ID COCH_HUMAN Reviewed; 550 AA. AC O43405; A8K9K9; D3DS84; Q96IU6; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 27-MAR-2024, entry version 215. DE RecName: Full=Cochlin; DE AltName: Full=COCH-5B2; DE Flags: Precursor; GN Name=COCH; Synonyms=COCH5B2; ORFNames=UNQ257/PRO294; 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 1). RC TISSUE=Cochlea; RX PubMed=9441737; DOI=10.1006/geno.1997.5067; RA Robertson N.G., Skvorak A.B., Yin Y., Weremowicz S., Johnson K.R., RA Kovatch K.A., Battey J.F., Bieber F.R., Morton C.C.; RT "Mapping and characterization of a novel cochlear gene in human and in RT mouse: a positional candidate gene for a deafness disorder, DFNA9."; RL Genomics 46:345-354(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Kidney; 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 [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-135; ASN-281; SER-352 RP AND VAL-402. RG SeattleSNPs variation discovery resource; RL Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP GLYCOSYLATION, SUBCELLULAR LOCATION, AND PROTEOLYTIC PROCESSING. RX PubMed=12843317; DOI=10.1136/jmg.40.7.479; RA Robertson N.G., Hamaker S.A., Patriub V., Aster J.C., Morton C.C.; RT "Subcellular localisation, secretion, and post-translational processing of RT normal cochlin, and of mutants causing the sensorineural deafness and RT vestibular disorder, DFNA9."; RL J. Med. Genet. 40:479-486(2003). RN [9] RP INTERACTION WITH SLC44A2. RX PubMed=17926100; DOI=10.1007/s10162-007-0099-2; RA Kommareddi P.K., Nair T.S., Raphael Y., Telian S.A., Kim A.H., Arts H.A., RA El-Kashlan H.K., Carey T.E.; RT "Cochlin isoforms and their interaction with CTL2 (SLC44A2) in the inner RT ear."; RL J. Assoc. Res. Otolaryngol. 8:435-446(2007). RN [10] RP FUNCTION, AND INTERACTION WITH ANXA2. RX PubMed=21886777; DOI=10.1371/journal.pone.0023070; RA Goel M., Sienkiewicz A.E., Picciani R., Lee R.K., Bhattacharya S.K.; RT "Cochlin induced TREK-1 co-expression and annexin A2 secretion: role in RT trabecular meshwork cell elongation and motility."; RL PLoS ONE 6:E23070-E23070(2011). RN [11] RP STRUCTURE BY NMR OF 27-126. RX PubMed=11574466; DOI=10.1093/emboj/20.19.5347; RA Liepinsh E., Trexler M., Kaikkonen A., Weigelt J., Banyai L., Patthy L., RA Otting G.; RT "NMR structure of the LCCL domain and implications for DFNA9 deafness RT disorder."; RL EMBO J. 20:5347-5353(2001). RN [12] RP VARIANTS DFNA9 GLY-66; GLU-88 AND ARG-117. RX PubMed=9806553; DOI=10.1038/3118; RA Robertson N.G., Lu L., Heller S., Merchant S.N., Eavey R.D., McKenna M., RA Nadol J.B. Jr., Miyamoto R.T., Linthicum F.H. Jr., Neto J.F.L., RA Hudspeth A.J., Seidman C.E., Morton C.C., Seidman J.G.; RT "Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic RT deafness with vestibular dysfunction."; RL Nat. Genet. 20:299-303(1998). RN [13] RP VARIANT DFNA9 SER-51. RX PubMed=9931344; DOI=10.1093/hmg/8.2.361; RA de Kok Y.J.M., Bom S.J.H., Brunt T.M., Kemperman M.H., van Beusekom E., RA van der Velde-Visser S.D., Robertson N.G., Morton C.C., Huygen P.L.M., RA Verhagen W.I.M., Brunner H.G., Cremers C.W.R.J., Cremers F.P.M.; RT "A Pro51Ser mutation in the COCH gene is associated with late onset RT autosomal dominant progressive sensorineural hearing loss with vestibular RT defects."; RL Hum. Mol. Genet. 