ID   GBRD_HUMAN              Reviewed;         452 AA.
AC   O14764; Q8N4N9;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   15-FEB-2005, sequence version 2.
DT   13-FEB-2019, entry version 180.
DE   RecName: Full=Gamma-aminobutyric acid receptor subunit delta;
DE   AltName: Full=GABA(A) receptor subunit delta;
DE   Flags: Precursor;
GN   Name=GABRD;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT HIS-220.
RA   Day T.M., Hartnett C., Blankenbiller K., Ramabhadran T.V.;
RL   Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA   Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA   Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA   McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA   Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA   Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA   Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA   Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA   Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA   Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA   Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA   Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA   Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA   Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA   Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA   Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA   Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA   Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA   Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA   Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA   Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA   Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA   Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [3]
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   VARIANTS GEFS+5 ALA-177 AND CYS-220, VARIANT HIS-220, CHARACTERIZATION
RP   OF VARIANTS GEFS+5 ALA-177 AND CYS-220, AND CHARACTERIZATION OF
RP   VARIANT HIS-220.
RX   PubMed=15115768; DOI=10.1093/hmg/ddh146;
RA   Dibbens L.M., Feng H.-J., Richards M.C., Harkin L.A., Hodgson B.L.,
RA   Scott D., Jenkins M., Petrou S., Sutherland G.R., Scheffer I.E.,
RA   Berkovic S.F., Macdonald R.L., Mulley J.C.;
RT   "GABRD encoding a protein for extra- or peri-synaptic GABAA receptors
RT   is a susceptibility locus for generalized epilepsies.";
RL   Hum. Mol. Genet. 13:1315-1319(2004).
RN   [5]
RP   VARIANT ILE-370.
RX   PubMed=27864847; DOI=10.1002/humu.23149;
RG   Clinical Study Group;
RA   Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D.,
RA   Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D.,
RA   Bigoni S., Barba C., Mari F., Montomoli M., Pisano T., Rosati A.,
RA   Guerrini R.;
RT   "Diagnostic targeted resequencing in 349 patients with drug-resistant
RT   pediatric epilepsies identifies causative mutations in 30 different
RT   genes.";
RL   Hum. Mutat. 38:216-225(2017).
RN   [6]
RP   VARIANT SER-62.
RX   PubMed=27932480; DOI=10.1681/ASN.2016040387;
RG   NephroS;
RG   UK study of Nephrotic Syndrome;
RA   Bierzynska A., Soderquest K., Dean P., Colby E., Rollason R.,
RA   Jones C., Inward C.D., McCarthy H.J., Simpson M.A., Lord G.M.,
RA   Williams M., Welsh G.I., Koziell A.B., Saleem M.A.;
RT   "MAGI2 mutations cause congenital nephrotic syndrome.";
RL   J. Am. Soc. Nephrol. 28:1614-1621(2017).
CC   -!- FUNCTION: GABA, the major inhibitory neurotransmitter in the
CC       vertebrate brain, mediates neuronal inhibition by binding to the
CC       GABA/benzodiazepine receptor and opening an integral chloride
CC       channel.
CC   -!- SUBUNIT: Generally pentameric. There are five types of GABA(A)
CC       receptor chains: alpha, beta, gamma, delta, and rho.
CC   -!- INTERACTION:
CC       Q7Z3S9:NOTCH2NLA; NbExp=3; IntAct=EBI-744352, EBI-945833;
CC       Q9UMX0:UBQLN1; NbExp=4; IntAct=EBI-744352, EBI-741480;
CC       Q9UMX0-2:UBQLN1; NbExp=3; IntAct=EBI-744352, EBI-10173939;
CC   -!- SUBCELLULAR LOCATION: Cell junction, synapse, postsynaptic cell
CC       membrane; Multi-pass membrane protein. Cell membrane; Multi-pass
CC       membrane protein.
CC   -!- DISEASE: Generalized epilepsy with febrile seizures plus 5
CC       (GEFS+5) [MIM:613060]: A rare autosomal dominant, familial
CC       condition with incomplete penetrance and large intrafamilial
CC       variability. Patients display febrile seizures persisting
CC       sometimes beyond the age of 6 years and/or a variety of afebrile
CC       seizure types. This disease combines febrile seizures, generalized
CC       seizures often precipitated by fever at age 6 years or more, and
CC       partial seizures, with a variable degree of severity.
CC       {ECO:0000269|PubMed:15115768}. Note=Disease susceptibility is
CC       associated with variations affecting the gene represented in this
CC       entry.
CC   -!- DISEASE: Epilepsy, idiopathic generalized 10 (EIG10) [MIM:613060]:
CC       A disorder characterized by recurring generalized seizures in the
CC       absence of detectable brain lesions and/or metabolic
CC       abnormalities. Generalized seizures arise diffusely and
CC       simultaneously from both hemispheres of the brain. Note=Disease
CC       susceptibility is associated with variations affecting the gene
CC       represented in this entry.
CC   -!- DISEASE: Juvenile myoclonic epilepsy 7 (EJM7) [MIM:613060]: A
CC       subtype of idiopathic generalized epilepsy. Patients have afebrile
CC       seizures only, with onset in adolescence (rather than in
CC       childhood) and myoclonic jerks which usually occur after awakening
CC       and are triggered by sleep deprivation and fatigue. Note=Disease
CC       susceptibility is associated with variations affecting the gene
CC       represented in this entry.
CC   -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9)
CC       family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily.
CC       GABRD sub-subfamily. {ECO:0000305}.
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DR   EMBL; AF016917; AAB70007.1; -; mRNA.
DR   EMBL; AL391845; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC033801; AAH33801.1; -; mRNA.
DR   CCDS; CCDS36.1; -.
DR   RefSeq; NP_000806.2; NM_000815.4.
DR   UniGene; Hs.113882; -.
DR   ProteinModelPortal; O14764; -.
DR   BioGrid; 108837; 17.
DR   ComplexPortal; CPX-2951; GABA-A receptor, alpha-6/beta-3/delta.
DR   ComplexPortal; CPX-2952; GABA-A receptor, alpha-6/beta-2/delta.
DR   ComplexPortal; CPX-2953; GABA-A receptor, alpha-4/beta-2/delta.
DR   ComplexPortal; CPX-2954; GABA-A receptor, alpha-4/beta-3/delta.
DR   CORUM; O14764; -.
DR   IntAct; O14764; 6.
DR   MINT; O14764; -.
DR   STRING; 9606.ENSP00000367848; -.
DR   ChEMBL; CHEMBL3591; -.
DR   DrugBank; DB00659; Acamprosate.
DR   DrugBank; DB00546; Adinazolam.
DR   DrugBank; DB00404; Alprazolam.
DR   DrugBank; DB00543; Amoxapine.
DR   DrugBank; DB01558; Bromazepam.
DR   DrugBank; DB00237; Butabarbital.
DR   DrugBank; DB00241; Butalbital.
DR   DrugBank; DB00475; Chlordiazepoxide.
DR   DrugBank; DB01594; Cinolazepam.
DR   DrugBank; DB00349; Clobazam.
DR   DrugBank; DB01068; Clonazepam.
DR   DrugBank; DB00628; Clorazepate.
DR   DrugBank; DB01559; Clotiazepam.
DR   DrugBank; DB01189; Desflurane.
DR   DrugBank; DB00829; Diazepam.
DR   DrugBank; DB00228; Enflurane.
DR   DrugBank; DB01049; Ergoloid mesylate.
DR   DrugBank; DB01215; Estazolam.
DR   DrugBank; DB00402; Eszopiclone.
DR   DrugBank; DB00898; Ethanol.
DR   DrugBank; DB00189; Ethchlorvynol.
DR   DrugBank; DB00292; Etomidate.
DR   DrugBank; DB01567; Fludiazepam.
DR   DrugBank; DB01205; Flumazenil.
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; DB00186; Lorazepam.
DR   DrugBank; DB00371; Meprobamate.
DR   DrugBank; DB00463; Metharbital.
DR   DrugBank; DB01028; Methoxyflurane.
DR   DrugBank; DB01107; Methyprylon.
DR   DrugBank; DB00683; Midazolam.
DR   DrugBank; DB01595; Nitrazepam.
DR   DrugBank; DB00334; Olanzapine.
DR   DrugBank; DB00842; Oxazepam.
DR   DrugBank; DB00312; Pentobarbital.
DR   DrugBank; DB01708; Prasterone.
DR   DrugBank; DB01588; Prazepam.
DR   DrugBank; DB00794; Primidone.
DR   DrugBank; DB00818; Propofol.
DR   DrugBank; DB01589; Quazepam.
DR   DrugBank; DB01236; Sevoflurane.
DR   DrugBank; DB00306; Talbutal.
DR   DrugBank; DB00231; Temazepam.
DR   DrugBank; DB11582; Thiocolchicoside.
DR   DrugBank; DB00273; Topiramate.
DR   DrugBank; DB00897; Triazolam.
DR   iPTMnet; O14764; -.
DR   PhosphoSitePlus; O14764; -.
DR   BioMuta; GABRD; -.
DR   PaxDb; O14764; -.
DR   PeptideAtlas; O14764; -.
DR   PRIDE; O14764; -.
DR   ProteomicsDB; 48213; -.
DR   DNASU; 2563; -.
DR   Ensembl; ENST00000378585; ENSP00000367848; ENSG00000187730.
DR   GeneID; 2563; -.
DR   KEGG; hsa:2563; -.
DR   UCSC; uc001aip.3; human.
DR   CTD; 2563; -.
DR   DisGeNET; 2563; -.
DR   EuPathDB; HostDB:ENSG00000187730.7; -.
DR   GeneCards; GABRD; -.
DR   HGNC; HGNC:4084; GABRD.
DR   HPA; HPA044371; -.
DR   MalaCards; GABRD; -.
DR   MIM; 137163; gene.
DR   MIM; 613060; phenotype.
DR   neXtProt; NX_O14764; -.
DR   OpenTargets; ENSG00000187730; -.
DR   Orphanet; 1606; 1p36 deletion syndrome.
DR   Orphanet; 36387; Generalized epilepsy with febrile seizures-plus.
DR   Orphanet; 307; Juvenile myoclonic epilepsy.
DR   PharmGKB; PA28498; -.
DR   eggNOG; KOG3643; Eukaryota.
DR   eggNOG; ENOG410XPWH; LUCA.
DR   GeneTree; ENSGT00940000160122; -.
DR   HOGENOM; HOG000231335; -.
DR   HOVERGEN; HBG051707; -.
DR   InParanoid; O14764; -.
DR   KO; K05184; -.
DR   OMA; EVNMEYT; -.
DR   OrthoDB; 480926at2759; -.
DR   PhylomeDB; O14764; -.
DR   TreeFam; TF315453; -.
DR   GeneWiki; GABRD; -.
DR   GenomeRNAi; 2563; -.
DR   PRO; PR:O14764; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   Bgee; ENSG00000187730; Expressed in 100 organ(s), highest expression level in right hemisphere of cerebellum.
DR   ExpressionAtlas; O14764; baseline and differential.
DR   Genevisible; O14764; HS.
DR   GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR   GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
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:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR   GO; GO:0099055; C:integral component of postsynaptic membrane; IEA:Ensembl.
DR   GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR   GO; GO:0045202; C:synapse; IBA:GO_Central.
DR   GO; GO:0005254; F:chloride channel activity; IEA:UniProtKB-KW.
DR   GO; GO:0004890; F:GABA-A receptor activity; TAS:ProtInc.
DR   GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; IEA:Ensembl.
DR   GO; GO:0007268; P:chemical synaptic transmission; 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:0007165; P:signal transduction; IBA:GO_Central.
DR   Gene3D; 2.70.170.10; -; 1.
DR   InterPro; IPR006028; GABAA/Glycine_rcpt.
DR   InterPro; IPR008098; GABAAd_rcpt.
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; IPR006029; Neurotrans-gated_channel_TM.
DR   InterPro; IPR018000; Neurotransmitter_ion_chnl_CS.
DR   PANTHER; PTHR18945; PTHR18945; 1.
DR   PANTHER; PTHR18945:SF34; PTHR18945:SF34; 1.
DR   Pfam; PF02931; Neur_chan_LBD; 1.
DR   Pfam; PF02932; Neur_chan_memb; 1.
DR   PRINTS; PR01722; GABAARDELTA.
DR   PRINTS; PR00253; GABAARECEPTR.
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   1: Evidence at protein level;
KW   Cell junction; Cell membrane; Chloride; Chloride channel;
KW   Complete proteome; Disease mutation; Disulfide bond; Epilepsy;
KW   Glycoprotein; Ion channel; Ion transport; Membrane; Phosphoprotein;
KW   Polymorphism; Postsynaptic cell membrane; Reference proteome; Signal;
KW   Synapse; Transmembrane; Transmembrane helix; Transport.
FT   SIGNAL        1     16       {ECO:0000255}.
FT   CHAIN        17    452       Gamma-aminobutyric acid receptor subunit
FT                                delta.
FT                                /FTId=PRO_0000000468.
FT   TOPO_DOM     17    248       Extracellular. {ECO:0000305}.
FT   TRANSMEM    249    271       Helical. {ECO:0000305}.
FT   TRANSMEM    275    297       Helical. {ECO:0000305}.
FT   TRANSMEM    309    331       Helical. {ECO:0000305}.
FT   TOPO_DOM    332    429       Cytoplasmic. {ECO:0000305}.
FT   TRANSMEM    430    452       Helical. {ECO:0000305}.
FT   MOD_RES     390    390       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P18506}.
FT   CARBOHYD    103    103       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    106    106       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    164    178       {ECO:0000250}.
FT   VARIANT      62     62       P -> S. {ECO:0000269|PubMed:27932480}.
FT                                /FTId=VAR_079270.
FT   VARIANT     177    177       E -> A (in GEFS+5; reduced receptor
FT                                current amplitudes; dbSNP:rs121434580).
FT                                {ECO:0000269|PubMed:15115768}.
FT                                /FTId=VAR_043151.
FT   VARIANT     220    220       R -> C (in GEFS+5; unknown pathological
FT                                significance; does not affect receptor
FT                                current amplitudes; dbSNP:rs139300921).
FT                                {ECO:0000269|PubMed:15115768}.
FT                                /FTId=VAR_043152.
FT   VARIANT     220    220       R -> H (polymorphism; is a risk factor
FT                                for epilepsy; reduced receptor current
FT                                amplitudes; dbSNP:rs41307846).
FT                                {ECO:0000269|PubMed:15115768,
FT                                ECO:0000269|Ref.1}.
FT                                /FTId=VAR_043153.
FT   VARIANT     370    370       V -> I (found in a patient with childhood
FT                                onset epileptic encephalopathy; unknown
FT                                pathological significance;
FT                                dbSNP:rs1057519556).
FT                                {ECO:0000269|PubMed:27864847}.
FT                                /FTId=VAR_078225.
SQ   SEQUENCE   452 AA;  50708 MW;  682501DE93144CE4 CRC64;
     MDAPARLLAP LLLLCAQQLR GTRAMNDIGD YVGSNLEISW LPNLDGLIAG YARNFRPGIG
     GPPVNVALAL EVASIDHISE ANMEYTMTVF LHQSWRDSRL SYNHTNETLG LDSRFVDKLW
     LPDTFIVNAK SAWFHDVTVE NKLIRLQPDG VILYSIRITS TVACDMDLAK YPMDEQECML
     DLESYGYSSE DIVYYWSESQ EHIHGLDKLQ LAQFTITSYR FTTELMNFKS AGQFPRLSLH
     FHLRRNRGVY IIQSYMPSVL LVAMSWVSFW ISQAAVPARV SLGITTVLTM TTLMVSARSS
     LPRASAIKAL DVYFWICYVF VFAALVEYAF AHFNADYRKK QKAKVKVSRP RAEMDVRNAI
     VLFSLSAAGV TQELAISRRQ RRVPGNLMGS YRSVGVETGE TKKEGAARSG GQGGIRARLR
     PIDADTIDIY ARAVFPAAFA AVNVIYWAAY AM
//