ID:GABR1_HUMAN DESCRIPTION: RecName: Full=Gamma-aminobutyric acid type B receptor subunit 1; Short=GABA-B receptor 1; Short=GABA-B-R1; Short=GABA-BR1; Short=GABABR1; Short=Gb1; Flags: Precursor; 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. Activated by (-)-baclofen, cgp27492 and blocked by phaclofen. FUNCTION: Isoform 1E function may be to regulate the availability of functional GABA-B-R1A/GABA-B-R2 heterodimers by competing for GABA-B-R2 dimerization. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites. COFACTOR: Calcium. Required for high affinity binding to GABA. SUBUNIT: 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. Isoform 1E (without C-terminal intracellular domain) is unable to dimerize via a coiled-coil interaction with GABA-B-R2. Interacts with the leucine zipper of the C-terminal bZIP domain of ATF4 via its C-terminal region. Interacts with JAKMIP1. INTERACTION: P61244:MAX; NbExp=3; IntAct=EBI-724156, EBI-751711; P16333:NCK1; NbExp=3; IntAct=EBI-724156, EBI-389883; SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. Cell junction, synapse, postsynaptic cell membrane; Multi-pass membrane protein. Note=Colocalizes with ATF4 in hippocampal neuron dendritic membranes (By similarity). 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. SUBCELLULAR LOCATION: Isoform 1E: Secreted (Probable). TISSUE SPECIFICITY: Highly expressed in brain and weakly in heart, small intestine and uterus. Isoform 1A is mostly expressed in granular cell and molecular layer. Isoform 1B is mostly expressed in Purkinje cells. Isoform 1E is predominantly expressed in peripheral tissues as kidney, lung, trachea, colon, small intestine, stomach, bone marrow, thymus and mammary gland. DOMAIN: Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABA-B receptor 2. The linker region between the transmembrane domain 3 (TM3) and the transmembrane domain 4 (TM4) probably play a role in the specificity for G-protein coupling. SIMILARITY: Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily. SIMILARITY: Contains 2 Sushi (CCP/SCR) domains.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00003 - 7 transmembrane sweet-taste receptor of 3 GCPR PF00084 - Sushi repeat (SCR repeat) PF01094 - Receptor family ligand binding region PF13458 - Periplasmic binding protein
SCOP Domains: 53822 - Periplasmic binding protein-like I 57535 - Complement control module/SCR domain
ModBase Predicted Comparative 3D Structure on Q9UBS5
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
KJ896844 - Synthetic construct Homo sapiens clone ccsbBroadEn_06238 GABBR1 gene, encodes complete protein. KR710932 - Synthetic construct Homo sapiens clone CCSBHm_00018292 GABBR1 (GABBR1) mRNA, encodes complete protein. BC051463 - Homo sapiens gamma-aminobutyric acid (GABA) B receptor, 1, mRNA (cDNA clone IMAGE:5299098), **** WARNING: chimeric clone ****. LF210829 - JP 2014500723-A/18332: Polycomb-Associated Non-Coding RNAs. AJ225028 - Homo sapiens mRNA for GABA-B R1a receptor. Y11044 - Homo sapiens mRNA for GABA-BR1a (hGB1a) receptor. JD171659 - Sequence 152683 from Patent EP1572962. BC050532 - Homo sapiens gamma-aminobutyric acid (GABA) B receptor, 1, mRNA (cDNA clone MGC:57575 IMAGE:5732186), complete cds. AJ012288 - Homo sapiens mRNA for GABA-BR1. BC023336 - Homo sapiens gamma-aminobutyric acid (GABA) B receptor, 1, mRNA (cDNA clone IMAGE:4934044). BC042598 - Homo sapiens gamma-aminobutyric acid (GABA) B receptor, 1, mRNA (cDNA clone MGC:24911 IMAGE:4938491), complete cds. BC041332 - Homo sapiens gamma-aminobutyric acid (GABA) B receptor, 1, mRNA (cDNA clone MGC:41792 IMAGE:5275467), complete cds. AB208790 - Homo sapiens mRNA for gamma-aminobutyric acid (GABA) B receptor 1 isoform c precursor variant protein. LF341444 - JP 2014500723-A/148947: Polycomb-Associated Non-Coding RNAs. JD205024 - Sequence 186048 from Patent EP1572962. JD097004 - Sequence 78028 from Patent EP1572962. JD228016 - Sequence 209040 from Patent EP1572962. JD080086 - Sequence 61110 from Patent EP1572962. JD209669 - Sequence 190693 from Patent EP1572962. JD119747 - Sequence 100771 from Patent EP1572962. JD270356 - Sequence 251380 from Patent EP1572962. JD378380 - Sequence 359404 from Patent EP1572962. JD354604 - Sequence 335628 from Patent EP1572962. JD419904 - Sequence 400928 from Patent EP1572962. JD298257 - Sequence 279281 from Patent EP1572962. JD238681 - Sequence 219705 from Patent EP1572962. JD516670 - Sequence 497694 from Patent EP1572962. JD381727 - Sequence 362751 from Patent EP1572962. JD433225 - Sequence 414249 from Patent EP1572962. JD404176 - Sequence 385200 from Patent EP1572962. LF341443 - JP 2014500723-A/148946: Polycomb-Associated Non-Coding RNAs. JD039423 - Sequence 20447 from Patent EP1572962. JD415106 - Sequence 396130 from Patent EP1572962. JD136445 - Sequence 117469 from Patent EP1572962. JD095141 - Sequence 76165 from Patent EP1572962. JD185115 - Sequence 166139 from Patent EP1572962. JD454866 - Sequence 435890 from Patent EP1572962. JD105042 - Sequence 86066 from Patent EP1572962. JD068365 - Sequence 49389 from Patent EP1572962. AK290191 - Homo sapiens cDNA FLJ77697 complete cds, highly similar to Homo sapiens gamma-aminobutyric acid (GABA) B receptor, 1 (GABBR1), transcript variant 2, mRNA. JD367845 - Sequence 348869 from Patent EP1572962. JD423503 - Sequence 404527 from Patent EP1572962. JD338833 - Sequence 319857 from Patent EP1572962. JD437156 - Sequence 418180 from Patent EP1572962. JD530381 - Sequence 511405 from Patent EP1572962. JD401394 - Sequence 382418 from Patent EP1572962. JD153775 - Sequence 134799 from Patent EP1572962. JD404258 - Sequence 385282 from Patent EP1572962. AJ225029 - Homo sapiens mRNA for GABA-B R1b receptor. AF099148 - Homo sapiens GABA-B1a receptor mRNA, complete cds. JD453406 - Sequence 434430 from Patent EP1572962. JD167863 - Sequence 148887 from Patent EP1572962. AK223619 - Homo sapiens mRNA for gamma-aminobutyric acid (GABA) B receptor 1 isoform b precursor variant, clone: FCC134B02. JD485384 - Sequence 466408 from Patent EP1572962. JD445499 - Sequence 426523 from Patent EP1572962. JD220121 - Sequence 201145 from Patent EP1572962. JD485996 - Sequence 467020 from Patent EP1572962. JD077791 - Sequence 58815 from Patent EP1572962. JD559757 - Sequence 540781 from Patent EP1572962. AJ012186 - Homo sapiens mRNA for GABAB receptor, subunit 1b. AK312308 - Homo sapiens cDNA, FLJ92613, Homo sapiens gamma-aminobutyric acid (GABA) B receptor, 1 (GABBR1),transcript variant 2, mRNA. AJ012185 - Homo sapiens mRNA for GABAB-receptor, subunit 1a. AJ012187 - Homo sapiens mRNA for GABAB receptor, subunit 1c. AB527851 - Synthetic construct DNA, clone: pF1KB8525, Homo sapiens GABBR1 gene for gamma-aminobutyric acid (GABA) B receptor, 1, without stop codon, in Flexi system. JD522169 - Sequence 503193 