NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|156119565|ref|NP_001092934|]
View 

vomeronasal 2 receptor, 8 [Rattus norvegicus]

Protein Classification

vomeronasal type-2 receptor( domain architecture ID 11659857)

vomeronasal type-2 receptor is a member of the class C family of seven-transmembrane G protein-coupled receptors and most likely involved with detecting protein pheromones for social and sexual cues between members of the same species

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

Name Accession Description Interval E-value
Periplasmic_Binding_Protein_type1 super family cl10011
Type 1 periplasmic binding fold superfamily; Type 1 periplasmic binding fold superfamily. This ...
43-503 1.20e-153

Type 1 periplasmic binding fold superfamily; Type 1 periplasmic binding fold superfamily. This model and hierarchy represent the ligand binding domains of the LacI family of transcriptional regulators, periplasmic binding proteins of the ABC-type transport systems, the family C G-protein couples receptors (GPCRs), membrane bound guanylyl cyclases including the family of natriuretic peptide receptors (NPRs), and the N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domains of the ionotropic glutamate receptors (iGluRs). In LacI-like transcriptional regulator and the bacterial periplasmic binding proteins, the ligands are monosaccharides, including lactose, ribose, fructose, xylose, arabinose, galactose/glucose and other sugars, with a few exceptions. Periplasmic sugar binding proteins are one of the components of ABC transporters and are involved in the active transport of water-soluble ligands. The LacI family of proteins consists of transcriptional regulators related to the lac repressor. In this case, the sugar binding domain binds a sugar which changes the DNA binding activity of the repressor domain. The periplasmic binding proteins are the primary receptors for chemotaxis and transport of many sugar based solutes. The core structures of periplasmic binding proteins are classified into two types, and they differ in number and order of beta strands: type 1 has six beta strands while type 2 has five beta strands per sub-domain. These two structural folds are thought to be distantly related via a common ancestor. Notably, while the N-terminal LIVBP-like domain of iGluRs belongs to the type 1 periplasmic-binding fold protein superfamily, the glutamate-binding domain of the iGluR is structurally similar to the type 2 periplasmic-binding fold.


The actual alignment was detected with superfamily member cd06365:

Pssm-ID: 471960 [Multi-domain]  Cd Length: 464  Bit Score: 458.65  E-value: 1.20e-153
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  43 VIGAFFPIHTYYTGnkIPHSFLPYYYVDNYLQYNFKNYQYILALIFAIEEINENPNLLSNISLGFDFYNVRFTEKDTLMN 122
Cdd:cd06365    1 IIGGVFPIHTFSEG--KKKDFKEPPSPLLCFRFSIKYYQHLLAFLFAIEEINKNPDLLPNITLGFHIYDSCSSERLALES 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 123 ACIWLTAHREkyILPNYKCGKKH-FTAALTGTSWTTSAQMGTLFQLFKFPQLSFGPYDHILSDRNQYSSLYQMAPMASSL 201
Cdd:cd06365   79 SLSILSGNSE--PIPNYSCREQRkLVAFIGDLSSSTSVAMARILGLYKYPQISYGAFDPLLSDKVQFPSFYRTVPSDTSQ 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 202 SLGIVSLLVHFRWSWVGLILPDDHKGNTILSDFRNEMERKGVCIAFLKMIPA--TWMSHFNKFWKNMDET-NVIIIYGDI 278
Cdd:cd06365  157 SLAIVQLLKHFGWTWVGLIISDDDYGEQFSQDLKKEMEKNGICVAFVEKIPTnsSLKRIIKYINQIIKSSaNVIIIYGDT 236
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 279 DSLEGLMRNIGQRLLTWKVWVMNIEPHVIAD--YFMLDSFHGSLIFTHHYTERIEFTNFVQTVNPYKYPEDIYLPKLWYL 356
Cdd:cd06365  237 DSLLELLFRLWEQLVTGKVWITTSQWDISTLpfEFYLNLFNGTLGFSQHSGEIPGFKEFLQSVHPSKYPEDIFLKTLWES 316
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 357 FFKCSFSDIDCQLLNNCQFNASLDILPRHIFDVSMSDESISIYNAVYAVAHSLHEMRLQQVQMQPYENGEEIMFFPWQVI 436
Cdd:cd06365  317 YFNCKWPDQNCKSLQNCCGNESLETLDVHSFDMTMSRLSYNVYNAVYAVAHALHEMLLCQPKTGPGNCSDRRNFQPWQLH 396
                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 437 SFLlyCNVSILI---DQRSLDWRQKFNTEYDIINLWNLPNGLGRKVKVGSFSTNAPQGHQLSLTEQIIQW 503
Cdd:cd06365  397 HYL--KKVQFTNpagDEVNFDEKGDLPTKYDILNWQIFPNGTGTKVKVGTFDPSAPSGQQLIINDSMIEW 464
7tmC_V2R_pheromone cd15283
vomeronasal type-2 pheromone receptors, member of the class C family of seven-transmembrane G ...
584-835 4.37e-142

vomeronasal type-2 pheromone receptors, member of the class C family of seven-transmembrane G protein-coupled receptors; This group represents vomeronasal type-2 pheromone receptors (V2Rs). Members of the V2R family of vomeronasal GPCRs are involved in detecting protein pheromones for social and sexual cues between the same species. V2Rs and G-alpha(o) protein are coexpressed in the basal layer of the vomeronasal organ (VNO), which is the sensory organ of the accessory olfactory system present in amphibians, reptiles, and non-primate mammals such as mice and rodents, but it is non-functional or absent in humans, apes, and monkeys. On the other hand, members of the V1R receptor family and G-alpha(i2) protein are coexpressed in the apical neurons of the VNO. Activation of V1R or V2R causes activation of phospholipase pathway, producing the second messengers diacylglycerol (DAG) and IP3. However, in contrast to V1Rs, V2Rs contain the long N-terminal extracellular domain, which is believed to bind pheromones.


:

Pssm-ID: 320410 [Multi-domain]  Cd Length: 252  Bit Score: 420.53  E-value: 4.37e-142
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 584 PLGMSLASIALCLSTLTAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTV 663
Cdd:cd15283    1 PLGIALTVLSLLGSVLTAAVLVVFIKHRDTPIVKANNSELSYLLLLSLKLCFLCSLLFIGQPSTWTCMLRQTAFGISFVL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 664 ALATVLAKAITVVIAFKATFPGRMIRWLMKSRAPNYIIPICTLIQVFICGIWMATSPPFIDQDFHAEHGHIIIFCNKGSS 743
Cdd:cd15283   81 CISCILAKTIVVVAAFKATRPGSNIMKWFGPGQQRAIIFICTLVQVVICAIWLATSPPFPDKNMHSEHGKIILECNEGSV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 744 VAFHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATEIFSILASSIALLS 823
Cdd:cd15283  161 VAFYCVLGYIGLLALVSFLLAFLARKLPDNFNEAKFITFSMLVFCAVWVAFVPAYISSPGKYMVAVEIFAILASSAGLLG 240
                        250
                 ....*....|..
gi 156119565 824 FIFAPKCYIILF 835
Cdd:cd15283  241 CIFAPKCYIILL 252
NCD3G pfam07562
Nine Cysteines Domain of family 3 GPCR; This conserved sequence contains several ...
511-564 1.30e-22

Nine Cysteines Domain of family 3 GPCR; This conserved sequence contains several highly-conserved Cys residues that are predicted to form disulphide bridges. It is predicted to lie outside the cell membrane, tethered to the pfam00003 in several receptor proteins.


:

Pssm-ID: 462210  Cd Length: 53  Bit Score: 91.55  E-value: 1.30e-22
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 156119565  511 PRSVCSESCGHGFRKLALEGKAVCCYKCTPCADNEISNeTDVDQCLKCPESHYA 564
Cdd:pfam07562   1 PSSVCSESCPPGQRKSQQGGAPVCCWDCVPCPEGEISN-TDSDTCKKCPEGQWP 53
 
Name Accession Description Interval E-value
PBP1_pheromone_receptor cd06365
Ligand-binding domain of the V2R pheromone receptor, a member of the family C receptors within ...
43-503 1.20e-153

Ligand-binding domain of the V2R pheromone receptor, a member of the family C receptors within the G-protein coupled receptor superfamily; Ligand-binding domain of the V2R pheromone receptor, a member of the family C receptors within the G-protein coupled receptor superfamily, which also includes the metabotropic glutamate receptor, the GABAb receptor, the calcium-sensing receptor (CaSR), the T1R taste receptor, and a small group of uncharacterized orphan receptors.


Pssm-ID: 380588 [Multi-domain]  Cd Length: 464  Bit Score: 458.65  E-value: 1.20e-153
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  43 VIGAFFPIHTYYTGnkIPHSFLPYYYVDNYLQYNFKNYQYILALIFAIEEINENPNLLSNISLGFDFYNVRFTEKDTLMN 122
Cdd:cd06365    1 IIGGVFPIHTFSEG--KKKDFKEPPSPLLCFRFSIKYYQHLLAFLFAIEEINKNPDLLPNITLGFHIYDSCSSERLALES 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 123 ACIWLTAHREkyILPNYKCGKKH-FTAALTGTSWTTSAQMGTLFQLFKFPQLSFGPYDHILSDRNQYSSLYQMAPMASSL 201
Cdd:cd06365   79 SLSILSGNSE--PIPNYSCREQRkLVAFIGDLSSSTSVAMARILGLYKYPQISYGAFDPLLSDKVQFPSFYRTVPSDTSQ 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 202 SLGIVSLLVHFRWSWVGLILPDDHKGNTILSDFRNEMERKGVCIAFLKMIPA--TWMSHFNKFWKNMDET-NVIIIYGDI 278
Cdd:cd06365  157 SLAIVQLLKHFGWTWVGLIISDDDYGEQFSQDLKKEMEKNGICVAFVEKIPTnsSLKRIIKYINQIIKSSaNVIIIYGDT 236
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 279 DSLEGLMRNIGQRLLTWKVWVMNIEPHVIAD--YFMLDSFHGSLIFTHHYTERIEFTNFVQTVNPYKYPEDIYLPKLWYL 356
Cdd:cd06365  237 DSLLELLFRLWEQLVTGKVWITTSQWDISTLpfEFYLNLFNGTLGFSQHSGEIPGFKEFLQSVHPSKYPEDIFLKTLWES 316
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 357 FFKCSFSDIDCQLLNNCQFNASLDILPRHIFDVSMSDESISIYNAVYAVAHSLHEMRLQQVQMQPYENGEEIMFFPWQVI 436
Cdd:cd06365  317 YFNCKWPDQNCKSLQNCCGNESLETLDVHSFDMTMSRLSYNVYNAVYAVAHALHEMLLCQPKTGPGNCSDRRNFQPWQLH 396
                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 437 SFLlyCNVSILI---DQRSLDWRQKFNTEYDIINLWNLPNGLGRKVKVGSFSTNAPQGHQLSLTEQIIQW 503
Cdd:cd06365  397 HYL--KKVQFTNpagDEVNFDEKGDLPTKYDILNWQIFPNGTGTKVKVGTFDPSAPSGQQLIINDSMIEW 464
7tmC_V2R_pheromone cd15283
vomeronasal type-2 pheromone receptors, member of the class C family of seven-transmembrane G ...
584-835 4.37e-142

vomeronasal type-2 pheromone receptors, member of the class C family of seven-transmembrane G protein-coupled receptors; This group represents vomeronasal type-2 pheromone receptors (V2Rs). Members of the V2R family of vomeronasal GPCRs are involved in detecting protein pheromones for social and sexual cues between the same species. V2Rs and G-alpha(o) protein are coexpressed in the basal layer of the vomeronasal organ (VNO), which is the sensory organ of the accessory olfactory system present in amphibians, reptiles, and non-primate mammals such as mice and rodents, but it is non-functional or absent in humans, apes, and monkeys. On the other hand, members of the V1R receptor family and G-alpha(i2) protein are coexpressed in the apical neurons of the VNO. Activation of V1R or V2R causes activation of phospholipase pathway, producing the second messengers diacylglycerol (DAG) and IP3. However, in contrast to V1Rs, V2Rs contain the long N-terminal extracellular domain, which is believed to bind pheromones.


Pssm-ID: 320410 [Multi-domain]  Cd Length: 252  Bit Score: 420.53  E-value: 4.37e-142
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 584 PLGMSLASIALCLSTLTAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTV 663
Cdd:cd15283    1 PLGIALTVLSLLGSVLTAAVLVVFIKHRDTPIVKANNSELSYLLLLSLKLCFLCSLLFIGQPSTWTCMLRQTAFGISFVL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 664 ALATVLAKAITVVIAFKATFPGRMIRWLMKSRAPNYIIPICTLIQVFICGIWMATSPPFIDQDFHAEHGHIIIFCNKGSS 743
Cdd:cd15283   81 CISCILAKTIVVVAAFKATRPGSNIMKWFGPGQQRAIIFICTLVQVVICAIWLATSPPFPDKNMHSEHGKIILECNEGSV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 744 VAFHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATEIFSILASSIALLS 823
Cdd:cd15283  161 VAFYCVLGYIGLLALVSFLLAFLARKLPDNFNEAKFITFSMLVFCAVWVAFVPAYISSPGKYMVAVEIFAILASSAGLLG 240
                        250
                 ....*....|..
gi 156119565 824 FIFAPKCYIILF 835
Cdd:cd15283  241 CIFAPKCYIILL 252
7tm_3 pfam00003
7 transmembrane sweet-taste receptor of 3 GCPR; This is a domain of seven transmembrane ...
579-829 2.83e-69

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: 229.47  E-value: 2.83e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  579 LAYQDPLGMSLASIALCLSTLTAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKdTCIMQQITFG 658
Cdd:pfam00003   1 LDLSAPWGIVLEALAALGILLTLVLLVVFLLHRKTPIVKASNRSLSFLLLLGLLLLFLLAFLFIGKPTV-TCALRRFLFG 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  659 VVFTVALATVLAKAITVVIAFKATFPGRMIRWLMKsrapnyIIPICTLIQVFICGIWMATsPPFIDQDFHAEhGHIIIFC 738
Cdd:pfam00003  80 VGFTLCFSCLLAKTFRLVLIFRRRKPGPRGWQLLL------LALGLLLVQVIILTEWLID-PPFPEKDNLSE-GKIILEC 151
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  739 NKGSSVAF-HCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVY-HSTMGKFM---VATEIFS 813
Cdd:pfam00003 152 EGSTSIAFlDFVLAYVGLLLLAGFLLAFKTRKLPDNFNEAKFITFSMLLSVLIWVAFIPMYlYGNKGKGTwdpVALAIFA 231
                         250
                  ....*....|....*.
gi 156119565  814 ILASSIALLSFIFAPK 829
Cdd:pfam00003 232 ILASGWVLLGLYFIPK 247
ANF_receptor pfam01094
Receptor family ligand binding region; This family includes extracellular ligand binding ...
84-435 1.30e-23

Receptor family ligand binding region; This family includes extracellular ligand binding domains of a wide range of receptors. This family also includes the bacterial amino acid binding proteins of known structure.


Pssm-ID: 460062 [Multi-domain]  Cd Length: 347  Bit Score: 103.23  E-value: 1.30e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565   84 LALIFAIEEINENPNLLSNISLGFDfynVRFTEKDTL--MNACIWLtahrekyilpnykcgKKHFTAALTG-TSWTTSAQ 160
Cdd:pfam01094   4 LAVRLAVEDINADPGLLPGTKLEYI---ILDTCCDPSlaLAAALDL---------------LKGEVVAIIGpSCSSVASA 65
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  161 MGTLFQLFKFPQLSFGPYDHILSDRNQYSSLYQMAPMASSLSLGIVSLLVHFRWSWVGLILPDDHKGNTILSDFRNEMER 240
Cdd:pfam01094  66 VASLANEWKVPLISYGSTSPALSDLNRYPTFLRTTPSDTSQADAIVDILKHFGWKRVALIYSDDDYGESGLQALEDALRE 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  241 KGVCIAFLKMIPATWMSH--FNKFWKNMD-ETNVIIIYGDIDSLEGLMR-----NIGQRLLTW--KVWVMNIEPHVIADY 310
Cdd:pfam01094 146 RGIRVAYKAVIPPAQDDDeiARKLLKEVKsRARVIVVCCSSETARRLLKaarelGMMGEGYVWiaTDGLTTSLVILNPST 225
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  311 fmLDSFHGSLIFTHHYTERIEFTNFVQtvnpykypEDIYLPKLWYLffkcsfsdidcqllnncqfnasldilprhifdvS 390
Cdd:pfam01094 226 --LEAAGGVLGFRLHPPDSPEFSEFFW--------EKLSDEKELYE---------------------------------N 262
                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 156119565  391 MSDESIS----IYNAVYAVAHSLHEMRLQQVQ------MQPYENGEEIMFFPWQV 435
Cdd:pfam01094 263 LGGLPVSygalAYDAVYLLAHALHNLLRDDKPgracgaLGPWNGGQKLLRYLKNV 317
NCD3G pfam07562
Nine Cysteines Domain of family 3 GPCR; This conserved sequence contains several ...
511-564 1.30e-22

Nine Cysteines Domain of family 3 GPCR; This conserved sequence contains several highly-conserved Cys residues that are predicted to form disulphide bridges. It is predicted to lie outside the cell membrane, tethered to the pfam00003 in several receptor proteins.


Pssm-ID: 462210  Cd Length: 53  Bit Score: 91.55  E-value: 1.30e-22
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 156119565  511 PRSVCSESCGHGFRKLALEGKAVCCYKCTPCADNEISNeTDVDQCLKCPESHYA 564
Cdd:pfam07562   1 PSSVCSESCPPGQRKSQQGGAPVCCWDCVPCPEGEISN-TDSDTCKKCPEGQWP 53
 
Name Accession Description Interval E-value
PBP1_pheromone_receptor cd06365
Ligand-binding domain of the V2R pheromone receptor, a member of the family C receptors within ...
43-503 1.20e-153

Ligand-binding domain of the V2R pheromone receptor, a member of the family C receptors within the G-protein coupled receptor superfamily; Ligand-binding domain of the V2R pheromone receptor, a member of the family C receptors within the G-protein coupled receptor superfamily, which also includes the metabotropic glutamate receptor, the GABAb receptor, the calcium-sensing receptor (CaSR), the T1R taste receptor, and a small group of uncharacterized orphan receptors.


Pssm-ID: 380588 [Multi-domain]  Cd Length: 464  Bit Score: 458.65  E-value: 1.20e-153
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  43 VIGAFFPIHTYYTGnkIPHSFLPYYYVDNYLQYNFKNYQYILALIFAIEEINENPNLLSNISLGFDFYNVRFTEKDTLMN 122
Cdd:cd06365    1 IIGGVFPIHTFSEG--KKKDFKEPPSPLLCFRFSIKYYQHLLAFLFAIEEINKNPDLLPNITLGFHIYDSCSSERLALES 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 123 ACIWLTAHREkyILPNYKCGKKH-FTAALTGTSWTTSAQMGTLFQLFKFPQLSFGPYDHILSDRNQYSSLYQMAPMASSL 201
Cdd:cd06365   79 SLSILSGNSE--PIPNYSCREQRkLVAFIGDLSSSTSVAMARILGLYKYPQISYGAFDPLLSDKVQFPSFYRTVPSDTSQ 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 202 SLGIVSLLVHFRWSWVGLILPDDHKGNTILSDFRNEMERKGVCIAFLKMIPA--TWMSHFNKFWKNMDET-NVIIIYGDI 278
Cdd:cd06365  157 SLAIVQLLKHFGWTWVGLIISDDDYGEQFSQDLKKEMEKNGICVAFVEKIPTnsSLKRIIKYINQIIKSSaNVIIIYGDT 236
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 279 DSLEGLMRNIGQRLLTWKVWVMNIEPHVIAD--YFMLDSFHGSLIFTHHYTERIEFTNFVQTVNPYKYPEDIYLPKLWYL 356
Cdd:cd06365  237 DSLLELLFRLWEQLVTGKVWITTSQWDISTLpfEFYLNLFNGTLGFSQHSGEIPGFKEFLQSVHPSKYPEDIFLKTLWES 316
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 357 FFKCSFSDIDCQLLNNCQFNASLDILPRHIFDVSMSDESISIYNAVYAVAHSLHEMRLQQVQMQPYENGEEIMFFPWQVI 436
Cdd:cd06365  317 YFNCKWPDQNCKSLQNCCGNESLETLDVHSFDMTMSRLSYNVYNAVYAVAHALHEMLLCQPKTGPGNCSDRRNFQPWQLH 396
                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 437 SFLlyCNVSILI---DQRSLDWRQKFNTEYDIINLWNLPNGLGRKVKVGSFSTNAPQGHQLSLTEQIIQW 503
Cdd:cd06365  397 HYL--KKVQFTNpagDEVNFDEKGDLPTKYDILNWQIFPNGTGTKVKVGTFDPSAPSGQQLIINDSMIEW 464
7tmC_V2R_pheromone cd15283
vomeronasal type-2 pheromone receptors, member of the class C family of seven-transmembrane G ...
584-835 4.37e-142

vomeronasal type-2 pheromone receptors, member of the class C family of seven-transmembrane G protein-coupled receptors; This group represents vomeronasal type-2 pheromone receptors (V2Rs). Members of the V2R family of vomeronasal GPCRs are involved in detecting protein pheromones for social and sexual cues between the same species. V2Rs and G-alpha(o) protein are coexpressed in the basal layer of the vomeronasal organ (VNO), which is the sensory organ of the accessory olfactory system present in amphibians, reptiles, and non-primate mammals such as mice and rodents, but it is non-functional or absent in humans, apes, and monkeys. On the other hand, members of the V1R receptor family and G-alpha(i2) protein are coexpressed in the apical neurons of the VNO. Activation of V1R or V2R causes activation of phospholipase pathway, producing the second messengers diacylglycerol (DAG) and IP3. However, in contrast to V1Rs, V2Rs contain the long N-terminal extracellular domain, which is believed to bind pheromones.


Pssm-ID: 320410 [Multi-domain]  Cd Length: 252  Bit Score: 420.53  E-value: 4.37e-142
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 584 PLGMSLASIALCLSTLTAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTV 663
Cdd:cd15283    1 PLGIALTVLSLLGSVLTAAVLVVFIKHRDTPIVKANNSELSYLLLLSLKLCFLCSLLFIGQPSTWTCMLRQTAFGISFVL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 664 ALATVLAKAITVVIAFKATFPGRMIRWLMKSRAPNYIIPICTLIQVFICGIWMATSPPFIDQDFHAEHGHIIIFCNKGSS 743
Cdd:cd15283   81 CISCILAKTIVVVAAFKATRPGSNIMKWFGPGQQRAIIFICTLVQVVICAIWLATSPPFPDKNMHSEHGKIILECNEGSV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 744 VAFHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATEIFSILASSIALLS 823
Cdd:cd15283  161 VAFYCVLGYIGLLALVSFLLAFLARKLPDNFNEAKFITFSMLVFCAVWVAFVPAYISSPGKYMVAVEIFAILASSAGLLG 240
                        250
                 ....*....|..
gi 156119565 824 FIFAPKCYIILF 835
Cdd:cd15283  241 CIFAPKCYIILL 252
7tmC_V2R_AA_sensing_receptor-like cd15044
vomeronasal type-2 pheromone receptors, amino acid-sensing receptors and closely related ...
584-835 3.32e-82

vomeronasal type-2 pheromone receptors, amino acid-sensing receptors and closely related proteins; member of the class C family of seven-transmembrane G protein-coupled receptors; This group is composed of vomeronasal type-2 pheromone receptors (V2Rs), a subgroup of broad-spectrum amino-acid sensing receptors including calcium-sensing receptor (CaSR) and GPRC6A, as well as their closely related proteins. Members of the V2R family of vomeronasal GPCRs are involved in detecting protein pheromones for social and sexual cues between the same species. V2Rs and G-alpha(o) protein are co-expressed in the basal layer of the vomeronasal organ (VNO), which is the sensory organ of the accessory olfactory system present in amphibians, reptiles, and non-primate mammals such as mice and rodents, but it is non-functional or absent in humans, apes, and monkeys. On the other hand, members of the V1R receptor family and G-alpha(i2) protein are co-expressed in the apical neurons of the VNO. Activation of V1R or V2R causes activation of phospholipase pathway, producing the second messengers diacylglycerol (DAG) and IP3. However, in contrast to V1Rs, V2Rs contain the long N-terminal extracellular domain, which is believed to bind pheromones. CaSR is a widely expressed GPCR that is involved in sensing small changes in extracellular levels of calcium ion to maintain a constant level of the extracellular calcium via modulating the synthesis and secretion of calcium regulating hormones, such as parathyroid hormone (PTH), in order to regulate Ca(2+)transport into or out of the extracellular fluid via kidney, intestine, and/or bone. For instance, when Ca2+ is high, CaSR downregulates PTH synthesis and secretion, leading to an increase in renal Ca2+ excretion, a decrease in intestinal Ca2+ absorption, and a reduction in release of skeletal Ca2+. GRPC6A (GPCR, class C, group 6, subtype A) is a widely expressed amino acid-sensing GPCR that is most closely related to CaSR. GPRC6A is most potently activated by the basic amino acids L-arginine, L-lysine, and L-ornithine and less potently by small aliphatic amino acids. Moreover, the receptor can be either activated or modulated by divalent cations such as Ca2+. GPRC6A is expressed in the testis, but not the ovary and specifically also binds to the osteoblast-derived hormone osteocalcin (OCN), which regulates testosterone production by the testis and male fertility independently of the hypothalamic-pituitary axis. Furthermore, GPRC6A knockout studies suggest that GRPC6A is involved in regulation of bone metabolism, male reproduction, energy homeostasis, glucose metabolism, and in activation of inflammation response, as well as prostate cancer growth and progression, among others.


Pssm-ID: 320172 [Multi-domain]  Cd Length: 251  Bit Score: 264.33  E-value: 3.32e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 584 PLGMSLASIALCLSTLTAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTV 663
Cdd:cd15044    1 PLGILLVILSILGIIFVLVVGGVFVRYRNTPIVKANNRELSYLILLSLFLCFSSSLFFIGEPQDWTCKLRQTMFGVSFTL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 664 ALATVLAKAITVVIAFKATFPGRMIRWlMKSRAPNYIIPICTLIQVFICGIWMATSPPFIDQDFHAEHGHIIIFCNKGSS 743
Cdd:cd15044   81 CISCILTKTLKVLLAFSADKPLTQKFL-MCLYLPILIVFTCTGIQVVICTVWLIFAPPTVEVNVSPLPRVIILECNEGSI 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 744 VAFHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATEIFSILASSIALLS 823
Cdd:cd15044  160 LAFGTMLGYIAFLAFLCFLFAFKARKLPDNYNEAKFITFGMLVFFIVWISFVPAYLSTKGKFVVAVEIIAILASSYGLLG 239
                        250
                 ....*....|..
gi 156119565 824 FIFAPKCYIILF 835
Cdd:cd15044  240 CIFLPKCYVILL 251
7tm_3 pfam00003
7 transmembrane sweet-taste receptor of 3 GCPR; This is a domain of seven transmembrane ...
579-829 2.83e-69

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: 229.47  E-value: 2.83e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  579 LAYQDPLGMSLASIALCLSTLTAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKdTCIMQQITFG 658
Cdd:pfam00003   1 LDLSAPWGIVLEALAALGILLTLVLLVVFLLHRKTPIVKASNRSLSFLLLLGLLLLFLLAFLFIGKPTV-TCALRRFLFG 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  659 VVFTVALATVLAKAITVVIAFKATFPGRMIRWLMKsrapnyIIPICTLIQVFICGIWMATsPPFIDQDFHAEhGHIIIFC 738
Cdd:pfam00003  80 VGFTLCFSCLLAKTFRLVLIFRRRKPGPRGWQLLL------LALGLLLVQVIILTEWLID-PPFPEKDNLSE-GKIILEC 151
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  739 NKGSSVAF-HCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVY-HSTMGKFM---VATEIFS 813
Cdd:pfam00003 152 EGSTSIAFlDFVLAYVGLLLLAGFLLAFKTRKLPDNFNEAKFITFSMLLSVLIWVAFIPMYlYGNKGKGTwdpVALAIFA 231
                         250
                  ....*....|....*.
gi 156119565  814 ILASSIALLSFIFAPK 829
Cdd:pfam00003 232 ILASGWVLLGLYFIPK 247
7tmC_V2R-like cd15280
vomeronasal type-2 receptor-like proteins, member of the class C family of seven-transmembrane ...
584-837 7.64e-62

vomeronasal type-2 receptor-like proteins, member of the class C family of seven-transmembrane G protein-coupled receptors; This group represents vomeronasal type-2 receptor-like proteins that are closely related to the V2R family of vomeronasal GPCRs. Members of the V2R family of vomeronasal GPCRs are involved in detecting protein pheromones for social and sexual cues between the same species. V2Rs and G-alpha(o) protein are coexpressed in the basal layer of the vomeronasal organ (VNO), which is the sensory organ of the accessory olfactory system present in amphibians, reptiles, and non-primate mammals such as mice and rodents, but it is non-functional or absent in humans, apes, and monkeys. On the other hand, members of the V1R receptor family and G-alpha(i2) protein are co-expressed in the apical neurons of the VNO. Activation of V1R or V2R causes activation of phospholipase pathway, generating the secondary messengers diacylglycerol (DAG) and IP3. However, in contrast to V1Rs, V2Rs contain the long N-terminal extracellular domain, which is believed to bind pheromones. Human V2R1-like protein, also known as putative calcium-sensing receptor-like 1 (CASRL1), is not included here because it is a nonfunctional pseudogene.


Pssm-ID: 320407 [Multi-domain]  Cd Length: 253  Bit Score: 209.64  E-value: 7.64e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 584 PLGMSLASIALCLSTLTAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTV 663
Cdd:cd15280    1 ALGITLIALSIFGALVVLAVTVVYIMHRHTPLVKANDRELSFLIQMSLVITFLTSILFIGKPENWSCMARQITLALGFSL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 664 ALATVLAKAITVVIAFKATFPGRMiRWLMKSRAPNYIIPICTLIQVFICGIWMATSPPFIDQDFHAEHGHIIIFCNKGSs 743
Cdd:cd15280   81 CLSSILGKTISLFLRYRASKSETR-LDSMHPIYQKIIVLICVLIEVGICTAYLILEPPRMYKNTEVQNVKIIFECNEGS- 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 744 VAFHCTL-GYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATEIFSILASSIALL 822
Cdd:cd15280  159 IEFLCSIfGFDVFLALLCFLTAFVARKLPDNFNEGKFITFGMLVFFIVWISFVPAYLSTRGKFKVAVEIFAILASSFGLL 238
                        250
                 ....*....|....*
gi 156119565 823 SFIFAPKCYIILFRP 837
Cdd:cd15280  239 GCIFVPKCYIILLKP 253
7tmC_CaSR cd15282
calcium-sensing receptor, member of the class C of seven-transmembrane G protein-coupled ...
584-835 8.19e-61

calcium-sensing receptor, member of the class C of seven-transmembrane G protein-coupled receptors; CaSR is a widely expressed GPCR that is involved in sensing small changes in extracellular levels of calcium ion to maintain a constant level of the extracellular calcium via modulating the synthesis and secretion of calcium regulating hormones, such as parathyroid hormone (PTH), in order to regulate Ca(2+)transport into or out of the extracellular fluid via kidney, intestine, and/or bone. For instance, when Ca2+ is high, CaSR downregulates PTH synthesis and secretion, leading to an increase in renal Ca2+ excretion, a decrease in intestinal Ca2+ absorption, and a reduction in release of skeletal Ca2+. CaSR is coupled to both G(q/11)-dependent activation of phospholipase and, subsequently, intracellular calcium mobilization and protein kinase C activation as well as G(i/o)-dependent inhibition of adenylate cyclase leading to inhibition of cAMP formation. CaSR is closely related to GRPC6A (GPCR, class C, group 6, subtype A), which is an amino acid-sensing GPCR that is most potently activated by the basic amino acids L-arginine, L-lysine, and L-ornithine. These receptors contain a large extracellular Venus flytrap-like domain in the N-terminus, cysteine-rich domain (CRD), and seven-transmembrane (7TM) domain, which are characteristics of the class C GPCRs. The Venus flytrap-like domain shares strong sequence homology to bacterial periplasmic binding proteins and possess the orthosteric amino acid and calcium binding sites for members of the class C, including CaSR, GABA-B1, GPRC6A, mGlu, and TASR1 receptors.


Pssm-ID: 320409 [Multi-domain]  Cd Length: 252  Bit Score: 206.72  E-value: 8.19e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 584 PLGMSLASIALCLSTLTAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTV 663
Cdd:cd15282    1 PFGIALTLFAVLGIFLTAFVLGVFIKFRNTPIVKATNRELSYLLLFSLICCFSSSLIFIGEPQDWTCRLRQPAFGISFVL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 664 ALATVLAKAITVVIAFKATFPGRMIRWLMKSRAPNYIIPICTLIQVFICGIWMATSPPFIDQDFHAEHGHIIIFCNKGSS 743
Cdd:cd15282   81 CISCILVKTNRVLLVFEAKIPTSLHRKWWGLNLQFLLVFLCTFVQIVICVIWLYTAPPSSYRNHELEDEIIFITCNEGSL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 744 VAFHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATEIFSILASSIALLS 823
Cdd:cd15282  161 MALGFLIGYTCLLAAICFFFAFKSRKLPENFNEAKFITFSMLIFFIVWISFIPAYASTYGKFVSAVEVIAILASSFGLLA 240
                        250
                 ....*....|..
gi 156119565 824 FIFAPKCYIILF 835
Cdd:cd15282  241 CIFFNKVYIILF 252
7tm_classC_mGluR-like cd13953
metabotropic glutamate receptor-like class C family of seven-transmembrane G protein-coupled ...
584-835 4.62e-57

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: 196.30  E-value: 4.62e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 584 PLGMSLASIALCLSTLTAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTV 663
Cdd:cd13953    1 PLAIVLLVLAALGLLLTIFIWVVFIRYRNTPVVKASNRELSYLLLFGILLCFLLAFLFLLPPSDVLCGLRRFLFGLSFTL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 664 ALATVLAKAITVVIAFKATFPGRMIRWLMKSRAPNYIIPICTLIQVFICGIWMATSPPFIDQDfHAEHGHIIIFCNKGSS 743
Cdd:cd13953   81 VFSTLLVKTNRIYRIFKSGLRSSLRPKLLSNKSQLLLVLFLLLVQVAILIVWLILDPPKVEKV-IDSDNKVVELCCSTGN 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 744 VAFHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATEIFSILASSIALLS 823
Cdd:cd13953  160 IGLILSLVYNILLLLICTYLAFKTRKLPDNFNEARYIGFSSLLSLVIWIAFIPTYFTTSGPYRDAILSFGLLLNATVLLL 239
                        250
                 ....*....|..
gi 156119565 824 FIFAPKCYIILF 835
Cdd:cd13953  240 CLFLPKIYIILF 251
PBP1_CaSR cd06364
ligand-binding domain of the CaSR calcium-sensing receptor, a member of the family C receptors ...
43-503 7.92e-55

ligand-binding domain of the CaSR calcium-sensing receptor, a member of the family C receptors within the G-protein coupled receptor superfamily; Ligand-binding domain of the CaSR calcium-sensing receptor, which is a member of the family C receptors within the G-protein coupled receptor superfamily. CaSR provides feedback control of extracellular calcium homeostasis by responding sensitively to acute fluctuations in extracellular ionized Ca2+ concentration. This ligand-binding domain has homology to the bacterial leucine-isoleucine-valine binding protein (LIVBP) and a leucine binding protein (LBP). CaSR is widely expressed in mammalian tissues and is active in tissues that are not directly involved in extracellular calcium homeostasis. Moreover, CaSR responds to aromatic, aliphatic, and polar amino acids, but not to positively charged or branched chain amino acids, which suggests that changes in plasma amino acid levels are likely to modulate whole body calcium metabolism. Additionally, the family C GPCRs includes at least two receptors with broad-spectrum amino acid-sensing properties: GPRC6A which recognizes basic and various aliphatic amino acids, its gold-fish homolog the 5.24 chemoreceptor, and a specific taste receptor (T1R) which responds to aliphatic, polar, charged, and branched amino acids, but not to aromatic amino acids.


Pssm-ID: 380587 [Multi-domain]  Cd Length: 473  Bit Score: 197.09  E-value: 7.92e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  43 VIGAFFPIHTYYTGNKIPHSFLPYYYvdNYLQYNFKNYQYILALIFAIEEINENPNLLSNISLGFDFYNVRFTEKDTLMN 122
Cdd:cd06364    1 IIGGLFPIHFRPVSPDPDFTTEPHSP--ECEGFNFRGFRWAQTMIFAIEEINNSPDLLPNITLGYRIYDSCATISKALRA 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 123 ACIWLTAHREkyILPNYKCGKKHFTAALTG-TSWTTSAQMGTLFQLFKFPQLSFGPYDHILSDRNQYSSLYQMAPMASSL 201
Cdd:cd06364   79 ALALVNGQEE--TNLDERCSGGPPVAAVIGeSGSTLSIAVARTLGLFYIPQVSYFASCACLSDKKQFPSFLRTIPSDYYQ 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 202 SLGIVSLLVHFRWSWVGLILPDDHKGNTILSDFRNEMERKGVCIAFLKMIPATW-MSHFNKFWKNMDETN--VIIIY-GD 277
Cdd:cd06364  157 SRALAQLVKHFGWTWVGAIASDDDYGRNGIKAFLEEAEKLGICIAFSETIPRTYsQEKILRIVEVIKKSTakVIVVFsSE 236
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 278 IDsLEGLMRNIGQRLLTWKVWVMN---IEPHVIADYFMLDSFHGSLIFTHHYTERIEFTNFVQTVNPYKYPEDIYLPKLW 354
Cdd:cd06364  237 GD-LEPLIKELVRQNITGRQWIASeawITSSLLATPEYFPVLGGTIGFAIRRGEIPGLKEFLLRVHPSKSPSNPFVKEFW 315
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 355 YLFFKCSFSDIDCQLLNN-----CQFNASLDILPRHIFDVSMSDESISIYNAVYAVAHSLHEMRLQQVQMQPYENG---E 426
Cdd:cd06364  316 EETFNCSLSSSSKSNSSSssrppCTGSENLENVQNPYTDVSQLRISYNVYKAVYAIAHALHDLLQCEPGKGPFSNGscaD 395
                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 156119565 427 EIMFFPWQVISFLLYCNVSILI-DQRSLDWRQKFNTEYDIINlWNL-PNGLGRKVKVGSFSTNAPQGHQLSLTEQIIQW 503
Cdd:cd06364  396 IKKVEPWQLLYYLKHVNFTTKFgEEVYFDENGDPVASYDIIN-WQLsDDGTIQFVTVGYYDASAPSGEELVINESKILW 473
7tmC_GPRC6A cd15281
class C of seven-transmembrane G protein-coupled receptors, subtype 6A; GRPC6A (GPCR, class C, ...
588-835 1.98e-49

class C of seven-transmembrane G protein-coupled receptors, subtype 6A; GRPC6A (GPCR, class C, group 6, subtype A) is a widely expressed amino acid-sensing GPCR that is most closely related to CaSR. GPRC6A is most potently activated by the basic amino acids L-arginine, L-lysine, and L-ornithine and less potently by small aliphatic amino acids. Moreover, the receptor can be either activated or modulated by divalent cations such as Ca2+ and Mg2+. GPRC6A is expressed in the testis, but not the ovary and specifically also binds to the osteoblast-derived hormone osteocalcin (OCN), which regulates testosterone production by the testis and male fertility independently of the hypothalamic-pituitary axis. Furthermore, GPRC6A knockout studies suggest that GRPC6A is involved in regulation of bone metabolism, male reproduction, energy homeostasis, glucose metabolism, and in activation of inflammation response, as well as prostate cancer growth and progression, among others. GPRC6A has been suggested to couple to the Gq subtype of G proteins, leading to IP3 production and intracellular calcium mobilization. GPRC6A contains a large extracellular Venus flytrap-like domain in the N-terminus, cysteine-rich domain (CRD), and seven-transmembrane (7TM) domain, which are characteristics of the class C GPCRs. The Venus flytrap-like domain shares strong sequence homology to bacterial periplasmic binding proteins and possess the orthosteric amino acid and calcium binding sites for members of the class C, including CaSR, GABA-B, GPRC6A, mGlu, and TAS1R receptors.


Pssm-ID: 320408  Cd Length: 249  Bit Score: 174.96  E-value: 1.98e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 588 SLASIALCLSTLTA---FVIG-IFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTV 663
Cdd:cd15281    1 GFAIVLLILSALGVlliFFISaLFTKNLNTPVVKAGGGPLCYVILLSHFGSFISTVFFIGEPSDLTCKTRQTLFGISFTL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 664 ALATVLAKAITVVIAFkaTFPGRMIRWLMKSRAPNYIIPICTLIQVFICGIWMATSPPFIDQDFhAEHGHIIIFCNKGSS 743
Cdd:cd15281   81 CVSCILVKSLKILLAF--SFDPKLQELLKCLYKPIMIVFICTGIQVIICTVWLVFYKPFVDKNF-SLPESIILECNEGSY 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 744 VAFHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATEIFSILASSIALLS 823
Cdd:cd15281  158 VAFGLMLGYIALLAFICFIFAFKGRKLPENYNEAKFITFGMLIYFIAWITFIPIYATTFGKYVPAVEMIVILISNYGILS 237
                        250
                 ....*....|..
gi 156119565 824 FIFAPKCYIILF 835
Cdd:cd15281  238 CTFLPKCYIILY 249
PBP1_GPCR_family_C-like cd06350
ligand-binding domain of membrane-bound glutamate receptors that mediate excitatory ...
43-342 1.64e-39

ligand-binding domain of membrane-bound glutamate receptors that mediate excitatory transmission on the cellular surface through initial binding of glutamate; categorized into ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (m; Ligand-binding domain of membrane-bound glutamate receptors that mediate excitatory transmission on the cellular surface through initial binding of glutamate and are categorized into ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs). The metabotropic glutamate receptors (mGluR) are key receptors in the modulation of excitatory synaptic transmission in the central nervous system. The mGluRs are coupled to G proteins and are thus distinct from the iGluRs which internally contain ligand-gated ion channels. The mGluR structure is divided into three regions: the extracellular region, the seven-spanning transmembrane region and the cytoplasmic region. The extracellular region is further divided into the ligand-binding domain (LBD) and the cysteine-rich domain. The LBD has sequence similarity to the LIVBP, which is a bacterial periplasmic protein (PBP), as well as to the extracellular region of both iGluR and the gamma-aminobutyric acid (GABA)b receptor. iGluRs are divided into three main subtypes based on pharmacological profile: NMDA, AMPA, and kainate receptors. All family C GPCRs have a large extracellular N terminus that contain a domain with homology to bacterial periplasmic amino acid-binding proteins.


Pssm-ID: 380573  Cd Length: 350  Bit Score: 149.75  E-value: 1.64e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  43 VIGAFFPIHTYYTGNKiphsflpyyyvDNYLQYNFKNYQYILALIFAIEEINENPNLLSNISLGFD------------FY 110
Cdd:cd06350    1 IIGGLFPVHYRDDADF-----------CCCGILNPRGVQLVEAMIYAIEEINNDSSLLPNVTLGYDirdtcssssvalES 69
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 111 NVRFTEKDTLMNACIwltahrekyiLPNYKCGKKHFTAALTGTSWTTSAQMGTLFQLFKFPQLSFGPYDHILSDRNQYSS 190
Cdd:cd06350   70 SLEFLLDNGIKLLAN----------SNGQNIGPPNIVAVIGAASSSVSIAVANLLGLFKIPQISYASTSPELSDKIRYPY 139
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 191 LYQMAPMASSLSLGIVSLLVHFRWSWVGLILPDDHKGNTILSDFRNEMERKGVCIAFLKMIPATWM-----SHFNKFwKN 265
Cdd:cd06350  140 FLRTVPSDTLQAKAIADLLKHFNWNYVSTVYSDDDYGRSGIEAFEREAKERGICIAQTIVIPENSTedeikRIIDKL-KS 218
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 266 MDETNVIIIYGDIDSLEGLMRNIGQRLLTWKVWVM-----------NIEPHVIadyfmldsfHGSLIFTHHYTERIEFTN 334
Cdd:cd06350  219 SPNAKVVVLFLTESDARELLKEAKRRNLTGFTWIGsdgwgdslvilEGYEDVL---------GGAIGVVPRSKEIPGFDD 289

                 ....*...
gi 156119565 335 FVQTVNPY 342
Cdd:cd06350  290 YLKSYAPY 297
7tmC_TAS1R1 cd15289
type 1 taste receptor subtype 1, member of the class C of seven-transmembrane G ...
589-835 5.85e-39

type 1 taste receptor subtype 1, member of the class C of seven-transmembrane G protein-coupled receptors; This group represents TAS1R1, which is a member of the type I taste receptor (TAS1R) family that belongs to the class C of G protein-coupled receptors. The functional TAS1Rs are obligatory heterodimers built from three known members, TAS1R1-3. TAS1R1 combines with TAS1R3 to form an umami taste receptor, which is responsible for the perception of savory taste, such as the food additive mono-sodium glutamate (MSG); whereas the combination of TAS1R2-TAS1R3 forms a sweet-taste receptor for sugars and D-amino acids. On the other hand, the type II taste receptors (TAS2Rs), which belong to the class A family of GPCRs, recognize bitter tasting compounds. In the case of sweet, for example, the TAS1R2-TAS1R3 heterodimer activates phospholipase C (PLC) via alpha-gustducin, a heterodimeric G protein that is involved in perception of sweet and bitter tastes. This activation leads to generation of inositol (1, 4, 5)-trisphosphate (IP3) and diacylglycerol (DAG), and consequently increases intracellular Ca2+ mobilization and activates a cation channel, TRPM5. In contrast to the TAS1R2-TAS1R3 heterodimer, TAS1R3 alone could activate adenylate cyclase leading to cAMP formation in the absence of alpha-gustducin. Each TAS1R contains a large extracellular Venus flytrap-like domain in the N-terminus, cysteine-rich domain (CRD) and seven-transmembrane (7TM) domain, which are characteristics of the class C GPCRs. The Venus flytrap-like domain shares strong sequence homology to bacterial periplasmic binding proteins and possess the orthosteric amino acid and calcium binding sites for members of the class C, including CaSR, GABA-B1, GPRC6A, mGlu, and TAS1R receptors.


Pssm-ID: 320416  Cd Length: 253  Bit Score: 145.26  E-value: 5.85e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 589 LASIALCLsTLTAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTVALATV 668
Cdd:cd15289    7 LTALTLLL-LLLAGTALLFALNLTTPVVKSAGGRTCFLMLGSLAAASCSLYCHFGEPTWLACLLKQPLFSLSFTVCLSCI 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 669 LAKAITVVIAFK--ATFPGRMIRWlMKSRAPNYIIPICTLIQVFICGIWMATSPPFIDQDFHAEHGHIIIFCNKGSSVAF 746
Cdd:cd15289   86 AVRSFQIVCIFKlaSKLPRFYETW-AKNHGPELFILISSAVQLLISLLWLVLNPPVPTKDYDRYPDLIVLECSQTLSVGS 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 747 HCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATEIFSILASSIALLSFIF 826
Cdd:cd15289  165 FLELLYNCLLSISCFVFSYMGKDLPANYNEAKCITFSLLIYFISWISFFTTYSIYRGKYLMAINVLAILSSLLGIFGGYF 244

                 ....*....
gi 156119565 827 APKCYIILF 835
Cdd:cd15289  245 LPKVYIILL 253
PBP1_taste_receptor cd06363
ligand-binding domain of the T1R taste receptor; Ligand-binding domain of the T1R taste ...
36-511 1.16e-34

ligand-binding domain of the T1R taste receptor; Ligand-binding domain of the T1R taste receptor. The T1R is a member of the family C receptors within the G-protein coupled receptor superfamily, which also includes the metabotropic glutamate receptors, GABAb receptors, the calcium-sensing receptor (CaSR), the V2R pheromone receptors, and a small group of uncharacterized orphan receptors.


Pssm-ID: 380586 [Multi-domain]  Cd Length: 418  Bit Score: 137.44  E-value: 1.16e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  36 FHQKGDVVIGAFFPIHtyYTGNKIPHsFLPYYYVDNYLQYNFKNYQYILALIFAIEEINENPNLLSNISLGFDFYnvrft 115
Cdd:cd06363    1 FRLPGDYLLGGLFPLH--ELTSTLPH-RPPEPTDCSCDRFNLHGYHLAQAMRFAVEEINNSSDLLPGVTLGYEIF----- 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 116 ekDTLMNACI------WLTAHREKYILPNYKCGKKHFTA-ALTGTSWTTSA-QMGTLFQLFKFPQLSFGPYDHILSDRNQ 187
Cdd:cd06363   73 --DTCSDAVNfrptlsFLSQNGSHDIEVQCNYTNYQPRVvAVIGPDSSELAlTTAKLLGFFLMPQISYGASSEELSNKLL 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 188 YSSLYQMAPMASSLSLGIVSLLVHFRWSWVGLILPDDHKGNTILSDFRNEMERKGVCIAFLKMIPATW--MSHFNKFWKN 265
Cdd:cd06363  151 YPSFLRTVPSDKYQVEAMVQLLQEFGWNWVAFLGSDDEYGQDGLQLFSEKAANTGICVAYQGLIPTDTdpKPKYQDILKK 230
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 266 MDET--NVIIIYGDIDSLEGLMRNIGQRLLTWKVWVMNiEPHVIADYFM----LDSFHGSLIFTHHYTERIEFTNFVQTV 339
Cdd:cd06363  231 INQTkvNVVVVFAPKQAAKAFFEEVIRQNLTGKVWIAS-EAWSLNDTVTslpgIQSIGTVLGFAIQTGTLPGFQEFIYAF 309
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 340 npykypediylpklwylffkcsfsdidcqllnncqfnasldilprhifdvsmsdeSISIYNAVYAVAHSLHemRLQQVQM 419
Cdd:cd06363  310 -------------------------------------------------------AFSVYAAVYAVAHALH--NLLGCNS 332
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 420 QPYENGeeIMFFPWQVISFLLYCNVSILIDQRSLDWRQKFNTEYDIInLWNLPNGLGRKVKVGSFSTNAPqghQLSLTEQ 499
Cdd:cd06363  333 GACPKG--RVVYPWQLLEELKKVNFTLLNQTIRFDENGDPNFGYDIV-QWIWNNSSWTFEVVGSYSTYPI---QLTINES 406
                        490
                 ....*....|..
gi 156119565 500 IIQWPEEFSEIP 511
Cdd:cd06363  407 KIKWHTKDSPVP 418
7tmC_mGluRs cd15045
metabotropic glutamate receptors, member of the class C family of seven-transmembrane G ...
587-835 2.13e-34

metabotropic glutamate receptors, member of the class C family of seven-transmembrane G protein-coupled receptors; The metabotropic glutamate receptors (mGluRs) are homodimeric class C G-protein coupled receptors which are activated by glutamate, the major excitatory neurotransmitter of the CNS. mGluRs are involved in regulating neuronal excitability and synaptic transmission via intracellular activation of second messenger signaling pathways. While the ionotropic glutamate receptor subtypes (AMPA, NMDA, and kainite) mediate fast excitatory postsynaptic transmission, mGluRs are known to mediate slower excitatory postsynaptic responses and to be involved in synaptic plasticity in the mammalian brain. In addition to seven-transmembrane helices, the class C GPCRs are characterized by a large N-terminal extracellular Venus flytrap-like domain, which is composed of two adjacent lobes separated by a cleft which binds an endogenous ligand. Moreover, they exist as either homo- or heterodimers, which are essential for their function. For instance, mGluRs form homodimers via interactions between the N-terminal Venus flytrap domains and the intermolecular disulphide bonds between cysteine residues located in the cysteine-rich domain (CRD). At least eight different subtypes of metabotropic receptors (mGluR1-8) have been identified and further classified into three groups based on their sequence homology, pharmacological properties, and signaling pathways. Group 1 (mGluR1 and mGluR5) receptors are predominantly located postsynaptically on neurons and are involved in long-term synaptic plasticity in the brain, including long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum. They are coupled to G(q/11) proteins, thereby activating phospholipase C to generate inositol-1,4,5-triphosphate (IP3) and diacyglycerol (DAG), which in turn lead to Ca2+ release and protein kinase C activation, respectively. Group I mGluR expression is shown to be strongly upregulated in animal models of epilepsy, brain injury, inflammatory, and neuropathic pain, as well as in patients with amyotrophic lateral sclerosis or multiple sclerosis. Group 2 (mGluR2 and mGluR3) and 3 (mGluR4, mGluR6, mGluR7, and mGluR8) receptors are predominantly localized presynaptically in the active region of neurotransmitter release. They are coupled to (Gi/o) proteins, which leads to inhibition of adenylate cyclase activity and cAMP formation, and consequently to a decrease in protein kinase A (PKA) activity. Ultimately, activation of these receptors leads to inhibition of neurotransmitter release such as glutamate and GABA via inhibition of Ca2+ channels and activation of K+ channels. Furthermore, while activation of Group 1 mGluRs increases NMDA (N-methyl-D-aspartate) receptor activity and risk of neurotoxicity, Group 2 and 3 mGluRs decrease NMDA receptor activity and prevent neurotoxicity.


Pssm-ID: 320173 [Multi-domain]  Cd Length: 253  Bit Score: 131.98  E-value: 2.13e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 587 MSLASIALclsTLTAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTVALA 666
Cdd:cd15045    7 MAFASLGI---LLTLFVLVVFVRYRDTPVVKASGRELSYVLLAGILLSYVMTFVLVAKPSTIVCGLQRFGLGLCFTVCYA 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 667 TVLAKaiTVVIAfkatfpgRMIRWLMKS-RAPNYIIP-----IC---TLIQVFICGIWMATSPPFIDQDFHAEHGHIIIF 737
Cdd:cd15045   84 AILTK--TNRIA-------RIFRLGKKSaKRPRFISPrsqlvITgllVSVQVLVLAVWLILSPPRATHHYPTRDKNVLVC 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 738 CN-KGSSVAfhCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMV--ATEIFSI 814
Cdd:cd15045  155 SSaLDASYL--IGLAYPILLIILCTVYAFKTRKIPEGFNEAKYIGFTMYTTCIIWLAFVPLYFTTASNIEVriTTLSVSI 232
                        250       260
                 ....*....|....*....|.
gi 156119565 815 LASSIALLSFIFAPKCYIILF 835
Cdd:cd15045  233 SLSATVQLACLFAPKVYIILF 253
7tmC_mGluRs_group2_3 cd15934
metabotropic glutamate receptors in group 2 and 3, member of the class C family of ...
584-835 3.00e-34

metabotropic glutamate receptors in group 2 and 3, member of the class C family of seven-transmembrane G protein-coupled receptors; The metabotropic glutamate receptors (mGluRs) are homodimeric class C G-protein coupled receptors which are activated by glutamate, the major excitatory neurotransmitter of the CNS. The mGluRs are involved in regulating neuronal excitability and synaptic transmission via intracellular activation of second messenger signaling pathways. While the ionotropic glutamate receptor subtypes (AMPA, NMDA, and kainite) mediate fast excitatory postsynaptic transmission, mGluRs are known to mediate slower excitatory postsynaptic responses and to be involved in synaptic plasticity in the mammalian brain. In addition to seven-transmembrane helices, the class C GPCRs are characterized by a large N-terminal extracellular Venus flytrap-like domain, which is composed of two adjacent lobes separated by a cleft which binds an endogenous ligand. Moreover, they exist as either homo- or heterodimers, which are essential for their function. For instance, mGluRs form homodimers via interactions between the N-terminal Venus flytrap domains and the intermolecular disulphide bonds between cysteine residues located in the cysteine-rich domain (CRD). At least eight different subtypes of metabotropic receptors (mGluR1-8) have been identified and further classified into three groups based on their sequence homology, pharmacological properties, and signaling pathways. Group 1 (mGluR1 and mGluR5) receptors are predominantly located postsynaptically on neurons and are involved in long-term synaptic plasticity in the brain, including long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum. They are coupled to G(q/11) proteins, thereby activating phospholipase C to generate inositol-1,4,5-triphosphate (IP3) and diacyglycerol (DAG), which in turn lead to Ca2+ release and protein kinase C activation, respectively. Group I mGluR expression is shown to be strongly upregulated in animal models of epilepsy, brain injury, inflammatory, and neuropathic pain, as well as in patients with amyotrophic lateral sclerosis or multiple sclerosis. Group 2 (mGluR2 and mGluR3) and 3 (mGluR4, mGluR6, mGluR7, and mGluR8) receptors are predominantly localized presynaptically in the active region of neurotransmitter release. They are coupled to (Gi/o) proteins, which leads to inhibition of adenylate cyclase activity and cAMP formation, and consequently to a decrease in protein kinase A (PKA) activity. Ultimately, activation of these receptors leads to inhibition of neurotransmitter release such as glutamate and GABA via inhibition of Ca2+ channels and activation of K+ channels. Furthermore, while activation of Group 1 mGluRs increases NMDA (N-methyl-D-aspartate) receptor activity and risk of neurotoxicity, Group 2 and 3 mGluRs decrease NMDA receptor activity and prevent neurotoxicity.


Pssm-ID: 320600  Cd Length: 252  Bit Score: 131.58  E-value: 3.00e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 584 PLGMSLASIALclstlTAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTV 663
Cdd:cd15934    6 PVVFALLGILA-----TLFVIVVFIRYNDTPVVKASGRELSYVLLTGILLCYLMTFVLLAKPSVITCALRRLGLGLGFSI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 664 ALATVLAKaiTVVIAfkatfpgRMIRWLMKS-RAPNYIIP-----ICTLI---QVFICGIWMATSPPFIDQDfHAEHGHI 734
Cdd:cd15934   81 CYAALLTK--TNRIS-------RIFNSGKRSaKRPRFISPksqlvICLGLisvQLIGVLVWLVVEPPGTRID-YPRRDQV 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 735 IIFCNkGSSVAFHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATEIFSI 814
Cdd:cd15934  151 VLKCK-ISDSSLLISLVYNMLLIILCTVYAFKTRKIPENFNEAKFIGFTMYTTCIIWLAFVPIYFGTSNDFKIQTTTLCV 229
                        250       260
                 ....*....|....*....|....
gi 156119565 815 ---LASSIALLSfIFAPKCYIILF 835
Cdd:cd15934  230 sisLSASVALGC-LFAPKVYIILF 252
PBP1_mGluR cd06362
ligand binding domain of metabotropic glutamate receptors (mGluR); Ligand binding domain of ...
40-412 3.79e-34

ligand binding domain of metabotropic glutamate receptors (mGluR); Ligand binding domain of the metabotropic glutamate receptors (mGluR), which are members of the family C of G-protein-coupled receptors that transduce extracellular signals into G-protein activation and ultimately into cellular responses. mGluRs bind to glutamate and function as an excitatory neurotransmitter; they are involved in learning, memory, anxiety, and the perception of pain. Eight subtypes of mGluRs have been cloned so far, and are classified into three groups according to their sequence similarities, transduction mechanisms, and pharmacological profiles. Group I is composed of mGlu1R and mGlu5R that both stimulate PLC hydrolysis. Group II includes mGlu2R and mGlu3R, which inhibit adenylyl cyclase, as do mGlu4R, mGlu6R, mGlu7R, and mGlu8R, which form group III.


Pssm-ID: 380585 [Multi-domain]  Cd Length: 460  Bit Score: 136.65  E-value: 3.79e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  40 GDVVIGAFFPIHTYYTG-NKIPHsflpyyyvdnylQYNFKNYQYILALIFAIEEINENPNLLSNISLGF----------- 107
Cdd:cd06362    1 GDINLGGLFPVHERSSSgECCGE------------IREERGIQRLEAMLFAIDEINSRPDLLPNITLGFvilddcssdtt 68
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 108 ------DFYNVRFTEKDTLMNACIWLTAHREKYILPNYKcgkkhfTAALTGTSWTTSA-QMGTLFQLFKFPQLSFGPYDH 180
Cdd:cd06362   69 aleqalHFIRDSLLSQESAGFCQCSDDPPNLDESFQFYD------VVGVIGAESSSVSiQVANLLRLFKIPQISYASTSD 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 181 ILSDRNQYSSLYQMAPMASSLSLGIVSLLVHFRWSWVGLILPDDHKGNTILSDFRNEMERKGVCIAFLKMIP--ATWMSH 258
Cdd:cd06362  143 ELSDKERYPYFLRTVPSDSFQAKAIVDILLHFNWTYVSVVYSEGSYGEEGYKAFKKLARKAGICIAESERISqdSDEKDY 222
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 259 FNKFWKNMDETN--VIIIYGDIDSLEGLMR-----NIGQRlLTW---KVWVMNIEPhvIADYfmLDSFHGSLIFTHHYTE 328
Cdd:cd06362  223 DDVIQKLLQKKNarVVVLFADQEDIRGLLRaakrlGASGR-FIWlgsDGWGTNIDD--LKGN--EDVALGALTVQPYSEE 297
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 329 RIEFTNFVQTVNPYKYPEDIYLPKLWYLFFKCSFSDIDCQLLNNCQFNASLDILPRHIFDVSmsdesiSIYNAVYAVAHS 408
Cdd:cd06362  298 VPRFDDYFKSLTPSNNTRNPWFREFWQELFQCSFRPSRENSCNDDKLLINKSEGYKQESKVS------FVIDAVYAFAHA 371

                 ....
gi 156119565 409 LHEM 412
Cdd:cd06362  372 LHKM 375
7tmC_mGluR2 cd15447
metabotropic glutamate receptor 2 in group 2, member of the class C family of ...
595-835 1.43e-33

metabotropic glutamate receptor 2 in group 2, member of the class C family of seven-transmembrane G protein-coupled receptors; The metabotropic glutamate receptors (mGluRs) in group 2 include mGluR 2 and 3. They are homodimeric class C G-protein coupled receptors which are activated by glutamate, the major excitatory neurotransmitter of the CNS. mGluRs are involved in regulating neuronal excitability and synaptic transmission via intracellular activation of second messenger signaling pathways. While the ionotropic glutamate receptor subtypes (AMPA, NMDA, and kainite) mediate fast excitatory postsynaptic transmission, mGluRs are known to mediate slower excitatory postsynaptic responses and to be involved in synaptic plasticity in the mammalian brain. In addition to seven-transmembrane helices, the class C GPCRs are characterized by a large N-terminal extracellular Venus flytrap-like domain, which is composed of two adjacent lobes separated by a cleft which binds an endogenous ligand. Moreover, they exist as either homo- or heterodimers, which are essential for their function. For instance, mGluRs form homodimers via interactions between the N-terminal Venus flytrap domains and the intermolecular disulphide bonds between cysteine residues located in the cysteine-rich domain (CRD). At least eight different subtypes of metabotropic receptors (mGluR1-8) have been identified and further classified into three groups based on their sequence homology, pharmacological properties, and signaling pathways. Group 1 (mGluR1 and mGluR5) receptors are predominantly located postsynaptically on neurons and are involved in long-term synaptic plasticity in the brain, including long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum. They are coupled to G(q/11) proteins, thereby activating phospholipase C to generate inositol-1,4,5-triphosphate (IP3) and diacyglycerol (DAG), which in turn lead to Ca2+ release and protein kinase C activation, respectively. Group 1 mGluR expression is shown to be strongly upregulated in animal models of epilepsy, brain injury, inflammatory, and neuropathic pain, as well as in patients with amyotrophic lateral sclerosis or multiple sclerosis. Group 2 (mGluR2 and mGluR3) and 3 (mGluR4, mGluR6, mGluR7, and mGluR8) receptors are predominantly localized presynaptically in the active region of neurotransmitter release. They are coupled to G(i/o) proteins, which leads to inhibition of adenylate cyclase activity and cAMP formation, and consequently to a decrease in protein kinase A (PKA) activity. Ultimately, activation of these receptors leads to inhibition of neurotransmitter release such as glutamate and GABA via inhibition of Ca2+ channels and activation of K+ channels. Furthermore, while activation of Group 1 mGluRs increases NMDA (N-methyl-D-aspartate) receptor activity and risk of neurotoxicity, Group 2 and 3 mGluRs decrease NMDA receptor activity and prevent neurotoxicity.


Pssm-ID: 320563  Cd Length: 254  Bit Score: 129.66  E-value: 1.43e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 595 CLSTL-TAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTVALATVLAKAI 673
Cdd:cd15447   11 CLGILsTLFVVGVFVKNNETPVVKASGRELCYILLLGVLLCYLMTFIFIAKPSTAVCTLRRLGLGTSFAVCYSALLTKTN 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 674 TVVIAFKATFPGrmirwlmkSRAPNYIIP-----ICTLI---QVFICGIWMATSPPFIDQDFHAEHGHIIIF-CNKGSSv 744
Cdd:cd15447   91 RIARIFSGAKDG--------AQRPRFISPasqvaICLALiscQLLVVLIWLLVEAPGTRKETAPERRYVVTLkCNSRDS- 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 745 AFHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATEIF--SILASSIALL 822
Cdd:cd15447  162 SMLISLTYNVLLIILCTLYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMciSVSLSGSVVL 241
                        250
                 ....*....|...
gi 156119565 823 SFIFAPKCYIILF 835
Cdd:cd15447  242 GCLFAPKLHIILF 254
7tmC_TAS1R cd15046
type 1 taste receptors, member of the class C of seven-transmembrane G protein-coupled ...
584-835 3.10e-32

type 1 taste receptors, member of the class C of seven-transmembrane G protein-coupled receptors; This subfamily represents the type I taste receptors (TAS1Rs) that belongs to the class C family of G protein-coupled receptors. The functional TAS1Rs are obligatory heterodimers built from three known members, TAS1R1-3. TAS1R1 combines with TAS1R3 to form an umami taste receptor, which is responsible for the perception of savory taste, such as the food additive mono-sodium glutamate (MSG); whereas the combination of TAS1R2-TAS1R3 forms a sweet-taste receptor for sugars and D-amino acids. On the other hand, the type II taste receptors (TAS2Rs), which belong to the class A family of GPCRs, recognize bitter tasting compounds. In the case of sweet, for example, the TAS1R2-TAS1R3 heterodimer activates phospholipase C (PLC) via alpha-gustducin, a heterodimeric G protein that is involved in perception of sweet and bitter tastes. This activation leads to generation of inositol (1, 4, 5)-trisphosphate (IP3) and diacylglycerol (DAG), and consequently increases intracellular Ca2+ mobilization and activates a cation channel, TRPM5. In contrast to the TAS1R2-TAS1R3 heterodimer, TAS1R3 alone could activate adenylate cyclase leading to cAMP formation in the absence of alpha-gustducin. Each TAS1R contains a large extracellular Venus flytrap-like domain in the N-terminus, cysteine-rich domain (CRD) and seven-transmembrane (7TM) domain, which are characteristics of the class C GPCRs. The Venus flytrap-like domain shares strong sequence homology to bacterial periplasmic binding proteins and possess the orthosteric amino acid and calcium binding sites for members of the class C, including CaSR, GABA-B1, GPRC6A, mGlu, and TAS1R receptors.


Pssm-ID: 320174 [Multi-domain]  Cd Length: 253  Bit Score: 126.10  E-value: 3.10e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 584 PLGMSLASIALCLSTLTAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTV 663
Cdd:cd15046    1 APTVAVLLLAALGLLSTLAILVIFWRNFNTPVVRSAGGPMCFLMLTLLLVAYMSVPVYFGPPKVSTCLLRQALFPLCFTV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 664 ALATVLAKAITVVIAFK--ATFPGRMIRWlMKSRAPNYIIPICTLIQVFICGIWMATSPPFIDQDFHAEHGHIIIFCNKG 741
Cdd:cd15046   81 CLACIAVRSFQIVCIFKmaSRFPRAYSYW-VKYHGPYVSIAFITVLKMVIVVIGMLATPPSPTTDTDPDPKITIVSCNPN 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 742 SSVAFHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATEIFSILASSIAL 821
Cdd:cd15046  160 YRNSSLFNTSLDLLLSVVCFSFSYMGKDLPTNYNEAKFITFSLTFYFTSWISFCTFMLAYSGVLVTIVDLLATLLSLLAF 239
                        250
                 ....*....|....
gi 156119565 822 LSFIFAPKCYIILF 835
Cdd:cd15046  240 SLGYFLPKCYIILF 253
7tmC_TAS1R3 cd15290
type 1 taste receptor subtype 3, member of the class C of seven-transmembrane G ...
585-835 8.73e-31

type 1 taste receptor subtype 3, member of the class C of seven-transmembrane G protein-coupled receptors; This group represents TAS1R3, which is a member of the type I taste receptor (TAS1R) family that belongs to the class C of G protein-coupled receptors. The functional TAS1Rs are obligatory heterodimers built from three known members, TAS1R1-3. TAS1R1 combines with TAS1R3 to form an umami taste receptor, which is responsible for the perception of savory taste, such as the food additive mono-sodium glutamate (MSG); whereas the combination of TAS1R2-TAS1R3 forms a sweet-taste receptor for sugars and D-amino acids. On the other hand, the type II taste receptors (TAS2Rs), which belong to the class A family of GPCRs, recognize bitter tasting compounds. In the case of sweet, for example, the TAS1R2-TAS1R3 heterodimer activates phospholipase C (PLC) via alpha-gustducin, a heterodimeric G protein that is involved in perception of sweet and bitter tastes. This activation leads to generation of inositol (1, 4, 5)-trisphosphate (IP3) and diacylglycerol (DAG), and consequently increases intracellular Ca2+ mobilization and activates a cation channel, TRPM5. In contrast to the TAS1R2-TAS1R3 heterodimer, TAS1R3 alone could activate adenylate cyclase leading to cAMP formation in the absence of alpha-gustducin. Each TAS1R contains a large extracellular Venus flytrap-like domain in the N-terminus, cysteine-rich domain (CRD) and seven-transmembrane (7TM) domain, which are characteristics of the class C GPCRs. The Venus flytrap-like domain shares strong sequence homology to bacterial periplasmic binding proteins and possess the orthosteric amino acid and calcium binding sites for members of the class C, including CaSR, GABA-B1, GPRC6A, mGlu, and TAS1R receptors.


Pssm-ID: 320417 [Multi-domain]  Cd Length: 253  Bit Score: 121.71  E-value: 8.73e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 585 LGMSLASIalclstLTAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTVA 664
Cdd:cd15290    8 LLGVLLLV------LQCSVGVLFLKHRGTPLVQASGGPLSIFALLSLMGACLSLLLFLGQPSDVVCRLQQPLNALFLTVC 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 665 LATVLAKAITVViaFKATFPGRMIRWLMKSRAPN--YIIPICTLIQVFICGIWMATSPPFIDQDFHAE-HGHIIIFCNKG 741
Cdd:cd15290   82 LSTILSISLQIF--LVTEFPKCAASHLHWLRGPGswLVVLICCLVQAGLCGWYVQDGPSLSEYDAKMTlFVEVFLRCPVE 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 742 SSVAFHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATEIFSILASSIAL 821
Cdd:cd15290  160 PWLGFGLMHGFNGALALISFMCTFMAQKPLKQYNLARDITFSTLIYCVTWVIFIPIYAGLQVKLRSIAQVGFILLSNLGL 239
                        250
                 ....*....|....
gi 156119565 822 LSFIFAPKCYIILF 835
Cdd:cd15290  240 LAAYYLPKCYLLLR 253
7tmC_mGluR_group1 cd15285
metabotropic glutamate receptors in group 1, member of the class C family of ...
590-835 8.34e-30

metabotropic glutamate receptors in group 1, member of the class C family of seven-transmembrane G protein-coupled receptors; Group 1 mGluRs includes mGluR1 and mGluR5, as well as their closely related invertebrate receptors. They are homodimeric class C G-protein coupled receptors which are activated by glutamate, the major excitatory neurotransmitter of the CNS. mGluRs are involved in regulating neuronal excitability and synaptic transmission via intracellular activation of second messenger signaling pathways. While the ionotropic glutamate receptor subtypes (AMPA, NMDA, and kainite) mediate fast excitatory postsynaptic transmission, mGluRs are known to mediate slower excitatory postsynaptic responses and to be involved in synaptic plasticity in the mammalian brain. In addition to seven-transmembrane helices, the class C GPCRs are characterized by a large N-terminal extracellular Venus flytrap-like domain, which is composed of two adjacent lobes separated by a cleft which binds an endogenous ligand. Moreover, they exist as either homo- or heterodimers, which are essential for their function. For instance, mGluRs form homodimers via interactions between the N-terminal Venus flytrap domains and the intermolecular disulphide bonds between cysteine residues located in the cysteine-rich domain (CRD). At least eight different subtypes of metabotropic receptors (mGluR1-8) have been identified and further classified into three groups based on their sequence homology, pharmacological properties, and signaling pathways. Group 1 (mGluR1 and mGluR5) receptors are predominantly located postsynaptically on neurons and are involved in long-term synaptic plasticity in the brain, including long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum. They are coupled to G(q/11) proteins, thereby activating phospholipase C to generate inositol-1,4,5-triphosphate (IP3) and diacyglycerol (DAG), which in turn lead to Ca2+ release and protein kinase C activation, respectively. Group 1 mGluR expression is shown to be strongly upregulated in animal models of epilepsy, brain injury, inflammatory, and neuropathic pain, as well as in patients with amyotrophic lateral sclerosis or multiple sclerosis. Group 2 (mGluR2 and mGluR3) and 3 (mGluR4, mGluR6, mGluR7, and mGluR8) receptors are predominantly localized presynaptically in the active region of neurotransmitter release. They are coupled to G(i/o) proteins, which leads to inhibition of adenylate cyclase activity and cAMP formation, and consequently to a decrease in protein kinase A (PKA) activity. Ultimately, activation of these receptors leads to inhibition of neurotransmitter release such as glutamate and GABA via inhibition of Ca2+ channels and activation of K+ channels. Furthermore, while activation of Group 1 mGluRs increases NMDA (N-methyl-D-aspartate) receptor activity and risk of neurotoxicity, Group 2 and 3 mGluRs decrease NMDA receptor activity and prevent neurotoxicity.


Pssm-ID: 320412  Cd Length: 250  Bit Score: 118.89  E-value: 8.34e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 590 ASIALCLSTL----TAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTVAL 665
Cdd:cd15285    3 AIVAMVFACVgilaTLFVTVVFIRHNDTPVVKASTRELSYIILAGILLCYASTFALLAKPSTISCYLQRILPGLSFAMIY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 666 ATVLAKaiTVVIA-----FKATFPGRMIRWlMKSRAPNYIIPICTLIQVFICGIWMATSPPFIdQDFHAEHGHIIIFCNK 740
Cdd:cd15285   83 AALVTK--TNRIArilagSKKKILTRKPRF-MSASAQVVITGILISVEVAIIVVMLILEPPDA-TLDYPTPKRVRLICNT 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 741 gSSVAFHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYhsTMGKFMVATEIFSILASSIA 820
Cdd:cd15285  159 -STLGFVVPLGFDFLLILLCTLYAFKTRNLPENFNEAKFIGFTMYTTCVIWLAFLPIY--FGSDNKEITLCFSVSLSATV 235
                        250
                 ....*....|....*
gi 156119565 821 LLSFIFAPKCYIILF 835
Cdd:cd15285  236 ALVFLFFPKVYIILF 250
7tmC_mGluR4 cd15452
metabotropic glutamate receptor 4 in group 3, member of the class C family of ...
600-858 3.04e-29

metabotropic glutamate receptor 4 in group 3, member of the class C family of seven-transmembrane G protein-coupled receptors; The receptors in group 3 include mGluRs 4, 6, 7, and 8. They are homodimeric class C G-protein coupled receptors which are activated by glutamate, the major excitatory neurotransmitter of the CNS. mGluRs are involved in regulating neuronal excitability and synaptic transmission via intracellular activation of second messenger signaling pathways. While the ionotropic glutamate receptor subtypes (AMPA, NMDA, and kainite) mediate fast excitatory postsynaptic transmission, mGluRs are known to mediate slower excitatory postsynaptic responses and to be involved in synaptic plasticity in the mammalian brain. In addition to seven-transmembrane helices, the class C GPCRs are characterized by a large N-terminal extracellular Venus flytrap-like domain, which is composed of two adjacent lobes separated by a cleft which binds an endogenous ligand. Moreover, they exist as either homo- or heterodimers, which are essential for their function. For instance, mGluRs form homodimers via interactions between the N-terminal Venus flytrap domains and the intermolecular disulphide bonds between cysteine residues located in the cysteine-rich domain (CRD). At least eight different subtypes of metabotropic receptors (mGluR1-8) have been identified and further classified into three groups based on their sequence homology, pharmacological properties, and signaling pathways. Group 1 (mGluR1 and mGluR5) receptors are predominantly located postsynaptically on neurons and are involved in long-term synaptic plasticity in the brain, including long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum. They are coupled to G(q/11) proteins, thereby activating phospholipase C to generate inositol-1,4,5-triphosphate (IP3) and diacyglycerol (DAG), which in turn lead to Ca2+ release and protein kinase C activation, respectively. Group 1 mGluR expression is shown to be strongly upregulated in animal models of epilepsy, brain injury, inflammatory, and neuropathic pain, as well as in patients with amyotrophic lateral sclerosis or multiple sclerosis. Group 2 (mGluR2 and mGluR3) and 3 (mGluR4, mGluR6, mGluR7, and mGluR8) receptors are predominantly localized presynaptically in the active region of neurotransmitter release. They are coupled to G(i/o) proteins, which leads to inhibition of adenylate cyclase activity and cAMP formation, and consequently to a decrease in protein kinase A (PKA) activity. Ultimately, activation of these receptors leads to inhibition of neurotransmitter release such as glutamate and GABA via inhibition of Ca2+ channels and activation of K+ channels. Furthermore, while activation of Group 1 mGluRs increases NMDA (N-methyl-D-aspartate) receptor activity and risk of neurotoxicity, Group 2 and 3 mGluRs decrease NMDA receptor activity and prevent neurotoxicity.


Pssm-ID: 320568 [Multi-domain]  Cd Length: 327  Bit Score: 119.31  E-value: 3.04e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 600 TAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTVALATVLAKAITVVIAF 679
Cdd:cd15452   17 TLFVVVTFVRYNDTPIVKASGRELSYVLLTGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSISYAALLTKTNRIYRIF 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 680 KAtfpGRmirwlMKSRAPNYIIPICTLIQVF---------ICgIWMATSP--PFID-QDFHAEHGHI---IIFCNKgSSV 744
Cdd:cd15452   97 EQ---GK-----RSVSAPRFISPASQLVITFslislqllgVC-VWFLVDPshSVVDyEDQRTPDPQFargVLKCDI-SDL 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 745 AFHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHST---MGKFMVATEIFSI---LASS 818
Cdd:cd15452  167 SLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIIWLAFIPIFFGTsqsAEKMYIQTTTLTIsvsLSAS 246
                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 156119565 819 IAlLSFIFAPKCYIILFRPNENTfhyirdkmhSRRNKSLK 858
Cdd:cd15452  247 VS-LGMLYMPKVYVILFHPEQNV---------PKRKRSLK 276
7tmC_mGluR_group2 cd15284
metabotropic glutamate receptors in group 2, member of the class C family of ...
595-835 1.24e-28

metabotropic glutamate receptors in group 2, member of the class C family of seven-transmembrane G protein-coupled receptors; The metabotropic glutamate receptors (mGluRs) in group 2 include mGluR 2 and 3. They are homodimeric class C G-protein coupled receptors which are activated by glutamate, the major excitatory neurotransmitter of the CNS. mGluRs are involved in regulating neuronal excitability and synaptic transmission via intracellular activation of second messenger signaling pathways. While the ionotropic glutamate receptor subtypes (AMPA, NMDA, and kainite) mediate fast excitatory postsynaptic transmission, mGluRs are known to mediate slower excitatory postsynaptic responses and to be involved in synaptic plasticity in the mammalian brain. In addition to seven-transmembrane helices, the class C GPCRs are characterized by a large N-terminal extracellular Venus flytrap-like domain, which is composed of two adjacent lobes separated by a cleft which binds an endogenous ligand. Moreover, they exist as either homo- or heterodimers, which are essential for their function. For instance, mGluRs form homodimers via interactions between the N-terminal Venus flytrap domains and the intermolecular disulphide bonds between cysteine residues located in the cysteine-rich domain (CRD). At least eight different subtypes of metabotropic receptors (mGluR1-8) have been identified and further classified into three groups based on their sequence homology, pharmacological properties, and signaling pathways. Group 1 (mGluR1 and mGluR5) receptors are predominantly located postsynaptically on neurons and are involved in long-term synaptic plasticity in the brain, including long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum. They are coupled to G(q/11) proteins, thereby activating phospholipase C to generate inositol-1,4,5-triphosphate (IP3) and diacyglycerol (DAG), which in turn lead to Ca2+ release and protein kinase C activation, respectively. Group 1 mGluR expression is shown to be strongly upregulated in animal models of epilepsy, brain injury, inflammatory, and neuropathic pain, as well as in patients with amyotrophic lateral sclerosis or multiple sclerosis. Group 2 (mGluR2 and mGluR3) and 3 (mGluR4, mGluR6, mGluR7, and mGluR8) receptors are predominantly localized presynaptically in the active region of neurotransmitter release. They are coupled to G(i/o) proteins, which leads to inhibition of adenylate cyclase activity and cAMP formation, and consequently to a decrease in protein kinase A (PKA) activity. Ultimately, activation of these receptors leads to inhibition of neurotransmitter release such as glutamate and GABA via inhibition of Ca2+ channels and activation of K+ channels. Furthermore, while activation of Group 1 mGluRs increases NMDA (N-methyl-D-aspartate) receptor activity and risk of neurotoxicity, Group 2 and 3 mGluRs decrease NMDA receptor activity and prevent neurotoxicity.


Pssm-ID: 320411  Cd Length: 254  Bit Score: 115.72  E-value: 1.24e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 595 CLSTL-TAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTVALATVLAKAI 673
Cdd:cd15284   11 CLGFLcTLFVIGVFIKHNNTPLVKASGRELCYILLFGVFLCYCMTFIFIAKPSPAICTLRRLGLGTSFAVCYSALLTKTN 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 674 TVVIAFKATFPGrmirwlmkSRAPNYIIP-----IC---TLIQVFICGIWMATSPPFIDQDFHAEHGHIIIF-CNKGSSv 744
Cdd:cd15284   91 RIARIFSGVKDG--------AQRPRFISPssqvfIClalISVQLLVVSVWLLVEAPGTRRYTLPEKRETVILkCNVRDS- 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 745 AFHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATEIF--SILASSIALL 822
Cdd:cd15284  162 SMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMciSVSLSGFVVL 241
                        250
                 ....*....|...
gi 156119565 823 SFIFAPKCYIILF 835
Cdd:cd15284  242 GCLFAPKVHIILF 254
7tmC_mGluR_group3 cd15286
metabotropic glutamate receptors in group 3, member of the class C family of ...
590-840 2.19e-27

metabotropic glutamate receptors in group 3, member of the class C family of seven-transmembrane G protein-coupled receptors; The metabotropic glutamate receptors (mGluRs) in group 3 include mGluRs 4, 6, 7, and 8. They are homodimeric class C G-protein coupled receptors which are activated by glutamate, the major excitatory neurotransmitter of the CNS. mGluRs are involved in regulating neuronal excitability and synaptic transmission via intracellular activation of second messenger signaling pathways. While the ionotropic glutamate receptor subtypes (AMPA, NMDA, and kainite) mediate fast excitatory postsynaptic transmission, mGluRs are known to mediate slower excitatory postsynaptic responses and to be involved in synaptic plasticity in the mammalian brain. In addition to seven-transmembrane helices, the class C GPCRs are characterized by a large N-terminal extracellular Venus flytrap-like domain, which is composed of two adjacent lobes separated by a cleft which binds an endogenous ligand. Moreover, they exist as either homo- or heterodimers, which are essential for their function. For instance, mGluRs form homodimers via interactions between the N-terminal Venus flytrap domains and the intermolecular disulphide bonds between cysteine residues located in the cysteine-rich domain (CRD). At least eight different subtypes of metabotropic receptors (mGluR1-8) have been identified and further classified into three groups based on their sequence homology, pharmacological properties, and signaling pathways. Group 1 (mGluR1 and mGluR5) receptors are predominantly located postsynaptically on neurons and are involved in long-term synaptic plasticity in the brain, including long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum. They are coupled to G(q/11) proteins, thereby activating phospholipase C to generate inositol-1,4,5-triphosphate (IP3) and diacyglycerol (DAG), which in turn lead to Ca2+ release and protein kinase C activation, respectively. Group 1 mGluR expression is shown to be strongly upregulated in animal models of epilepsy, brain injury, inflammatory, and neuropathic pain, as well as in patients with amyotrophic lateral sclerosis or multiple sclerosis. Group 2 (mGluR2 and mGluR3) and 3 (mGluR4, mGluR6, mGluR7, and mGluR8) receptors are predominantly localized presynaptically in the active region of neurotransmitter release. They are coupled to G(i/o) proteins, which leads to inhibition of adenylate cyclase activity and cAMP formation, and consequently to a decrease in protein kinase A (PKA) activity. Ultimately, activation of these receptors leads to inhibition of neurotransmitter release such as glutamate and GABA via inhibition of Ca2+ channels and activation of K+ channels. Furthermore, while activation of Group 1 mGluRs increases NMDA (N-methyl-D-aspartate) receptor activity and risk of neurotoxicity, Group 2 and 3 mGluRs decrease NMDA receptor activity and prevent neurotoxicity.


Pssm-ID: 320413  Cd Length: 271  Bit Score: 112.59  E-value: 2.19e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 590 ASIALCLSTL----TAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTVAL 665
Cdd:cd15286    3 AAVPVALAVLgiiaTLFVLVTFVRYNDTPIVRASGRELSYVLLTGIFLCYAITFLMVAEPGVGVCSLRRLFLGLGMSLSY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 666 ATVLAKAITVVIAF----KATFPGRMIrwlmkSRAPNYIIPIcTLIQVFICG--IWMATSPP--FIDQDFH----AEHGH 733
Cdd:cd15286   83 AALLTKTNRIYRIFeqgkKSVTPPRFI-----SPTSQLVITF-SLISVQLLGvlAWFAVDPPhaLIDYEEGrtpdPEQAR 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 734 IIIFCNKgSSVAFHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMG---KFMVATE 810
Cdd:cd15286  157 GVLRCDM-SDLSLICCLGYSLLLMVTCTVYAIKARGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTAQsaeKLYIQTA 235
                        250       260       270
                 ....*....|....*....|....*....|...
gi 156119565 811 IFSI---LASSIAlLSFIFAPKCYIILFRPNEN 840
Cdd:cd15286  236 TLTVsmsLSASVS-LGMLYMPKVYVILFHPEQN 267
7tmC_mGluR3 cd15448
metabotropic glutamate receptor 3 in group 2, member of the class C family of ...
600-835 4.56e-25

metabotropic glutamate receptor 3 in group 2, member of the class C family of seven-transmembrane G protein-coupled receptors; The metabotropic glutamate receptors (mGluRs) in group 2 include mGluR 2 and 3. They are homodimeric class C G-protein coupled receptors which are activated by glutamate, the major excitatory neurotransmitter of the CNS. mGluRs are involved in regulating neuronal excitability and synaptic transmission via intracellular activation of second messenger signaling pathways. While the ionotropic glutamate receptor subtypes (AMPA, NMDA, and kainite) mediate fast excitatory postsynaptic transmission, mGluRs are known to mediate slower excitatory postsynaptic responses and to be involved in synaptic plasticity in the mammalian brain. In addition to seven-transmembrane helices, the class C GPCRs are characterized by a large N-terminal extracellular Venus flytrap-like domain, which is composed of two adjacent lobes separated by a cleft which binds an endogenous ligand. Moreover, they exist as either homo- or heterodimers, which are essential for their function. For instance, mGluRs form homodimers via interactions between the N-terminal Venus flytrap domains and the intermolecular disulphide bonds between cysteine residues located in the cysteine-rich domain (CRD). At least eight different subtypes of metabotropic receptors (mGluR1-8) have been identified and further classified into three groups based on their sequence homology, pharmacological properties, and signaling pathways. Group 1 (mGluR1 and mGluR5) receptors are predominantly located postsynaptically on neurons and are involved in long-term synaptic plasticity in the brain, including long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum. They are coupled to G(q/11) proteins, thereby activating phospholipase C to generate inositol-1,4,5-triphosphate (IP3) and diacyglycerol (DAG), which in turn lead to Ca2+ release and protein kinase C activation, respectively. Group 1 mGluR expression is shown to be strongly upregulated in animal models of epilepsy, brain injury, inflammatory, and neuropathic pain, as well as in patients with amyotrophic lateral sclerosis or multiple sclerosis. Group 2 (mGluR2 and mGluR3) and 3 (mGluR4, mGluR6, mGluR7, and mGluR8) receptors are predominantly localized presynaptically in the active region of neurotransmitter release. They are coupled to G(i/o) proteins, which leads to inhibition of adenylate cyclase activity and cAMP formation, and consequently to a decrease in protein kinase A (PKA) activity. Ultimately, activation of these receptors leads to inhibition of neurotransmitter release such as glutamate and GABA via inhibition of Ca2+ channels and activation of K+ channels. Furthermore, while activation of Group 1 mGluRs increases NMDA (N-methyl-D-aspartate) receptor activity and risk of neurotoxicity, Group 2 and 3 mGluRs decrease NMDA receptor activity and prevent neurotoxicity.


Pssm-ID: 320564  Cd Length: 254  Bit Score: 105.03  E-value: 4.56e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 600 TAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTVALATVLAKAITVVIAF 679
Cdd:cd15448   17 TCMVITVFIKHNNTPLVKASGRELCYILLFGVFLSYCMTFFFIAKPSPVICTLRRLGLGTSFAVCYSALLTKTNCIARIF 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 680 KATFPGRMIRWLMKSRAPNYIIPICTLIQVFICGIWMATSPPFIDQDFHAEHGHIIIF-CN-KGSSVAFhcTLGYLCFLA 757
Cdd:cd15448   97 DGVKNGAQRPKFISPSSQVFICLSLILVQIVVVSVWLILEAPGTRRYTLPEKRETVILkCNvKDSSMLI--SLTYDVVLV 174
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 758 LGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATEIF--SILASSIALLSFIFAPKCYIILF 835
Cdd:cd15448  175 ILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMciSVSLSGFVVLGCLFAPKVHIILF 254
7tmC_mGluR8 cd15454
metabotropic glutamate receptor 8 in group 3, member of the class C family of ...
600-840 2.59e-24

metabotropic glutamate receptor 8 in group 3, member of the class C family of seven-transmembrane G protein-coupled receptors; The receptors in group 3 include mGluRs 4, 6, 7, and 8. They are homodimeric class C G-protein coupled receptors which are activated by glutamate, the major excitatory neurotransmitter of the CNS. mGluRs are involved in regulating neuronal excitability and synaptic transmission via intracellular activation of second messenger signaling pathways. While the ionotropic glutamate receptor subtypes (AMPA, NMDA, and kainite) mediate fast excitatory postsynaptic transmission, mGluRs are known to mediate slower excitatory postsynaptic responses and to be involved in synaptic plasticity in the mammalian brain. In addition to seven-transmembrane helices, the class C GPCRs are characterized by a large N-terminal extracellular Venus flytrap-like domain, which is composed of two adjacent lobes separated by a cleft which binds an endogenous ligand. Moreover, they exist as either homo- or heterodimers, which are essential for their function. For instance, mGluRs form homodimers via interactions between the N-terminal Venus flytrap domains and the intermolecular disulphide bonds between cysteine residues located in the cysteine-rich domain (CRD). At least eight different subtypes of metabotropic receptors (mGluR1-8) have been identified and further classified into three groups based on their sequence homology, pharmacological properties, and signaling pathways. Group 1 (mGluR1 and mGluR5) receptors are predominantly located postsynaptically on neurons and are involved in long-term synaptic plasticity in the brain, including long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum. They are coupled to G(q/11) proteins, thereby activating phospholipase C to generate inositol-1,4,5-triphosphate (IP3) and diacyglycerol (DAG), which in turn lead to Ca2+ release and protein kinase C activation, respectively. Group 1 mGluR expression is shown to be strongly upregulated in animal models of epilepsy, brain injury, inflammatory, and neuropathic pain, as well as in patients with amyotrophic lateral sclerosis or multiple sclerosis. Group 2 (mGluR2 and mGluR3) and 3 (mGluR4, mGluR6, mGluR7, and mGluR8) receptors are predominantly localized presynaptically in the active region of neurotransmitter release. They are coupled to G(i/o) proteins, which leads to inhibition of adenylate cyclase activity and cAMP formation, and consequently to a decrease in protein kinase A (PKA) activity. Ultimately, activation of these receptors leads to inhibition of neurotransmitter release such as glutamate and GABA via inhibition of Ca2+ channels and activation of K+ channels. Furthermore, while activation of Group 1 mGluRs increases NMDA (N-methyl-D-aspartate) receptor activity and risk of neurotoxicity, Group 2 and 3 mGluRs decrease NMDA receptor activity and prevent neurotoxicity.


Pssm-ID: 320570 [Multi-domain]  Cd Length: 311  Bit Score: 104.33  E-value: 2.59e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 600 TAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTVALATVLAKAITVviaf 679
Cdd:cd15454   17 TTFVIVTFVRYNDTPIVRASGRELSYVLLTGIFLCYAITFLMIATPDTGICSFRRVFLGLGMCFSYAALLTKTNRI---- 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 680 katfpGRMIRWLMKS-RAPNYIIPIC------TLIQVFICG--IWMATSPPFIDQDF------HAEHGHIIIFCNKgSSV 744
Cdd:cd15454   93 -----HRIFEQGKKSvTAPKFISPASqlvitfSLISVQLLGvfVWFAVDPPHTIVDYgeqrtlDPEKARGVLKCDI-SDL 166
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 745 AFHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMG---KFMVATEIFSI---LASS 818
Cdd:cd15454  167 SLICSLGYSILLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIIWLAFIPIFFGTAQsaeRMYIQTTTLTIsmsLSAS 246
                        250       260
                 ....*....|....*....|..
gi 156119565 819 IAlLSFIFAPKCYIILFRPNEN 840
Cdd:cd15454  247 VS-LGMLYMPKVYIIIFHPEQN 267
7tmC_mGluR7 cd15451
metabotropic glutamate receptor 7 in group 3, member of the class C family of ...
600-840 8.15e-24

metabotropic glutamate receptor 7 in group 3, member of the class C family of seven-transmembrane G protein-coupled receptors; The receptors in group 3 include mGluRs 4, 6, 7, and 8. They are homodimeric class C G-protein coupled receptors which are activated by glutamate, the major excitatory neurotransmitter of the CNS. mGluRs are involved in regulating neuronal excitability and synaptic transmission via intracellular activation of second messenger signaling pathways. While the ionotropic glutamate receptor subtypes (AMPA, NMDA, and kainite) mediate fast excitatory postsynaptic transmission, mGluRs are known to mediate slower excitatory postsynaptic responses and to be involved in synaptic plasticity in the mammalian brain. In addition to seven-transmembrane helices, the class C GPCRs are characterized by a large N-terminal extracellular Venus flytrap-like domain, which is composed of two adjacent lobes separated by a cleft which binds an endogenous ligand. Moreover, they exist as either homo- or heterodimers, which are essential for their function. For instance, mGluRs form homodimers via interactions between the N-terminal Venus flytrap domains and the intermolecular disulphide bonds between cysteine residues located in the cysteine-rich domain (CRD). At least eight different subtypes of metabotropic receptors (mGluR1-8) have been identified and further classified into three groups based on their sequence homology, pharmacological properties, and signaling pathways. Group 1 (mGluR1 and mGluR5) receptors are predominantly located postsynaptically on neurons and are involved in long-term synaptic plasticity in the brain, including long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum. They are coupled to G(q/11) proteins, thereby activating phospholipase C to generate inositol-1,4,5-triphosphate (IP3) and diacyglycerol (DAG), which in turn lead to Ca2+ release and protein kinase C activation, respectively. Group 1 mGluR expression is shown to be strongly upregulated in animal models of epilepsy, brain injury, inflammatory, and neuropathic pain, as well as in patients with amyotrophic lateral sclerosis or multiple sclerosis. Group 2 (mGluR2 and mGluR3) and 3 (mGluR4, mGluR6, mGluR7, and mGluR8) receptors are predominantly localized presynaptically in the active region of neurotransmitter release. They are coupled to G(i/o) proteins, which leads to inhibition of adenylate cyclase activity and cAMP formation, and consequently to a decrease in protein kinase A (PKA) activity. Ultimately, activation of these receptors leads to inhibition of neurotransmitter release such as glutamate and GABA via inhibition of Ca2+ channels and activation of K+ channels. Furthermore, while activation of Group 1 mGluRs increases NMDA (N-methyl-D-aspartate) receptor activity and risk of neurotoxicity, Group 2 and 3 mGluRs decrease NMDA receptor activity and prevent neurotoxicity.


Pssm-ID: 320567  Cd Length: 307  Bit Score: 102.79  E-value: 8.15e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 600 TAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTVALATVLAKAITVVIAF 679
Cdd:cd15451   17 TIFVMATFIRYNDTPIVRASGRELSYVLLTGIFLCYIITFLMIAKPDVAVCSFRRIFLGLGMCISYAALLTKTNRIYRIF 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 680 KatfpgrmiRWLMKSRAPNYIIP------ICTLIQVFICG--IWMATSPP--FIDQDFHA----EHGHIIIFCNKgSSVA 745
Cdd:cd15451   97 E--------QGKKSVTAPRLISPtsqlaiTSSLISVQLLGvlIWFAVDPPniIIDYDEQKtmnpEQARGVLKCDI-TDLQ 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 746 FHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMG---KFMVATEIFSI---LASSI 819
Cdd:cd15451  168 IICSLGYSILLMVTCTVYAIKTRGVPENFNEAKPIGFTMYTTCIVWLAFIPIFFGTAQsaeKLYIQTTTLTIsmnLSASV 247
                        250       260
                 ....*....|....*....|.
gi 156119565 820 AlLSFIFAPKCYIILFRPNEN 840
Cdd:cd15451  248 A-LGMLYMPKVYIIIFHPELN 267
7tmC_TAS1R2a-like cd15287
type 1 taste receptor subtype 2a and similar proteins, member of the class C of ...
593-835 1.26e-23

type 1 taste receptor subtype 2a and similar proteins, member of the class C of seven-transmembrane G protein-coupled receptors; This group includes TAS1R2a and its similar proteins found in fish. They are members of the type I taste receptor (TAS1R) family that belongs to the class C of G protein-coupled receptors. The functional TAS1Rs are obligatory heterodimers built from three known members, TAS1R1-3. TAS1R1 combines with TAS1R3 to form an umami taste receptor, which is responsible for the perception of savory taste, such as the food additive mono-sodium glutamate (MSG); whereas the combination of TAS1R2-TAS1R3 forms a sweet-taste receptor for sugars and D-amino acids. On the other hand, the type II taste receptors (TAS2Rs), which belong to the class A family of GPCRs, recognize bitter tasting compounds. In the case of sweet, for example, the TAS1R2-TAS1R3 heterodimer activates phospholipase C (PLC) via alpha-gustducin, a heterodimeric G protein that is involved in perception of sweet and bitter tastes. This activation leads to generation of inositol (1, 4, 5)-trisphosphate (IP3) and diacylglycerol (DAG), and consequently increases intracellular Ca2+ mobilization and activates a cation channel, TRPM5. In contrast to the TAS1R2-TAS1R3 heterodimer, TAS1R3 alone could activate adenylate cyclase leading to cAMP formation in the absence of alpha-gustducin. Each TAS1R contains a large extracellular Venus flytrap-like domain in the N-terminus, cysteine-rich domain (CRD) and seven-transmembrane (7TM) domain, which are characteristics of the class C GPCRs. The Venus flytrap-like domain shares strong sequence homology to bacterial periplasmic binding proteins and possess the orthosteric amino acid and calcium binding sites for members of the class C, including CaSR, GABA-B1, GPRC6A, mGlu, and TAS1R receptors.


Pssm-ID: 320414  Cd Length: 252  Bit Score: 100.91  E-value: 1.26e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 593 ALCLSTLTAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTVALATVLAKA 672
Cdd:cd15287   10 ACVLVGLTLAVSVLFAINYNTPVVRSAGGPMCFLILGCLSLCSVSVFFYFGKPTVASCILRYFPFLLFYTVCLACFVVRS 89
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 673 ITVVIAFK--ATFPgRMIRWLMKSRAPNYIIPICTLIQVFICGIWMATSPPFIDQDFHAEHGHIIIFCNkGSSVAFHCTL 750
Cdd:cd15287   90 FQIVCIFKiaAKFP-KLHSWWVKYHGQWLLIAVAFVIQALLLITGFSFSPPKPYNDTSWYPDKIILSCD-INLKATSMSL 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 751 GYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATEIFSILASSIALLSFIFAPKC 830
Cdd:cd15287  168 VLLLSLCCLCFIFSYMGKDLPKNYNEAKAITFCLLLLILTWIIFATEYMLYRGKYIQLLNALAVLSSLYSFLLWYFLPKC 247

                 ....*
gi 156119565 831 YIILF 835
Cdd:cd15287  248 YIIIF 252
ANF_receptor pfam01094
Receptor family ligand binding region; This family includes extracellular ligand binding ...
84-435 1.30e-23

Receptor family ligand binding region; This family includes extracellular ligand binding domains of a wide range of receptors. This family also includes the bacterial amino acid binding proteins of known structure.


Pssm-ID: 460062 [Multi-domain]  Cd Length: 347  Bit Score: 103.23  E-value: 1.30e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565   84 LALIFAIEEINENPNLLSNISLGFDfynVRFTEKDTL--MNACIWLtahrekyilpnykcgKKHFTAALTG-TSWTTSAQ 160
Cdd:pfam01094   4 LAVRLAVEDINADPGLLPGTKLEYI---ILDTCCDPSlaLAAALDL---------------LKGEVVAIIGpSCSSVASA 65
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  161 MGTLFQLFKFPQLSFGPYDHILSDRNQYSSLYQMAPMASSLSLGIVSLLVHFRWSWVGLILPDDHKGNTILSDFRNEMER 240
Cdd:pfam01094  66 VASLANEWKVPLISYGSTSPALSDLNRYPTFLRTTPSDTSQADAIVDILKHFGWKRVALIYSDDDYGESGLQALEDALRE 145
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  241 KGVCIAFLKMIPATWMSH--FNKFWKNMD-ETNVIIIYGDIDSLEGLMR-----NIGQRLLTW--KVWVMNIEPHVIADY 310
Cdd:pfam01094 146 RGIRVAYKAVIPPAQDDDeiARKLLKEVKsRARVIVVCCSSETARRLLKaarelGMMGEGYVWiaTDGLTTSLVILNPST 225
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  311 fmLDSFHGSLIFTHHYTERIEFTNFVQtvnpykypEDIYLPKLWYLffkcsfsdidcqllnncqfnasldilprhifdvS 390
Cdd:pfam01094 226 --LEAAGGVLGFRLHPPDSPEFSEFFW--------EKLSDEKELYE---------------------------------N 262
                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 156119565  391 MSDESIS----IYNAVYAVAHSLHEMRLQQVQ------MQPYENGEEIMFFPWQV 435
Cdd:pfam01094 263 LGGLPVSygalAYDAVYLLAHALHNLLRDDKPgracgaLGPWNGGQKLLRYLKNV 317
NCD3G pfam07562
Nine Cysteines Domain of family 3 GPCR; This conserved sequence contains several ...
511-564 1.30e-22

Nine Cysteines Domain of family 3 GPCR; This conserved sequence contains several highly-conserved Cys residues that are predicted to form disulphide bridges. It is predicted to lie outside the cell membrane, tethered to the pfam00003 in several receptor proteins.


Pssm-ID: 462210  Cd Length: 53  Bit Score: 91.55  E-value: 1.30e-22
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 156119565  511 PRSVCSESCGHGFRKLALEGKAVCCYKCTPCADNEISNeTDVDQCLKCPESHYA 564
Cdd:pfam07562   1 PSSVCSESCPPGQRKSQQGGAPVCCWDCVPCPEGEISN-TDSDTCKKCPEGQWP 53
7tmC_mGluR6 cd15453
metabotropic glutamate receptor 6 in group 3, member of the class C family of ...
600-840 3.68e-22

metabotropic glutamate receptor 6 in group 3, member of the class C family of seven-transmembrane G protein-coupled receptors; The receptors in group 3 include mGluRs 4, 6, 7, and 8. They are homodimeric class C G-protein coupled receptors which are activated by glutamate, the major excitatory neurotransmitter of the CNS. mGluRs are involved in regulating neuronal excitability and synaptic transmission via intracellular activation of second messenger signaling pathways. While the ionotropic glutamate receptor subtypes (AMPA, NMDA, and kainite) mediate fast excitatory postsynaptic transmission, mGluRs are known to mediate slower excitatory postsynaptic responses and to be involved in synaptic plasticity in the mammalian brain. In addition to seven-transmembrane helices, the class C GPCRs are characterized by a large N-terminal extracellular Venus flytrap-like domain, which is composed of two adjacent lobes separated by a cleft which binds an endogenous ligand. Moreover, they exist as either homo- or heterodimers, which are essential for their function. For instance, mGluRs form homodimers via interactions between the N-terminal Venus flytrap domains and the intermolecular disulphide bonds between cysteine residues located in the cysteine-rich domain (CRD). At least eight different subtypes of metabotropic receptors (mGluR1-8) have been identified and further classified into three groups based on their sequence homology, pharmacological properties, and signaling pathways. Group 1 (mGluR1 and mGluR5) receptors are predominantly located postsynaptically on neurons and are involved in long-term synaptic plasticity in the brain, including long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum. They are coupled to G(q/11) proteins, thereby activating phospholipase C to generate inositol-1,4,5-triphosphate (IP3) and diacyglycerol (DAG), which in turn lead to Ca2+ release and protein kinase C activation, respectively. Group 1 mGluR expression is shown to be strongly upregulated in animal models of epilepsy, brain injury, inflammatory, and neuropathic pain, as well as in patients with amyotrophic lateral sclerosis or multiple sclerosis. Group 2 (mGluR2 and mGluR3) and 3 (mGluR4, mGluR6, mGluR7, and mGluR8) receptors are predominantly localized presynaptically in the active region of neurotransmitter release. They are coupled to G(i/o) proteins, which leads to inhibition of adenylate cyclase activity and cAMP formation, and consequently to a decrease in protein kinase A (PKA) activity. Ultimately, activation of these receptors leads to inhibition of neurotransmitter release such as glutamate and GABA via inhibition of Ca2+ channels and activation of K+ channels. Furthermore, while activation of Group 1 mGluRs increases NMDA (N-methyl-D-aspartate) receptor activity and risk of neurotoxicity, Group 2 and 3 mGluRs decrease NMDA receptor activity and prevent neurotoxicity.


Pssm-ID: 320569 [Multi-domain]  Cd Length: 273  Bit Score: 97.41  E-value: 3.68e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 600 TAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTVALATVLAKAITVVIAF 679
Cdd:cd15453   17 TTTVVITFVRFNNTPIVRASGRELSYVLLTGIFLIYAITFLMVAEPGAAVCAFRRLFLGLGTTLSYSALLTKTNRIYRIF 96
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 680 ----KATFPgrmirwlmksraPNYIIPICTLI--------QVFICGIWMATSPPFIDQDFH------AEHGHIIIFCNKG 741
Cdd:cd15453   97 eqgkRSVTP------------PPFISPTSQLVitfsltslQVVGVIAWLGAQPPHSVIDYEeqrtvdPEQARGVLKCDMS 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 742 SSVAFHCtLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMG---KFMVATEIFSI---L 815
Cdd:cd15453  165 DLSLIGC-LGYSLLLMVTCTVYAIKARGVPETFNEAKPIGFTMYTTCIIWLAFVPIFFGTAQsaeKIYIQTTTLTVslsL 243
                        250       260
                 ....*....|....*....|....*
gi 156119565 816 ASSIAlLSFIFAPKCYIILFRPNEN 840
Cdd:cd15453  244 SASVS-LGMLYVPKTYVILFHPEQN 267
7tmC_mGluR5 cd15450
metabotropic glutamate receptor 5 in group 1, member of the class C family of ...
590-834 7.39e-22

metabotropic glutamate receptor 5 in group 1, member of the class C family of seven-transmembrane G protein-coupled receptors; Group 1 mGluRs includes mGluR1 and mGluR5, as well as their closely related invertebrate receptors. They are homodimeric class C G-protein coupled receptors which are activated by glutamate, the major excitatory neurotransmitter of the CNS. mGluRs are involved in regulating neuronal excitability and synaptic transmission via intracellular activation of second messenger signaling pathways. While the ionotropic glutamate receptor subtypes (AMPA, NMDA, and kainite) mediate fast excitatory postsynaptic transmission, mGluRs are known to mediate slower excitatory postsynaptic responses and to be involved in synaptic plasticity in the mammalian brain. In addition to seven-transmembrane helices, the class C GPCRs are characterized by a large N-terminal extracellular Venus flytrap-like domain, which is composed of two adjacent lobes separated by a cleft which binds an endogenous ligand. Moreover, they exist as either homo- or heterodimers, which are essential for their function. For instance, mGluRs form homodimers via interactions between the N-terminal Venus flytrap domains and the intermolecular disulphide bonds between cysteine residues located in the cysteine-rich domain (CRD). At least eight different subtypes of metabotropic receptors (mGluR1-8) have been identified and further classified into three groups based on their sequence homology, pharmacological properties, and signaling pathways. Group 1 (mGluR1 and mGluR5) receptors are predominantly located postsynaptically on neurons and are involved in long-term synaptic plasticity in the brain, including long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum. They are coupled to G(q/11) proteins, thereby activating phospholipase C to generate inositol-1,4,5-triphosphate (IP3) and diacyglycerol (DAG), which in turn lead to Ca2+ release and protein kinase C activation, respectively. Group 1 mGluR expression is shown to be strongly upregulated in animal models of epilepsy, brain injury, inflammatory, and neuropathic pain, as well as in patients with amyotrophic lateral sclerosis or multiple sclerosis. Group 2 (mGluR2 and mGluR3) and 3 (mGluR4, mGluR6, mGluR7, and mGluR8) receptors are predominantly localized presynaptically in the active region of neurotransmitter release. They are coupled to G(i/o) proteins, which leads to inhibition of adenylate cyclase activity and cAMP formation, and consequently to a decrease in protein kinase A (PKA) activity. Ultimately, activation of these receptors leads to inhibition of neurotransmitter release such as glutamate and GABA via inhibition of Ca2+ channels and activation of K+ channels. Furthermore, while activation of Group 1 mGluRs increases NMDA (N-methyl-D-aspartate) receptor activity and risk of neurotoxicity, Group 2 and 3 mGluRs decrease NMDA receptor activity and prevent neurotoxicity.


Pssm-ID: 320566  Cd Length: 250  Bit Score: 95.82  E-value: 7.39e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 590 ASIALCLSTL-TAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTV---AL 665
Cdd:cd15450    6 AVVFACLGLLaTLFVTVIFIIYRDTPVVKSSSRELCYIILAGICLGYLCTFCLIAKPKQIYCYLQRIGIGLSPAMsysAL 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 666 ATVLAKAITVVIAFKATFPGRMIRWlMKSRAPNYIIPICTLIQVFICGIWMATSPPFIDQDFHAEHgHIIIFCNKgSSVA 745
Cdd:cd15450   86 VTKTNRIARILAGSKKKICTKKPRF-MSACAQLVIAFILICIQLGIIVALFIMEPPDIMHDYPSIR-EVYLICNT-TNLG 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 746 FHCTLGYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTmgKFMVATEIFSILASSIALLSFI 825
Cdd:cd15450  163 VVTPLGYNGLLILSCTFYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGS--NYKIITMCFSVSLSATVALGCM 240

                 ....*....
gi 156119565 826 FAPKCYIIL 834
Cdd:cd15450  241 FVPKVYIIL 249
7tmC_TAS1R2 cd15288
type 1 taste receptor subtype 2, member of the class C of seven-transmembrane G ...
596-835 4.87e-20

type 1 taste receptor subtype 2, member of the class C of seven-transmembrane G protein-coupled receptors; This group represents TAS1R2, which is a member of the type I taste receptor (TAS1R) family that belongs to the class C of G protein-coupled receptors. The functional TAS1Rs are obligatory heterodimers built from three known members, TAS1R1-3. TAS1R1 combines with TAS1R3 to form an umami taste receptor, which is responsible for the perception of savory taste, such as the food additive mono-sodium glutamate (MSG); whereas the combination of TAS1R2-TAS1R3 forms a sweet-taste receptor for sugars and D-amino acids. On the other hand, the type II taste receptors (TAS2Rs), which belong to the class A family of GPCRs, recognize bitter tasting compounds. In the case of sweet, for example, the TAS1R2-TAS1R3 heterodimer activates phospholipase C (PLC) via alpha-gustducin, a heterodimeric G protein that is involved in perception of sweet and bitter tastes. This activation leads to generation of inositol (1, 4, 5)-trisphosphate (IP3) and diacylglycerol (DAG), and consequently increases intracellular Ca2+ mobilization and activates a cation channel, TRPM5. In contrast to the TAS1R2-TAS1R3 heterodimer, TAS1R3 alone could activate adenylate cyclase leading to cAMP formation in the absence of alpha-gustducin. Each TAS1R contains a large extracellular Venus flytrap-like domain in the N-terminus, cysteine-rich domain (CRD) and seven-transmembrane (7TM) domain, which are characteristics of the class C GPCRs. The Venus flytrap-like domain shares strong sequence homology to bacterial periplasmic binding proteins and possess the orthosteric amino acid and calcium binding sites for members of the class C, including CaSR, GABA-B1, GPRC6A, mGlu, and TAS1R receptors.


Pssm-ID: 320415  Cd Length: 254  Bit Score: 90.62  E-value: 4.87e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 596 LSTLTAFVIgiFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTVALATVLAKAITV 675
Cdd:cd15288   15 LSTLAILVI--FGRHFQTPVVRSAGGRMCFLMLAPLLVAYVNVPVYVGIPTVFTCLCRQTLFPLCFTVCISCIAVRSFQI 92
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 676 VIAFK--ATFPgRMIRWLMKSRAPNYIIPICTLIQVFICGIWMATSPPFIDQDFHAEHGHIIIF-CNKGSSVAFHCTLGY 752
Cdd:cd15288   93 VCIFKmaRRLP-RAYSYWVKYNGPYVFVALITLLKVVIVVINVLAHPTAPTTRADPDDPQVMILqCNPNYRLALLFNTSL 171
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 753 LCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWI---TFLPVYHStmgkfmVATEIFSILASSIALLSF---IF 826
Cdd:cd15288  172 DLLLSVLGFCFAYMGKELPTNYNEAKFITLCMTFYFASSVflcTFMSVYEG------VLVTIFDALVTVINLLGIslgYF 245

                 ....*....
gi 156119565 827 APKCYIILF 835
Cdd:cd15288  246 GPKCYMILF 254
7tmC_mGluR1 cd15449
metabotropic glutamate receptor 1 in group 1, member of the class C family of ...
595-834 9.11e-20

metabotropic glutamate receptor 1 in group 1, member of the class C family of seven-transmembrane G protein-coupled receptors; Group 1 mGluRs includes mGluR1 and mGluR5, as well as their closely related invertebrate receptors. They are homodimeric class C G-protein coupled receptors which are activated by glutamate, the major excitatory neurotransmitter of the CNS. mGluRs are involved in regulating neuronal excitability and synaptic transmission via intracellular activation of second messenger signaling pathways. While the ionotropic glutamate receptor subtypes (AMPA, NMDA, and kainite) mediate fast excitatory postsynaptic transmission, mGluRs are known to mediate slower excitatory postsynaptic responses and to be involved in synaptic plasticity in the mammalian brain. In addition to seven-transmembrane helices, the class C GPCRs are characterized by a large N-terminal extracellular Venus flytrap-like domain, which is composed of two adjacent lobes separated by a cleft which binds an endogenous ligand. Moreover, they exist as either homo- or heterodimers, which are essential for their function. For instance, mGluRs form homodimers via interactions between the N-terminal Venus flytrap domains and the intermolecular disulphide bonds between cysteine residues located in the cysteine-rich domain (CRD). At least eight different subtypes of metabotropic receptors (mGluR1-8) have been identified and further classified into three groups based on their sequence homology, pharmacological properties, and signaling pathways. Group 1 (mGluR1 and mGluR5) receptors are predominantly located postsynaptically on neurons and are involved in long-term synaptic plasticity in the brain, including long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum. They are coupled to G(q/11) proteins, thereby activating phospholipase C to generate inositol-1,4,5-triphosphate (IP3) and diacyglycerol (DAG), which in turn lead to Ca2+ release and protein kinase C activation, respectively. Group 1 mGluR expression is shown to be strongly upregulated in animal models of epilepsy, brain injury, inflammatory, and neuropathic pain, as well as in patients with amyotrophic lateral sclerosis or multiple sclerosis. Group 2 (mGluR2 and mGluR3) and 3 (mGluR4, mGluR6, mGluR7, and mGluR8) receptors are predominantly localized presynaptically in the active region of neurotransmitter release. They are coupled to G(i/o) proteins, which leads to inhibition of adenylate cyclase activity and cAMP formation, and consequently to a decrease in protein kinase A (PKA) activity. Ultimately, activation of these receptors leads to inhibition of neurotransmitter release such as glutamate and GABA via inhibition of Ca2+ channels and activation of K+ channels. Furthermore, while activation of Group 1 mGluRs increases NMDA (N-methyl-D-aspartate) receptor activity and risk of neurotoxicity, Group 2 and 3 mGluRs decrease NMDA receptor activity and prevent neurotoxicity.


Pssm-ID: 320565  Cd Length: 250  Bit Score: 89.69  E-value: 9.11e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 595 CLSTL-TAFVIGIFVKYRDTPIVKANNQALSYILLITLTFCFLCSLTFIGQPNKDTCIMQQITFGVVFTV---ALATVLA 670
Cdd:cd15449   11 CLGILvTMFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMcysALVTKTN 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 671 KAITVVIAFKATFPGRMIRWlMKSRAPNYIIPICTLIQVFICGIWMATSPPFIDQDFHAEHgHIIIFCNKgSSVAFHCTL 750
Cdd:cd15449   91 RIARILAGSKKKICTRKPRF-MSAWAQVVIASILISVQLTLVVTLIIMEPPMPILSYPSIK-EVYLICNT-SNLGVVAPL 167
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 751 GYLCFLALGGYTMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTmgKFMVATEIFSILASSIALLSFIFAPKC 830
Cdd:cd15449  168 GYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGS--NYKIITTCFAVSLSVTVALGCMFTPKM 245

                 ....
gi 156119565 831 YIIL 834
Cdd:cd15449  246 YIII 249
PBP1_mGluR_groupI cd06374
ligand binding domain of the group I metabotropic glutamate receptor; Ligand binding domain of ...
40-484 1.89e-19

ligand binding domain of the group I metabotropic glutamate receptor; Ligand binding domain of the group I metabotropic glutamate receptor, a family containing mGlu1R and mGlu5R, all of which stimulate phospholipase C (PLC) hydrolysis. The metabotropic glutamate receptor is a member of the family C of G-protein-coupled receptors that transduce extracellular signals into G-protein activation and ultimately into intracellular responses. The mGluRs are classified into three groups which comprise eight subtypes.


Pssm-ID: 380597 [Multi-domain]  Cd Length: 474  Bit Score: 92.41  E-value: 1.89e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  40 GDVVIGAFFPIHTYYTGNKIPhsflPYYYVDNYLQYNFknyQYILALIFAIEEINENPNLLSNISLGFDFynvrfteKDT 119
Cdd:cd06374    8 GDIIIGALFPVHHQPPLKKVF----SRKCGEIREQYGI---QRVEAMFRTLDKINKDPNLLPNITLGIEI-------RDS 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 120 LMNACIWL----------TAHREKYILPNYKC--------GKKHFTAALTGT-SWTTSAQMGTLFQLFKFPQLSFGPYDH 180
Cdd:cd06374   74 CWYSPVALeqsiefirdsVASVEDEKDTQNTPdptplsppENRKPIVGVIGPgSSSVTIQVQNLLQLFHIPQIGYSATSI 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 181 ILSDRNQYSSLYQMAPMASSLSLGIVSLLVHFRWSWVGLILPDDHKGNTILSDFRNEMERKGVCIAFLKMIPATWMSH-F 259
Cdd:cd06374  154 DLSDKSLYKYFLRVVPSDYLQARAMLDIVKRYNWTYVSTVHTEGNYGESGIEAFKELAAEEGICIAHSDKIYSNAGEEeF 233
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 260 NKFWKNMDET----NVIIIYGDIDSLEGL---MRNIGQR----LLTWKVWvmNIEPHVIADYfmLDSFHGSLI------- 321
Cdd:cd06374  234 DRLLRKLMNTpnkaRVVVCFCEGETVRGLlkaMRRLNATghflLIGSDGW--ADRKDVVEGY--EDEAAGGITikihspe 309
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 322 ---FTHHYTERIEFTNfvqTVNPykypediYLPKLWYLFFKCSF---SDIDCQLLNNCQFNASLDIlpRHIFDVSMSdes 395
Cdd:cd06374  310 vesFDEYYFNLKPETN---SRNP-------WFREFWQHRFDCRLpghPDENPYFKKCCTGEESLLG--NYVQDSKLG--- 374
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 396 iSIYNAVYAVAHSLHEMrlQQVQMQPYENGEEIMFFPWQVISFLLYC-NVSIL-IDQRSLDWRQKFNT--EYDIINLWNL 471
Cdd:cd06374  375 -FVINAIYAMAHALHRM--QEDLCGGYSVGLCPAMLPINGSLLLDYLlNVSFVgVSGDTIMFDENGDPpgRYDIMNFQKT 451
                        490
                 ....*....|...
gi 156119565 472 PNGLGRKVKVGSF 484
Cdd:cd06374  452 GEGSYDYVQVGSW 464
PBP1_GPC6A-like cd06361
ligand-binding domain of the promiscuous L-alpha-amino acid receptor GPRC6A which is a ...
43-299 2.09e-19

ligand-binding domain of the promiscuous L-alpha-amino acid receptor GPRC6A which is a broad-spectrum amino acid-sensing receptor; This family includes the ligand-binding domain of the promiscuous L-alpha-amino acid receptor GPRC6A which is a broad-spectrum amino acid-sensing receptor, and its fish homolog, the 5.24 chemoreceptor. GPRC6A is a member of the family C of G-protein-coupled receptors that transduce extracellular signals into G-protein activation and ultimately into cellular responses.


Pssm-ID: 380584 [Multi-domain]  Cd Length: 401  Bit Score: 91.28  E-value: 2.09e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  43 VIGAFFPIHT-----YYTGNKIPHSFLPYYYVDNYLQynfknyqyILALIFAIEEINeNPNLLSNISLGFDFYNVrFTEK 117
Cdd:cd06361    1 IIGGLFPIHEkvldlHDRPTKPQIFICTGFDLRGFLQ--------SLAMIHAIEMIN-NSTLLPGIKLGYEIYDT-CSDV 70
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 118 DTLMNACIWLTAHREkYILPNYKCGKKHFTA---ALTGTSWT-TSAQMGTLFQLFKFPQLSFGPYDHILSDRNQYSSLYQ 193
Cdd:cd06361   71 TKALQATLRLLSKFN-SSNELLECDYTDYVPpvkAVIGASYSeISIAVARLLNLQLIPQISYESSAPILSDKLRFPSFLR 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 194 MAPMASSLSLGIVSLLVHFRWSWVGLILPDDHKGNTILSDFRNEMERKGVCIAFLKMIPA-----TWMSHFNKFW---KN 265
Cdd:cd06361  150 TVPSDFHQTKAMAKLISHFGWNWVGIIYTDDDYGRSALESFIIQAEAENVCIAFKEVLPAylsdpTMNVRINDTIqtiQS 229
                        250       260       270
                 ....*....|....*....|....*....|....
gi 156119565 266 MDETNVIIIYGDIDSLEGLMRNIgQRLLTWKVWV 299
Cdd:cd06361  230 SSQVNVVVLFLKPSLVKKLFKEV-IERNISKIWI 262
PBP1_mGluR_groupII cd06375
ligand binding domain of the group II metabotropic glutamate receptor; Ligand binding domain ...
40-482 3.40e-15

ligand binding domain of the group II metabotropic glutamate receptor; Ligand binding domain of the group II metabotropic glutamate receptor, a family that contains mGlu2R and mGlu3R, all of which inhibit adenylyl cyclase. The metabotropic glutamate receptor is a member of the family C of G-protein-coupled receptors that transduce extracellular signals into G-protein activation and ultimately into intracellular responses. The mGluRs are classified into three groups which comprise eight subtypes