8:361-366(1999). RN [14] RP VARIANT DFNA9 SER-51. RX PubMed=10400989; DOI=10.1093/hmg/8.8.1425; RA Fransen E., Verstreken M., Verhagen W.I.M., Wuyts F.L., Huygen P.L.M., RA D'Haese P., Robertson N.G., Morton C.C., McGuirt W.T., Smith R.J.H., RA Declau F., Van de Heyning P.H., Van Camp G.; RT "High prevalence of symptoms of Meniere's disease in three families with a RT mutation in the COCH gene."; RL Hum. Mol. Genet. 8:1425-1429(1999). RN [15] RP VARIANT DFNA9 ASN-109. RX PubMed=11295836; DOI=10.1002/humu.37; RA Kamarinos M., McGill J., Lynch M., Dahl H.-H.M.; RT "Identification of a novel COCH mutation, I109N, highlights the similar RT clinical features observed in DFNA9 families."; RL Hum. Mutat. 17:351-351(2001). RN [16] RP ERRATUM OF PUBMED:11295836. RA Kamarinos M., McGill J., Lynch M., Dahl H.-H.M.; RL Hum. Mutat. 18:547-548(2001). RN [17] RP VARIANT DFNA9 THR-119. RX PubMed=14512963; DOI=10.1038/sj.ejhg.5201043; RA Usami S., Takahashi K., Yuge I., Ohtsuka A., Namba A., Abe S., Fransen E., RA Patthy L., Otting G., Van Camp G.; RT "Mutations in the COCH gene are a frequent cause of autosomal dominant RT progressive cochleo-vestibular dysfunction, but not of Meniere's disease."; RL Eur. J. Hum. Genet. 11:744-748(2003). RN [18] RP CHARACTERIZATION OF VARIANTS DFNA9 SER-51; GLY-66; GLU-88; ASN-109 AND RP ARG-117. RX PubMed=12928864; DOI=10.1007/s00439-003-0992-7; RA Grabski R., Szul T., Sasaki T., Timpl R., Mayne R., Hicks B., Sztul E.; RT "Mutations in COCH that result in non-syndromic autosomal dominant deafness RT (DFNA9) affect matrix deposition of cochlin."; RL Hum. Genet. 113:406-416(2003). RN [19] RP VARIANT DFNA9 TRP-87. RX PubMed=16835921; DOI=10.1002/ajmg.a.31354; RA Collin R.W., Pauw R.J., Schoots J., Huygen P.L., Hoefsloot L.H., RA Cremers C.W., Kremer H.; RT "Identification of a novel COCH mutation, G87W, causing autosomal dominant RT hearing impairment (DFNA9)."; RL Am. J. Med. Genet. A 140:1791-1794(2006). RN [20] RP VARIANT DFNA9 THR-109. RX PubMed=17561763; DOI=10.1177/000348940711600506; RA Pauw R.J., Huygen P.L., Collin R.W., Cruysberg J.R., Hoefsloot L.H., RA Kremer H., Cremers C.W.; RT "Phenotype description of a novel DFNA9/COCH mutation, I109T."; RL Ann. Otol. Rhinol. Laryngol. 116:349-357(2007). RN [21] RP VARIANTS DFNA9 THR-512 AND TYR-542. RX PubMed=18312449; DOI=10.1111/j.1399-0004.2008.00972.x; RA Yuan H.J., Han D.Y., Sun Q., Yan D., Sun H.J., Tao R., Cheng J., Qin W., RA Angeli S., Ouyang X.M., Yang S.Z., Feng L., Cao J.Y., Feng G.Y., Wang Y.F., RA Dai P., Zhai S.Q., Yang W.Y., He L., Liu X.Z.; RT "Novel mutations in the vWFA2 domain of COCH in two Chinese DFNA9 RT families."; RL Clin. Genet. 73:391-394(2008). RN [22] RP VARIANT DFNA9 CYS-527, CHARACTERIZATION OF VARIANT DFNA9 CYS-527, RP SUBCELLULAR LOCATION, INTERACTION WITH COLLAGEN, SUBUNIT, AND RP HOMODIMERIZATION. RX PubMed=22610276; DOI=10.1007/s00109-012-0911-2; RA Cho H.J., Park H.J., Trexler M., Venselaar H., Lee K.Y., Robertson N.G., RA Baek J.I., Kang B.S., Morton C.C., Vriend G., Patthy L., Kim U.K.; RT "A novel COCH mutation associated with autosomal dominant nonsyndromic RT hearing loss disrupts the structural stability of the vWFA2 domain."; RL J. Mol. Med. 90:1321-1331(2012). RN [23] RP VARIANT DFNA9 TYR-162. RX PubMed=22931125; DOI=10.1111/cge.12006; RA Gao J., Xue J., Chen L., Ke X., Qi Y., Liu Y.; RT "Whole exome sequencing identifies a novel DFNA9 mutation, C162Y."; RL Clin. Genet. 