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 13-FEB-2019, entry version 187. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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; RP SER-352 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., RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., RA 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., RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., RA Quetier F., 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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 RT processing of normal cochlin, and of mutants causing the sensorineural RT deafness and 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., RA Arts H.A., El-Kashlan H.K., Carey T.E.; RT "Cochlin isoforms and their interaction with CTL2 (SLC44A2) in the RT inner 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 RT in 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., RA Patthy L., 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., RA McKenna M., Nadol J.B. Jr., Miyamoto R.T., Linthicum F.H. Jr., RA Neto J.F.L., 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., RA van Beusekom E., van der Velde-Visser S.D., Robertson N.G., RA Morton C.C., Huygen P.L.M., Verhagen W.I.M., Brunner H.G., RA 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 RT vestibular 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 RT with a 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 RT similar clinical features observed in DFNA9 families."; RL Hum. Mutat. 17:351-351(2001). RN [16] RP ERRATUM. 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., RA Fransen E., 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 RT 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., RA Sztul E.; RT "Mutations in COCH that result in non-syndromic autosomal dominant RT deafness (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 RT dominant 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., RA Qin W., Angeli S., Ouyang X.M., Yang S.Z., Feng L., Cao J.Y., RA Feng G.Y., Wang Y.F., 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., RA Robertson N.G., Baek J.I., Kang B.S., Morton C.C., Vriend G., RA 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 RT DFNA9 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 RT identify 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., RA 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 CC in the trabecular meshwork. {ECO:0000269|PubMed:21886777}. CC -!- SUBUNIT: Monomer (PubMed:22610276). May form homodimer CC (PubMed:22610276). Interacts with type II collagen CC (PubMed:22610276). Interacts with SLC44A2 (PubMed:17926100). CC Interacts with ANXA2 (PubMed:21886777). CC {ECO:0000269|PubMed:17926100, ECO:0000269|PubMed:21886777, CC ECO:0000269|PubMed:22610276}. 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 Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed in inner ear structures; the cochlea CC and 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 CC form of non-syndromic hearing loss characterized by onset in the CC fourth or fifth decade of life and initially involves the high CC frequencies. Hearing loss is progressive and usually complete by CC the sixth decade. In addition to cochlear involvement, DFNA9 CC patients also exhibit a spectrum of vestibular dysfunctions. CC Penetrance of the vestibular symptoms is often incomplete, and CC some patients are minimally affected, whereas others suffer from CC severe balance disturbances and episodes of vertigo. Affected CC individuals have mucopolysaccharide depositions in the channels of CC the cochlear and vestibular nerves. These depositions apparently CC 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 CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Deafness, autosomal