CCG4_HUMAN
ID CCG4_HUMAN Reviewed; 327 AA.
AC Q9UBN1; B2RCK0;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Voltage-dependent calcium channel gamma-4 subunit;
DE AltName: Full=Neuronal voltage-gated calcium channel gamma-4 subunit;
DE AltName: Full=Transmembrane AMPAR regulatory protein gamma-4;
DE Short=TARP gamma-4;
GN Name=CACNG4;
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 [GENOMIC DNA].
RX PubMed=10613843; DOI=10.1101/gr.9.12.1204;
RA Burgess D.L., Davis C.F., Gefrides L.A., Noebels J.L.;
RT "Identification of three novel Ca(2+) channel gamma subunit genes reveals
RT molecular diversification by tandem and chromosome duplication.";
RL Genome Res. 9:1204-1213(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Black J.L. III, Lennon V.A.;
RT "Identification of the Homo sapiens putative voltage-gated calcium channel
RT gamma-4 subunit.";
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Caudate nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [6]
RP FUNCTION, AND SUBUNIT.
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 [7]
RP FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH CACNA1C, IDENTIFICATION IN A
RP COMPLEX WITH CACNA1C; CACNA2D1 AND CACNB1, SUBUNIT, AND SUBCELLULAR
RP LOCATION.
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 (PubMed:21127204). Regulates
CC the trafficking and gating properties of AMPA-selective glutamate
CC receptors (AMPARs), including GRIA1 and GRIA4. Promotes their targeting
CC to the cell membrane and synapses and modulates their gating properties
CC by slowing their rates of activation, deactivation and desensitization
CC and by mediating their resensitization (PubMed:21172611).
CC {ECO:0000269|PubMed:21127204, 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 (PubMed:21127204). Acts as an auxiliary subunit for AMPA-
CC selective glutamate receptors (AMPARs) (PubMed:21172611). Interacts
CC with GRIA1 (PubMed:21172611). {ECO:0000269|PubMed:21127204,
CC ECO:0000269|PubMed:21172611}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:21127204};
CC Multi-pass membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in heart left ventricle.
CC {ECO:0000269|PubMed:21127204}.
CC -!- SIMILARITY: Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.
CC {ECO:0000305}.
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DR EMBL; AF142625; AAF03090.1; -; Genomic_DNA.
DR EMBL; AF142622; AAF03090.1; JOINED; Genomic_DNA.
DR EMBL; AF142623; AAF03090.1; JOINED; Genomic_DNA.
DR EMBL; AF142624; AAF03090.1; JOINED; Genomic_DNA.
DR EMBL; AF162692; AAF14538.1; -; mRNA.
DR EMBL; AK315149; BAG37597.1; -; mRNA.
DR EMBL; CH471099; EAW89020.1; -; Genomic_DNA.
DR EMBL; BC034532; AAH34532.1; -; mRNA.
DR CCDS; CCDS11667.1; -.
DR RefSeq; NP_055220.1; NM_014405.3.
DR AlphaFoldDB; Q9UBN1; -.
DR SMR; Q9UBN1; -.
DR BioGRID; 117994; 75.
DR IntAct; Q9UBN1; 6.
DR STRING; 9606.ENSP00000262138; -.
DR ChEMBL; CHEMBL2363032; -.
DR DrugBank; DB13746; Bioallethrin.
DR DrugBank; DB11148; Butamben.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB00153; Ergocalciferol.
DR DrugBank; DB00421; Spironolactone.
DR TCDB; 8.A.16.2.3; the ca(+) channel auxiliary subunit Gama1-Gama8 (ccaGama) family.
DR GlyGen; Q9UBN1; 2 sites.
DR iPTMnet; Q9UBN1; -.
DR PhosphoSitePlus; Q9UBN1; -.
DR BioMuta; CACNG4; -.
DR DMDM; 10719940; -.
DR jPOST; Q9UBN1; -.
DR MassIVE; Q9UBN1; -.
DR PaxDb; Q9UBN1; -.
DR PeptideAtlas; Q9UBN1; -.
DR PRIDE; Q9UBN1; -.
DR ProteomicsDB; 84011; -.
DR Antibodypedia; 19199; 174 antibodies from 28 providers.
DR DNASU; 27092; -.
DR Ensembl; ENST00000262138.4; ENSP00000262138.3; ENSG00000075461.6.
DR GeneID; 27092; -.
DR KEGG; hsa:27092; -.
DR MANE-Select; ENST00000262138.4; ENSP00000262138.3; NM_014405.4; NP_055220.1.
DR UCSC; uc002jft.3; human.
DR CTD; 27092; -.
DR DisGeNET; 27092; -.
DR GeneCards; CACNG4; -.
DR HGNC; HGNC:1408; CACNG4.
DR HPA; ENSG00000075461; Tissue enhanced (brain, prostate).
DR MIM; 606404; gene.
DR neXtProt; NX_Q9UBN1; -.
DR OpenTargets; ENSG00000075461; -.
DR PharmGKB; PA26018; -.
DR VEuPathDB; HostDB:ENSG00000075461; -.
DR eggNOG; ENOG502QPQH; Eukaryota.
DR GeneTree; ENSGT01050000244893; -.
DR HOGENOM; CLU_053704_0_1_1; -.
DR InParanoid; Q9UBN1; -.
DR OMA; MGLPMGD; -.
DR OrthoDB; 1117127at2759; -.
DR PhylomeDB; Q9UBN1; -.
DR TreeFam; TF327980; -.
DR PathwayCommons; Q9UBN1; -.
DR Reactome; R-HSA-112308; Presynaptic depolarization and calcium channel opening.
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; Q9UBN1; -.
DR BioGRID-ORCS; 27092; 19 hits in 1061 CRISPR screens.
DR ChiTaRS; CACNG4; human.
DR GeneWiki; CACNG4; -.
DR GenomeRNAi; 27092; -.
DR Pharos; Q9UBN1; Tbio.
DR PRO; PR:Q9UBN1; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9UBN1; protein.
DR Bgee; ENSG00000075461; Expressed in cortical plate and 127 other tissues.
DR ExpressionAtlas; Q9UBN1; baseline and differential.
DR Genevisible; Q9UBN1; HS.
DR GO; GO:0032281; C:AMPA glutamate receptor complex; ISS:UniProtKB.
DR GO; GO:0044297; C:cell body; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IEA:Ensembl.
DR GO; GO:1990454; C:L-type voltage-gated calcium channel complex; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098839; C:postsynaptic density membrane; IBA:GO_Central.
DR GO; GO:0036477; C:somatodendritic compartment; IEA:Ensembl.
DR GO; GO:0005246; F:calcium channel regulator activity; IDA:UniProtKB.
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: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:2000969; P:positive regulation of AMPA receptor activity; 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:2000311; P:regulation of AMPA receptor activity; IDA:UniProtKB.
DR GO; GO:0098962; P:regulation of postsynaptic neurotransmitter receptor activity; IEA:Ensembl.
DR GO; GO:0042220; P:response to cocaine; IEA:Ensembl.
DR GO; GO:0019226; P:transmission of nerve impulse; IBA:GO_Central.
DR InterPro; IPR004031; PMP22/EMP/MP20/Claudin.
DR InterPro; IPR005423; VDCC_g4su.
DR InterPro; IPR008368; VDCC_gsu.
DR PANTHER; PTHR12107:SF7; PTHR12107:SF7; 1.
DR Pfam; PF00822; PMP22_Claudin; 1.
DR PRINTS; PR01792; VDCCGAMMA.
DR PRINTS; PR01603; VDCCGAMMA4.
PE 1: Evidence at protein level;
KW Calcium; Calcium channel; Calcium transport; Cell membrane; Glycoprotein;
KW Ion channel; Ion transport; Membrane; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..327
FT /note="Voltage-dependent calcium channel gamma-4 subunit"
FT /id="PRO_0000164678"
FT TOPO_DOM 1..9
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..107
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 108..128
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 129..136
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 137..157
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 158..186
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 187..207
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 208..327
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 235..261
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JJV4"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 45
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 327 AA; 36579 MW; 79630ACC03B1DAE6 CRC64;
MVRCDRGLQM LLTTAGAFAA FSLMAIAIGT DYWLYSSAHI CNGTNLTMDD GPPPRRARGD
LTHSGLWRVC CIEGIYKGHC FRINHFPEDN DYDHDSSEYL LRIVRASSVF PILSTILLLL
GGLCIGAGRI YSRKNNIVLS AGILFVAAGL SNIIGIIVYI SSNTGDPSDK RDEDKKNHYN
YGWSFYFGAL SFIVAETVGV LAVNIYIEKN KELRFKTKRE FLKASSSSPY ARMPSYRYRR
RRSRSSSRST EASPSRDVSP MGLKITGAIP MGELSMYTLS REPLKVTTAA SYSPDQEASF
LQVHDFFQQD LKEGFHVSML NRRTTPV
