Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9Z0U4 (GABR1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Gamma-aminobutyric acid type B receptor subunit 1

Short name=GABA-B receptor 1
Short name=GABA-B-R1
Short name=GABA-BR1
Short name=GABABR1
Short name=Gb1
Gene names
Name:Gabbr1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length991 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Calcium is required for high affinity binding to GABA. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases 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. Ref.1

Subunit structure

Heterodimer of GABBR1 and GABBR2. Homodimers may form, but are inactive. Interacts with the leucine zipper of the C-terminal bZIP domain of ATF4 via its C-terminal region. Interacts with JAKMIP1. Ref.4 Ref.6 Ref.7 Ref.9

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junctionsynapsepostsynaptic cell membrane; Multi-pass membrane protein. Cell projectiondendrite. Note: Coexpression of GABBR1 and GABBR2 is required for GABBR1 maturation and transport to the plasma membrane. Colocalizes with ATF4 in hippocampal neuron dendritic membranes. Ref.1 Ref.7

Tissue specificity

Isoform 1A, isoform 1B and isoform 1C are expressed in testis, stomach, spinal cord and brain including cerebral cortical layers, pyramidal cell layers of the hippocampus, granular cell layers of the dentate gyrus, basal ganglia, cerebellum (predominantly in Purkinje cells followed by granular layer). Isoform 1B is also expressed in kidney and liver. Isoform 1D is expressed in forebrain, cerebellum, eye, kidney, and urinary bladder. Ref.1 Ref.2 Ref.5

Domain

Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABBR2. The linker region between the transmembrane domain 3 (TM3) and the transmembrane domain 4 (TM4) probably plays a role in the specificity for G-protein coupling.

Sequence similarities

Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily.

Contains 2 Sushi (CCP/SCR) domains.

Ontologies

Keywords
   Cellular componentCell junction
Cell membrane
Cell projection
Membrane
Postsynaptic cell membrane
Synapse
   Coding sequence diversityAlternative splicing
   DomainCoiled coil
Repeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

gamma-aminobutyric acid signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of adenylate cyclase activity

Inferred from direct assay Ref.1. Source: MGI

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 15147298. Source: RGD

negative regulation of dopamine secretion

Inferred from direct assay PubMed 12872287. Source: RGD

negative regulation of epinephrine secretion

Inferred from mutant phenotype PubMed 14568556. Source: RGD

negative regulation of gamma-aminobutyric acid secretion

Inferred from mutant phenotype PubMed 14654095. Source: RGD

negative regulation of synaptic transmission

Inferred from direct assay PubMed 12604336. Source: RGD

osteoblast differentiation

Inferred from mutant phenotype PubMed 12054677. Source: RGD

positive regulation of glutamate secretion

Inferred from mutant phenotype PubMed 18765663. Source: RGD

positive regulation of growth hormone secretion

Inferred from mutant phenotype PubMed 12218349. Source: RGD

regulation of cAMP biosynthetic process

Inferred from direct assay PubMed 8782915. Source: RGD

regulation of glutamate secretion

Inferred from direct assay PubMed 15561437. Source: RGD

response to ethanol

Inferred from expression pattern PubMed 16246313. Source: RGD

response to nicotine

Inferred from expression pattern PubMed 12435490. Source: RGD

   Cellular_componentG-protein coupled receptor heterodimeric complex

Inferred from sequence or structural similarity. Source: UniProtKB

axolemma

Inferred from direct assay PubMed 17924569. Source: RGD

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

dendritic shaft

Inferred from direct assay PubMed 17241134. Source: RGD

dendritic spine

Inferred from direct assay PubMed 16983643. Source: RGD

endoplasmic reticulum membrane

Inferred from direct assay PubMed 17924569. Source: RGD

extracellular space

Inferred from direct assay PubMed 18765663. Source: RGD

integral component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular membrane-bounded organelle

Inferred from direct assay PubMed 17241134. Source: RGD

membrane raft

Inferred from direct assay PubMed 19054408. Source: RGD

mitochondrial membrane

Inferred from direct assay PubMed 17924569. Source: RGD

neuron projection

Inferred from direct assay PubMed 17241134. Source: RGD

neuronal cell body

Inferred from direct assay PubMed 17241134. Source: RGD

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

synaptic vesicle

Inferred from direct assay PubMed 17924569. Source: RGD

   Molecular_functionG-protein coupled GABA receptor activity

Inferred from direct assay Ref.3. Source: RGD

transcription factor binding

Inferred from physical interaction Ref.7. Source: RGD

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Gabbr2O888718EBI-7090268,EBI-7090239

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1E (identifier: Q9Z0U4-1)

Also known as: 1C;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 1A (identifier: Q9Z0U4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     771-801: Missing.
Isoform 1B (identifier: Q9Z0U4-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-163: MLLLLLVPLF...PHCQVNRTPH → MGPGGPCTPV...PHPRVPPHPS
     771-801: Missing.
Isoform 1C (identifier: Q9Z0U4-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-163: MLLLLLVPLF...PHCQVNRTPH → MGPGGPCTPV...PHPRVPPHPS
Isoform 1D (identifier: Q9Z0U4-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-163: MLLLLLVPLF...PHCQVNRTPH → MGPGGPCTPV...PHPRVPPHPS
     771-801: Missing.
     935-991: KEERVSELRH...DGSRVHLLYK → VCGDKQPGPPVSEGGLPVVGPSIEV

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1616 Potential
Chain17 – 991975Gamma-aminobutyric acid type B receptor subunit 1
PRO_0000012951

Regions

Topological domain17 – 590574Extracellular Potential
Transmembrane591 – 61121Helical; Name=1; Potential
Topological domain612 – 63019Cytoplasmic Potential
Transmembrane631 – 65121Helical; Name=2; Potential
Topological domain652 – 66615Extracellular Potential
Transmembrane667 – 68721Helical; Name=3; Potential
Topological domain688 – 70922Cytoplasmic Potential
Transmembrane710 – 73021Helical; Name=4; Potential
Topological domain731 – 79767Extracellular Potential
Transmembrane798 – 81821Helical; Name=5; Potential
Topological domain819 – 83416Cytoplasmic Potential
Transmembrane835 – 85521Helical; Name=6; Potential
Topological domain856 – 8638Extracellular Potential
Transmembrane864 – 88421Helical; Name=7; Potential
Topological domain885 – 991107Cytoplasmic Potential
Domain29 – 9567Sushi 1
Domain97 – 15862Sushi 2
Region918 – 94629Interaction with ATF4
Coiled coil901 – 95555 Potential

Sites

Binding site2461Agonist By similarity
Binding site2691Agonist By similarity
Binding site2861Agonist By similarity
Binding site3661Agonist By similarity
Binding site3941Agonist By similarity
Binding site4651Agonist By similarity

Amino acid modifications

Glycosylation231N-linked (GlcNAc...) Potential
Glycosylation831N-linked (GlcNAc...) Potential
Glycosylation4081N-linked (GlcNAc...) Potential
Glycosylation4391N-linked (GlcNAc...) Potential
Glycosylation4811N-linked (GlcNAc...) Potential
Glycosylation5011N-linked (GlcNAc...) Potential
Glycosylation5131N-linked (GlcNAc...) Potential
Disulfide bond99 ↔ 144 Ref.10
Disulfide bond130 ↔ 156 Ref.10
Disulfide bond219 ↔ 245 By similarity
Disulfide bond375 ↔ 409 By similarity

Natural variations

Alternative sequence1 – 163163MLLLL…NRTPH → MGPGGPCTPVGWPLPLLLVM AAGVAPVWASHSPHLPRPHP RVPPHPS in isoform 1B, isoform 1C and isoform 1D.
VSP_002044
Alternative sequence771 – 80131Missing in isoform 1A, isoform 1B and isoform 1D.
VSP_002045
Alternative sequence935 – 99157KEERV…HLLYK → VCGDKQPGPPVSEGGLPVVG PSIEV in isoform 1D.
VSP_002046

Experimental info

Mutagenesis2471S → A: No change in the affinity for GABA. Ref.8
Mutagenesis2681S → A: No change in the affinity for GABA. Ref.8
Mutagenesis2691S → A: Decrease in the affinity for GABA. Ref.8

Secondary structure

................... 991
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1E (1C) [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: 012CD293D4B444A2

FASTA991111,534
        10         20         30         40         50         60 
MLLLLLVPLF LRPLGAGGAQ TPNATSEGCQ IIHPPWEGGI RYRGLTRDQV KAINFLPVDY 

        70         80         90        100        110        120 
EIEYVCRGER EVVGPKVRKC LANGSWTDMD TPSRCVRICS KSYLTLENGK VFLTGGDLPA 

       130        140        150        160        170        180 
LDGARVEFRC DPDFHLVGSS RSVCSQGQWS TPKPHCQVNR TPHSERRAVY IGALFPMSGG 

       190        200        210        220        230        240 
WPGGQACQPA VEMALEDVNS RRDILPDYEL KLIHHDSKCD PGQATKYLYE LLYNDPIKII 

