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Conserved domains on  [gi|386769098|ref|NP_001245881|]
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smog, isoform D [Drosophila melanogaster]

Protein Classification

7tmC_GPR158-like domain-containing protein( domain architecture ID 11607178)

7tmC_GPR158-like domain-containing protein

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
7tmC_GPR158-like cd15293
orphan GPR158 and similar proteins, member of the class C family of seven-transmembrane G ...
529-780 3.12e-108

orphan GPR158 and similar proteins, member of the class C family of seven-transmembrane G protein-coupled receptors; This group includes orphan receptors GPR158, GPR158-like (also called GPR179) and similar proteins. These orphan receptors are closely related to the type B receptor for gamma-aminobutyric acid (GABA-B), which is activated by its endogenous ligand GABA, the principal inhibitory neurotransmitter. The functional GABA-B receptor is an obligatory heterodimer composed of two related subunits, GABA-B1, which is primarily involved in GABA ligand binding, and GABA-B2, which is responsible for both G-protein coupling and trafficking of the heterodimer to the plasma membrane. Activation of GABA-B couples to G(i/o)-type G proteins, which in turn modulate three major downstream effectors: adenylate cyclase, voltage-sensitive Ca2+ channels, and inwardly-rectifying K+ channels. Consequently, GABA-B receptor produces slow and sustained inhibitory responses by decreased neurotransmitter release via inhibition of Ca2+ channels and by postsynaptic hyperpolarization via the activation of K+ channels through the G-protein beta-gamma dimer. The GABA-B is expressed in both pre- and postsynaptic sites of glutamatergic and GABAergic neurons in the brain where it regulates synaptic activity. Thus, the GABA-B receptor agonist, baclofen, is used to treat muscle tightness and cramping caused by spasticity in multiple sclerosis patients. Moreover, GABA-B antagonists improves cognitive performance in mammals, while GABA-B agonists suppress cognitive behavior. In most of the class C family members, the extracellular Venus-flytrap domain in the N-terminus is connected to the seven-transmembrane (7TM) via a cysteine-rich domain (CRD). However, in the GABA-B receptor, the CRD is absent in both subunits and the Venus-flytrap ligand-binding domain is directly connected to the 7TM via a 10-15 amino acids linker, suggesting that GABA-B receptor may utilize a different activation mechanism.


:

Pssm-ID: 320420  Cd Length: 252  Bit Score: 334.95  E-value: 3.12e-108
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 529 CLRLLVAIVLGACILCCIVLGVIVFRQRKCKAIASGMWTVLETILLGIVLLYASVAVHFFPASTERCLLEPWLRELGFIT 608
Cdd:cd15293    1 VLRIAVLAVQAICILLCLVLALVVFRFRKVKVIKAASPILLELILFGALLLYFPVFILYFEPSVFRCILRPWFRHLGFAI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 609 CYGAIILKLYRHLVDFRTRKAHRWVLRDVDLLKYLGTMVFAVICYMAAFTASSLDLLESAQLESLREADTNTCHPLKWEL 688
Cdd:cd15293   81 VYGALILKTYRILVVFRSRSARRVHLTDRDLLKRLGLIVLVVLGYLAAWTAVNPPNVEVGLTLTSSGLKFNVCSLDWWDY 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 689 VTQTSEMLILCFGLHLSIASRNANTQFRERQFLVTALTLEFLVSSSFYFLRFVYLPEMSPSAILLALFIRSQLTNSFALG 768
Cdd:cd15293  161 VMAIAELLFLLWGVYLCYAVRKAPSAFNESRYISLAIYNELLLSVIFNIIRFFLLPSLHPDLLFLLFFLHTQLTVTVTLL 240
                        250
                 ....*....|..
gi 386769098 769 LIFVPKLWYQHK 780
Cdd:cd15293  241 LIFGPKFYLVLR 252
 