recessive, 110 (DFNB110) CC [MIM:618094]: A form of non-syndromic, sensorineural deafness CC characterized by prelingual hearing loss. Sensorineural deafness CC results from damage to the neural receptors of the inner ear, the CC nerve pathways to the brain, or the area of the brain that CC receives sound information. DFNB110 affected individuals CC additionally exhibit mild, age-dependent vestibular dysfunction. CC {ECO:0000269|PubMed:29449721}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The Japanese Horseshoe CC Crab 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 CC 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 UniGene; Hs.21016; -. DR PDB; 1JBI; NMR; -; A=28-124. DR PDBsum; 1JBI; -. DR ProteinModelPortal; O43405; -. DR SMR; O43405; -. DR BioGrid; 108051; 17. DR IntAct; O43405; 4. DR MINT; O43405; -. DR STRING; 9606.ENSP00000216361; -. DR TCDB; 8.A.54.1.3; the integrin (integrin) family. DR iPTMnet; O43405; -. DR PhosphoSitePlus; O43405; -. DR BioMuta; COCH; -. DR EPD; O43405; -. DR jPOST; O43405; -. DR MaxQB; O43405; -. DR PaxDb; O43405; -. DR PeptideAtlas; O43405; -. DR PRIDE; O43405; -. DR ProteomicsDB; 48929; -. DR Ensembl; ENST00000396618; ENSP00000379862; ENSG00000100473. [O43405-1] DR Ensembl; ENST00000475087; ENSP00000451528; ENSG00000100473. [O43405-2] DR Ensembl; ENST00000643575; ENSP00000494838; ENSG00000100473. [O43405-1] DR Ensembl; ENST00000644874; ENSP00000496360; ENSG00000100473. [O43405-1] DR GeneID; 1690; -. DR KEGG; hsa:1690; -. DR UCSC; uc001wqp.3; human. [O43405-1] DR CTD; 1690; -. DR DisGeNET; 1690; -. DR EuPathDB; HostDB:ENSG00000100473.15; -. DR GeneCards; COCH; -. DR GeneReviews; COCH; -. DR H-InvDB; HIX0023242; -. DR HGNC; HGNC:2180; COCH. DR HPA; HPA065086; -. 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; Autosomal dominant non-syndromic sensorineural deafness type DFNA. DR PharmGKB; PA26693; -. DR eggNOG; ENOG410IR8D; Eukaryota. DR eggNOG; ENOG410XRIU; LUCA. DR GeneTree; ENSGT00940000159386; -. DR HOGENOM; HOG000013195; -. DR HOVERGEN; HBG005372; -. DR InParanoid; O43405; -. DR OMA; AQKFFTA; -. DR OrthoDB; 200139at2759; -. DR PhylomeDB; O43405; -. DR TreeFam; TF318242; -. DR ChiTaRS; COCH; human. DR EvolutionaryTrace; O43405; -. DR GeneWiki; COCH; -. DR GenomeRNAi; 1690; -. DR PRO; PR:O43405; -. DR Proteomes; UP000005640; Chromosome 14. DR Bgee; ENSG00000100473; Expressed in 220 organ(s), highest expression level in caudate nucleus. DR ExpressionAtlas; O43405; baseline and differential. DR Genevisible; O43405; HS. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB. DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005518; F:collagen binding; IDA:UniProtKB. DR GO; GO:0042742; P:defense response to bacterium; IEA:InterPro. DR GO; GO:0003429; P:growth plate cartilage chondrocyte morphogenesis; IBA:GO_Central. DR GO; GO:0045089; P:positive regulation of innate immune response; IEA:InterPro. DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB. DR GO; GO:0007605; P:sensory perception of sound; TAS:ProtInc. DR Gene3D; 2.170.130.20; -; 1. DR Gene3D; 3.40.50.410; -; 2. DR InterPro; IPR030743; Cochlin. DR InterPro; IPR004043; LCCL. DR InterPro; IPR036609; LCCL_sf. DR InterPro; IPR002035; VWF_A. DR InterPro; IPR036465; vWFA_dom_sf. DR PANTHER; PTHR44729; PTHR44729; 1. DR Pfam; PF03815; LCCL; 1. DR Pfam; PF00092; VWA; 2. DR SMART; SM00603; LCCL; 1. DR SMART; SM00327; VWA; 2. DR SUPFAM; SSF53300; SSF53300; 2. DR SUPFAM; SSF69848; SSF69848; 1. DR PROSITE; PS50820; LCCL; 1. DR PROSITE; PS50234; VWFA; 2. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; Deafness; KW Disease mutation; Disulfide bond; Extracellular matrix; Glycoprotein; KW Hearing; Non-syndromic deafness; Polymorphism; Reference proteome; KW Repeat; Secreted; Signal. FT SIGNAL 1 24 {ECO:0000255}. FT CHAIN 25 550 Cochlin. FT /FTId=PRO_0000020968. FT DOMAIN 28 121 LCCL. {ECO:0000255|PROSITE- FT ProRule:PRU00123}. FT DOMAIN 165 346 VWFA 1. {ECO:0000255|PROSITE- FT ProRule:PRU00219}. FT DOMAIN 367 537 VWFA 2. {ECO:0000255|PROSITE- FT ProRule:PRU00219}. FT CARBOHYD 100 100 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 221 221 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 34 50 FT DISULFID 54 74 FT VAR_SEQ 493 550 GITIFSVGVAWAPLDDLKDMASKPKESHAFFTREFTGLEPI FT VSDVIRGICRDFLESQQ -> AK (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_056538. FT VARIANT 38 38 G -> D (in DFNA9). FT {ECO:0000269|PubMed:25388789}. FT /FTId=VAR_079876. FT VARIANT 51 51 P -> S (in DFNA9; some families may FT manifest Meniere disease-like symptoms; FT does not affect protein deposition to the FT extracellular matrix; dbSNP:rs28938175). FT {ECO:0000269|PubMed:10400989, FT ECO:0000269|PubMed:12928864, FT ECO:0000269|PubMed:9931344}. FT /FTId=VAR_008532. FT VARIANT 66 66 V -> G (in DFNA9; affects protein FT deposition to the extracellular matrix; FT dbSNP:rs121908927). FT {ECO:0000269|PubMed:12928864, FT ECO:0000269|PubMed:9806553}. FT /FTId=VAR_008533. FT VARIANT 87 87 G -> V (in DFNA9). FT {ECO:0000269|PubMed:23993205}. FT /FTId=VAR_072249. FT VARIANT 87 87 G -> W (in DFNA9). FT {ECO:0000269|PubMed:16835921}. FT /FTId=VAR_072250. FT VARIANT 88 88 G -> E (in DFNA9; affects protein FT deposition to the extracellular matrix; FT dbSNP:rs121908928). FT {ECO:0000269|PubMed:12928864, FT ECO:0000269|PubMed:9806553}. FT /FTId=VAR_008534. FT VARIANT 98 550 Missing (in DFNB110). FT {ECO:0000269|PubMed:29449721}. FT /FTId=VAR_081173. FT VARIANT 109 109 I -> N (in DFNA9; affects protein FT deposition to the extracellular matrix; FT dbSNP:rs121908930). FT {ECO:0000269|PubMed:11295836, FT ECO:0000269|PubMed:12928864}. FT /FTId=VAR_008535. FT VARIANT 109 109 I -> T (in DFNA9; dbSNP:rs121908930). FT {ECO:0000269|PubMed:17561763}. FT /FTId=VAR_072251. FT VARIANT 117 117 W -> R (in DFNA9; does not affect protein FT deposition to the extracellular matrix; FT dbSNP:rs121908929). FT {ECO:0000269|PubMed:12928864, FT ECO:0000269|PubMed:9806553}. FT /FTId=VAR_008536. FT VARIANT 119 119 A -> T (in DFNA9; dbSNP:rs121908931). FT {ECO:0000269|PubMed:14512963}. FT /FTId=VAR_017175. FT VARIANT 135 135 G -> R (in dbSNP:rs28400035). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_022259. FT VARIANT 162 162 C -> Y (in DFNA9). FT {ECO:0000269|PubMed:22931125}. FT /FTId=VAR_070034. FT VARIANT 281 281 D -> N (in dbSNP:rs28362775). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_022260. FT VARIANT 352 352 T -> S (in dbSNP:rs1045644). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_011925. FT VARIANT 402 402 I -> V (in dbSNP:rs28362778). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_022261. FT VARIANT 512 512 M -> T (in DFNA9; dbSNP:rs121908934). FT {ECO:0000269|PubMed:18312449}. FT /FTId=VAR_072252. FT VARIANT 518 518 E -> G (in dbSNP:rs17097468). FT /FTId=VAR_050896. FT VARIANT 527 527 F -> C (in DFNA9; induces disulfide bond FT dimer formation; keeps dimer in the cell FT and reduces secretion; monomeric and/or FT homodimeric mutant forms do not prevent FT interaction with type II collagen). FT {ECO:0000269|PubMed:22610276}. FT /FTId=VAR_072253. FT VARIANT 532 532 P -> S (in dbSNP:rs1801963). FT /FTId=VAR_011926. FT VARIANT 542 542 C -> Y (in DFNA9; dbSNP:rs121908932). FT {ECO:0000269|PubMed:18312449}. FT /FTId=VAR_072254. FT TURN 38 40 {ECO:0000244|PDB:1JBI}. FT STRAND 43 50 {ECO:0000244|PDB:1JBI}. FT STRAND 56 58 {ECO:0000244|PDB:1JBI}. FT STRAND 61 68 {ECO:0000244|PDB:1JBI}. FT HELIX 73 80 {ECO:0000244|PDB:1JBI}. FT STRAND 88 95 {ECO:0000244|PDB:1JBI}. FT STRAND 110 112 {ECO:0000244|PDB:1JBI}. FT STRAND 120 124 {ECO:0000244|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 //