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Conserved domains on  [gi|34328063|ref|NP_058672|]
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metabotropic glutamate receptor 1 isoform alpha precursor [Mus musculus]

Protein Classification

G-protein coupled receptor( domain architecture ID 11570924)

G-protein coupled receptor (GPCR) transmits physiological signals from the outside of the cell to the inside by binding to an extracellular agonist, which induces conformational changes that lead to the activation of heterotrimeric G proteins, which then bind to and activate numerous downstream effector proteins

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PBP1_mGluR_groupI cd06374
ligand binding domain of the group I metabotropic glutamate receptor; Ligand binding domain of ...
36-510 0e+00

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: 910.19  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   36 RSVARMDGDVIIGALFSVHHQPPAEKVPERKCGEIREQYGIQRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVA 115
Cdd:cd06374    1 RLVARMPGDIIIGALFPVHHQPPLKKVFSRKCGEIREQYGIQRVEAMFRTLDKINKDPNLLPNITLGIEIRDSCWYSPVA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  116 LEQSIEFIRDSLISIRDEKDGLNRCLPdgQTLPPGRTKKPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDK 195
Cdd:cd06374   81 LEQSIEFIRDSVASVEDEKDTQNTPDP--TPLSPPENRKPIVGVIGPGSSSVTIQVQNLLQLFHIPQIGYSATSIDLSDK 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  196 TLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESGMDAFKELAAQEGLCIAHSDKIYSNAGEKSFDRLLR 275
Cdd:cd06374  159 SLYKYFLRVVPSDYLQARAMLDIVKRYNWTYVSTVHTEGNYGESGIEAFKELAAEEGICIAHSDKIYSNAGEEEFDRLLR 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  276 KLRERLPKARVVVCFCEGMTVRGLLSAMRRLGVVGEFSLIGSDGWADRDEVIEGYEVEANGGITIKLQSPEVRSFDDYFL 355
Cdd:cd06374  239 KLMNTPNKARVVVCFCEGETVRGLLKAMRRLNATGHFLLIGSDGWADRKDVVEGYEDEAAGGITIKIHSPEVESFDEYYF 318
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  356 KLRLDTNTRNPWFPEFWQHRFQCRLPGHLLENPNFKKVCTGNESLEENYVQDSKMGFVINAIYAMAHGLQNMHHALCPGY 435
Cdd:cd06374  319 NLKPETNSRNPWFREFWQHRFDCRLPGHPDENPYFKKCCTGEESLLGNYVQDSKLGFVINAIYAMAHALHRMQEDLCGGY 398
                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34328063  436 -VGLCDAMKPIDGRKLLDFLIKSSFVGVSGEEVWFDEKGDAPGRYDIMNLQYTEANRYDYVHVGTWHEGVLNIDDY 510
Cdd:cd06374  399 sVGLCPAMLPINGSLLLDYLLNVSFVGVSGDTIMFDENGDPPGRYDIMNFQKTGEGSYDYVQVGSWKNGSLKMDDE 474
7tmC_mGluR1 cd15449
metabotropic glutamate receptor 1 in group 1, member of the class C family of ...
591-840 8.26e-158

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: 470.27  E-value: 8.26e-158
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  591 IESIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAM 670
Cdd:cd15449    1 IESIIAVAFSCLGILVTMFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAM 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  671 CYSALVTKTNRIARILAGSKKKICTRKPRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPILSYPSIKEVYLICNTSN 750
Cdd:cd15449   81 CYSALVTKTNRIARILAGSKKKICTRKPRFMSAWAQVVIASILISVQLTLVVTLIIMEPPMPILSYPSIKEVYLICNTSN 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  751 LGVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSNYKIITTCFAVSLSVTVALGCM 830
Cdd:cd15449  161 LGVVAPLGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSNYKIITTCFAVSLSVTVALGCM 240
                        250
                 ....*....|
gi 34328063  831 FTPKMYIIIA 840
Cdd:cd15449  241 FTPKMYIIIA 250
NCD3G pfam07562
Nine Cysteines Domain of family 3 GPCR; This conserved sequence contains several ...
521-571 2.06e-19

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: 82.69  E-value: 2.06e-19
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 34328063    521 RSVCSEPCLKGQIKVIRKGEVSCCWICTACKENEFVQ-DEFTCRACDLGWWP 571
Cdd:pfam07562    2 SSVCSESCPPGQRKSQQGGAPVCCWDCVPCPEGEISNtDSDTCKKCPEGQWP 53
GluR_Homer-bdg pfam10606
Homer-binding domain of metabotropic glutamate receptor; This is the proline-rich region of ...
1149-1199 1.09e-14

Homer-binding domain of metabotropic glutamate receptor; This is the proline-rich region of metabotropic glutamate receptor proteins that binds Homer-related synaptic proteins. The Homer proteins form a physical tether linking mGluRs with the inositol trisphosphate receptors (IP3R) that appears to be due to the proline-rich "Homer ligand" (PPXXFr). Activation of PI turnover triggers intracellular calcium release. MGluR function is altered in the mouse model of human Fragile X syndrome mental retardation, a disorder caused by loss of function mutations in the Fragile X mental retardation gene Fmr1. Homer 3 (and to a lesser extent Homer 1b/c) has been shown to form a multimeric complex with mGlu1a and the IP3 receptor, indicating that Homers may play a role in the localization of receptors to their signalling partners.


:

Pssm-ID: 431390  Cd Length: 51  Bit Score: 69.41  E-value: 1.09e-14
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 34328063   1149 ALTPPSPFRDSVASGSSVPSSPVSESVLCTPPNVTYASVILRDYKQSSSTL 1199
Cdd:pfam10606    1 ALTPPSPFRDSVCSGSSSPGSPVSESMLCSPPSPTYTSLILRDYSQSSSTL 51
 
Name Accession Description Interval E-value
PBP1_mGluR_groupI cd06374
ligand binding domain of the group I metabotropic glutamate receptor; Ligand binding domain of ...
36-510 0e+00

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: 910.19  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   36 RSVARMDGDVIIGALFSVHHQPPAEKVPERKCGEIREQYGIQRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVA 115
Cdd:cd06374    1 RLVARMPGDIIIGALFPVHHQPPLKKVFSRKCGEIREQYGIQRVEAMFRTLDKINKDPNLLPNITLGIEIRDSCWYSPVA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  116 LEQSIEFIRDSLISIRDEKDGLNRCLPdgQTLPPGRTKKPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDK 195
Cdd:cd06374   81 LEQSIEFIRDSVASVEDEKDTQNTPDP--TPLSPPENRKPIVGVIGPGSSSVTIQVQNLLQLFHIPQIGYSATSIDLSDK 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  196 TLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESGMDAFKELAAQEGLCIAHSDKIYSNAGEKSFDRLLR 275
Cdd:cd06374  159 SLYKYFLRVVPSDYLQARAMLDIVKRYNWTYVSTVHTEGNYGESGIEAFKELAAEEGICIAHSDKIYSNAGEEEFDRLLR 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  276 KLRERLPKARVVVCFCEGMTVRGLLSAMRRLGVVGEFSLIGSDGWADRDEVIEGYEVEANGGITIKLQSPEVRSFDDYFL 355
Cdd:cd06374  239 KLMNTPNKARVVVCFCEGETVRGLLKAMRRLNATGHFLLIGSDGWADRKDVVEGYEDEAAGGITIKIHSPEVESFDEYYF 318
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  356 KLRLDTNTRNPWFPEFWQHRFQCRLPGHLLENPNFKKVCTGNESLEENYVQDSKMGFVINAIYAMAHGLQNMHHALCPGY 435
Cdd:cd06374  319 NLKPETNSRNPWFREFWQHRFDCRLPGHPDENPYFKKCCTGEESLLGNYVQDSKLGFVINAIYAMAHALHRMQEDLCGGY 398
                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34328063  436 -VGLCDAMKPIDGRKLLDFLIKSSFVGVSGEEVWFDEKGDAPGRYDIMNLQYTEANRYDYVHVGTWHEGVLNIDDY 510
Cdd:cd06374  399 sVGLCPAMLPINGSLLLDYLLNVSFVGVSGDTIMFDENGDPPGRYDIMNFQKTGEGSYDYVQVGSWKNGSLKMDDE 474
7tmC_mGluR1 cd15449
metabotropic glutamate receptor 1 in group 1, member of the class C family of ...
591-840 8.26e-158

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: 470.27  E-value: 8.26e-158
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  591 IESIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAM 670
Cdd:cd15449    1 IESIIAVAFSCLGILVTMFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAM 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  671 CYSALVTKTNRIARILAGSKKKICTRKPRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPILSYPSIKEVYLICNTSN 750
Cdd:cd15449   81 CYSALVTKTNRIARILAGSKKKICTRKPRFMSAWAQVVIASILISVQLTLVVTLIIMEPPMPILSYPSIKEVYLICNTSN 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  751 LGVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSNYKIITTCFAVSLSVTVALGCM 830
Cdd:cd15449  161 LGVVAPLGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSNYKIITTCFAVSLSVTVALGCM 240
                        250
                 ....*....|
gi 34328063  831 FTPKMYIIIA 840
Cdd:cd15449  241 FTPKMYIIIA 250
ANF_receptor pfam01094
Receptor family ligand binding region; This family includes extracellular ligand binding ...
77-487 1.07e-82

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: 273.88  E-value: 1.07e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063     77 QRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVALEQSIEFIrdslisirdekdglnrclpdgqtlppgrtKKPI 156
Cdd:pfam01094    1 LVLLAVRLAVEDINADPGLLPGTKLEYIILDTCCDPSLALAAALDLL-----------------------------KGEV 51
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063    157 AGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNY 236
Cdd:pfam01094   52 VAIIGPSCSSVASAVASLANEWKVPLISYGSTSPALSDLNRYPTFLRTTPSDTSQADAIVDILKHFGWKRVALIYSDDDY 131
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063    237 GESGMDAFKELAAQEGLCIAHSDKIYSNAGEKsfDRLLRKLRERLPKARVVVCFCEGMTVRGLLSAMRRLGVVGE-FSLI 315
Cdd:pfam01094  132 GESGLQALEDALRERGIRVAYKAVIPPAQDDD--EIARKLLKEVKSRARVIVVCCSSETARRLLKAARELGMMGEgYVWI 209
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063    316 GSDGWADRDEVIEG-YEVEANGGITIKLQSPEVRSFDDYFLKLrldtntrnpwfpefwqhrfqcrlpghllenpnfkkvc 394
Cdd:pfam01094  210 ATDGLTTSLVILNPsTLEAAGGVLGFRLHPPDSPEFSEFFWEK------------------------------------- 252
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063    395 tgNESLEENYVQDSKMGFV-----INAIYAMAHGLQNMHHALCPGYVglCDAMKPID-GRKLLDFLIKSSFVGVSGeEVW 468
Cdd:pfam01094  253 --LSDEKELYENLGGLPVSygalaYDAVYLLAHALHNLLRDDKPGRA--CGALGPWNgGQKLLRYLKNVNFTGLTG-NVQ 327
                          410       420
                   ....*....|....*....|
gi 34328063    469 FDEKGDAP-GRYDIMNLQYT 487
Cdd:pfam01094  328 FDENGDRInPDYDILNLNGS 347
7tm_3 pfam00003
7 transmembrane sweet-taste receptor of 3 GCPR; This is a domain of seven transmembrane ...
586-834 1.37e-74

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: 247.57  E-value: 1.37e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063    586 LEWSDIESIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTsCYLQRLLVG 665
Cdd:pfam00003    1 LDLSAPWGIVLEALAALGILLTLVLLVVFLLHRKTPIVKASNRSLSFLLLLGLLLLFLLAFLFIGKPTVT-CALRRFLFG 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063    666 LSSAMCYSALVTKTNRIARILAGSKKkictrkprFMSAWAQVIIASILISVQLTLVVTLIIMePPMPILSYPSIKEVYLI 745
Cdd:pfam00003   80 VGFTLCFSCLLAKTFRLVLIFRRRKP--------GPRGWQLLLLALGLLLVQVIILTEWLID-PPFPEKDNLSEGKIILE 150
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063    746 CNTSN----LGVVapVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSNYK------IITT 815
Cdd:pfam00003  151 CEGSTsiafLDFV--LAYVGLLLLAGFLLAFKTRKLPDNFNEAKFITFSMLLSVLIWVAFIPMYLYGNKGkgtwdpVALA 228
                          250
                   ....*....|....*....
gi 34328063    816 CFAVSLSVTVALGCMFTPK 834
Cdd:pfam00003  229 IFAILASGWVLLGLYFIPK 247
NCD3G pfam07562
Nine Cysteines Domain of family 3 GPCR; This conserved sequence contains several ...
521-571 2.06e-19

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: 82.69  E-value: 2.06e-19
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 34328063    521 RSVCSEPCLKGQIKVIRKGEVSCCWICTACKENEFVQ-DEFTCRACDLGWWP 571
Cdd:pfam07562    2 SSVCSESCPPGQRKSQQGGAPVCCWDCVPCPEGEISNtDSDTCKKCPEGQWP 53
LivK COG0683
ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid ...
156-308 1.61e-16

ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid transport and metabolism];


Pssm-ID: 440447 [Multi-domain]  Cd Length: 314  Bit Score: 81.90  E-value: 1.61e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  156 IAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYKYFLRVVPSDTLQARAMLD-IVKRYNWTYVSAVHTEG 234
Cdd:COG0683   72 VDAIVGPLSSGVALAVAPVAEEAGVPLISPSATAPALTGPECSPYVFRTAPSDAQQAEALADyLAKKLGAKKVALLYDDY 151
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 34328063  235 NYGESGMDAFKELAAQEGLCIAHSDKIysNAGEKSFDRLLRKLRERLPKArvVVCFCEGMTVRGLLSAMRRLGV 308
Cdd:COG0683  152 AYGQGLAAAFKAALKAAGGEVVGEEYY--PPGTTDFSAQLTKIKAAGPDA--VFLAGYGGDAALFIKQAREAGL 221
GluR_Homer-bdg pfam10606
Homer-binding domain of metabotropic glutamate receptor; This is the proline-rich region of ...
1149-1199 1.09e-14

Homer-binding domain of metabotropic glutamate receptor; This is the proline-rich region of metabotropic glutamate receptor proteins that binds Homer-related synaptic proteins. The Homer proteins form a physical tether linking mGluRs with the inositol trisphosphate receptors (IP3R) that appears to be due to the proline-rich "Homer ligand" (PPXXFr). Activation of PI turnover triggers intracellular calcium release. MGluR function is altered in the mouse model of human Fragile X syndrome mental retardation, a disorder caused by loss of function mutations in the Fragile X mental retardation gene Fmr1. Homer 3 (and to a lesser extent Homer 1b/c) has been shown to form a multimeric complex with mGlu1a and the IP3 receptor, indicating that Homers may play a role in the localization of receptors to their signalling partners.


Pssm-ID: 431390  Cd Length: 51  Bit Score: 69.41  E-value: 1.09e-14
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 34328063   1149 ALTPPSPFRDSVASGSSVPSSPVSESVLCTPPNVTYASVILRDYKQSSSTL 1199
Cdd:pfam10606    1 ALTPPSPFRDSVCSGSSSPGSPVSESMLCSPPSPTYTSLILRDYSQSSSTL 51
 
Name Accession Description Interval E-value
PBP1_mGluR_groupI cd06374
ligand binding domain of the group I metabotropic glutamate receptor; Ligand binding domain of ...
36-510 0e+00

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: 910.19  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   36 RSVARMDGDVIIGALFSVHHQPPAEKVPERKCGEIREQYGIQRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVA 115
Cdd:cd06374    1 RLVARMPGDIIIGALFPVHHQPPLKKVFSRKCGEIREQYGIQRVEAMFRTLDKINKDPNLLPNITLGIEIRDSCWYSPVA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  116 LEQSIEFIRDSLISIRDEKDGLNRCLPdgQTLPPGRTKKPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDK 195
Cdd:cd06374   81 LEQSIEFIRDSVASVEDEKDTQNTPDP--TPLSPPENRKPIVGVIGPGSSSVTIQVQNLLQLFHIPQIGYSATSIDLSDK 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  196 TLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESGMDAFKELAAQEGLCIAHSDKIYSNAGEKSFDRLLR 275
Cdd:cd06374  159 SLYKYFLRVVPSDYLQARAMLDIVKRYNWTYVSTVHTEGNYGESGIEAFKELAAEEGICIAHSDKIYSNAGEEEFDRLLR 238
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  276 KLRERLPKARVVVCFCEGMTVRGLLSAMRRLGVVGEFSLIGSDGWADRDEVIEGYEVEANGGITIKLQSPEVRSFDDYFL 355
Cdd:cd06374  239 KLMNTPNKARVVVCFCEGETVRGLLKAMRRLNATGHFLLIGSDGWADRKDVVEGYEDEAAGGITIKIHSPEVESFDEYYF 318
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  356 KLRLDTNTRNPWFPEFWQHRFQCRLPGHLLENPNFKKVCTGNESLEENYVQDSKMGFVINAIYAMAHGLQNMHHALCPGY 435
Cdd:cd06374  319 NLKPETNSRNPWFREFWQHRFDCRLPGHPDENPYFKKCCTGEESLLGNYVQDSKLGFVINAIYAMAHALHRMQEDLCGGY 398
                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34328063  436 -VGLCDAMKPIDGRKLLDFLIKSSFVGVSGEEVWFDEKGDAPGRYDIMNLQYTEANRYDYVHVGTWHEGVLNIDDY 510
Cdd:cd06374  399 sVGLCPAMLPINGSLLLDYLLNVSFVGVSGDTIMFDENGDPPGRYDIMNFQKTGEGSYDYVQVGSWKNGSLKMDDE 474
PBP1_mGluR cd06362
ligand binding domain of metabotropic glutamate receptors (mGluR); Ligand binding domain of ...
43-509 0e+00

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: 652.05  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   43 GDVIIGALFSVHHQPPaekvPERKCGEIREQYGIQRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVALEQSIEF 122
Cdd:cd06362    1 GDINLGGLFPVHERSS----SGECCGEIREERGIQRLEAMLFAIDEINSRPDLLPNITLGFVILDDCSSDTTALEQALHF 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  123 IRDSLISIRDEKDglNRCLPDGQTLPPGRTKKPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYKYFL 202
Cdd:cd06362   77 IRDSLLSQESAGF--CQCSDDPPNLDESFQFYDVVGVIGAESSSVSIQVANLLRLFKIPQISYASTSDELSDKERYPYFL 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  203 RVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESGMDAFKELAAQEGLCIAHSDKIYSNAGEKSFDrLLRKLRERLP 282
Cdd:cd06362  155 RTVPSDSFQAKAIVDILLHFNWTYVSVVYSEGSYGEEGYKAFKKLARKAGICIAESERISQDSDEKDYD-DVIQKLLQKK 233
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  283 KARVVVCFCEGMTVRGLLSAMRRLGVVGEFSLIGSDGWADRDEVIEGYEVEANGGITIKLQSPEVRSFDDYFLKLRLDTN 362
Cdd:cd06362  234 NARVVVLFADQEDIRGLLRAAKRLGASGRFIWLGSDGWGTNIDDLKGNEDVALGALTVQPYSEEVPRFDDYFKSLTPSNN 313
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  363 TRNPWFPEFWQHRFQCRLPGhllENPNFKKVCTGNESLEENYVQDSKMGFVINAIYAMAHGLQNMHHALCPGYVGLC-DA 441
Cdd:cd06362  314 TRNPWFREFWQELFQCSFRP---SRENSCNDDKLLINKSEGYKQESKVSFVIDAVYAFAHALHKMHKDLCPGDTGLCqDL 390
                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  442 MKPIDGRKLLDFLIKSSFVGVSGEEVWFDEKGDAPGRYDIMNLQYTEANRYDYVHVGTWH--EGVLNIDD 509
Cdd:cd06362  391 MKCIDGSELLEYLLNVSFTGEAGGEIRFDENGDGPGRYDIMNFQRNNDGSYEYVRVGVWDqyTQKLSLND 460
7tmC_mGluR1 cd15449
metabotropic glutamate receptor 1 in group 1, member of the class C family of ...
591-840 8.26e-158

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: 470.27  E-value: 8.26e-158
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  591 IESIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAM 670
Cdd:cd15449    1 IESIIAVAFSCLGILVTMFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAM 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  671 CYSALVTKTNRIARILAGSKKKICTRKPRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPILSYPSIKEVYLICNTSN 750
Cdd:cd15449   81 CYSALVTKTNRIARILAGSKKKICTRKPRFMSAWAQVVIASILISVQLTLVVTLIIMEPPMPILSYPSIKEVYLICNTSN 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  751 LGVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSNYKIITTCFAVSLSVTVALGCM 830
Cdd:cd15449  161 LGVVAPLGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSNYKIITTCFAVSLSVTVALGCM 240
                        250
                 ....*....|
gi 34328063  831 FTPKMYIIIA 840
Cdd:cd15449  241 FTPKMYIIIA 250
PBP1_mGluR_groupIII cd06376
ligand-binding domain of the group III metabotropic glutamate receptor; Ligand-binding domain ...
40-509 1.02e-157

ligand-binding domain of the group III metabotropic glutamate receptor; Ligand-binding domain of the group III metabotropic glutamate receptor, a family which contains mGlu4R, mGluR6R, mGluR7, and mGluR8; 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: 380599 [Multi-domain]  Cd Length: 467  Bit Score: 478.91  E-value: 1.02e-157
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   40 RMDGDVIIGALFSVHhqppAEKVPERKCGEIREQYGIQRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVALEQS 119
Cdd:cd06376    2 RVEGDITLGGLFPVH----ARGLAGVPCGEIKKEKGIHRLEAMLYALDQINSDPDLLPNVTLGARILDTCSRDTYALEQS 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  120 IEFIRdSLISiRDEKDGlnRClPDGQtlPPGRTK-KPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLY 198
Cdd:cd06376   78 LTFVQ-ALIQ-KDTSDV--RC-TNGD--PPVFVKpEKVVGVIGASASSVSIMVANILRLFQIPQISYASTAPELSDDRRY 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  199 KYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESGMDAFKELAAQEG-LCIAHSDKIYSNAGEKSFDrLLRKL 277
Cdd:cd06376  151 DFFSRVVPPDSFQAQAMVDIVKALGWNYVSTLASEGNYGEKGVESFVQISREAGgVCIAQSEKIPRERRTGDFD-KIIKR 229
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  278 RERLPKARVVVCFCEGMTVRGLLSAMRRLGVVGEFSLIGSDGWADRDEVIEGYEVEANGGITIKLQSPEVRSFDDYFLKL 357
Cdd:cd06376  230 LLETPNARAVVIFADEDDIRRVLAAAKRANKTGHFLWVGSDSWGAKISPVLQQEDVAEGAITILPKRASIEGFDAYFTSR 309
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  358 RLDTNTRNPWFPEFWQHRFQCRLPGHLLENPNFKKVCTGNESL--EENYVQDSKMGFVINAIYAMAHGLQNMHHALCPGY 435
Cdd:cd06376  310 TLENNRRNVWFAEFWEENFNCKLTSSGSKKEDTLRKCTGQERIgrDSGYEQEGKVQFVVDAVYAMAHALHNMNKDLCPGY 389
                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 34328063  436 VGLCDAMKPIDGRKLLDFLIKSSFVGVSGEEVWFDEKGDAPGRYDIMNLQYTEANRYDYVHVGTWHEG-VLNIDD 509
Cdd:cd06376  390 RGLCPEMEPAGGKKLLKYIRNVNFNGSAGTPVMFNKNGDAPGRYDIFQYQTTNGSNYGYRLIGQWTDElQLNIED 464
PBP1_ABC_transporter_GPCR_C-like cd04509
Family C of G-protein coupled receptors and their close homologs, the type 1 ...
46-342 2.39e-155

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: 466.40  E-value: 2.39e-155
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   46 IIGALFSVHHQPPAEkvpeRKCGEIREQYGIQRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVALEQSIEFIRD 125
Cdd:cd04509    1 KVGVLFAVHGKGPSG----VPCGDIVAQYGIQRFEAMEQALDDINADPNLLPNNTLGIVIYDDCCDPKQALEQSNKFVND 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  126 SLISIRDEKDGLNrclpdgQTLPPGRTKKPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYKYFLRVV 205
Cdd:cd04509   77 LIQKDTSDVRCTN------GEPPVFVKPEGIKGVIGHLCSSVTIPVSNILELFGIPQITYAATAPELSDDRGYQLFLRVV 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  206 PSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESGMDAFKELAAQEGLCIAHSDKIYSNAGEKSFDRLLRKLRERLPkAR 285
Cdd:cd04509  151 PLDSDQAPAMADIVKEKVWQYVSIVHDEGQYGEGGARAFQDGLKKGGLCIAFSDGITAGEKTKDFDRLVARLKKENN-IR 229
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 34328063  286 VVVCFCEGMTVRGLLSAMRRLGVVGEFSLIGSDGWADRDEVIEGYEVEANGGITIKL 342
Cdd:cd04509  230 FVVYFGYHPEMGQILRAARRAGLVGKFQFMGSDGWANVSLSLNIAEESAEGLITIKP 286
PBP1_mGluR_groupII cd06375
ligand binding domain of the group II metabotropic glutamate receptor; Ligand binding domain ...
40-504 1.30e-151

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: 462.75  E-value: 1.30e-151
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   40 RMDGDVIIGALFSVHhqppaEK-VPERKCGEIREQYGIQRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVALEQ 118
Cdd:cd06375    2 KLEGDLVLGGLFPVH-----EKgEGMEECGRINEDRGIQRLEAMLFAIDRINRDPHLLPGVRLGVHILDTCSRDTYALEQ 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  119 SIEFIRDSLISIrdeKDGLNRCLPDGQTLPPGRTKKPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLY 198
Cdd:cd06375   77 SLEFVRASLTKV---DDSEYMCPDDGSYAIQEDSPLPIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRY 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  199 KYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESGMDAFKELAAQEGLCIAHSDKIYSNAGEKSFDrLLRKLR 278
Cdd:cd06375  154 DYFARTVPPDFYQAKAMAEILRFFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSADRKSFD-GVIREL 232
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  279 ERLPKARVVVCFCEGMTVRGLLSAMRRLGVvgEFSLIGSDGWADRDEVIEGYEVEANGGITIKLQSPEVRSFDDYFLKLR 358
Cdd:cd06375  233 LQKPNARVVVLFTRSDDARELLAAAKRLNA--SFTWVASDGWGAQESIVKGSEDVAEGAITLELASHPIPDFDRYFQSLT 310
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  359 LDTNTRNPWFPEFWQHRFQCRLPGhlleNPNFKKVCTGNESLEE-NYVQDSKMGFVINAIYAMAHGLQNMHHALCPGYVG 437
Cdd:cd06375  311 PYNNHRNPWFRDFWEQKFQCSLQN----KSQAASVSDKHLSIDSsNYEQESKIMFVVNAVYAMAHALHNMQRTLCPNTTR 386
                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 34328063  438 LCDAMKPIDGRKLL-DFLIKSSFVGV-----SGEEVWFDEKGDAPGRYDIMNLQYTEAN-RYDYVHVGTWHEGV 504
Cdd:cd06375  387 LCDAMRSLDGKKLYkDYLLNVSFTAPfppadAGSEVKFDAFGDGLGRYNIFNYQRAGGSyGYRYKGVGKWANSL 460
7tmC_mGluR_group1 cd15285
metabotropic glutamate receptors in group 1, member of the class C family of ...
592-839 7.94e-150

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: 449.39  E-value: 7.94e-150
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  592 ESIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMC 671
Cdd:cd15285    2 EAIVAMVFACVGILATLFVTVVFIRHNDTPVVKASTRELSYIILAGILLCYASTFALLAKPSTISCYLQRILPGLSFAMI 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  672 YSALVTKTNRIARILAGSKKKICTRKPRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPILSYPSIKEVYLICNTSNL 751
Cdd:cd15285   82 YAALVTKTNRIARILAGSKKKILTRKPRFMSASAQVVITGILISVEVAIIVVMLILEPPDATLDYPTPKRVRLICNTSTL 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  752 GVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSNYKIITTCFAVSLSVTVALGCMF 831
Cdd:cd15285  162 GFVVPLGFDFLLILLCTLYAFKTRNLPENFNEAKFIGFTMYTTCVIWLAFLPIYFGSDNKEITLCFSVSLSATVALVFLF 241

                 ....*...
gi 34328063  832 TPKMYIII 839
Cdd:cd15285  242 FPKVYIIL 249
7tmC_mGluR5 cd15450
metabotropic glutamate receptor 5 in group 1, member of the class C family of ...
592-840 1.51e-129

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: 396.28  E-value: 1.51e-129
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  592 ESIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMC 671
Cdd:cd15450    2 EPIAAVVFACLGLLATLFVTVIFIIYRDTPVVKSSSRELCYIILAGICLGYLCTFCLIAKPKQIYCYLQRIGIGLSPAMS 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  672 YSALVTKTNRIARILAGSKKKICTRKPRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPILSYPSIKEVYLICNTSNL 751
Cdd:cd15450   82 YSALVTKTNRIARILAGSKKKICTKKPRFMSACAQLVIAFILICIQLGIIVALFIMEPPDIMHDYPSIREVYLICNTTNL 161
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  752 GVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSNYKIITTCFAVSLSVTVALGCMF 831
Cdd:cd15450  162 GVVTPLGYNGLLILSCTFYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSNYKIITMCFSVSLSATVALGCMF 241

                 ....*....
gi 34328063  832 TPKMYIIIA 840
Cdd:cd15450  242 VPKVYIILA 250
PBP1_GPCR_family_C-like cd06350
ligand-binding domain of membrane-bound glutamate receptors that mediate excitatory ...
46-509 1.98e-122

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: 381.64  E-value: 1.98e-122
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   46 IIGALFSVHHQPPAEKvperKCGEIREQYGIQRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVALEQSIEFIRD 125
Cdd:cd06350    1 IIGGLFPVHYRDDADF----CCCGILNPRGVQLVEAMIYAIEEINNDSSLLPNVTLGYDIRDTCSSSSVALESSLEFLLD 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  126 SLISIRDEKDGlnrclpdgqtlpPGRTKKPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYKYFLRVV 205
Cdd:cd06350   77 NGIKLLANSNG------------QNIGPPNIVAVIGAASSSVSIAVANLLGLFKIPQISYASTSPELSDKIRYPYFLRTV 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  206 PSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESGMDAFKELAAQEGLCIAHSDKIYSNAGEKSFDrLLRKLRERLPKAR 285
Cdd:cd06350  145 PSDTLQAKAIADLLKHFNWNYVSTVYSDDDYGRSGIEAFEREAKERGICIAQTIVIPENSTEDEIK-RIIDKLKSSPNAK 223
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  286 VVVCFCEGMTVRGLLSAMRRLGVVGeFSLIGSDGWADRDEVIEGYEVEANGGITIKLQSPEVRSFDDYFLklrldtntrn 365
Cdd:cd06350  224 VVVLFLTESDARELLKEAKRRNLTG-FTWIGSDGWGDSLVILEGYEDVLGGAIGVVPRSKEIPGFDDYLK---------- 292
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  366 pwfpefwqhrfqcrlpghllenpnfkkvctgnesleenyvqdSKMGFVINAIYAmahglqnmhhalcpgyvglcdamkpi 445
Cdd:cd06350  293 ------------------------------------------SYAPYVIDAVYA-------------------------- 304
                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34328063  446 dgrklldflikssfvgvsgeEVWFDEKGDAPGRYDIMNLQYTEANRYDYVHVGTWH--EGVLNIDD 509
Cdd:cd06350  305 --------------------TVKFDENGDGNGGYDIVNLQRTGTGNYEYVEVGTWDsnSGGLSLNS 350
7tmC_mGluRs cd15045
metabotropic glutamate receptors, member of the class C family of seven-transmembrane G ...
593-839 1.74e-121

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: 375.04  E-value: 1.74e-121
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  593 SIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCY 672
Cdd:cd15045    3 AIGAMAFASLGILLTLFVLVVFVRYRDTPVVKASGRELSYVLLAGILLSYVMTFVLVAKPSTIVCGLQRFGLGLCFTVCY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  673 SALVTKTNRIARILAGSKKKIctRKPRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPILSYP-SIKEVYLICNTSNL 751
Cdd:cd15045   83 AAILTKTNRIARIFRLGKKSA--KRPRFISPRSQLVITGLLVSVQVLVLAVWLILSPPRATHHYPtRDKNVLVCSSALDA 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  752 GVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGS----NYKIITTCFAVSLSVTVAL 827
Cdd:cd15045  161 SYLIGLAYPILLIILCTVYAFKTRKIPEGFNEAKYIGFTMYTTCIIWLAFVPLYFTTasniEVRITTLSVSISLSATVQL 240
                        250
                 ....*....|..
gi 34328063  828 GCMFTPKMYIII 839
Cdd:cd15045  241 ACLFAPKVYIIL 252
7tmC_mGluRs_group2_3 cd15934
metabotropic glutamate receptors in group 2 and 3, member of the class C family of ...
593-839 5.11e-112

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: 349.99  E-value: 5.11e-112
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  593 SIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCY 672
Cdd:cd15934    3 AIVPVVFALLGILATLFVIVVFIRYNDTPVVKASGRELSYVLLTGILLCYLMTFVLLAKPSVITCALRRLGLGLGFSICY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  673 SALVTKTNRIARILAGSKKKicTRKPRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPILSYPSIKEVYLICNTSNLG 752
Cdd:cd15934   83 AALLTKTNRISRIFNSGKRS--AKRPRFISPKSQLVICLGLISVQLIGVLVWLVVEPPGTRIDYPRRDQVVLKCKISDSS 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  753 VVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFG--SNYKIITT--CFAVSLSVTVALG 828
Cdd:cd15934  161 LLISLVYNMLLIILCTVYAFKTRKIPENFNEAKFIGFTMYTTCIIWLAFVPIYFGtsNDFKIQTTtlCVSISLSASVALG 240
                        250
                 ....*....|.
gi 34328063  829 CMFTPKMYIII 839
Cdd:cd15934  241 CLFAPKVYIIL 251
PBP1_glutamate_receptors-like cd06269
ligand-binding domain of family C G-protein couples receptors (GPCRs), membrane bound guanylyl ...
46-508 4.56e-103

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: 328.99  E-value: 4.56e-103
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   46 IIGALFSVHHqppaekvperkcgeiREQYGIQRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVALEQSIEFIRD 125
Cdd:cd06269    1 TIGALLPVHD---------------YLESGAKVLPAFELALSDVNSRPDLLPKTTLGLAIRDSECNPTQALLSACDLLAA 65
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  126 slisirdekdglnrclpdgqtlppgrtkKPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYKYFLRVV 205
Cdd:cd06269   66 ----------------------------AKVVAILGPGCSASAAPVANLARHWDIPVLSYGATAPGLSDKSRYAYFLRTV 117
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  206 PSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESGMDAFKELAAQEGLCIAHSDKIYSNAgEKSFDRLLRKLRERLpkAR 285
Cdd:cd06269  118 PPDSKQADAMLALVRRLGWNKVVLIYSDDEYGEFGLEGLEELFQEKGGLITSRQSFDENK-DDDLTKLLRNLRDTE--AR 194
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  286 VVVCFCEGMTVRGLLSAMRRLGVVG-EFSLIGSDGWADR-DEVIEGYEVEANGGITIKLQSPEVRSFDDYFLKLRLdtnt 363
Cdd:cd06269  195 VIILLASPDTARSLMLEAKRLDMTSkDYVWFVIDGEASSsDEHGDEARQAAEGAITVTLIFPVVKEFLKFSMELKL---- 270
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  364 rnpwfpefwqhrfqcrlpghllenpnfkKVCTGNESLEENYVQDSKMGFVINAIYAmahglqnmhhalcpgyvglcdamk 443
Cdd:cd06269  271 ----------------------------KSSKRKQGLNEEYELNNFAAFFYDAVLA------------------------ 298
                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34328063  444 pidgrklldflikssfvgvsgeevwfdekgDAPGRYDIMNLQYTEanRYDYVHVGTWH-EGVLNID 508
Cdd:cd06269  299 ------------------------------DRPGQFSIINLQYTE--AGDYRKVGTWDsEGGLNMS 332
Periplasmic_Binding_Protein_type1 cd01391
Type 1 periplasmic binding fold superfamily; Type 1 periplasmic binding fold superfamily. This ...
46-481 1.45e-91

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.


Pssm-ID: 380477 [Multi-domain]  Cd Length: 280  Bit Score: 295.72  E-value: 1.45e-91
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   46 IIGALFSVHHQppaekvperkcgeIREQYGIQRVEAMFHTLDKINAdpvllpnitlGSEIRDSCWHSSVALEQSIEFIRD 125
Cdd:cd01391    1 IIGVVTSSLHQ-------------IREQFGIQRVEAIFHTADKLGA----------SVEIRDSCWHGSVALEQSIEFIRD 57
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  126 slisirdekdglnrclpdgqtlppgrtkkPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYKYFLRVV 205
Cdd:cd01391   58 -----------------------------NIAGVIGPGSSSVAIVIQNLAQLFDIPQLALDATSQDLSDKTLYKYFLSVV 108
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  206 PSDTLQARAMLDIVKRYNWTYVSAVHTE-GNYGESGMDAFKELAAQEGLCIAHSDKIYSNAGEKSFDrLLRKLRERLPKA 284
Cdd:cd01391  109 FSDTLGARLGLDIVKRKNWTYVAAIHGEgLNSGELRMAGFKELAKQEGICIVASDKADWNAGEKGFD-RALRKLREGLKA 187
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  285 RVVVCFCEgMTVRGLLSAMRRLGVVGEFSLIGSDGWADRDEVieGYEVEANGGITIKLQspevrsfddyflklrldtntr 364
Cdd:cd01391  188 RVIVCAND-MTARGVLSAMRRLGLVGDVSVIGSDGWADRDEV--GYEVEANGLTTIKQQ--------------------- 243
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  365 npwfpefwqhrfqcrlpghllenpnfkkvctgnesleenyvqdsKMGFVINAIYAMAHGLQNMHhalcpgyvglcdamkp 444
Cdd:cd01391  244 --------------------------------------------KMGFGITAIKAMADGSQNMH---------------- 263
                        410       420       430
                 ....*....|....*....|....*....|....*..
gi 34328063  445 idgrklldflikssfvgvsgEEVWFDEKGDAPGRYDI 481
Cdd:cd01391  264 --------------------EEVWFDEKGDALGRYIL 280
7tm_classC_mGluR-like cd13953
metabotropic glutamate receptor-like class C family of seven-transmembrane G protein-coupled ...
593-839 1.18e-85

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: 278.35  E-value: 1.18e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  593 SIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCY 672
Cdd:cd13953    3 AIVLLVLAALGLLLTIFIWVVFIRYRNTPVVKASNRELSYLLLFGILLCFLLAFLFLLPPSDVLCGLRRFLFGLSFTLVF 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  673 SALVTKTNRIARILagSKKKICTRKPRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPILSYPSIKEVYLIC-NTSNL 751
Cdd:cd13953   83 STLLVKTNRIYRIF--KSGLRSSLRPKLLSNKSQLLLVLFLLLVQVAILIVWLILDPPKVEKVIDSDNKVVELCcSTGNI 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  752 GVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGS--NYKIITTCFAVSLSVTVALGC 829
Cdd:cd13953  161 GLILSLVYNILLLLICTYLAFKTRKLPDNFNEARYIGFSSLLSLVIWIAFIPTYFTTsgPYRDAILSFGLLLNATVLLLC 240
                        250
                 ....*....|
gi 34328063  830 MFTPKMYIII 839
Cdd:cd13953  241 LFLPKIYIIL 250
PBP1_CaSR cd06364
ligand-binding domain of the CaSR calcium-sensing receptor, a member of the family C receptors ...
46-516 5.44e-85

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: 284.92  E-value: 5.44e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   46 IIGALFSVHHQPPAEKV-----PERKCGEIREQYGIQRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVALEQSI 120
Cdd:cd06364    1 IIGGLFPIHFRPVSPDPdfttePHSPECEGFNFRGFRWAQTMIFAIEEINNSPDLLPNITLGYRIYDSCATISKALRAAL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  121 efirdSLISIRDEKDGLNRClpdgqtlppgRTKKPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYKY 200
Cdd:cd06364   81 -----ALVNGQEETNLDERC----------SGGPPVAAVIGESGSTLSIAVARTLGLFYIPQVSYFASCACLSDKKQFPS 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  201 FLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESGMDAFKELAAQEGLCIAHSDKIYSNAGEKSFDRLLRKLRER 280
Cdd:cd06364  146 FLRTIPSDYYQSRALAQLVKHFGWTWVGAIASDDDYGRNGIKAFLEEAEKLGICIAFSETIPRTYSQEKILRIVEVIKKS 225
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  281 LpkARVVVCFCEGMTVRGLLSAMRRLGVVGeFSLIGSDGWADrDEVI---EGYEVeANGGITIKLQSPEVRSFDDYFLKL 357
Cdd:cd06364  226 T--AKVIVVFSSEGDLEPLIKELVRQNITG-RQWIASEAWIT-SSLLatpEYFPV-LGGTIGFAIRRGEIPGLKEFLLRV 300
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  358 RLDTNTRNPWFPEFWQHRFQCRLPGHLLENPNFK--KVCTGNESLE--ENYVQD-SKMGF---VINAIYAMAHGLQNMHH 429
Cdd:cd06364  301 HPSKSPSNPFVKEFWEETFNCSLSSSSKSNSSSSsrPPCTGSENLEnvQNPYTDvSQLRIsynVYKAVYAIAHALHDLLQ 380
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  430 alC-----PGYVGLCDAMKPIDGRKLLDFLIKSSFVGVSGEEVWFDEKGDAPGRYDIMNLQYTEANRYDYVHVGTWHEGV 504
Cdd:cd06364  381 --CepgkgPFSNGSCADIKKVEPWQLLYYLKHVNFTTKFGEEVYFDENGDPVASYDIINWQLSDDGTIQFVTVGYYDASA 458
                        490
                 ....*....|..
gi 34328063  505 LNIDDYKIQMNK 516
Cdd:cd06364  459 PSGEELVINESK 470
ANF_receptor pfam01094
Receptor family ligand binding region; This family includes extracellular ligand binding ...
77-487 1.07e-82