Name Accession Description Interval E-value
7tmC_GPR158-like cd15293
orphan GPR158 and similar proteins, member of the class C family of seven-transmembrane G ...
529-780 3.12e-108

orphan GPR158 and similar proteins, member of the class C family of seven-transmembrane G protein-coupled receptors; This group includes orphan receptors GPR158, GPR158-like (also called GPR179) and similar proteins. These orphan receptors are closely related to the type B receptor for gamma-aminobutyric acid (GABA-B), which is activated by its endogenous ligand GABA, the principal inhibitory neurotransmitter. The functional GABA-B receptor is an obligatory heterodimer composed of two related subunits, GABA-B1, which is primarily involved in GABA ligand binding, and GABA-B2, which is responsible for both G-protein coupling and trafficking of the heterodimer to the plasma membrane. Activation of GABA-B couples to G(i/o)-type G proteins, which in turn modulate three major downstream effectors: adenylate cyclase, voltage-sensitive Ca2+ channels, and inwardly-rectifying K+ channels. Consequently, GABA-B receptor produces slow and sustained inhibitory responses by decreased neurotransmitter release via inhibition of Ca2+ channels and by postsynaptic hyperpolarization via the activation of K+ channels through the G-protein beta-gamma dimer. The GABA-B is expressed in both pre- and postsynaptic sites of glutamatergic and GABAergic neurons in the brain where it regulates synaptic activity. Thus, the GABA-B receptor agonist, baclofen, is used to treat muscle tightness and cramping caused by spasticity in multiple sclerosis patients. Moreover, GABA-B antagonists improves cognitive performance in mammals, while GABA-B agonists suppress cognitive behavior. In most of the class C family members, the extracellular Venus-flytrap domain in the N-terminus is connected to the seven-transmembrane (7TM) via a cysteine-rich domain (CRD). However, in the GABA-B receptor, the CRD is absent in both subunits and the Venus-flytrap ligand-binding domain is directly connected to the 7TM via a 10-15 amino acids linker, suggesting that GABA-B receptor may utilize a different activation mechanism.


Pssm-ID: 320420  Cd Length: 252  Bit Score: 334.95  E-value: 3.12e-108
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 529 CLRLLVAIVLGACILCCIVLGVIVFRQRKCKAIASGMWTVLETILLGIVLLYASVAVHFFPASTERCLLEPWLRELGFIT 608
Cdd:cd15293    1 VLRIAVLAVQAICILLCLVLALVVFRFRKVKVIKAASPILLELILFGALLLYFPVFILYFEPSVFRCILRPWFRHLGFAI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 609 CYGAIILKLYRHLVDFRTRKAHRWVLRDVDLLKYLGTMVFAVICYMAAFTASSLDLLESAQLESLREADTNTCHPLKWEL 688
Cdd:cd15293   81 VYGALILKTYRILVVFRSRSARRVHLTDRDLLKRLGLIVLVVLGYLAAWTAVNPPNVEVGLTLTSSGLKFNVCSLDWWDY 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 689 VTQTSEMLILCFGLHLSIASRNANTQFRERQFLVTALTLEFLVSSSFYFLRFVYLPEMSPSAILLALFIRSQLTNSFALG 768
Cdd:cd15293  161 VMAIAELLFLLWGVYLCYAVRKAPSAFNESRYISLAIYNELLLSVIFNIIRFFLLPSLHPDLLFLLFFLHTQLTVTVTLL 240
                        250
                 ....*....|..
gi 386769098 769 LIFVPKLWYQHK 780
Cdd:cd15293  241 LIFGPKFYLVLR 252
7tm_3 pfam00003
7 transmembrane sweet-taste receptor of 3 GCPR; This is a domain of seven transmembrane ...
524-774 8.71e-33

7 transmembrane sweet-taste receptor of 3 GCPR; This is a domain of seven transmembrane regions that forms the C-terminus of some subclass 3 G-coupled-protein receptors. It is often associated with a downstream cysteine-rich linker domain, NCD3G pfam07562, which is the human sweet-taste receptor, and the N-terminal domain, ANF_receptor pfam01094. The seven TM regions assemble in such a way as to produce a docking pocket into which such molecules as cyclamate and lactisole have been found to bind and consequently confer the taste of sweetness.


Pssm-ID: 459626 [Multi-domain]  Cd Length: 247  Bit Score: 127.39  E-value: 8.71e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098  524 LNVDACLRLLVAIVLGACILCCIVLGVIVFRQRKCKAIASGMWTVLETILLGIVLLYASVAVHFFPaSTERCLLEPWLRE 603
Cdd:pfam00003   1 LDLSAPWGIVLEALAALGILLTLVLLVVFLLHRKTPIVKASNRSLSFLLLLGLLLLFLLAFLFIGK-PTVTCALRRFLFG 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098  604 LGFITCYGAIILKLYRHLVDFRTRKAhrwVLRDVDLLKYLGTMVFAVICYMAAFTASSLDLLESAQLESLREADTNTCHP 683
Cdd:pfam00003  80 VGFTLCFSCLLAKTFRLVLIFRRRKP---GPRGWQLLLLALGLLLVQVIILTEWLIDPPFPEKDNLSEGKIILECEGSTS 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098  684 LKWELVTQTSEMLILCFGLHLSIASRNANTQFRERQFLVTALTLEFLVSSSFYFLRFVYLPEMSPSAILLALFIRSQLTN 763
Cdd:pfam00003 157 IAFLDFVLAYVGLLLLAGFLLAFKTRKLPDNFNEAKFITFSMLLSVLIWVAFIPMYLYGNKGKGTWDPVALAIFAILASG 236
                         250
                  ....*....|.
gi 386769098  764 SFALGLIFVPK 774
Cdd:pfam00003 237 WVLLGLYFIPK 247
 
Name Accession Description Interval E-value
7tmC_GPR158-like cd15293
orphan GPR158 and similar proteins, member of the class C family of seven-transmembrane G ...
529-780 3.12e-108

orphan GPR158 and similar proteins, member of the class C family of seven-transmembrane G protein-coupled receptors; This group includes orphan receptors GPR158, GPR158-like (also called GPR179) and similar proteins. These orphan receptors are closely related to the type B receptor for gamma-aminobutyric acid (GABA-B), which is activated by its endogenous ligand GABA, the principal inhibitory neurotransmitter. The functional GABA-B receptor is an obligatory heterodimer composed of two related subunits, GABA-B1, which is primarily involved in GABA ligand binding, and GABA-B2, which is responsible for both G-protein coupling and trafficking of the heterodimer to the plasma membrane. Activation of GABA-B couples to G(i/o)-type G proteins, which in turn modulate three major downstream effectors: adenylate cyclase, voltage-sensitive Ca2+ channels, and inwardly-rectifying K+ channels. Consequently, GABA-B receptor produces slow and sustained inhibitory responses by decreased neurotransmitter release via inhibition of Ca2+ channels and by postsynaptic hyperpolarization via the activation of K+ channels through the G-protein beta-gamma dimer. The GABA-B is expressed in both pre- and postsynaptic sites of glutamatergic and GABAergic neurons in the brain where it regulates synaptic activity. Thus, the GABA-B receptor agonist, baclofen, is used to treat muscle tightness and cramping caused by spasticity in multiple sclerosis patients. Moreover, GABA-B antagonists improves cognitive performance in mammals, while GABA-B agonists suppress cognitive behavior. In most of the class C family members, the extracellular Venus-flytrap domain in the N-terminus is connected to the seven-transmembrane (7TM) via a cysteine-rich domain (CRD). However, in the GABA-B receptor, the CRD is absent in both subunits and the Venus-flytrap ligand-binding domain is directly connected to the 7TM via a 10-15 amino acids linker, suggesting that GABA-B receptor may utilize a different activation mechanism.


Pssm-ID: 320420  Cd Length: 252  Bit Score: 334.95  E-value: 3.12e-108
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 529 CLRLLVAIVLGACILCCIVLGVIVFRQRKCKAIASGMWTVLETILLGIVLLYASVAVHFFPASTERCLLEPWLRELGFIT 608
Cdd:cd15293    1 VLRIAVLAVQAICILLCLVLALVVFRFRKVKVIKAASPILLELILFGALLLYFPVFILYFEPSVFRCILRPWFRHLGFAI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 609 CYGAIILKLYRHLVDFRTRKAHRWVLRDVDLLKYLGTMVFAVICYMAAFTASSLDLLESAQLESLREADTNTCHPLKWEL 688
Cdd:cd15293   81 VYGALILKTYRILVVFRSRSARRVHLTDRDLLKRLGLIVLVVLGYLAAWTAVNPPNVEVGLTLTSSGLKFNVCSLDWWDY 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 689 VTQTSEMLILCFGLHLSIASRNANTQFRERQFLVTALTLEFLVSSSFYFLRFVYLPEMSPSAILLALFIRSQLTNSFALG 768
Cdd:cd15293  161 VMAIAELLFLLWGVYLCYAVRKAPSAFNESRYISLAIYNELLLSVIFNIIRFFLLPSLHPDLLFLLFFLHTQLTVTVTLL 240
                        250
                 ....*....|..
gi 386769098 769 LIFVPKLWYQHK 780
Cdd:cd15293  241 LIFGPKFYLVLR 252
7tm_3 pfam00003
7 transmembrane sweet-taste receptor of 3 GCPR; This is a domain of seven transmembrane ...
524-774 8.71e-33

7 transmembrane sweet-taste receptor of 3 GCPR; This is a domain of seven transmembrane regions that forms the C-terminus of some subclass 3 G-coupled-protein receptors. It is often associated with a downstream cysteine-rich linker domain, NCD3G pfam07562, which is the human sweet-taste receptor, and the N-terminal domain, ANF_receptor pfam01094. The seven TM regions assemble in such a way as to produce a docking pocket into which such molecules as cyclamate and lactisole have been found to bind and consequently confer the taste of sweetness.


Pssm-ID: 459626 [Multi-domain]  Cd Length: 247  Bit Score: 127.39  E-value: 8.71e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098  524 LNVDACLRLLVAIVLGACILCCIVLGVIVFRQRKCKAIASGMWTVLETILLGIVLLYASVAVHFFPaSTERCLLEPWLRE 603
Cdd:pfam00003   1 LDLSAPWGIVLEALAALGILLTLVLLVVFLLHRKTPIVKASNRSLSFLLLLGLLLLFLLAFLFIGK-PTVTCALRRFLFG 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098  604 LGFITCYGAIILKLYRHLVDFRTRKAhrwVLRDVDLLKYLGTMVFAVICYMAAFTASSLDLLESAQLESLREADTNTCHP 683
Cdd:pfam00003  80 VGFTLCFSCLLAKTFRLVLIFRRRKP---GPRGWQLLLLALGLLLVQVIILTEWLIDPPFPEKDNLSEGKIILECEGSTS 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098  684 LKWELVTQTSEMLILCFGLHLSIASRNANTQFRERQFLVTALTLEFLVSSSFYFLRFVYLPEMSPSAILLALFIRSQLTN 763
Cdd:pfam00003 157 IAFLDFVLAYVGLLLLAGFLLAFKTRKLPDNFNEAKFITFSMLLSVLIWVAFIPMYLYGNKGKGTWDPVALAIFAILASG 236
                         250
                  ....*....|.
gi 386769098  764 SFALGLIFVPK 774
Cdd:pfam00003 237 WVLLGLYFIPK 247
7tmC_GABA-B-like cd15047
gamma-aminobutyric acid type B receptor and related proteins, member of the class C family of ...
530-777 3.74e-29

gamma-aminobutyric acid type B receptor and related proteins, member of the class C family of seven-transmembrane G protein-coupled receptors; The type B receptor for gamma-aminobutyric acid, GABA-B, is activated by its endogenous ligand GABA, the principal inhibitory neurotransmitter. The functional GABA-B receptor is an obligatory heterodimer composed of two related subunits, GABA-B1, which is primarily involved in GABA ligand binding, and GABA-B2, which is responsible for both G-protein coupling and trafficking of the heterodimer to the plasma membrane. Activation of GABA-B couples to G(i/o)-type G proteins, which in turn modulate three major downstream effectors: adenylate cyclase, voltage-sensitive Ca2+ channels, and inwardly-rectifying K+ channels. Consequently, GABA-B receptor produces slow and sustained inhibitory responses by decreased neurotransmitter release via inhibition of Ca2+ channels and by postsynaptic hyperpolarization via the activation of K+ channels through the G-protein beta-gamma dimer. The GABA-B is expressed in both pre- and postsynaptic sites of glutamatergic and GABAergic neurons in the brain where it regulates synaptic activity. Thus, the GABA-B receptor agonist, baclofen, is used to treat muscle tightness and cramping caused by spasticity in multiple sclerosis patients. Moreover, GABA-B antagonists improves cognitive performance in mammals, while GABA-B agonists suppress cognitive behavior. In most of the class C family members, the extracellular Venus-flytrap domain in the N-terminus is connected to the seven-transmembrane (7TM) via a cysteine-rich domain (CRD). However, in the GABA-B receptor, the CRD is absent in both subunits and the Venus-flytrap ligand-binding domain is directly connected to the 7TM via a 10-15 amino acids linker, suggesting that GABA-B receptor may utilize a different activation mechanism. Also included in this group are orphan receptors, GPR156 and GPR158, which are closely related to the GABA-B receptor family.


Pssm-ID: 320175  Cd Length: 263  Bit Score: 117.28  E-value: 3.74e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 530 LRLLVAIVLGACILCCIVLGVIVFRQRKCKAIASGMWTVLETILLGIVLLYASVAVHFFP---ASTERCLLEPWLRELGF 606
Cdd:cd15047    2 LFIVFTVLSGIGILLALVFLIFNIKFRKNRVIKMSSPLFNNLILLGCILCYISVILFGLDdskPSSFLCTARPWLLSIGF 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 607 ITCYGAIILKLYR-HLVdFRTRKAHRWVLRDVDLLKYLGTMVFAVICYMAAFTAssLDLLESAQLESLREADTNTC---- 681
Cdd:cd15047   82 TLVFGALFAKTWRiYRI-FTNKKLKRIVIKDKQLLKIVGILLLIDIIILILWTI--VDPLKPTRVLVLSEISDDVKyeyv 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 682 -------HPLKWELVTQTSEMLILCFGLHLSIASRNANTQ-FRERQFLVTALTLEFLVSSSFYFLRFVylPEMSPSA--I 751
Cdd:cd15047  159 vhccsssNGIIWLGILLAYKGLLLLFGCFLAWKTRNVDIEeFNESKYIGISIYNVLFLSVIGVPLSFV--LTDSPDTsyL 236
                        250       260
                 ....*....|....*....|....*.
gi 386769098 752 LLALFIrsQLTNSFALGLIFVPKLWY 777
Cdd:cd15047  237 IISAAI--LFCTTATLCLLFVPKFWL 260
7tm_classC_mGluR-like cd13953
metabotropic glutamate receptor-like class C family of seven-transmembrane G protein-coupled ...
532-776 1.86e-20

metabotropic glutamate receptor-like class C family of seven-transmembrane G protein-coupled receptors superfamily; The class C GPCRs consist of glutamate receptors (mGluR1-8), the extracellular calcium-sensing receptors (caSR), the gamma-amino-butyric acid type B receptors (GABA-B), the vomeronasal type-2 pheromone receptors (V2R), the type 1 taste receptors (TAS1R), and the promiscuous L-alpha-amino acid receptor (GPRC6A), as well as several orphan receptors. Structurally, these receptors are typically composed of a large extracellular domain containing a Venus flytrap module which possesses the orthosteric agonist-binding site, a cysteine-rich domain (CRD) with the exception of GABA-B receptors, and the seven-transmembrane domains responsible for G protein activation. Moreover, the Venus flytrap module shows high structural homology with bacterial periplasmic amino acid-binding proteins, which serve as primary receptors in transport of a variety of soluble substrates such as amino acids and polysaccharides, among many others. The class C GPCRs exist as either homo- or heterodimers, which are essential for their function. The GABA-B1 and GABA-B2 receptors form a heterodimer via interactions between the N-terminal Venus flytrap modules and the C-terminal coiled-coiled domains. On the other hand, heterodimeric CaSRs and Tas1Rs and homodimeric mGluRs utilize Venus flytrap interactions and intermolecular disulphide bonds between cysteine residues located in the cysteine-rich domain (CRD), which can also acts as a molecular link to mediate the signal between the Venus flytrap and the 7TMs. Furthermore, members of the class C GPCRs bind a variety of endogenous ligands, ranging from amino acids, ions, to pheromones and sugar molecules, and play important roles in many physiological processes such as synaptic transmission, calcium homeostasis, and the sensation of sweet and umami tastes.


