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   24-JAN-2024, entry version 162.
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; 14.
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; DB09235; Efonidipine.
DR   DrugBank; DB00228; Enflurane.
DR   DrugBank; DB00153; Ergocalciferol.
DR   DrugBank; DB00622; Nicardipine.
DR   DrugBank; DB00421; Spironolactone.
DR   DrugBank; DB00661; Verapamil.
DR   TCDB; 8.A.16.2.6; the ca(+) channel auxiliary subunit Gama1-Gama8 (ccaGama) family.
DR   GlyGen; Q8WXS5; 2 sites.
DR   iPTMnet; Q8WXS5; -.
DR   PhosphoSitePlus; Q8WXS5; -.
DR   BioMuta; CACNG8; -.
DR   DMDM; 313104245; -.
DR   MassIVE; Q8WXS5; -.
DR   PaxDb; 9606-ENSP00000270458; -.
DR   PeptideAtlas; Q8WXS5; -.
DR   ProteomicsDB; 75095; -.
DR   Antibodypedia; 32771; 107 antibodies from 25 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   AGR; HGNC:13628; -.
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; SMYNTER; -.
DR   OrthoDB; 2957055at2759; -.
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 1054 CRISPR screens.
DR   ChiTaRS; CACNG8; human.
DR   GenomeRNAi; 59283; -.
DR   Pharos; Q8WXS5; Tbio.
DR   PRO; PR:Q8WXS5; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q8WXS5; Protein.
DR   Bgee; ENSG00000142408; Expressed in postcentral gyrus and 73 other cell types or tissues.
DR   ExpressionAtlas; Q8WXS5; baseline and differential.
DR   GO; GO:0032281; C:AMPA glutamate receptor complex; ISS:UniProtKB.
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   Gene3D; 1.20.140.150; -; 1.
DR   InterPro; IPR004031; PMP22/EMP/MP20/Claudin.
DR   InterPro; IPR008372; VDCC_g8su.
DR   InterPro; IPR008368; VDCC_gsu.
DR   PANTHER; PTHR12107; VOLTAGE-DEPENDENT CALCIUM CHANNEL GAMMA SUBUNIT; 1.
DR   PANTHER; PTHR12107:SF2; VOLTAGE-DEPENDENT CALCIUM CHANNEL GAMMA-8 SUBUNIT; 1.
DR   Pfam; PF00822; PMP22_Claudin; 1.
DR   PRINTS; PR01792; VDCCGAMMA.
DR   PRINTS; PR01796; VDCCGAMMA8.
DR   Genevisible; Q8WXS5; HS.
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
//