CCG8_HUMAN
ID CCG8_HUMAN Reviewed; 425 AA.
AC Q8WXS5; Q9BXT0; Q9BY23;
DT 10-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Voltage-dependent calcium channel gamma-8 subunit;
DE AltName: Full=Neuronal voltage-gated calcium channel gamma-8 subunit;
DE AltName: Full=Transmembrane AMPAR regulatory protein gamma-8;
DE Short=TARP gamma-8;
GN Name=CACNG8; Synonyms=CACNG6;
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].
RX PubMed=11738816; DOI=10.1016/s0378-1119(01)00738-7;
RA Chu P.-J., Robertson H.M., Best P.M.;
RT "Calcium channel gamma subunits provide insights into the evolution of this
RT gene family.";
RL Gene 280:37-48(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-204.
RC TISSUE=Cerebellum;
RA Black J.L. III, Kryzer T.J., Lennon V.A.;
RT "Proposed Homo sapiens voltage-gated calcium channel gamma-6 subunit.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 12-425.
RX PubMed=11170751; DOI=10.1006/geno.2000.6440;
RA Burgess D.L., Gefrides L.A., Foreman P.J., Noebels J.L.;
RT "A cluster of three novel Ca(2+) channel gamma subunit genes on chromosome
RT 19q13.4: evolution and expression profile of the gamma subunit gene
RT family.";
RL Genomics 71:339-350(2001).
RN [5]
RP FUNCTION.
RX PubMed=21172611; DOI=10.1016/j.neuron.2010.11.026;
RA Kato A.S., Gill M.B., Ho M.T., Yu H., Tu Y., Siuda E.R., Wang H.,
RA Qian Y.W., Nisenbaum E.S., Tomita S., Bredt D.S.;
RT "Hippocampal AMPA receptor gating controlled by both TARP and cornichon
RT proteins.";
RL Neuron 68:1082-1096(2010).
RN [6]
RP FUNCTION.
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 [7]
RP TISSUE SPECIFICITY.
RX PubMed=21127204; DOI=10.1096/fj.10-172353;
RA Yang L., Katchman A., Morrow J.P., Doshi D., Marx S.O.;
RT "Cardiac L-type calcium channel (Cav1.2) associates with gamma subunits.";
RL FASEB J. 25:928-936(2011).
CC -!- FUNCTION: Regulates the activity of L-type calcium channels that
CC contain CACNA1C as pore-forming subunit (By similarity). Regulates the
CC trafficking and gating properties of AMPA-selective glutamate receptors
CC (AMPARs). Promotes their targeting to the cell membrane and synapses
CC and modulates their gating properties by slowing their rates of
CC activation, deactivation and desensitization and by mediating their
CC resensitization. Does not show subunit-specific AMPA receptor
CC regulation and regulates all AMPAR subunits.
CC {ECO:0000250|UniProtKB:Q8VHW2, ECO:0000269|PubMed:20805473,
CC ECO:0000269|PubMed:21172611}.
CC -!- SUBUNIT: Interacts with CACNA1C. Identified in a complex with the L-
CC type calcium channel subunits CACNA1C, CACNA2D1 and either CACNB1 or
CC CACNB2. Acts as an auxiliary subunit for AMPA-selective glutamate
CC receptors (AMPARs). Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4,
CC CNIH2, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5 and CACNG7. Interacts with
CC CNIH2. {ECO:0000250|UniProtKB:Q8VHW2}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8VHW2};
CC Multi-pass membrane protein {ECO:0000305}. Postsynaptic density
CC membrane {ECO:0000250|UniProtKB:Q8VHW2}.
CC -!- TISSUE SPECIFICITY: Detected in heart left ventricle.
CC {ECO:0000269|PubMed:21127204}.
CC -!- PTM: Palmitoylated. Probably palmitoylated by ZDHHC3 and ZDHHC7.
CC {ECO:0000250|UniProtKB:Q8VHW5}.
CC -!- SIMILARITY: Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAK15019.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
CC Sequence=AAL50049.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF361354; AAL50049.1; ALT_FRAME; mRNA.
DR EMBL; AC008440; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF234892; AAK15019.1; ALT_SEQ; mRNA.
DR EMBL; AF288388; AAK20031.1; -; mRNA.
DR CCDS; CCDS33104.1; -.
DR RefSeq; NP_114101.4; NM_031895.5.
DR AlphaFoldDB; Q8WXS5; -.
DR SMR; Q8WXS5; -.
DR BioGRID; 121869; 13.
DR IntAct; Q8WXS5; 1.
DR MINT; Q8WXS5; -.
DR STRING; 9606.ENSP00000270458; -.
DR BindingDB; Q8WXS5; -.
DR ChEMBL; CHEMBL4296110; -.
DR DrugBank; DB13746; Bioallethrin.
DR DrugBank; DB11148; Butamben.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB00153; Ergocalciferol.
DR DrugBank; DB00421; Spironolactone.
DR TCDB; 8.A.16.2.6; the ca(+) channel auxiliary subunit Gama1-Gama8 (ccaGama) family.
DR iPTMnet; Q8WXS5; -.
DR PhosphoSitePlus; Q8WXS5; -.
DR BioMuta; CACNG8; -.
DR DMDM; 313104245; -.
DR MassIVE; Q8WXS5; -.
DR PaxDb; Q8WXS5; -.
DR PeptideAtlas; Q8WXS5; -.
DR PRIDE; Q8WXS5; -.
DR ProteomicsDB; 75095; -.
DR Antibodypedia; 32771; 89 antibodies from 24 providers.
DR DNASU; 59283; -.
