Q9Y698 (CCG2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Voltage-dependent calcium channel gamma-2 subunit

Alternative name(s):
Neuronal voltage-gated calcium channel gamma-2 subunit
Transmembrane AMPAR regulatory protein gamma-2
Short name=TARP gamma-2

Gene names

Name:

CACNG2

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	323 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state. Ref.5
Subunit structure	The L-type calcium channel is composed of five subunits: alpha-1, alpha-2/delta, beta and gamma. Interacts with the PDZ domains of DLG4/PSD-95 and DLG1/SAP97. May interact with GOPC By similarity. Acts as an auxiliary subunit for AMPA-selective glutamate receptors (AMPARs). Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4, CNIH2, CNIH3, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8 By similarity. Interacts with GRIA1. Ref.5
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Brain.
Post-translational modification	Phosphorylation of Thr-321 impairs interaction with DLG1 and DLG4.
Involvement in disease	Mental retardation, autosomal dominant 10 (MRD10) [MIM:614256]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6
Sequence similarities	Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.

Ontologies

Keywords
Biological process	Calcium transport Ion transport Transport
Cellular component	Membrane
Disease	Disease mutation Mental retardation
Domain	Transmembrane Transmembrane helix
Ligand	Calcium
Molecular function	Calcium channel Ion channel Voltage-gated channel
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	membrane depolarization Traceable author statement. Source: Reactome membrane hyperpolarization Inferred from electronic annotation. Source: Compara neuromuscular junction development Inferred from electronic annotation. Source: Compara regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity Inferred from sequence or structural similarity. Source: UniProtKB synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid selective glutamate receptor complex Inferred from sequence or structural similarity. Source: UniProtKB endocytic vesicle membrane Traceable author statement. Source: Reactome voltage-gated calcium channel complex Traceable author statement Ref.1. Source: ProtInc
Molecular_function	voltage-gated calcium channel activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 323	323	Voltage-dependent calcium channel gamma-2 subunit		PRO_0000164673
Regions
	Transmembrane	10 – 30	21	Helical; Potential
	Transmembrane	104 – 124	21	Helical; Potential
	Transmembrane	134 – 154	21	Helical; Potential
	Transmembrane	182 – 202	21	Helical; Potential
Amino acid modifications
	Modified residue	253	1	Phosphoserine By similarity
	Modified residue	271	1	Phosphotyrosine By similarity
	Modified residue	321	1	Phosphothreonine By similarity
	Glycosylation	48	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	143	1	V → L in MRD10; significantly reduced ability to bind GRIA1 or GRIA2 AMPARs; cell surface expression of GRIA1 is reduced in transfected hippocampal neurons and HEK293 cells producing mutant protein compared to cells producing the wild-type. Ref.6		VAR_066599

Sequences

	Sequence		Length	Mass (Da)
	Q9Y698 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: BF46A87E96B27934	FASTA	323	35,966
	10 20 30 40 50 60 MGLFDRGVQM LLTTVGAFAA FSLMTIAVGT DYWLYSRGVC KTKSVSENET SKKNEEVMTH 70 80 90 100 110 120 SGLWRTCCLE GNFKGLCKQI DHFPEDADYE ADTAEYFLRA VRASSIFPIL SVILLFMGGL 130 140 150 160 170 180 CIAASEFYKT RHNIILSAGI FFVSAGLSNI IGIIVYISAN AGDPSKSDSK KNSYSYGWSF 190 200 210 220 230 240 YFGALSFIIA EMVGVLAVHM FIDRHKQLRA TARATDYLQA SAITRIPSYR YRYQRRSRSS 250 260 270 280 290 300 SRSTEPSHSR DASPVGIKGF NTLPSTEISM YTLSRDPLKA ATTPTATYNS DRDNSFLQVH 310 320 NCIQKENKDS LHSNTANRRT TPV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and cloning of putative human neuronal voltage-gated calcium channel gamma-2 and gamma-3 subunits: neurologic implications." Black J.L. III, Lennon V.A. Mayo Clin. Proc. 74:357-361(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Cerebellum.
[2]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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].
[5]	"Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating." Shi Y., Suh Y.H., Milstein A.D., Isozaki K., Schmid S.M., Roche K.W., Nicoll R.A. Proc. Natl. Acad. Sci. U.S.A. 107:16315-16319(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH GRIA1.
[6]	"Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability." Hamdan F.F., Gauthier J., Araki Y., Lin D.T., Yoshizawa Y., Higashi K., Park A.R., Spiegelman D., Dobrzeniecka S., Piton A., Tomitori H., Daoud H., Massicotte C., Henrion E., Diallo O., Shekarabi M., Marineau C., Shevell M. , Maranda B., Mitchell G., Nadeau A., D'Anjou G., Vanasse M., Srour M., Lafreniere R.G., Drapeau P., Lacaille J.C., Kim E., Lee J.R., Igarashi K., Huganir R.L., Rouleau G.A., Michaud J.L. Am. J. Hum. Genet. 88:306-316(2011) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MRD10 LEU-143, CHARACTERIZATION OF VARIANT MRD10 LEU-143.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF096322 mRNA. Translation: AAD22738.1. CR456414 mRNA. Translation: CAG30300.1. AL022313, AL031845, AL049749 Genomic DNA. Translation: CAI19227.1. AL031845, AL022313, AL049749 Genomic DNA. Translation: CAI17986.1. BC069612 mRNA. Translation: AAH69612.1. BC112297 mRNA. Translation: AAI12298.1. BC112299 mRNA. Translation: AAI12300.1.
IPI	IPI00001962.
RefSeq	NP_006069.1. NM_006078.3.
UniGene	Hs.146766.
3D structure databases
ProteinModelPortal	Q9Y698.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48977N.
STRING	9606.ENSP00000300105.
Protein family/group databases
TCDB	8.A.16.2.1. Ca+ channel auxiliary subunit gamma1-gamma8 (CCAgamma) family.
PTM databases
PhosphoSite	Q9Y698.
Polymorphism databases
DMDM	6685289.
Proteomic databases
PaxDb	Q9Y698.
PRIDE	Q9Y698.
Protocols and materials databases
DNASU	10369.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000300105; ENSP00000300105; ENSG00000166862.
GeneID	10369.
KEGG	hsa:10369.
UCSC	uc003aps.2. human.
Organism-specific databases
CTD	10369.
GeneCards	GC22M036959.
HGNC	HGNC:1406. CACNG2.
MIM	602911. gene. 614256. phenotype.
neXtProt	NX_Q9Y698.
Orphanet	178469. Autosomal dominant nonsyndromic intellectual deficit.
PharmGKB	PA26016.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG43469.
HOGENOM	HOG000233440.
HOVERGEN	HBG003682.
InParanoid	Q9Y698.
KO	K04867.
OMA	ANARATD.
OrthoDB	EOG4P5K9M.
PhylomeDB	Q9Y698.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System.
Gene expression databases
Bgee	Q9Y698.
CleanEx	HS_CACNG2.
Genevestigator	Q9Y698.
GermOnline	ENSG00000166862. Homo sapiens.
Family and domain databases
InterPro	IPR004031. PMP22/EMP/MP20/Claudin. IPR005422. VDCC_g2su. IPR008368. VDCC_gsu. [Graphical view]
Pfam	PF00822. PMP22_Claudin. 1 hit. [Graphical view]
PRINTS	PR01792. VDCCGAMMA. PR01602. VDCCGAMMA2.
ProtoNet	Search...
Other
GenomeRNAi	10369.
NextBio	39303.
SOURCE	Search...

Entry information

Entry name

CCG2_HUMAN

Accession

Primary (citable) accession number: Q9Y698
Secondary accession number(s): Q2M1M1, Q5TGT3, Q9UGZ7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	November 1, 1999
Last modified:	May 1, 2013
This is version 109 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.