       250        260        270        280        290        300 
LMPGCSSVST LVAEAARMWN LIVLSYGSSS PALSNRQRFP TFFRTHPSAT LHNPTRVKLF 

       310        320        330        340        350        360 
EKWGWKKIAT IQQTTEVFTS TLDDLEERVK EAGIEITFRQ SFFSDPAVPV KNLKRQDARI 

       370        380        390        400        410        420 
IVGLFYETEA RKVFCEVYKE RLFGKKYVWF LIGWYADNWF KTYDPSINCT VEEMTEAVEG 

       430        440        450        460        470        480 
HITTEIVMLN PANTRSISNM TSQEFVEKLT KRLKRHPEET GGFQEAPLAY DAIWALALAL 

       490        500        510        520        530        540 
NKTSGGGGRS GVRLEDFNYN NQTITDQIYR AMNSSSFEGV SGHVVFDASG SRMAWTLIEQ 

       550        560        570        580        590        600 
LQGGSYKKIG YYDSTKDDLS WSKTDKWIGG SPPADQTLVI KTFRFLSQKL FISVSVLSSL 

       610        620        630        640        650        660 
GIVLAVVCLS FNIYNSHVRY IQNSQPNLNN LTAVGCSLAL AAVFPLGLDG YHIGRSQFPF 

       670        680        690        700        710        720 
VCQARLWLLG LGFSLGYGSM FTKIWWVHTV FTKKEEKKEW RKTLEPWKLY ATVGLLVGMD 

       730        740        750        760        770        780 
VLTLAIWQIV DPLHRTIETF AKEEPKEDID VSILPQLEHC SSKKMNTWLG ELWSFAVSSD 

       790        800        810        820        830        840 
VQRRATVGGD SPICVWPAPE SIFYGYKGLL LLLGIFLAYE TKSVSTEKIN DHRAVGMAIY 

       850        860        870        880        890        900 
NVAVLCLITA PVTMILSSQQ DAAFAFASLA IVFSSYITLV VLFVPKMRRL ITRGEWQSET 

       910        920        930        940        950        960 
QDTMKTGSST NNNEEEKSRL LEKENRELEK IIAEKEERVS ELRHQLQSRQ QLRSRRHPPT 

       970        980        990 
PPDPSGGLPR GPSEPPDRLS CDGSRVHLLY K 

« Hide

Isoform 1A [UniParc].

Checksum: 05B7FBBCBE9DBF94
Show »

FASTA960108,204
Isoform 1B [UniParc].

Checksum: B3417F53BE4877E9
Show »

FASTA84495,038
Isoform 1C [UniParc].

Checksum: E7E9EDA9132D37F2
Show »

FASTA87598,368
Isoform 1D [UniParc].

Checksum: 5EFD7B169A727FDE
Show »

