CCG2_HUMAN
ID CCG2_HUMAN Reviewed; 323 AA.
AC Q9Y698; Q2M1M1; Q5TGT3; Q9UGZ7;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Voltage-dependent calcium channel gamma-2 subunit;
DE AltName: Full=Neuronal voltage-gated calcium channel gamma-2 subunit;
DE AltName: Full=Transmembrane AMPAR regulatory protein gamma-2;
DE Short=TARP gamma-2;
GN Name=CACNG2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Cerebellum;
RX PubMed=10221464; DOI=10.4065/74.4.357;
RA Black J.L. III, Lennon V.A.;
RT "Identification and cloning of putative human neuronal voltage-gated
RT calcium channel gamma-2 and gamma-3 subunits: neurologic implications.";
RL Mayo Clin. Proc. 74:357-361(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND INTERACTION WITH GRIA1.
RX PubMed=20805473; DOI=10.1073/pnas.1011706107;
RA Shi Y., Suh Y.H., Milstein A.D., Isozaki K., Schmid S.M., Roche K.W.,
RA Nicoll R.A.;
RT "Functional comparison of the effects of TARPs and cornichons on AMPA
RT receptor trafficking and gating.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:16315-16319(2010).
RN [6]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.90 ANGSTROMS) OF 2-208.
RX PubMed=30122377; DOI=10.1016/j.neuron.2018.07.027;
RA Twomey E.C., Yelshanskaya M.V., Vassilevski A.A., Sobolevsky A.I.;
RT "Mechanisms of channel block in calcium-permeable AMPA receptors.";
RL Neuron 99:956-968.e4(2018).
RN [7]
RP VARIANT MRD10 LEU-143, AND CHARACTERIZATION OF VARIANT MRD10 LEU-143.
RX PubMed=21376300; DOI=10.1016/j.ajhg.2011.02.001;
RA Hamdan F.F., Gauthier J., Araki Y., Lin D.T., Yoshizawa Y., Higashi K.,
RA Park A.R., Spiegelman D., Dobrzeniecka S., Piton A., Tomitori H., Daoud H.,
RA Massicotte C., Henrion E., Diallo O., Shekarabi M., Marineau C.,
RA Shevell M., Maranda B., Mitchell G., Nadeau A., D'Anjou G., Vanasse M.,
RA Srour M., Lafreniere R.G., Drapeau P., Lacaille J.C., Kim E., Lee J.R.,
RA Igarashi K., Huganir R.L., Rouleau G.A., Michaud J.L.;
RT "Excess of de novo deleterious mutations in genes associated with
RT glutamatergic systems in nonsyndromic intellectual disability.";
RL Am. J. Hum. Genet. 88:306-316(2011).
CC -!- FUNCTION: Regulates the trafficking and gating properties of AMPA-
CC selective glutamate receptors (AMPARs). Promotes their targeting to the
CC cell membrane and synapses and modulates their gating properties by
CC slowing their rates of activation, deactivation and desensitization.
CC Does not show subunit-specific AMPA receptor regulation and regulates
CC all AMPAR subunits. Thought to stabilize the calcium channel in an
CC inactivated (closed) state. {ECO:0000269|PubMed:20805473}.
CC -!- SUBUNIT: The L-type calcium channel is composed of five subunits:
CC alpha-1, alpha-2/delta, beta and gamma. Interacts with the PDZ domains
CC of DLG4/PSD-95 and DLG1/SAP97. May interact with GOPC (By similarity).
CC Acts as an auxiliary subunit for AMPA-selective glutamate receptors
CC (AMPARs). Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4, CNIH2,
CC CNIH3, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8 (By similarity).
CC Interacts with GRIA1 and GRIA2 (PubMed:20805473). Interacts with MPP2
CC (By similarity). {ECO:0000250|UniProtKB:Q71RJ2,
CC ECO:0000269|PubMed:20805473}.
CC -!- INTERACTION:
CC Q9Y698; O43516-4: WIPF1; NbExp=3; IntAct=EBI-6659211, EBI-12052927;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Synapse,
CC synaptosome {ECO:0000250|UniProtKB:Q71RJ2}.
CC -!- TISSUE SPECIFICITY: Brain.
CC -!- PTM: Phosphorylation of Thr-321 impairs interaction with DLG1 and DLG4.
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 10
CC (MRD10) [MIM:614256]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period.
CC {ECO:0000269|PubMed:21376300}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.
CC {ECO:0000305}.
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DR EMBL; AF096322; AAD22738.1; -; mRNA.
DR EMBL; CR456414; CAG30300.1; -; mRNA.
DR EMBL; AL022313; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL031845; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL049749; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069612; AAH69612.1; -; mRNA.
DR EMBL; BC112297; AAI12298.1; -; mRNA.
DR EMBL; BC112299; AAI12300.1; -; mRNA.
DR CCDS; CCDS13931.1; -.
DR RefSeq; NP_006069.1; NM_006078.3.
DR PDB; 6DLZ; EM; 3.90 A; A/B/C/D=2-208.
DR PDB; 6DM0; EM; 4.40 A; A/B/C/D=2-208.
DR PDB; 6DM1; EM; 4.20 A; A/B/C/D=2-208.
DR PDB; 6O9G; EM; 4.80 A; A/B/C/D=2-208.
DR PDB; 6TNO; X-ray; 1.90 A; B/D/F=225-232.
DR PDBsum; 6DLZ; -.
DR PDBsum; 6DM0; -.
DR PDBsum; 6DM1; -.
DR PDBsum; 6O9G; -.
DR PDBsum; 6TNO; -.
DR AlphaFoldDB; Q9Y698; -.
DR SMR; Q9Y698; -.
DR BioGRID; 115648; 27.
DR CORUM; Q9Y698; -.
DR DIP; DIP-48977N; -.
DR IntAct; Q9Y698; 15.
DR STRING; 9606.ENSP00000300105; -.
DR BindingDB; Q9Y698; -.
DR ChEMBL; CHEMBL4296111; -.
DR DrugBank; DB13746; Bioallethrin.
DR DrugBank; DB11148; Butamben.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB00153; Ergocalciferol.
DR DrugBank; DB00898; Ethanol.
DR DrugBank; DB00421; Spironolactone.
DR TCDB; 8.A.16.2.1; the ca(+) channel auxiliary subunit Gama1-Gama8 (ccaGama) family.
DR GlyGen; Q9Y698; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y698; -.
DR PhosphoSitePlus; Q9Y698; -.
DR BioMuta; CACNG2; -.
DR DMDM; 6685289; -.
DR MassIVE; Q9Y698; -.
DR PaxDb; Q9Y698; -.
DR PeptideAtlas; Q9Y698; -.
DR PRIDE; Q9Y698; -.
DR ProteomicsDB; 86635; -.
DR Antibodypedia; 25748; 232 antibodies from 36 providers.
DR DNASU; 10369; -.
DR Ensembl; ENST00000300105.7; ENSP00000300105.6; ENSG00000166862.7.
DR GeneID; 10369; -.
DR KEGG; hsa:10369; -.
DR MANE-Select; ENST00000300105.7; ENSP00000300105.6; NM_006078.5; NP_006069.1.
DR UCSC; uc003aps.3; human.
DR CTD; 10369; -.
DR DisGeNET; 10369; -.
DR GeneCards; CACNG2; -.
DR HGNC; HGNC:1406; CACNG2.
DR HPA; ENSG00000166862; Tissue enriched (brain).
DR MalaCards; CACNG2; -.
DR MIM; 602911; gene.
DR MIM; 614256; phenotype.
DR neXtProt; NX_Q9Y698; -.
DR OpenTargets; ENSG00000166862; -.
DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability.
DR PharmGKB; PA26016; -.
DR VEuPathDB; HostDB:ENSG00000166862; -.
DR eggNOG; ENOG502QSNI; Eukaryota.
DR GeneTree; ENSGT01050000244893; -.
DR HOGENOM; CLU_053704_0_1_1; -.
DR InParanoid; Q9Y698; -.
DR OMA; CIQKESK; -.
DR OrthoDB; 1117127at2759; -.
DR PhylomeDB; Q9Y698; -.
DR TreeFam; TF327980; -.
DR PathwayCommons; Q9Y698; -.
DR Reactome; R-HSA-112308; Presynaptic depolarization and calcium channel opening.
DR Reactome; R-HSA-399719; Trafficking of AMPA receptors.
DR Reactome; R-HSA-5682910; LGI-ADAM interactions.
DR SignaLink; Q9Y698; -.
DR SIGNOR; Q9Y698; -.
DR BioGRID-ORCS; 10369; 24 hits in 1061 CRISPR screens.
DR ChiTaRS; CACNG2; human.
DR GeneWiki; CACNG2; -.
DR GenomeRNAi; 10369; -.
DR Pharos; Q9Y698; Tbio.
DR PRO; PR:Q9Y698; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q9Y698; protein.
DR Bgee; ENSG00000166862; Expressed in right hemisphere of cerebellum and 53 other tissues.
DR Genevisible; Q9Y698; HS.
DR GO; GO:0032281; C:AMPA glutamate receptor complex; ISS:UniProtKB.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0044300; C:cerebellar mossy fiber; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IEA:Ensembl.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098839; C:postsynaptic density membrane; IBA:GO_Central.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl.
DR GO; GO:0036477; C:somatodendritic compartment; IEA:Ensembl.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; TAS:ProtInc.
DR GO; GO:0016247; F:channel regulator activity; IBA:GO_Central.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IEA:Ensembl.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IBA:GO_Central.
DR GO; GO:0060082; P:eye blink reflex; IEA:Ensembl.
DR GO; GO:0051899; P:membrane depolarization; IEA:Ensembl.
DR GO; GO:0060081; P:membrane hyperpolarization; IEA:Ensembl.
DR GO; GO:0007528; P:neuromuscular junction development; IEA:Ensembl.
DR GO; GO:0099590; P:neurotransmitter receptor internalization; IBA:GO_Central.
DR GO; GO:0099645; P:neurotransmitter receptor localization to postsynaptic specialization membrane; IEA:Ensembl.
DR GO; GO:0098943; P:neurotransmitter receptor transport, postsynaptic endosome to lysosome; IBA:GO_Central.
DR GO; GO:2000969; P:positive regulation of AMPA receptor activity; IEA:Ensembl.
DR GO; GO:1904510; P:positive regulation of protein localization to basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IBA:GO_Central.
DR GO; GO:0098970; P:postsynaptic neurotransmitter receptor diffusion trapping; IBA:GO_Central.
DR GO; GO:0006612; P:protein targeting to membrane; IEA:Ensembl.
DR GO; GO:2000311; P:regulation of AMPA receptor activity; ISS:UniProtKB.
DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
DR GO; GO:0019226; P:transmission of nerve impulse; IBA:GO_Central.
DR InterPro; IPR004031; PMP22/EMP/MP20/Claudin.
DR InterPro; IPR005422; VDCC_g2su.
DR InterPro; IPR008368; VDCC_gsu.
DR PANTHER; PTHR12107:SF1; PTHR12107:SF1; 1.
DR Pfam; PF00822; PMP22_Claudin; 1.
DR PRINTS; PR01792; VDCCGAMMA.
DR PRINTS; PR01602; VDCCGAMMA2.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Calcium channel; Calcium transport; Disease variant;
KW Glycoprotein; Intellectual disability; Ion channel; Ion transport;
KW Membrane; Phosphoprotein; Reference proteome; Synapse; Synaptosome;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..323
FT /note="Voltage-dependent calcium channel gamma-2 subunit"
FT /id="PRO_0000164673"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 104..124
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 134..154
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 182..202
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 233..261
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 253
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q71RJ2"
FT MOD_RES 271
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O88602"
FT MOD_RES 321
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O88602"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 143
FT /note="V -> L (in MRD10; significantly reduced ability to
FT bind GRIA1 or GRIA2 AMPARs; cell surface expression of
FT GRIA1 is reduced in transfected hippocampal neurons and
FT HEK293 cells producing mutant protein compared to cells
FT producing the wild-type)"
FT /evidence="ECO:0000269|PubMed:21376300"
FT /id="VAR_066599"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:6TNO"
SQ SEQUENCE 323 AA; 35966 MW; BF46A87E96B27934 CRC64;
MGLFDRGVQM LLTTVGAFAA FSLMTIAVGT DYWLYSRGVC KTKSVSENET SKKNEEVMTH
SGLWRTCCLE GNFKGLCKQI DHFPEDADYE ADTAEYFLRA VRASSIFPIL SVILLFMGGL
CIAASEFYKT RHNIILSAGI FFVSAGLSNI IGIIVYISAN AGDPSKSDSK KNSYSYGWSF
YFGALSFIIA EMVGVLAVHM FIDRHKQLRA TARATDYLQA SAITRIPSYR YRYQRRSRSS
SRSTEPSHSR DASPVGIKGF NTLPSTEISM YTLSRDPLKA ATTPTATYNS DRDNSFLQVH
NCIQKENKDS LHSNTANRRT TPV