Pssm-ID: 320091 [Multi-domain]  Cd Length: 251  Bit Score: 91.91  E-value: 1.86e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 532 LLVAIVLGACILCCIVLGVIVFRQRKCKAIASGMWTVLETILLGIVLLYASVAVHFFPASTERCLLEPWLRELGFITCYG 611
Cdd:cd13953    4 IVLLVLAALGLLLTIFIWVVFIRYRNTPVVKASNRELSYLLLFGILLCFLLAFLFLLPPSDVLCGLRRFLFGLSFTLVFS 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 612 AIILKLYRHLVDFRTRKAHRW---VLRDVDLLKYLGTMVFAVICYMAAFTASSLDLLESAQLESLREADTNTCHPLKWEL 688
Cdd:cd13953   84 TLLVKTNRIYRIFKSGLRSSLrpkLLSNKSQLLLVLFLLLVQVAILIVWLILDPPKVEKVIDSDNKVVELCCSTGNIGLI 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 689 VTQTSEMLILCFGLHLSIASRNANTQFRERQFLVTALTLEFLVSSSFYFLRFVYLPEMSPSAILLALFirsqLTNSFALG 768
Cdd:cd13953  164 LSLVYNILLLLICTYLAFKTRKLPDNFNEARYIGFSSLLSLVIWIAFIPTYFTTSGPYRDAILSFGLL----LNATVLLL 239

                 ....*...
gi 386769098 769 LIFVPKLW 776
Cdd:cd13953  240 CLFLPKIY 247
7tmC_GABA-B-R2 cd15294
gamma-aminobutyric acid type B receptor subunit 2, member of the class C family of ...
530-775 5.53e-04

gamma-aminobutyric acid type B receptor subunit 2, member of the class C family of seven-transmembrane G protein-coupled receptors; The type B receptor for gamma-aminobutyric acid, GABA-B, is activated by its endogenous ligand GABA, the principal inhibitory neurotransmitter. The functional GABA-B receptor is an obligatory heterodimer composed of two related subunits, GABA-B1, which is primarily involved in GABA ligand binding, and GABA-B2, which is responsible for both G-protein coupling and trafficking of the heterodimer to the plasma membrane. Activation of GABA-B couples to G(i/o)-type G proteins, which in turn modulate three major downstream effectors: adenylate cyclase, voltage-sensitive Ca2+ channels, and inwardly-rectifying K+ channels. Consequently, GABA-B receptor produces slow and sustained inhibitory responses by decreased neurotransmitter release via inhibition of Ca2+ channels and by postsynaptic hyperpolarization via the activation of K+ channels through the G-protein beta-gamma dimer. The GABA-B is expressed in both pre- and postsynaptic sites of glutamatergic and GABAergic neurons in the brain where it regulates synaptic activity. Thus, the GABA-B receptor agonist, baclofen, is used to treat muscle tightness and cramping caused by spasticity in multiple sclerosis patients. Moreover, GABA-B antagonists improves cognitive performance in mammals, while GABA-B agonists suppress cognitive behavior. In most of the class C family members, the extracellular Venus-flytrap domain in the N-terminus is connected to the seven-transmembrane (7TM) via a cysteine-rich domain (CRD). However, in the GABA-B receptor, the CRD is absent in both subunits and the Venus-flytrap ligand-binding domain is directly connected to the 7TM via a 10-15 amino acids linker, suggesting that GABA-B receptor may utilize a different activation mechanism.


Pssm-ID: 320421  Cd Length: 270  Bit Score: 42.80  E-value: 5.53e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 530 LRLLVAIVLGACILCCIVLGVIVFRQRKCKAIASGMWTVLETILLGIVLLYASVAV-----HFFPAST--ERCLLEPWLR 602
Cdd:cd15294    2 LYSILSSLTIIGIILASAFLAFNIKFRNHRYIKMSSPYMNNLIILGCMLTYASVILlgldgSLVSEKTfeTLCTARTWIL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 603 ELGFITCYGAIILKLYRHLVDFRTRKAHRWVLRDVDLLKYLGTMVFAVICYMAAFTASSLDLLESAQLESL---READT- 678
Cdd:cd15294   82 CVGFTLAFGAMFSKTWRVHSIFTNVKLNKKAIKDYKLFIIVGVLLLIDICILITWQIVDPFYRTVKELEPEpdpAGDDIl 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 386769098 679 --------NTCHPLKWELVTQTSEMLILCFGLHLSIASRNANT-QFRERQFLVTALTLEFLVSSSFYFLRFVYLPEMSPS 749
Cdd:cd15294  162 irpeleycESTHMTIFLGIIYAYKGLLMVFGCFLAWETRNVSIpALNDSKYIGMSVYNVVIMCVIGAAVSFILRDQPNVQ 241
                        250       260
                 ....*....|....*....|....*.
gi 386769098 750 AILLALFIrsQLTNSFALGLIFVPKL 775
Cdd:cd15294  242 FCIISLFI--IFCTTITLCLVFVPKL 265
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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