FASTA81290,921

References

[1]"Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors."
Kaupmann K., Huggel K., Heid J., Flor P.J., Bischoff S., Mickel S.J., McMaster G., Angst C., Bittiger H., Froestl W., Bettler B.
Nature 386:239-246(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1A AND 1B), FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Strain: RICO.
Tissue: Brain cortex and Cerebellum.
[2]"Cloning and tissue distribution of novel splice variants of the rat GABAB receptor."
Isomoto S., Kaibara M., Sakurai-Yamashita Y., Nagayama Y., Uezono Y., Yano K., Taniyama K.
Biochem. Biophys. Res. Commun. 253:10-15(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1C AND 1D), TISSUE SPECIFICITY.
Tissue: Cerebellum.
[3]"Alternative splicing generates a novel isoform of the rat metabotropic GABA(B)R1 receptor."
Pfaff T., Malitschek B., Kaupmann K., Prezeau L., Pin J.-P., Bettler B., Karschin A.
Eur. J. Neurosci. 11:2874-2882(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1E).
Strain: Wistar.
Tissue: Hippocampus.
[4]"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1A), INTERACTION WITH GABBR2.
Tissue: Brain.
[5]"Synthesis of the nanomolar photoaffinity GABA(B) receptor ligand CGP 71872 reveals diversity in the tissue distribution of GABA(B) receptor forms."
Belley M., Sullivan R., Reeves A., Evans J.F., O'Neill G.P., Ng G.Y.K.
Bioorg. Med. Chem. 7:2697-2704(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[6]"Role of heteromer formation in GABAB receptor function."
Kuner R., Koehr G., Gruenewald S., Eisenhardt G., Bach A., Kornau H.-C.
Science 283:74-77(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GABBR2.
[7]"The metabotropic GABAB receptor directly interacts with the activating transcription factor 4."
Nehring R.B., Horikawa H.P.M., El Far O., Kneussel M., Brandstatter J.H., Stamm S., Wischmeyer E., Betz H., Karschin A.
J. Biol. Chem. 275:35185-35191(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATF4, SUBCELLULAR LOCATION.
[8]"Ca(2+) requirement for high-affinity gamma-aminobutyric acid (GABA) binding at GABA(B) receptors: involvement of serine 269 of the GABA(B)R1 subunit."
Galvez T., Urwyler S., Prezeau L., Mosbacher J., Joly C., Malitschek B., Heid J., Brabet I., Froestl W., Bettler B., Kaupmann K., Pin J.-P.
Mol. Pharmacol. 57:419-426(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF SER-247; SER-268 AND SER-269.
[9]"Marlin-1, a novel RNA-binding protein associates with GABA receptors."
Couve A., Restituito S., Brandon J.M., Charles K.J., Bawagan H., Freeman K.B., Pangalos M.N., Calver A.R., Moss S.J.
J. Biol. Chem. 279:13934-13943(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH JAKMIP1.
[10]"Structural analysis of the complement control protein (CCP) modules of GABA(B) receptor 1a: only one of the two CCP modules is compactly folded."
Blein S., Ginham R., Uhrin D., Smith B.O., Soares D.C., Veltel S., McIlhinney R.A., White J.H., Barlow P.N.
J. Biol. Chem. 279:48292-48306(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 96-159, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y10369 mRNA. Translation: CAA71398.1.
Y10370 mRNA. Translation: CAA71399.1.
AB016160 mRNA. Translation: BAA34708.1.
AB016161 mRNA. Translation: BAA34709.1.
AF110797, AF110796 Genomic DNA. Translation: AAD19656.1.
AF110797, AF110796 Genomic DNA. Translation: AAD19657.1.
AF110797, AF110796 Genomic DNA. Translation: AAD19658.1.
AF110797, AF110796 Genomic DNA. Translation: AAD19659.1.
RefSeqNP_112290.2. NM_031028.3.
XP_006255941.1. XM_006255879.1.
UniGeneRn.30059.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1SRZNMR-A96-159[»]
1SS2NMR-A96-159[»]
DisProtDP00463.
ProteinModelPortalQ9Z0U4.
SMRQ9Z0U4. Positions 96-159.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid249557. 2 interactions.
IntActQ9Z0U4. 1 interaction.

Chemistry

BindingDBQ9Z0U4.
ChEMBLCHEMBL2111474.
GuidetoPHARMACOLOGY240.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ9Z0U4.

Proteomic databases

PaxDbQ9Z0U4.
PRIDEQ9Z0U4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID81657.
KEGGrno:81657.
UCSCRGD:621537. rat. [Q9Z0U4-1]

Organism-specific databases

CTD2550.
RGD621537. Gabbr1.

Phylogenomic databases

eggNOGCOG0683.
HOGENOMHOG000016575.
HOVERGENHBG051688.
InParanoidQ9Z0U4.
KOK04615.
PhylomeDBQ9Z0U4.
TreeFamTF313965.

Gene expression databases

ArrayExpressQ9Z0U4.
GenevestigatorQ9Z0U4.

Family and domain databases

InterProIPR001828. ANF_lig-bd_rcpt.
IPR017978. GPCR_3_C.
IPR002455. GPCR_3_GABA_rcpt_B.
IPR002456. GPCR_3_GABA_rcpt_B1.
IPR028082. Peripla_BP_I.
IPR000436. Sushi_SCR_CCP.
[Graphical view]
PfamPF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF00084. Sushi. 2 hits.
[Graphical view]
PRINTSPR01177. GABAB1RECPTR.
PR01176. GABABRECEPTR.
SMARTSM00032. CCP. 2 hits.
[Graphical view]
SUPFAMSSF53822. SSF53822. 1 hit.
SSF57535. SSF57535. 2 hits.
PROSITEPS50259. G_PROTEIN_RECEP_F3_4. 1 hit.
PS50923. SUSHI. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9Z0U4.
NextBio615214.
PROQ9Z0U4.

Entry information

Entry nameGABR1_RAT
AccessionPrimary (citable) accession number: Q9Z0U4
Secondary accession number(s): O08620 expand/collapse secondary AC list , O08621, Q9Z0F9, Q9Z308
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: May 1, 1999
Last modified: April 16, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries