O75899 (GABR2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Gamma-aminobutyric acid type B receptor subunit 2
Short name=GABA-B receptor 2
Short name=GABA-B-R2
Short name=GABA-BR2
Short name=GABABR2
Short name=Gb2

Alternative name(s):
G-protein coupled receptor 51
HG20

Gene names

Name:	GABBR2
Synonyms:	GPR51, GPRC3B

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	941 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	Receptor for GABA. The activity of this receptor is mediated by G-proteins that inhibit adenylyl cyclase activity, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipids hydrolysis. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA-B-R inhibit neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA-B-R decrease neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception.
Subunit structure	Heterodimer of GABA-B-R1 and GABA-B-R2. Neither of which is effective on its own and homodimeric assembly does not seem to happen. Interacts with ATF4 via its C-terminal region. Ref.9 Ref.10
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › synapse › postsynaptic cell membrane; Multi-pass membrane protein. Note: Moreover coexpression of GABA-B-R1 and GABA-B-R2 appears to be a prerequisite for maturation and transport of GABA-B-R1 to the plasma membrane.
Tissue specificity	Highly expressed in brain, especially in cerebral cortex, thalamus, hippocampus, frontal, occipital and temporal lobe, occipital pole and cerebellum, followed by corpus callosum, caudate nucleus, spinal cord, amygdala and medulla. Weakly expressed in heart, testis and skeletal muscle.
Domain	Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABA-B receptor 1.
Sequence similarities	Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily.
Sequence caution	The sequence AAH35071.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Membrane Postsynaptic cell membrane Synapse
Coding sequence diversity	Polymorphism
Domain	Coiled coil Signal Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	negative regulation of adenylate cyclase activity Traceable author statement. Source: ProtInc synaptic transmission Traceable author statement. Source: Reactome
Cellular component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Traceable author statement. Source: ProtInc postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	G-protein coupled GABA receptor activity Traceable author statement. Source: ProtInc G-protein coupled receptor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 41	41	Potential
	Chain	42 – 941	900	Gamma-aminobutyric acid type B receptor subunit 2		PRO_0000012952
Regions
	Topological domain	42 – 483	442	Extracellular Potential
	Transmembrane	484 – 504	21	Helical; Name=1; Potential
	Topological domain	505 – 522	18	Cytoplasmic Potential
	Transmembrane	523 – 543	21	Helical; Name=2; Potential
	Topological domain	544 – 551	8	Extracellular Potential
	Transmembrane	552 – 572	21	Helical; Name=3; Potential
	Topological domain	573 – 597	25	Cytoplasmic Potential
	Transmembrane	598 – 618	21	Helical; Name=4; Potential
	Topological domain	619 – 654	36	Extracellular Potential
	Transmembrane	655 – 675	21	Helical; Name=5; Potential
	Topological domain	676 – 691	16	Cytoplasmic Potential
	Transmembrane	692 – 712	21	Helical; Name=6; Potential
	Topological domain	713 – 720	8	Extracellular Potential
	Transmembrane	721 – 741	21	Helical; Name=7; Potential
	Topological domain	742 – 941	200	Cytoplasmic Potential
	Coiled coil	781 – 819	39	Potential
Amino acid modifications
	Modified residue	884	1	Phosphoserine Ref.11
	Glycosylation	90	1	N-linked (GlcNAc...) Potential
	Glycosylation	298	1	N-linked (GlcNAc...) Potential
	Glycosylation	389	1	N-linked (GlcNAc...) Potential
	Glycosylation	404	1	N-linked (GlcNAc...) Potential
	Glycosylation	453	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	163	1	L → P. Corresponds to variant rs35449008 [ dbSNP | Ensembl ].		VAR_049280
	Natural variant	628	1	Y → F. Ref.3		VAR_010148
	Natural variant	869	1	T → A. Ref.3 Corresponds to variant rs10985765 [ dbSNP | Ensembl ].		VAR_010149
Experimental info
	Sequence conflict	6	1	S → R in AAC99345. Ref.2
	Sequence conflict	12	1	P → R in AAC99345. Ref.2
	Sequence conflict	424	1	G → E in AAD30389. Ref.5
	Sequence conflict	797	1	R → H in AAH35071. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	O75899 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 09F1773DB0673C5D	FASTA	941	105,821
	10 20 30 40 50 60 MASPRSSGQP GPPPPPPPPP ARLLLLLLLP LLLPLAPGAW GWARGAPRPP PSSPPLSIMG 70 80 90 100 110 120 LMPLTKEVAK GSIGRGVLPA VELAIEQIRN ESLLRPYFLD LRLYDTECDN AKGLKAFYDA 130 140 150 160 170 180 IKYGPNHLMV FGGVCPSVTS IIAESLQGWN LVQLSFAATT PVLADKKKYP YFFRTVPSDN 190 200 210 220 230 240 AVNPAILKLL KHYQWKRVGT LTQDVQRFSE VRNDLTGVLY GEDIEISDTE SFSNDPCTSV 250 260 270 280 290 300 KKLKGNDVRI ILGQFDQNMA AKVFCCAYEE NMYGSKYQWI IPGWYEPSWW EQVHTEANSS 310 320 330 340 350 360 RCLRKNLLAA MEGYIGVDFE PLSSKQIKTI SGKTPQQYER EYNNKRSGVG PSKFHGYAYD 370 380 390 400 410 420 GIWVIAKTLQ RAMETLHASS RHQRIQDFNY TDHTLGRIIL NAMNETNFFG VTGQVVFRNG 430 440 450 460 470 480 ERMGTIKFTQ FQDSREVKVG EYNAVADTLE IINDTIRFQG SEPPKDKTII LEQLRKISLP 490 500 510 520 530 540 LYSILSALTI LGMIMASAFL FFNIKNRNQK LIKMSSPYMN NLIILGGMLS YASIFLFGLD 550 560 570 580 590 600 GSFVSEKTFE TLCTVRTWIL TVGYTTAFGA MFAKTWRVHA IFKNVKMKKK IIKDQKLLVI 610 620 630 640 650 660 VGGMLLIDLC ILICWQAVDP LRRTVEKYSM EPDPAGRDIS IRPLLEHCEN THMTIWLGIV 670 680 690 700 710 720 YAYKGLLMLF GCFLAWETRN VSIPALNDSK YIGMSVYNVG IMCIIGAAVS FLTRDQPNVQ 730 740 750 760 770 780 FCIVALVIIF CSTITLCLVF VPKLITLRTN PDAATQNRRF QFTQNQKKED SKTSTSVTSV 790 800 810 820 830 840 NQASTSRLEG LQSENHRLRM KITELDKDLE EVTMQLQDTP EKTTYIKQNH YQELNDILNL 850 860 870 880 890 900 GNFTESTDGG KAILKNHLDQ NPQLQWNTTE PSRTCKDPIE DINSPEHIQR RLSLQLPILH 910 920 930 940 HAYLPSIGGV DASCVSPCVS PTASPRHRHV PPSFRVMVSG L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Heterodimerization is required for the formation of a functional GABA(B) receptor." White J.H., Wise A., Main M.J., Green A., Fraser N.J., Disney G.H., Barnes A.A., Emson P., Foord S.M., Marshall F.H. Nature 396:679-682(1998) [PubMed: 9872316] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Cerebellum.
[2]	"Cloning of a novel G-protein-coupled receptor GPR 51 resembling GABAB receptors expressed predominantly in nervous tissues and mapped proximal to the hereditary sensory neuropathy type 1 locus on chromosome 9." Ng G.Y.K., McDonald T., Bonnert T., Rigby M., Heavens R., Whiting P., Chateauneuf A., Coulombe N., Kargman S., Caskey T., Evans J.F., O'Neill G.P., Liu Q. Genomics 56:288-295(1999) [PubMed: 10087195] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal brain.
[3]	"Molecular identification of the human GABABR2: cell surface expression and coupling to adenylyl cyclase in the absence of GABABR1." Martin S.C., Russek S.J., Farb D.H. Mol. Cell. Neurosci. 13:180-191(1999) [PubMed: 10328880] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS PHE-628 AND ALA-869. Tissue: Brain.
[4]	"Distribution of the GABA(B) receptor subunit gb2 in rat CNS." Clark J.A., Mezey E., Lam A.S., Bonner T.I. Brain Res. 860:41-52(2000) [PubMed: 10727622] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[5]	"Cloning and characterization of a novel human GABA-B receptor subtype with high affinity for GABA and low affinity for baclofen." Liu M., Parker R., McCrea K., Watson J., Baker E., Sutherland G., Herzog H. Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	Borowsky B., Laz T., Gerald C. Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Hippocampus.
[7]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-941. Tissue: Hippocampus.
