GBRG3_HUMAN
ID GBRG3_HUMAN Reviewed; 467 AA.
AC Q99928; G3V594; Q9HD46; Q9NYT2;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 04-MAY-2001, sequence version 2.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Gamma-aminobutyric acid receptor subunit gamma-3;
DE AltName: Full=GABA(A) receptor subunit gamma-3;
DE Flags: Precursor;
GN Name=GABRG3;
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] (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=8719414; DOI=10.1016/0922-4106(95)90070-5;
RA Hadingham K.L., Wafford K.A., Thompson S.A., Palmer K.J., Whiting P.J.;
RT "Expression and pharmacology of human GABAA receptors containing gamma 3
RT subunits.";
RL Eur. J. Pharmacol. 291:301-309(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Han M.K., Chen Y.-H., Nurmi E.L., Sutcliffe J.S.;
RT "Gene structure and organization of the GABAA receptor gamma 3 subunit
RT (GABRG3) gene.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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] (ISOFORM 2).
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 19-467.
RA Kim S.-J., Gonen D., Yang Z.-Y., Reliford A., Dy A., Leventhal B.L.,
RA Cook E.H. Jr.;
RT "Genomic organization of GABAA receptor gamma 3 subunit gene (GABRG3).";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP VARIANT ALA-352.
RX PubMed=26566883; DOI=10.1136/jmedgenet-2015-103179;
RA Rafiullah R., Aslamkhan M., Paramasivam N., Thiel C., Mustafa G.,
RA Wiemann S., Schlesner M., Wade R.C., Rappold G.A., Berkel S.;
RT "Homozygous missense mutation in the LMAN2L gene segregates with
RT intellectual disability in a large consanguineous Pakistani family.";
RL J. Med. Genet. 53:138-144(2016).
CC -!- FUNCTION: GABA, the major inhibitory neurotransmitter in the vertebrate
CC brain, mediates neuronal inhibition by binding to the
CC GABA/benzodiazepine receptor and opening an integral chloride channel.
CC -!- SUBUNIT: Generally pentameric. There are five types of GABA(A) receptor
CC chains: alpha, beta, gamma, delta, and rho.
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane; Multi-pass membrane
CC protein. Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99928-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99928-2; Sequence=VSP_047543, VSP_047544;
CC -!- PTM: May be palmitoylated. {ECO:0000250}.
CC -!- MISCELLANEOUS: This subunit carries the benzodiazepine binding site.
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRG3 sub-
CC subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Forbidden fruit - Issue 56
CC of March 2005;
CC URL="https://web.expasy.org/spotlight/back_issues/056";
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DR EMBL; S82769; AAB39369.1; -; mRNA.
DR EMBL; AF269144; AAF99698.1; -; Genomic_DNA.
DR EMBL; AF269135; AAF99698.1; JOINED; Genomic_DNA.
DR EMBL; AF269136; AAF99698.1; JOINED; Genomic_DNA.
DR EMBL; AF269137; AAF99698.1; JOINED; Genomic_DNA.
DR EMBL; AF269138; AAF99698.1; JOINED; Genomic_DNA.
DR EMBL; AF269139; AAF99698.1; JOINED; Genomic_DNA.
DR EMBL; AF269140; AAF99698.1; JOINED; Genomic_DNA.
DR EMBL; AF269141; AAF99698.1; JOINED; Genomic_DNA.
DR EMBL; AF269142; AAF99698.1; JOINED; Genomic_DNA.
DR EMBL; AF269143; AAF99698.1; JOINED; Genomic_DNA.
DR EMBL; AC104002; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC127511; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC135326; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC136896; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC144833; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC145436; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; EU606049; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471151; EAW57658.1; -; Genomic_DNA.
DR EMBL; BC045709; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AH009226; AAF63215.1; -; Genomic_DNA.
DR CCDS; CCDS45195.1; -. [Q99928-1]
DR CCDS; CCDS59251.1; -. [Q99928-2]
DR RefSeq; NP_001257802.1; NM_001270873.1. [Q99928-2]
DR RefSeq; NP_150092.2; NM_033223.4. [Q99928-1]
DR AlphaFoldDB; Q99928; -.
DR SMR; Q99928; -.
DR BioGRID; 108841; 3.
DR STRING; 9606.ENSP00000479113; -.
DR ChEMBL; CHEMBL3885573; -.
DR ChEMBL; CHEMBL3885577; -.
DR DrugBank; DB12537; 1,2-Benzodiazepine.
DR DrugBank; DB00546; Adinazolam.
DR DrugBank; DB06579; Adipiplon.
DR DrugBank; DB00404; Alprazolam.
DR DrugBank; DB00543; Amoxapine.
DR DrugBank; DB11901; Apalutamide.
DR DrugBank; DB14719; Bentazepam.
DR DrugBank; DB11859; Brexanolone.
DR DrugBank; DB01558; Bromazepam.
DR DrugBank; DB09017; Brotizolam.
DR DrugBank; DB00237; Butabarbital.
DR DrugBank; DB00241; Butalbital.
DR DrugBank; DB01489; Camazepam.
DR DrugBank; DB00475; Chlordiazepoxide.
DR DrugBank; DB14715; Cinazepam.
DR DrugBank; DB01594; Cinolazepam.
DR DrugBank; DB00349; Clobazam.
DR DrugBank; DB01068; Clonazepam.
DR DrugBank; DB00628; Clorazepic acid.
DR DrugBank; DB01559; Clotiazepam.
DR DrugBank; DB01553; Cloxazolam.
DR DrugBank; DB01511; Delorazepam.
DR DrugBank; DB01189; Desflurane.
DR DrugBank; DB00829; Diazepam.
DR DrugBank; DB13837; Doxefazepam.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB01215; Estazolam.
DR DrugBank; DB00402; Eszopiclone.
DR DrugBank; DB00898; Ethanol.
DR DrugBank; DB00189; Ethchlorvynol.
DR DrugBank; DB01545; Ethyl loflazepate.
DR DrugBank; DB09166; Etizolam.
DR DrugBank; DB00292; Etomidate.
DR DrugBank; DB01567; Fludiazepam.
DR DrugBank; DB01205; Flumazenil.
DR DrugBank; DB01544; Flunitrazepam.
DR DrugBank; DB00690; Flurazepam.
DR DrugBank; DB01437; Glutethimide.
DR DrugBank; DB00801; Halazepam.
DR DrugBank; DB01159; Halothane.
DR DrugBank; DB00753; Isoflurane.
DR DrugBank; DB01587; Ketazolam.
DR DrugBank; DB00555; Lamotrigine.
DR DrugBank; DB13643; Loprazolam.
DR DrugBank; DB00186; Lorazepam.
DR DrugBank; DB13872; Lormetazepam.
DR DrugBank; DB13437; Medazepam.
DR DrugBank; DB00603; Medroxyprogesterone acetate.
DR DrugBank; DB01043; Memantine.
DR DrugBank; DB00371; Meprobamate.
DR DrugBank; DB00463; Metharbital.
DR DrugBank; DB01028; Methoxyflurane.
DR DrugBank; DB01107; Methyprylon.
DR DrugBank; DB15489; Mexazolam.
DR DrugBank; DB00683; Midazolam.
DR DrugBank; DB01595; Nitrazepam.
DR DrugBank; DB14028; Nordazepam.
DR DrugBank; DB00334; Olanzapine.
DR DrugBank; DB00842; Oxazepam.
DR DrugBank; DB14672; Oxazepam acetate.
DR DrugBank; DB00312; Pentobarbital.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB13335; Pinazepam.
DR DrugBank; DB01708; Prasterone.
DR DrugBank; DB01588; Prazepam.
DR DrugBank; DB00794; Primidone.
DR DrugBank; DB00818; Propofol.
DR DrugBank; DB01589; Quazepam.
DR DrugBank; DB12404; Remimazolam.
DR DrugBank; DB01236; Sevoflurane.
DR DrugBank; DB09118; Stiripentol.
DR DrugBank; DB00306; Talbutal.
DR DrugBank; DB01956; Taurine.
DR DrugBank; DB00231; Temazepam.
DR DrugBank; DB11582; Thiocolchicoside.
DR DrugBank; DB00897; Triazolam.
DR DrugCentral; Q99928; -.
DR GlyGen; Q99928; 2 sites.
DR iPTMnet; Q99928; -.
DR PhosphoSitePlus; Q99928; -.
DR BioMuta; GABRG3; -.
DR DMDM; 13959689; -.
DR MassIVE; Q99928; -.
DR PaxDb; Q99928; -.
DR PeptideAtlas; Q99928; -.
DR PRIDE; Q99928; -.
DR ProteomicsDB; 33459; -.
DR ProteomicsDB; 78522; -. [Q99928-1]
DR Antibodypedia; 5045; 104 antibodies from 19 providers.
DR DNASU; 2567; -.
DR Ensembl; ENST00000555083.5; ENSP00000452244.1; ENSG00000182256.13. [Q99928-2]
DR Ensembl; ENST00000615808.5; ENSP00000479113.1; ENSG00000182256.13. [Q99928-1]
DR GeneID; 2567; -.
DR KEGG; hsa:2567; -.
DR MANE-Select; ENST00000615808.5; ENSP00000479113.1; NM_033223.5; NP_150092.2.
DR UCSC; uc001zbf.5; human. [Q99928-1]
DR CTD; 2567; -.
DR DisGeNET; 2567; -.
DR GeneCards; GABRG3; -.
DR GeneReviews; GABRG3; -.
DR HGNC; HGNC:4088; GABRG3.
DR HPA; ENSG00000182256; Tissue enhanced (brain, retina, testis).
DR MalaCards; GABRG3; -.
DR MIM; 600233; gene.
DR neXtProt; NX_Q99928; -.
DR OpenTargets; ENSG00000182256; -.
DR PharmGKB; PA28502; -.
DR VEuPathDB; HostDB:ENSG00000182256; -.
DR eggNOG; KOG3642; Eukaryota.
DR GeneTree; ENSGT00940000155607; -.
DR HOGENOM; CLU_010920_2_0_1; -.
DR InParanoid; Q99928; -.
DR OMA; PDSTRWI; -.
DR OrthoDB; 1057372at2759; -.
DR PhylomeDB; Q99928; -.
DR TreeFam; TF315453; -.
DR PathwayCommons; Q99928; -.
DR Reactome; R-HSA-1236394; Signaling by ERBB4.
DR Reactome; R-HSA-977443; GABA receptor activation.
DR SignaLink; Q99928; -.
DR BioGRID-ORCS; 2567; 10 hits in 1081 CRISPR screens.
DR ChiTaRS; GABRG3; human.
DR GeneWiki; GABRG3; -.
DR GenomeRNAi; 2567; -.
DR Pharos; Q99928; Tclin.
DR PRO; PR:Q99928; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q99928; protein.
DR Bgee; ENSG00000182256; Expressed in cortical plate and 77 other tissues.
DR ExpressionAtlas; Q99928; baseline and differential.
DR Genevisible; Q99928; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0032590; C:dendrite membrane; IBA:GO_Central.
DR GO; GO:1902711; C:GABA-A receptor complex; IBA:GO_Central.
DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099699; C:integral component of synaptic membrane; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0098794; C:postsynapse; IBA:GO_Central.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0005231; F:excitatory extracellular ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0004890; F:GABA-A receptor activity; IEA:Ensembl.
DR GO; GO:0022851; F:GABA-gated chloride ion channel activity; IBA:GO_Central.
DR GO; GO:0005237; F:inhibitory extracellular ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; IBA:GO_Central.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:1902476; P:chloride transmembrane transport; IBA:GO_Central.
DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IBA:GO_Central.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:0060078; P:regulation of postsynaptic membrane potential; IBA:GO_Central.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0051932; P:synaptic transmission, GABAergic; IBA:GO_Central.
DR Gene3D; 1.20.58.390; -; 1.
DR Gene3D; 2.70.170.10; -; 1.
DR InterPro; IPR006028; GABAA/Glycine_rcpt.
DR InterPro; IPR005440; GABBAg3_rcpt.
DR InterPro; IPR005437; GABRG-1/4.
DR InterPro; IPR006202; Neur_chan_lig-bd.
DR InterPro; IPR036734; Neur_chan_lig-bd_sf.
DR InterPro; IPR006201; Neur_channel.
DR InterPro; IPR036719; Neuro-gated_channel_TM_sf.
DR InterPro; IPR038050; Neuro_actylchol_rec.
DR InterPro; IPR006029; Neurotrans-gated_channel_TM.
DR InterPro; IPR018000; Neurotransmitter_ion_chnl_CS.
DR PANTHER; PTHR18945; PTHR18945; 1.
DR Pfam; PF02931; Neur_chan_LBD; 1.
DR Pfam; PF02932; Neur_chan_memb; 1.
DR PRINTS; PR00253; GABAARECEPTR.
DR PRINTS; PR01620; GABAARGAMMA.
DR PRINTS; PR01623; GABAARGAMMA3.
DR PRINTS; PR00252; NRIONCHANNEL.
DR SUPFAM; SSF63712; SSF63712; 1.
DR SUPFAM; SSF90112; SSF90112; 1.
DR TIGRFAMs; TIGR00860; LIC; 1.
DR PROSITE; PS00236; NEUROTR_ION_CHANNEL; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Chloride; Chloride channel;
KW Disulfide bond; Glycoprotein; Ion channel; Ion transport; Lipoprotein;
KW Membrane; Palmitate; Postsynaptic cell membrane; Reference proteome;
KW Signal; Synapse; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..467
FT /note="Gamma-aminobutyric acid receptor subunit gamma-3"
FT /id="PRO_0000000481"
FT TOPO_DOM 18..254
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 255..277
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TRANSMEM 281..303
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TRANSMEM 315..337
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 338..443
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 444..467
FT /note="Helical"
FT /evidence="ECO:0000305"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 228
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 171..185
FT /evidence="ECO:0000250"
FT VAR_SEQ 239..253
FT /note="DYVVMTIYFELSRRM -> RNLLKEAQLSKAREA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_047543"
FT VAR_SEQ 254..467
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_047544"
FT VARIANT 352
FT /note="T -> A (found in a patient with MRT52; unknown
FT pathological significance; dbSNP:rs2066712)"
FT /evidence="ECO:0000269|PubMed:26566883"
FT /id="VAR_033957"
FT CONFLICT 172
FT /note="Q -> R (in Ref. 5; BC045709)"
FT /evidence="ECO:0000305"
FT CONFLICT 386
FT /note="T -> P (in Ref. 1; AAB39369)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 467 AA; 54289 MW; 1B22D145166438D6 CRC64;
MAPKLLLLLC LFSGLHARSR KVEEDEYEDS SSNQKWVLAP KSQDTDVTLI LNKLLREYDK
KLRPDIGIKP TVIDVDIYVN SIGPVSSINM EYQIDIFFAQ TWTDSRLRFN STMKILTLNS
NMVGLIWIPD TIFRNSKTAE AHWITTPNQL LRIWNDGKIL YTLRLTINAE CQLQLHNFPM
DEHSCPLIFS SYGYPKEEMI YRWRKNSVEA ADQKSWRLYQ FDFMGLRNTT EIVTTSAGDY
VVMTIYFELS RRMGYFTIQT YIPCILTVVL SWVSFWIKKD ATPARTALGI TTVLTMTTLS
TIARKSLPRV SYVTAMDLFV TVCFLFVFAA LMEYATLNYY SSCRKPTTTK KTTSLLHPDS
SRWIPERISL QAPSNYSLLD MRPPPTAMIT LNNSVYWQEF EDTCVYECLD GKDCQSFFCC
YEECKSGSWR KGRIHIDILE LDSYSRVFFP TSFLLFNLVY WVGYLYL