from Patent EP1572962. JD291172 - Sequence 272196 from Patent EP1572962. JD256196 - Sequence 237220 from Patent EP1572962. JD438766 - Sequence 419790 from Patent EP1572962. JD394593 - Sequence 375617 from Patent EP1572962. JD451970 - Sequence 432994 from Patent EP1572962. JD090134 - Sequence 71158 from Patent EP1572962. JD051800 - Sequence 32824 from Patent EP1572962. JD433886 - Sequence 414910 from Patent EP1572962. JD042730 - Sequence 23754 from Patent EP1572962. JD096748 - Sequence 77772 from Patent EP1572962. JD162723 - Sequence 143747 from Patent EP1572962. JD478971 - Sequence 459995 from Patent EP1572962. JD543505 - Sequence 524529 from Patent EP1572962. JD210598 - Sequence 191622 from Patent EP1572962. JD455390 - Sequence 436414 from Patent EP1572962. JD269928 - Sequence 250952 from Patent EP1572962. JD479901 - Sequence 460925 from Patent EP1572962. JD174587 - Sequence 155611 from Patent EP1572962. JD134538 - Sequence 115562 from Patent EP1572962. JD510276 - Sequence 491300 from Patent EP1572962. AF301005 - Homo sapiens gamma-aminobutyric acid receptor GABA-B1e mRNA, complete cds. LF341438 - JP 2014500723-A/148941: Polycomb-Associated Non-Coding RNAs. LF341434 - JP 2014500723-A/148937: Polycomb-Associated Non-Coding RNAs. LF341432 - JP 2014500723-A/148935: Polycomb-Associated Non-Coding RNAs. JD291638 - Sequence 272662 from Patent EP1572962. JD178247 - Sequence 159271 from Patent EP1572962. JD471395 - Sequence 452419 from Patent EP1572962. JD480975 - Sequence 461999 from Patent EP1572962. JD215277 - Sequence 196301 from Patent EP1572962. JD071583 - Sequence 52607 from Patent EP1572962. JD468822 - Sequence 449846 from Patent EP1572962. JD318440 - Sequence 299464 from Patent EP1572962. JD128791 - Sequence 109815 from Patent EP1572962. JD191329 - Sequence 172353 from Patent EP1572962. MA446406 - JP 2018138019-A/18332: Polycomb-Associated Non-Coding RNAs. MA577021 - JP 2018138019-A/148947: Polycomb-Associated Non-Coding RNAs. MA577020 - JP 2018138019-A/148946: Polycomb-Associated Non-Coding RNAs. MA577015 - JP 2018138019-A/148941: Polycomb-Associated Non-Coding RNAs. MA577011 - JP 2018138019-A/148937: Polycomb-Associated Non-Coding RNAs. MA577009 - JP 2018138019-A/148935: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q9UBS5 (Reactome details) participates in the following event(s):
R-HSA-420688 GABAB heterodimeric receptor binds GABA R-HSA-749454 The Ligand:GPCR:Gi complex dissociates R-HSA-749456 Liganded Gi-activating GPCRs bind inactive heterotrimeric G-protein Gi R-HSA-380073 Liganded Gi-activating GPCR acts as a GEF for Gi R-HSA-1013020 Activation of GIRK/Kir3 Channels R-HSA-420499 Class C/3 (Metabotropic glutamate/pheromone receptors) R-HSA-977444 GABA B receptor activation R-HSA-418594 G alpha (i) signalling events R-HSA-500792 GPCR ligand binding R-HSA-977443 GABA receptor activation R-HSA-388396 GPCR downstream signalling R-HSA-372790 Signaling by GPCR R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission R-HSA-162582 Signal Transduction R-HSA-112315 Transmission across Chemical Synapses R-HSA-997272 Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits R-HSA-1296041 Activation of G protein gated Potassium channels R-HSA-112316 Neuronal System R-HSA-991365 Activation of GABAB receptors R-HSA-1296059 G protein gated Potassium channels R-HSA-1296065 Inwardly rectifying K+ channels R-HSA-1296071 Potassium Channels