UniProtKB - P29033 (CXB2_HUMAN)
Protein
Gap junction beta-2 protein
Gene
GJB2
Organism
Homo sapiens (Human)
Status
Functioni
Structural component of gap junctions (PubMed:17551008, PubMed:19340074, PubMed:21094651, PubMed:26753910, PubMed:16849369, PubMed:19384972). Gap junctions are dodecameric channels that connect the cytoplasm of adjoining cells. They are formed by the docking of two hexameric hemichannels, one from each cell membrane (PubMed:17551008, PubMed:19340074, PubMed:21094651, PubMed:26753910). Small molecules and ions diffuse from one cell to a neighboring cell via the central pore (PubMed:21094651, PubMed:16849369, PubMed:19384972).6 Publications
Caution
The role of Thr-34 and Ile-37 variants in deafness was unclear (PubMed:9139825, PubMed:9422505, PubMed:14694360, PubMed:17935238 and PubMed:16849369). However, their pathogenicity has been definitely confirmed (PubMed:31160754).
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 42 | Calcium; shared with neighboring subunitCombined sources1 Publication | 1 | |
Metal bindingi | 45 | Calcium; via carbonyl oxygenCombined sources1 Publication | 1 | |
Metal bindingi | 47 | CalciumCombined sources1 Publication | 1 |
GO - Molecular functioni
- calcium ion binding Source: UniProtKB
- gap junction channel activity Source: UniProtKB
- gap junction channel activity involved in cell communication by electrical coupling Source: ARUK-UCL
- identical protein binding Source: IntAct
GO - Biological processi
- aging Source: Ensembl
- cell-cell signaling Source: UniProtKB
- cellular response to dexamethasone stimulus Source: Ensembl
- cellular response to glucagon stimulus Source: Ensembl
- cellular response to oxidative stress Source: Ensembl
- decidualization Source: Ensembl
- epididymis development Source: Ensembl
- gap junction assembly Source: ARUK-UCL
- gap junction-mediated intercellular transport Source: UniProtKB
- inner ear development Source: Ensembl
- response to antibiotic Source: Ensembl
- response to estradiol Source: Ensembl
- response to human chorionic gonadotropin Source: Ensembl
- response to ischemia Source: Ensembl
- response to lipopolysaccharide Source: Ensembl
- response to progesterone Source: Ensembl
- response to retinoic acid Source: Ensembl
- sensory perception of sound Source: UniProtKB-KW
- transmembrane transport Source: ARUK-UCL
Keywordsi
Biological process | Hearing |
Ligand | Calcium, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | P29033 |
Reactomei | R-HSA-190704, Oligomerization of connexins into connexons R-HSA-190827, Transport of connexins along the secretory pathway R-HSA-190861, Gap junction assembly R-HSA-190872, Transport of connexons to the plasma membrane |
SIGNORi | P29033 |
Protein family/group databases
TCDBi | 1.A.24.1.3, the gap junction-forming connexin (connexin) family |
Names & Taxonomyi
Protein namesi | Recommended name: Gap junction beta-2 proteinAlternative name(s): Connexin-262 Publications Short name: Cx261 Publication |
Gene namesi | Name:GJB2 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:4284, GJB2 |
MIMi | 121011, gene |
neXtProti | NX_P29033 |
VEuPathDBi | HostDB:ENSG00000165474.5 |
Subcellular locationi
Plasma membrane
- Cell membrane 6 Publications; Multi-pass membrane protein 4 Publications
Other locations
- gap junction 6 Publications
Note: Colocalizes with GJB4 at gap junction plaques in the cochlea.By similarity
Cytosol
- cytosol Source: Ensembl
Plasma Membrane
- connexin complex Source: UniProtKB
- integral component of plasma membrane Source: UniProtKB
- lateral plasma membrane Source: Ensembl
- plasma membrane Source: ARUK-UCL
Other locations
- astrocyte projection Source: Ensembl
- cell body Source: Ensembl
- endoplasmic reticulum-Golgi intermediate compartment Source: Reactome
- gap junction Source: ARUK-UCL
- perinuclear region of cytoplasm Source: Ensembl
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Intramembranei | 2 – 13 | 1 PublicationAdd BLAST | 12 | |
Topological domaini | 14 – 20 | Cytoplasmic1 Publication | 7 | |
Transmembranei | 21 – 40 | Helical1 PublicationAdd BLAST | 20 | |
Topological domaini | 41 – 73 | Extracellular1 PublicationAdd BLAST | 33 | |
Transmembranei | 74 – 94 | Helical1 PublicationAdd BLAST | 21 | |
Topological domaini | 95 – 135 | Cytoplasmic1 PublicationAdd BLAST | 41 | |
Transmembranei | 136 – 156 | Helical1 PublicationAdd BLAST | 21 | |
Topological domaini | 157 – 189 | Extracellular1 PublicationAdd BLAST | 33 | |
Transmembranei | 190 – 210 | Helical1 PublicationAdd BLAST | 21 | |
Topological domaini | 211 – 226 | Cytoplasmic1 PublicationAdd BLAST | 16 |
Keywords - Cellular componenti
Cell junction, Cell membrane, Gap junction, MembranePathology & Biotechi
Involvement in diseasei
Deafness, autosomal recessive, 1A (DFNB1A)27 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of non-syndromic 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_083826 | 24 – 226 | Missing in DFNB1A. 1 PublicationAdd BLAST | 203 | |
Natural variantiVAR_023605 | 32 | R → H in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs111033190EnsemblClinVar. | 1 | |
Natural variantiVAR_002138 | 34 | M → T in DFNB1A; it is correctly synthesized and targeted to the plasma membrane; it inefficiently forms intercellular channels that display an abnormal electrical behavior. 6 PublicationsCorresponds to variant dbSNP:rs35887622EnsemblClinVar. | 1 | |
Natural variantiVAR_002139 | 37 | V → I in DFNB1A. 10 PublicationsCorresponds to variant dbSNP:rs72474224EnsemblClinVar. | 1 | |
Natural variantiVAR_002141 | 77 | W → R in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs104894397EnsemblClinVar. | 1 | |
Natural variantiVAR_023607 | 79 | L → P in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs1555341957EnsemblClinVar. | 1 | |
Natural variantiVAR_023608 | 80 | Q → K in DFNB1A. 1 Publication | 1 | |
Natural variantiVAR_002143 | 84 | V → L in DFNB1A; sorted to the plasma membrane normally and forms gap junctions that were morphologically and electrically indistinguishable from those of control; the mutation reduces the permeability of GJB2 gap junction channels to inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), resulting in blockade of the Ins(1,4,5)P3-induced inward calcium current in neighboring cells. 2 PublicationsCorresponds to variant dbSNP:rs104894409EnsemblClinVar. | 1 | |
Natural variantiVAR_060800 | 84 | V → M in DFNB1A; the mutant disrupts cellular communication. 1 PublicationCorresponds to variant dbSNP:rs104894409EnsemblClinVar. | 1 | |
Natural variantiVAR_015458 | 86 | T → R in DFNB1A; does not form gap junctions since the mutated protein is confined in the cytoplasm and not transported to the cell membrane; when the mutation is coexpressed with the wild-type protein ionic and biochemical coupling is normal consistent with the recessive nature of the mutation. 2 PublicationsCorresponds to variant dbSNP:rs1291519904EnsemblClinVar. | 1 | |
Natural variantiVAR_015937 | 90 | L → P in DFNB1A. 2 PublicationsCorresponds to variant dbSNP:rs80338945EnsemblClinVar. | 1 | |
Natural variantiVAR_023609 | 93 | M → I in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs397516871EnsemblClinVar. | 1 | |
Natural variantiVAR_002144 | 95 | V → M in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs111033299EnsemblClinVar. | 1 | |
Natural variantiVAR_002145 | 113 | S → R in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs80338946EnsemblClinVar. | 1 | |
Natural variantiVAR_060801 | 118 | Missing in DFNB1A. | 1 | |
Natural variantiVAR_023610 | 120 | Missing in DFNB1A. 1 Publication | 1 | |
Natural variantiVAR_023611 | 129 | E → K in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs397516875EnsemblClinVar. | 1 | |
Natural variantiVAR_069520 | 130 | G → A in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs779018464EnsemblClinVar. | 1 | |
Natural variantiVAR_069521 | 130 | G → D in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs779018464EnsemblClinVar. | 1 | |
Natural variantiVAR_015460 | 143 | R → W in DFNB1A. 4 PublicationsCorresponds to variant dbSNP:rs80338948EnsemblClinVar. | 1 | |
Natural variantiVAR_015941 | 159 | D → V in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs28931592EnsemblClinVar. | 1 | |
Natural variantiVAR_023613 | 178 | V → A in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs568612627EnsemblClinVar. | 1 | |
Natural variantiVAR_015943 | 184 | R → P in DFNB1A. 2 PublicationsCorresponds to variant dbSNP:rs80338950EnsemblClinVar. | 1 | |
Natural variantiVAR_009969 | 184 | R → W in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs998045226EnsemblClinVar. | 1 | |
Natural variantiVAR_023616 | 203 | I → K in DFNB1A. 1 Publication | 1 | |
Natural variantiVAR_023617 | 214 | L → P in DFNB1A. 1 Publication | 1 |
Deafness, autosomal dominant, 3A (DFNA3A)7 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of non-syndromic 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_008709 | 44 | W → C in DFNA3A. 1 PublicationCorresponds to variant dbSNP:rs104894407EnsemblClinVar. | 1 | |
Natural variantiVAR_032749 | 44 | W → S in DFNA3A; does not affect protein trafficking; affects the ability to form functional channels; dominant negative effect. 1 PublicationCorresponds to variant dbSNP:rs104894413EnsemblClinVar. | 1 | |
Natural variantiVAR_060798 | 46 | D → E in DFNA3A; the mutant is targeted to the plasma membrane but fails to transfer ionic calcium or propidium iodide intercellularly suggesting disruption of both ionic and biochemical coupling; heterozygous gap junctions also show dysfunctional intercellular couplings and hemichannel opening confirming the dominant-negative nature of the mutation. 1 Publication | 1 | |
Natural variantiVAR_002140 | 75 | R → W in PPKDFN and DFNA3A; does not affect protein trafficking; affects the ability to form functional channels; dominant negative effect. 2 PublicationsCorresponds to variant dbSNP:rs104894402EnsemblClinVar. | 1 | |
Natural variantiVAR_015940 | 143 | R → Q in DFNA3A. 1 PublicationCorresponds to variant dbSNP:rs104894401EnsemblClinVar. | 1 | |
Natural variantiVAR_032752 | 179 | D → N in DFNA3A. 1 PublicationCorresponds to variant dbSNP:rs28931595EnsemblClinVar. | 1 | |
Natural variantiVAR_023614 | 184 | R → Q in DFNA3A. 1 PublicationCorresponds to variant dbSNP:rs80338950EnsemblClinVar. | 1 | |
Natural variantiVAR_023615 | 197 | A → S in DFNA3A. 1 PublicationCorresponds to variant dbSNP:rs777236559Ensembl. | 1 | |
Natural variantiVAR_015944 | 202 | C → F in DFNA3A. 1 PublicationCorresponds to variant dbSNP:rs104894406EnsemblClinVar. | 1 |
Vohwinkel syndrome (VOWNKL)4 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disease characterized by hyperkeratosis, constriction on fingers and toes and congenital deafness.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_008710 | 66 | D → H in VOWNKL and PPKDFN; impairs trafficking; localizes intracellularly closed to the nucleus; affects the ability to form functional channels; phenotype can be rescued by coexpression with wild-type protein. 3 PublicationsCorresponds to variant dbSNP:rs104894403EnsemblClinVar. | 1 | |
Natural variantiVAR_069522 | 130 | G → V in VOWNKL. 2 Publications | 1 |
Keratoderma, palmoplantar, with deafness (PPKDFN)7 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disorder characterized by the association of palmoplantar hyperkeratosis with progressive, bilateral, high-frequency, sensorineural deafness.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_009965 | 59 | G → A in PPKDFN; impairs trafficking; localizes intracellularly closed to the nucleus; affects the ability to form functional channels; phenotype can be rescued by coexpression with wild-type protein. 2 PublicationsCorresponds to variant dbSNP:rs104894404EnsemblClinVar. | 1 | |
Natural variantiVAR_008710 | 66 | D → H in VOWNKL and PPKDFN; impairs trafficking; localizes intracellularly closed to the nucleus; affects the ability to form functional channels; phenotype can be rescued by coexpression with wild-type protein. 3 PublicationsCorresponds to variant dbSNP:rs104894403EnsemblClinVar. | 1 | |
Natural variantiVAR_060799 | 73 | H → R in PPKDFN; the mutant has a dominant-negative effect on connexin trafficking. 1 PublicationCorresponds to variant dbSNP:rs121912968EnsemblClinVar. | 1 | |
Natural variantiVAR_015936 | 75 | R → Q in PPKDFN; the mutant protein completely prevents the formation of functional channels. 2 PublicationsCorresponds to variant dbSNP:rs28931593EnsemblClinVar. | 1 | |
Natural variantiVAR_002140 | 75 | R → W in PPKDFN and DFNA3A; does not affect protein trafficking; affects the ability to form functional channels; dominant negative effect. 2 PublicationsCorresponds to variant dbSNP:rs104894402EnsemblClinVar. | 1 |
Keratitis-ichthyosis-deafness syndrome, autosomal dominant (KIDAD)3 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant form of keratitis-ichthyosis-deafness syndrome, a disease characterized by the association of hyperkeratotic skin lesions with vascularizing keratitis and profound sensorineural hearing loss. Clinical features include deafness, ichthyosis, photophobia, absent or decreased eyebrows, sparse or absent scalp hair, decreased sweating and dysplastic finger and toenails.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_015453 | 12 | G → R in KIDAD. 1 PublicationCorresponds to variant dbSNP:rs104894408EnsemblClinVar. | 1 | |
Natural variantiVAR_015454 | 17 | S → F in KIDAD. 1 PublicationCorresponds to variant dbSNP:rs28929485EnsemblClinVar. | 1 | |
Natural variantiVAR_015456 | 50 | D → N in KIDAD and HID syndrome. 4 PublicationsCorresponds to variant dbSNP:rs28931594EnsemblClinVar. | 1 | |
Natural variantiVAR_015935 | 50 | D → Y in KIDAD. 1 PublicationCorresponds to variant dbSNP:rs28931594EnsemblClinVar. | 1 |
Bart-Pumphrey syndrome (BAPS)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disorder characterized by sensorineural hearing loss, palmoplantar keratoderma, knuckle pads, and leukonychia, It shows considerable phenotypic variability.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_032750 | 54 | N → K in BAPS. 1 PublicationCorresponds to variant dbSNP:rs104894412EnsemblClinVar. | 1 | |
Natural variantiVAR_032751 | 59 | G → S in BAPS. 1 PublicationCorresponds to variant dbSNP:rs104894410EnsemblClinVar. | 1 |
Ichthyosis hystrix-like with deafness syndrome (HID syndrome)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant keratinizing disorder characterized by sensorineural deafness and spiky hyperkeratosis affecting the entire skin. HID syndrome is considered to differ from the similar KID syndrome in the extent and time of occurrence of skin symptoms and the severity of the associated keratitis.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_015456 | 50 | D → N in KIDAD and HID syndrome. 4 PublicationsCorresponds to variant dbSNP:rs28931594EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 2 – 10 | Missing : Strongly reduced insertion into the cell membrane and strongly reduced gap junction plaque assembly. 1 Publication | 9 | |
Mutagenesisi | 2 – 7 | Missing : Loss of gap junction ion conductance. 1 Publication | 6 | |
Mutagenesisi | 34 | M → A: Loss of gap junction ion conductance, probably due to very low open probability of the channels. Can form functional channels with wild-type, but with strongly reduced channel conductance. No visible effect on channel assembly and membrane insertion. 1 Publication | 1 |
Keywords - Diseasei
Deafness, Disease variant, Ectodermal dysplasia, Ichthyosis, Non-syndromic deafness, Palmoplantar keratodermaOrganism-specific databases
DisGeNETi | 2706 |
GeneReviewsi | GJB2 |
MalaCardsi | GJB2 |
MIMi | 124500, phenotype 148210, phenotype 148350, phenotype 149200, phenotype 220290, phenotype 601544, phenotype 602540, phenotype |
OpenTargetsi | ENSG00000165474 |
Orphaneti | 90635, Autosomal dominant non-syndromic sensorineural deafness type DFNA 90636, Autosomal recessive non-syndromic sensorineural deafness type DFNB 494, Keratoderma hereditarium mutilans 477, KID syndrome 2698, Knuckle pads-leukonychia-sensorineural deafness-palmoplantar hyperkeratosis syndrome 2202, Palmoplantar keratoderma-deafness syndrome 166286, Porokeratotic eccrine ostial and dermal duct nevus |
PharmGKBi | PA28695 |
Miscellaneous databases
Pharosi | P29033, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4295738 |
Genetic variation databases
BioMutai | GJB2 |
DMDMi | 77416855 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000057855 | 1 – 226 | Gap junction beta-2 proteinAdd BLAST | 226 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 53 ↔ 180 | Combined sources2 Publications | ||
Disulfide bondi | 60 ↔ 174 | Combined sources2 Publications | ||
Disulfide bondi | 64 ↔ 169 | Combined sources2 Publications |
Keywords - PTMi
Disulfide bondProteomic databases
jPOSTi | P29033 |
MassIVEi | P29033 |
PaxDbi | P29033 |
PeptideAtlasi | P29033 |
PRIDEi | P29033 |
ProteomicsDBi | 54514 |
PTM databases
iPTMneti | P29033 |
PhosphoSitePlusi | P29033 |
Expressioni
Gene expression databases
Bgeei | ENSG00000165474, Expressed in ectocervix and 162 other tissues |
ExpressionAtlasi | P29033, baseline and differential |
Genevisiblei | P29033, HS |
Organism-specific databases
HPAi | ENSG00000165474, Group enriched (cervix, uterine, esophagus, lymphoid tissue, tongue, vagina) |
Interactioni
Subunit structurei
A hemichannel or connexon is composed of a hexamer of connexins. A functional gap junction is formed by the apposition of two hemichannels (PubMed:17551008, PubMed:19340074, PubMed:21094651, PubMed:26753910).
Interacts with CNST (PubMed:19864490). Forms heteromeric channels with GJB4 (By similarity).
By similarity5 PublicationsBinary interactionsi
Hide detailsP29033
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 108972, 60 interactors |
CORUMi | P29033 |
DIPi | DIP-59742N |
IntActi | P29033, 50 interactors |
STRINGi | 9606.ENSP00000372295 |
Chemistry databases
BindingDBi | P29033 |
Miscellaneous databases
RNActi | P29033, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P29033 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P29033 |
Family & Domainsi
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502QWM8, Eukaryota |
GeneTreei | ENSGT00990000203622 |
HOGENOMi | CLU_037388_4_1_1 |
InParanoidi | P29033 |
OMAi | YAFYFMY |
OrthoDBi | 1174178at2759 |
PhylomeDBi | P29033 |
TreeFami | TF329606 |
Family and domain databases
Gene3Di | 1.20.1440.80, 1 hit |
InterProi | View protein in InterPro IPR000500, Connexin IPR002268, Connexin26 IPR019570, Connexin_CCC IPR017990, Connexin_CS IPR013092, Connexin_N IPR038359, Connexin_N_sf |
PANTHERi | PTHR11984, PTHR11984, 1 hit |
Pfami | View protein in Pfam PF00029, Connexin, 1 hit |
PRINTSi | PR00206, CONNEXIN PR01139, CONNEXINB2 |
SMARTi | View protein in SMART SM00037, CNX, 1 hit SM01089, Connexin_CCC, 1 hit |
PROSITEi | View protein in PROSITE PS00407, CONNEXINS_1, 1 hit PS00408, CONNEXINS_2, 1 hit |
i Sequence
Sequence statusi: Complete.
P29033-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MDWGTLQTIL GGVNKHSTSI GKIWLTVLFI FRIMILVVAA KEVWGDEQAD
60 70 80 90 100
FVCNTLQPGC KNVCYDHYFP ISHIRLWALQ LIFVSTPALL VAMHVAYRRH
110 120 130 140 150
EKKRKFIKGE IKSEFKDIEE IKTQKVRIEG SLWWTYTSSI FFRVIFEAAF
160 170 180 190 200
MYVFYVMYDG FSMQRLVKCN AWPCPNTVDC FVSRPTEKTV FTVFMIAVSG
210 220
ICILLNVTEL CYLLIRYCSG KSKKPV
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 86 | T → S in AAD21314 (PubMed:1324944).Curated | 1 | |
Sequence conflicti | 112 | K → N in AAY25170 (PubMed:15666300).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_015453 | 12 | G → R in KIDAD. 1 PublicationCorresponds to variant dbSNP:rs104894408EnsemblClinVar. | 1 | |
Natural variantiVAR_015454 | 17 | S → F in KIDAD. 1 PublicationCorresponds to variant dbSNP:rs28929485EnsemblClinVar. | 1 | |
Natural variantiVAR_083826 | 24 – 226 | Missing in DFNB1A. 1 PublicationAdd BLAST | 203 | |
Natural variantiVAR_002137 | 27 | V → I7 PublicationsCorresponds to variant dbSNP:rs2274084EnsemblClinVar. | 1 | |
Natural variantiVAR_023605 | 32 | R → H in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs111033190EnsemblClinVar. | 1 | |
Natural variantiVAR_016839 | 32 | R → L1 PublicationCorresponds to variant dbSNP:rs111033190EnsemblClinVar. | 1 | |
Natural variantiVAR_002138 | 34 | M → T in DFNB1A; it is correctly synthesized and targeted to the plasma membrane; it inefficiently forms intercellular channels that display an abnormal electrical behavior. 6 PublicationsCorresponds to variant dbSNP:rs35887622EnsemblClinVar. | 1 | |
Natural variantiVAR_002139 | 37 | V → I in DFNB1A. 10 PublicationsCorresponds to variant dbSNP:rs72474224EnsemblClinVar. | 1 | |
Natural variantiVAR_008709 | 44 | W → C in DFNA3A. 1 PublicationCorresponds to variant dbSNP:rs104894407EnsemblClinVar. | 1 | |
Natural variantiVAR_032749 | 44 | W → S in DFNA3A; does not affect protein trafficking; affects the ability to form functional channels; dominant negative effect. 1 PublicationCorresponds to variant dbSNP:rs104894413EnsemblClinVar. | 1 | |
Natural variantiVAR_015455 | 45 | G → E in deafness. 1 PublicationCorresponds to variant dbSNP:rs72561723EnsemblClinVar. | 1 | |
Natural variantiVAR_023606 | 46 – 48 | DEQ → E May contribute to deafness. 1 Publication | 3 | |
Natural variantiVAR_060798 | 46 | D → E in DFNA3A; the mutant is targeted to the plasma membrane but fails to transfer ionic calcium or propidium iodide intercellularly suggesting disruption of both ionic and biochemical coupling; heterozygous gap junctions also show dysfunctional intercellular couplings and hemichannel opening confirming the dominant-negative nature of the mutation. 1 Publication | 1 | |
Natural variantiVAR_015456 | 50 | D → N in KIDAD and HID syndrome. 4 PublicationsCorresponds to variant dbSNP:rs28931594EnsemblClinVar. | 1 | |
Natural variantiVAR_015935 | 50 | D → Y in KIDAD. 1 PublicationCorresponds to variant dbSNP:rs28931594EnsemblClinVar. | 1 | |
Natural variantiVAR_032750 | 54 | N → K in BAPS. 1 PublicationCorresponds to variant dbSNP:rs104894412EnsemblClinVar. | 1 | |
Natural variantiVAR_009965 | 59 | G → A in PPKDFN; impairs trafficking; localizes intracellularly closed to the nucleus; affects the ability to form functional channels; phenotype can be rescued by coexpression with wild-type protein. 2 PublicationsCorresponds to variant dbSNP:rs104894404EnsemblClinVar. | 1 | |
Natural variantiVAR_032751 | 59 | G → S in BAPS. 1 PublicationCorresponds to variant dbSNP:rs104894410EnsemblClinVar. | 1 | |
Natural variantiVAR_008710 | 66 | D → H in VOWNKL and PPKDFN; impairs trafficking; localizes intracellularly closed to the nucleus; affects the ability to form functional channels; phenotype can be rescued by coexpression with wild-type protein. 3 PublicationsCorresponds to variant dbSNP:rs104894403EnsemblClinVar. | 1 | |
Natural variantiVAR_015457 | 71 | I → T in deafness. 1 PublicationCorresponds to variant dbSNP:rs1373154561EnsemblClinVar. | 1 | |
Natural variantiVAR_060799 | 73 | H → R in PPKDFN; the mutant has a dominant-negative effect on connexin trafficking. 1 PublicationCorresponds to variant dbSNP:rs121912968EnsemblClinVar. | 1 | |
Natural variantiVAR_015936 | 75 | R → Q in PPKDFN; the mutant protein completely prevents the formation of functional channels. 2 PublicationsCorresponds to variant dbSNP:rs28931593EnsemblClinVar. | 1 | |
Natural variantiVAR_002140 | 75 | R → W in PPKDFN and DFNA3A; does not affect protein trafficking; affects the ability to form functional channels; dominant negative effect. 2 PublicationsCorresponds to variant dbSNP:rs104894402EnsemblClinVar. | 1 | |
Natural variantiVAR_002141 | 77 | W → R in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs104894397EnsemblClinVar. | 1 | |
Natural variantiVAR_023607 | 79 | L → P in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs1555341957EnsemblClinVar. | 1 | |
Natural variantiVAR_023608 | 80 | Q → K in DFNB1A. 1 Publication | 1 | |
Natural variantiVAR_002142 | 83 | F → L1 PublicationCorresponds to variant dbSNP:rs111033218EnsemblClinVar. | 1 | |
Natural variantiVAR_002143 | 84 | V → L in DFNB1A; sorted to the plasma membrane normally and forms gap junctions that were morphologically and electrically indistinguishable from those of control; the mutation reduces the permeability of GJB2 gap junction channels to inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), resulting in blockade of the Ins(1,4,5)P3-induced inward calcium current in neighboring cells. 2 PublicationsCorresponds to variant dbSNP:rs104894409EnsemblClinVar. | 1 | |
Natural variantiVAR_060800 | 84 | V → M in DFNB1A; the mutant disrupts cellular communication. 1 PublicationCorresponds to variant dbSNP:rs104894409EnsemblClinVar. | 1 | |
Natural variantiVAR_015458 | 86 | T → R in DFNB1A; does not form gap junctions since the mutated protein is confined in the cytoplasm and not transported to the cell membrane; when the mutation is coexpressed with the wild-type protein ionic and biochemical coupling is normal consistent with the recessive nature of the mutation. 2 PublicationsCorresponds to variant dbSNP:rs1291519904EnsemblClinVar. | 1 | |
Natural variantiVAR_015937 | 90 | L → P in DFNB1A. 2 PublicationsCorresponds to variant dbSNP:rs80338945EnsemblClinVar. | 1 | |
Natural variantiVAR_023609 | 93 | M → I in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs397516871EnsemblClinVar. | 1 | |
Natural variantiVAR_002144 | 95 | V → M in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs111033299EnsemblClinVar. | 1 | |
Natural variantiVAR_015938 | 111 | I → T1 PublicationCorresponds to variant dbSNP:rs1316789942Ensembl. | 1 | |
Natural variantiVAR_002145 | 113 | S → R in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs80338946EnsemblClinVar. | 1 | |
Natural variantiVAR_009966 | 114 | E → G5 PublicationsCorresponds to variant dbSNP:rs2274083EnsemblClinVar. | 1 | |
Natural variantiVAR_069519 | 117 | D → H1 Publication | 1 | |
Natural variantiVAR_060801 | 118 | Missing in DFNB1A. | 1 | |
Natural variantiVAR_023610 | 120 | Missing in DFNB1A. 1 Publication | 1 | |
Natural variantiVAR_015459 | 123 | T → N1 PublicationCorresponds to variant dbSNP:rs111033188EnsemblClinVar. | 1 | |
Natural variantiVAR_015939 | 127 | R → H3 PublicationsCorresponds to variant dbSNP:rs111033196EnsemblClinVar. | 1 | |
Natural variantiVAR_023611 | 129 | E → K in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs397516875EnsemblClinVar. | 1 | |
Natural variantiVAR_069520 | 130 | G → A in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs779018464EnsemblClinVar. | 1 | |
Natural variantiVAR_069521 | 130 | G → D in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs779018464EnsemblClinVar. | 1 | |
Natural variantiVAR_069522 | 130 | G → V in VOWNKL. 2 Publications | 1 | |
Natural variantiVAR_069523 | 142 | Missing 1 Publication | 1 | |
Natural variantiVAR_015940 | 143 | R → Q in DFNA3A. 1 PublicationCorresponds to variant dbSNP:rs104894401EnsemblClinVar. | 1 | |
Natural variantiVAR_015460 | 143 | R → W in DFNB1A. 4 PublicationsCorresponds to variant dbSNP:rs80338948EnsemblClinVar. | 1 | |
Natural variantiVAR_069524 | 148 | A → P1 Publication | 1 | |
Natural variantiVAR_009967 | 153 | V → I May contribute to deafness. 3 PublicationsCorresponds to variant dbSNP:rs111033186EnsemblClinVar. | 1 | |
Natural variantiVAR_015941 | 159 | D → V in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs28931592EnsemblClinVar. | 1 | |
Natural variantiVAR_002146 | 160 | G → S2 PublicationsCorresponds to variant dbSNP:rs34988750EnsemblClinVar. | 1 | |
Natural variantiVAR_015942 | 165 | R → W1 PublicationCorresponds to variant dbSNP:rs376898963EnsemblClinVar. | 1 | |
Natural variantiVAR_023612 | 167 | V → M May contribute to deafness. 1 PublicationCorresponds to variant dbSNP:rs111033360EnsemblClinVar. | 1 | |
Natural variantiVAR_057959 | 168 | K → R in a patient with congenital erythrokeratodermia; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs200104362EnsemblClinVar. | 1 | |
Natural variantiVAR_009968 | 169 | C → Y. Corresponds to variant dbSNP:rs774518779EnsemblClinVar. | 1 | |
Natural variantiVAR_023613 | 178 | V → A in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs568612627EnsemblClinVar. | 1 | |
Natural variantiVAR_032752 | 179 | D → N in DFNA3A. 1 PublicationCorresponds to variant dbSNP:rs28931595EnsemblClinVar. | 1 | |
Natural variantiVAR_015943 | 184 | R → P in DFNB1A. 2 PublicationsCorresponds to variant dbSNP:rs80338950EnsemblClinVar. | 1 | |
Natural variantiVAR_023614 | 184 | R → Q in DFNA3A. 1 PublicationCorresponds to variant dbSNP:rs80338950EnsemblClinVar. | 1 | |
Natural variantiVAR_009969 | 184 | R → W in DFNB1A. 1 PublicationCorresponds to variant dbSNP:rs998045226EnsemblClinVar. | 1 | |
Natural variantiVAR_015461 | 191 | F → L1 PublicationCorresponds to variant dbSNP:rs397516878EnsemblClinVar. | 1 | |
Natural variantiVAR_023615 | 197 | A → S in DFNA3A. 1 PublicationCorresponds to variant dbSNP:rs777236559Ensembl. | 1 | |
Natural variantiVAR_015944 | 202 | C → F in DFNA3A. 1 PublicationCorresponds to variant dbSNP:rs104894406EnsemblClinVar. | 1 | |
Natural variantiVAR_023616 | 203 | I → K in DFNB1A. 1 Publication | 1 | |
Natural variantiVAR_009970 | 203 | I → T2 PublicationsCorresponds to variant dbSNP:rs76838169EnsemblClinVar. | 1 | |
Natural variantiVAR_023617 | 214 | L → P in DFNB1A. 1 Publication | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M86849 mRNA Translation: AAD21314.1 AF281280 Genomic DNA Translation: AAF91440.1 AF479776 Genomic DNA Translation: AAL87696.1 AY255853 Genomic DNA Translation: AAP34178.1 AY275646 Genomic DNA Translation: AAQ94940.1 AY275647 Genomic DNA Translation: AAQ94941.1 AY275648 Genomic DNA Translation: AAQ94942.1 AY275649 Genomic DNA Translation: AAQ94943.1 AY275650 Genomic DNA Translation: AAQ94944.1 AY275651 Genomic DNA Translation: AAQ94945.1 AY275652 Genomic DNA Translation: AAQ94946.1 AY275653 Genomic DNA Translation: AAQ94947.1 AY275654 Genomic DNA Translation: AAQ94948.1 AY280971 Genomic DNA Translation: AAQ17213.1 AY953438 Genomic DNA Translation: AAY25169.1 AY953441 Genomic DNA Translation: AAY25170.1 BT006732 mRNA Translation: AAP35378.1 AL138688 Genomic DNA No translation available. BC017048 mRNA Translation: AAH17048.1 BC071703 mRNA Translation: AAH71703.1 |
CCDSi | CCDS9290.1 |
PIRi | A43424 |
RefSeqi | NP_003995.2, NM_004004.5 XP_011533351.1, XM_011535049.2 |
Genome annotation databases
Ensembli | ENST00000382844; ENSP00000372295; ENSG00000165474 ENST00000382848; ENSP00000372299; ENSG00000165474 |
GeneIDi | 2706 |
KEGGi | hsa:2706 |
UCSCi | uc001umy.4, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
Connexin-deafness homepage |
Hereditary hearing loss homepage Gene page |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | M86849 mRNA Translation: AAD21314.1 AF281280 Genomic DNA Translation: AAF91440.1 AF479776 Genomic DNA Translation: AAL87696.1 AY255853 Genomic DNA Translation: AAP34178.1 AY275646 Genomic DNA Translation: AAQ94940.1 AY275647 Genomic DNA Translation: AAQ94941.1 AY275648 Genomic DNA Translation: AAQ94942.1 AY275649 Genomic DNA Translation: AAQ94943.1 AY275650 Genomic DNA Translation: AAQ94944.1 AY275651 Genomic DNA Translation: AAQ94945.1 AY275652 Genomic DNA Translation: AAQ94946.1 AY275653 Genomic DNA Translation: AAQ94947.1 AY275654 Genomic DNA Translation: AAQ94948.1 AY280971 Genomic DNA Translation: AAQ17213.1 AY953438 Genomic DNA Translation: AAY25169.1 AY953441 Genomic DNA Translation: AAY25170.1 BT006732 mRNA Translation: AAP35378.1 AL138688 Genomic DNA No translation available. BC017048 mRNA Translation: AAH17048.1 BC071703 mRNA Translation: AAH71703.1 |
CCDSi | CCDS9290.1 |
PIRi | A43424 |
RefSeqi | NP_003995.2, NM_004004.5 XP_011533351.1, XM_011535049.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1XIR | model | - | A | 1-226 | [»] | |
2ZW3 | X-ray | 3.50 | A/B/C/D/E/F | 1-226 | [»] | |
3IZ1 | electron microscopy | 6.00 | A/B/C | 1-226 | [»] | |
3IZ2 | electron microscopy | 10.00 | A/B/C | 8-226 | [»] | |
5ER7 | X-ray | 3.29 | A/B | 1-226 | [»] | |
5ERA | X-ray | 3.80 | A/B | 1-226 | [»] | |
5KJ3 | NMR | - | A | 1-22 | [»] | |
5KJG | NMR | - | A | 1-22 | [»] | |
6UVR | electron microscopy | 4.00 | A/B/C/D/E/F/G/H/I/J/K/L | 1-226 | [»] | |
6UVS | electron microscopy | 4.20 | A/B/C/D/E/F/G/H/I/J/K/L | 1-226 | [»] | |
6UVT | electron microscopy | 7.50 | A/B/C/D/E/F/G/H/I/J/K/L | 1-226 | [»] | |
SMRi | P29033 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 108972, 60 interactors |
CORUMi | P29033 |
DIPi | DIP-59742N |
IntActi | P29033, 50 interactors |
STRINGi | 9606.ENSP00000372295 |
Chemistry databases
BindingDBi | P29033 |
ChEMBLi | CHEMBL4295738 |
Protein family/group databases
TCDBi | 1.A.24.1.3, the gap junction-forming connexin (connexin) family |
PTM databases
iPTMneti | P29033 |
PhosphoSitePlusi | P29033 |
Genetic variation databases
BioMutai | GJB2 |
DMDMi | 77416855 |
Proteomic databases
jPOSTi | P29033 |
MassIVEi | P29033 |
PaxDbi | P29033 |
PeptideAtlasi | P29033 |
PRIDEi | P29033 |
ProteomicsDBi | 54514 |
Protocols and materials databases
Antibodypediai | 4587, 319 antibodies |
DNASUi | 2706 |
Genome annotation databases
Ensembli | ENST00000382844; ENSP00000372295; ENSG00000165474 ENST00000382848; ENSP00000372299; ENSG00000165474 |
GeneIDi | 2706 |
KEGGi | hsa:2706 |
UCSCi | uc001umy.4, human |
Organism-specific databases
CTDi | 2706 |
DisGeNETi | 2706 |
GeneCardsi | GJB2 |
GeneReviewsi | GJB2 |
HGNCi | HGNC:4284, GJB2 |
HPAi | ENSG00000165474, Group enriched (cervix, uterine, esophagus, lymphoid tissue, tongue, vagina) |
MalaCardsi | GJB2 |
MIMi | 121011, gene 124500, phenotype 148210, phenotype 148350, phenotype 149200, phenotype 220290, phenotype 601544, phenotype 602540, phenotype |
neXtProti | NX_P29033 |
OpenTargetsi | ENSG00000165474 |
Orphaneti | 90635, Autosomal dominant non-syndromic sensorineural deafness type DFNA 90636, Autosomal recessive non-syndromic sensorineural deafness type DFNB 494, Keratoderma hereditarium mutilans 477, KID syndrome 2698, Knuckle pads-leukonychia-sensorineural deafness-palmoplantar hyperkeratosis syndrome 2202, Palmoplantar keratoderma-deafness syndrome 166286, Porokeratotic eccrine ostial and dermal duct nevus |
PharmGKBi | PA28695 |
VEuPathDBi | HostDB:ENSG00000165474.5 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QWM8, Eukaryota |
GeneTreei | ENSGT00990000203622 |
HOGENOMi | CLU_037388_4_1_1 |
InParanoidi | P29033 |
OMAi | YAFYFMY |
OrthoDBi | 1174178at2759 |
PhylomeDBi | P29033 |
TreeFami | TF329606 |
Enzyme and pathway databases
PathwayCommonsi | P29033 |
Reactomei | R-HSA-190704, Oligomerization of connexins into connexons R-HSA-190827, Transport of connexins along the secretory pathway R-HSA-190861, Gap junction assembly R-HSA-190872, Transport of connexons to the plasma membrane |
SIGNORi | P29033 |
Miscellaneous databases
BioGRID-ORCSi | 2706, 32 hits in 873 CRISPR screens |
ChiTaRSi | GJB2, human |
EvolutionaryTracei | P29033 |
GeneWikii | GJB2 |
GenomeRNAii | 2706 |
Pharosi | P29033, Tbio |
PROi | PR:P29033 |
RNActi | P29033, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000165474, Expressed in ectocervix and 162 other tissues |
ExpressionAtlasi | P29033, baseline and differential |
Genevisiblei | P29033, HS |
Family and domain databases
Gene3Di | 1.20.1440.80, 1 hit |
InterProi | View protein in InterPro IPR000500, Connexin IPR002268, Connexin26 IPR019570, Connexin_CCC IPR017990, Connexin_CS IPR013092, Connexin_N IPR038359, Connexin_N_sf |
PANTHERi | PTHR11984, PTHR11984, 1 hit |
Pfami | View protein in Pfam PF00029, Connexin, 1 hit |
PRINTSi | PR00206, CONNEXIN PR01139, CONNEXINB2 |
SMARTi | View protein in SMART SM00037, CNX, 1 hit SM01089, Connexin_CCC, 1 hit |
PROSITEi | View protein in PROSITE PS00407, CONNEXINS_1, 1 hit PS00408, CONNEXINS_2, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CXB2_HUMAN | |
Accessioni | P29033Primary (citable) accession number: P29033 Secondary accession number(s): Q508A5 Q9NNY4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 1992 |
Last sequence update: | October 11, 2005 | |
Last modified: | February 10, 2021 | |
This is version 222 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 13
Human chromosome 13: entries, gene names and cross-references to MIM - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human entries with genetic variants
List of human entries with genetic variants