83:477-481(2013). RN [24] RP VARIANT DFNA9 VAL-87. RX PubMed=23993205; DOI=10.1016/j.ijporl.2013.07.031; RA Chen D.Y., Chai Y.C., Yang T., Wu H.; RT "Clinical characterization of a novel COCH mutation G87V in a Chinese DFNA9 RT family."; RL Int. J. Pediatr. Otorhinolaryngol. 77:1711-1715(2013). RN [25] RP VARIANT DFNA9 ASP-38. RX PubMed=25388789; DOI=10.1186/s12967-014-0311-1; RA Wei Q., Zhu H., Qian X., Chen Z., Yao J., Lu Y., Cao X., Xing G.; RT "Targeted genomic capture and massively parallel sequencing to identify RT novel variants causing Chinese hereditary hearing loss."; RL J. Transl. Med. 12:311-311(2014). RN [26] RP VARIANT DFNB110 98-ARG--GLN-550 DEL, AND INVOLVEMENT IN DFNB110. RX PubMed=29449721; DOI=10.1038/s41431-017-0066-2; RA JanssensdeVarebeke S.P.F., Van Camp G., Peeters N., Elinck E., RA Widdershoven J., Cox T., Deben K., Ketelslagers K., Crins T., Wuyts W.; RT "Bi-allelic inactivating variants in the COCH gene cause autosomal RT recessive prelingual hearing impairment."; RL Eur. J. Hum. Genet. 26:587-591(2018). CC -!- FUNCTION: Plays a role in the control of cell shape and motility in the CC trabecular meshwork. {ECO:0000269|PubMed:21886777}. CC -!- SUBUNIT: Monomer (PubMed:22610276). May form homodimer CC (PubMed:22610276). Interacts with type II collagen (PubMed:22610276). CC Interacts with SLC44A2 (PubMed:17926100). Interacts with ANXA2 CC (PubMed:21886777). {ECO:0000269|PubMed:17926100, CC ECO:0000269|PubMed:21886777, ECO:0000269|PubMed:22610276}. CC -!- INTERACTION: CC O43405-2; O76024: WFS1; NbExp=3; IntAct=EBI-25896722, EBI-720609; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix {ECO:0000269|PubMed:12843317, ECO:0000269|PubMed:22610276}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O43405-1; Sequence=Displayed; CC Name=2; CC IsoId=O43405-2; Sequence=VSP_056538; CC -!- TISSUE SPECIFICITY: Expressed in inner ear structures; the cochlea and CC the vestibule. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:12843317}. CC -!- PTM: A 50 kDa form is created by proteolytic cleavage. CC {ECO:0000269|PubMed:12843317}. CC -!- DISEASE: Deafness, autosomal dominant, 9 (DFNA9) [MIM:601369]: A form CC of non-syndromic hearing loss characterized by onset in the fourth or CC fifth decade of life and initially involves the high frequencies. CC Hearing loss is progressive and usually complete by the sixth decade. CC In addition to cochlear involvement, DFNA9 patients also exhibit a CC spectrum of vestibular dysfunctions. Penetrance of the vestibular CC symptoms is often incomplete, and some patients are minimally affected, CC whereas others suffer from severe balance disturbances and episodes of CC vertigo. Affected individuals have mucopolysaccharide depositions in CC the channels of the cochlear and vestibular nerves. These depositions CC apparently cause strangulation and degeneration of dendritic fibers. CC {ECO:0000269|PubMed:10400989, ECO:0000269|PubMed:11295836, CC ECO:0000269|PubMed:12928864, ECO:0000269|PubMed:14512963, CC ECO:0000269|PubMed:16835921, ECO:0000269|PubMed:17561763, CC ECO:0000269|PubMed:18312449, ECO:0000269|PubMed:22610276, CC ECO:0000269|PubMed:22931125, ECO:0000269|PubMed:23993205, CC ECO:0000269|PubMed:25388789, ECO:0000269|PubMed:9806553, CC ECO:0000269|PubMed:9931344}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Deafness, autosomal