVFSNKLIGT FRMVLQKVVE ENRVEVSDTL
110 120 130 140 150
IDDNNAIIKT SLSMEVRYQA ADGTVGPWDD GDFLGDESLQ EEEKDSQETD
160 170 180 190 200
GLLPGSRPST RTPGEKSFRS KGKEKTKGGR DGEHKAGRSV FSAMKLGKTR
210 220 230 240 250
SHKEEPQRQD EPAVLEMEDL DHLAIRLGDG LDPDSVSLAS VTALTSNVSN
260 270 280 290 300
KRSKPDIKME PSAGRPMDYQ VSITVIEARQ LVGLNMDPVV CVEVGDDKKY
310 320 330 340 350
TSMKESTNCP YYNEYFVFDF HVSPDVMFDK IIKISVIHSK NLLRSGTLVG
360 370 380 390 400
SFKMDVGTVY SQPEHQFHHK WAILSDPDDI SAGLKGYVKC DVAVVGKGDN
410 420 430 440 450
IKTPHKANET DEDDIEGNLL LPEGVPPERQ WARFYVKIYR AEGLPRMNTS
460 470 480 490 500
LMANVKKAFI GENKDLVDPY VQVFFAGQKG KTSVQKSSYE PLWNEQVVFT
510 520 530 540 550
DLFPPLCKRM KVQIRDSDKV NDVAIGTHFI DLRKISNDGD KGFLPTLGPA
560 570 580 590 600
WVNMYGSTRN YTLLDEHQDL NEGLGEGVSF RARLMLGLAV EILDTSNPEL
610 620 630 640 650
TSSTEVQVEQ ATPVSESCTG RMEEFFLFGA FLEASMIDRK NGDKPVTFEV
660 670 680 690 700
TIGNYGNEVD GTSRPQRPRP RKEPGDEEEV DLIQNSSDDE GDEAGDLASV
710 720 730 740 750
SSTPPMRPQI TDRNYFHLPY LERKPCIYIK SWWPDQRRRL YNANIMDHIA
760 770 780 790 800
DKLEEGLNDV QEMIKTEKSY PERRLRGVLE ELSCGCHRFL SLSDKDQGHS
810 820 830 840 850
SRTRLDRERL KSCMRELESM GQQAKSLRAQ VKRHTVRDKL RLCQNFLQKL
860 870 880 890 900
RFLADEPQHS IPDVFIWMMS NNKRIAYARV PSKDLLFSIV EEELGKDCAK
910 920 930 940 950
VKTLFLKLPG KRGFGSAGWT VQAKLELYLW LGLSKQRKDF LCGLPCGFEE
960 970 980 990 1000
VKAAQGLGLH SFPPISLVYT KKQTFQLRAH MYQARSLFAA DSTGLSDPFA
1010 1020 1030 1040 1050
RVFFINQSQC TEVLNETLCP TWDQMLVFDN LELYGEAHEL RDDPPIIVIE
1060 1070 1080 1090 1100
IYDQDSMGKA DFMGRTFAKP LVKMADEAYC PPRFPPQLEY YQIYRGNATA
1110 1120 1130 1140 1150
GDLLAAFELL QIGPSGKADL PPINGPVDMD RGPIMPVPVG IRPVLSKYRV
1160 1170 1180 1190 1200
EVLFWGLRDL KRVNLAQVDR PRVDIECAGK GVQSSLIHNY KKNPNFNTLV
1210 1220 1230 1240 1250
KWFEVDLPEN ELLHPPLNIR VVDCRAFGRY TLVGSHAVSS LRRFIYRPPD
1260 1270 1280 1290 1300
RSAANWNTTG EVVVSMEPEV PVKKLETLVK LDATSDAVVK VDVAEDEKER
1310 1320 1330 1340 1350
KKKKKKGPSE EAEEEEPDES MLDWWSKYFA SIDTMKEQLR QHETSGIDLE
1360 1370 1380 1390 1400
EKEEMDSTEG LKGPVKNKEK SRAAKEEKKK KNQNPGPGQG SEAPEKKKAK
1410 1420 1430 1440 1450
IDELKVYPKE LESEFDNFED WLHTFNLLRG KTGDDEDGST EEERIVGRFK
1460 1470 1480 1490 1500
GSLCVYKVPL PEDVSREAGY DPTYGMFQGI PSNDPINVLV RIYVVRATDL
1510 1520 1530 1540 1550
HPADINGKAD PYIAIKLGKT DIRDKENYIS KQLNPVFGKS FDIEASFPME
1560 1570 1580 1590 1600
SMLTVAVYDW DLVGTDDLIG ETKIDLENRF YSKHRATCGI AQTYSIHGYN
1610 1620 1630 1640 1650
IWRDPMKPSQ ILTRLCKEGK VDGPHFGPHG RVKVANRVFT GPSEIEDENG
1660 1670 1680 1690 1700
QRKPTDEHVA LSALRHWEDI PRVGCRLVPE HVETRPLLNP DKPGIEQGRL
1710 1720 1730 1740 1750
ELWVDMFPMD MPAPGTPLDI SPRKPKKYEL RVIVWNTDEV VLEDDDFFTG
1760 1770 1780 1790 1800
EKSSDIFVRG WLKGQQEDKQ DTDVHYHSLT GEGNFNWRYL FPFDYLAAEE
1810 1820 1830 1840 1850
KIVMSKKESM FSWDETEYKI PARLTLQIWD ADHFSADDFL GAIELDLNRF
1860 1870 1880 1890 1900
PRGAKTAKQC TMEMATGEVD VPLVSIFKQK RVKGWWPLLA RNENDEFELT
1910 1920 1930 1940 1950
GKVEAELHLL TAEEAEKNPV GLARNEPDPL EKPNRPDTAF VWFLNPLKSI
1960 1970 1980 1990
KYLICTRYKW LIIKIVLALL GLLMLALFLY SLPGYMVKKL LGA
Length:1,993
Mass (Da):226,339
Last modified:December 16, 2008 - v2
Checksum:i23F6321854110EC8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1629H → P in AAG30298 (Ref. 2) Curated1
Sequence conflicti1811F → C in AAG30298 (Ref. 2) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03048736 Genomic DNA. No translation available.
AABR03049539 Genomic DNA. No translation available.
AF315944 mRNA. Translation: AAG30298.1.
RefSeqiXP_006239895.1. XM_006239833.2.
UniGeneiRn.148993.

Genome annotation databases

EnsembliENSRNOT00000044278; ENSRNOP00000046997; ENSRNOG00000009967.
GeneIDi84573.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03048736 Genomic DNA. No translation available.
AABR03049539 Genomic DNA. No translation available.
AF315944 mRNA. Translation: AAG30298.1.
RefSeqiXP_006239895.1. XM_006239833.2.
UniGeneiRn.148993.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3L9BX-ray1.95A1-124[»]
ProteinModelPortaliQ9ERC5.
SMRiQ9ERC5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000046997.

PTM databases

iPTMnetiQ9ERC5.
PhosphoSitePlusiQ9ERC5.

Proteomic databases

PaxDbiQ9ERC5.
PRIDEiQ9ERC5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000044278; ENSRNOP00000046997; ENSRNOG00000009967.
GeneIDi84573.

Organism-specific databases

CTDi9381.
RGDi620646. Otof.

Phylogenomic databases

eggNOGiKOG1326. Eukaryota.
ENOG410XPT2. LUCA.
GeneTreeiENSGT00550000074414.
HOGENOMiHOG000006770.
HOVERGENiHBG108221.
InParanoidiQ9ERC5.

Miscellaneous databases

EvolutionaryTraceiQ9ERC5.
PROiQ9ERC5.

Gene expression databases

BgeeiENSRNOG00000009967.
ExpressionAtlasiQ9ERC5. baseline and differential.

Family and domain databases

Gene3Di2.60.40.150. 8 hits.
InterProiIPR000008. C2_dom.
IPR012968. FerIin_dom.
IPR012561. Ferlin_B-domain.
IPR032362. Ferlin_C.
IPR029996. Otoferlin.
[Graphical view]
PANTHERiPTHR12546:SF32. PTHR12546:SF32. 5 hits.
PfamiPF00168. C2. 6 hits.
PF08150. FerB. 1 hit.
PF08151. FerI. 1 hit.
PF16165. Ferlin_C. 1 hit.
[Graphical view]
PRINTSiPR00360. C2DOMAIN.
SMARTiSM00239. C2. 6 hits.
SM01201. FerB. 1 hit.
SM01202. FerI. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 8 hits.
PROSITEiPS50004. C2. 4 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiOTOF_RAT
AccessioniPrimary (citable) accession number: Q9ERC5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: December 16, 2008
Last modified: November 2, 2016
This is version 97 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.