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O43405 (COCH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cochlin
Alternative name(s):
COCH-5B2
Gene names
Name:COCH
Synonyms:COCH5B2
ORF Names:UNQ257/PRO294
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length550 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a role in the control of cell shape and motility in the trabecular meshwork. Ref.8

Subunit structure

Interacts with SLC44A2. Interacts with ANXA2. Ref.7 Ref.8

Subcellular location

Secretedextracellular spaceextracellular matrix Ref.6.

Tissue specificity

Expressed in inner ear structures; the cochlea and the vestibule.

Post-translational modification

N-glycosylated. Ref.6

A 50 kDa form is created by proteolytic cleavage.

Involvement in disease

Deafness, autosomal dominant, 9 (DFNA9) [MIM:601369]: A form of non-syndromic hearing loss characterized by onset in the fourth or fifth decade of life and initially involves the high frequencies. Hearing loss is progressive and usually complete by the sixth decade. In addition to cochlear involvement, DFNA9 patients also exhibit a spectrum of vestibular dysfunctions. Penetrance of the vestibular symptoms is often incomplete, and some patients are minimally affected, whereas others suffer from severe balance disturbances and episodes of vertigo. Affected individuals have mucopolysaccharide depositions in the channels of the cochlear and vestibular nerves. These depositions apparently cause strangulation and degeneration of dendritic fibers.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17

Sequence similarities

Contains 1 LCCL domain.

Contains 2 VWFA domains.

Ontologies

Keywords
   Biological processHearing
   Cellular componentExtracellular matrix
Secreted
   Coding sequence diversityPolymorphism
   DiseaseDeafness
Disease mutation
Non-syndromic deafness
   DomainRepeat
Signal
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processregulation of cell shape

Inferred from mutant phenotype Ref.8. Source: UniProtKB

sensory perception of sound

Traceable author statement Ref.10. Source: ProtInc

   Cellular_componentproteinaceous extracellular matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionprotein binding

Inferred from physical interaction Ref.8. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Chain25 – 550526Cochlin
PRO_0000020968

Regions

Domain28 – 12194LCCL
Domain165 – 346182VWFA 1
Domain367 – 537171VWFA 2

Amino acid modifications

Glycosylation1001N-linked (GlcNAc...) Potential
Glycosylation2211N-linked (GlcNAc...) Potential
Disulfide bond34 ↔ 50
Disulfide bond54 ↔ 74

Natural variations

Natural variant511P → S in DFNA9; some families may manifest Meniere disease-like symptoms; does not affect protein deposition to the extracellular matrix. Ref.11 Ref.12 Ref.16
Corresponds to variant rs28938175 [ dbSNP | Ensembl ].
VAR_008532
Natural variant661V → G in DFNA9; affects protein deposition to the extracellular matrix. Ref.10 Ref.16
VAR_008533
Natural variant881G → E in DFNA9; affects protein deposition to the extracellular matrix. Ref.10 Ref.16
VAR_008534
Natural variant1091I → N in DFNA9; affects protein deposition to the extracellular matrix. Ref.13 Ref.16
VAR_008535
Natural variant1171W → R in DFNA9; does not affect protein deposition to the extracellular matrix. Ref.10 Ref.16
VAR_008536
Natural variant1191A → T in DFNA9. Ref.15
VAR_017175
Natural variant1351G → R. Ref.4
Corresponds to variant rs28400035 [ dbSNP | Ensembl ].
VAR_022259
Natural variant1621C → Y in DFNA9. Ref.17
VAR_070034
Natural variant2811D → N. Ref.4
Corresponds to variant rs28362775 [ dbSNP | Ensembl ].
VAR_022260
Natural variant3521T → S. Ref.4
Corresponds to variant rs1045644 [ dbSNP | Ensembl ].
VAR_011925
Natural variant4021I → V. Ref.4
Corresponds to variant rs28362778 [ dbSNP | Ensembl ].
VAR_022261
Natural variant5181E → G.
Corresponds to variant rs17097468 [ dbSNP | Ensembl ].
VAR_050896
Natural variant5321P → S.
Corresponds to variant rs1801963 [ dbSNP | Ensembl ].
VAR_011926

Secondary structure

................. 550
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O43405 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: 74D7D51290098B30

FASTA55059,483
        10         20         30         40         50         60 
MSAAWIPALG LGVCLLLLPG PAGSEGAAPI AITCFTRGLD IRKEKADVLC PGGCPLEEFS 

        70         80         90        100        110        120 
VYGNIVYASV SSICGAAVHR GVISNSGGPV RVYSLPGREN YSSVDANGIQ SQMLSRWSAS 

       130        140        150        160        170        180 
FTVTKGKSST QEATGQAVST AHPPTGKRLK KTPEKKTGNK DCKADIAFLI DGSFNIGQRR 

       190        200        210        220        230        240 
FNLQKNFVGK VALMLGIGTE GPHVGLVQAS EHPKIEFYLK NFTSAKDVLF AIKEVGFRGG 

       250        260        270        280        290        300 
NSNTGKALKH TAQKFFTVDA GVRKGIPKVV VVFIDGWPSD DIEEAGIVAR EFGVNVFIVS 

       310        320        330        340        350        360 
VAKPIPEELG MVQDVTFVDK AVCRNNGFFS YHMPNWFGTT KYVKPLVQKL CTHEQMMCSK 

       370        380        390        400        410        420 
TCYNSVNIAF LIDGSSSVGD SNFRLMLEFV SNIAKTFEIS DIGAKIAAVQ FTYDQRTEFS 

       430        440        450        460        470        480 
FTDYSTKENV LAVIRNIRYM SGGTATGDAI SFTVRNVFGP IRESPNKNFL VIVTDGQSYD 

       490        500        510        520        530        540 
DVQGPAAAAH DAGITIFSVG VAWAPLDDLK DMASKPKESH AFFTREFTGL EPIVSDVIRG 

       550 
ICRDFLESQQ 

« Hide

References

« Hide 'large scale' references
[1]"Mapping and characterization of a novel cochlear gene in human and in mouse: a positional candidate gene for a deafness disorder, DFNA9."
Robertson N.G., Skvorak A.B., Yin Y., Weremowicz S., Johnson K.R., Kovatch K.A., Battey J.F., Bieber F.R., Morton C.C.
Genomics 46:345-354(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Cochlea.
[2]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.
[4]SeattleSNPs variation discovery resource
Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-135; ASN-281; SER-352 AND VAL-402.
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"Subcellular localisation, secretion, and post-translational processing of normal cochlin, and of mutants causing the sensorineural deafness and vestibular disorder, DFNA9."
Robertson N.G., Hamaker S.A., Patriub V., Aster J.C., Morton C.C.
J. Med. Genet. 40:479-486(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING.
[7]"Cochlin isoforms and their interaction with CTL2 (SLC44A2) in the inner ear."
Kommareddi P.K., Nair T.S., Raphael Y., Telian S.A., Kim A.H., Arts H.A., El-Kashlan H.K., Carey T.E.
J. Assoc. Res. Otolaryngol. 8:435-446(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SLC44A2.
[8]"Cochlin induced TREK-1 co-expression and annexin A2 secretion: role in trabecular meshwork cell elongation and motility."
Goel M., Sienkiewicz A.E., Picciani R., Lee R.K., Bhattacharya S.K.
PLoS ONE 6:E23070-E23070(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ANXA2.
[9]"NMR structure of the LCCL domain and implications for DFNA9 deafness disorder."
Liepinsh E., Trexler M., Kaikkonen A., Weigelt J., Banyai L., Patthy L., Otting G.
EMBO J. 20:5347-5353(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 27-126.
[10]"Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction."
Robertson N.G., Lu L., Heller S., Merchant S.N., Eavey R.D., McKenna M., Nadol J.B. Jr., Miyamoto R.T., Linthicum F.H. Jr., Neto J.F.L., Hudspeth A.J., Seidman C.E., Morton C.C., Seidman J.G.
Nat. Genet. 20:299-303(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS DFNA9 GLY-66; GLU-88 AND ARG-117.
[11]"A Pro51Ser mutation in the COCH gene is associated with late onset autosomal dominant progressive sensorineural hearing loss with vestibular defects."
de Kok Y.J.M., Bom S.J.H., Brunt T.M., Kemperman M.H., van Beusekom E., van der Velde-Visser S.D., Robertson N.G., Morton C.C., Huygen P.L.M., Verhagen W.I.M., Brunner H.G., Cremers C.W.R.J., Cremers F.P.M.
Hum. Mol. Genet. 8:361-366(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DFNA9 SER-51.
[12]"High prevalence of symptoms of Meniere's disease in three families with a mutation in the COCH gene."
Fransen E., Verstreken M., Verhagen W.I.M., Wuyts F.L., Huygen P.L.M., D'Haese P., Robertson N.G., Morton C.C., McGuirt W.T., Smith R.J.H., Declau F., Van de Heyning P.H., Van Camp G.
Hum. Mol. Genet. 8:1425-1429(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DFNA9 SER-51.
[13]"Identification of a novel COCH mutation, I109N, highlights the similar clinical features observed in DFNA9 families."
Kamarinos M., McGill J., Lynch M., Dahl H.-H.M.
Hum. Mutat. 17:351-351(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DFNA9 ASN-109.
[14]Erratum
Kamarinos M., McGill J., Lynch M., Dahl H.-H.M.
Hum. Mutat. 18:547-548(2001)
[15]"Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere's disease."
Usami S., Takahashi K., Yuge I., Ohtsuka A., Namba A., Abe S., Fransen E., Patthy L., Otting G., Van Camp G.
Eur. J. Hum. Genet. 11:744-748(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DFNA9 THR-119.
[16]"Mutations in COCH that result in non-syndromic autosomal dominant deafness (DFNA9) affect matrix deposition of cochlin."
Grabski R., Szul T., Sasaki T., Timpl R., Mayne R., Hicks B., Sztul E.
Hum. Genet. 113:406-416(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS DFNA9 SER-51; GLY-66; GLU-88; ASN-109 AND ARG-117.
[17]"Whole exome sequencing identifies a novel DFNA9 mutation, C162Y."
Gao J., Xue J., Chen L., Ke X., Qi Y., Liu Y.
Clin. Genet. 83:477-481(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DFNA9 TYR-162.
+Additional computationally mapped references.

Web resources

Protein Spotlight

The Japanese Horseshoe Crab and Deafness - Issue 4 of November 2000

Hereditary hearing loss homepage

Gene page

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF006740 mRNA. Translation: AAC39545.1.
AY358900 mRNA. Translation: AAQ89259.1.
AK292724 mRNA. Translation: BAF85413.1.
AY916789 Genomic DNA. Translation: AAW82432.1.
CH471078 Genomic DNA. Translation: EAW65963.1.
CH471078 Genomic DNA. Translation: EAW65965.1.
CCDSCCDS9640.1.
RefSeqNP_001128530.1. NM_001135058.1.
NP_004077.1. NM_004086.2.
XP_006720136.1. XM_006720073.1.
UniGeneHs.21016.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1JBINMR-A28-124[»]
ProteinModelPortalO43405.
SMRO43405. Positions 28-124, 161-548.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108051. 1 interaction.
IntActO43405. 3 interactions.
STRING9606.ENSP00000216361.

PTM databases

PhosphoSiteO43405.

Proteomic databases

MaxQBO43405.
PaxDbO43405.
PRIDEO43405.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000216361; ENSP00000216361; ENSG00000100473.
ENST00000396618; ENSP00000379862; ENSG00000100473.
GeneID1690.
KEGGhsa:1690.
UCSCuc001wqp.2. human.

Organism-specific databases

CTD1690.
GeneCardsGC14P031343.
GeneReviewsCOCH.
H-InvDBHIX0023242.
HGNCHGNC:2180. COCH.
HPAHPA050122.
MIM601369. phenotype.
603196. gene.
neXtProtNX_O43405.
Orphanet90635. Autosomal dominant nonsyndromic sensorineural deafness type DFNA.
45360. Meniere disease.
PharmGKBPA26693.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG277584.
HOGENOMHOG000013195.
HOVERGENHBG005372.
InParanoidO43405.
OMAAQKFFTA.
OrthoDBEOG71RXJM.
PhylomeDBO43405.
TreeFamTF318242.

Gene expression databases

ArrayExpressO43405.
BgeeO43405.
CleanExHS_COCH.
GenevestigatorO43405.

Family and domain databases

Gene3D2.170.130.20. 1 hit.
3.40.50.410. 2 hits.
InterProIPR004043. LCCL.
IPR002035. VWF_A.
[Graphical view]
PfamPF03815. LCCL. 1 hit.
PF00092. VWA. 2 hits.
[Graphical view]
SMARTSM00603. LCCL. 1 hit.
SM00327. VWA. 2 hits.
[Graphical view]
SUPFAMSSF53300. SSF53300. 2 hits.
SSF69848. SSF69848. 1 hit.
PROSITEPS50820. LCCL. 1 hit.
PS50234. VWFA. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCOCH. human.
EvolutionaryTraceO43405.
GeneWikiCOCH.
GenomeRNAi1690.
NextBio6926.
PROO43405.
SOURCESearch...

Entry information

Entry nameCOCH_HUMAN
AccessionPrimary (citable) accession number: O43405
Secondary accession number(s): A8K9K9, D3DS84
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 1, 1998
Last modified: July 9, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM