CCG2_MOUSE
ID CCG2_MOUSE Reviewed; 323 AA.
AC O88602;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Voltage-dependent calcium channel gamma-2 subunit;
DE AltName: Full=Neuronal voltage-gated calcium channel gamma-2 subunit;
DE AltName: Full=Stargazin;
DE AltName: Full=Transmembrane AMPAR regulatory protein gamma-2;
DE Short=TARP gamma-2;
GN Name=Cacng2; Synonyms=Stg;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DISEASE.
RC STRAIN=ICR; TISSUE=Brain;
RX PubMed=9697694; DOI=10.1038/1228;
RA Letts V.A., Felix R., Biddlecome G.H., Arikkath J., Mahaffey C.L.,
RA Valenzuela A., Bartlett F.S. II, Mori Y., Campbell K.P., Frankel W.N.;
RT "The mouse stargazer gene encodes a neuronal Ca2+-channel gamma subunit.";
RL Nat. Genet. 19:340-347(1998).
RN [2]
RP PHOSPHORYLATION AT THR-321, INTERACTION WITH DLG1 AND DLG4, AND MUTAGENESIS
RP OF THR-321 AND VAL-323.
RX PubMed=11805122; DOI=10.1074/jbc.m200528200;
RA Choi J., Ko J., Park E., Lee J.-R., Yoon J., Lim S., Kim E.;
RT "Phosphorylation of stargazin by protein kinase A regulates its interaction
RT with PSD-95.";
RL J. Biol. Chem. 277:12359-12363(2002).
RN [3]
RP INTERACTION WITH GOPC.
RX PubMed=15136571; DOI=10.1074/jbc.m402214200;
RA Ives J.H., Fung S., Tiwari P., Payne H.L., Thompson C.L.;
RT "Microtubule-associated protein light chain 2 is a stargazin-AMPA receptor
RT complex-interacting protein in vivo.";
RL J. Biol. Chem. 279:31002-31009(2004).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-271, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 (By similarity).
CC {ECO:0000250|UniProtKB:Q71RJ2, ECO:0000250|UniProtKB:Q9Y698}.
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. Acts as an
CC auxiliary subunit for AMPA-selective glutamate receptors (AMPARs).
CC Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4, CNIH2, CNIH3,
CC CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8. Interacts with GRIA1 and
CC GRIA2 (By similarity). Interacts with MPP2.
CC {ECO:0000250|UniProtKB:Q71RJ2, ECO:0000250|UniProtKB:Q9Y698}.
CC -!- INTERACTION:
CC O88602; P23818: Gria1; NbExp=2; IntAct=EBI-770326, EBI-445486;
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 by PKA impairs interaction with DLG1
CC and DLG4. {ECO:0000269|PubMed:11805122}.
CC -!- DISEASE: Note=Defects in Cacng2 cause the stargazer (stg) phenotype.
CC Stg mice have spike-wave seizures characteristic of absence epilepsy,
CC with accompanying defects in the cerebellum and inner ear.
CC {ECO:0000269|PubMed:9697694}.
CC -!- SIMILARITY: Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.
CC {ECO:0000305}.
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DR EMBL; AF077739; AAC40201.1; -; mRNA.
DR CCDS; CCDS27608.1; -.
DR RefSeq; NP_031609.1; NM_007583.2.
DR PDB; 3JXT; X-ray; 1.50 A; C/D=318-323.
DR PDB; 4X3H; X-ray; 2.40 A; B=225-233.
DR PDB; 5KBS; EM; 8.70 A; A/B/C/D=2-208.
DR PDB; 5KBT; EM; 6.40 A; A/B/C/D=2-208.
DR PDB; 5KBU; EM; 7.80 A; A/B/C/D=2-208.
DR PDB; 5WEO; EM; 4.20 A; A/B/C/D=2-208.
DR PDBsum; 3JXT; -.
DR PDBsum; 4X3H; -.
DR PDBsum; 5KBS; -.
DR PDBsum; 5KBT; -.
DR PDBsum; 5KBU; -.
DR PDBsum; 5WEO; -.
DR AlphaFoldDB; O88602; -.
DR SMR; O88602; -.
DR BioGRID; 198444; 4.
DR DIP; DIP-32457N; -.
DR ELM; O88602; -.
DR IntAct; O88602; 5.
DR MINT; O88602; -.
DR STRING; 10090.ENSMUSP00000019290; -.
DR GlyGen; O88602; 1 site.
DR iPTMnet; O88602; -.
DR PhosphoSitePlus; O88602; -.
DR PaxDb; O88602; -.
DR PeptideAtlas; O88602; -.
DR PRIDE; O88602; -.
DR ProteomicsDB; 281326; -.
DR ABCD; O88602; 2 sequenced antibodies.
DR Antibodypedia; 25748; 232 antibodies from 36 providers.
DR DNASU; 12300; -.
DR Ensembl; ENSMUST00000019290; ENSMUSP00000019290; ENSMUSG00000019146.
DR GeneID; 12300; -.
DR KEGG; mmu:12300; -.
DR UCSC; uc007wop.2; mouse.
DR CTD; 10369; -.
DR MGI; MGI:1316660; Cacng2.
DR VEuPathDB; HostDB:ENSMUSG00000019146; -.
DR eggNOG; ENOG502QSNI; Eukaryota.
DR GeneTree; ENSGT01050000244893; -.
DR HOGENOM; CLU_053704_0_1_1; -.
DR InParanoid; O88602; -.
DR OMA; CIQKESK; -.
DR OrthoDB; 1117127at2759; -.
DR PhylomeDB; O88602; -.
DR TreeFam; TF327980; -.
DR Reactome; R-MMU-112308; Presynaptic depolarization and calcium channel opening.
DR Reactome; R-MMU-5682910; LGI-ADAM interactions.
DR BioGRID-ORCS; 12300; 1 hit in 70 CRISPR screens.
DR ChiTaRS; Cacng2; mouse.
DR PRO; PR:O88602; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; O88602; protein.
DR Bgee; ENSMUSG00000019146; Expressed in ventral horn of spinal cord and 94 other tissues.
DR ExpressionAtlas; O88602; baseline and differential.
DR Genevisible; O88602; MM.
DR GO; GO:0032281; C:AMPA glutamate receptor complex; IDA:MGI.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0044300; C:cerebellar mossy fiber; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IDA:SynGO.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IDA:SynGO.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0098839; C:postsynaptic density membrane; ISS:SynGO.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:0036477; C:somatodendritic compartment; IDA:UniProtKB.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; IEA:InterPro.
DR GO; GO:0016247; F:channel regulator activity; IBA:GO_Central.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISO:MGI.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IMP:MGI.
DR GO; GO:0060082; P:eye blink reflex; IEA:Ensembl.
DR GO; GO:0051899; P:membrane depolarization; IMP:MGI.
DR GO; GO:0060081; P:membrane hyperpolarization; IMP:MGI.
DR GO; GO:0050877; P:nervous system process; IMP:MGI.
DR GO; GO:0007528; P:neuromuscular junction development; IMP:MGI.
DR GO; GO:0099590; P:neurotransmitter receptor internalization; IMP:SynGO.
DR GO; GO:0099645; P:neurotransmitter receptor localization to postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:0098943; P:neurotransmitter receptor transport, postsynaptic endosome to lysosome; IMP:SynGO.
DR GO; GO:2000969; P:positive regulation of AMPA receptor activity; ISO:MGI.
DR GO; GO:1904510; P:positive regulation of protein localization to basolateral plasma membrane; ISO:MGI.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; IBA:GO_Central.
DR GO; GO:0098970; P:postsynaptic neurotransmitter receptor diffusion trapping; IDA:SynGO.
DR GO; GO:0006612; P:protein targeting to membrane; ISO:MGI.
DR GO; GO:2000311; P:regulation of AMPA receptor activity; IDA:SynGO.
DR GO; GO:0042391; P:regulation of membrane potential; IMP:MGI.
DR GO; GO:0099072; P:regulation of postsynaptic membrane neurotransmitter receptor levels; IDA:SynGO.
DR GO; GO:0098962; P:regulation of postsynaptic neurotransmitter receptor activity; IC:SynGO.
DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl.
DR GO; GO:0019226; P:transmission of nerve impulse; IGI:MGI.
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; Glycoprotein;
KW Ion channel; Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW Synapse; Synaptosome; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel.
FT CHAIN 1..323
FT /note="Voltage-dependent calcium channel gamma-2 subunit"
FT /id="PRO_0000164674"
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:0007744|PubMed:18034455"
FT MOD_RES 321
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000269|PubMed:11805122"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 321
FT /note="T->A: Abolishes phosphorylation."
FT /evidence="ECO:0000269|PubMed:11805122"
FT MUTAGEN 321
FT /note="T->D,E: No interaction with DLG1 and DLG4."
FT /evidence="ECO:0000269|PubMed:11805122"
FT MUTAGEN 323
FT /note="V->A: No interaction with DLG1 and DLG4."
FT /evidence="ECO:0000269|PubMed:11805122"
FT STRAND 226..229
FT /evidence="ECO:0007829|PDB:4X3H"
FT STRAND 321..323
FT /evidence="ECO:0007829|PDB:3JXT"
SQ SEQUENCE 323 AA; 35895 MW; AA9D475606A0FBA4 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 DASPVGVKGF NTLPSTEISM YTLSRDPLKA ATTPTATYNS DRDNSFLQVH
NCIQKDSKDS LHANTANRRT TPV
