UniProt functional annotation for Q9UBS5



	UniProt functional annotation for Q9UBS5

UniProt code: Q9UBS5.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:9872316, PubMed:9872744, PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054). Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins (PubMed:18165688). 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:10906333, PubMed:10773016, PubMed:10075644, PubMed:9872744, PubMed:24305054). Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644). Calcium is required for high affinity binding to GABA (By similarity). Plays a critical role in the fine- tuning of inhibitory synaptic transmission (PubMed:9844003). 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:9844003, PubMed:9872316, PubMed:10075644, PubMed:9872744, PubMed:22660477). Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (Probable). Activated by (-)-baclofen, cgp27492 and blocked by phaclofen (PubMed:9844003, PubMed:9872316, PubMed:24305054). {ECO:0000250|UniProtKB:Q9Z0U4, ECO:0000269|PubMed:10075644, ECO:0000269|PubMed:10773016, ECO:0000269|PubMed:10906333, ECO:0000269|PubMed:15617512, ECO:0000269|PubMed:18165688, ECO:0000269|PubMed:22660477, ECO:0000269|PubMed:24305054, ECO:0000269|PubMed:9844003, ECO:0000269|PubMed:9872316, ECO:0000269|PubMed:9872744, ECO:0000305}.

Function: Isoform 1E may regulate the formation of functional GABBR1/GABBR2 heterodimers by competing for GABBR2 binding. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites.

Subunit: Heterodimer of GABBR1 and GABBR2 (PubMed:9872316, PubMed:10773016, PubMed:9872744, PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054). Homodimers may form, but are inactive (PubMed:9872316, PubMed:15617512). Isoform 1E (without C- terminal intracellular domain) is unable to dimerize via a coiled-coil interaction with GABBR2 (PubMed:10906333). Interacts (via C-terminus) with ATF4 (via leucine zipper domain) (By similarity). Interacts with JAKMIP1 (PubMed:14718537). {ECO:0000250|UniProtKB:Q9Z0U4, ECO:0000269|PubMed:10773016, ECO:0000269|PubMed:10906333, ECO:0000269|PubMed:14718537, ECO:0000269|PubMed:15617512, ECO:0000269|PubMed:18165688, ECO:0000269|PubMed:22660477, ECO:0000269|PubMed:24305054, ECO:0000269|PubMed:9872316, ECO:0000269|PubMed:9872744}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:15617512}; Multi-pass membrane protein {ECO:0000305}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000250|UniProtKB:Q9Z0U4}; Multi-pass membrane protein {ECO:0000305}. Cell projection, dendrite {ECO:0000250|UniProtKB:Q9Z0U4}. Note=Colocalizes with ATF4 in hippocampal neuron dendritic membranes (By similarity). Coexpression of GABBR1 and GABBR2 is required for GABBR1 maturation and transport to the plasma membrane (PubMed:15617512). {ECO:0000250|UniProtKB:Q9Z0U4, ECO:0000269|PubMed:15617512}.

Subcellular location: [Isoform 1E]: Secreted {ECO:0000305}.

Tissue specificity: Highly expressed in brain (PubMed:9844003, PubMed:9753614, PubMed:9872744). Weakly expressed in heart, small intestine and uterus. Isoform 1A: Mainly expressed in granular cell and molecular layer (PubMed:9844003). Isoform 1B: Mainly expressed in Purkinje cells (PubMed:9844003). Isoform 1E: Predominantly expressed in peripheral tissues as kidney, lung, trachea, colon, small intestine, stomach, bone marrow, thymus and mammary gland (PubMed:10906333). {ECO:0000269|PubMed:10906333, ECO:0000269|PubMed:9753614, ECO:0000269|PubMed:9844003, ECO:0000269|PubMed:9872744}.

Domain: Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABBR2 (PubMed:9872744). 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 (PubMed:9844003). {ECO:0000305|PubMed:9844003, ECO:0000305|PubMed:9872744}.

Miscellaneous: [Isoform 1E]: Major isoform in almost all peripheral tissues, although containing a premature stop codon in the mRNA and thus being a potential target for nonsense-mediated mRNA decay. May act as an antagonist of GABA-B receptors, being able to disrupt the normal association between isoform 1A and GABBR2. {ECO:0000269|PubMed:10906333}.

Similarity: Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:9872316, PubMed:9872744, PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054). Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins (PubMed:18165688). 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:10906333, PubMed:10773016, PubMed:10075644, PubMed:9872744, PubMed:24305054). Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644). Calcium is required for high affinity binding to GABA (By similarity). Plays a critical role in the fine- tuning of inhibitory synaptic transmission (PubMed:9844003). 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:9844003, PubMed:9872316, PubMed:10075644, PubMed:9872744, PubMed:22660477). Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (Probable). Activated by (-)-baclofen, cgp27492 and blocked by phaclofen (PubMed:9844003, PubMed:9872316, PubMed:24305054). {ECO:0000250\|UniProtKB:Q9Z0U4, ECO:0000269\|PubMed:10075644, ECO:0000269\|PubMed:10773016, ECO:0000269\|PubMed:10906333, ECO:0000269\|PubMed:15617512, ECO:0000269\|PubMed:18165688, ECO:0000269\|PubMed:22660477, ECO:0000269\|PubMed:24305054, ECO:0000269\|PubMed:9844003, ECO:0000269\|PubMed:9872316, ECO:0000269\|PubMed:9872744, ECO:0000305}.



Function:		Isoform 1E may regulate the formation of functional GABBR1/GABBR2 heterodimers by competing for GABBR2 binding. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites.


Subunit:		Heterodimer of GABBR1 and GABBR2 (PubMed:9872316, PubMed:10773016, PubMed:9872744, PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054). Homodimers may form, but are inactive (PubMed:9872316, PubMed:15617512). Isoform 1E (without C- terminal intracellular domain) is unable to dimerize via a coiled-coil interaction with GABBR2 (PubMed:10906333). Interacts (via C-terminus) with ATF4 (via leucine zipper domain) (By similarity). Interacts with JAKMIP1 (PubMed:14718537). {ECO:0000250\|UniProtKB:Q9Z0U4, ECO:0000269\|PubMed:10773016, ECO:0000269\|PubMed:10906333, ECO:0000269\|PubMed:14718537, ECO:0000269\|PubMed:15617512, ECO:0000269\|PubMed:18165688, ECO:0000269\|PubMed:22660477, ECO:0000269\|PubMed:24305054, ECO:0000269\|PubMed:9872316, ECO:0000269\|PubMed:9872744}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:15617512}; Multi-pass membrane protein {ECO:0000305}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000250\|UniProtKB:Q9Z0U4}; Multi-pass membrane protein {ECO:0000305}. Cell projection, dendrite {ECO:0000250\|UniProtKB:Q9Z0U4}. Note=Colocalizes with ATF4 in hippocampal neuron dendritic membranes (By similarity). Coexpression of GABBR1 and GABBR2 is required for GABBR1 maturation and transport to the plasma membrane (PubMed:15617512). {ECO:0000250\|UniProtKB:Q9Z0U4, ECO:0000269\|PubMed:15617512}.
Subcellular location:		[Isoform 1E]: Secreted {ECO:0000305}.
Tissue specificity:		Highly expressed in brain (PubMed:9844003, PubMed:9753614, PubMed:9872744). Weakly expressed in heart, small intestine and uterus. Isoform 1A: Mainly expressed in granular cell and molecular layer (PubMed:9844003). Isoform 1B: Mainly expressed in Purkinje cells (PubMed:9844003). Isoform 1E: Predominantly expressed in peripheral tissues as kidney, lung, trachea, colon, small intestine, stomach, bone marrow, thymus and mammary gland (PubMed:10906333). {ECO:0000269\|PubMed:10906333, ECO:0000269\|PubMed:9753614, ECO:0000269\|PubMed:9844003, ECO:0000269\|PubMed:9872744}.
Domain:		Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABBR2 (PubMed:9872744). 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 (PubMed:9844003). {ECO:0000305\|PubMed:9844003, ECO:0000305\|PubMed:9872744}.
Miscellaneous:		[Isoform 1E]: Major isoform in almost all peripheral tissues, although containing a premature stop codon in the mRNA and thus being a potential target for nonsense-mediated mRNA decay. May act as an antagonist of GABA-B receptors, being able to disrupt the normal association between isoform 1A and GABBR2. {ECO:0000269\|PubMed:10906333}.
Similarity:		Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily. {ECO:0000305}.