Reviewed, UniProtKB/Swiss-Prot O95452 (CXB6_HUMAN)

Names and origin

Protein names

Recommended name:
    Gap junction beta-6 protein
Alternative name(s):
    Connexin-30
      Short name=Cx30

Gene names

Name:

GJB6

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	261 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
Subunit structure	A connexon is composed of a hexamer of connexins.
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › gap junction.
Involvement in disease	Defects in GJB6 are the cause of ectodermal dysplasia type 2 (ED2) [MIM:129500]; also known as Clouston syndrome. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. ED2 is an autosomal dominant condition characterized by atrichosis, nail hypoplasia and deformities, hyperpigmentation of the skin, normal teeth, normal sweat and sebaceous gland function. Palmoplantar hyperkeratosis is a frequent features. Hearing impairment has been detected in few cases of ED2. Ref.11 Ref.12 Defects in GJB6 are a cause of non-syndromic sensorineural deafness autosomal recessive type 1 (DFNB1) [MIM:220290]. DFNB1 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. Ref.1 Defects in GJB6 are the cause of non-syndromic sensorineural deafness autosomal dominant type 3B (DFNA3B) [MIM:612643]. Defects in GJB6 are a cause of a syndrome resembling Vohwinkel syndrome and Bart-Pumphrey syndrome (VSBPSL). Clinical features include palmoplantar keratoderma with pseudoainhum, knuckle pads and hearing loss.
Sequence similarities	Belongs to the connexin family. Beta-type (group I) subfamily.

Ontologies

Keywords
Biological process	Hearing
Cellular component	Cell junction Cell membrane Gap junction Membrane
Coding sequence diversity	Polymorphism
Disease	Deafness Disease mutation Ectodermal dysplasia Non-syndromic deafness Palmoplantar keratoderma
Domain	Transmembrane
Gene Ontology (GO)
Biological process	cell communication Inferred from electronic annotation. Source: InterPro sensory perception of sound Ref.2 Traceable author statement. Source: ProtInc
Cellular component	connexon complex Inferred from electronic annotation. Source: InterPro integral to membrane 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
	Chain	1 – 261	261	Gap junction beta-6 protein		PRO_0000057871
Regions
	Topological domain	1 – 22	22	Cytoplasmic Potential
	Transmembrane	23 – 45	23	Potential
	Topological domain	46 – 75	30	Extracellular Potential
	Transmembrane	76 – 98	23	Potential
	Topological domain	99 – 131	33	Cytoplasmic Potential
	Transmembrane	132 – 154	23	Potential
	Topological domain	155 – 192	38	Extracellular Potential
	Transmembrane	193 – 215	23	Potential
	Topological domain	216 – 261	46	Cytoplasmic Potential
Natural variations
	Natural variant	5	1	T → M in DFNA3B.		VAR_008711
	Natural variant	11	1	G → R in ED2. Ref.11		VAR_015696
	Natural variant	37	1	V → E in ED2. Ref.12		VAR_016838
	Natural variant	59	1	G → R in VSBPSL.		VAR_057960
	Natural variant	88	1	A → V in ED2. Ref.11		VAR_015697
	Natural variant	139	1	S → G Ref.2		VAR_022424
	Natural variant	159	1	N → S: dbSNP rs35277762.		VAR_048825
	Natural variant	199	1	S → T Ref.2		VAR_022425
Experimental info
	Sequence conflict	11	1	G → E in AAV67951. Ref.9
	Sequence conflict	124	1	Q → H in CAA06611. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O95452-1 [UniParc]. Last modified September 19, 2003. Version 2. Checksum: 394A2D97E08EEB43	FASTA	261	30,387
	10 20 30 40 50 60 MDWGTLHTFI GGVNKHSTSI GKVWITVIFI FRVMILVVAA QEVWGDEQED FVCNTLQPGC 70 80 90 100 110 120 KNVCYDHFFP VSHIRLWALQ LIFVSTPALL VAMHVAYYRH ETTRKFRRGE KRNDFKDIED 130 140 150 160 170 180 IKKQKVRIEG SLWWTYTSSI FFRIIFEAAF MYVFYFLYNG YHLPWVLKCG IDPCPNLVDC 190 200 210 220 230 240 FISRPTEKTV FTIFMISASV ICMLLNVAEL CYLLLKVCFR RSKRAQTQKN HPNHALKESK 250 260 QNEMNELISD SGQNAITGFP S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus." Grifa A., Wagner C.A., D'Ambrosio L., Melchionda S., Bernardi F., Lopez-Bigas N., Rabionet R., Arbones M., Monica M.D., Estivill X., Zelante L., Lang F., Gasparini P. Nat. Genet. 23:16-18(1999) [PubMed: 10471490] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT DFNA3B MET-5.
[2]	"Human connexin 30 (GJB6), a candidate gene for nonsyndromic hearing loss: molecular cloning, tissue-specific expression, and assignment to chromosome 13q12." Kelley P.M., Abe S., Askew J.W., Smith S.D., Usami S., Kimberling W.J. Genomics 62:172-176(1999) [PubMed: 10610709] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-139 AND THR-199.
[3]	"Human connexin30, updated ORF." Enriquez A.D., Scherer S.S. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Corpus callosum.
[4]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain cortex.
[5]	"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries." Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T. DNA Res. 12:117-126(2005) [PubMed: 16303743] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Thyroid.
[6]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed: 15057823] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[9]	"Gene structure and promoter analysis of the human GJB6 gene encoding connexin 30." Essenfelder G.M., Larderet G., Waksman G., Lamartine J. Gene 350:33-40(2005) [PubMed: 15792634] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-40, GENE STRUCTURE. Tissue: Hair follicle.
[10]	"A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment." del Castillo F.J., Rodriguez-Ballesteros M., Alvarez A., Hutchin T., Leonardi E., de Oliveira C.A., Azaiez H., Brownstein Z., Avenarius M.R., Marlin S., Pandya A., Shahin H., Siemering K.R., Weil D., Wuyts W., Aguirre L.A., Martin Y., Moreno-Pelayo M.A. , Villamar M., Avraham K.B., Dahl H.H., Kanaan M., Nance W.E., Petit C., Smith R.J., Van Camp G., Sartorato E.L., Murgia A., Moreno F., del Castillo I. J. Med. Genet. 42:588-594(2005) [PubMed: 15994881] [Abstract] Cited for: INVOLVEMENT IN DFNB1.
[11]	"Mutations in GJB6 cause hidrotic ectodermal dysplasia." Lamartine J., Munhoz Essenfelder G., Kibar Z., Lanneluc I., Callouet E., Laoudj D., Lemaitre G., Hand C., Hayflick S.J., Zonana J., Antonarakis S., Radhakrishna U., Kelsell D.P., Christianson A.L., Pitaval A., Der Kaloustian V., Fraser C., Blanchet-Bardon C., Rouleau G.A., Waksman G. Nat. Genet. 26:142-144(2000) [PubMed: 11017065] [Abstract] Cited for: VARIANTS ED2 ARG-11 AND VAL-88.
[12]	"A novel connexin 30 mutation in Clouston syndrome." Smith F.J., Morley S.M., McLean W.H.I. J. Invest. Dermatol. 118:530-532(2002) [PubMed: 11874494] [Abstract] Cited for: VARIANT ED2 GLU-37.
[13]	"Novel mutation p.Gly59Arg in GJB6 encoding connexin 30 underlies palmoplantar keratoderma with pseudoainhum, knuckle pads and hearing loss." Nemoto-Hasebe I., Akiyama M., Kudo S., Ishiko A., Tanaka A., Arita K., Shimizu H. Br. J. Dermatol. 0:0-0(2009) [PubMed: 19416251] [Abstract] Cited for: VARIANT VSBPSL ARG-59.
+	Additional computationally mapped references.

Web resources

Connexin-deafness homepage

Hereditary hearing loss homepage

Gene page

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	AJ005585 Genomic DNA. Translation: CAA06611.1. AY297110 mRNA. Translation: AAP51162.1. AK289592 mRNA. Translation: BAF82281.1. AK075247 mRNA. Translation: BAG52094.1. AL355984 Genomic DNA. Translation: CAI14832.1. CH471075 Genomic DNA. Translation: EAX08254.1. BC038934 mRNA. Translation: AAH38934.1. AY789474 mRNA. Translation: AAV67951.1. AY789475 mRNA. Translation: AAV67952.1. AY789476 mRNA. Translation: AAV67953.1.
IPI	IPI00030763.
RefSeq	NP_001103689.1. NP_001103690.1. NP_001103691.1. NP_006774.2.
UniGene	Hs.511757
3D structure databases
ModBase	Search...
Proteomic databases
PRIDE	O95452.
Genome annotation databases
Ensembl	ENSG00000121742. Homo sapiens. [Contig view]
GeneID	10804.
KEGG	hsa:10804.
Organism-specific databases
GeneCards	GC13M019694.
H-InvDB	HIX0026551.
HGNC	HGNC:4288. GJB6.
HPA	HPA014846.
MIM	129500. phenotype. 220290. phenotype. 604418. gene. 612643. phenotype.
Orphanet	189. Clouston syndrome. 477. KID/HID syndrome. 87884. Nonsyndromic genetic deafness.
PharmGKB	PA28699.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O95452.
HOVERGEN	O95452.
OMA	O95452. IFEASFM.
Enzyme and pathway databases
Reactome	REACT_9480. Gap junction trafficking and regulation.
Gene expression databases
ArrayExpress	O95452.
Bgee	O95452.
CleanEx	HS_GJB6.
GermOnline	ENSG00000121742. Homo sapiens.
Family and domain databases
InterPro	IPR000500. Connexin. IPR019570. Connexin_CCC. IPR017990. Connexin_CS. IPR013092. Connexin_N. IPR017991. connexins_rgn. [Graphical view]
PANTHER	PTHR11984. Connexin. 1 hit.
Pfam	PF00029. Connexin. 1 hit. PF10582. Connexin_CCC. 1 hit. [Graphical view]
PRINTS	PR00206. CONNEXIN.
SMART	SM00037. CNX. 1 hit. [Graphical view]
PROSITE	PS00407. CONNEXINS_1. 1 hit. PS00408. CONNEXINS_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	41041.
SOURCE	Search...

Entry information

Entry name

CXB6_HUMAN

Accession

Primary (citable) accession number: O95452
Secondary accession number(s): B3KQN2 , Q5Q1H9, Q5Q1I0, Q5Q1I1, Q5T5U0, Q8IUP0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	September 19, 2003
Last modified:	June 16, 2009
This is version 77 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)