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Protein

Gamma-aminobutyric acid type B receptor subunit 1

Gene

Gabbr1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:9872315, PubMed:9872317, PubMed:9872744). Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins (PubMed:9872317, PubMed:10658574). 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 (PubMed:10075644, PubMed:9872315, PubMed:9872744, PubMed:10924501). Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:9069281, PubMed:10457184, PubMed:9872315, PubMed:9872744, PubMed:10924501, PubMed:10692480). Calcium is required for high affinity binding to GABA (PubMed:10692480). Plays a critical role in the fine-tuning of inhibitory synaptic transmission (PubMed:9872744). 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 (PubMed:9872744, PubMed:10924501, PubMed:10692480). Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (By similarity).HMP:8 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei246AgonistHMP:1
Binding sitei269AgonistHMP:1
Binding sitei286AgonistHMP:1
Binding sitei366AgonistHMP:1
Binding sitei394AgonistHMP:1
Binding sitei465AgonistHMP:1

GO - Molecular functioni

  • extracellular matrix protein binding Source: CAFA
  • G-protein coupled GABA receptor activity Source: RGD
  • protein heterodimerization activity Source: CAFA
  • transcription factor binding Source: RGD

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-RNO-1296041. Activation of G protein gated Potassium channels.
R-RNO-418594. G alpha (i) signalling events.
R-RNO-420499. Class C/3 (Metabotropic glutamate/pheromone receptors).
R-RNO-977444. GABA B receptor activation.
R-RNO-997272. Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Gabbr1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 20

Organism-specific databases

RGDi621537. Gabbr1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini17 – 590ExtracellularIEP:Add BLAST574
Transmembranei591 – 611Helical; Name=1IEP:Add BLAST21
Topological domaini612 – 630CytoplasmicIEP:Add BLAST19
Transmembranei631 – 651Helical; Name=2IEP:Add BLAST21
Topological domaini652 – 666ExtracellularIEP:Add BLAST15
Transmembranei667 – 687Helical; Name=3IEP:Add BLAST21
Topological domaini688 – 709CytoplasmicIEP:Add BLAST22
Transmembranei710 – 730Helical; Name=4IEP:Add BLAST21
Topological domaini731 – 797ExtracellularIEP:Add BLAST67
Transmembranei798 – 818Helical; Name=5IEP:Add BLAST21
Topological domaini819 – 834CytoplasmicIEP:Add BLAST16
Transmembranei835 – 855Helical; Name=6IEP:Add BLAST21
Topological domaini856 – 863ExtracellularIEP:8
Transmembranei864 – 884Helical; Name=7IEP:Add BLAST21
Topological domaini885 – 991CytoplasmicIEP:Add BLAST107

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi247S → A: No change in the affinity for GABA. 1 Publication1
Mutagenesisi268S → A: No change in the affinity for GABA. 1 Publication1
Mutagenesisi269S → A: Decrease in the affinity for GABA. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL2753.
GuidetoPHARMACOLOGYi240.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16IEP:Add BLAST16
ChainiPRO_000001295117 – 991Gamma-aminobutyric acid type B receptor subunit 1Add BLAST975

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi23N-linked (GlcNAc...) asparagineIEP:1
Glycosylationi83N-linked (GlcNAc...) asparagineIEP:1
Disulfide bondi99 ↔ 144IEP:1 Publication
Disulfide bondi130 ↔ 156IEP:1 Publication
Disulfide bondi219 ↔ 245IEP:
Disulfide bondi375 ↔ 409IEP:
Glycosylationi408N-linked (GlcNAc...) asparagineIEP:1
Glycosylationi439N-linked (GlcNAc...) asparagineIEP:1
Glycosylationi481N-linked (GlcNAc...) asparagineIEP:1
Glycosylationi501N-linked (GlcNAc...) asparagineIEP:1
Glycosylationi513N-linked (GlcNAc...) asparagineIEP:1
Modified residuei903PhosphothreonineHMP:1
Modified residuei960PhosphothreonineND:1

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ9Z0U4.
PRIDEiQ9Z0U4.

PTM databases

iPTMnetiQ9Z0U4.
PhosphoSitePlusiQ9Z0U4.
UniCarbKBiQ9Z0U4.

Expressioni

Tissue specificityi

Ubiquitously expressed in tissues including the forebrain, cerebellum, eye, atrium, ventricle, lung, stomach, small intestine, colon, liver, spleen, kidney, urinary bladder and skeletal muscle (PubMed:9875211). Expressed at low levels in testis, and more highly in brain regions (PubMed:9069281). Expression is high the brain regions including cerebral cortical layers, with higher expression in VIb than in the II-V layers, pyramidal CA1-CA3 cell layers and granular cell layers of the hippocampus, granular cell layers of the dentate gyrus, including the caudate, putamen, nucleus accumbens and olfactory tubercle, the granular layer cell layers of the medial habenula, in the cerebellum, predominantly in Purkinje cells, and in the granule cell layer (PubMed:9069281, PubMed:9872315 PubMed:9872744, PubMed:10727622). Also expressed in areas of the brain including the medial geniculate nucleus, substantia nigra, pars compacta, the ventral tegmental area, and in several thalamic, amygdaloid and hypothalamic nuclei, such as the arcuate nucleus of the hypothalamus and mammilary bodies of the hypothalamus (PubMed:9069281, PubMed:9872744). Expressed in the amacrine cell of the retina (PubMed:10924501). Isoform 1A: Expressed in the brain, spinal cord, stomach, testis, adrenal gland, pituitary, spleen and prostate (PubMed:10658574). Isoform 1B: Expressed in the brain, spinal cord, stomach, testis, kidney and liver (PubMed:10658574). Expressed in Isoform 1C: Ubiquitously expressed (PubMed:9875211). Isoform 1D: Expressed in the forebrain, cerebellum, eye, kidney and urinary bladder (PubMed:9875211). Isoform 1E: Ubiquitously expressed with high expression the pyramidal CA1-CA3 cell layers of the hippocampus, the granule cell layers of the dentate gyrus and olfactory tubercle, the whole cortex, and Purkinje cells of the cerebellum (PubMed:10457184). Moderate expression in the granule cell layer of the cerebellum (PubMed:10457184).8 Publications

Developmental stagei

At E17 during embryonic development, highly expressed in brain regions including the striatum, olfactory bulb, septal nuclei, lateral habenula, pyramidal CA1-CA2 cell layers of the hippocampus and in the neuroepithelial cells of the ventricular zone. On the day of birth, expressed in the regions of the brain including hippocampus, thalamic nuclei, cortex and cerebellum.1 Publication

Gene expression databases

BgeeiENSRNOG00000000774.
ExpressionAtlasiQ9Z0U4. baseline and differential.

Interactioni

Subunit structurei

Heterodimer of GABBR1 and GABBR2 (PubMed:9872315, PubMed:9872317, PubMed:9872744). Homodimers may form, but are inactive (PubMed:9872317). Interacts (via C-terminus) with ATF4 (via leucine zipper domain) (PubMed:10924501). Interacts with JAKMIP1 (PubMed:14718537).5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Gabbr2O888718EBI-7090268,EBI-7090239

GO - Molecular functioni

  • extracellular matrix protein binding Source: CAFA
  • protein heterodimerization activity Source: CAFA
  • transcription factor binding Source: RGD

Protein-protein interaction databases

BioGridi249557. 2 interactors.
CORUMiQ9Z0U4.
IntActiQ9Z0U4. 2 interactors.
STRINGi10116.ENSRNOP00000047788.

Chemistry databases

BindingDBiQ9Z0U4.

Structurei

Secondary structure

1991
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi96 – 98ND:3
Helixi101 – 104ND:4
Beta strandi109 – 112ND:4
Turni120 – 123ND:4
Beta strandi125 – 130ND:6
Beta strandi134 – 136ND:3
Beta strandi141 – 145ND:5
Beta strandi148 – 151ND:4
Beta strandi156 – 158ND:3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1SRZNMR-A96-159[»]
1SS2NMR-A96-159[»]
DisProtiDP00463.
ProteinModelPortaliQ9Z0U4.
SMRiQ9Z0U4.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Z0U4.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini29 – 95Sushi 1IEP:Add BLAST67
Domaini97 – 158Sushi 2IEP:Add BLAST62

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni918 – 946Interaction with ATF41 PublicationAdd BLAST29

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili901 – 955IEP:Add BLAST55

Domaini

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 similaritiesi

Keywords - Domaini

Coiled coil, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1055. Eukaryota.
ENOG410XNN1. LUCA.
GeneTreeiENSGT00530000063129.
HOGENOMiHOG000016575.
HOVERGENiHBG051688.
InParanoidiQ9Z0U4.
KOiK04615.
PhylomeDBiQ9Z0U4.
TreeFamiTF313965.

Family and domain databases

CDDicd15291. 7tmC_GABA-B-R1. 1 hit.
cd00033. CCP. 1 hit.
InterProiView protein in InterPro
IPR001828. ANF_lig-bd_rcpt.
IPR002455. GPCR3_GABA-B.
IPR017978. GPCR_3_C.
IPR002456. GPCR_3_GABA_rcpt_B1.
IPR028082. Peripla_BP_I.
IPR035976. Sushi/SCR/CCP_sf.
IPR000436. Sushi_SCR_CCP_dom.
PANTHERiPTHR10519. PTHR10519. 1 hit.
PfamiView protein in Pfam
PF00003. 7tm_3. 1 hit.
PF01094. ANF_receptor. 1 hit.
PF00084. Sushi. 1 hit.
SMARTiView protein in SMART
SM00032. CCP. 2 hits.
SUPFAMiSSF53822. SSF53822. 1 hit.
SSF57535. SSF57535. 2 hits.
PROSITEiView protein in PROSITE
PS50259. G_PROTEIN_RECEP_F3_4. 1 hit.
PS50923. SUSHI. 1 hit.

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1ETAS: (identifier: Q9Z0U4-1) [UniParc]FASTAAdd to basket
Also known as: 1CIBD:

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.

« Hide

        10         20         30         40         50
MLLLLLVPLF LRPLGAGGAQ TPNATSEGCQ IIHPPWEGGI RYRGLTRDQV
60 70 80 90 100
KAINFLPVDY EIEYVCRGER EVVGPKVRKC LANGSWTDMD TPSRCVRICS
110 120 130 140 150
KSYLTLENGK VFLTGGDLPA LDGARVEFRC DPDFHLVGSS RSVCSQGQWS
160 170 180 190 200
TPKPHCQVNR TPHSERRAVY IGALFPMSGG WPGGQACQPA VEMALEDVNS
210 220 230 240 250
RRDILPDYEL KLIHHDSKCD PGQATKYLYE LLYNDPIKII LMPGCSSVST
260 270 280 290 300
LVAEAARMWN LIVLSYGSSS PALSNRQRFP TFFRTHPSAT LHNPTRVKLF
310 320 330 340 350
EKWGWKKIAT IQQTTEVFTS TLDDLEERVK EAGIEITFRQ SFFSDPAVPV
360 370 380 390 400
KNLKRQDARI IVGLFYETEA RKVFCEVYKE RLFGKKYVWF LIGWYADNWF
410 420 430 440 450
KTYDPSINCT VEEMTEAVEG HITTEIVMLN PANTRSISNM TSQEFVEKLT
460 470 480 490 500
KRLKRHPEET GGFQEAPLAY DAIWALALAL NKTSGGGGRS GVRLEDFNYN
510 520 530 540 550
NQTITDQIYR AMNSSSFEGV SGHVVFDASG SRMAWTLIEQ LQGGSYKKIG
560 570 580 590 600
YYDSTKDDLS WSKTDKWIGG SPPADQTLVI KTFRFLSQKL FISVSVLSSL
610 620 630 640 650
GIVLAVVCLS FNIYNSHVRY IQNSQPNLNN LTAVGCSLAL AAVFPLGLDG
660 670 680 690 700
YHIGRSQFPF VCQARLWLLG LGFSLGYGSM FTKIWWVHTV FTKKEEKKEW
710 720 730 740 750
RKTLEPWKLY ATVGLLVGMD VLTLAIWQIV DPLHRTIETF AKEEPKEDID
760 770 780 790 800
VSILPQLEHC SSKKMNTWLG ELWSFAVSSD VQRRATVGGD SPICVWPAPE
810 820 830 840 850
SIFYGYKGLL LLLGIFLAYE TKSVSTEKIN DHRAVGMAIY NVAVLCLITA
860 870 880 890 900
PVTMILSSQQ DAAFAFASLA IVFSSYITLV VLFVPKMRRL ITRGEWQSET
910 920 930 940 950
QDTMKTGSST NNNEEEKSRL LEKENRELEK IIAEKEERVS ELRHQLQSRQ
960 970 980 990
QLRSRRHPPT PPDPSGGLPR GPSEPPDRLS CDGSRVHLLY K
Length:991
Mass (Da):111,534
Last modified:May 1, 1999 - v1
Checksum:i012CD293D4B444A2
GO
Isoform 1A (identifier: Q9Z0U4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     771-801: Missing.