Pssm-ID: 380598 [Multi-domain]  Cd Length: 462  Bit Score: 79.10  E-value: 3.40e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  40 GDVVIGAFFPIHTYYTGNKIPHSflpyyyvdnyLQYNfKNYQYILALIFAIEEINENPNLLSNISLG------------- 106
Cdd:cd06375    5 GDLVLGGLFPVHEKGEGMEECGR----------INED-RGIQRLEAMLFAIDRINRDPHLLPGVRLGvhildtcsrdtya 73
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 107 ----FDFYNVRFTEKDT--LMNACIWLTAHREKYILPnykcgkkhfTAALTGTSWTT-SAQMGTLFQLFKFPQLSFGPYD 179
Cdd:cd06375   74 leqsLEFVRASLTKVDDseYMCPDDGSYAIQEDSPLP---------IAGVIGGSYSSvSIQVANLLRLFQIPQISYASTS 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 180 HILSDRNQYSSLYQMAPMASSLSLGIVSLLVHFRWSWVGLILPDDHKGNTILSDFRNEMERKGVCIAFLKMIPATWM-SH 258
Cdd:cd06375  145 AKLSDKSRYDYFARTVPPDFYQAKAMAEILRFFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSADrKS 224
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 259 FNKFWKNMDE---TNVIIIYGDIDSLEGLMRnIGQRLLTWKVWVMN-----IEPHVIADYFMLDsfhGSLIFTHHYTERI 330
Cdd:cd06375  225 FDGVIRELLQkpnARVVVLFTRSDDARELLA-AAKRLNASFTWVASdgwgaQESIVKGSEDVAE---GAITLELASHPIP 300
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 331 EFTNFVQTVNPYKYPEDIYLPKLWYLFFKCSFSDIDCQlLNNCQFNASLDILPrhifdvsMSDESISIY--NAVYAVAHS 408
Cdd:cd06375  301 DFDRYFQSLTPYNNHRNPWFRDFWEQKFQCSLQNKSQA-ASVSDKHLSIDSSN-------YEQESKIMFvvNAVYAMAHA 372
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 409 LHEMR------LQQV--QMQPYENGEeimFFPwqviSFLLYCNVSILIDQRSLDWRQKFNT------EYDIINLWNLPNG 474
Cdd:cd06375  373 LHNMQrtlcpnTTRLcdAMRSLDGKK---LYK----DYLLNVSFTAPFPPADAGSEVKFDAfgdglgRYNIFNYQRAGGS 445

                 ....*....
gi 156119565 475 LG-RKVKVG 482
Cdd:cd06375  446 YGyRYKGVG 454
PBP1_glutamate_receptors-like cd06269
ligand-binding domain of family C G-protein couples receptors (GPCRs), membrane bound guanylyl ...
85-364 5.01e-15

ligand-binding domain of family C G-protein couples receptors (GPCRs), membrane bound guanylyl cyclases such as natriuretic peptide receptors (NPRs), and N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain of ionotropic glutamate rece; This CD represents the ligand-binding domain of the family C G-protein couples receptors (GPCRs), membrane bound guanylyl cyclases such as the family of natriuretic peptide receptors (NPRs), and the N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the ionotropic glutamate receptors, all of which are structurally similar and related to the periplasmic-binding fold type 1 family. The family C GPCRs consists of metabotropic glutamate receptor (mGluR), a calcium-sensing receptor (CaSR), gamma-aminobutyric acid receptor (GABAbR), the promiscuous L-alpha-amino acid receptor GPR6A, families of taste and pheromone receptors, and orphan receptors. Truncated splicing variants of the orphan receptors are not included in this CD. The family C GPCRs are activated by endogenous agonists such as amino acids, ions, and sugar based molecules. Their amino terminal ligand-binding region is homologous to the bacterial leucine-isoleucine-valine binding protein (LIVBP) and a leucine binding protein (LBP). The ionotropic glutamate receptors (iGluRs) have an integral ion channel and are subdivided into three major groups based on their pharmacology and structural similarities: NMDA receptors, AMPA receptors, and kainate receptors. The family of membrane bound guanylyl cyclases is further divided into three subfamilies: the ANP receptor (GC-A)/C-type natriuretic peptide receptor (GC-B), the heat-stable enterotoxin receptor (GC-C)/sensory organ specific membrane GCs such as retinal receptors (GC-E, GC-F), and olfactory receptors (GC-D and GC-G).


Pssm-ID: 380493 [Multi-domain]  Cd Length: 332  Bit Score: 77.07  E-value: 5.01e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  85 ALIFAIEEINENPNLLSNISLGfdfYNVRFTEKD---TLMNACIWLTAHrEKYILpnykcgkkhftaaLTGTSWTTSAQM 161
Cdd:cd06269   21 AFELALSDVNSRPDLLPKTTLG---LAIRDSECNptqALLSACDLLAAA-KVVAI-------------LGPGCSASAAPV 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 162 GTLFQLFKFPQLSFGPYDHILSDRNQYSSLYQMAPMASSLSLGIVSLLVHFRWSWVGLILPDDHKGNTILSDFRNEMERK 241
Cdd:cd06269   84 ANLARHWDIPVLSYGATAPGLSDKSRYAYFLRTVPPDSKQADAMLALVRRLGWNKVVLIYSDDEYGEFGLEGLEELFQEK 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 242 GVCIAFLKMIPATWMSHFNKFWKNMDETNVIIIYG-----DIDSLEGLMRNIGqrlLTWK--VWVMN---IEPHVIADYF 311
Cdd:cd06269  164 GGLITSRQSFDENKDDDLTKLLRNLRDTEARVIILlaspdTARSLMLEAKRLD---MTSKdyVWFVIdgeASSSDEHGDE 240
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 156119565 312 MLDSFHGSLIFTHHYTERIEFTNFVQTVNPYKYPEDIYLPKLWYLF-FKCSFSD 364
Cdd:cd06269  241 ARQAAEGAITVTLIFPVVKEFLKFSMELKLKSSKRKQGLNEEYELNnFAAFFYD 294
PBP1_SAP_GC-like cd06370
Ligand-binding domain of membrane bound guanylyl cyclases; Ligand-binding domain of membrane ...
63-429 1.68e-12

Ligand-binding domain of membrane bound guanylyl cyclases; Ligand-binding domain of membrane bound guanylyl cyclases (GCs), which are known to be activated by sperm-activating peptides (SAPs), such as speract or resact. These ligand peptides are released by a range of invertebrates to stimulate the metabolism and motility of spermatozoa and are also potent chemoattractants. These GCs contain a single transmembrane segment, an extracellular ligand binding domain, and intracellular protein kinase-like and cyclase catalytic domains. GCs of insect and nematodes, which exhibit high sequence similarity to the speract receptor are also included in this model.


Pssm-ID: 380593 [Multi-domain]  Cd Length: 400  Bit Score: 70.35  E-value: 1.68e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  63 FLPYYYVDNYlqyNFKNYQYILALIFAIEEINENPNLLSNISLGFDFYNVRFTEKDTLmNAciwLTAHREK----YILPN 138
Cdd:cd06370    6 LTPYSGAGSY---DRQGRVISGAITLAVDDVNNDPNLLPGHTLSFVWNDTRCDELLSI-RA---MTELWKRgvsaFIGPG 78
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 139 YKCgkkhftaaltgtswTTSAQMGTLFQLfkfPQLSFGPYDHILSDRNQYSSLYQMAPMASSLSLGIVSLLVHFRWSWVG 218
Cdd:cd06370   79 CTC--------------ATEARLAAAFNL---PMISYKCADPEVSDKSLYPTFARTIPPDSQISKSVIALLKHFNWNKVS 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 219 LILPDDHKGNTILSDFRNEMERKGVCIAFLKMIPA---TWMSHFNKFWKNMDET----NVIIIYGDIDSLEGLMRNIGQR 291
Cdd:cd06370  142 IVYENETKWSKIADTIKELLELNNIEINHEEYFPDpypYTTSHGNPFDKIVEETkektRIYVFLGDYSLLREFMYYAEDL 221
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 292 LLTWK----VWVMNIEpHVIADYFMLDSFHGSLIFTHHYTERIE--FTNF-VQTVNPYKYPEdiylpklwYLFFkcsfsd 364
Cdd:cd06370  222 GLLDNgdyvVIGVELD-QYDVDDPAKYPNFLSGDYTKNDTKEALeaFRSVlIVTPSPPTNPE--------YEKF------ 286
                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 156119565 365 idCQLLNN----CQFNASLDILPRHIFDVSMsdESISIYNAVYAVAHSLHEMrLQQVQmQPYeNGEEIM 429
Cdd:cd06370  287 --TKKVKEynklPPFNFPNPEGIEKTKEVPI--YAAYLYDAVMLYARALNET-LAEGG-DPR-DGTAII 348
7tmC_GABA-B-like cd15047
gamma-aminobutyric acid type B receptor and related proteins, member of the class C family of ...
591-833 3.02e-10

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: 61.81  E-value: 3.02e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 591 SIALCLSTLTAFVIGIFV-KYRDTPIVKANnqalSYILLITLTF-CFLCSLTFI------GQPNKDTCIMQQITFGVVFT 662
Cdd:cd15047    7 TVLSGIGILLALVFLIFNiKFRKNRVIKMS----SPLFNNLILLgCILCYISVIlfglddSKPSSFLCTARPWLLSIGFT 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 663 VALATVLAKAITVVIAFKATFPGRMI---RWLMKsrapnyIIPICTLIQVFICGIWMATSPPFIDQDFHAE--------H 731
Cdd:cd15047   83 LVFGALFAKTWRIYRIFTNKKLKRIVikdKQLLK------IVGILLLIDIIILILWTIVDPLKPTRVLVLSeisddvkyE 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 732 GHIIIFCNKGSSVAFHCTLGYLCFLALGGYTMAFLSRTLPD-SFNESKFLSLSLLVFFCVWITFLPVYHSTMGKFMVATE 810
Cdd:cd15047  157 YVVHCCSSSNGIIWLGILLAYKGLLLLFGCFLAWKTRNVDIeEFNESKYIGISIYNVLFLSVIGVPLSFVLTDSPDTSYL 236
                        250       260
                 ....*....|....*....|....*
gi 156119565 811 IFS--ILASSIALLSFIFAPKCYII 833
Cdd:cd15047  237 IISaaILFCTTATLCLLFVPKFWLL 261
7tmC_GPR158-like cd15293
orphan GPR158 and similar proteins, member of the class C family of seven-transmembrane G ...
589-834 4.15e-10

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: 61.08  E-value: 4.15e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 589 LASIALCLSTLTAFVIGIFvKYRDTPIVKANNQALSYILLI-TLTFCFLCSLTFIgQPNKDTCIMQQITFGVVFTVALAT 667
Cdd:cd15293    7 LAVQAICILLCLVLALVVF-RFRKVKVIKAASPILLELILFgALLLYFPVFILYF-EPSVFRCILRPWFRHLGFAIVYGA 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 668 VLAKAITVVIAFKATfpgrmirwlmKSRAPN--------YIIPICTLIQVFICgIWMATSPPFIDQDFHAEHGHIIIF-C 738
Cdd:cd15293   85 LILKTYRILVVFRSR----------SARRVHltdrdllkRLGLIVLVVLGYLA-AWTAVNPPNVEVGLTLTSSGLKFNvC 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 739 NkgSSVAFHCTLGY-LCFLALGGYtMAFLSRTLPDSFNESKFLSLSLLVFFCVWITFLPVYHSTMGK----FMVATEIFS 813
Cdd:cd15293  154 S--LDWWDYVMAIAeLLFLLWGVY-LCYAVRKAPSAFNESRYISLAIYNELLLSVIFNIIRFFLLPSlhpdLLFLLFFLH 230
                        250       260
                 ....*....|....*....|.
gi 156119565 814 ILASSIALLSFIFAPKCYIIL 834
Cdd:cd15293  231 TQLTVTVTLLLIFGPKFYLVL 251
PBP1_GABAb_receptor cd06366
ligand-binding domain of GABAb receptors, which are metabotropic transmembrane receptors for ...
83-286 5.62e-10

ligand-binding domain of GABAb receptors, which are metabotropic transmembrane receptors for gamma-aminobutyric acid (GABA); Ligand-binding domain of GABAb receptors, which are metabotropic transmembrane receptors for gamma-aminobutyric acid (GABA). GABA is the major inhibitory neurotransmitter in the mammalian CNS and, like glutamate and other transmitters, acts via both ligand gated ion channels (GABAa receptors) and G-protein coupled receptors (GABAb receptor or GABAbR). GABAa receptors are members of the ionotropic receptor superfamily which includes alpha-adrenergic and glycine receptors. The GABAb receptor is a member of a receptor superfamily which includes the mGlu receptors. The GABAb receptor is coupled to G alpha-i proteins, and activation causes a decrease in calcium, an increase in potassium membrane conductance, and inhibition of cAMP formation. The response is thus inhibitory and leads to hyperpolarization and decreased neurotransmitter release, for example.


Pssm-ID: 380589 [Multi-domain]  Cd Length: 404  Bit Score: 62.26  E-value: 5.62e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  83 ILALIFAIEEINENPNLLSNislgfdfYNVRFTEKDTL------MNACIWLtAHREKYILpnykcgkkhftaALTGTSWT 156
Cdd:cd06366   21 LPAAEMALEHINNRSDILPG-------YNLELIWNDTQcdpglgLKALYDL-LYTPPPKV------------MLLGPGCS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 157 TS----AQMGTLFQLfkfPQLSFGPYDHILSDRNQYSSLYQMAPMASSLSLGIVSLLVHFRWSWVGLILPDDHKGNTILS 232
Cdd:cd06366   81 SVtepvAEASKYWNL---VQLSYAATSPALSDRKRYPYFFRTVPSDTAFNPARIALLKHFGWKRVATIYQNDEVFSSTAE 157
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 156119565 233 DFRNEMERKGVCIA----FLKMIPATWMshfnkfwKNMDETNVIIIYGDIDslEGLMR 286
Cdd:cd06366  158 DLEELLEEANITIVatesFSSEDPTDQL-------ENLKEKDARIIIGLFY--EDAAR 206
PBP1_ABC_transporter_GPCR_C-like cd04509
Family C of G-protein coupled receptors and their close homologs, the type 1 ...
81-286 7.56e-08

Family C of G-protein coupled receptors and their close homologs, the type 1 periplasmic-binding proteins of ATP-binding cassette transporter-like systems; This CD includes members of the family C of G-protein coupled receptors and their close homologs, the type 1 periplasmic-binding proteins of ATP-binding cassette transporter-like systems. The family C GPCR includes glutamate/glycine-gated ion channels such as the NMDA receptor, G-protein-coupled receptors, metabotropic glutamate, GABA-B, calcium sensing, pheromone receptors, and atrial natriuretic peptide-guanylate cyclase receptors. The glutamate receptors that form cation-selective ion channels, iGluR, can be classified into three different subgroups according to their binding-affinity for the agonists NMDA (N-methyl-D-asparate), AMPA (alpha-amino-3-dihydro-5-methyl-3-oxo-4-isoxazolepropionic acid), and kainate. L-glutamate is a major neurotransmitter in the brain of vertebrates and acts through either mGluRs or iGluRs. mGluRs subunits possess seven transmembrane segments and a large N-terminal extracellular domain. ABC-type leucine-isoleucine-valine binding protein (LIVBP) is a bacterial periplasmic binding protein that has homology with the amino-terminal domain of the glutamate-receptor ion channels (iGluRs). The extracellular regions of iGluRs are made of two PBP-like domains in tandem, a LIVBP-like domain that constitutes the N terminus (included in this model) followed by a domain related to lysine-arginine-ornithine-binding protein (LAOBP) that belongs to the type 2 periplasmic binding fold protein superfamily. The uncharacterized periplasmic components of various ABC-type transport systems are also included in this family.


Pssm-ID: 380490  Cd Length: 306  Bit Score: 55.00  E-value: 7.56e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  81 QYILALIFAIEEINENPNLLSNISLGFDFYN------VRFTEKDTLMNACIWLTAHREKYILPNYKCG-KKHFTAALTGT 153
Cdd:cd04509   28 QRFEAMEQALDDINADPNLLPNNTLGIVIYDdccdpkQALEQSNKFVNDLIQKDTSDVRCTNGEPPVFvKPEGIKGVIGH 107
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565 154 SWTTSAQM-GTLFQLFKFPQLSFGPYDHILSDRNQYSSLYQMAPMASSLSLGIVSLLVHFRWSWVGLILPDDHKGNTILS 232
Cdd:cd04509  108 LCSSVTIPvSNILELFGIPQITYAATAPELSDDRGYQLFLRVVPLDSDQAPAMADIVKEKVWQYVSIVHDEGQYGEGGAR 187
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 156119565 233 DFRNEMERKGVCIAFLKMIPA-TWMSHFNKFWKNMDETN---VIIIYGDIDSLEGLMR 286
Cdd:cd04509  188 AFQDGLKKGGLCIAFSDGITAgEKTKDFDRLVARLKKENnirFVVYFGYHPEMGQILR 245
PBP1_NPR_GC-like cd06352
ligand-binding domain of membrane guanylyl-cyclase receptors; Ligand-binding domain of ...
89-240 1.74e-03

ligand-binding domain of membrane guanylyl-cyclase receptors; Ligand-binding domain of membrane guanylyl-cyclase receptors. Membrane guanylyl cyclases (GC) have a single membrane-spanning region and are activated by endogenous and exogenous peptides. This family can be divided into three major subfamilies: the natriuretic peptide receptors (NPRs), sensory organ-specific membrane GCs, and the enterotoxin/guanylin receptors. The binding of peptide ligands to the receptor results in the activation of the cytosolic catalytic domain. Three types of NPRs have been cloned from mammalian tissues: NPR-A/GC-A, NPR-B/ GC-B, and NPR-C. In addition, two of the GCs, GC-D and GC-G, appear to be pseudogenes in humans. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are produced in the heart, and both bind to the NPR-A. NPR-C, also termed the clearance receptor, binds each of the natriuretic peptides and can alter circulating levels of these peptides. The ligand binding domain of the NPRs exhibits strong structural similarity to the type 1 periplasmic binding fold protein family.


Pssm-ID: 380575 [Multi-domain]  Cd Length: 391  Bit Score: 41.57  E-value: 1.74e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 156119565  89 AIEEINENPNLLSNISLGFDFYNVRFTEKDTLMNAciwLTAHREkyilpnYKCGkkhftaALTGTSWTTSAQ-MGTLFQL 167
Cdd:cd06352   27 AIERINSEGLLLPGFNFEFTYRDSCCDESEAVGAA---ADLIYK------RNVD------VFIGPACSAAADaVGRLATY 91
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 156119565 168 FKFPQLSFGPYDHILSDRNQYSSLYQMAPMASSLSLGIVSLLVHFRWSWVGLILPDDH-KGNTILSDFRNEMER 240
Cdd:cd06352   92 WNIPIITWGAVSASFLDKSRYPTLTRTSPNSLSLAEALLALLKQFNWKRAAIIYSDDDsKCFSIANDLEDALNQ 165
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH