OTOF

OTOF
Identifikatori
Aliasi	OTOF
Vanjski ID-jevi	OMIM: 603681 MGI: 1891247 HomoloGene: 12892 GeneCards: OTOF
Lokacija gena (čovjek)
Hrom.	Hromosom 2 (čovjek)
Kraj	26,558,756 bp
Lokacija gena (miš)
Hrom.	Hromosom 5 (miš)
Kraj	30,619,276 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• calcium ion binding; • molekularna funkcija;
Ćelijska komponenta	• integral component of membrane; • citosol; • međućelijske veze; • ćelijska membrana; • basolateral plasma membrane; • sinapsa; • synaptic vesicle membrane; • endoplasmic reticulum membrane; • Endoplazmatski retikulum; • membrana; • GO:0016023 citoplazmatska vezikula;
Biološki proces	• membrane fusion; • sluh; • synaptic vesicle exocytosis;
	Izvori:Amigo / QuickGO
Ortolozi
	9381
	83762
	ENSG00000115155
	ENSMUSG00000062372
	Q9HC10
	Q9ESF1
	NM_001287489; NM_004802; NM_194248; NM_194322; NM_194323
	NM_001100395; NM_001286421; NM_031875; NM_001313767
	NP_001274418; NP_004793; NP_919224; NP_919303; NP_919304
	NP_001093865; NP_001273350; NP_001300696; NP_114081
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Otoferlin jest protein koji je kod ljudi kodiran genom OTOF sa hromosoma 2.^[5]^[6]^[7]

Amiokiselininska sekvenca

Dužina polipeptidnog lanca je 1.997 aminokiselina, a molkekulska težina 226.753 Da.^[8]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
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

Funkcija

Mutacije u ovom genu uzrok su neurosenzorne nesindromske recesivna gluhoće, DFNB9. Kratki oblik kodiranog proteina ima tri C2 domena, jedan karboksi-terminal, transmembranski domen koji se nalazi iu faktoru spermatogeneze C. elegans FER-1 i ljudskom disferlinu, dok duga obrazac ima šest C2 domena. Homologni proteini otoferlina kod ljudi za koje se pokazalo da su povezani s ljudskim bolestima su disferlin i mioferlin. I disferlin i mioferlin imaju po sedam C2 domena. C2A u dužem obliku otoferlina sa šest C2 domena je strukturno sličan disferlinu C2A. Međutim, petlja 1 na mjestu vezivanja za kalcij otoferlina C2A je značajno kraća od homologne petlje u domenima disferlina i mioferlina C2A. Zbog toga se ne može vezati za kalcij. Otoferlin C2A također nije u stanju da se veže za fosfolipide i stoga je strukturno i funkcionalno drugačiji od drugih C2 domena.^[9] Homologija sugerira da ovaj protein može biti uključen u fuziju vezikulske membrane. Slično disferlinu i mioferlinu, otoferlin ima FerA domen i pokazalo se da njegov FerA domen stupa u interakciju sa blizanci-ionskim lipidima na način ovisan o kalciju i s negativno nabijenim lipidima na način koji ne ovisi o kalciju.^[10] Procijenjeni naboj FerA domena među proteinima ferlina značajno varira. Na pH 7, procijenjeni naboj disferlina je –8,4 dok je otoferlin FerA +8,5.^[10] Za ovaj gen nađeno je nekoliko varijanti transkripta koje kodiraju više izoformi.^[7]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000115155 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000062372 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Yasunaga S, Grati M, Cohen-Salmon M, El-Amraoui A, Mustapha M, Salem N, El-Zir E, Loiselet J, Petit C (april 1999). "A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness". Nature Genetics. 21 (4): 363–9. doi:10.1038/7693. PMID 10192385. S2CID 19269361.
^ Rodríguez-Ballesteros M, Reynoso R, Olarte M, Villamar M, Morera C, Santarelli R, Arslan E, Medá C, Curet C, Völter C, Sainz-Quevedo M, Castorina P, Ambrosetti U, Berrettini S, Frei K, Tedín S, Smith J, Cruz Tapia M, Cavallé L, Gelvez N, Primignani P, Gómez-Rosas E, Martín M, Moreno-Pelayo MA, Tamayo M, Moreno-Barral J, Moreno F, del Castillo I (juni 2008). "A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy". Human Mutation. 29 (6): 823–31. doi:10.1002/humu.20708. PMID 18381613. S2CID 19170712.
^ ^a ^b "Entrez Gene: OTOF otoferlin".
^ "UniProt, Q9HC10" (jezik: engleski). Pristupljeno 14. 11. 2021.
^ Helfmann S, Neumann P, Tittmann K, Moser T, Ficner R, Reisinger E (februar 2011). "The crystal structure of the C₂A domain of otoferlin reveals an unconventional top loop region". Journal of Molecular Biology. 406 (3): 479–90. doi:10.1016/j.jmb.2010.12.031. PMID 21216247.
^ ^a ^b Harsini FM, Chebrolu S, Fuson KL, White MA, Rice AM, Sutton RB (juli 2018). "FerA is a Membrane-Associating Four-Helix Bundle Domain in the Ferlin Family of Membrane-Fusion Proteins". Scientific Reports. 8 (1): 10949. doi:10.1038/s41598-018-29184-1. PMC 6053371. PMID 30026467.

Dopunska literatura

Fukushima K, Ramesh A, Srisailapathy CR, Ni L, Wayne S, O'Neill ME, Van Camp G, Coucke P, Jain P, Wilcox ER, Smith SD, Kenyon JB, Zbar RI, Smith RJ (oktobar 1995). "An autosomal recessive nonsyndromic form of sensorineural hearing loss maps to 3p-DFNB6". Genome Research. 5 (3): 305–8. doi:10.1101/gr.5.3.305. PMID 8593615.
Yasunaga S, Petit C (maj 2000). "Physical map of the region surrounding the OTOFERLIN locus on chromosome 2p22-p23". Genomics. 66 (1): 110–2. doi:10.1006/geno.2000.6185. PMID 10843812.
Adato A, Raskin L, Petit C, Bonne-Tamir B (juni 2000). "Deafness heterogeneity in a Druze isolate from the Middle East: novel OTOF and PDS mutations, low prevalence of GJB2 35delG mutation and indication for a new DFNB locus". European Journal of Human Genetics. 8 (6): 437–42. doi:10.1038/sj.ejhg.5200489. PMID 10878664.
Yasunaga S, Grati M, Chardenoux S, Smith TN, Friedman TB, Lalwani AK, Wilcox ER, Petit C (septembar 2000). "OTOF encodes multiple long and short isoforms: genetic evidence that the long ones underlie recessive deafness DFNB9". American Journal of Human Genetics. 67 (3): 591–600. doi:10.1086/303049. PMC 1287519. PMID 10903124.
Migliosi V, Modamio-Høybjør S, Moreno-Pelayo MA, Rodríguez-Ballesteros M, Villamar M, Tellería D, Menéndez I, Moreno F, Del Castillo I (juli 2002). "Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss". Journal of Medical Genetics. 39 (7): 502–6. doi:10.1136/jmg.39.7.502. PMC 1735186. PMID 12114484.
Mirghomizadeh F, Pfister M, Apaydin F, Petit C, Kupka S, Pusch CM, Zenner HP, Blin N (juli 2002). "Substitutions in the conserved C2C domain of otoferlin cause DFNB9, a form of nonsyndromic autosomal recessive deafness". Neurobiology of Disease. 10 (2): 157–64. doi:10.1006/nbdi.2002.0488. PMID 12127154. S2CID 37646982.
Mirghomizadeh F, Pfister M, Blin N, Pusch CM (januar 2003). "Uncommon cytidine-homopolymer dimorphism in 5'-UTR of the human otoferlin gene". International Journal of Molecular Medicine. 11 (1): 63–4. doi:10.3892/ijmm.11.1.63. PMID 12469219.
Varga R, Kelley PM, Keats BJ, Starr A, Leal SM, Cohn E, Kimberling WJ (januar 2003). "Non-syndromic recessive auditory neuropathy is the result of mutations in the otoferlin (OTOF) gene". Journal of Medical Genetics. 40 (1): 45–50. doi:10.1136/jmg.40.1.45. PMC 1735255. PMID 12525542.
Piechotta K, Garbarini N, England R, Delpire E (decembar 2003). "Characterization of the interaction of the stress kinase SPAK with the Na+-K+-2Cl- cotransporter in the nervous system: evidence for a scaffolding role of the kinase". The Journal of Biological Chemistry. 278 (52): 52848–56. doi:10.1074/jbc.M309436200. PMID 14563843.
Varga R, Avenarius MR, Kelley PM, Keats BJ, Berlin CI, Hood LJ, Morlet TG, Brashears SM, Starr A, Cohn ES, Smith RJ, Kimberling WJ (juli 2006). "OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele". Journal of Medical Genetics. 43 (7): 576–81. doi:10.1136/jmg.2005.038612. PMC 2593030. PMID 16371502.
Roux I, Safieddine S, Nouvian R, Grati M, Simmler MC, Bahloul A, Perfettini I, Le Gall M, Rostaing P, Hamard G, Triller A, Avan P, Moser T, Petit C (oktobar 2006). "Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse". Cell. 127 (2): 277–89. doi:10.1016/j.cell.2006.08.040. PMID 17055430. S2CID 15233556.

Vanjski linkovi

GeneReviews/NCBI/NIH/UW entry on OTOF-Related Deafness

Šablon:Ostali proteini ćelijske membrane

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000115155 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000062372 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid10192385-5] Yasunaga S, Grati M, Cohen-Salmon M, El-Amraoui A, Mustapha M, Salem N, El-Zir E, Loiselet J, Petit C (april 1999). "A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness". Nature Genetics. 21 (4): 363–9. doi:10.1038/7693. PMID 10192385. S2CID 19269361.

[pmid18381613-6] Rodríguez-Ballesteros M, Reynoso R, Olarte M, Villamar M, Morera C, Santarelli R, Arslan E, Medá C, Curet C, Völter C, Sainz-Quevedo M, Castorina P, Ambrosetti U, Berrettini S, Frei K, Tedín S, Smith J, Cruz Tapia M, Cavallé L, Gelvez N, Primignani P, Gómez-Rosas E, Martín M, Moreno-Pelayo MA, Tamayo M, Moreno-Barral J, Moreno F, del Castillo I (juni 2008). "A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy". Human Mutation. 29 (6): 823–31. doi:10.1002/humu.20708. PMID 18381613. S2CID 19170712.

[entrez-7] "Entrez Gene: OTOF otoferlin".

[UniProt-8] "UniProt, Q9HC10" (jezik: engleski). Pristupljeno 14. 11. 2021.

[9] Helfmann S, Neumann P, Tittmann K, Moser T, Ficner R, Reisinger E (februar 2011). "The crystal structure of the C₂A domain of otoferlin reveals an unconventional top loop region". Journal of Molecular Biology. 406 (3): 479–90. doi:10.1016/j.jmb.2010.12.031. PMID 21216247.

[FerA-10] Harsini FM, Chebrolu S, Fuson KL, White MA, Rice AM, Sutton RB (juli 2018). "FerA is a Membrane-Associating Four-Helix Bundle Domain in the Ferlin Family of Membrane-Fusion Proteins". Scientific Reports. 8 (1): 10949. doi:10.1038/s41598-018-29184-1. PMC 6053371. PMID 30026467.

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