P17302 (CXA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gap junction alpha-1 protein

Alternative name(s):
Connexin-43
Short name=Cx43
Gap junction 43 kDa heart protein

Gene names

Name:	GJA1
Synonyms:	GJAL

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	382 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. May play a critical role in the physiology of hearing by participating in the recycling of potassium to the cochlear endolymph.
Subunit structure	A connexon is composed of a hexamer of connexins. Interacts (via C-terminus) with TJP1. Interacts (via C-terminus) with SRC (via SH3 domain) By similarity. Interacts with SGSM3. Interacts with KIAA1432/CIP150. Interacts with CNST and CSNK1D. Ref.16 Ref.17
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › gap junction.
Tissue specificity	Expressed in the heart and fetal cochlea. Ref.15
Post-translational modification	Phosphorylated at Ser-368 by PRKCG; phosphorylation induces disassembly of gap junction plaques and inhibition of gap junction activity By similarity. Phosphorylation at Ser-325, Ser-328 and Ser-330 by CK1 modulates gap junction assembly. Ref.10 Ref.16 Ref.19
Involvement in disease	Defects in GJA1 are the cause of autosomal dominant oculodentodigital dysplasia (ODDD) [MIM:164200]; also known as oculodentoosseous dysplasia. ODDD is a highly penetrant syndrome presenting with craniofacial (ocular, nasal, dental) and limb dysmorphisms, spastic paraplegia, and neurodegeneration. Craniofacial anomalies tipically include a thin nose with hypoplastic alae nasi, small anteverted nares, prominent columnella, and microcephaly. Brittle nails and hair abnormalities of hypotrichosis and slow growth are present. Ocular defects include microphthalmia, microcornea, cataracts, glaucoma, and optic atrophy. Syndactyly type 3 and conductive deafness can occur in some cases. Cardiac abnormalities are observed in rare instances. Ref.18 Ref.20 Ref.23 Ref.25 Ref.26 Ref.27 Ref.28 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Defects in GJA1 are the cause of autosomal recessive oculodentodigital dysplasia (ODDD autosomal recessive) [MIM:257850]. Defects in GJA1 may be the cause of syndactyly type 3 (SDTY3) [MIM:186100]. Syndactyly is an autosomal dominant trait and is the most common congenital anomaly of the hand or foot. It is marked by persistence of the webbing between adjacent digits, so they are more or less completely attached. In this type there is usually complete and bilateral syndactyly between the fourth and fifth fingers. Usually it is soft tissue syndactyly but occasionally the distal phalanges are fused. The fifth finger is short with absent or rudimentary middle phalanx. The feet are not affected. Ref.25 Defects in GJA1 are a cause of hypoplastic left heart syndrome (HLHS) [MIM:241550]. HLHS refers to the abnormal development of the left-sided cardiac structures, resulting in obstruction to blood flow from the left ventricular outflow tract. In addition, the syndrome includes underdevelopment of the left ventricle, aorta, and aortic arch, as well as mitral atresia or stenosis. Ref.22 Defects in GJA1 are a cause of Hallermann-Streiff syndrome (HSS) [MIM:234100]. HSS is a disorder characterized by a typical skull shape (brachycephaly with frontal bossing), hypotrichosis, microphthalmia, cataracts, beaked nose, micrognathia, skin atrophy, dental anomalies and proportionate short stature. Mental retardation is present in a minority of cases. Ref.24 Defects in GJA1 are a cause of atrioventricular septal defect type 3 (AVSD3) [MIM:600309]. A congenital heart malformation characterized by a common atrioventricular junction coexisting with deficient atrioventricular septation. The complete form involves underdevelopment of the lower part of the atrial septum and the upper part of the ventricular septum. A less severe form, known as ostium primum atrial septal defect, has a deficiency of the atrial septum. Ref.22
Sequence similarities	Belongs to the connexin family. Alpha-type (group II) subfamily.
Caution	Ref.21 reported a mutation Pro-364 linked to congenital heart diseases. Ref.12 later shown that it is an artifact. Ref.15 reported 2 mutations (Phe-11 and Ala-24) linked to non-syndromic autosomal recessive deafness (DFNBG). These mutations have subsequently been shown (Ref.20) to involve the pseudogene of connexin-43 located on chromosome 5.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Gap junction Membrane
Coding sequence diversity	Polymorphism
Disease	Cataract Disease mutation
Domain	Transmembrane Transmembrane helix
PTM	Disulfide bond Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell-cell signaling Traceable author statement. Source: ProtInc cellular membrane organization Traceable author statement. Source: Reactome gap junction assembly Traceable author statement. Source: UniProtKB muscle contraction Traceable author statement. Source: ProtInc positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype. Source: UniProtKB
Cellular component	Golgi-associated vesicle membrane Traceable author statement. Source: Reactome connexon complex Traceable author statement. Source: ProtInc endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to plasma membrane Traceable author statement. Source: UniProtKB membrane raft Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular function	ion transmembrane transporter activity Traceable author statement. Source: ProtInc signal transducer activity Inferred from mutant phenotype. Source: UniProtKB
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 – 382	381	Gap junction alpha-1 protein		PRO_0000057801
Regions
	Topological domain	2 – 13	12	Cytoplasmic Potential
	Transmembrane	14 – 36	23	Helical; Potential
	Topological domain	37 – 76	40	Extracellular Potential
	Transmembrane	77 – 99	23	Helical; Potential
	Topological domain	100 – 154	55	Cytoplasmic Potential
	Transmembrane	155 – 177	23	Helical; Potential
	Topological domain	178 – 208	31	Extracellular Potential
	Transmembrane	209 – 231	23	Helical; Potential
	Topological domain	232 – 382	151	Cytoplasmic Potential
Amino acid modifications
	Modified residue	247	1	Phosphotyrosine Ref.19
	Modified residue	262	1	Phosphoserine Ref.10
	Modified residue	306	1	Phosphoserine By similarity
	Modified residue	313	1	Phosphotyrosine Ref.19
	Modified residue	314	1	Phosphoserine By similarity
	Modified residue	325	1	Phosphoserine; by CK1 Ref.16
	Modified residue	326	1	Phosphothreonine By similarity
	Modified residue	328	1	Phosphoserine; by CK1 Ref.16
	Modified residue	330	1	Phosphoserine; by CK1 Ref.16
	Modified residue	365	1	Phosphoserine By similarity
	Modified residue	368	1	Phosphoserine; by PKC/PRKCG By similarity
	Modified residue	369	1	Phosphoserine By similarity
	Modified residue	373	1	Phosphoserine By similarity
	Disulfide bond	54 ↔ 192		Ref.9
	Disulfide bond	187 ↔ 198		Ref.9
Natural variations
	Natural variant	2	1	G → V in ODDD. Ref.35		VAR_058990
	Natural variant	7	1	L → V in ODDD. Ref.36		VAR_058991
	Natural variant	11	1	L → P in ODDD. Ref.33		VAR_058992
	Natural variant	17	1	Y → S in ODDD. Ref.20		VAR_015747
	Natural variant	18	1	S → P in ODDD. Ref.20		VAR_015748
	Natural variant	21	1	G → R in ODDD; involvement of only the fourth and fifth fingers; SDTY3. Ref.20		VAR_015749
	Natural variant	22	1	G → E in ODDD; involvement of only the fourth and fifth fingers; SDTY3. Ref.20		VAR_015750
	Natural variant	23	1	K → T in ODDD. Ref.20		VAR_015751
	Natural variant	27	1	S → P in ODDD. Ref.25		VAR_038356
	Natural variant	31	1	I → M in ODDD. Ref.25		VAR_038357
	Natural variant	40	1	A → V in ODDD. Ref.20 Ref.25 Ref.31 Ref.36		VAR_015752
	Natural variant	41	1	V → L in ectodermal and oculodentodigital dysplasia; with skin hyperkeratosis; associated with GJB2 variant His-127. Ref.30		VAR_058993
	Natural variant	49	1	Q → K in ODDD. Ref.20		VAR_015753
	Natural variant	49	1	Q → P in ODDD. Ref.36		VAR_058994
	Natural variant	49	1	Q → QQ in ODDD. Ref.36		VAR_058995
	Natural variant	52	1	F → FF in ODDD. Ref.20		VAR_015754
	Natural variant	59	1	P → H in ODDD. Ref.28		VAR_058996
	Natural variant	69	1	S → Y in ODDD. Ref.25		VAR_038358
	Natural variant	76	1	R → H in HSS; overlapping features with oculodentodigital dysplasia. Ref.24		VAR_058997
	Natural variant	76	1	R → S in ODDD. Ref.20		VAR_015755
	Natural variant	90	1	L → V in ODDD. Ref.20		VAR_015756
	Natural variant	95	1	H → R in ODDD. Ref.27		VAR_058998
	Natural variant	96	1	V → A in ODDD. Ref.36		VAR_058999
	Natural variant	96	1	V → E in ODDD. Ref.32		VAR_059000
	Natural variant	96	1	V → M in ODDD. Ref.23 Corresponds to variant rs28931601 [ dbSNP | Ensembl ].		VAR_059001
	Natural variant	98	1	Y → C in ODDD. Ref.20		VAR_015757
	Natural variant	102	1	K → N in ODDD. Ref.20		VAR_015758
	Natural variant	106	1	L → P in ODDD. Ref.36		VAR_059002
	Natural variant	110	1	E → D in ODDD. Ref.31		VAR_059003
	Natural variant	113	1	L → P in ODDD. Ref.25 Ref.32		VAR_038359
	Natural variant	124	1	D → E. Corresponds to variant rs2228966 [ dbSNP | Ensembl ].		VAR_014094
	Natural variant	130	1	I → T in ODDD. Ref.20		VAR_015759
	Natural variant	134	1	K → E in ODDD. Ref.20		VAR_015760
	Natural variant	134	1	K → N in ODDD. Ref.25		VAR_038360
	Natural variant	138	1	G → R in ODDD. Ref.20		VAR_015761
	Natural variant	143	1	G → S in SDTY3. Ref.25 Corresponds to variant rs28931600 [ dbSNP | Ensembl ].		VAR_038361
	Natural variant	147	1	M → T in ODDD. Ref.31		VAR_059004
	Natural variant	148	1	R → Q. Ref.25 Corresponds to variant rs2228960 [ dbSNP | Ensembl ].		VAR_014095
	Natural variant	154	1	T → A in ODDD. Ref.34 Ref.36		VAR_059005
	Natural variant	154	1	T → N in ODDD. Ref.32		VAR_059006
	Natural variant	168	1	A → T. Corresponds to variant rs2228961 [ dbSNP | Ensembl ].		VAR_014096
	Natural variant	169	1	Missing in ODDD.		VAR_059007
	Natural variant	185	1	Y → H. Corresponds to variant rs2228962 [ dbSNP | Ensembl ].		VAR_014097
	Natural variant	194	1	H → P in ODDD; atypical form of ODDD characterized by the predominance of the ocular involvement and by the absence of hand and/or foot syndactyly and absence of any neurologic signs. Ref.26		VAR_059008
	Natural variant	201	1	S → F in ODDD. Ref.36		VAR_059009
	Natural variant	202	1	R → C. Corresponds to variant rs2228964 [ dbSNP | Ensembl ].		VAR_014098
	Natural variant	202	1	R → H in ODDD. Ref.20 Ref.25 Ref.36		VAR_015762
	Natural variant	204	1	T → M. Corresponds to variant rs2228965 [ dbSNP | Ensembl ].		VAR_014099
	Natural variant	216	1	V → L in ODDD. Ref.20		VAR_015763
	Natural variant	220	1	S → Y in ODDD. Ref.32		VAR_059010
	Natural variant	239	1	R → W in congenital heart malformations. Ref.29 Corresponds to variant rs2227887 [ dbSNP | Ensembl ].		VAR_014100
	Natural variant	251	1	S → T in congenital heart malformations. Ref.29		VAR_059011
	Natural variant	253	1	A → P in congenital heart malformations. Ref.29		VAR_059012
	Natural variant	253	1	A → V. Ref.20 Corresponds to variant rs17653265 [ dbSNP | Ensembl ].		VAR_015764
	Natural variant	283	1	P → L in congenital heart malformations. Ref.29 Corresponds to variant rs2228974 [ dbSNP | Ensembl ].		VAR_014101
	Natural variant	290	1	T → N in congenital heart malformations. Ref.29 Corresponds to variant rs2227881 [ dbSNP | Ensembl ].		VAR_014102
	Natural variant	326	1	T → A. Ref.21		VAR_059013
	Natural variant	352	1	E → G in heart malformations. Ref.21		VAR_059014
	Natural variant	362	1	R → Q in HLHS and AVSD3; associated with Gln-376 in one individual with atrioventricular septal defect;; abolishes phosphorylation by PKA and PKC. Ref.22 Corresponds to variant rs2227885 [ dbSNP | Ensembl ].		VAR_032924
	Natural variant	364	1	S → P in heart malformations; shows abnormalities in the regulation of cell-cell communication as compared with cells expressing normal GJA1. Ref.21		VAR_059015
	Natural variant	365	1	S → N in heart malformations. Ref.21		VAR_059016
	Natural variant	373	1	S → G. Ref.21		VAR_059017
	Natural variant	376	1	R → Q in HLHS and AVSD3; associated with Gln-362 in one individual with atrioventricular septal defect; abolishes phosphorylation by PKA and PKC. Ref.22		VAR_032925

Sequences

	Sequence		Length	Mass (Da)
	P17302 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 7DDDAD8040284176	FASTA	382	43,008
	10 20 30 40 50 60 MGDWSALGKL LDKVQAYSTA GGKVWLSVLF IFRILLLGTA VESAWGDEQS AFRCNTQQPG 70 80 90 100 110 120 CENVCYDKSF PISHVRFWVL QIIFVSVPTL LYLAHVFYVM RKEEKLNKKE EELKVAQTDG 130 140 150 160 170 180 VNVDMHLKQI EIKKFKYGIE EHGKVKMRGG LLRTYIISIL FKSIFEVAFL LIQWYIYGFS 190 200 210 220 230 240 LSAVYTCKRD PCPHQVDCFL SRPTEKTIFI IFMLVVSLVS LALNIIELFY VFFKGVKDRV 250 260 270 280 290 300 KGKSDPYHAT SGALSPAKDC GSQKYAYFNG CSSPTAPLSP MSPPGYKLVT GDRNNSSCRN 310 320 330 340 350 360 YNKQASEQNW ANYSAEQNRM GQAGSTISNS HAQPFDFPDD NQNSKKLAAG HELQPLAIVD 370 380 QRPSSRASSR ASSRPRPDDL EI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular characterization and functional expression of the human cardiac gap junction channel." Fishman G.I., Spray D.C., Leinwand L.A. J. Cell Biol. 111:589-598(1990) [PubMed: 1696265] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Heart muscle.
[2]	"The human connexin gene family of gap junction proteins: distinct chromosomal locations but similar structures." Fishman G.I., Eddy R.L., Shows T.B., Rosenthal L., Leinwand L.A. Genomics 10:250-256(1991) [PubMed: 1646158] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Sporadic cases of dilated cardiomyopathies associated with atrioventricular conduction defects are not linked to mutation within the connexins 40 and 43 genes." Haefliger J.-A., Goy J.J., Waeber G. Eur. Heart J. 20:1843-1843(1999) [PubMed: 10581143] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[6]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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]. Tissue: Brain.
[9]	"Intercellular calcium signaling via gap junction in connexin-43-transfected cells." Toyofuku T., Yabuki M., Otsu K., Kuzuya T., Hori M., Tada M. J. Biol. Chem. 273:1519-1528(1998) [PubMed: 9430691] [Abstract] Cited for: DISULFIDE BONDS.
[10]	"Phosphorylation of serine 262 in the gap junction protein connexin-43 regulates DNA synthesis in cell-cell contact forming cardiomyocytes." Doble B.W., Dang X., Ping P., Fandrich R.R., Nickel B.E., Jin Y., Cattini P.A., Kardami E. J. Cell Sci. 117:507-514(2004) [PubMed: 14702389] [Abstract] Cited for: PHOSPHORYLATION AT SER-262.
[11]	"Connexin expression and turnover: implications for cardiac excitability." Saffitz J.E., Laing J.G., Yamada K.A. Circ. Res. 86:723-728(2000) [PubMed: 10764404] [Abstract] Cited for: REVIEW.
[12]	"Failure to detect connexin43 mutations in 38 cases of sporadic and familial heterotaxy." Gebbia M., Towbin J.A., Casey B. Circulation 94:1909-1912(1996) [PubMed: 8873667] [Abstract] Cited for: SHOWS THAT HEART LATERALIZATION DEFECT ARE NOT DUE TO GJA1.
[13]	"Absence of mutations in the regulatory domain of the gap junction protein connexin 43 in patients with visceroatrial heterotaxy." Penman Splitt M., Tsai M.Y., Burn J., Goodship J.A. Heart 77:369-370(1997) [PubMed: 9155619] [Abstract] Cited for: SHOWS THAT HEART LATERALIZATION DEFECT ARE NOT DUE TO GJA1.
[14]	"Connexin43 gene mutations and heterotaxy." Toth T., Hajdu J., Marton T., Nagy B., Papp Z. Circulation 97:117-118(1998) [PubMed: 9443444] [Abstract] Cited for: SHOWS THAT HEART LATERALIZATION DEFECT ARE NOT DUE TO GJA1.
[15]	"Mutations in GJA1 (connexin 43) are associated with non-syndromic autosomal recessive deafness." Liu X.Z., Xia X.J., Adams J., Chen Z.Y., Welch K.O., Tekin M., Ouyang X.M., Kristiansen A., Pandya A., Balkany T., Arnos K.S., Nance W.E. Hum. Mol. Genet. 10:2945-2951(2001) [PubMed: 11741837] [Abstract] Cited for: ASSOCIATION WITH NON-SYNDROMIC AUTOSOMAL RECESSIVE DEAFNESS, TISSUE SPECIFICITY.
[16]	"Casein kinase 1 regulates connexin-43 gap junction assembly." Cooper C.D., Lampe P.D. J. Biol. Chem. 277:44962-44968(2002) [PubMed: 12270943] [Abstract] Cited for: PHOSPHORYLATION AT SER-325; SER-328 AND SER-330 BY CSNK1D/CK1, INTERACTION WITH CSNK1D.
[17]	"Molecular cloning and functional analysis of a novel Cx43 partner protein CIP150." Akiyama M., Ishida N., Ogawa T., Yogo K., Takeya T. Biochem. Biophys. Res. Commun. 335:1264-1271(2005) [PubMed: 16112082] [Abstract] Cited for: INTERACTION WITH KIAA1432.
[18]	"A nonsense mutation in the first transmembrane domain of connexin 43 underlies autosomal recessive oculodentodigital syndrome." Richardson R.J., Joss S., Tomkin S., Ahmed M., Sheridan E., Dixon M.J. J. Med. Genet. 43:E37-E37(2006) [PubMed: 16816024] [Abstract] Cited for: INVOLVEMENT IN ODDD AUTOSOMAL RECESSIVE.
[19]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-247 AND TYR-313, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[20]	"Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia." Paznekas W.A., Boyadjiev S.A., Shapiro R.E., Daniels O., Wollnik B., Keegan C.E., Innis J.W., Dinulos M.B., Christian C., Hannibal M.C., Jabs E.W. Am. J. Hum. Genet. 72:408-418(2003) [PubMed: 12457340] [Abstract] Cited for: NON-ASSOCIATION WITH NON-SYNDROMIC AUTOSOMAL RECESSIVE DEAFNESS, VARIANTS ODDD SER-17; PRO-18; ARG-21; GLU-22; THR-23; VAL-40; LYS-49; PHE-52 INS; SER-76; VAL-90; CYS-98; ASN-102; THR-130; GLU-134; ARG-138; HIS-202 AND LEU-216, VARIANT VAL-253.
[21]	"Mutations of the connexin43 gap-junction gene in patients with heart malformations and defects of laterality." Britz-Cunningham S.H., Shah M.M., Zuppan C.W., Fletcher W.H. N. Engl. J. Med. 332:1323-1329(1995) [PubMed: 7715640] [Abstract] Cited for: VARIANTS HEART MALFORMATIONS GLY-352; PRO-364 AND ASN-365, VARIANTS ALA-326 AND GLY-373, CHARACTERIZATION OF VARIANT HEART MALFORMATIONS PRO-364.
[22]	"Identification of connexin43 (alpha1) gap junction gene mutations in patients with hypoplastic left heart syndrome by denaturing gradient gel electrophoresis (DGGE)." Dasgupta C., Martinez A.-M., Zuppan C.W., Shah M.M., Bailey L.L., Fletcher W.H. Mutat. Res. 479:173-186(2001) [PubMed: 11470490] [Abstract] Cited for: VARIANTS HLHS GLN-362 AND GLN-376, VARIANTS AVSD3 GLN-362 AND GLN-376, CHARACTERIZATION OF VARIANTS HLHS GLN-362 AND GLN-376.
[23]	"Novel Connexin 43 (GJA1) mutation causes oculo-dento-digital dysplasia with curly hair." Kjaer K.W., Hansen L., Eiberg H., Leicht P., Opitz J.M., Tommerup N. Am. J. Med. Genet. A 127:152-157(2004) [PubMed: 15108203] [Abstract] Cited for: VARIANT ODDD MET-96.
[24]	"A homozygous GJA1 gene mutation causes a Hallermann-Streiff/ODDD spectrum phenotype." Pizzuti A., Flex E., Mingarelli R., Salpietro C., Zelante L., Dallapiccola B. Hum. Mutat. 23:286-286(2004) [PubMed: 14974090] [Abstract] Cited for: VARIANT HSS HIS-76.
[25]	"Expression of Gja1 correlates with the phenotype observed in oculodentodigital syndrome/type III syndactyly." Richardson R.R., Donnai D., Meire F., Dixon M.J. J. Med. Genet. 41:60-67(2004) [PubMed: 14729836] [Abstract] Cited for: VARIANTS ODDD PRO-27; MET-31; VAL-40; TYR-69; PRO-113; ASN-134; GLN-148 AND HIS-202, VARIANT SDTY3 SER-143.
[26]	"A novel GJA1 mutation causes oculodentodigital dysplasia without syndactyly." Vitiello C., D'Adamo P., Gentile F., Vingolo E.M., Gasparini P., Banfi S. Am. J. Med. Genet. A 133:58-60(2005) [PubMed: 15637728] [Abstract] Cited for: VARIANT ODDD PRO-194.
[27]	"Letter to the editor: Novel GJA1 mutation in oculodentodigital dysplasia." Honkaniemi J., Kalkkila J.P., Koivisto P., Kahara V., Latvala T., Simola K. Am. J. Med. Genet. A 139:48-49(2005) [PubMed: 16222672] [Abstract] Cited for: VARIANT ODDD ARG-95.
[28]	"A novel mutation in the GJA1 gene in a family with oculodentodigital dysplasia." Vasconcellos J.P.C., Melo M.B., Schimiti R.B., Bressanim N.C., Costa F.F., Costa V.P. Arch. Ophthalmol. 123:1422-1426(2005) [PubMed: 16219735] [Abstract] Cited for: VARIANT ODDD HIS-59.
[29]	"Mutations of connexin43 in fetuses with congenital heart malformations." Chen P., Xie L.-J., Huang G.-Y., Zhao X.-Q., Chang C. Chin. Med. J. 118:971-976(2005) [PubMed: 15978203] [Abstract] Cited for: VARIANTS CONGENITAL HEART MALFORMATIONS TRP-239; THR-251; PRO-253; LEU-283 AND ASN-290.
[30]	"Bigenic connexin mutations in a patient with hidrotic ectodermal dysplasia." Kellermayer R., Keller M., Ratajczak P., Richardson E., Harangi F., Merei E., Melegh B., Kosztolanyi G., Richard G. Eur. J. Dermatol. 15:75-79(2005) [PubMed: 15757815] [Abstract] Cited for: VARIANT ECTODERMAL AND OCULODENTODIGITAL DYSPLASIA LEU-41.
[31]	"Novel GJA1 mutations in patients with oculo-dento-digital dysplasia (ODDD)." Debeer P., Van Esch H., Huysmans C., Pijkels E., De Smet L., Van de Ven W., Devriendt K., Fryns J.-P. Eur. J. Med. Genet. 48:377-387(2005) [PubMed: 16378922] [Abstract] Cited for: VARIANTS ODDD VAL-40; ASP-110; THR-147 AND PHE-169 DEL.
[32]	"Clinical and genetic variability of oculodentodigital dysplasia." Wiest T., Herrmann O., Stoegbauer F., Grasshoff U., Enders H., Koch M.J., Grond-Ginsbach C., Schwaninger M. Clin. Genet. 70:71-72(2006) [PubMed: 16813608] [Abstract] Cited for: VARIANTS ODDD GLU-96; PRO-113; ASN-154 AND TYR-220.
[33]	"A novel GJA 1 mutation in oculo-dento-digital dysplasia with curly hair and hyperkeratosis." Kelly S.C., Ratajczak P., Keller M., Purcell S.M., Griffin T., Richard G. Eur. J. Dermatol. 16:241-245(2006) [PubMed: 16709485] [Abstract] Cited for: VARIANT ODDD PRO-11.
[34]	"Oculodentodigital dysplasia with mandibular retrognathism and absence of syndactyly: a case report with a novel mutation in the connexin 43 gene." van Es R.J.J., Wittebol-Post D., Beemer F.A. Int. J. Oral Maxillofac. Surg. 36:858-860(2007) [PubMed: 17509830] [Abstract] Cited for: VARIANT ODDD ALA-154.
[35]	"A new GJA1 (connexin 43) mutation causing oculodentodigital dysplasia associated to uncommon features." de la Parra D.R., Zenteno J.C. Ophthalmic Genet. 28:198-202(2007) [PubMed: 18161618] [Abstract] Cited for: VARIANT ODDD VAL-2.
[36]	"GJA1 mutations, variants, and connexin 43 dysfunction as it relates to the oculodentodigital dysplasia phenotype." Paznekas W.A., Karczeski B., Vermeer S., Lowry R.B., Delatycki M., Laurence F., Koivisto P.A., Van Maldergem L., Boyadjiev S.A., Bodurtha J.N., Jabs E.W. Hum. Mutat. 30:724-733(2009) [PubMed: 19338053] [Abstract] Cited for: VARIANTS ODDD VAL-7; VAL-40; PRO-49; GLN-49 INS; ALA-96; PRO-106; ALA-154; PHE-201 AND HIS-202.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	X52947 mRNA. Translation: CAA37122.1. M65188 mRNA. Translation: AAA52131.1. AF151980 Genomic DNA. Translation: AAD37802.2. CR541660 mRNA. Translation: CAG46461.1. AK312324 mRNA. Translation: BAG35246.1. AL139098 Genomic DNA. Translation: CAI20002.1. CH471051 Genomic DNA. Translation: EAW48178.1. BC026329 mRNA. Translation: AAH26329.1.
IPI	IPI00218487.
PIR	A35853.
RefSeq	NP_000156.1. NM_000165.3.
UniGene	Hs.74471.
3D structure databases
ProteinModelPortal	P17302.
SMR	P17302. Positions 3-234, 255-382.
ModBase	Search...
Protein-protein interaction databases
IntAct	P17302. 2 interactions.
MINT	MINT-147603.
STRING	P17302.
PTM databases
PhosphoSite	P17302.
Polymorphism databases
DMDM	117706.
Proteomic databases
PeptideAtlas	P17302.
PRIDE	P17302.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000282561; ENSP00000282561; ENSG00000152661.
GeneID	2697.
KEGG	hsa:2697.
UCSC	uc003pyr.1. human.
Organism-specific databases
CTD	2697.
GeneCards	GC06P121798.
H-InvDB	HIX0006183.
HGNC	HGNC:4274. GJA1.
HPA	CAB010753.
MIM	121014. gene. 164200. phenotype. 186100. phenotype. 234100. phenotype. 241550. phenotype. 257850. phenotype. 600309. phenotype.
neXtProt	NX_P17302.
Orphanet	90636. Autosomal recessive nonsyndromic sensorineural deafness type DFNB. 2248. Hypoplastic left heart syndrome. 2710. Oculodentodigital dysplasia. 93404. Syndactyly type 3.
PharmGKB	PA28685.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG06210.
HOGENOM	HBG717760.
HOVERGEN	HBG009576.
InParanoid	P17302.
OMA	TDGANVD.
OrthoDB	EOG402WSC.
PhylomeDB	P17302.
Enzyme and pathway databases
Reactome	REACT_11123. Membrane Trafficking.
Gene expression databases
ArrayExpress	P17302.
Bgee	P17302.
CleanEx	HS_GJA1.
Genevestigator	P17302.
GermOnline	ENSG00000152661. Homo sapiens.
Family and domain databases
InterPro	IPR000500. Connexin. IPR002261. Connexin43. IPR013124. Connexin43_C. IPR019570. Connexin_CCC. IPR017990. Connexin_CS. IPR013092. Connexin_N. [Graphical view]
KO	K07372.
PANTHER	PTHR11984. Connexin. 1 hit.
Pfam	PF00029. Connexin. 1 hit. PF03508. Connexin43. 1 hit. PF10582. Connexin_CCC. 1 hit. [Graphical view]
PRINTS	PR00206. CONNEXIN. PR01132. CONNEXINA1.
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
DrugBank	DB01136. Carvedilol.
NextBio	10668.
SOURCE	Search...

Entry information

Entry name

CXA1_HUMAN

Accession

Primary (citable) accession number: P17302
Secondary accession number(s): B2R5U9, Q6FHU1, Q9Y5I8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 153 of the entry and version 2 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.