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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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	Gap junction protein that acts as a regulator of bladder capacity. A 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. Negative regulator of bladder functional capacity: acts by enhancing intercellular electrical and chemical transmission, thus sensitizing bladder muscles to cholinergic neural stimuli and causing them to contract By similarity.
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). Interacts with UBQLN4 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 Ref.22.
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.18 Sumoylated with SUMO1, SUMO2 and SUMO3, which may regulate the level of functional Cx43 gap junctions at the plasma membrane. May be desumoylated by SENP1 or SENP2. Ref.22 S-nitrosylation at Cys-271 is enriched at the muscle endothelial gap junction in arteries, it augments channel permeability and may regulate of smooth muscle cell to endothelial cell communication.
Involvement in disease	Oculodentodigital dysplasia (ODDD) [MIM:164200]: A disease characterized by a typical facial appearance and variable involvement of the eyes, dentition, and fingers. Characteristic facial features include a narrow, pinched nose with hypoplastic alae nasi, prominent columella and thin anteverted nares together with a narrow nasal bridge, and prominent epicanthic folds giving the impression of hypertelorism. The teeth are usually small and carious. Typical eye findings include microphthalmia and microcornea. The characteristic digital malformation is complete syndactyly of the fourth and fifth fingers (syndactyly type III) but the third finger may be involved and associated camptodactyly is a common finding. Cardiac abnormalities are observed in rare instances. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19 Ref.20 Ref.25 Ref.27 Ref.28 Ref.29 Ref.30 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Oculodentodigital dysplasia, autosomal recessive (ODDD-AR) [MIM:257850]: A disease characterized by a typical facial appearance and variable involvement of the eyes, dentition, and fingers. Characteristic facial features include a narrow, pinched nose with hypoplastic alae nasi, prominent columella and thin anteverted nares together with a narrow nasal bridge, and prominent epicanthic folds giving the impression of hypertelorism. The teeth are usually small and carious. Typical eye findings include microphthalmia and microcornea. The characteristic digital malformation is complete syndactyly of the fourth and fifth fingers (syndactyly type III) but the third finger may be involved and associated camptodactyly is a common finding. Cardiac abnormalities are observed in rare instances. Note: The disease is caused by mutations affecting the gene represented in this entry. Syndactyly 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. Note: The disease may be caused by mutations affecting the gene represented in this entry. Ref.27 Hypoplastic left heart syndrome 1 (HLHS1) [MIM:241550]: A syndrome due to defective development of the aorta proximal to the entrance of the ductus arteriosus, and hypoplasia of the left ventricle and mitral valve. As a result of the abnormal circulation, the ductus arteriosus and foramen ovale are patent and the right atrium, right ventricle, and pulmonary artery are enlarged. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.24 Hallermann-Streiff syndrome (HSS) [MIM:234100]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.26 Atrioventricular septal defect 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; the valve itself is also shared. A less severe form, known as ostium primum atrial septal defect, is characterized by separate atrioventricular valvar orifices despite a common junction. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.24
Sequence similarities	Belongs to the connexin family. Alpha-type (group II) subfamily.
Caution	Ref.23 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 Isopeptide bond Phosphoprotein S-nitrosylation Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ATP transport Inferred from electronic annotation. Source: Compara apoptotic process Inferred from electronic annotation. Source: Compara cell communication by electrical coupling Inferred from direct assay PubMed 16790700PubMed 23348765. Source: BHF-UCL cellular membrane organization Traceable author statement. Source: Reactome gap junction assembly Traceable author statement PubMed 15709751. Source: UniProtKB heart development Traceable author statement Ref.23. Source: ProtInc muscle contraction Traceable author statement Ref.23. Source: ProtInc negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara neuron projection morphogenesis Inferred from electronic annotation. Source: Compara positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype PubMed 12761501. Source: UniProtKB positive regulation of protein catabolic process Inferred from electronic annotation. Source: Compara protein oligomerization Inferred from electronic annotation. Source: Compara regulation of atrial cardiac muscle cell action potential Traceable author statement PubMed 23348765. Source: BHF-UCL regulation of calcium ion transport Inferred from electronic annotation. Source: Compara regulation of tight junction assembly Inferred from electronic annotation. Source: Compara response to pH Inferred from electronic annotation. Source: Compara response to peptide hormone stimulus Inferred from electronic annotation. Source: Compara vascular transport Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi-associated vesicle membrane Traceable author statement. Source: Reactome connexon complex Traceable author statement PubMed 1850831. Source: ProtInc early endosome Inferred from electronic annotation. Source: Compara endoplasmic reticulum membrane Traceable author statement. Source: Reactome fascia adherens Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement PubMed 15709751. Source: UniProtKB intercalated disc Inferred from direct assay PubMed 22889254. Source: BHF-UCL lysosome Inferred from electronic annotation. Source: Compara membrane raft Inferred from sequence or structural similarity. Source: BHF-UCL mitochondrial outer membrane Inferred from electronic annotation. Source: Compara multivesicular body Inferred from electronic annotation. Source: Compara
Molecular_function	gap junction channel activity Inferred from direct assay PubMed 16790700PubMed 23348765. Source: BHF-UCL ion transmembrane transporter activity Traceable author statement Ref.1. Source: ProtInc signal transducer activity Inferred from mutant phenotype PubMed 12761501. 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 By similarity

Modified residue

255

1

Phosphoserine Ref.18 Ref.21

Modified residue

262

1

Phosphoserine Ref.10 Ref.18

Modified residue

271

1

S-nitrosocysteine By similarity

Modified residue

306

1

Phosphoserine Ref.21

Modified residue

313

1

Phosphotyrosine By similarity

Modified residue

314

1

Phosphoserine Ref.21

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

344

1

Phosphoserine Ref.21

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

Cross-link

144

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.22

Cross-link

237

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.22

Natural variations

Natural variant

2

1

G → V in ODDD. Ref.37

VAR_058990

Natural variant

7

1

L → V in ODDD. Ref.38

VAR_058991

Natural variant

11

1

L → P in ODDD. Ref.35

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.27

VAR_038356

Natural variant

31

1

I → M in ODDD. Ref.27

VAR_038357

Natural variant

40

1

A → V in ODDD. Ref.20 Ref.27 Ref.33 Ref.38

VAR_015752

Natural variant

41

1

V → L in ectodermal and oculodentodigital dysplasia; with skin hyperkeratosis; associated with GJB2 variant His-127. Ref.32

VAR_058993

Natural variant

49

1

Q → K in ODDD. Ref.20

VAR_015753

Natural variant

49

1

Q → P in ODDD. Ref.38

VAR_058994

Natural variant

49

1

Q → QQ in ODDD. Ref.38

VAR_058995

Natural variant

52

1

F → FF in ODDD. Ref.20

VAR_015754

Natural variant

59

1

P → H in ODDD. Ref.30

VAR_058996

Natural variant

69

1

S → Y in ODDD. Ref.27

VAR_038358

Natural variant

76

1

R → H in HSS; overlapping features with oculodentodigital dysplasia. Ref.26

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.29

VAR_058998

Natural variant

96

1

V → A in ODDD. Ref.38

VAR_058999

Natural variant

96

1

V → E in ODDD. Ref.34

VAR_059000

Natural variant

96

1

V → M in ODDD. Ref.25
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.38

VAR_059002

Natural variant

110

1

E → D in ODDD. Ref.33

VAR_059003

Natural variant

113

1

L → P in ODDD. Ref.27 Ref.34

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.27

VAR_038360

Natural variant

138

1

G → R in ODDD. Ref.20

VAR_015761

Natural variant

143

1

G → S in SDTY3. Ref.27
Corresponds to variant rs28931600 [ dbSNP | Ensembl ].

VAR_038361

Natural variant

147

1

M → T in ODDD. Ref.33

VAR_059004

Natural variant

148

1

R → Q. Ref.27
Corresponds to variant rs2228960 [ dbSNP | Ensembl ].

VAR_014095

Natural variant

154

1

T → A in ODDD. Ref.36 Ref.38

VAR_059005

Natural variant

154

1

T → N in ODDD. Ref.34

VAR_059006

Natural variant

168

1

A → T.
Corresponds to variant rs2228961 [ dbSNP | Ensembl ].

VAR_014096

Natural variant

169

1

Missing in ODDD. Ref.33

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.28

VAR_059008

Natural variant

201

1

S → F in ODDD. Ref.38

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.27 Ref.38

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.34

VAR_059010

Natural variant

239

1

R → W in congenital heart malformations. Ref.31
Corresponds to variant rs2227887 [ dbSNP | Ensembl ].

VAR_014100

Natural variant

251

1

S → T in congenital heart malformations. Ref.31

VAR_059011

Natural variant

253

1

A → P in congenital heart malformations. Ref.31

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.31
Corresponds to variant rs2228974 [ dbSNP | Ensembl ].

VAR_014101

Natural variant

290

1

T → N in congenital heart malformations. Ref.31
Corresponds to variant rs2227881 [ dbSNP | Ensembl ].

VAR_014102

Natural variant

326

1

T → A. Ref.23

VAR_059013

Natural variant

352

1

E → G in heart malformations. Ref.23

VAR_059014

Natural variant

362

1

R → Q in HLHS1 and AVSD3; associated with Gln-376 in one individual with atrioventricular septal defect; abolishes phosphorylation by PKA and PKC. Ref.24
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.23

VAR_059015

Natural variant

365

1

S → N in heart malformations. Ref.23

VAR_059016

Natural variant

373

1

S → G. Ref.23

VAR_059017

Natural variant

376

1

R → Q in HLHS1 and AVSD3; associated with Gln-362 in one individual with atrioventricular septal defect; abolishes phosphorylation by PKA and PKC. Ref.24

VAR_032925

Secondary structure

1

.

.

.

.

.

.

.

382

Helix Strand Turn

Details...

Helix

240 – 242

3

Helix

246 – 253

8

Helix

255 – 257

3

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH KIAA1432.
[18]	"Cellular sublocalization of Cx43 and the establishment of functional coupling in IMR-32 neuroblastoma cells." Arnold J.M., Phipps M.W., Chen J., Phipps J. Mol. Carcinog. 42:159-169(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-255 AND SER-262.
[19]	"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] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN ODDD-AR.
[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] [Europe PMC] [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]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-255; SER-306; SER-314 AND SER-344, MASS SPECTROMETRY.
[22]	"The gap junction channel protein connexin 43 is covalently modified and regulated by SUMOylation." Kjenseth A., Fykerud T.A., Sirnes S., Bruun J., Yohannes Z., Kolberg M., Omori Y., Rivedal E., Leithe E. J. Biol. Chem. 287:15851-15861(2012) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION AT LYS-144 AND LYS-237, SUBCELLULAR LOCATION.
[23]	"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] [Europe PMC] [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.
[24]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS HLHS1 GLN-362 AND GLN-376, VARIANTS AVSD3 GLN-362 AND GLN-376, CHARACTERIZATION OF VARIANTS HLHS1 GLN-362 AND GLN-376.
[25]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ODDD MET-96.
[26]	"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] [Europe PMC] [Abstract] Cited for: VARIANT HSS HIS-76.
[27]	"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] [Europe PMC] [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.
[28]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ODDD PRO-194.
[29]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ODDD ARG-95.
[30]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ODDD HIS-59.
[31]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS CONGENITAL HEART MALFORMATIONS TRP-239; THR-251; PRO-253; LEU-283 AND ASN-290.
[32]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ECTODERMAL AND OCULODENTODIGITAL DYSPLASIA LEU-41.
[33]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ODDD VAL-40; ASP-110; THR-147 AND PHE-169 DEL.
[34]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS ODDD GLU-96; PRO-113; ASN-154 AND TYR-220.
[35]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ODDD PRO-11.
[36]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ODDD ALA-154.
[37]	"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] [Europe PMC] [Abstract] Cited for: VARIANT ODDD VAL-2.
[38]	"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] [Europe PMC] [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

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LL2	NMR	-	A	234-259	[»]

ProteinModelPortal

P17302.

ModBase

Search...

Protein-protein interaction databases

IntAct

P17302. 2 interactions.

MINT

MINT-147603.

STRING

9606.ENSP00000282561.

PTM databases

PhosphoSite

P17302.

Polymorphism databases

DMDM

117706.

Proteomic databases

PaxDb

P17302.

PeptideAtlas

P17302.

PRIDE

P17302.

Protocols and materials databases

DNASU

2697.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000282561; ENSP00000282561; ENSG00000152661.

GeneID

2697.

KEGG

hsa:2697.

UCSC

uc003pyr.3. human.

Organism-specific databases

CTD

2697.

GeneCards

GC06P121756.

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

NOG45368.

HOGENOM

HOG000231127.

HOVERGEN

HBG009576.

InParanoid

P17302.

KO

K07372.

OMA

GANVDMH.

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]

PANTHER

PTHR11984. PTHR11984. 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

ChiTaRS

GJA1. human.

DrugBank

DB01136. Carvedilol.

GenomeRNAi

2697.

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:	May 1, 2013
This is version 167 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.