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P48169 (GBRA4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Gamma-aminobutyric acid receptor subunit alpha-4
Alternative name(s):
GABA(A) receptor subunit alpha-4
Gene names
Name:GABRA4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length554 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 junctionsynapsepostsynaptic 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 processIon transport
Transport
   Cellular componentCell junction
Cell membrane
Membrane
Postsynaptic cell membrane
Synapse
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   LigandChloride
   Molecular functionChloride channel
Ion channel
Ligand-gated ion channel
Receptor
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcentral nervous system development

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

synaptic transmission

Traceable author statement. Source: Reactome

transmembrane transport

Traceable author statement. Source: Reactome

transport

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

chloride channel complex

Inferred from electronic annotation. Source: UniProtKB-KW

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionGABA-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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3535 Potential
Chain36 – 554519Gamma-aminobutyric acid receptor subunit alpha-4
PRO_0000000441

Regions

Topological domain36 – 258223Extracellular Probable
Transmembrane259 – 28022Helical; Probable
Transmembrane285 – 30622Helical; Probable
Transmembrane318 – 34023Helical; Probable
Topological domain341 – 523183Cytoplasmic Probable
Transmembrane524 – 54320Helical; Probable

Amino acid modifications

Glycosylation471N-linked (GlcNAc...) Potential
Glycosylation1441N-linked (GlcNAc...) Potential
Glycosylation1571N-linked (GlcNAc...) Potential
Disulfide bond172 ↔ 186 By similarity

Natural variations

Natural variant191A → T.
Corresponds to variant rs16859837 [ dbSNP | Ensembl ].
VAR_046552
Natural variant261L → M.
Corresponds to variant rs2229940 [ dbSNP | Ensembl ].
VAR_046553
Natural variant5161S → R in a breast cancer sample; somatic mutation. Ref.7
VAR_036032

Experimental info

Sequence conflict3161A → L in AAB52519. Ref.1
Sequence conflict3791N → D in AAB52519. Ref.1
Sequence conflict4631Y → H in AAB52519. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P48169 [UniParc].

Last modified September 23, 2008. Version 2.
Checksum: B159F9934FB02390

FASTA55461,623
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.
CCDSCCDS3473.1.
PIRG01928.
RefSeqNP_000800.2. NM_000809.3.
NP_001191195.1. NM_001204266.1.
NP_001191196.1. NM_001204267.1.
UniGeneHs.248112.

3D structure databases

ProteinModelPortalP48169.
SMRP48169. Positions 49-345.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108831. 3 interactions.
IntActP48169. 1 interaction.
STRING9606.ENSP00000264318.

Chemistry

BindingDBP48169.
ChEMBLCHEMBL2093872.
DrugBankDB00404. Alprazolam.
DB00189. Ethchlorvynol.
DB01544. Flunitrazepam.
DB00690. Flurazepam.
DB00186. Lorazepam.
DB00371. Meprobamate.
DB00683. Midazolam.
GuidetoPHARMACOLOGY407.

PTM databases

PhosphoSiteP48169.

Polymorphism databases

DMDM206729865.

Proteomic databases

PaxDbP48169.
PRIDEP48169.

Protocols and materials databases

DNASU2557.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264318; ENSP00000264318; ENSG00000109158.
GeneID2557.
KEGGhsa:2557.
UCSCuc003gxg.3. human.

Organism-specific databases

CTD2557.
GeneCardsGC04M046836.
HGNCHGNC:4078. GABRA4.
HPAHPA057756.
MIM137141. gene.
neXtProtNX_P48169.
PharmGKBPA28492.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG238757.
HOGENOMHOG000231337.
HOVERGENHBG051707.
InParanoidP48169.
KOK05175.
OMAPNPFSHA.
OrthoDBEOG7JX342.
PhylomeDBP48169.
TreeFamTF315453.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.
REACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressP48169.
BgeeP48169.
CleanExHS_GABRA4.
GenevestigatorP48169.

Family and domain databases

Gene3D2.70.170.10. 1 hit.
InterProIPR006028. GABAA/Glycine_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]
PANTHERPTHR18945. PTHR18945. 1 hit.
PfamPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 1 hit.
[Graphical view]
PRINTSPR01079. GABAARALPHA.
PR01617. GABAARALPHA4.
PR00253. GABAARECEPTR.
PR00252. NRIONCHANNEL.
SUPFAMSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 2 hits.
TIGRFAMsTIGR00860. LIC. 1 hit.
PROSITEPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGABRA4.
GenomeRNAi2557.
NextBio10099.
PROP48169.
SOURCESearch...

Entry information

Entry nameGBRA4_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM