Q9Y6H8 (CXA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gap junction alpha-3 protein

Alternative name(s):
Connexin-46
Short name=Cx46

Gene names

Name:

GJA3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	435 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 is a component of lens fiber gap junctions, can form both junctional and non-junctional ("hemi-") channels.
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › gap junction.
Involvement in disease	Defects in GJA3 are the cause of cataract zonular pulverulent cataract type 3 (CZP3) [MIM:601885]. A form of zonular 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. Ref.1 Ref.4 Ref.6 Ref.12 Defects in GJA3 are a cause of cataract autosomal dominant (ADC) [MIM:604219]. Cataract is 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. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. Ref.5 Ref.7 Ref.8 Ref.9 Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20
Sequence similarities	Belongs to the connexin family. Alpha-type (group II) subfamily.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Gap junction Membrane
Coding sequence diversity	Polymorphism
Disease	Cataract Disease mutation
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell-cell signaling Traceable author statement. Source: ProtInc visual perception Traceable author statement. Source: ProtInc
Cellular component	connexon complex Inferred from electronic annotation. Source: InterPro integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 435	434	Gap junction alpha-3 protein		PRO_0000057810
Regions
	Topological domain	2 – 19	18	Cytoplasmic Potential
	Transmembrane	20 – 40	21	Helical; Potential
	Topological domain	41 – 76	36	Extracellular Potential
	Transmembrane	77 – 97	21	Helical; Potential
	Topological domain	98 – 152	55	Cytoplasmic Potential
	Transmembrane	153 – 173	21	Helical; Potential
	Topological domain	174 – 201	28	Extracellular Potential
	Transmembrane	202 – 222	21	Helical; Potential
	Topological domain	223 – 435	213	Cytoplasmic Potential
Natural variations
	Natural variant	2	1	G → D in ADC; nuclear pulverulent and posterior polar cataract; the mutant affects the formation of gap junction plaques; affects hemichannel permeability. Ref.17		VAR_066710
	Natural variant	3	1	D → Y in CZP3. Ref.12		VAR_066711
	Natural variant	11	1	L → S in cataract; autosomal dominant congenital/infantile "ant-egg" cataract. Ref.13		VAR_030020
	Natural variant	28	1	V → M in ADC. Ref.11		VAR_066712
	Natural variant	32	1	F → L in ADC; nuclear pulverulent cataract. Ref.5		VAR_030021
	Natural variant	33	1	R → L in ADC. Ref.15		VAR_066713
	Natural variant	44	1	V → M in ADC; nuclear cataract. Ref.16 Ref.20		VAR_066714
	Natural variant	45	1	W → S in ADC; nuclear progressive cataract. Ref.9		VAR_038796
	Natural variant	47	1	D → N in ADC; nuclear cataract. Ref.18		VAR_066715
	Natural variant	59	1	P → L in ADC; nuclear punctate cataract. Ref.7		VAR_030022
	Natural variant	63	1	N → S in CZP3. Ref.1		VAR_009158
	Natural variant	76	1	R → G in ADC. Ref.11		VAR_066716
	Natural variant	76	1	R → H in CZP3; not fully penetrant mutation. Ref.6		VAR_030023
	Natural variant	87	1	T → M in ADC; pearl box cataract. Ref.14		VAR_066717
	Natural variant	187	1	P → L in CZP3. Ref.4		VAR_023447
	Natural variant	187	1	P → S in ADC; central nuclear cataract with punctate opacities. Ref.19		VAR_066718
	Natural variant	188	1	N → T in ADC; nuclear pulverulent cataract. Ref.8		VAR_066719
	Natural variant	299	1	L → M. Ref.1 Ref.3 Corresponds to variant rs968566 [ dbSNP | Ensembl ].		VAR_022426

Sequences

	Sequence		Length	Mass (Da)
	Q9Y6H8 [UniParc]. Last modified November 2, 2010. Version 4. Checksum: 6DE161AE6476EB40	FASTA	435	47,410
	10 20 30 40 50 60 MGDWSFLGRL LENAQEHSTV IGKVWLTVLF IFRILVLGAA AEDVWGDEQS DFTCNTQQPG 70 80 90 100 110 120 CENVCYDRAF PISHIRFWAL QIIFVSTPTL IYLGHVLHIV RMEEKKKERE EEEQLKRESP 130 140 150 160 170 180 SPKEPPQDNP SSRDDRGRVR MAGALLRTYV FNIIFKTLFE VGFIAGQYFL YGFELKPLYR 190 200 210 220 230 240 CDRWPCPNTV DCFISRPTEK TIFIIFMLAV ACASLLLNML EIYHLGWKKL KQGVTSRLGP 250 260 270 280 290 300 DASEAPLGTA DPPPLPPSSR PPAVAIGFPP YYAHTAAPLG QARAVGYPGA PPPAADFKLL 310 320 330 340 350 360 ALTEARGKGQ SAKLYNGHHH LLMTEQNWAN QAAERQPPAL KAYPAASTPA APSPVGSSSP 370 380 390 400 410 420 PLAHEAEAGA APLLLDGSGS SLEGSALAGT PEEEEQAVTT AAQMHQPPLP LGDPGRASKA 430 SRASSGRARP EDLAI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Connexin46 mutations in autosomal dominant congenital cataract." Mackay D., Ionides A., Kibar Z., Rouleau G., Berry V., Moore A., Shiels A., Bhattacharya S. Am. J. Hum. Genet. 64:1357-1364(1999) [PubMed: 10205266] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS CZP3 SER-63 AND MET-299. Tissue: Lens fibers.
[2]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed: 15057823] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MET-299.
[4]	"Further evidence of autosomal dominant congenital zonular pulverulent cataracts linked to 13q11 (CZP3) and a novel mutation in connexin 46 (GJA3)." Rees M.I., Watts P., Fenton I., Clarke A., Snell R.G., Owen M.J., Gray J. Hum. Genet. 106:206-209(2000) [PubMed: 10746562] [Abstract] Cited for: VARIANT CZP3 LEU-187.
[5]	"A novel mutation in GJA3 (connexin46) for autosomal dominant congenital nuclear pulverulent cataract." Jiang H., Jin Y., Bu L., Zhang W., Liu J., Cui B., Kong X., Hu L. Mol. Vis. 9:579-583(2003) [PubMed: 14627959] [Abstract] Cited for: VARIANT ADC LEU-32.
[6]	"A novel mutation in the Connexin 46 gene causes autosomal dominant congenital cataract with incomplete penetrance." Burdon K.P., Wirth M.G., Mackey D.A., Russell-Eggitt I.M., Craig J.E., Elder J.E., Dickinson J.L., Sale M.M. J. Med. Genet. 41:E106-E106(2004) [PubMed: 15286166] [Abstract] Cited for: VARIANT CZP3 HIS-76.
[7]	"A novel missense mutation in the gene for gap-junction protein alpha3 (GJA3) associated with autosomal dominant 'nuclear punctate' cataracts linked to chromosome 13q." Bennett T.M., Mackay D.S., Knopf H.L.S., Shiels A. Mol. Vis. 10:376-382(2004) [PubMed: 15208569] [Abstract] Cited for: VARIANT ADC LEU-59.
[8]	"A novel connexin46 (GJA3) mutation in autosomal dominant congenital nuclear pulverulent cataract." Li Y., Wang J., Dong B., Man H. Mol. Vis. 10:668-671(2004) [PubMed: 15448617] [Abstract] Cited for: VARIANT ADC THR-188.
[9]	"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: 16234473] [Abstract] Cited for: VARIANT ADC SER-45.
[10]	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)
[11]	"Novel mutations in GJA3 associated with autosomal dominant congenital cataract in the Indian population." Devi R.R., Reena C., Vijayalakshmi P. Mol. Vis. 11:846-852(2005) [PubMed: 16254549] [Abstract] Cited for: VARIANTS ADC MET-28 AND GLY-76.
[12]	"A novel mutation in the connexin 46 gene (GJA3) causes autosomal dominant zonular pulverulent cataract in a Hispanic family." Addison P.K., Berry V., Holden K.R., Espinal D., Rivera B., Su H., Srivastava A.K., Bhattacharya S.S. Mol. Vis. 12:791-795(2006) [PubMed: 16885921] [Abstract] Cited for: VARIANT CZP3 TYR-3.
[13]	"The congenital 'ant-egg' cataract phenotype is caused by a missense mutation in connexin46." Hansen L., Yao W., Eiberg H., Funding M., Riise R., Kjaer K.W., Hejtmancik J.F., Rosenberg T. Mol. Vis. 12:1033-1039(2006) [PubMed: 16971895] [Abstract] Cited for: VARIANT ADC SER-11.
[14]	"A novel 'pearl box' cataract associated with a mutation in the connexin 46 (GJA3) gene." Guleria K., Vanita V., Singh D., Singh J.R. Mol. Vis. 13:797-803(2007) [PubMed: 17615540] [Abstract] Cited for: VARIANT ADC MET-87.
[15]	"A novel mutation in the connexin 46 (GJA3) gene associated with autosomal dominant congenital cataract in an Indian family." Guleria K., Sperling K., Singh D., Varon R., Singh J.R., Vanita V. Mol. Vis. 13:1657-1665(2007) [PubMed: 17893674] [Abstract] Cited for: VARIANT ADC LEU-33.
[16]	"Mutation analysis of congenital cataract in a Chinese family identified a novel missense mutation in the connexin 46 gene (GJA3)." Zhou Z., Hu S., Wang B., Zhou N., Zhou S., Ma X., Qi Y. Mol. Vis. 16:713-719(2010) [PubMed: 20431721] [Abstract] Cited for: VARIANT ADC MET-44.
[17]	"A novel GJA3 mutation associated with congenital nuclear pulverulent and posterior polar cataract in a chinese family." Yao K., Wang W., Zhu Y., Jin C., Shentu X., Jiang J., Zhang Y., Ni S. Hum. Mutat. 32:1367-1370(2011) [PubMed: 21681855] [Abstract] Cited for: VARIANT ADC ASP-2, CHARACTERIZATION OF VARIANT ADC ASP-2.
[18]	"A novel mutation in the GJA3 (connexin46) gene is associated with autosomal dominant congenital nuclear cataract in a Chinese family." Yang G., Xing B., Liu G., Lu X., Jia X., Lu X., Wang X., Yu H., Fu Y., Zhao J. Mol. Vis. 17:1070-1073(2011) [PubMed: 21552498] [Abstract] Cited for: VARIANT ADC ASN-47.
[19]	"A novel mutation in the connexin 46 (GJA3) gene associated with congenital cataract in a Chinese pedigree." Ding X., Wang B., Luo Y., Hu S., Zhou G., Zhou Z., Wang J., Ma X., Qi Y. Mol. Vis. 17:1343-1349(2011) [PubMed: 21647269] [Abstract] Cited for: VARIANT ADC SER-187.
[20]	"A recurrent missense mutation in GJA3 associated with autosomal dominant cataract linked to chromosome 13q." Bennett T.M., Shiels A. Mol. Vis. 17:2255-2262(2011) [PubMed: 21897748] [Abstract] Cited for: VARIANT ADC MET-44.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF075290 Genomic DNA. Translation: AAD42925.1. AL138688 Genomic DNA. No translation available. BC121137 mRNA. Translation: AAI21138.1.
IPI	IPI00221385.
RefSeq	NP_068773.2. NM_021954.3.
UniGene	Hs.130313.
3D structure databases
ProteinModelPortal	Q9Y6H8.
SMR	Q9Y6H8. Positions 3-228, 308-435.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9Y6H8.
Protein family/group databases
TCDB	1.A.24.1.5. gap junction-forming connexin family.
PTM databases
PhosphoSite	Q9Y6H8.
Polymorphism databases
DMDM	311033478.
Proteomic databases
PRIDE	Q9Y6H8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000241125; ENSP00000241125; ENSG00000121743.
GeneID	2700.
KEGG	hsa:2700.
UCSC	uc001umx.1. human.
Organism-specific databases
CTD	2700.
GeneCards	GC13M020712.
H-InvDB	HIX0037357.
HGNC	HGNC:4277. GJA3.
MIM	121015. gene. 601885. phenotype. 604219. phenotype.
neXtProt	NX_Q9Y6H8.
Orphanet	98984. Pulverulent cataract.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG08744.
GeneTree	ENSGT00560000076859.
HOGENOM	HBG717760.
HOVERGEN	HBG009576.
InParanoid	Q9Y6H8.
OMA	EQNWANQ.
OrthoDB	EOG4868D1.
PhylomeDB	Q9Y6H8.
Enzyme and pathway databases
Reactome	REACT_11123. Membrane Trafficking.
Gene expression databases
ArrayExpress	Q9Y6H8.
Bgee	Q9Y6H8.
CleanEx	HS_GJA3.
Genevestigator	Q9Y6H8.
GermOnline	ENSG00000121743. Homo sapiens.
Family and domain databases
InterPro	IPR000500. Connexin. IPR002262. Connexin46. IPR019570. Connexin_CCC. IPR017990. Connexin_CS. IPR013092. Connexin_N. [Graphical view]
KO	K07612.
PANTHER	PTHR11984. Connexin. 1 hit.
Pfam	PF00029. Connexin. 1 hit. PF10582. Connexin_CCC. 1 hit. [Graphical view]
PRINTS	PR00206. CONNEXIN. PR01133. CONNEXINA3.
SMART	SM00037. CNX. 1 hit. SM01089. Connexin_CCC. 1 hit. [Graphical view]
PROSITE	PS00407. CONNEXINS_1. 1 hit. PS00408. CONNEXINS_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

CXA3_HUMAN

Accession

Primary (citable) accession number: Q9Y6H8
Secondary accession number(s): Q0VAB7, Q9H537

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	November 2, 2010
Last modified:	January 25, 2012
This is version 102 of the entry and version 4 of the sequence. [Complete history]

Entry status

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.