COCH_HUMAN
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 03-AUG-2022, entry version 206.
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/";
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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; 40.
DR IntAct; O43405; 16.
DR MINT; O43405; -.
DR STRING; 9606.ENSP00000379862; -.
DR TCDB; 8.A.54.1.3; the integrin (integrin) family.
DR GlyGen; O43405; 2 sites, 1 N-linked glycan (1 site).
DR iPTMnet; O43405; -.
DR PhosphoSitePlus; O43405; -.
DR BioMuta; COCH; -.
DR EPD; O43405; -.
DR jPOST; O43405; -.
DR MassIVE; O43405; -.
DR MaxQB; O43405; -.
DR PaxDb; O43405; -.
DR PeptideAtlas; O43405; -.
DR PRIDE; O43405; -.
DR ProteomicsDB; 48929; -. [O43405-1]
DR ProteomicsDB; 76856; -.
DR Antibodypedia; 22996; 213 antibodies from 26 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 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; 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; CPANCPL; -.
DR OrthoDB; 200139at2759; -.
DR PhylomeDB; O43405; -.
DR TreeFam; TF318242; -.
DR PathwayCommons; O43405; -.
DR SignaLink; O43405; -.
DR BioGRID-ORCS; 1690; 21 hits in 1074 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 198 other tissues.
DR ExpressionAtlas; O43405; baseline and differential.
DR Genevisible; O43405; HS.
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:0042742; P:defense response to bacterium; IEA:InterPro.
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; PTHR24020:SF36; PTHR24020:SF36; 2.
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; 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