DR Ensembl; ENST00000270458.4; ENSP00000270458.3; ENSG00000142408.7.
DR GeneID; 59283; -.
DR KEGG; hsa:59283; -.
DR MANE-Select; ENST00000270458.4; ENSP00000270458.3; NM_031895.6; NP_114101.4.
DR UCSC; uc061clu.1; human.
DR CTD; 59283; -.
DR DisGeNET; 59283; -.
DR GeneCards; CACNG8; -.
DR HGNC; HGNC:13628; CACNG8.
DR HPA; ENSG00000142408; Tissue enriched (brain).
DR MIM; 606900; gene.
DR neXtProt; NX_Q8WXS5; -.
DR OpenTargets; ENSG00000142408; -.
DR PharmGKB; PA26022; -.
DR VEuPathDB; HostDB:ENSG00000142408; -.
DR eggNOG; ENOG502QUEC; Eukaryota.
DR GeneTree; ENSGT01050000244893; -.
DR HOGENOM; CLU_053704_0_1_1; -.
DR InParanoid; Q8WXS5; -.
DR OMA; HNCFPKL; -.
DR OrthoDB; 1117127at2759; -.
DR PhylomeDB; Q8WXS5; -.
DR TreeFam; TF327980; -.
DR PathwayCommons; Q8WXS5; -.
DR Reactome; R-HSA-399719; Trafficking of AMPA receptors.
DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
DR Reactome; R-HSA-5576893; Phase 2 - plateau phase.
DR Reactome; R-HSA-5682910; LGI-ADAM interactions.
DR SignaLink; Q8WXS5; -.
DR BioGRID-ORCS; 59283; 13 hits in 991 CRISPR screens.
DR ChiTaRS; CACNG8; human.
DR GenomeRNAi; 59283; -.
DR Pharos; Q8WXS5; Tdark.
DR PRO; PR:Q8WXS5; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8WXS5; protein.
DR Bgee; ENSG00000142408; Expressed in postcentral gyrus and 74 other tissues.
DR ExpressionAtlas; Q8WXS5; baseline and differential.
DR Genevisible; Q8WXS5; 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:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:1990454; C:L-type voltage-gated calcium channel complex; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; IBA:GO_Central.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; NAS:UniProtKB.
DR GO; GO:0005246; F:calcium channel regulator activity; ISS:UniProtKB.
DR GO; GO:0016247; F:channel regulator activity; IBA:GO_Central.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IBA:GO_Central.
DR GO; GO:0006816; P:calcium ion transport; NAS:UniProtKB.
DR GO; GO:0099590; P:neurotransmitter receptor internalization; IBA:GO_Central.
DR GO; GO:0098943; P:neurotransmitter receptor transport, postsynaptic endosome to lysosome; IBA:GO_Central.
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:2000311; P:regulation of AMPA receptor activity; IDA:UniProtKB.
DR GO; GO:0019226; P:transmission of nerve impulse; IBA:GO_Central.
DR InterPro; IPR004031; PMP22/EMP/MP20/Claudin.
DR InterPro; IPR008372; VDCC_g8su.
DR InterPro; IPR008368; VDCC_gsu.
DR Pfam; PF00822; PMP22_Claudin; 1.
DR PRINTS; PR01792; VDCCGAMMA.
DR PRINTS; PR01796; VDCCGAMMA8.
PE 2: Evidence at transcript level;
KW Calcium; Calcium channel; Calcium transport; Cell membrane; Ion channel;
KW Ion transport; Lipoprotein; Membrane; Palmitate; Phosphoprotein;
KW Postsynaptic cell membrane; Reference proteome; Synapse; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..425
FT /note="Voltage-dependent calcium channel gamma-8 subunit"
FT /id="PRO_0000164690"
FT TRANSMEM 19..39
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 129..149
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 158..178
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 208..228
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 318..338
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 272..304
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 343..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 377..425
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 386..402
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 409..425
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 252
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHW2"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VHW2"
FT CONFLICT 16
FT /note="E -> K (in Ref. 3; AAK15019)"
FT /evidence="ECO:0000305"
FT CONFLICT 362
FT /note="A -> S (in Ref. 1; AAL50049)"
FT /evidence="ECO:0000305"
FT CONFLICT 386
FT /note="G -> R (in Ref. 1; AAL50049)"
FT /evidence="ECO:0000305"
FT CONFLICT 394
FT /note="A -> T (in Ref. 1; AAL50049)"
FT /evidence="ECO:0000305"
FT CONFLICT 409
FT /note="E -> G (in Ref. 1; AAL50049)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 425 AA; 43313 MW; E8C33CC5CF6184A1 CRC64;
MESLKRWNEE RGLWCEKGVQ VLLTTVGAFA AFGLMTIAIS TDYWLYTRAL ICNTTNLTAG
GDDGTPHRGG GGASEKKDPG GLTHSGLWRI CCLEGLKRGV CVKINHFPED TDYDHDSAEY
LLRVVRASSI FPILSAILLL LGGVCVAASR VYKSKRNIIL GAGILFVAAG LSNIIGVIVY
ISANAGEPGP KRDEEKKNHY SYGWSFYFGG LSFILAEVIG VLAVNIYIER SREAHCQSRS
DLLKAGGGAG GSGGSGPSAI LRLPSYRFRY RRRSRSSSRS SEPSPSRDAS PGGPGGPGFA
STDISMYTLS RDPSKGSVAA GLAGAGGGGG GAVGAFGGAA GGAGGGGGGG GGAGAERDRG
GASGFLTLHN AFPKEAGGGV TVTVTGPPAP PAPAPPAPSA PAPGTLAKEA AASNTNTLNR
KTTPV
