OTOF_HUMAN
ID OTOF_HUMAN Reviewed; 1997 AA.
AC Q9HC10; B4DJX0; B5MCC1; B9A0H6; Q53R90; Q9HC08; Q9HC09; Q9Y650;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Otoferlin;
DE AltName: Full=Fer-1-like protein 2;
GN Name=OTOF; Synonyms=FER1L2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND INVOLVEMENT IN DFNB9.
RC TISSUE=Fetus;
RX PubMed=10192385; DOI=10.1038/7693;
RA Yasunaga S., Grati M., Cohen-Salmon M., El-Amraoui A., Mustapha M.,
RA Salem N., El-Zir E., Loiselet J., Petit C.;
RT "A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes
RT DFNB9, a nonsyndromic form of deafness.";
RL Nat. Genet. 21:363-369(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), AND ALTERNATIVE SPLICING.
RC TISSUE=Brain;
RX PubMed=10903124; DOI=10.1086/303049;
RA Yasunaga S., Grati M., Chardenoux S., Smith T.N., Friedman T.B.,
RA Lalwani A.K., Wilcox E.R., Petit C.;
RT "OTOF encodes multiple long and short isoforms: genetic evidence that the
RT long ones underlie recessive deafness DFNB9.";
RL Am. J. Hum. Genet. 67:591-600(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1174-1997 (ISOFORM 5).
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP VARIANTS CYS-82 AND SER-773.
RX PubMed=12114484; DOI=10.1136/jmg.39.7.502;
RA Migliosi V., Modamio-Hoeybjoer S., Moreno-Pelayo M.A.,
RA Rodriguez-Ballesteros M., Villamar M., Telleria D., Menendez I., Moreno F.,
RA Del Castillo I.;
RT "Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is
RT frequently found in Spanish patients with prelingual non-syndromic hearing
RT loss.";
RL J. Med. Genet. 39:502-506(2002).
RN [7]
RP VARIANTS DFNB9 GLN-490 AND THR-515.
RX PubMed=12127154; DOI=10.1006/nbdi.2002.0488;
RA Mirghomizadeh F., Pfister M., Apaydin F., Petit C., Kupka S., Pusch C.M.,
RA Zenner H.P., Blin N.;
RT "Substitutions in the conserved C2C domain of otoferlin cause DFNB9, a form
RT of nonsyndromic autosomal recessive deafness.";
RL Neurobiol. Dis. 10:157-164(2002).
RN [8]
RP VARIANT DFNB9 PRO-1011.
RX PubMed=16097006; DOI=10.1002/ajmg.a.30907;
RA Tekin M., Akcayoz D., Incesulu A.;
RT "A novel missense mutation in a C2 domain of OTOF results in autosomal
RT recessive auditory neuropathy.";
RL Am. J. Med. Genet. A 138:6-10(2005).
RN [9]
RP INVOLVEMENT IN DFNB9, AND VARIANT TRP-822.
RX PubMed=16283880; DOI=10.1111/j.1399-0004.2005.00539.x;
RA Hutchin T., Coy N.N., Conlon H., Telford E., Bromelow K., Blaydon D.,
RA Taylor G., Coghill E., Brown S., Trembath R., Liu X.Z.,
RA Bitner-Glindzicz M., Mueller R.;
RT "Assessment of the genetic causes of recessive childhood non-syndromic
RT deafness in the UK - implications for genetic testing.";
RL Clin. Genet. 68:506-512(2005).
RN [10]
RP VARIANTS DFNB9 GLN-490; HIS-794 AND ALA-1825, VARIANTS AUNB1 THR-515;
RP PRO-1011; GLN-1939 AND ARG-1987, AND VARIANTS VAL-53; CYS-82; MET-575;
RP SER-773; TRP-822; PRO-1083; GLN-1157; GLU-1322; MET-1625; SER-1646 AND
RP ASP-1888.
RX PubMed=16371502; DOI=10.1136/jmg.2005.038612;
RA Varga R., Avenarius M.R., Kelley P.M., Keats B.J., Berlin C.I., Hood L.J.,
RA Morlet T.G., Brashears S.M., Starr A., Cohn E.S., Smith R.J.H.,
RA Kimberling W.J.;
RT "OTOF mutations revealed by genetic analysis of hearing loss families
RT including a potential temperature sensitive auditory neuropathy allele.";
RL J. Med. Genet. 43:576-581(2006).
