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Conserved domains on  [gi|281364904|ref|NP_001162962|]
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uncharacterized protein Dmel_CG31760, isoform B [Drosophila melanogaster]

Protein Classification

furin-like repeat-containing protein; G-protein coupled receptor( domain architecture ID 12373492)

furin-like repeat (FU)-containing protein contains a cysteine-rich region; similar to Homo sapiens protein disulfide isomerase CRELD2 that might play a role in the unfolded protein response, as well as regulate transport of alpha4-beta2 neuronal acetylcholine receptor| G-protein coupled receptor (GPCR) transmits physiological signals from the outside of the cell to the inside by binding to an extracellular agonist, which induces conformational changes that lead to the activation of heterotrimeric G proteins, which then bind to and activate numerous downstream effector proteins

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 ...
510-759 2.08e-107

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: 331.10  E-value: 2.08e-107
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 510 PFRISLLTISIGCACGTFVLAGYLFRHRRVKVFKVASPIFLMITLIGCAIMYLEMVAIFPYLDTTWCIATKWTRHMGFCI 589
Cdd:cd15293    1 VLRIAVLAVQAICILLCLVLALVVFRFRKVKVIKAASPILLELILFGALLLYFPVFILYFEPSVFRCILRPWFRHLGFAI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 590 TYTSLLMKTWRVSLTYRVKSAHKIKLNDQQLLQWMVPILLVMLIYLGTWTISATPTAEVILD--QSQLKFKQCSYNWWDH 667
Cdd:cd15293   81 VYGALILKTYRILVVFRSRSARRVHLTDRDLLKRLGLIVLVVLGYLAAWTAVNPPNVEVGLTltSSGLKFNVCSLDWWDY 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 668 SLAIGEVFFLAWGIRVCYNVRNAESLYNEARLISYAIYNIALVNIAMVVFHVMLFPNAGPDYKYMLGFVRTQLSTTTTIA 747
Cdd:cd15293  161 VMAIAELLFLLWGVYLCYAVRKAPSAFNESRYISLAIYNELLLSVIFNIIRFFLLPSLHPDLLFLLFFLHTQLTVTVTLL 240
                        250
                 ....*....|..
gi 281364904 748 LVFGPKILRVFK 759
Cdd:cd15293  241 LIFGPKFYLVLR 252
FU smart00261
Furin-like repeats;
486-508 6.94e-03

Furin-like repeats;


:

Pssm-ID: 214589 [Multi-domain]  Cd Length: 45  Bit Score: 35.18  E-value: 6.94e-03
                           10        20
                   ....*....|....*....|....*...
gi 281364904   486 KCLPCAPGCDTCTGPEP-----CLANYH 508
Cdd:smart00261   3 ECKPCHPECATCTGPGPddctsCKHGFF 30
DivIVA super family cl34642
Cell division septum initiation protein DivIVA, interacts with FtsZ and MinD [Cell cycle ...
793-823 9.96e-03

Cell division septum initiation protein DivIVA, interacts with FtsZ and MinD [Cell cycle control, cell division, chromosome partitioning];


The actual alignment was detected with superfamily member COG3599:

Pssm-ID: 442818 [Multi-domain]  Cd Length: 125  Bit Score: 37.14  E-value: 9.96e-03
                         10        20        30
                 ....*....|....*....|....*....|.
gi 281364904 793 LYQENEELKEQVQKLAHQIEFMKTVHMQMNN 823
Cdd:COG3599   39 LIRENKELKEKLEELEEELEEYRELEETLQK 69
 
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 ...
510-759 2.08e-107

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: 331.10  E-value: 2.08e-107
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 510 PFRISLLTISIGCACGTFVLAGYLFRHRRVKVFKVASPIFLMITLIGCAIMYLEMVAIFPYLDTTWCIATKWTRHMGFCI 589
Cdd:cd15293    1 VLRIAVLAVQAICILLCLVLALVVFRFRKVKVIKAASPILLELILFGALLLYFPVFILYFEPSVFRCILRPWFRHLGFAI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 590 TYTSLLMKTWRVSLTYRVKSAHKIKLNDQQLLQWMVPILLVMLIYLGTWTISATPTAEVILD--QSQLKFKQCSYNWWDH 667
Cdd:cd15293   81 VYGALILKTYRILVVFRSRSARRVHLTDRDLLKRLGLIVLVVLGYLAAWTAVNPPNVEVGLTltSSGLKFNVCSLDWWDY 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 668 SLAIGEVFFLAWGIRVCYNVRNAESLYNEARLISYAIYNIALVNIAMVVFHVMLFPNAGPDYKYMLGFVRTQLSTTTTIA 747
Cdd:cd15293  161 VMAIAELLFLLWGVYLCYAVRKAPSAFNESRYISLAIYNELLLSVIFNIIRFFLLPSLHPDLLFLLFFLHTQLTVTVTLL 240
                        250
                 ....*....|..
gi 281364904 748 LVFGPKILRVFK 759
Cdd:cd15293  241 LIFGPKFYLVLR 252
7tm_3 pfam00003
7 transmembrane sweet-taste receptor of 3 GCPR; This is a domain of seven transmembrane ...
507-753 5.78e-45

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: 162.44  E-value: 5.78e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904  507 YHWPFRISLLTISIGCACGTFVLAGYLFRHRRVKVFKVASPIFLMITLIGCAIMYLeMVAIFPYLDTTWCIATKWTRHMG 586
Cdd:pfam00003   3 LSAPWGIVLEALAALGILLTLVLLVVFLLHRKTPIVKASNRSLSFLLLLGLLLLFL-LAFLFIGKPTVTCALRRFLFGVG 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904  587 FCITYTSLLMKTWRVSLTYRVKSAHKiklNDQQLLQWMVPILLVMLIYLGTWTISaTPTAEVILDQSQLKFKQCSYN--- 663
Cdd:pfam00003  82 FTLCFSCLLAKTFRLVLIFRRRKPGP---RGWQLLLLALGLLLVQVIILTEWLID-PPFPEKDNLSEGKIILECEGStsi 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904  664 WWDHSLAIGEVFFLAWGIRVCYNVRNAESLYNEARLISYAIYNIALVNIAMVVFHVMLFPNAGPDYKYMLGFVRTQLSTT 743
Cdd:pfam00003 158 AFLDFVLAYVGLLLLAGFLLAFKTRKLPDNFNEAKFITFSMLLSVLIWVAFIPMYLYGNKGKGTWDPVALAIFAILASGW 237
                         250
                  ....*....|
gi 281364904  744 TTIALVFGPK 753
Cdd:pfam00003 238 VLLGLYFIPK 247
FU smart00261
Furin-like repeats;
486-508 6.94e-03

Furin-like repeats;


Pssm-ID: 214589 [Multi-domain]  Cd Length: 45  Bit Score: 35.18  E-value: 6.94e-03
                           10        20
                   ....*....|....*....|....*...
gi 281364904   486 KCLPCAPGCDTCTGPEP-----CLANYH 508
Cdd:smart00261   3 ECKPCHPECATCTGPGPddctsCKHGFF 30
DivIVA COG3599
Cell division septum initiation protein DivIVA, interacts with FtsZ and MinD [Cell cycle ...
793-823 9.96e-03

Cell division septum initiation protein DivIVA, interacts with FtsZ and MinD [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 442818 [Multi-domain]  Cd Length: 125  Bit Score: 37.14  E-value: 9.96e-03
                         10        20        30
                 ....*....|....*....|....*....|.
gi 281364904 793 LYQENEELKEQVQKLAHQIEFMKTVHMQMNN 823
Cdd:COG3599   39 LIRENKELKEKLEELEEELEEYRELEETLQK 69
 
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 ...
510-759 2.08e-107

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: 331.10  E-value: 2.08e-107
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 510 PFRISLLTISIGCACGTFVLAGYLFRHRRVKVFKVASPIFLMITLIGCAIMYLEMVAIFPYLDTTWCIATKWTRHMGFCI 589
Cdd:cd15293    1 VLRIAVLAVQAICILLCLVLALVVFRFRKVKVIKAASPILLELILFGALLLYFPVFILYFEPSVFRCILRPWFRHLGFAI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 590 TYTSLLMKTWRVSLTYRVKSAHKIKLNDQQLLQWMVPILLVMLIYLGTWTISATPTAEVILD--QSQLKFKQCSYNWWDH 667
Cdd:cd15293   81 VYGALILKTYRILVVFRSRSARRVHLTDRDLLKRLGLIVLVVLGYLAAWTAVNPPNVEVGLTltSSGLKFNVCSLDWWDY 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 668 SLAIGEVFFLAWGIRVCYNVRNAESLYNEARLISYAIYNIALVNIAMVVFHVMLFPNAGPDYKYMLGFVRTQLSTTTTIA 747
Cdd:cd15293  161 VMAIAELLFLLWGVYLCYAVRKAPSAFNESRYISLAIYNELLLSVIFNIIRFFLLPSLHPDLLFLLFFLHTQLTVTVTLL 240
                        250
                 ....*....|..
gi 281364904 748 LVFGPKILRVFK 759
Cdd:cd15293  241 LIFGPKFYLVLR 252
7tm_3 pfam00003
7 transmembrane sweet-taste receptor of 3 GCPR; This is a domain of seven transmembrane ...
507-753 5.78e-45

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: 162.44  E-value: 5.78e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904  507 YHWPFRISLLTISIGCACGTFVLAGYLFRHRRVKVFKVASPIFLMITLIGCAIMYLeMVAIFPYLDTTWCIATKWTRHMG 586
Cdd:pfam00003   3 LSAPWGIVLEALAALGILLTLVLLVVFLLHRKTPIVKASNRSLSFLLLLGLLLLFL-LAFLFIGKPTVTCALRRFLFGVG 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904  587 FCITYTSLLMKTWRVSLTYRVKSAHKiklNDQQLLQWMVPILLVMLIYLGTWTISaTPTAEVILDQSQLKFKQCSYN--- 663
Cdd:pfam00003  82 FTLCFSCLLAKTFRLVLIFRRRKPGP---RGWQLLLLALGLLLVQVIILTEWLID-PPFPEKDNLSEGKIILECEGStsi 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904  664 WWDHSLAIGEVFFLAWGIRVCYNVRNAESLYNEARLISYAIYNIALVNIAMVVFHVMLFPNAGPDYKYMLGFVRTQLSTT 743
Cdd:pfam00003 158 AFLDFVLAYVGLLLLAGFLLAFKTRKLPDNFNEAKFITFSMLLSVLIWVAFIPMYLYGNKGKGTWDPVALAIFAILASGW 237
                         250
                  ....*....|
gi 281364904  744 TTIALVFGPK 753
Cdd:pfam00003 238 VLLGLYFIPK 247
7tmC_GABA-B-like cd15047
gamma-aminobutyric acid type B receptor and related proteins, member of the class C family of ...
510-759 2.16e-42

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: 155.41  E-value: 2.16e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 510 PFRISLLTISIGCACGTFVLAGYLFRHRRVKVFKVASPIFLMITLIGCAIMYlemVAIFPYLDTTW------CIATKWTR 583
Cdd:cd15047    1 PLFIVFTVLSGIGILLALVFLIFNIKFRKNRVIKMSSPLFNNLILLGCILCY---ISVILFGLDDSkpssflCTARPWLL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 584 HMGFCITYTSLLMKTWRVSLTYRVKSAHKIKLNDQQLLQWMVPILLVMLIYLGTWTISATPTAEVILD----------QS 653
Cdd:cd15047   78 SIGFTLVFGALFAKTWRIYRIFTNKKLKRIVIKDKQLLKIVGILLLIDIIILILWTIVDPLKPTRVLVlseisddvkyEY 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 654 QLKFKQCSYNW-WDHSLAIGEVFFLAWGIRVCYNVRNAESL-YNEARLISYAIYNIALVniAMVVFHVMLFPNAGPDYKY 731
Cdd:cd15047  158 VVHCCSSSNGIiWLGILLAYKGLLLLFGCFLAWKTRNVDIEeFNESKYIGISIYNVLFL--SVIGVPLSFVLTDSPDTSY 235
                        250       260
                 ....*....|....*....|....*...
gi 281364904 732 MLGFVRTQLSTTTTIALVFGPKILRVFK 759
Cdd:cd15047  236 LIISAAILFCTTATLCLLFVPKFWLLKR 263
7tm_classC_mGluR-like cd13953
metabotropic glutamate receptor-like class C family of seven-transmembrane G protein-coupled ...
510-754 3.44e-23

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: 99.62  E-value: 3.44e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 510 PFRISLLTISIGCACGTFVLAGYLFRHRRVKVFKVASPIFLMITLIGCAIMYLEMVA-IFPYLDTTwCIATKWTRHMGFC 588
Cdd:cd13953    1 PLAIVLLVLAALGLLLTIFIWVVFIRYRNTPVVKASNRELSYLLLFGILLCFLLAFLfLLPPSDVL-CGLRRFLFGLSFT 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 589 ITYTSLLMKTWRVsltYRVKSAHKIKLNDQQLLQWMVPILLVMLIYL------GTWTISATPTAEVILDQSQLKFKQCSY 662
Cdd:cd13953   80 LVFSTLLVKTNRI---YRIFKSGLRSSLRPKLLSNKSQLLLVLFLLLvqvailIVWLILDPPKVEKVIDSDNKVVELCCS 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 663 NWWDHSLAIG--EVFFLAWGIRVCYNVRNAESLYNEARLISYAIYNIALVNIAMVVFHVMLFpnagPDYKYMLGFVRTQL 740
Cdd:cd13953  157 TGNIGLILSLvyNILLLLICTYLAFKTRKLPDNFNEARYIGFSSLLSLVIWIAFIPTYFTTS----GPYRDAILSFGLLL 232
                        250
                 ....*....|....
gi 281364904 741 STTTTIALVFGPKI 754
Cdd:cd13953  233 NATVLLLCLFLPKI 246
7tmC_GABA-B-R1 cd15291
gamma-aminobutyric acid type B receptor subunit 1, member of the class C family of ...
513-757 1.48e-09

gamma-aminobutyric acid type B receptor subunit 1, 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: 320418  Cd Length: 274  Bit Score: 60.04  E-value: 1.48e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 513 ISLL-TISIGCACGTFVLAGYlFRHRRVkvFKVASPIFLMITLIGCAimyLEMVAIFPY-LD---------TTWCIATKW 581
Cdd:cd15291    6 MCLLaSLGIFAAVFLLIFNIY-NRHRRY--IQLSQPHCNNVMLVGCI---LCLASVFLLgLDgrhvsrshfPLVCQARLW 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 582 TRHMGFCITYTSLLMKTWRVsltYRVKSAHKIKLNDQQLLQ-----WMVPILLVM-LIYLGTWTI------------SAT 643
Cdd:cd15291   80 LLCLGFTLAYGSMFTKVWRV---HRLTTKKKEKKETRKTLEpwklyAVVGILLVVdVIILAIWQIvdplhrtieefpLEE 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 644 PTAEVILDQSQLKFKQCS---YNWWdhslaIGEVF-----FLAWGIRVCYNVRNAESLY-NEARLISYAIYNIALvnIAM 714
Cdd:cd15291  157 PKDTDEDVKILPQLEHCSskkQNTW-----LGIVYgykglLLLFGLFLAYETRNVKVEKiNDSRFVGMSIYNVVV--LCL 229
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 281364904 715 VVFHVMLFPNAGPDYKYMLGFVRTQLSTTTTIALVFGPKILRV 757
Cdd:cd15291  230 ITAPVTMIISSQQDASFAFVSLAILFSSYITLVLIFVPKIREL 272
7tmC_GABA-B-R2 cd15294
gamma-aminobutyric acid type B receptor subunit 2, member of the class C family of ...
516-755 2.90e-09

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: 58.98  E-value: 2.90e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 516 LTISIGCACGTFVLAGYLF---RHRRVKVFKVASPIFLMITLIGCAIMYLEMvaIFPYLDTTW---------CIATKWTR 583
Cdd:cd15294    4 SILSSLTIIGIILASAFLAfniKFRNHRYIKMSSPYMNNLIILGCMLTYASV--ILLGLDGSLvsektfetlCTARTWIL 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 584 HMGFCITYTSLLMKTWRVSLTYRVKSAHKIKLNDQQLLQWMVPILLVMLIYLGTWTISATPTAEV-------------IL 650
Cdd:cd15294   82 CVGFTLAFGAMFSKTWRVHSIFTNVKLNKKAIKDYKLFIIVGVLLLIDICILITWQIVDPFYRTVkelepepdpagddIL 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281364904 651 DQSQLKFKQCSY-NWWDHSL----AIGEVF--FLAWGIRvcyNVrNAESLyNEARLISYAIYNIALVNIAMVVFHVMLfp 723
Cdd:cd15294  162 IRPELEYCESTHmTIFLGIIyaykGLLMVFgcFLAWETR---NV-SIPAL-NDSKYIGMSVYNVVIMCVIGAAVSFIL-- 234
                        250       260       270
                 ....*....|....*....|....*....|..
gi 281364904 724 NAGPDYKYMLGFVRTQLSTTTTIALVFGPKIL 755
Cdd:cd15294  235 RDQPNVQFCIISLFIIFCTTITLCLVFVPKLI 266
FU smart00261
Furin-like repeats;
486-508 6.94e-03

Furin-like repeats;


Pssm-ID: 214589 [Multi-domain]  Cd Length: 45  Bit Score: 35.18  E-value: 6.94e-03
                           10        20
                   ....*....|....*....|....*...
gi 281364904   486 KCLPCAPGCDTCTGPEP-----CLANYH 508
Cdd:smart00261   3 ECKPCHPECATCTGPGPddctsCKHGFF 30
DivIVA COG3599
Cell division septum initiation protein DivIVA, interacts with FtsZ and MinD [Cell cycle ...
793-823 9.96e-03

Cell division septum initiation protein DivIVA, interacts with FtsZ and MinD [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 442818 [Multi-domain]  Cd Length: 125  Bit Score: 37.14  E-value: 9.96e-03
                         10        20        30
                 ....*....|....*....|....*....|.
gi 281364904 793 LYQENEELKEQVQKLAHQIEFMKTVHMQMNN 823
Cdd:COG3599   39 LIRENKELKEKLEELEEELEEYRELEETLQK 69
 
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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