Protein: Otoferlin (Fer-1-like protein 2) (Q9ERC5)
Organism: Rattus norvegicus (Rat)
Function: Key calcium ion sensor involved in the Ca(2+)-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).
Subcellular location: Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q9ESF1}. Basolateral cell membrane {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q9ESF1}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q9ESF1}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q9ESF1}. Presynaptic cell membrane {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q9ESF1}. Cell membrane {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q9ESF1}. 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. {ECO:0000250|UniProtKB:Q9ESF1}.
Interaction partners:
- Synaptotagmin-4
- Synaptotagmin-2
- C-terminal-binding protein 2
- Synaptotagmin-1
- Pejvakin
Sequence:
MALIVHLKTVSELRGRADRIAKVTFRGQSFYSRVLENCEDVADFDETFRWPVASSIDRNEVLEIQIFNYSKVFSNKLIGTFRMVLQKVVEENRVEVSDTLIDDNNAIIKTSLSMEVRYQAADGTVGPWDDGDFLGDESLQEEEKDSQETDGLLPGSRPSTRTPGEKSFRSKGKEKTKGGRDGEHKAGRSVFSAMKLGKTRSHKEEPQRQDEPAVLEMEDLDHLAIRLGDGLDPDSVSLASVTALTSNVSNKRSKPDIKMEPSAGRPMDYQVSITVIEARQLVGLNMDPVVCVEVGDDKKYTSMKESTNCPYYNEYFVFDFHVSPDVMFDKIIKISVIHSKNLLRSGTLVGSFKMDVGTVYSQPEHQFHHKWAILSDPDDISAGLKGYVKCDVAVVGKGDNIKTPHKANETDEDDIEGNLLLPEGVPPERQWARFYVKIYRAEGLPRMNTSLMANVKKAFIGENKDLVDPYVQVFFAGQKGKTSVQKSSYEPLWNEQVVFTDLFPPLCKRMKVQIRDSDKVNDVAIGTHFIDLRKISNDGDKGFLPTLGPAWVNMYGSTRNYTLLDEHQDLNEGLGEGVSFRARLMLGLAVEILDTSNPELTSSTEVQVEQATPVSESCTGRMEEFFLFGAFLEASMIDRKNGDKPVTFEVTIGNYGNEVDGTSRPQRPRPRKEPGDEEEVDLIQNSSDDEGDEAGDLASVSSTPPMRPQITDRNYFHLPYLERKPCIYIKSWWPDQRRRLYNANIMDHIADKLEEGLNDVQEMIKTEKSYPERRLRGVLEELSCGCHRFLSLSDKDQGHSSRTRLDRERLKSCMRELESMGQQAKSLRAQVKRHTVRDKLRLCQNFLQKLRFLADEPQHSIPDVFIWMMSNNKRIAYARVPSKDLLFSIVEEELGKDCAKVKTLFLKLPGKRGFGSAGWTVQAKLELYLWLGLSKQRKDFLCGLPCGFEEVKAAQGLGLHSFPPISLVYTKKQTFQLRAHMYQARSLFAADSTGLSDPFARVFFINQSQCTEVLNETLCPTWDQMLVFDNLELYGEAHELRDDPPIIVIEIYDQDSMGKADFMGRTFAKPLVKMADEAYCPPRFPPQLEYYQIYRGNATAGDLLAAFELLQIGPSGKADLPPINGPVDMDRGPIMPVPVGIRPVLSKYRVEVLFWGLRDLKRVNLAQVDRPRVDIECAGKGVQSSLIHNYKKNPNFNTLVKWFEVDLPENELLHPPLNIRVVDCRAFGRYTLVGSHAVSSLRRFIYRPPDRSAANWNTTGEVVVSMEPEVPVKKLETLVKLDATSDAVVKVDVAEDEKERKKKKKKGPSEEAEEEEPDESMLDWWSKYFASIDTMKEQLRQHETSGIDLEEKEEMDSTEGLKGPVKNKEKSRAAKEEKKKKNQNPGPGQGSEAPEKKKAKIDELKVYPKELESEFDNFEDWLHTFNLLRGKTGDDEDGSTEEERIVGRFKGSLCVYKVPLPEDVSREAGYDPTYGMFQGIPSNDPINVLVRIYVVRATDLHPADINGKADPYIAIKLGKTDIRDKENYISKQLNPVFGKSFDIEASFPMESMLTVAVYDWDLVGTDDLIGETKIDLENRFYSKHRATCGIAQTYSIHGYNIWRDPMKPSQILTRLCKEGKVDGPHFGPHGRVKVANRVFTGPSEIEDENGQRKPTDEHVALSALRHWEDIPRVGCRLVPEHVETRPLLNPDKPGIEQGRLELWVDMFPMDMPAPGTPLDISPRKPKKYELRVIVWNTDEVVLEDDDFFTGEKSSDIFVRGWLKGQQEDKQDTDVHYHSLTGEGNFNWRYLFPFDYLAAEEKIVMSKKESMFSWDETEYKIPARLTLQIWDADHFSADDFLGAIELDLNRFPRGAKTAKQCTMEMATGEVDVPLVSIFKQKRVKGWWPLLARNENDEFELTGKVEAELHLLTAEEAEKNPVGLARNEPDPLEKPNRPDTAFVWFLNPLKSIKYLICTRYKWLIIKIVLALLGLLMLALFLYSLPGYMVKKLLGA