RN [11]
RP VARIANTS [LARGE SCALE ANALYSIS] LYS-1323 AND VAL-1547.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [12]
RP VARIANTS AUNB1 HIS-255; GLU-964; PRO-1138 AND CYS-1795, AND VARIANTS
RP GLN-1236 AND LYS-1688.
RX PubMed=18381613; DOI=10.1002/humu.20708;
RA Rodriguez-Ballesteros M., Reynoso R., Olarte M., Villamar M., Morera C.,
RA Santarelli R., Arslan E., Meda C., Curet C., Voelter C., Sainz-Quevedo M.,
RA Castorina P., Ambrosetti U., Berrettini S., Frei K., Tedin S., Smith J.,
RA Cruz Tapia M., Cavalle L., Gelvez N., Primignani P., Gomez-Rosas E.,
RA Martin M., Moreno-Pelayo M.A., Tamayo M., Moreno-Barral J., Moreno F.,
RA del Castillo I.;
RT "A multicenter study on the prevalence and spectrum of mutations in the
RT otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and
RT auditory neuropathy.";
RL Hum. Mutat. 29:823-831(2008).
RN [13]
RP VARIANT DFNB9 GLN-1157.
RX PubMed=26437881; DOI=10.1002/ajmg.a.37421;
RA Komara M., John A., Suleiman J., Ali B.R., Al-Gazali L.;
RT "Clinical and molecular delineation of dysequilibrium syndrome type 2 and
RT profound sensorineural hearing loss in an inbred Arab family.";
RL Am. J. Med. Genet. A 170A:540-543(2016).
RN [14]
RP VARIANT TRP-822.
RX PubMed=27535533; DOI=10.1038/nature19057;
RG Exome Aggregation Consortium;
RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T.,
RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T.,
RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J.,
RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M.,
RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N.,
RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P.,
RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A.,
RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G.,
RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M.,
RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C.,
RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M.,
RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M.,
RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P.,
RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G.,
RA Daly M.J., MacArthur D.G.;
RT "Analysis of protein-coding genetic variation in 60,706 humans.";
RL Nature 536:285-291(2016).
CC -!- FUNCTION: Key calcium ion sensor involved in the Ca(2+)-triggered
CC synaptic vesicle-plasma membrane fusion and in the control of
CC neurotransmitter release at these output synapses. Interacts in a
CC calcium-dependent manner to the presynaptic SNARE proteins at ribbon
CC synapses of cochlear inner hair cells (IHCs) to trigger exocytosis of
CC neurotransmitter. Also essential to synaptic exocytosis in immature
CC outer hair cells (OHCs). May also play a role within the recycling of
CC endosomes (By similarity). {ECO:0000250|UniProtKB:Q9ESF1}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC Note=Binds Ca(2+). The ions are bound to the C2 1 domain.
CC {ECO:0000250};
CC -!- SUBUNIT: Interacts with SNAP2; the interaction is direct. Interacts
CC with STX1; the interaction is direct. Interacts with RAB8B (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II
CC membrane protein {ECO:0000250|UniProtKB:Q9ESF1}. Basolateral cell
CC membrane {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II membrane
CC protein {ECO:0000250|UniProtKB:Q9ESF1}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q9ESF1}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q9ESF1}. Presynaptic cell membrane
CC {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q9ESF1}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9ESF1}; Single-pass type II membrane protein
CC {ECO:0000250|UniProtKB:Q9ESF1}. Note=Detected at basolateral cell
CC membrane with synaptic vesicles surrounding the ribbon and at the
CC presynaptic plasma membrane in the inner hair cells (IHCs) at postnatal
CC day 30 (P30). Colocalizes with GPR25 and RAB8B in inner hair cells.
CC {ECO:0000250|UniProtKB:Q9ESF1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=Long;
CC IsoId=Q9HC10-1; Sequence=Displayed;
CC Name=2; Synonyms=Short-1;
CC IsoId=Q9HC10-2; Sequence=VSP_001507, VSP_001508, VSP_001511;
CC Name=3; Synonyms=Short-2;
CC IsoId=Q9HC10-3; Sequence=VSP_001509, VSP_001510;
CC Name=4; Synonyms=Short-3;
CC IsoId=Q9HC10-4; Sequence=VSP_001507, VSP_001508;
CC Name=5;
CC IsoId=Q9HC10-5; Sequence=VSP_001511;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 3 are found in adult brain.
CC Isoform 2 is expressed in the fetus and in adult brain, heart,
CC placenta, skeletal muscle and kidney.
CC -!- DOMAIN: The N-terminal first 124 residues can be classified as C2
CC domain, based on their 3D-structure. They are not sufficient for
CC calcium ion or phospholipid binding (By similarity).
CC {ECO:0000250|UniProtKB:Q9ERC5}.
CC -!- DISEASE: Deafness, autosomal recessive, 9 (DFNB9) [MIM:601071]: A form
CC of non-syndromic sensorineural hearing loss. Sensorineural deafness
CC results from damage to the neural receptors of the inner ear, the nerve
CC pathways to the brain, or the area of the brain that receives sound
CC information. {ECO:0000269|PubMed:10192385, ECO:0000269|PubMed:12127154,
CC ECO:0000269|PubMed:16097006, ECO:0000269|PubMed:16283880,
CC ECO:0000269|PubMed:16371502, ECO:0000269|PubMed:26437881}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Auditory neuropathy, autosomal recessive, 1 (AUNB1)
CC [MIM:601071]: A form of sensorineural hearing loss with absent or
CC severely abnormal auditory brainstem response, in the presence of
CC normal cochlear outer hair cell function and normal otoacoustic
CC emissions. Auditory neuropathies result from a lesion in the area
CC including the inner hair cells, connections between the inner hair
CC cells and the cochlear branch of the auditory nerve, the auditory nerve
CC itself and auditory pathways of the brainstem. In some cases AUNB1
CC phenotype can be temperature sensitive. {ECO:0000269|PubMed:16371502,
CC ECO:0000269|PubMed:18381613}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ferlin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAG58982.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF107403; AAD26117.1; -; mRNA.
DR EMBL; AF183185; AAG12991.1; -; mRNA.
DR EMBL; AF183186; AAG12992.1; -; mRNA.
DR EMBL; AF183187; AAG17468.1; -; mRNA.
DR EMBL; AC093378; AAY15083.1; -; Genomic_DNA.
DR EMBL; AC108070; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471053; EAX00684.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX00686.1; -; Genomic_DNA.
DR EMBL; AK296272; BAG58982.1; ALT_INIT; mRNA.
DR CCDS; CCDS1724.1; -. [Q9HC10-2]
DR CCDS; CCDS1725.1; -. [Q9HC10-1]
DR CCDS; CCDS1726.1; -. [Q9HC10-4]
DR CCDS; CCDS46241.1; -. [Q9HC10-3]
DR CCDS; CCDS74497.1; -. [Q9HC10-5]
DR RefSeq; NP_001274418.1; NM_001287489.1. [Q9HC10-5]
DR RefSeq; NP_004793.2; NM_004802.3. [Q9HC10-4]
DR RefSeq; NP_919224.1; NM_194248.2. [Q9HC10-1]
DR RefSeq; NP_919303.1; NM_194322.2. [Q9HC10-3]
DR RefSeq; NP_919304.1; NM_194323.2. [Q9HC10-2]
DR AlphaFoldDB; Q9HC10; -.
DR SMR; Q9HC10; -.
DR BioGRID; 114782; 18.
DR IntAct; Q9HC10; 4.
DR STRING; 9606.ENSP00000272371; -.
DR iPTMnet; Q9HC10; -.
DR PhosphoSitePlus; Q9HC10; -.
DR BioMuta; OTOF; -.
DR DMDM; 116242695; -.
DR jPOST; Q9HC10; -.
DR MassIVE; Q9HC10; -.
DR MaxQB; Q9HC10; -.
DR PaxDb; Q9HC10; -.
DR PeptideAtlas; Q9HC10; -.
DR PRIDE; Q9HC10; -.
DR ProteomicsDB; 81618; -. [Q9HC10-1]
DR ProteomicsDB; 81619; -. [Q9HC10-2]
DR ProteomicsDB; 81620; -. [Q9HC10-3]
DR ProteomicsDB; 81621; -. [Q9HC10-4]
DR ProteomicsDB; 81622; -. [Q9HC10-5]
DR Antibodypedia; 2369; 62 antibodies from 22 providers.
DR DNASU; 9381; -.
DR Ensembl; ENST00000272371.7; ENSP00000272371.2; ENSG00000115155.19. [Q9HC10-1]
DR Ensembl; ENST00000338581.10; ENSP00000345137.6; ENSG00000115155.19. [Q9HC10-4]
DR Ensembl; ENST00000339598.8; ENSP00000344521.3; ENSG00000115155.19. [Q9HC10-2]
DR Ensembl; ENST00000403946.7; ENSP00000385255.3; ENSG00000115155.19. [Q9HC10-5]
DR GeneID; 9381; -.
DR KEGG; hsa:9381; -.
DR MANE-Select; ENST00000272371.7; ENSP00000272371.2; NM_194248.3; NP_919224.1.
DR UCSC; uc002rhh.3; human. [Q9HC10-1]
DR CTD; 9381; -.
DR DisGeNET; 9381; -.
DR GeneCards; OTOF; -.
DR GeneReviews; OTOF; -.
DR HGNC; HGNC:8515; OTOF.
DR HPA; ENSG00000115155; Group enriched (bone marrow, brain).
DR MalaCards; OTOF; -.
DR MIM; 601071; phenotype.
DR MIM; 603681; gene.
DR neXtProt; NX_Q9HC10; -.
DR OpenTargets; ENSG00000115155; -.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR PharmGKB; PA32841; -.
DR VEuPathDB; HostDB:ENSG00000115155; -.
DR eggNOG; KOG1326; Eukaryota.
DR GeneTree; ENSGT00940000155086; -.
DR HOGENOM; CLU_001183_1_0_1; -.
DR InParanoid; Q9HC10; -.
DR OMA; YWDDKPC; -.
DR OrthoDB; 20162at2759; -.
DR PhylomeDB; Q9HC10; -.
DR TreeFam; TF316871; -.
DR PathwayCommons; Q9HC10; -.
DR Reactome; R-HSA-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane.
DR Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea.
DR SignaLink; Q9HC10; -.
DR BioGRID-ORCS; 9381; 20 hits in 1068 CRISPR screens.
DR ChiTaRS; OTOF; human.
DR GeneWiki; OTOF; -.
DR GenomeRNAi; 9381; -.
DR Pharos; Q9HC10; Tbio.
DR PRO; PR:Q9HC10; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9HC10; protein.
DR Bgee; ENSG00000115155; Expressed in nucleus accumbens and 84 other tissues.
DR ExpressionAtlas; Q9HC10; baseline and differential.
DR Genevisible; Q9HC10; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0048787; C:presynaptic active zone membrane; IBA:GO_Central.
DR GO; GO:0030672; C:synaptic vesicle membrane; ISS:UniProtKB.
DR GO; GO:0035612; F:AP-2 adaptor complex binding; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0061025; P:membrane fusion; TAS:ProtInc.
DR GO; GO:0007009; P:plasma membrane organization; IBA:GO_Central.
DR GO; GO:0007605; P:sensory perception of sound; TAS:ProtInc.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; ISS:UniProtKB.
DR GO; GO:0016082; P:synaptic vesicle priming; IBA:GO_Central.
DR CDD; cd08373; C2A_Ferlin; 1.
DR CDD; cd04011; C2B_Ferlin; 1.
DR CDD; cd04018; C2C_Ferlin; 1.
DR CDD; cd04017; C2D_Ferlin; 1.
DR CDD; cd04037; C2E_Ferlin; 1.
DR CDD; cd08374; C2F_Ferlin; 1.
DR Gene3D; 2.60.40.150; -; 6.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR037726; C2A_Ferlin.
DR InterPro; IPR037720; C2B_Ferlin.
DR InterPro; IPR037722; C2C_Ferlin.
DR InterPro; IPR037723; C2D_Ferlin.
DR InterPro; IPR037724; C2E_Ferlin.
DR InterPro; IPR037725; C2F_Ferlin.
DR InterPro; IPR012968; FerIin_dom.
DR InterPro; IPR037721; Ferlin.
DR InterPro; IPR012561; Ferlin_B-domain.
DR InterPro; IPR032362; Ferlin_C.
DR InterPro; IPR029996; Otoferlin.
DR PANTHER; PTHR12546; PTHR12546; 1.
DR PANTHER; PTHR12546:SF32; PTHR12546:SF32; 1.
DR Pfam; PF00168; C2; 6.
DR Pfam; PF08150; FerB; 1.
DR Pfam; PF08151; FerI; 1.
DR Pfam; PF16165; Ferlin_C; 1.
DR SMART; SM00239; C2; 6.
DR SMART; SM01201; FerB; 1.
DR SMART; SM01202; FerI; 1.
DR SUPFAM; SSF49562; SSF49562; 7.
DR PROSITE; PS50004; C2; 7.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell membrane; Cell projection; Coiled coil;
KW Cytoplasmic vesicle; Deafness; Disease variant; Endoplasmic reticulum;
KW Golgi apparatus; Hearing; Membrane; Metal-binding; Neuropathy;
KW Non-syndromic deafness; Reference proteome; Repeat; Signal-anchor; Synapse;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..1997
FT /note="Otoferlin"
FT /id="PRO_0000057881"
FT TOPO_DOM 1..1963
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1964..1984
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1985..1997
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 1..98
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 236..357
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 400..531
FT /note="C2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 944..1069
FT /note="C2 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1115..1242
FT /note="C2 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1464..1593
FT /note="C2 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 1714..1865
FT /note="C2 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 128..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 642..694
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1299..1324
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1343..1405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 792..821
FT /evidence="ECO:0000255"
FT COMPBIAS 649..664
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1299..1315
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1359..1387
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 976
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 976
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 982
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1038
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1038
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1040
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1040
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1046
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1508
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1508
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1514
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1563
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1563
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1565
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1565
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1571
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1836
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1839
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 1842
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT VAR_SEQ 1..747
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:10192385,
FT ECO:0000303|PubMed:10903124"
FT /id="VSP_001507"
FT VAR_SEQ 1..690
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10903124"
FT /id="VSP_001509"
FT VAR_SEQ 691..738
FT /note="MRPQVTDRNYFHLPYLERKPCIYIKSWWPDQRRRLYNANIMDHIADKL ->
FT MMTDTQDGPSESSQIMRSLTPLINREEAFGEAGEAGLWPSITHTPDSQ (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:10903124"
FT /id="VSP_001510"
FT VAR_SEQ 1245..1264
FT /note="Missing (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:10192385,
FT ECO:0000303|PubMed:10903124"
FT /id="VSP_001508"
FT VAR_SEQ 1943..1997
FT /note="SFIWFLNPLKSARYFLWHTYRWLLLKLLLLLLLLLLLALFLYSVPGYLVKKI
FT LGA -> AFVWFLNPLKSIKYLICTRYKWLIIKIVLALLGLLMLGLFLYSLPGYMVKKL
FT LGA (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:10903124,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_001511"
FT VARIANT 53
FT /note="A -> V (in dbSNP:rs1879761)"
FT /evidence="ECO:0000269|PubMed:16371502"
FT /id="VAR_032226"
FT VARIANT 82
FT /note="R -> C (in dbSNP:rs13031859)"
FT /evidence="ECO:0000269|PubMed:12114484,
FT ECO:0000269|PubMed:16371502"
FT /id="VAR_032227"
FT VARIANT 255
FT /note="Q -> H (in AUNB1; dbSNP:rs397515611)"
FT /evidence="ECO:0000269|PubMed:18381613"
FT /id="VAR_046003"
FT VARIANT 490
FT /note="P -> Q (in DFNB9; dbSNP:rs80356585)"
FT /evidence="ECO:0000269|PubMed:12127154,
FT ECO:0000269|PubMed:16371502"
FT /id="VAR_032228"
FT VARIANT 515
FT /note="I -> T (in DFNB9 and AUNB1; temperature sensitive
FT AUNB1 phenotype with severe hearing loss during febrile
FT illness; dbSNP:rs80356586)"
FT /evidence="ECO:0000269|PubMed:12127154,
FT ECO:0000269|PubMed:16371502"
FT /id="VAR_032229"
FT VARIANT 575
FT /note="V -> M (in dbSNP:rs55676840)"
FT /evidence="ECO:0000269|PubMed:16371502"
FT /id="VAR_032230"
FT VARIANT 773
FT /note="R -> S"
FT /evidence="ECO:0000269|PubMed:12114484,
FT ECO:0000269|PubMed:16371502"
FT /id="VAR_032231"
FT VARIANT 794
FT /note="R -> H (in DFNB9; dbSNP:rs80356592)"
FT /evidence="ECO:0000269|PubMed:16371502"
FT /id="VAR_032232"
FT VARIANT 818
FT /note="R -> W (in dbSNP:rs2272070)"
FT /id="VAR_028028"
FT VARIANT 822
FT /note="R -> W (in dbSNP:rs80356570)"
FT /evidence="ECO:0000269|PubMed:16283880,
FT ECO:0000269|PubMed:16371502, ECO:0000269|PubMed:27535533"
FT /id="VAR_032233"
FT VARIANT 964
FT /note="A -> E (in AUNB1; dbSNP:rs201329629)"
FT /evidence="ECO:0000269|PubMed:18381613"
FT /id="VAR_046004"
FT VARIANT 1011
FT /note="L -> P (in AUNB1 and DFNB9; dbSNP:rs80356596)"
FT /evidence="ECO:0000269|PubMed:16097006,
FT ECO:0000269|PubMed:16371502"
FT /id="VAR_032234"
FT VARIANT 1083
FT /note="A -> P (in dbSNP:rs80356574)"
FT /evidence="ECO:0000269|PubMed:16371502"
FT /id="VAR_032235"
FT VARIANT 1138
FT /note="L -> P (in AUNB1; dbSNP:rs397515599)"
FT /evidence="ECO:0000269|PubMed:18381613"
FT /id="VAR_046005"
FT VARIANT 1157
FT /note="R -> Q (in DFNB9; dbSNP:rs56054534)"
FT /evidence="ECO:0000269|PubMed:16371502,
FT ECO:0000269|PubMed:26437881"
FT /id="VAR_032236"
FT VARIANT 1236
FT /note="R -> Q (in dbSNP:rs368633281)"
FT /evidence="ECO:0000269|PubMed:18381613"
FT /id="VAR_046006"
FT VARIANT 1322
FT /note="D -> E (in dbSNP:rs80356576)"
FT /evidence="ECO:0000269|PubMed:16371502"
FT /id="VAR_032237"
FT VARIANT 1323
FT /note="E -> K (in a breast cancer sample; somatic mutation;
FT dbSNP:rs546115388)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035895"
FT VARIANT 1547
FT /note="I -> V (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035896"
FT VARIANT 1625
FT /note="V -> M (in dbSNP:rs80356579)"
FT /evidence="ECO:0000269|PubMed:16371502"
FT /id="VAR_032238"
FT VARIANT 1646
FT /note="P -> S (in dbSNP:rs17005371)"
FT /evidence="ECO:0000269|PubMed:16371502"
FT /id="VAR_028029"
FT VARIANT 1680
FT /note="R -> H (in dbSNP:rs11893228)"
FT /id="VAR_028030"
FT VARIANT 1688
FT /note="T -> K"
FT /evidence="ECO:0000269|PubMed:18381613"
FT /id="VAR_046007"
FT VARIANT 1795
FT /note="F -> C (in AUNB1; dbSNP:rs397515606)"
FT /evidence="ECO:0000269|PubMed:18381613"
FT /id="VAR_046008"
FT VARIANT 1825
FT /note="P -> A (in DFNB9; dbSNP:rs28937591)"
FT /evidence="ECO:0000269|PubMed:16371502"
FT /id="VAR_032239"
FT VARIANT 1886
FT /note="V -> A (in dbSNP:rs45442103)"
FT /id="VAR_049057"
FT VARIANT 1888
FT /note="G -> D (in dbSNP:rs80356583)"
FT /evidence="ECO:0000269|PubMed:16371502"
FT /id="VAR_032240"
FT VARIANT 1939
FT /note="R -> Q (in AUNB1; dbSNP:rs80356605)"
FT /evidence="ECO:0000269|PubMed:16371502"
FT /id="VAR_032241"
FT VARIANT 1987
FT /note="P -> R (in AUNB1; dbSNP:rs80356606)"
FT /evidence="ECO:0000269|PubMed:16371502"
FT /id="VAR_032242"
FT CONFLICT 1088
FT /note="L -> P (in Ref. 1; AAD26117 and 2; AAG12992/
FT AAG17468)"
FT /evidence="ECO:0000305"
FT CONFLICT 1787
FT /note="G -> S (in Ref. 5; BAG58982)"
FT /evidence="ECO:0000305"
FT CONFLICT Q9HC10-3:21
FT /note="P -> L (in Ref. 2; AAG12992)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1997 AA; 226753 MW; 24DE196371FB7385 CRC64;
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
