Q5T442 (CXG2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gap junction gamma-2 protein

Alternative name(s):
Connexin-46.6
Short name=Cx46.6
Connexin-47
Short name=Cx47
Gap junction alpha-12 protein

Gene names

Name:	GJC2
Synonyms:	GJA12

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	439 AA.
Sequence status	Complete.
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 role in myelination in central and peripheral nervous systems. Ref.5
Subunit structure	A connexon is composed of a hexamer of connexins. Interacts with TJP1 By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › gap junction.
Tissue specificity	Expressed in central nervous system, in sciatic nerve and sural nerve. Also detected in skeletal muscles. Ref.5
Involvement in disease	Leukodystrophy, hypomyelinating, 2 (HLD2) [MIM:608804]: An autosomal recessive hypomyelinating leukodystrophy with symptoms of Pelizaeus-Merzbacher disease. Clinically characterized by nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria, and progressive spasticity. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Spastic paraplegia 44, autosomal recessive (SPG44) [MIM:613206]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG39 is associated with a motor axonopathy affecting upper and lower limbs and resulting in progressive wasting of distal upper and lower extremity muscles. Note: The disease is caused by mutations affecting the gene represented in this entry. Lymphedema, hereditary, 1C (LMPH1C) [MIM:613480]: A chronic disabling condition which results in swelling of the extremities due to altered lymphatic flow. Patients with lymphedema suffer from recurrent local infections and physical impairment. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.8
Sequence similarities	Belongs to the connexin family. Gamma-type subfamily.
Caution	It is uncertain whether Met-1 or Met-4 is the initiator.
Sequence caution	The sequence AAB94511.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAH35840.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Gap junction Membrane
Disease	Disease mutation Hereditary spastic paraplegia Leukodystrophy Neurodegeneration
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW cell-cell signaling Inferred from electronic annotation. Source: Compara response to toxic substance Inferred from electronic annotation. Source: Compara
Cellular_component	connexon complex Inferred from electronic annotation. Source: InterPro integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW myelin sheath Inferred from electronic annotation. Source: Compara
Molecular_function	gap junction channel activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 439	439	Gap junction gamma-2 protein		PRO_0000057842
Regions
	Topological domain	1 – 25	25	Cytoplasmic Potential
	Transmembrane	26 – 46	21	Helical; Potential
	Topological domain	47 – 78	32	Extracellular Potential
	Transmembrane	79 – 99	21	Helical; Potential
	Topological domain	100 – 216	117	Cytoplasmic Potential
	Transmembrane	217 – 237	21	Helical; Potential
	Topological domain	238 – 265	28	Extracellular Potential
	Transmembrane	266 – 286	21	Helical; Potential
	Topological domain	287 – 439	153	Cytoplasmic Potential
	Compositional bias	143 – 176	34	Glu-rich
Amino acid modifications
	Modified residue	371	1	Phosphoserine By similarity
Natural variations
	Natural variant	19	1	H → P Associated with lymphedema in a small family. Ref.8		VAR_063876
	Natural variant	36	1	I → M in SPG44; does not form functional homotypic channels. Ref.7		VAR_063172
	Natural variant	48	1	S → L in LMPH1C. Ref.8		VAR_063877
	Natural variant	90	1	P → S in HLD2. Ref.5		VAR_023754
	Natural variant	125	1	R → Q Associated with lymphedema in a small family. Ref.8		VAR_063878
	Natural variant	149	1	G → S Associated with lymphedema in a small family. Ref.8		VAR_063879
	Natural variant	260	1	R → C in LMPH1C. Ref.8		VAR_063880
	Natural variant	272	1	Y → D in HLD2. Ref.5		VAR_023755
	Natural variant	286	1	M → T in HLD2. Ref.5		VAR_023756
	Natural variant	316	1	P → L Associated with lymphedema in a small family. Ref.8		VAR_063881
Experimental info
	Sequence conflict	83	1	Q → H in AAB94511. Ref.1
	Sequence conflict	252	1	H → Q in AAB94511. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q5T442 [UniParc]. Last modified December 21, 2004. Version 1. Checksum: 09725B5DC476672A	FASTA	439	47,002
	10 20 30 40 50 60 MTNMSWSFLT RLLEEIHNHS TFVGKVWLTV LVVFRIVLTA VGGEAIYSDE QAKFTCNTRQ 70 80 90 100 110 120 PGCDNVCYDA FAPLSHVRFW VFQIVVISTP SVMYLGYAVH RLARASEQER RRALRRRPGP 130 140 150 160 170 180 RRAPRAHLPP PHAGWPEPAD LGEEEPMLGL GEEEEEEETG AAEGAGEEAE EAGAEEACTK 190 200 210 220 230 240 AVGADGKAAG TPGPTGQHDG RRRIQREGLM RVYVAQLVAR AAFEVAFLVG QYLLYGFEVR 250 260 270 280 290 300 PFFPCSRQPC PHVVDCFVSR PTEKTVFLLV MYVVSCLCLL LNLCEMAHLG LGSAQDAVRG 310 320 330 340 350 360 RRGPPASAPA PAPRPPPCAF PAAAAGLACP PDYSLVVRAA ERARAHDQNL ANLALQALRD 370 380 390 400 410 420 GAAAGDRDRD SSPCVGLPAA SRGPPRAGAP ASRTGSATSA GTVGEQGRPG THERPGAKPR 430 AGSEKGSASS RDGKTTVWI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and molecular characterization of human connexin46.6, a new gap junction gene." Bloemker B.K., Swaroop A., Kimberling W.J. Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Chondrosarcoma.
[4]	"Human connexin47, updated ORF." Enriquez A.D., Scherer S.S. Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 4-439. Tissue: Corpus callosum.
[5]	"Mutations in the gene encoding gap junction protein alpha 12 (connexin 46.6) cause Pelizaeus-Merzbacher-like disease." Uhlenberg B., Schuelke M., Rueschendorf F., Ruf N., Kaindl A.M., Henneke M., Thiele H., Stoltenburg-Didinger G., Aksu F., Topaloglu H., Nuernberg P., Huebner C., Weschke B., Gaertner J. Am. J. Hum. Genet. 75:251-260(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DISEASE, VARIANTS HLD2 SER-90; ASP-272 AND THR-286, TISSUE SPECIFICITY.
[6]	Erratum Uhlenberg B., Schuelke M., Rueschendorf F., Ruf N., Kaindl A.M., Henneke M., Thiele H., Stoltenburg-Didinger G., Aksu F., Topaloglu H., Nuernberg P., Huebner C., Weschke B., Gaertner J. Am. J. Hum. Genet. 75:737-737(2004)
[7]	"Hereditary spastic paraplegia is a novel phenotype for GJA12/GJC2 mutations." Orthmann-Murphy J.L., Salsano E., Abrams C.K., Bizzi A., Uziel G., Freidin M.M., Lamantea E., Zeviani M., Scherer S.S., Pareyson D. Brain 132:426-438(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SPG44 MET-36, CHARACTERIZATION OF VARIANT SPG44 MET-36.
[8]	"GJC2 missense mutations cause human lymphedema." Ferrell R.E., Baty C.J., Kimak M.A., Karlsson J.M., Lawrence E.C., Franke-Snyder M., Meriney S.D., Feingold E., Finegold D.N. Am. J. Hum. Genet. 86:943-948(2010) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LMPH1C LEU-48 AND CYS-260, VARIANTS PRO-19; GLN-125; SER-149 AND LEU-316.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF014643 Genomic DNA. Translation: AAB94511.1. Different initiation. AL359510 Genomic DNA. Translation: CAI15069.1. BC035840 mRNA. Translation: AAH35840.1. Different initiation. BC089439 mRNA. Translation: AAH89439.1. AY285161 mRNA. Translation: AAP37488.1.
IPI	IPI00007029.
RefSeq	NP_065168.2. NM_020435.3.
UniGene	Hs.100072. Hs.743715.
3D structure databases
ProteinModelPortal	Q5T442.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q5T442. 1 interaction.
STRING	9606.ENSP00000355675.
PTM databases
PhosphoSite	Q5T442.
Polymorphism databases
DMDM	74744875.
Proteomic databases
PaxDb	Q5T442.
PRIDE	Q5T442.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000366714; ENSP00000355675; ENSG00000198835.
GeneID	57165.
KEGG	hsa:57165.
UCSC	uc001hsk.3. human.
Organism-specific databases
CTD	57165.
GeneCards	GC01P228337.
HGNC	HGNC:17494. GJC2.
MIM	608803. gene. 608804. phenotype. 613206. phenotype. 613480. phenotype.
neXtProt	NX_Q5T442.
Orphanet	320401. Autosomal recessive spastic paraplegia type 44. 79452. Milroy disease. 280282. Pelizaeus-Merzbacher-like due to GJC2 mutation.
PharmGKB	PA162389696.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG313094.
HOGENOM	HOG000231126.
HOVERGEN	HBG009576.
InParanoid	Q5T442.
KO	K07619.
OMA	DRDSPPC.
OrthoDB	EOG45HRXR.
PhylomeDB	Q5T442.
Enzyme and pathway databases
Reactome	REACT_11123. Membrane Trafficking.
Gene expression databases
Bgee	Q5T442.
CleanEx	HS_GJC2.
Genevestigator	Q5T442.
GermOnline	ENSG00000198835. Homo sapiens.
Family and domain databases
InterPro	IPR000500. Connexin. IPR019570. Connexin_CCC. IPR017990. Connexin_CS. IPR013092. Connexin_N. [Graphical view]
PANTHER	PTHR11984. PTHR11984. 1 hit.
Pfam	PF00029. Connexin. 1 hit. PF10582. Connexin_CCC. 1 hit. [Graphical view]
PRINTS	PR00206. CONNEXIN.
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
GenomeRNAi	57165.
NextBio	63173.
SOURCE	Search...

Entry information

Entry name

CXG2_HUMAN

Accession

Primary (citable) accession number: Q5T442
Secondary accession number(s): O43440, Q7Z7J2, Q8IWJ9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2005
Last sequence update:	December 21, 2004
Last modified:	May 29, 2013
This is version 91 of the entry and version 1 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.