recessive, 110 (DFNB110) [MIM:618094]: A CC form of non-syndromic, sensorineural deafness characterized by CC prelingual hearing loss. Sensorineural deafness results from damage to CC the neural receptors of the inner ear, the nerve pathways to the brain, CC or the area of the brain that receives sound information. DFNB110 CC affected individuals additionally exhibit mild, age-dependent CC vestibular dysfunction. {ECO:0000269|PubMed:29449721}. Note=The disease CC is caused by variants affecting the gene represented in this entry. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The Japanese Horseshoe Crab CC and Deafness - Issue 4 of November 2000; CC URL="https://web.expasy.org/spotlight/back_issues/004"; CC -!- WEB RESOURCE: Name=Hereditary hearing loss homepage; Note=Gene page; CC URL="https://hereditaryhearingloss.org/dominant-genes"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/coch/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF006740; AAC39545.1; -; mRNA. DR EMBL; AY358900; AAQ89259.1; -; mRNA. DR EMBL; AK292724; BAF85413.1; -; mRNA. DR EMBL; AY916789; AAW82432.1; -; Genomic_DNA. DR EMBL; AL049830; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471078; EAW65963.1; -; Genomic_DNA. DR EMBL; CH471078; EAW65964.1; -; Genomic_DNA. DR EMBL; CH471078; EAW65965.1; -; Genomic_DNA. DR EMBL; BC007230; AAH07230.1; -; mRNA. DR CCDS; CCDS9640.1; -. [O43405-1] DR RefSeq; NP_001128530.1; NM_001135058.1. [O43405-1] DR RefSeq; NP_004077.1; NM_004086.2. [O43405-1] DR PDB; 1JBI; NMR; -; A=28-124. DR PDBsum; 1JBI; -. DR AlphaFoldDB; O43405; -. DR SMR; O43405; -. DR BioGRID; 108051; 47. DR IntAct; O43405; 19. DR MINT; O43405; -. DR STRING; 9606.ENSP00000216361; -. DR TCDB; 8.A.54.1.3; the integrin (integrin) family. DR GlyCosmos; O43405; 2 sites, No reported glycans. DR GlyGen; O43405; 8 sites, 1 N-linked glycan (1 site), 2 O-linked glycans (6 sites). DR iPTMnet; O43405; -. DR PhosphoSitePlus; O43405; -. DR BioMuta; COCH; -. DR EPD; O43405; -. DR jPOST; O43405; -. DR MassIVE; O43405; -. DR MaxQB; O43405; -. DR PaxDb; 9606-ENSP00000379862; -. DR PeptideAtlas; O43405; -. DR ProteomicsDB; 48929; -. [O43405-1] DR ProteomicsDB; 76856; -. DR Pumba; O43405; -. DR Antibodypedia; 22996; 230 antibodies from 27 providers. DR DNASU; 1690; -. DR Ensembl; ENST00000396618.9; ENSP00000379862.3; ENSG00000100473.18. [O43405-1] DR Ensembl; ENST00000475087.5; ENSP00000451528.1; ENSG00000100473.18. [O43405-2] DR Ensembl; ENST00000643575.1; ENSP00000494838.1; ENSG00000100473.18. [O43405-1] DR Ensembl; ENST00000644874.2; ENSP00000496360.1; ENSG00000100473.18. [O43405-1] DR GeneID; 1690; -. DR KEGG; hsa:1690; -. DR MANE-Select; ENST00000396618.9; ENSP00000379862.3; NM_004086.3; NP_004077.1. DR UCSC; uc001wqp.3; human. [O43405-1] DR AGR; HGNC:2180; -. DR CTD; 1690; -. DR DisGeNET; 1690; -. DR GeneCards; COCH; -. DR GeneReviews; COCH; -. DR HGNC; HGNC:2180; COCH. DR HPA; ENSG00000100473; Tissue enriched (pancreas). DR MalaCards; COCH; -. DR MIM; 601369; phenotype. DR MIM; 603196; gene. DR MIM; 618094; phenotype. DR neXtProt; NX_O43405; -. DR OpenTargets; ENSG00000100473; -. DR Orphanet; 90635; Rare autosomal dominant non-syndromic sensorineural deafness type DFNA. DR PharmGKB; PA26693; -. DR VEuPathDB; HostDB:ENSG00000100473; -. DR eggNOG; KOG1216; Eukaryota. DR GeneTree; ENSGT00940000159386; -. DR InParanoid; O43405; -. DR OMA; TAITCFT; -. DR OrthoDB; 2883115at2759; -. DR PhylomeDB; O43405; -. DR TreeFam; TF318242; -. DR PathwayCommons; O43405; -. DR SignaLink; O43405; -. DR BioGRID-ORCS; 1690; 22 hits in 1153 CRISPR screens. DR ChiTaRS; COCH; human. DR EvolutionaryTrace; O43405; -. DR GeneWiki; COCH; -. DR GenomeRNAi; 1690; -. DR Pharos; O43405; Tbio. DR PRO; PR:O43405; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; O43405; Protein. DR Bgee; ENSG00000100473; Expressed in buccal mucosa cell and 200 other cell types or tissues. DR ExpressionAtlas; O43405; baseline and differential. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW. DR GO; GO:0005518; F:collagen binding; IDA:UniProtKB. DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB. DR GO; GO:0007605; P:sensory perception of sound; TAS:ProtInc. DR CDD; cd01472; vWA_collagen; 1. DR CDD; cd01482; vWA_collagen_alphaI-XII-like; 1. DR Gene3D; 2.170.130.20; LCCL-like domain; 1. DR Gene3D; 3.40.50.410; von Willebrand factor, type A domain; 2. DR InterPro; IPR004043; LCCL. DR InterPro; IPR036609; LCCL_sf. DR InterPro; IPR002035; VWF_A. DR InterPro; IPR036465; vWFA_dom_sf. DR PANTHER; PTHR24020:SF36; COCHLIN; 1. DR PANTHER; PTHR24020; COLLAGEN ALPHA; 1. DR Pfam; PF03815; LCCL; 1. DR Pfam; PF00092; VWA; 2. DR PRINTS; PR00453; VWFADOMAIN. DR SMART; SM00603; LCCL; 1. DR SMART; SM00327; VWA; 2. DR SUPFAM; SSF69848; LCCL domain; 1. DR SUPFAM; SSF53300; vWA-like; 2. DR PROSITE; PS50820; LCCL; 1. DR PROSITE; PS50234; VWFA; 2. DR Genevisible; O43405; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Deafness; Disease variant; KW Disulfide bond; Extracellular matrix; Glycoprotein; Hearing; KW Non-syndromic deafness; Reference proteome; Repeat; Secreted; Signal. FT SIGNAL 1..24 FT /evidence="ECO:0000255" FT CHAIN 25..550 FT /note="Cochlin" FT /id="PRO_0000020968" FT DOMAIN 28..121 FT /note="LCCL" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00123" FT DOMAIN 165..346 FT /note="VWFA 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219" FT DOMAIN 367..537 FT /note="VWFA 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00219" FT REGION 128..159 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 100 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 221 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 34..50 FT DISULFID 54..74 FT VAR_SEQ 493..550 FT /note="GITIFSVGVAWAPLDDLKDMASKPKESHAFFTREFTGLEPIVSDVIRGICRD FT FLESQQ -> AK (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_056538" FT VARIANT 38 FT /note="G -> D (in DFNA9)" FT /evidence="ECO:0000269|PubMed:25388789" FT /id="VAR_079876" FT VARIANT 51 FT /note="P -> S (in DFNA9; some families may manifest Meniere FT disease-like symptoms; does not affect protein deposition FT to the extracellular matrix; dbSNP:rs28938175)" FT /evidence="ECO:0000269|PubMed:10400989, FT ECO:0000269|PubMed:12928864, ECO:0000269|PubMed:9931344" FT /id="VAR_008532" FT VARIANT 66 FT /note="V -> G (in DFNA9; affects protein deposition to the FT extracellular matrix; dbSNP:rs121908927)" FT /evidence="ECO:0000269|PubMed:12928864, FT ECO:0000269|PubMed:9806553" FT /id="VAR_008533" FT VARIANT 87 FT /note="G -> V (in DFNA9)" FT /evidence="ECO:0000269|PubMed:23993205" FT /id="VAR_072249" FT VARIANT 87 FT /note="G -> W (in DFNA9)" FT /evidence="ECO:0000269|PubMed:16835921" FT /id="VAR_072250" FT VARIANT 88 FT /note="G -> E (in DFNA9; affects protein deposition to the FT extracellular matrix; dbSNP:rs121908928)" FT /evidence="ECO:0000269|PubMed:12928864, FT ECO:0000269|PubMed:9806553" FT /id="VAR_008534" FT VARIANT 98..550 FT /note="Missing (in DFNB110)" FT /evidence="ECO:0000269|PubMed:29449721" FT /id="VAR_081173" FT VARIANT 109 FT /note="I -> N (in DFNA9; affects protein deposition to the FT extracellular matrix; dbSNP:rs121908930)" FT /evidence="ECO:0000269|PubMed:11295836, FT ECO:0000269|PubMed:12928864" FT /id="VAR_008535" FT VARIANT 109 FT /note="I -> T (in DFNA9; dbSNP:rs121908930)" FT /evidence="ECO:0000269|PubMed:17561763" FT /id="VAR_072251" FT VARIANT 117 FT /note="W -> R (in DFNA9; does not affect protein deposition FT to the extracellular matrix; dbSNP:rs121908929)" FT /evidence="ECO:0000269|PubMed:12928864, FT ECO:0000269|PubMed:9806553" FT /id="VAR_008536" FT VARIANT 119 FT /note="A -> T (in DFNA9; dbSNP:rs121908931)" FT /evidence="ECO:0000269|PubMed:14512963" FT /id="VAR_017175" FT VARIANT 135 FT /note="G -> R (in dbSNP:rs28400035)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_022259" FT VARIANT 162 FT /note="C -> Y (in DFNA9)" FT /evidence="ECO:0000269|PubMed:22931125" FT /id="VAR_070034" FT VARIANT 281 FT /note="D -> N (in dbSNP:rs28362775)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_022260" FT VARIANT 352 FT /note="T -> S (in dbSNP:rs1045644)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_011925" FT VARIANT 402 FT /note="I -> V (in dbSNP:rs28362778)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_022261" FT VARIANT 512 FT /note="M -> T (in DFNA9; dbSNP:rs121908934)" FT /evidence="ECO:0000269|PubMed:18312449" FT /id="VAR_072252" FT VARIANT 518 FT /note="E -> G (in dbSNP:rs17097468)" FT /id="VAR_050896" FT VARIANT 527 FT /note="F -> C (in DFNA9; induces disulfide bond dimer FT formation; keeps dimer in the cell and reduces secretion; FT monomeric and/or homodimeric mutant forms do not prevent FT interaction with type II collagen)" FT /evidence="ECO:0000269|PubMed:22610276" FT /id="VAR_072253" FT VARIANT 532 FT /note="P -> S (in dbSNP:rs1801963)" FT /id="VAR_011926" FT VARIANT 542 FT /note="C -> Y (in DFNA9; dbSNP:rs121908932)" FT /evidence="ECO:0000269|PubMed:18312449" FT /id="VAR_072254" FT TURN 38..40 FT /evidence="ECO:0007829|PDB:1JBI" FT STRAND 43..50 FT /evidence="ECO:0007829|PDB:1JBI" FT STRAND 56..58 FT /evidence="ECO:0007829|PDB:1JBI" FT STRAND 61..68 FT /evidence="ECO:0007829|PDB:1JBI" FT HELIX 73..80 FT /evidence="ECO:0007829|PDB:1JBI" FT STRAND 88..95 FT /evidence="ECO:0007829|PDB:1JBI" FT STRAND 110..112 FT /evidence="ECO:0007829|PDB:1JBI" FT STRAND 120..124 FT /evidence="ECO:0007829|PDB:1JBI" SQ SEQUENCE 550 AA; 59483 MW; 74D7D51290098B30 CRC64; MSAAWIPALG LGVCLLLLPG PAGSEGAAPI AITCFTRGLD IRKEKADVLC PGGCPLEEFS VYGNIVYASV SSICGAAVHR GVISNSGGPV RVYSLPGREN YSSVDANGIQ SQMLSRWSAS FTVTKGKSST QEATGQAVST AHPPTGKRLK KTPEKKTGNK DCKADIAFLI DGSFNIGQRR FNLQKNFVGK VALMLGIGTE GPHVGLVQAS EHPKIEFYLK NFTSAKDVLF AIKEVGFRGG NSNTGKALKH TAQKFFTVDA GVRKGIPKVV VVFIDGWPSD DIEEAGIVAR EFGVNVFIVS VAKPIPEELG MVQDVTFVDK AVCRNNGFFS YHMPNWFGTT KYVKPLVQKL CTHEQMMCSK TCYNSVNIAF LIDGSSSVGD SNFRLMLEFV SNIAKTFEIS DIGAKIAAVQ FTYDQRTEFS FTDYSTKENV LAVIRNIRYM SGGTATGDAI SFTVRNVFGP IRESPNKNFL VIVTDGQSYD DVQGPAAAAH DAGITIFSVG VAWAPLDDLK DMASKPKESH AFFTREFTGL EPIVSDVIRG ICRDFLESQQ //