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) [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	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
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	gamma-aminobutyric acid signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of adenylate cyclase activity Traceable author statement Ref.3. Source: ProtInc synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytoplasm Inferred from electronic annotation. Source: Compara integral to plasma membrane Traceable author statement Ref.3. Source: ProtInc neuron projection Inferred from electronic annotation. Source: Compara postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	G-protein coupled GABA receptor activity Traceable author statement Ref.3. Source: ProtInc
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

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

Secondary structure

1

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941

Helix Strand Turn

Details...

Beta strand

55 – 62

8

Helix

71 – 90

20

Turn

91 – 96

6

Beta strand

98 – 105

8

Helix

110 – 123

14

Beta strand

128 – 132

5

Helix

136 – 144

9

Helix

147 – 149

3

Beta strand

152 – 157

6

Helix

161 – 164

4

Turn

166 – 168

3

Beta strand

172 – 176

5

Helix

179 – 181

3

Helix

182 – 192

11

Beta strand

197 – 205

9

Helix

206 – 218

13

Beta strand

219 – 223

5

Beta strand

225 – 234

10

Helix

237 – 245

9

Beta strand

250 – 254

5

Helix

257 – 269

13

Beta strand

278 – 283

6

Turn

287 – 291

5

Helix

304 – 311

8

Beta strand

315 – 319

5

Helix

335 – 346

12

Helix

355 – 378

24

Beta strand

379 – 381

3

Helix

385 – 387

3

Helix

393 – 404

12

Beta strand

407 – 410

4

Beta strand

413 – 418

6

Beta strand

421 – 423

3

Beta strand

425 – 432

8

Beta strand

435 – 443

9

Turn

444 – 447

4

Beta strand

448 – 451

4

Turn

453 – 455

3

Beta strand

459 – 462

4

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GABBR1.
+	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

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4F11	X-ray	2.38	A	42-466	[»]
4F12	X-ray	3.02	A	42-466	[»]

ProteinModelPortal

O75899.

ModBase

Search...

Protein-protein interaction databases

IntAct

O75899. 2 interactions.

MINT

MINT-1398863.

STRING

9606.ENSP00000259455.

Protein family/group databases

GPCRDB

Search...

PTM databases

PhosphoSite

O75899.

Proteomic databases

PaxDb

O75899.

PRIDE

O75899.

Protocols and materials databases

DNASU

9568.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000259455; ENSP00000259455; ENSG00000136928.

GeneID

9568.

KEGG

hsa:9568.

UCSC

uc004ays.3. human.

Organism-specific databases

CTD

9568.

GeneCards

GC09M101050.

HGNC

HGNC:4507. GABBR2.

HPA

HPA013820.

MIM

607340. gene.

neXtProt

NX_O75899.

PharmGKB

PA28896.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG273984.

HOVERGEN

HBG080355.

InParanoid

O75899.

KO

K04615.

OMA

YRETKQL.

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]

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

BindingDB

O75899.

ChEMBL

CHEMBL5034.

ChiTaRS

GABBR2. human.

DrugBank

DB00181. Baclofen.

GenomeRNAi

9568.

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:	May 1, 2013
This is version 131 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.