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P48165 (CXA8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. 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 alpha-8 protein
Alternative name(s):
Connexin-50
Short name=Cx50
Lens fiber protein MP70
Gene names
Name:GJA8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length433 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
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. This particular connexin only forms junctional channels.

Subcellular location

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

Tissue specificity

Eye lens.

Involvement in disease

Cataract 1, multiple types (CTRCT1) [MIM:116200]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT1 includes congenital, zonular pulverulent, nuclear progressive, nuclear pulverulent, nuclear total, total, and posterior subcapsular types of cataract. Zonular or lamellar cataracts are opacities, broad or narrow, usually consisting of powdery white dots affecting only certain layers or zones between the cortex and nucleus of an otherwise clear lens. The opacity may be so dense as to render the entire central region of the lens completely opaque, or so translucent that vision is hardly if at all impeded. Zonular cataracts generally do not involve the embryonic nucleus, though sometimes they involve the fetal nucleus. Usually sharply separated from a clear cortex outside them, they may have projections from their outer edges known as riders or spokes. In some cases cataract is associated with microcornea without any other systemic anomaly or dysmorphism. Microcornea is defined by a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.4 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17

Sequence similarities

Belongs to the connexin family. Alpha-type (group II) subfamily.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 433432Gap junction alpha-8 protein
PRO_0000057830

Regions

Topological domain2 – 2322Cytoplasmic Potential
Transmembrane24 – 4623Helical; Potential
Topological domain47 – 7630Extracellular Potential
Transmembrane77 – 9923Helical; Potential
Topological domain100 – 15051Cytoplasmic Potential
Transmembrane151 – 17323Helical; Potential
Topological domain174 – 20431Extracellular Potential
Transmembrane205 – 22723Helical; Potential
Topological domain228 – 433206Cytoplasmic Potential

Natural variations

Natural variant231R → T in CTRCT1; nuclear progressive cataract. Ref.9
VAR_038797
Natural variant441V → E in CTRCT1; cataract with microcornea. Ref.12
VAR_038798
Natural variant471D → N in CTRCT1; incomplete penetrance; results in loss of function. Ref.13 Ref.15 Ref.16
VAR_069579
Natural variant481E → K in CTRCT1; zonular pulverulent. Ref.7
VAR_038799
Natural variant641V → G in CTRCT1; zonular pulverulent and nuclear progressive cataract. Ref.4 Ref.10
VAR_037642
Natural variant671D → G in CTRCT1. Ref.17
VAR_070021
Natural variant761R → C in CTRCT1. Ref.17
VAR_070022
Natural variant881P → S in CTRCT1; zonular pulverulent. Ref.6
VAR_002005
Natural variant1981R → Q in CTRCT1; cataract with microcornea. Ref.12
VAR_038800
Natural variant2471I → M Neutral polymorphism originally found in a family with cataract; does not affect gap junctions formation and gap junctional currents. Ref.8 Ref.14 Ref.17
Corresponds to variant rs80358202 [ dbSNP | Ensembl ].
VAR_038801

Experimental info

Sequence conflict110 – 1112EA → D in AAA77062. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P48165 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: D2BF6CD1C8768636

FASTA43348,229
        10         20         30         40         50         60 
MGDWSFLGNI LEEVNEHSTV IGRVWLTVLF IFRILILGTA AEFVWGDEQS DFVCNTQQPG 

        70         80         90        100        110        120 
CENVCYDEAF PISHIRLWVL QIIFVSTPSL MYVGHAVHYV RMEEKRKSRE AEELGQQAGT 

       130        140        150        160        170        180 
NGGPDQGSVK KSSGSKGTKK FRLEGTLLRT YICHIIFKTL FEVGFIVGHY FLYGFRILPL 

       190        200        210        220        230        240 
YRCSRWPCPN VVDCFVSRPT EKTIFILFML SVASVSLFLN VMELGHLGLK GIRSALKRPV 

       250        260        270        280        290        300 
EQPLGEIPEK SLHSIAVSSI QKAKGYQLLE EEKIVSHYFP LTEVGMVETS PLPAKPFNQF 

