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   24-JAN-2024, entry version 197.
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; 4.
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; DB05087; Ganaxolone.
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   DrugBank; DB00909; Zonisamide.
DR   DrugCentral; Q99928; -.
DR   GlyCosmos; Q99928; 2 sites, No reported glycans.
DR   GlyGen; Q99928; 2 sites.
DR   iPTMnet; Q99928; -.
DR   PhosphoSitePlus; Q99928; -.
DR   BioMuta; GABRG3; -.
DR   DMDM; 13959689; -.
DR   MassIVE; Q99928; -.
DR   PaxDb; 9606-ENSP00000479113; -.
DR   PeptideAtlas; Q99928; -.
DR   ProteomicsDB; 33459; -.
DR   ProteomicsDB; 78522; -. [Q99928-1]
DR   Antibodypedia; 5045; 109 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   AGR; HGNC:4088; -.
DR   CTD; 2567; -.
DR   DisGeNET; 2567; -.
DR   GeneCards; GABRG3; -.
DR   GeneReviews; GABRG3; -.
DR   HGNC; HGNC:4088; GABRG3.
DR   HPA; ENSG00000182256; Tissue enhanced (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; MYWQELE; -.
DR   OrthoDB; 4265336at2759; -.
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; 12 hits in 1167 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 male germ line stem cell (sensu Vertebrata) in testis and 79 other cell types or tissues.
DR   ExpressionAtlas; Q99928; baseline and differential.
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:0015630; C:microtubule cytoskeleton; IDA:HPA.
DR   GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR   GO; GO:0005730; C:nucleolus; IDA:HPA.
DR   GO; GO:0005886; C:plasma membrane; IDA:HPA.
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: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 monoatomic ion channel activity; IBA:GO_Central.
DR   GO; GO:1904315; F:transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential; IEA:Ensembl.
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:0060078; P:regulation of postsynaptic membrane potential; IBA:GO_Central.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR   GO; GO:0051932; P:synaptic transmission, GABAergic; IBA:GO_Central.
DR   CDD; cd19000; LGIC_ECD_GABAAR_G; 1.
DR   CDD; cd19054; LGIC_TM_GABAAR_gamma; 1.
DR   Gene3D; 2.70.170.10; Neurotransmitter-gated ion-channel ligand-binding domain; 1.
DR   Gene3D; 1.20.58.390; Neurotransmitter-gated ion-channel transmembrane domain; 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   NCBIfam; TIGR00860; LIC; 1.
DR   PANTHER; PTHR18945:SF195; GAMMA-AMINOBUTYRIC ACID RECEPTOR SUBUNIT GAMMA-3; 1.
DR   PANTHER; PTHR18945; NEUROTRANSMITTER GATED ION CHANNEL; 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; SSF90112; Neurotransmitter-gated ion-channel transmembrane pore; 1.
DR   SUPFAM; SSF63712; Nicotinic receptor ligand binding domain-like; 1.
DR   PROSITE; PS00236; NEUROTR_ION_CHANNEL; 1.
DR   Genevisible; Q99928; HS.
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; uncertain
FT                   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
//