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Q5T442 (CXG2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 102. 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·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:GJC2
Synonyms:GJA12
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length439 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. May play a role in myelination in central and peripheral nervous systems. Ref.5

Subunit structure

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

Subcellular location

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

Tissue specificity

Expressed in central nervous system, in sciatic nerve and sural nerve. Also detected in skeletal muscles. Ref.5

Involvement in disease

Leukodystrophy, hypomyelinating, 2 (HLD2) [MIM:608804]: An autosomal recessive hypomyelinating leukodystrophy with symptoms of Pelizaeus-Merzbacher disease. Clinically characterized by nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria, and progressive spasticity.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5

Spastic paraplegia 44, autosomal recessive (SPG44) [MIM:613206]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.7

Lymphedema, hereditary, 1C (LMPH1C) [MIM:613480]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.8

Sequence similarities

Belongs to the connexin family. Gamma-type subfamily.

Caution

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

Sequence caution

The sequence AAB94511.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAH35840.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 439439Gap junction gamma-2 protein
PRO_0000057842

Regions

Topological domain1 – 2525Cytoplasmic Potential
Transmembrane26 – 4621Helical; Potential
Topological domain47 – 7832Extracellular Potential
Transmembrane79 – 9921Helical; Potential
Topological domain100 – 216117Cytoplasmic Potential
Transmembrane217 – 23721Helical; Potential
Topological domain238 – 26528Extracellular Potential
Transmembrane266 – 28621Helical; Potential
Topological domain287 – 439153Cytoplasmic Potential
Compositional bias143 – 17634Glu-rich

Amino acid modifications

Modified residue3711Phosphoserine By similarity

Natural variations

Natural variant191H → P Associated with lymphedema in a small family. Ref.8
VAR_063876
Natural variant361I → M in SPG44; does not form functional homotypic channels. Ref.7
VAR_063172
Natural variant481S → L in LMPH1C. Ref.8
VAR_063877
Natural variant901P → S in HLD2. Ref.5
VAR_023754
Natural variant1251R → Q Associated with lymphedema in a small family. Ref.8
VAR_063878
Natural variant1491G → S Associated with lymphedema in a small family. Ref.8
VAR_063879
Natural variant2601R → C in LMPH1C. Ref.8
VAR_063880
Natural variant2721Y → D in HLD2. Ref.5
VAR_023755
Natural variant2861M → T in HLD2. Ref.5
VAR_023756
Natural variant3161P → L Associated with lymphedema in a small family. Ref.8
VAR_063881

Experimental info

Sequence conflict831Q → H in AAB94511. Ref.1
Sequence conflict2521H → Q in AAB94511. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q5T442 [UniParc].

Last modified December 21, 2004. Version 1.
Checksum: 09725B5DC476672A

FASTA43947,002
        10         20         30         40         50         60 
MTNMSWSFLT RLLEEIHNHS TFVGKVWLTV LVVFRIVLTA VGGEAIYSDE QAKFTCNTRQ 

        70         80         90        100        110        120 
PGCDNVCYDA FAPLSHVRFW VFQIVVISTP SVMYLGYAVH RLARASEQER RRALRRRPGP 

       130        140        150        160        170        180 
RRAPRAHLPP PHAGWPEPAD LGEEEPMLGL GEEEEEEETG AAEGAGEEAE EAGAEEACTK 

       190        200        210        220        230        240 
AVGADGKAAG TPGPTGQHDG RRRIQREGLM RVYVAQLVAR AAFEVAFLVG QYLLYGFEVR 

       250        260        270        280        290        300 
PFFPCSRQPC PHVVDCFVSR PTEKTVFLLV MYVVSCLCLL LNLCEMAHLG LGSAQDAVRG 

       310        320        330        340        350        360 
RRGPPASAPA PAPRPPPCAF PAAAAGLACP PDYSLVVRAA ERARAHDQNL ANLALQALRD 

       370        380        390        400        410        420 
GAAAGDRDRD SSPCVGLPAA SRGPPRAGAP ASRTGSATSA GTVGEQGRPG THERPGAKPR 

       430 
AGSEKGSASS RDGKTTVWI 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and molecular characterization of human connexin46.6, a new gap junction gene."
Bloemker B.K., Swaroop A., Kimberling W.J.
Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"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].
[3]"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].
Tissue: Brain and Chondrosarcoma.
[4]"Human connexin47, updated ORF."
Enriquez A.D., Scherer S.S.
Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-439.
Tissue: Corpus callosum.
[5]"Mutations in the gene encoding gap junction protein alpha 12 (connexin 46.6) cause Pelizaeus-Merzbacher-like disease."
Uhlenberg B., Schuelke M., Rueschendorf F., Ruf N., Kaindl A.M., Henneke M., Thiele H., Stoltenburg-Didinger G., Aksu F., Topaloglu H., Nuernberg P., Huebner C., Weschke B., Gaertner J.
Am. J. Hum. Genet. 75:251-260(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISEASE, VARIANTS HLD2 SER-90; ASP-272 AND THR-286, TISSUE SPECIFICITY.
[6]Erratum
Uhlenberg B., Schuelke M., Rueschendorf F., Ruf N., Kaindl A.M., Henneke M., Thiele H., Stoltenburg-Didinger G., Aksu F., Topaloglu H., Nuernberg P., Huebner C., Weschke B., Gaertner J.
Am. J. Hum. Genet. 75:737-737(2004)
[7]"Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations."
Orthmann-Murphy J.L., Salsano E., Abrams C.K., Bizzi A., Uziel G., Freidin M.M., Lamantea E., Zeviani M., Scherer S.S., Pareyson D.
Brain 132:426-438(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SPG44 MET-36, CHARACTERIZATION OF VARIANT SPG44 MET-36.
[8]"GJC2 missense mutations cause human lymphedema."
Ferrell R.E., Baty C.J., Kimak M.A., Karlsson J.M., Lawrence E.C., Franke-Snyder M., Meriney S.D., Feingold E., Finegold D.N.
Am. J. Hum. Genet. 86:943-948(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LMPH1C LEU-48 AND CYS-260, VARIANTS PRO-19; GLN-125; SER-149 AND LEU-316.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF014643 Genomic DNA. Translation: AAB94511.1. Different initiation.
AL359510 Genomic DNA. Translation: CAI15069.1.
BC035840 mRNA. Translation: AAH35840.1. Different initiation.
BC089439 mRNA. Translation: AAH89439.1.
AY285161 mRNA. Translation: AAP37488.1.
CCDSCCDS1569.1.
RefSeqNP_065168.2. NM_020435.3.
UniGeneHs.100072.
Hs.743715.

3D structure databases

ProteinModelPortalQ5T442.
SMRQ5T442. Positions 6-111, 197-289.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121419. 1 interaction.
IntActQ5T442. 1 interaction.
STRING9606.ENSP00000355675.

Chemistry

GuidetoPHARMACOLOGY731.

PTM databases

PhosphoSiteQ5T442.

Polymorphism databases

DMDM74744875.

Proteomic databases

PaxDbQ5T442.
PRIDEQ5T442.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000366714; ENSP00000355675; ENSG00000198835.
GeneID57165.
KEGGhsa:57165.
UCSCuc001hsk.3. human.

Organism-specific databases

CTD57165.
GeneCardsGC01P228337.
HGNCHGNC:17494. GJC2.
MIM608803. gene.
608804. phenotype.
613206. phenotype.
613480. phenotype.
neXtProtNX_Q5T442.
Orphanet320401. Autosomal recessive spastic paraplegia type 44.
79452. Milroy disease.
280282. Pelizaeus-Merzbacher-like due to GJC2 mutation.
PharmGKBPA162389696.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG313094.
HOGENOMHOG000231126.
HOVERGENHBG009576.
InParanoidQ5T442.
KOK07619.
OMADRDSPPC.
OrthoDBEOG79SDXT.
PhylomeDBQ5T442.
TreeFamTF329606.

Enzyme and pathway databases

ReactomeREACT_11123. Membrane Trafficking.

Gene expression databases

BgeeQ5T442.
CleanExHS_GJC2.
GenevestigatorQ5T442.

Family and domain databases

InterProIPR000500. Connexin.
IPR019570. Connexin_CCC.
IPR017990. Connexin_CS.
IPR013092. Connexin_N.
[Graphical view]
PANTHERPTHR11984. PTHR11984. 1 hit.
PfamPF00029. Connexin. 1 hit.
PF10582. Connexin_CCC. 1 hit.
[Graphical view]
PRINTSPR00206. CONNEXIN.
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

GeneWikiGJC2.
GenomeRNAi57165.
NextBio63173.
PROQ5T442.
SOURCESearch...

Entry information

Entry nameCXG2_HUMAN
AccessionPrimary (citable) accession number: Q5T442
Secondary accession number(s): O43440, Q7Z7J2, Q8IWJ9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 8, 2005
Last sequence update: December 21, 2004
Last modified: July 9, 2014
This is version 102 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