[9]	"Identification of a GABAB receptor subunit, gb2, required for functional GABAB receptor activity." Ng G.Y.K., Clark J., Coulombe N., Ethier N., Hebert T.E., Sullivan R., Kargman S., Chateauneuf A., Tsukamoto N., McDonald T., Whiting P., Mezey E., Johnson M.P., Liu Q., Kolakowski L.F. Jr., Evans J.F., Bonner T.I., O'Neill G.P. J. Biol. Chem. 274:7607-7610(1999) [PubMed: 10075644] [Abstract] Cited for: INTERACTION WITH GABBR1.
[10]	"Coexpression of full-length gamma-aminobutyric acid(B) (GABA(B)) receptors with truncated receptors and metabotropic glutamate receptor 4 supports the GABA(B) heterodimer as the functional receptor." Sullivan R., Chateauneuf A., Coulombe N., Kolakowski L.F. Jr., Johnson M.P., Hebert T.E., Ethier N., Belley M., Metters K., Abramovitz M., O'Neill G.P., Ng G.Y.K. J. Pharmacol. Exp. Ther. 293:460-467(2000) [PubMed: 10773016] [Abstract] Cited for: INTERACTION WITH GABBR1.
[11]	"Phosphoproteomic analysis of synaptosomes from human cerebral cortex." DeGiorgis J.A., Jaffe H., Moreira J.E., Carlotti C.G. Jr., Leite J.P., Pant H.C., Dosemeci A. J. Proteome Res. 4:306-315(2005) [PubMed: 15822905] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-884, MASS SPECTROMETRY. Tissue: Brain cortex.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ012188 mRNA. Translation: CAA09942.1. AF069755 mRNA. Translation: AAC99345.1. AF099033 mRNA. Translation: AAD45867.1. AF056085 mRNA. Translation: AAC63228.1. AF095784 mRNA. Translation: AAD30389.1. AF074483 mRNA. Translation: AAD03336.1. AL445495 , AL353782, AL356282, AL591502 Genomic DNA. Translation: CAD13322.2. AL353782 , AL356282, AL445495, AL591502 Genomic DNA. Translation: CAH71298.1. AL356282 , AL353782, AL445495, AL591502 Genomic DNA. Translation: CAH72233.1. AL591502 , AL353782, AL356282, AL445495 Genomic DNA. Translation: CAI12581.1. BC035071 mRNA. Translation: AAH35071.2. Different initiation.
IPI	IPI00027250.
RefSeq	NP_005449.5. NM_005458.7.
UniGene	Hs.198612.
3D structure databases
ProteinModelPortal	O75899.
ModBase	Search...
Protein-protein interaction databases
IntAct	O75899. 2 interactions.
MINT	MINT-1398863.
STRING	O75899.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	O75899.
Proteomic databases
PRIDE	O75899.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000259455; ENSP00000259455; ENSG00000136928.
GeneID	9568.
KEGG	hsa:9568.
UCSC	uc004ays.1. human.
Organism-specific databases
CTD	9568.
GeneCards	GC09M101050.
H-InvDB	HIX0201398.
HGNC	HGNC:4507. GABBR2.
HPA	HPA013820.
MIM	607340. gene.
neXtProt	NX_O75899.
PharmGKB	PA28896.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG16445.
GeneTree	ENSGT00530000063129.
HOVERGEN	HBG080355.
InParanoid	O75899.
OMA	HENIDDV.
OrthoDB	EOG4PG606.
PhylomeDB	O75899.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction. REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	O75899.
Bgee	O75899.
CleanEx	HS_GABBR2.
Genevestigator	O75899.
GermOnline	ENSG00000136928. Homo sapiens.
Family and domain databases
InterPro	IPR001828. ANF_lig-bd_rcpt. IPR000337. GPCR_3. IPR017978. GPCR_3_C. IPR017979. GPCR_3_CS. IPR002455. GPCR_3_GABA_rcpt_B. IPR002457. GPCR_3_GABA_rcpt_B2. [Graphical view]
KO	K04615.
Pfam	PF00003. 7tm_3. 1 hit. PF01094. ANF_receptor. 1 hit. [Graphical view]
PRINTS	PR01178. GABAB2RECPTR. PR01176. GABABRECEPTR. PR00248. GPCRMGR.
PROSITE	PS00979. G_PROTEIN_RECEP_F3_1. False negative. PS00980. G_PROTEIN_RECEP_F3_2. False negative. PS00981. G_PROTEIN_RECEP_F3_3. 1 hit. PS50259. G_PROTEIN_RECEP_F3_4. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00181. Baclofen.
NextBio	35881.
SOURCE	Search...

Entry information

Entry name

GABR2_HUMAN

Accession

Primary (citable) accession number: O75899
Secondary accession number(s): O75974 , O75975, Q5VXZ2, Q8WX04, Q9P1R2, Q9UNR1, Q9UNS9

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	November 1, 1998
Last modified:	January 25, 2012
This is version 119 of the entry and version 1 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.