       310        320        330        340        350        360 
EEKISTGPLG DLSRGYQETL PSYAQVGAQE VEGEGPPAEE GAEPEVGEKK EEAERLTTEE 

       370        380        390        400        410        420 
QEKVAVPEGE KVETPGVDKE GEKEEPQSEK VSKQGLPAEK TPSLCPELTT DDARPLSRLS 

       430 
KASSRARSDD LTV 

« Hide

References

« Hide 'large scale' references
[1]"The human lens intrinsic membrane protein MP70 (Cx50) gene: clonal analysis and chromosome mapping."
Church R.L., Wang J.-H., Steele E.
Curr. Eye Res. 14:215-221(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Lens.
[2]Erratum
Church R.L., Wang J.-H., Steele E.
Curr. Eye Res. 14:979-981(1995) [PubMed] [Europe PMC] [Abstract]
[3]Mackay D., Shiels A.
Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"A novel mutation in GJA8 associated with autosomal dominant congenital cataract in a family in the Northeast of China."
Zheng J.Q., Ma Z.W., Sun H.M., Lin Y., Liu P., Fu S.B., Liu S.W.
Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT CTRCT1 GLY-64.
[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]"A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant 'zonular pulverulent' cataract, on chromosome 1q."
Shiels A., Mackay D., Ionides A., Berry V., Moore A., Bhattacharya S.
Am. J. Hum. Genet. 62:526-532(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CTRCT1 SER-88.
[7]"Connexin 50 mutation in a family with congenital 'zonular nuclear' pulverulent cataract of Pakistani origin."
Berry V., Mackay D., Khaliq S., Francis P.J., Hameed A., Anwar K., Mehdi S.Q., Newbold R.J., Ionides A., Shiels A., Moore T., Bhattacharya S.S.
Hum. Genet. 105:168-170(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CTRCT1 LYS-48.
[8]"Mutation in the connexin 50 gene (GJA8) in a Russian family with zonular pulverulent cataract."
Polyakov A.V., Shagina I.A., Khlebnikova O.V., Evgrafov O.V.
Clin. Genet. 60:476-478(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MET-247, INVOLVEMENT IN CTRCT1.
[9]"A novel GJA8 mutation in an Iranian family with progressive autosomal dominant congenital nuclear cataract."
Willoughby C.E., Arab S., Gandhi R., Zeinali S., Arab S., Luk D., Billingsley G., Munier F.L., Heon E.
J. Med. Genet. 40:E124-E124(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CTRCT1 THR-23.
[10]"Two novel mutations of connexin genes in Chinese families with autosomal dominant congenital nuclear cataract."
Ma Z.W., Zheng J.Q., Li J., Li X.R., Tang X., Yuan X.Y., Zhang X.M., Sun H.M.
Br. J. Ophthalmol. 89:1535-1537(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CTRCT1 GLY-64.
[11]Erratum
Ma Z.W., Zheng J.Q., Li J., Li X.R., Tang X., Yuan X.Y., Zhang X.M., Sun H.M.
Br. J. Ophthalmol. 90:125-125(2006)
[12]"Novel mutations in GJA8 associated with autosomal dominant congenital cataract and microcornea."
Devi R.R., Vijayalakshmi P.
Mol. Vis. 12:190-195(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CTRCT1 GLU-44 AND GLN-198.
[13]"A novel connexin50 mutation associated with congenital nuclear pulverulent cataracts."
Arora A., Minogue P.J., Liu X., Addison P.K., Russel-Eggitt I., Webster A.R., Hunt D.M., Ebihara L., Beyer E.C., Berthoud V.M., Moore A.T.
J. Med. Genet. 45:155-160(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CTRCT1 ASN-47, CHARACTERIZATION OF VARIANT CTRCT1 ASN-47.
[14]"The GJA8 allele encoding CX50I247M is a rare polymorphism, not a cataract-causing mutation."
Graw J., Schmidt W., Minogue P.J., Rodriguez J., Tong J.J., Klopp N., Illig T., Ebihara L., Berthoud V.M., Beyer E.C.
Mol. Vis. 15:1881-1885(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MET-247, CHARACTERIZATION OF VARIANT MET-247.
[15]"Another evidence for a D47N mutation in GJA8 associated with autosomal dominant congenital cataract."
Wang L., Luo Y., Wen W., Zhang S., Lu Y.
Mol. Vis. 17:2380-2385(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CTRCT1 ASN-47.
[16]"Genetic linkage analyses and Cx50 mutation detection in a large multiplex Chinese family with hereditary nuclear cataract."
He W., Li X., Chen J., Xu L., Zhang F., Dai Q., Cui H., Wang D.M., Yu J., Hu S., Lu S.
Ophthalmic Genet. 32:48-53(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CTRCT1 ASN-47, CHARACTERIZATION OF VARIANT CTRCT1 ASN-47.
[17]"Whole exome sequencing in dominant cataract identifies a new causative factor, CRYBA2, and a variety of novel alleles in known genes."
Reis L.M., Tyler R.C., Muheisen S., Raggio V., Salviati L., Han D.P., Costakos D., Yonath H., Hall S., Power P., Semina E.V.
Hum. Genet. 132:761-770(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CTRCT1 GLY-67 AND CYS-76, VARIANT MET-247.
+Additional computationally mapped references.

Web resources

Eye disease Gap junction protein, alpha 8 (GJA8)

Leiden Open Variation Database (LOVD)

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U34802 Genomic DNA. Translation: AAA77062.1.
AF217524 Genomic DNA. Translation: AAF32309.1.
EF672108 Genomic DNA. Translation: ABS11172.1.
AL445591 Genomic DNA. Translation: CAH72387.1.
CCDSCCDS30834.1.
PIRI39176.
RefSeqNP_005258.2. NM_005267.4.
UniGeneHs.632441.

3D structure databases

ProteinModelPortalP48165.
SMRP48165. Positions 3-227.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108970. 1 interaction.
STRING9606.ENSP00000240986.

Chemistry

GuidetoPHARMACOLOGY732.

Protein family/group databases

TCDB1.A.24.1.5. the gap junction-forming connexin (connexin) family.

PTM databases

PhosphoSiteP48165.

Polymorphism databases

DMDM13124697.

Proteomic databases

PaxDbP48165.
PRIDEP48165.

Protocols and materials databases

DNASU2703.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000240986; ENSP00000240986; ENSG00000121634.
ENST00000369235; ENSP00000358238; ENSG00000121634.
ENST00000578156; ENSP00000462620; ENSG00000264499.
ENST00000583918; ENSP00000462853; ENSG00000264499.
GeneID2703.
KEGGhsa:2703.
UCSCuc001epu.2. human.

Organism-specific databases

CTD2703.
GeneCardsGC01P147374.
HGNCHGNC:4281. GJA8.
MIM116200. phenotype.
600897. gene.
neXtProtNX_P48165.
Orphanet1377. Cataract-microcornea syndrome.
98984. Pulverulent cataract.
PharmGKBPA28692.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG299365.
HOGENOMHOG000231127.
HOVERGENHBG009576.
InParanoidP48165.
KOK07617.
OMAKPFSQFE.
OrthoDBEOG7P2XSS.
PhylomeDBP48165.
TreeFamTF329606.

Enzyme and pathway databases

ReactomeREACT_11123. Membrane Trafficking.

Gene expression databases

BgeeP48165.
CleanExHS_GJA8.
GenevestigatorP48165.

Family and domain databases

InterProIPR000500. Connexin.
IPR002266. Connexin50.
IPR019570. Connexin_CCC.
IPR017990. Connexin_CS.
IPR013092. Connexin_N.
[Graphical view]
PANTHERPTHR11984. PTHR11984. 1 hit.
PfamPF00029. Connexin. 1 hit.
PF03509. Connexin50. 1 hit.
PF10582. Connexin_CCC. 1 hit.
[Graphical view]
PRINTSPR00206. CONNEXIN.
PR01137. CONNEXINA8.
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

GeneWikiGJA8.
GenomeRNAi2703.
NextBio10688.
PROP48165.
SOURCESearch...

Entry information

Entry nameCXA8_HUMAN
AccessionPrimary (citable) accession number: P48165
Secondary accession number(s): A7L5M5, Q5VVN9, Q9NP25
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 134 of the entry and version 3 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