O43405 (COCH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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)

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	Secreted › extracellular space › extracellular 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
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	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of cell shape Inferred from mutant phenotype Ref.8. Source: UniProtKB sensory perception of sound Traceable author statement Ref.10. Source: ProtInc
Cellular_component	proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
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; 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 variant

66

1

V → G in DFNA9; affects protein deposition to the extracellular matrix. Ref.10 Ref.16

VAR_008533

Natural variant

88

1

G → E in DFNA9; affects protein deposition to the extracellular matrix. Ref.10 Ref.16

VAR_008534

Natural variant

109

1

I → N in DFNA9; affects protein deposition to the extracellular matrix. Ref.13 Ref.16

VAR_008535

Natural variant

117

1

W → R in DFNA9; does not affect protein deposition to the extracellular matrix. Ref.10 Ref.16

VAR_008536

Natural variant

119

1

A → T in DFNA9. Ref.15

VAR_017175

Natural variant

135

1

G → R. Ref.4
Corresponds to variant rs28400035 [ dbSNP | Ensembl ].

VAR_022259

Natural variant

281

1

D → N. Ref.4
Corresponds to variant rs28362775 [ dbSNP | Ensembl ].

VAR_022260

Natural variant

352

1

T → S. Ref.4
Corresponds to variant rs1045644 [ dbSNP | Ensembl ].

VAR_011925

Natural variant

402

1

I → V. Ref.4
Corresponds to variant rs28362778 [ dbSNP | Ensembl ].

VAR_022261

Natural variant

518

1

E → G.
Corresponds to variant rs17097468 [ dbSNP | Ensembl ].

VAR_050896

Natural variant

532

1

P → S.
Corresponds to variant rs1801963 [ dbSNP | Ensembl ].

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

Beta strand

120 – 124

5

Sequences

	Sequence		Length	Mass (Da)
	O43405 [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] [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. , 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. , 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. , 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.
+	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

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.

IPI

IPI00012386.

RefSeq

NP_001128530.1. NM_001135058.1.
NP_004077.1. NM_004086.2.

UniGene

Hs.21016.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

O43405.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000216361.

PTM databases

PhosphoSite

O43405.

Proteomic databases

PaxDb

O43405.

PRIDE

O43405.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000216361; ENSP00000216361; ENSG00000100473.
ENST00000396618; ENSP00000379862; ENSG00000100473.

GeneID

1690.

KEGG

hsa:1690.

UCSC

uc001wqp.2. human.

Organism-specific databases

CTD

1690.

GeneCards

GC14P031343.

H-InvDB

HIX0023242.

HGNC

HGNC:2180. COCH.

HPA

HPA050122.

MIM

601369. phenotype.
603196. gene.

neXtProt

NX_O43405.

Orphanet

90635. Autosomal dominant nonsyndromic sensorineural deafness type DFNA.
45360. Meniere disease.

PharmGKB

PA26693.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG277584.

HOGENOM

HOG000013195.

HOVERGEN

HBG005372.

InParanoid

O43405.

OMA

AQKFFTA.

OrthoDB

EOG4TTGJ5.

PhylomeDB

O43405.

Gene expression databases

ArrayExpress

O43405.

Bgee

O43405.

CleanEx

HS_COCH.

Genevestigator

O43405.

GermOnline

ENSG00000100473. Homo sapiens.

Family and domain databases

Gene3D

2.170.130.20. 1 hit.
3.40.50.410. 2 hits.

InterPro

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

Pfam

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

SMART

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

SUPFAM

SSF69848. LCCL. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

ChiTaRS

COCH. human.

EvolutionaryTrace

O43405.

GenomeRNAi

1690.

NextBio

6926.

SOURCE

Search...

Entry information

Entry name

COCH_HUMAN

Accession

Primary (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:	May 29, 2013
This is version 133 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.