O14764 (GBRD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gamma-aminobutyric acid receptor subunit delta

Alternative name(s):
GABA(A) receptor subunit delta

Gene names

Name:

GABRD

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	452 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Subunit structure	Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho.
Subcellular location	Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein.
Involvement in disease	Generalized epilepsy with febrile seizures plus 5 (GEFS+5) [MIM:613060]: A rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.4 Epilepsy, idiopathic generalized 10 (EIG10) [MIM:613060]: A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Juvenile myoclonic epilepsy 7 (EJM7) [MIM:613060]: A subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
Sequence similarities	Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRD sub-subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Transport
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Polymorphism
Disease	Disease mutation Epilepsy
Domain	Signal Transmembrane Transmembrane helix
Ligand	Chloride
Molecular function	Chloride channel Ion channel
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	synaptic transmission Inferred from electronic annotation. Source: Compara transport Traceable author statement PubMed 2176788. Source: ProtInc
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW chloride channel complex Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Traceable author statement PubMed 2176788. Source: ProtInc postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	GABA-A receptor activity Traceable author statement PubMed 2176788. Source: ProtInc chloride channel activity Inferred from electronic annotation. Source: UniProtKB-KW extracellular ligand-gated ion channel activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 16	16	Potential
	Chain	17 – 452	436	Gamma-aminobutyric acid receptor subunit delta		PRO_0000000468
Regions
	Topological domain	17 – 248	232	Extracellular Probable
	Transmembrane	249 – 271	23	Helical; Probable
	Transmembrane	275 – 297	23	Helical; Probable
	Transmembrane	309 – 331	23	Helical; Probable
	Topological domain	332 – 429	98	Cytoplasmic Probable
	Transmembrane	430 – 452	23	Helical; Probable
Amino acid modifications
	Glycosylation	103	1	N-linked (GlcNAc...) Potential
	Glycosylation	106	1	N-linked (GlcNAc...) Potential
	Disulfide bond	164 ↔ 178		By similarity
Natural variations
	Natural variant	177	1	E → A in GEFS+5; reduced receptor current amplitudes. Ref.4		VAR_043151
	Natural variant	220	1	R → C in a GEFS+ family; does not affect receptor current amplitudes; could be a rare polymorphism. Ref.4		VAR_043152
	Natural variant	220	1	R → H Associated with susceptibility to EIG10 and EJM7; reduced receptor current amplitudes. Ref.1 Ref.4 Corresponds to variant rs41307846 [ dbSNP | Ensembl ].		VAR_043153

Sequences

	Sequence		Length	Mass (Da)
	O14764 [UniParc]. Last modified February 15, 2005. Version 2. Checksum: 682501DE93144CE4	FASTA	452	50,708
	10 20 30 40 50 60 MDAPARLLAP LLLLCAQQLR GTRAMNDIGD YVGSNLEISW LPNLDGLIAG YARNFRPGIG 70 80 90 100 110 120 GPPVNVALAL EVASIDHISE ANMEYTMTVF LHQSWRDSRL SYNHTNETLG LDSRFVDKLW 130 140 150 160 170 180 LPDTFIVNAK SAWFHDVTVE NKLIRLQPDG VILYSIRITS TVACDMDLAK YPMDEQECML 190 200 210 220 230 240 DLESYGYSSE DIVYYWSESQ EHIHGLDKLQ LAQFTITSYR FTTELMNFKS AGQFPRLSLH 250 260 270 280 290 300 FHLRRNRGVY IIQSYMPSVL LVAMSWVSFW ISQAAVPARV SLGITTVLTM TTLMVSARSS 310 320 330 340 350 360 LPRASAIKAL DVYFWICYVF VFAALVEYAF AHFNADYRKK QKAKVKVSRP RAEMDVRNAI 370 380 390 400 410 420 VLFSLSAAGV TQELAISRRQ RRVPGNLMGS YRSVGVETGE TKKEGAARSG GQGGIRARLR 430 440 450 PIDADTIDIY ARAVFPAAFA AVNVIYWAAY AM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Day T.M., Hartnett C., Blankenbiller K., Ramabhadran T.V. Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT HIS-220.
[2]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies." Dibbens L.M., Feng H.-J., Richards M.C., Harkin L.A., Hodgson B.L., Scott D., Jenkins M., Petrou S., Sutherland G.R., Scheffer I.E., Berkovic S.F., Macdonald R.L., Mulley J.C. Hum. Mol. Genet. 13:1315-1319(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GEFS+5 ALA-177, VARIANTS CYS-220 AND HIS-220, CHARACTERIZATION OF VARIANT GEFS+5 ALA-177, CHARACTERIZATION OF VARIANTS CYS-220 AND HIS-220.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF016917 mRNA. Translation: AAB70007.1. AL391845 Genomic DNA. Translation: CAI15436.1. BC033801 mRNA. Translation: AAH33801.1.
IPI	IPI00375475.
RefSeq	NP_000806.2. NM_000815.4.
UniGene	Hs.113882.
3D structure databases
ProteinModelPortal	O14764.
ModBase	Search...
Protein-protein interaction databases
IntAct	O14764. 2 interactions.
MINT	MINT-1461496.
STRING	9606.ENSP00000367848.
PTM databases
PhosphoSite	O14764.
Proteomic databases
PaxDb	O14764.
PRIDE	O14764.
Protocols and materials databases
DNASU	2563.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000378585; ENSP00000367848; ENSG00000187730.
GeneID	2563.
KEGG	hsa:2563.
UCSC	uc001aip.2. human.
Organism-specific databases
CTD	2563.
GeneCards	GC01P001950.
HGNC	HGNC:4084. GABRD.
MIM	137163. gene. 613060. phenotype.
neXtProt	NX_O14764.
Orphanet	1606. 1p36 deletion syndrome. 36387. Generalized epilepsy with febrile seizures-plus context. 307. Juvenile myoclonic epilepsy.
PharmGKB	PA28498.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG308574.
HOGENOM	HOG000231335.
HOVERGEN	HBG051707.
InParanoid	O14764.
KO	K05184.
OMA	EYTMTVF.
OrthoDB	EOG4H9XKN.
PhylomeDB	O14764.
Gene expression databases
Bgee	O14764.
CleanEx	HS_GABRD.
Genevestigator	O14764.
GermOnline	ENSG00000187730. Homo sapiens.
Family and domain databases
Gene3D	2.70.170.10. 1 hit.
InterPro	IPR006028. GABAA_rcpt. IPR008098. GABAAd_rcpt. IPR006202. Neur_chan_lig-bd. IPR006201. Neur_channel. IPR006029. Neurotrans-gated_channel_TM. IPR018000. Neurotransmitter_ion_chnl_CS. [Graphical view]
PANTHER	PTHR18945. PTHR18945. 1 hit.
Pfam	PF02931. Neur_chan_LBD. 1 hit. PF02932. Neur_chan_memb. 1 hit. [Graphical view]
PRINTS	PR01722. GABAARDELTA. PR00253. GABAARECEPTR. PR00252. NRIONCHANNEL.
SUPFAM	SSF90112. Neu_channel_TM. 1 hit. SSF63712. Neur_chan_LBD. 1 hit.
TIGRFAMs	TIGR00860. LIC. 1 hit.
PROSITE	PS00236. NEUROTR_ION_CHANNEL. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O14764.
ChEMBL	CHEMBL3591.
GenomeRNAi	2563.
NextBio	10127.
SOURCE	Search...

Entry information

Entry name

GBRD_HUMAN

Accession

Primary (citable) accession number: O14764
Secondary accession number(s): Q8N4N9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	February 15, 2005
Last modified:	May 29, 2013
This is version 125 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.