Reviewed, UniProtKB/Swiss-Prot O43405 (COCH_HUMAN)

Names and origin

Protein names

Recommended name:
    Cochlin
Alternative name(s):
    COCH-5B2

Gene names

Name:	COCH
Synonyms:	COCH5B2
ORF Names:	UNQ257/PRO294

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	550 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Subcellular location	Secreted › extracellular space › extracellular matrix.
Tissue specificity	Expressed in inner ear structures; the cochlea and the vestibule.
Post-translational modification	N-glycosylated. A 50 kDa form is created by proteolytic cleavage.
Involvement in disease	Defects in COCH are the cause of non-syndromic sensorineural deafness autosomal dominant type 9 (DFNA9) [MIM:601369]. DFNA9 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA9 is characterized by onset in the fourth or fifth decade of life and initially involves the high frequencies. Deafness 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. Defects in COCH may contribute to Meniere disease [MIM:156000]. Meniere disease is an autosomal dominant disorder characterized by hearing loss associated with episodic vertigo. Antibodies against COCH are found in 10% of Meniere patients.
Sequence similarities	Contains 1 LCCL domain. Contains 2 VWFA domains.

Ontologies

Keywords
Biological process	Hearing
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Disease	Deafness Disease mutation Non-syndromic deafness
Domain	Repeat Signal
PTM	Glycoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	sensory perception of sound Ref.6 Traceable author statement. Source: ProtInc
Cellular component	proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Potential

Chain

25 – 550

526

Cochlin

PRO_0000020968

Regions

Domain

28 – 121

94

LCCL

Domain

165 – 346

182

VWFA 1

Domain

367 – 537

171

VWFA 2

Amino acid modifications

Glycosylation

100

1

N-linked (GlcNAc...) Potential

Glycosylation

221

1

N-linked (GlcNAc...) Potential

Disulfide bond

34 ↔ 50

Disulfide bond

54 ↔ 74

Natural variations

Natural variant

51

1

P → S in DFNA9; Meniere disease; does not affect protein deposition to the extracellular matrix.

VAR_008532

Natural variant

66

1

V → G in DFNA9; affects protein deposition to the extracellular matrix.

VAR_008533

Natural variant

88

1

G → E in DFNA9; affects protein deposition to the extracellular matrix.

VAR_008534

Natural variant

109

1

I → N in DFNA9; affects protein deposition to the extracellular matrix.

VAR_008535

Natural variant

117

1

W → R in DFNA9; does not affect protein deposition to the extracellular matrix.

VAR_008536

Natural variant

119

1

A → T in DFNA9.

VAR_017175

Natural variant

135

1

G → R: dbSNP rs28400035.

VAR_022259

Natural variant

281

1

D → N: dbSNP rs28362775.

VAR_022260

Natural variant

352

1

T → S: dbSNP rs1045644.

VAR_011925

Natural variant

402

1

I → V: dbSNP rs28362778.

VAR_022261

Natural variant

532

1

P → S: dbSNP rs1801963.

VAR_011926

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

550

Helix Strand Turn

Details...

Turn

38 – 40

3

Beta strand

43 – 50

8

Beta strand

56 – 58

3

Beta strand

61 – 68

8

Helix

73 – 80

8

Beta strand

88 – 95

8

Beta strand

110 – 112

3

Sequences

	Sequence		Length	Mass (Da)
	O43405-1 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 74D7D51290098B30	FASTA	550	59,483
	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

References

	« Hide 'large scale' referencesShow '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: 9441737] [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. , 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: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	SeattleSNPs program for genomic applications 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.
[4]	"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: 12843317] [Abstract] Cited for: GLYCOSYLATION, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING.
[5]	"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: 11574466] [Abstract] Cited for: STRUCTURE BY NMR OF 27-126.
[6]	"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: 9806553] [Abstract] Cited for: VARIANTS DFNA9 GLY-66; GLU-88 AND ARG-117.
[7]	"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: 9931344] [Abstract] Cited for: VARIANT DFNA9 SER-51.
[8]	"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: 10400989] [Abstract] Cited for: VARIANT DFNA9 SER-51.
[9]	"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: 11295836] [Abstract] Cited for: VARIANT DFNA9 ASN-109.
[10]	Erratum Kamarinos M., McGill J., Lynch M., Dahl H.-H.M. Hum. Mutat. 18:547-548(2001)
[11]	"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: 14512963] [Abstract] Cited for: VARIANT DFNA9 THR-119.
[12]	"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: 12928864] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS DFNA9 SER-51; GLY-66; GLU-88; ASN-109 AND ARG-117.
[13]	"COCH5B2 is a target antigen of anti-inner ear antibodies in autoimmune inner ear diseases." Boulassel M.-R., Tomasi J.-P., Deggouj N., Gersdorff M. Otol. Neurotol. 22:614-618(2001) [PubMed: 11568667] [Abstract] Cited for: DISEASE.
+	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

GeneReviews

SeattleSNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF006740 mRNA. Translation: AAC39545.1.
AY358900 mRNA. Translation: AAQ89259.1.
AY916789 Genomic DNA. Translation: AAW82432.1.

RefSeq

NP_001128530.1.
NP_004077.1.

UniGene

Hs.21016

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JBI	NMR	-	A	28-124	[»]

ModBase

Search...

Genome annotation databases

Ensembl

ENSG00000100473. Homo sapiens. [Contig view]

GeneID

1690.

KEGG

hsa:1690.

Organism-specific databases

H-InvDB

HIX0022288.

HGNC

HGNC:2180. COCH.

MIM

156000. phenotype.
601369. phenotype.
603196. gene.

Orphanet

87884. Deafness, genetic, nonsyndromic.
45360. Meniere's disease.

PharmGKB

PA26693.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

O43405.

HOVERGEN

O43405.

Gene expression databases

ArrayExpress

O43405.

CleanEx

HS_COCH.

GermOnline

ENSG00000100473. Homo sapiens.

Family and domain databases

InterPro

IPR004043. LCCL.
IPR002035. VWF_A.
[Graphical view]

Gene3D

G3DSA:2.170.130.20. LCCL. 1 hit.

Pfam

PF03815. LCCL. 1 hit.
PF00092. VWA. 2 hits.
[Graphical view]

PRINTS

PR00453. VWFADOMAIN.

SMART

SM00603. LCCL. 1 hit.
SM00327. VWA. 2 hits.
[Graphical view]

PROSITE

PS50820. LCCL. 1 hit.
PS50234. VWFA. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

LinkHub

O43405.

NextBio

6926.

SOURCE

Search...

Entry information

Entry name

COCH_HUMAN

Accession

Primary (citable) accession number: O43405

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	June 1, 1998
Last modified:	November 25, 2008
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)