P48169 (GBRA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gamma-aminobutyric acid receptor subunit alpha-4

Alternative name(s):
GABA(A) receptor subunit alpha-4

Gene names

Name:

GABRA4

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	554 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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.
Induction	The alpha4 beta2 gamma 2L receptor is not repressed by diazepam. Ref.1
Sequence similarities	Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA4 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
Domain	Signal Transmembrane Transmembrane helix
Ligand	Chloride
Molecular function	Chloride channel Ion channel Ligand-gated ion channel Receptor
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	central nervous system development Inferred from electronic annotation. Source: Compara gamma-aminobutyric acid signaling pathway Traceable author statement Ref.1. Source: ProtInc ion transmembrane transport Traceable author statement. Source: Reactome regulation of response to drug Inferred from electronic annotation. Source: Compara
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 Ref.1. Source: ProtInc postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	GABA-A receptor activity Inferred from electronic annotation. Source: InterPro benzodiazepine receptor activity Traceable author statement Ref.1. 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 – 35	35	Potential
	Chain	36 – 554	519	Gamma-aminobutyric acid receptor subunit alpha-4		PRO_0000000441
Regions
	Topological domain	36 – 258	223	Extracellular Probable
	Transmembrane	259 – 280	22	Helical; Probable
	Transmembrane	285 – 306	22	Helical; Probable
	Transmembrane	318 – 340	23	Helical; Probable
	Topological domain	341 – 523	183	Cytoplasmic Probable
	Transmembrane	524 – 543	20	Helical; Probable
Amino acid modifications
	Glycosylation	47	1	N-linked (GlcNAc...) Potential
	Glycosylation	144	1	N-linked (GlcNAc...) Potential
	Glycosylation	157	1	N-linked (GlcNAc...) Potential
	Disulfide bond	172 ↔ 186		By similarity
Natural variations
	Natural variant	19	1	A → T. Corresponds to variant rs16859837 [ dbSNP | Ensembl ].		VAR_046552
	Natural variant	26	1	L → M. Corresponds to variant rs2229940 [ dbSNP | Ensembl ].		VAR_046553
	Natural variant	516	1	S → R in a breast cancer sample; somatic mutation. Ref.7		VAR_036032
Experimental info
	Sequence conflict	316	1	A → L in AAB52519. Ref.1
	Sequence conflict	379	1	N → D in AAB52519. Ref.1
	Sequence conflict	463	1	Y → H in AAB52519. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P48169 [UniParc]. Last modified September 23, 2008. Version 2. Checksum: B159F9934FB02390	FASTA	554	61,623
	10 20 30 40 50 60 MVSAKKVPAI ALSAGVSFAL LRFLCLAVCL NESPGQNQKE EKLCTENFTR ILDSLLDGYD 70 80 90 100 110 120 NRLRPGFGGP VTEVKTDIYV TSFGPVSDVE MEYTMDVFFR QTWIDKRLKY DGPIEILRLN 130 140 150 160 170 180 NMMVTKVWTP DTFFRNGKKS VSHNMTAPNK LFRIMRNGTI LYTMRLTISA ECPMRLVDFP 190 200 210 220 230 240 MDGHACPLKF GSYAYPKSEM IYTWTKGPEK SVEVPKESSS LVQYDLIGQT VSSETIKSIT 250 260 270 280 290 300 GEYIVMTVYF HLRRKMGYFM IQTYIPCIMT VILSQVSFWI NKESVPARTV FGITTVLTMT 310 320 330 340 350 360 TLSISARHSL PKVSYATAMD WFIAVCFAFV FSALIEFAAV NYFTNIQMEK AKRKTSKPPQ 370 380 390 400 410 420 EVPAAPVQRE KHPEAPLQNT NANLNMRKRT NALVHSESDV GNRTEVGNHS SKSSTVVQES 430 440 450 460 470 480 SKGTPRSYLA SSPNPFSRAN AAETISAARA LPSASPTSIR TGYMPRKASV GSASTRHVFG 490 500 510 520 530 540 SRLQRIKTTV NTIGATGKLS ATPPPSAPPP SGSGTSKIDK YARILFPVTF GAFNMVYWVV 550 YLSKDTMEKS ESLM

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of the human GABAA receptor alpha 4 subunit: identification of a unique diazepam-insensitive binding site." Yang W., Drewe J.A., Lan N.C. Eur. J. Pharmacol. 291:319-325(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION. Tissue: Brain cortex.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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.
[6]	"Mapping of the alpha 4 subunit gene (GABRA4) to human chromosome 4 defines an alpha 2-alpha 4-beta 1-gamma 1 gene cluster: further evidence that modern GABAA receptor gene clusters are derived from an ancestral cluster." McLean P.J., Farb D.H., Russek S.J. Genomics 26:580-586(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-57.
[7]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-516.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Forbidden fruit - Issue 56 of March 2005

Cross-references

Sequence databases
EMBL GenBank DDBJ	U30461 mRNA. Translation: AAB52519.1. AK090780 mRNA. Translation: BAG52228.1. AC107383 Genomic DNA. No translation available. CH471069 Genomic DNA. Translation: EAW93029.1. BC035055 mRNA. Translation: AAH35055.1. U20166 Genomic DNA. Translation: AAA74743.1.
IPI	IPI00008225.
PIR	G01928.
RefSeq	NP_000800.2. NM_000809.3. NP_001191195.1. NM_001204266.1. NP_001191196.1. NM_001204267.1.
UniGene	Hs.248112.
3D structure databases
ProteinModelPortal	P48169.
ModBase	Search...
Protein-protein interaction databases
IntAct	P48169. 1 interaction.
STRING	9606.ENSP00000264318.
PTM databases
PhosphoSite	P48169.
Polymorphism databases
DMDM	206729865.
Proteomic databases
PaxDb	P48169.
PRIDE	P48169.
Protocols and materials databases
DNASU	2557.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264318; ENSP00000264318; ENSG00000109158.
GeneID	2557.
KEGG	hsa:2557.
UCSC	uc003gxg.3. human.
Organism-specific databases
CTD	2557.
GeneCards	GC04M046836.
HGNC	HGNC:4078. GABRA4.
MIM	137141. gene.
neXtProt	NX_P48169.
PharmGKB	PA28492.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG238757.
HOGENOM	HOG000231337.
HOVERGEN	HBG051707.
InParanoid	P48169.
KO	K05175.
OMA	THANLNM.
OrthoDB	EOG4MPHQ4.
PhylomeDB	P48169.
Enzyme and pathway databases
Reactome	REACT_13685. Neuronal System. REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	P48169.
Bgee	P48169.
CleanEx	HS_GABRA4.
Genevestigator	P48169.
GermOnline	ENSG00000109158. Homo sapiens.
Family and domain databases
Gene3D	2.70.170.10. 1 hit.
InterPro	IPR006028. GABAA_rcpt. IPR001390. GABAAa_rcpt. IPR005434. GABBAa4_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	PR01079. GABAARALPHA. PR01617. GABAARALPHA4. 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	P48169.
ChEMBL	CHEMBL2472.
DrugBank	DB00404. Alprazolam. DB00189. Ethchlorvynol. DB01544. Flunitrazepam. DB00690. Flurazepam. DB00186. Lorazepam. DB00371. Meprobamate. DB00683. Midazolam.
GenomeRNAi	2557.
NextBio	10099.
SOURCE	Search...

Entry information

Entry name

GBRA4_HUMAN

Accession

Primary (citable) accession number: P48169
Secondary accession number(s): Q8IYR7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	September 23, 2008
Last modified:	May 1, 2013
This is version 130 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.