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O75712 (CXB3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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:
Gap junction beta-3 protein
Alternative name(s):
Connexin-31
Short name=Cx31
Gene names
Name:GJB3
Synonyms:CX31
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length270 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Interacts with CNST By similarity.

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junctiongap junction.

Involvement in disease

Erythrokeratodermia variabilis (EKV) [MIM:133200]: A genodermatosis characterized by the appearance of two independent skin lesions: transient figurate erythematous patches and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.3 Ref.9 Ref.11

Deafness, autosomal dominant, 2B (DFNA2B) [MIM:612644]: A form of non-syndromic sensorineural deafness characterized by progressive high frequency hearing loss in adulthood, with milder expression in females.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence similarities

Belongs to the connexin family. Beta-type (group I) subfamily.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 270270Gap junction beta-3 protein
PRO_0000057862

Regions

Topological domain1 – 2020Cytoplasmic Potential
Transmembrane21 – 4020Helical; Potential
Topological domain41 – 7535Extracellular Potential
Transmembrane76 – 9823Helical; Potential
Topological domain99 – 12628Cytoplasmic Potential
Transmembrane127 – 14923Helical; Potential
Topological domain150 – 18738Extracellular Potential
Transmembrane188 – 21023Helical; Potential
Topological domain211 – 27060Cytoplasmic Potential

Natural variations

Natural variant121G → D in EKV. Ref.3
VAR_002147
Natural variant121G → R in EKV. Ref.3
VAR_002148
Natural variant321R → W. Ref.7 Ref.10 Ref.12 Ref.13
Corresponds to variant rs1805063 [ dbSNP | Ensembl ].
VAR_011978
Natural variant421R → P in EKV. Ref.9 Ref.11
VAR_015085
Natural variant861C → S in EKV. Ref.3
VAR_002149
Natural variant1371F → L in EKV. Ref.11
VAR_015086
Natural variant1411I → V in DFNA2B.
VAR_015087
Natural variant1831E → K in DFNA2B. Ref.8
Corresponds to variant rs74315318 [ dbSNP | Ensembl ].
VAR_002150
Natural variant2001V → I. Ref.12 Ref.13
Corresponds to variant rs61734064 [ dbSNP | Ensembl ].
VAR_022423

Sequences

Sequence LengthMass (Da)Tools
O75712 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: E46D36E5835646A4

FASTA27030,818
        10         20         30         40         50         60 
MDWKTLQALL SGVNKYSTAF GRIWLSVVFV FRVLVYVVAA ERVWGDEQKD FDCNTKQPGC 

        70         80         90        100        110        120 
TNVCYDNYFP ISNIRLWALQ LIFVTCPSLL VILHVAYREE RERRHRQKHG DQCAKLYDNA 

       130        140        150        160        170        180 
GKKHGGLWWT YLFSLIFKLI IEFLFLYLLH TLWHGFNMPR LVQCANVAPC PNIVDCYIAR 

       190        200        210        220        230        240 
PTEKKIFTYF MVGASAVCIV LTICELCYLI CHRVLRGLHK DKPRGGCSPS SSASRASTCR 

       250        260        270 
CHHKLVEAGE VDPDPGNNKL QASAPNLTPI 

« Hide

References

« Hide 'large scale' references
[1]"Human gap junction protein connexin31: molecular cloning and expression analysis."
Wenzel K., Manthey D., Willecke K., Grzeschik K.-H., Traub O.
Biochem. Biophys. Res. Commun. 248:910-915(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta.
[2]"Molecular cloning of human connexin 31 and 31.1 genes."
Xia J.-H., Pan Q., Liu C.-Y., Zheng D., Xie W.
Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis."
Richard G., Smith L.E., Bailey R.A., Itin P., Hohl D., Epstein E.H. Jr., DiGiovanna J.J., Compton J.G., Bale S.J.
Nat. Genet. 20:366-369(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS EKV ASP-12; ARG-12 AND SER-86.
[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. 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: Cerebellum.
[5]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]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].
[7]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT TRP-32.
Tissue: Skin and Urinary bladder.
[8]"Mutations in the gene encoding gap junction protein beta-3 associated with autosomal dominant hearing impairment."
Xia J.-H., Liu C.-Y., Tang B.S., Pan Q., Huang L., Dai H.P., Zhang B.R., Xie W., Hu D.X., Zheng D., Shi X.L., Wang D.A., Xia K., Yu K.P., Liao X.D., Feng Y., Yang Y.F., Xiao J.Y., Xie D.H., Huang J.Z.
Nat. Genet. 20:370-373(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DFNA2B LYS-183.
[9]"Identification of a novel mutation R42P in the gap junction protein beta-3 associated with autosomal dominant erythrokeratoderma variabilis."
Wilgoss A., Leigh I.M., Barnes M.R., Dopping-Hepenstal P., Eady R.A.J., Walter J.M., Kennedy C.T., Kelsell D.P.
J. Invest. Dermatol. 113:1119-1122(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EKV PRO-42.
[10]"Connexin mutations associated with palmoplantar keratoderma and profound deafness in a single family."
Kelsell D.P., Wilgoss A.L., Richard G., Stevens H.P., Munro C.S., Leigh I.M.
Eur. J. Hum. Genet. 8:141-144(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TRP-32.
[11]"The spectrum of mutations in erythrokeratodermias -- novel and de novo mutations in GJB3."
Richard G., Brown N., Smith L.E., Terrinoni A., Melino G., Mackie R.M., Bale S.J., Uitto J.
Hum. Genet. 106:321-329(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EKV PRO-42 AND LEU-137.
[12]"Identification of seven novel SNPS (five nucleotide and two amino acid substitutions) in the connexin31 (GJB3) gene."
Lopez-Bigas N., Rabionet R., Martinez E., Banchs I., Volpini V., Vance J.M., Arbones M.L., Estivill X.
Hum. Mutat. 15:481-482(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TRP-32 AND ILE-200.
[13]"Connexin mutations in Brazilian patients with skin disorders with or without hearing loss."
Alexandrino F., de Oliveira C.A., Magalhaes R.F., Florence M.E., de Souza E.M., Sartorato E.L.
Am. J. Med. Genet. A 149:681-684(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TRP-32 AND ILE-200.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ004856 Genomic DNA. Translation: CAA06165.1.
AF052692 mRNA. Translation: AAD11816.1.
AF099730 Genomic DNA. Translation: AAC95471.1.
AK312890 mRNA. Translation: BAG35737.1.
AL121988 Genomic DNA. Translation: CAB90269.1.
CH471059 Genomic DNA. Translation: EAX07442.1.
BC012918 mRNA. Translation: AAH12918.1.
BC110640 mRNA. Translation: AAI10641.1.
CCDSCCDS384.1.
PIRJE0274.
RefSeqNP_001005752.1. NM_001005752.1.
NP_076872.1. NM_024009.2.
UniGeneHs.522561.

3D structure databases

ProteinModelPortalO75712.
SMRO75712. Positions 2-210.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108973. 3 interactions.
IntActO75712. 1 interaction.
STRING9606.ENSP00000362460.

Chemistry

GuidetoPHARMACOLOGY720.

PTM databases

PhosphoSiteO75712.

Proteomic databases

MaxQBO75712.
PaxDbO75712.
PRIDEO75712.

Protocols and materials databases

DNASU2707.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000373362; ENSP00000362460; ENSG00000188910.
ENST00000373366; ENSP00000362464; ENSG00000188910.
GeneID2707.
KEGGhsa:2707.
UCSCuc001bxx.3. human.

Organism-specific databases

CTD2707.
GeneCardsGC01P035246.
GeneReviewsGJB3.
H-InvDBHIX0000402.
HGNCHGNC:4285. GJB3.
MIM133200. phenotype.
603324. gene+phenotype.
612644. phenotype.
neXtProtNX_O75712.
Orphanet90635. Autosomal dominant nonsyndromic sensorineural deafness type DFNA.
90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB.
317. Erythrokeratodermia variabilis.
139512. Neuropathy with hearing impairment.
495. Transgrediens et progrediens palmoplantar keratoderma.
PharmGKBPA28696.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG39157.
HOGENOMHOG000231127.
HOVERGENHBG009576.
InParanoidO75712.
KOK07622.
OMAHTLWHGF.
OrthoDBEOG7P2XSS.
PhylomeDBO75712.
TreeFamTF329606.

Enzyme and pathway databases

ReactomeREACT_11123. Membrane Trafficking.

Gene expression databases

ArrayExpressO75712.
BgeeO75712.
CleanExHS_GJB3.
GenevestigatorO75712.

Family and domain databases

InterProIPR000500. Connexin.
IPR002269. Connexin31.
IPR019570. Connexin_CCC.
IPR017990. Connexin_CS.
IPR013092. Connexin_N.
[Graphical view]
PANTHERPTHR11984. PTHR11984. 1 hit.
PTHR11984:SF29. PTHR11984:SF29. 1 hit.
PfamPF00029. Connexin. 1 hit.
PF10582. Connexin_CCC. 1 hit.
[Graphical view]
PRINTSPR00206. CONNEXIN.
PR01140. CONNEXINB3.
SMARTSM00037. CNX. 1 hit.
SM01089. Connexin_CCC. 1 hit.
[Graphical view]
PROSITEPS00407. CONNEXINS_1. 1 hit.
PS00408. CONNEXINS_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSGJB3. human.
GeneWikiGJB3.
GenomeRNAi2707.
NextBio10702.
PROO75712.
SOURCESearch...

Entry information

Entry nameCXB3_HUMAN
AccessionPrimary (citable) accession number: O75712
Secondary accession number(s): B2R790, Q2TAZ8
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 1, 1998
Last modified: July 9, 2014
This is version 137 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

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 1

Human chromosome 1: entries, gene names and cross-references to MIM