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Protein

Gap junction gamma-2 protein

Gene

GJC2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. May play a role in myelination in central and peripheral nervous systems.1 Publication

Caution

It is uncertain whether Met-1 or Met-4 is the initiator.Curated

GO - Molecular functioni

  • gap junction channel activity involved in cell communication by electrical coupling Source: UniProtKB

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-HSA-190861 Gap junction assembly

Names & Taxonomyi

Protein namesi
Recommended name:
Gap junction gamma-2 protein
Alternative name(s):
Connexin-46.6
Short name:
Cx46.6
Connexin-47
Short name:
Cx47
Gap junction alpha-12 protein
Gene namesi
Name:GJC2
Synonyms:GJA12
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000198835.3
HGNCiHGNC:17494 GJC2
MIMi608803 gene
neXtProtiNX_Q5T442

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 25CytoplasmicSequence analysisAdd BLAST25
Transmembranei26 – 46HelicalSequence analysisAdd BLAST21
Topological domaini47 – 78ExtracellularSequence analysisAdd BLAST32
Transmembranei79 – 99HelicalSequence analysisAdd BLAST21
Topological domaini100 – 216CytoplasmicSequence analysisAdd BLAST117
Transmembranei217 – 237HelicalSequence analysisAdd BLAST21
Topological domaini238 – 265ExtracellularSequence analysisAdd BLAST28
Transmembranei266 – 286HelicalSequence analysisAdd BLAST21
Topological domaini287 – 439CytoplasmicSequence analysisAdd BLAST153

Keywords - Cellular componenti

Cell junction, Cell membrane, Gap junction, Membrane

Pathology & Biotechi

Involvement in diseasei

Leukodystrophy, hypomyelinating, 2 (HLD2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive hypomyelinating leukodystrophy with symptoms of Pelizaeus-Merzbacher disease. Clinically characterized by nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria, and progressive spasticity.
See also OMIM:608804
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02375490P → S in HLD2. 1 PublicationCorresponds to variant dbSNP:rs74315312EnsemblClinVar.1
Natural variantiVAR_023755272Y → D in HLD2. 1 PublicationCorresponds to variant dbSNP:rs74315314EnsemblClinVar.1
Natural variantiVAR_023756286M → T in HLD2. 1 PublicationCorresponds to variant dbSNP:rs74315311EnsemblClinVar.1
Spastic paraplegia 44, autosomal recessive (SPG44)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.
See also OMIM:613206
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06317236I → M in SPG44; does not form functional homotypic channels. 1 PublicationCorresponds to variant dbSNP:rs75469429EnsemblClinVar.1
Lymphedema, hereditary, 1C (LMPH1C)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections and physical impairment.
See also OMIM:613480
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06387748S → L in LMPH1C. 1 PublicationCorresponds to variant dbSNP:rs267606847EnsemblClinVar.1
Natural variantiVAR_063880260R → C in LMPH1C. 1 PublicationCorresponds to variant dbSNP:rs267606846EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Hereditary spastic paraplegia, Leukodystrophy, Neurodegeneration

Organism-specific databases

DisGeNETi57165
MalaCardsiGJC2
MIMi608804 phenotype
613206 phenotype
613480 phenotype
OpenTargetsiENSG00000198835
Orphaneti320401 Autosomal recessive spastic paraplegia type 44
79452 Milroy disease
280282 Pelizaeus-Merzbacher-like disease due to GJC2 mutation
PharmGKBiPA162389696

Polymorphism and mutation databases

BioMutaiGJC2
DMDMi74744875

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000578421 – 439Gap junction gamma-2 proteinAdd BLAST439

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei371PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ5T442
PeptideAtlasiQ5T442
PRIDEiQ5T442
ProteomicsDBi64429

PTM databases

iPTMnetiQ5T442
PhosphoSitePlusiQ5T442

Expressioni

Tissue specificityi

Expressed in central nervous system, in sciatic nerve and sural nerve. Also detected in skeletal muscles.1 Publication

Gene expression databases

BgeeiENSG00000198835 Expressed in 141 organ(s), highest expression level in C1 segment of cervical spinal cord
CleanExiHS_GJC2
GenevisibleiQ5T442 HS

Interactioni

Subunit structurei

A connexon is composed of a hexamer of connexins. Interacts with TJP1 (By similarity).By similarity

Protein-protein interaction databases

BioGridi121419, 1 interactor
IntActiQ5T442, 1 interactor
STRINGi9606.ENSP00000355675

Structurei

3D structure databases

ProteinModelPortaliQ5T442
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi143 – 176Glu-richAdd BLAST34

Sequence similaritiesi

Belongs to the connexin family. Gamma-type subfamily.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFK3 Eukaryota
ENOG410Z7PN LUCA
GeneTreeiENSGT00910000143998
HOGENOMiHOG000231126
HOVERGENiHBG009576
InParanoidiQ5T442
KOiK07619
OMAiARAHDQN
OrthoDBiEOG091G08B8
PhylomeDBiQ5T442
TreeFamiTF329606

Family and domain databases

Gene3Di1.20.1440.80, 2 hits
InterProiView protein in InterPro
IPR000500 Connexin
IPR019570 Connexin_CCC
IPR017990 Connexin_CS
IPR013092 Connexin_N
IPR038359 Connexin_N_sf
PANTHERiPTHR11984 PTHR11984, 1 hit
PfamiView protein in Pfam
PF00029 Connexin, 1 hit
PRINTSiPR00206 CONNEXIN
SMARTiView protein in SMART
SM00037 CNX, 1 hit
SM01089 Connexin_CCC, 1 hit
PROSITEiView protein in PROSITE
PS00407 CONNEXINS_1, 1 hit
PS00408 CONNEXINS_2, 1 hit

Sequencei

Sequence statusi: Complete.

Q5T442-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MTNMSWSFLT RLLEEIHNHS TFVGKVWLTV LVVFRIVLTA VGGEAIYSDE
60 70 80 90 100
QAKFTCNTRQ PGCDNVCYDA FAPLSHVRFW VFQIVVISTP SVMYLGYAVH
110 120 130 140 150
RLARASEQER RRALRRRPGP RRAPRAHLPP PHAGWPEPAD LGEEEPMLGL
160 170 180 190 200
GEEEEEEETG AAEGAGEEAE EAGAEEACTK AVGADGKAAG TPGPTGQHDG
210 220 230 240 250
RRRIQREGLM RVYVAQLVAR AAFEVAFLVG QYLLYGFEVR PFFPCSRQPC
260 270 280 290 300
PHVVDCFVSR PTEKTVFLLV MYVVSCLCLL LNLCEMAHLG LGSAQDAVRG
310 320 330 340 350
RRGPPASAPA PAPRPPPCAF PAAAAGLACP PDYSLVVRAA ERARAHDQNL
360 370 380 390 400
ANLALQALRD GAAAGDRDRD SSPCVGLPAA SRGPPRAGAP ASRTGSATSA
410 420 430
GTVGEQGRPG THERPGAKPR AGSEKGSASS RDGKTTVWI
Length:439
Mass (Da):47,002
Last modified:December 21, 2004 - v1
Checksum:i09725B5DC476672A
GO

Sequence cautioni

The sequence AAB94511 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH35840 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti83Q → H in AAB94511 (Ref. 1) Curated1
Sequence conflicti252H → Q in AAB94511 (Ref. 1) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06387619H → P Associated with lymphedema in a small family. 1 Publication1
Natural variantiVAR_06317236I → M in SPG44; does not form functional homotypic channels. 1 PublicationCorresponds to variant dbSNP:rs75469429EnsemblClinVar.1
Natural variantiVAR_06387748S → L in LMPH1C. 1 PublicationCorresponds to variant dbSNP:rs267606847EnsemblClinVar.1
Natural variantiVAR_02375490P → S in HLD2. 1 PublicationCorresponds to variant dbSNP:rs74315312EnsemblClinVar.1
Natural variantiVAR_063878125R → Q Associated with lymphedema in a small family. 1 Publication1
Natural variantiVAR_063879149G → S Associated with lymphedema in a small family. 1 PublicationCorresponds to variant dbSNP:rs577325764Ensembl.1
Natural variantiVAR_063880260R → C in LMPH1C. 1 PublicationCorresponds to variant dbSNP:rs267606846EnsemblClinVar.1
Natural variantiVAR_023755272Y → D in HLD2. 1 PublicationCorresponds to variant dbSNP:rs74315314EnsemblClinVar.1
Natural variantiVAR_023756286M → T in HLD2. 1 PublicationCorresponds to variant dbSNP:rs74315311EnsemblClinVar.1
Natural variantiVAR_063881316P → L Associated with lymphedema in a small family. 1 PublicationCorresponds to variant dbSNP:rs760502262EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF014643 Genomic DNA Translation: AAB94511.1 Different initiation.
AL359510 Genomic DNA No translation available.
BC035840 mRNA Translation: AAH35840.1 Different initiation.
BC089439 mRNA Translation: AAH89439.1
AY285161 mRNA Translation: AAP37488.1
CCDSiCCDS1569.1
RefSeqiNP_065168.2, NM_020435.3
UniGeneiHs.100072
Hs.743715

Genome annotation databases

EnsembliENST00000366714; ENSP00000355675; ENSG00000198835
GeneIDi57165
KEGGihsa:57165
UCSCiuc001hsk.4 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF014643 Genomic DNA Translation: AAB94511.1 Different initiation.
AL359510 Genomic DNA No translation available.
BC035840 mRNA Translation: AAH35840.1 Different initiation.
BC089439 mRNA Translation: AAH89439.1
AY285161 mRNA Translation: AAP37488.1
CCDSiCCDS1569.1
RefSeqiNP_065168.2, NM_020435.3
UniGeneiHs.100072
Hs.743715

3D structure databases

ProteinModelPortaliQ5T442
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121419, 1 interactor
IntActiQ5T442, 1 interactor
STRINGi9606.ENSP00000355675

PTM databases

iPTMnetiQ5T442
PhosphoSitePlusiQ5T442

Polymorphism and mutation databases

BioMutaiGJC2
DMDMi74744875

Proteomic databases

PaxDbiQ5T442
PeptideAtlasiQ5T442
PRIDEiQ5T442
ProteomicsDBi64429

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000366714; ENSP00000355675; ENSG00000198835
GeneIDi57165
KEGGihsa:57165
UCSCiuc001hsk.4 human

Organism-specific databases

CTDi57165
DisGeNETi57165
EuPathDBiHostDB:ENSG00000198835.3
GeneCardsiGJC2
HGNCiHGNC:17494 GJC2
MalaCardsiGJC2
MIMi608803 gene
608804 phenotype
613206 phenotype
613480 phenotype
neXtProtiNX_Q5T442
OpenTargetsiENSG00000198835
Orphaneti320401 Autosomal recessive spastic paraplegia type 44
79452 Milroy disease
280282 Pelizaeus-Merzbacher-like disease due to GJC2 mutation
PharmGKBiPA162389696
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFK3 Eukaryota
ENOG410Z7PN LUCA
GeneTreeiENSGT00910000143998
HOGENOMiHOG000231126
HOVERGENiHBG009576
InParanoidiQ5T442
KOiK07619
OMAiARAHDQN
OrthoDBiEOG091G08B8
PhylomeDBiQ5T442
TreeFamiTF329606

Enzyme and pathway databases

ReactomeiR-HSA-190861 Gap junction assembly

Miscellaneous databases

GeneWikiiGJC2
GenomeRNAii57165
PROiPR:Q5T442
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198835 Expressed in 141 organ(s), highest expression level in C1 segment of cervical spinal cord
CleanExiHS_GJC2
GenevisibleiQ5T442 HS

Family and domain databases

Gene3Di1.20.1440.80, 2 hits
InterProiView protein in InterPro
IPR000500 Connexin
IPR019570 Connexin_CCC
IPR017990 Connexin_CS
IPR013092 Connexin_N
IPR038359 Connexin_N_sf
PANTHERiPTHR11984 PTHR11984, 1 hit
PfamiView protein in Pfam
PF00029 Connexin, 1 hit
PRINTSiPR00206 CONNEXIN
SMARTiView protein in SMART
SM00037 CNX, 1 hit
SM01089 Connexin_CCC, 1 hit
PROSITEiView protein in PROSITE
PS00407 CONNEXINS_1, 1 hit
PS00408 CONNEXINS_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCXG2_HUMAN
AccessioniPrimary (citable) accession number: Q5T442
Secondary accession number(s): O43440, Q7Z7J2, Q8IWJ9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 8, 2005
Last sequence update: December 21, 2004
Last modified: November 7, 2018
This is version 137 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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