Show »
Length:960
Mass (Da):108,204
Checksum:i05B7FBBCBE9DBF94
GO
Isoform 1B (identifier: Q9Z0U4-3) [UniParc]FASTAAdd to basket

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

Show »
Length:844
Mass (Da):95,038
Checksum:iB3417F53BE4877E9
GO
Isoform 1C (identifier: Q9Z0U4-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-163: MLLLLLVPLF...PHCQVNRTPH → MGPGGPCTPV...PHPRVPPHPS

Show »
Length:875
Mass (Da):98,368
Checksum:iE7E9EDA9132D37F2
GO
Isoform 1D (identifier: Q9Z0U4-5) [UniParc]FASTAAdd to basket

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

Show »
Length:812
Mass (Da):90,921
Checksum:i5EFD7B169A727FDE
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0020441 – 163MLLLL…NRTPH → MGPGGPCTPVGWPLPLLLVM AAGVAPVWASHSPHLPRPHP RVPPHPS in isoform 1B, isoform 1C and isoform 1D. IBD:Add BLAST163
Alternative sequenceiVSP_002045771 – 801Missing in isoform 1A, isoform 1B and isoform 1D. IBD:Add BLAST31
Alternative sequenceiVSP_002046935 – 991KEERV…HLLYK → VCGDKQPGPPVSEGGLPVVG PSIEV in isoform 1D. IBD:Add BLAST57

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_112290.2. NM_031028.3. [Q9Z0U4-2]
XP_006255941.1. XM_006255879.3. [Q9Z0U4-1]
UniGeneiRn.30059.

Genome annotation databases

EnsembliENSRNOT00000051634; ENSRNOP00000047498; ENSRNOG00000000774. [Q9Z0U4-2]
ENSRNOT00000082545; ENSRNOP00000075630; ENSRNOG00000000774. [Q9Z0U4-5]
ENSRNOT00000084582; ENSRNOP00000075610; ENSRNOG00000000774. [Q9Z0U4-3]
ENSRNOT00000085050; ENSRNOP00000075181; ENSRNOG00000000774. [Q9Z0U4-4]
ENSRNOT00000088396; ENSRNOP00000072226; ENSRNOG00000000774. [Q9Z0U4-3]
GeneIDi81657.
KEGGirno:81657.
UCSCiRGD:621537. rat. [Q9Z0U4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiGABR1_RAT
AccessioniPrimary (citable) accession number: Q9Z0U4
Secondary accession number(s): O08620
, O08621, Q9Z0F9, Q9Z308
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: May 1, 1999
Last modified: November 22, 2017
This is version 161 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families