OTOF_HUMAN » Otoferlin

OTOF_HUMAN » Otoferlin
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Topology in Vesicle membrane
Topologyvesicle lumenal side
cytoplasmic side
OTOF_HUMAN » Otoferlin » Fer-1-like protein 2;
Hydrophobic Thickness 32.0 ± 4.2 Å
Tilt Angle 0 ± 18°
ΔGtransfer -31.4 kcal/mol
ΔGfold -29.4 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology In
TM Segments 1964-1985 (1958-1986)
Pathways none
PDB none
OPM 3l9b (RAT)
Complexes none
Interactions none
Domains

AA: 5-100, PDBID: 3L9B, Subunit A, Seq Identity:84%, C2 domain

AA: 254-357, PDBID: 2FJU, Subunit B, Seq Identity:25%, C2 domain

AA: 360-410, FerI (NUC094) domain

AA: 417-530, PDBID: 1UGK, Subunit A, Seq Identity:28%, C2 domain

AA: 842-917, FerB (NUC096) domain

AA: 960-1059, PDBID: 3NSJ, Subunit A, Seq Identity:33%, C2 domain

AA: 1492-1596, PDBID: 1DQV, Subunit A, Seq Identity:34%, C2 domain

AA: 1732-1868, PDBID: 3L9B, Subunit A, Seq Identity:15%, C2 domain

AA: 1898-1994, Ferlin C-terminus

UniProt annotation for OTOF_HUMAN » Otoferlin
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).

SUBUNIT: Interacts with SNAP2; the interaction is direct. Interacts with STX1; the interaction is direct. Interacts with RAB8B (By similarity).

TISSUE SPECIFICITY: Isoform 1 and isoform 3 are found in adult brain. Isoform 2 is expressed in the fetus and in adult brain, heart, placenta, skeletal muscle and kidney.

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).

DISEASE: Deafness, autosomal recessive, 9 (DFNB9) OMIM: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. Note=The disease is caused by mutations affecting the gene represented in this entry.

DISEASE: Auditory neuropathy, autosomal recessive, 1 (AUNB1) OMIM: A form of sensorineural hearing loss with absent or severely abnormal auditory brainstem response, in the presence of normal cochlear outer hair cell function and normal otoacoustic emissions. Auditory neuropathies result from a lesion in the area including the inner hair cells, connections between the inner hair cells and the cochlear branch of the auditory nerve, the auditory nerve itself and auditory pathways of the brainstem. In some cases AUNB1 phenotype can be temperature sensitive. Note=The disease is caused by mutations affecting the gene represented in this entry.

UniProt features for OTOF_HUMAN » Otoferlin
CHAIN 1 1997 Otoferlin.
DOMAIN 241 338 C2 1.
DOMAIN 404 514 C2 2.
DOMAIN 947 1052 C2 3.
DOMAIN 1479 1577 C2 4.
COILED 792 821 Potential.
Amino Acid Sequence for OTOF_HUMAN » Otoferlin
MALLIHLKTV SELRGRGDRI AKVTFRGQSF YSRVLENCED VADFDETFRW PVASSIDRNE MLEIQVFNYS KVFSNKLIGT FRMVLQKVVE ESHVEVTDTL IDDNNAIIKT SLCVEVRYQA TDGTVGSWDD GDFLGDESLQ EEEKDSQETD GLLPGSRPSS RPPGEKSFRR AGRSVFSAMK LGKNRSHKEE PQRPDEPAVL EMEDLDHLAI RLGDGLDPDS VSLASVTALT TNVSNKRSKP DIKMEPSAGR PMDYQVSITV IEARQLVGLN MDPVVCVEVG DDKKYTSMKE STNCPYYNEY FVFDFHVSPD VMFDKIIKIS VIHSKNLLRS GTLVGSFKMD VGTVYSQPEH QFHHKWAILS DPDDISSGLK GYVKCDVAVV GKGDNIKTPH KANETDEDDI EGNLLLPEGV PPERQWARFY VKIYRAEGLP RMNTSLMANV KKAFIGENKD LVDPYVQVFF AGQKGKTSVQ KSSYEPLWNE QVVFTDLFPP LCKRMKVQIR DSDKVNDVAI GTHFIDLRKI SNDGDKGFLP TLGPAWVNMY GSTRNYTLLD EHQDLNEGLG EGVSFRARLL LGLAVEIVDT SNPELTSSTE VQVEQATPIS ESCAGKMEEF FLFGAFLEAS MIDRRNGDKP ITFEVTIGNY GNEVDGLSRP QRPRPRKEPG DEEEVDLIQN ASDDEAGDAG DLASVSSTPP MRPQVTDRNY FHLPYLERKP CIYIKSWWPD QRRRLYNANI MDHIADKLEE GLNDIQEMIK TEKSYPERRL RGVLEELSCG CCRFLSLADK DQGHSSRTRL DRERLKSCMR ELENMGQQAR MLRAQVKRHT VRDKLRLCQN FLQKLRFLAD EPQHSIPDIF IWMMSNNKRV AYARVPSKDL LFSIVEEETG KDCAKVKTLF LKLPGKRGFG SAGWTVQAKV ELYLWLGLSK QRKEFLCGLP CGFQEVKAAQ GLGLHAFPPV SLVYTKKQAF QLRAHMYQAR SLFAADSSGL SDPFARVFFI NQSQCTEVLN ETLCPTWDQM LVFDNLELYG EAHELRDDPP IIVIEIYDQD SMGKADFMGR TFAKPLVKMA DEAYCPPRFP PQLEYYQIYR GNATAGDLLA AFELLQIGPA GKADLPPING PVDVDRGPIM PVPMGIRPVL SKYRVEVLFW GLRDLKRVNL AQVDRPRVDI ECAGKGVQSS LIHNYKKNPN FNTLVKWFEV DLPENELLHP PLNIRVVDCR AFGRYTLVGS HAVSSLRRFI YRPPDRSAPS WNTTVRLLRR CRVLCNGGSS SHSTGEVVVT MEPEVPIKKL ETMVKLDATS EAVVKVDVAE EEKEKKKKKK GTAEEPEEEE PDESMLDWWS KYFASIDTMK EQLRQQEPSG IDLEEKEEVD NTEGLKGSMK GKEKARAAKE EKKKKTQSSG SGQGSEAPEK KKPKIDELKV YPKELESEFD NFEDWLHTFN LLRGKTGDDE DGSTEEERIV GRFKGSLCVY KVPLPEDVSR EAGYDSTYGM FQGIPSNDPI NVLVRVYVVR ATDLHPADIN GKADPYIAIR LGKTDIRDKE NYISKQLNPV FGKSFDIEAS FPMESMLTVA VYDWDLVGTD DLIGETKIDL ENRFYSKHRA TCGIAQTYST HGYNIWRDPM KPSQILTRLC KDGKVDGPHF GPPGRVKVAN RVFTGPSEIE DENGQRKPTD EHVALLALRH WEDIPRAGCR LVPEHVETRP LLNPDKPGIE QGRLELWVDM FPMDMPAPGT PLDISPRKPK KYELRVIIWN TDEVVLEDDD FFTGEKSSDI FVRGWLKGQQ EDKQDTDVHY HSLTGEGNFN WRYLFPFDYL AAEEKIVISK KESMFSWDET EYKIPARLTL QIWDADHFSA DDFLGAIELD LNRFPRGAKT AKQCTMEMAT GEVDVPLVSI FKQKRVKGWW PLLARNENDE FELTGKVEAE LHLLTAEEAE KNPVGLARNE PDPLEKPNRP DTSFIWFLNP LKSARYFLWH TYRWLLLKLL LLLLLLLLLA LFLYSVPGYL VKKILGA