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: 273.88  E-value: 1.07e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063     77 QRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVALEQSIEFIrdslisirdekdglnrclpdgqtlppgrtKKPI 156
Cdd:pfam01094    1 LVLLAVRLAVEDINADPGLLPGTKLEYIILDTCCDPSLALAAALDLL-----------------------------KGEV 51
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063    157 AGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNY 236
Cdd:pfam01094   52 VAIIGPSCSSVASAVASLANEWKVPLISYGSTSPALSDLNRYPTFLRTTPSDTSQADAIVDILKHFGWKRVALIYSDDDY 131
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063    237 GESGMDAFKELAAQEGLCIAHSDKIYSNAGEKsfDRLLRKLRERLPKARVVVCFCEGMTVRGLLSAMRRLGVVGE-FSLI 315
Cdd:pfam01094  132 GESGLQALEDALRERGIRVAYKAVIPPAQDDD--EIARKLLKEVKSRARVIVVCCSSETARRLLKAARELGMMGEgYVWI 209
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063    316 GSDGWADRDEVIEG-YEVEANGGITIKLQSPEVRSFDDYFLKLrldtntrnpwfpefwqhrfqcrlpghllenpnfkkvc 394
Cdd:pfam01094  210 ATDGLTTSLVILNPsTLEAAGGVLGFRLHPPDSPEFSEFFWEK------------------------------------- 252
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063    395 tgNESLEENYVQDSKMGFV-----INAIYAMAHGLQNMHHALCPGYVglCDAMKPID-GRKLLDFLIKSSFVGVSGeEVW 468
Cdd:pfam01094  253 --LSDEKELYENLGGLPVSygalaYDAVYLLAHALHNLLRDDKPGRA--CGALGPWNgGQKLLRYLKNVNFTGLTG-NVQ 327
                          410       420
                   ....*....|....*....|
gi 34328063    469 FDEKGDAP-GRYDIMNLQYT 487
Cdd:pfam01094  328 FDENGDRInPDYDILNLNGS 347
7tmC_mGluR2 cd15447
metabotropic glutamate receptor 2 in group 2, member of the class C family of ...
597-839 3.00e-82

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: 269.11  E-value: 3.00e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  597 IAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCYSALV 676
Cdd:cd15447    7 VTISCLGILSTLFVVGVFVKNNETPVVKASGRELCYILLLGVLLCYLMTFIFIAKPSTAVCTLRRLGLGTSFAVCYSALL 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  677 TKTNRIARILAGSKKKIctRKPRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPILSYPSIKE--VYLICNTSNLGVV 754
Cdd:cd15447   87 TKTNRIARIFSGAKDGA--QRPRFISPASQVAICLALISCQLLVVLIWLLVEAPGTRKETAPERRyvVTLKCNSRDSSML 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  755 APVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYF--GSNYKIITT--CFAVSLSVTVALGCM 830
Cdd:cd15447  165 ISLTYNVLLIILCTLYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYvtSSDYRVQTTtmCISVSLSGSVVLGCL 244

                 ....*....
gi 34328063  831 FTPKMYIII 839
Cdd:cd15447  245 FAPKLHIIL 253
7tmC_mGluR_group2 cd15284
metabotropic glutamate receptors in group 2, member of the class C family of ...
597-839 4.51e-79

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: 260.17  E-value: 4.51e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  597 IAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCYSALV 676
Cdd:cd15284    7 VTIACLGFLCTLFVIGVFIKHNNTPLVKASGRELCYILLFGVFLCYCMTFIFIAKPSPAICTLRRLGLGTSFAVCYSALL 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  677 TKTNRIARILAGSKKKIctRKPRFMSAWAQVIIASILISVQLTLVVTLIIMEPP-MPILSYPSIKE-VYLICNTSNLGVV 754
Cdd:cd15284   87 TKTNRIARIFSGVKDGA--QRPRFISPSSQVFICLALISVQLLVVSVWLLVEAPgTRRYTLPEKREtVILKCNVRDSSML 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  755 APVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYF--GSNYKIITT--CFAVSLSVTVALGCM 830
Cdd:cd15284  165 ISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYvtSSDYRVQTTtmCISVSLSGFVVLGCL 244

                 ....*....
gi 34328063  831 FTPKMYIII 839
Cdd:cd15284  245 FAPKVHIIL 253
7tmC_mGluR_group3 cd15286
metabotropic glutamate receptors in group 3, member of the class C family of ...
593-846 2.18e-76

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: 253.57  E-value: 2.18e-76
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  593 SIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCY 672
Cdd:cd15286    3 AAVPVALAVLGIIATLFVLVTFVRYNDTPIVRASGRELSYVLLTGIFLCYAITFLMVAEPGVGVCSLRRLFLGLGMSLSY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  673 SALVTKTNRIARILAGSKKKICTrkPRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPILSY-------PSIKEVYLI 745
Cdd:cd15286   83 AALLTKTNRIYRIFEQGKKSVTP--PRFISPTSQLVITFSLISVQLLGVLAWFAVDPPHALIDYeegrtpdPEQARGVLR 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  746 CNTSNLGVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGS-----NYKIITTCFAVS 820
Cdd:cd15286  161 CDMSDLSLICCLGYSLLLMVTCTVYAIKARGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTaqsaeKLYIQTATLTVS 240
                        250       260
                 ....*....|....*....|....*...
gi 34328063  821 --LSVTVALGCMFTPKMYIIIAKPERNV 846
Cdd:cd15286  241 msLSASVSLGMLYMPKVYVILFHPEQNV 268
7tmC_mGluR4 cd15452
metabotropic glutamate receptor 4 in group 3, member of the class C family of ...
588-846 1.10e-75

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: 253.75  E-value: 1.10e-75
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  588 WSDIESIIAIafscLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLS 667
Cdd:cd15452    2 WAVVPLLLAV----LGIIATLFVVVTFVRYNDTPIVKASGRELSYVLLTGIFLCYATTFLMIAEPDLGTCSLRRIFLGLG 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  668 SAMCYSALVTKTNRIARILAGSKKKICTrkPRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPILSY-------PSIK 740
Cdd:cd15452   78 MSISYAALLTKTNRIYRIFEQGKRSVSA--PRFISPASQLVITFSLISLQLLGVCVWFLVDPSHSVVDYedqrtpdPQFA 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  741 EVYLICNTSNLGVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSN-------YKII 813
Cdd:cd15452  156 RGVLKCDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIIWLAFIPIFFGTSqsaekmyIQTT 235
                        250       260       270
                 ....*....|....*....|....*....|...
gi 34328063  814 TTCFAVSLSVTVALGCMFTPKMYIIIAKPERNV 846
Cdd:cd15452  236 TLTISVSLSASVSLGMLYMPKVYVILFHPEQNV 268
7tm_3 pfam00003
7 transmembrane sweet-taste receptor of 3 GCPR; This is a domain of seven transmembrane ...
586-834 1.37e-74

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: 247.57  E-value: 1.37e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063    586 LEWSDIESIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTsCYLQRLLVG 665
Cdd:pfam00003    1 LDLSAPWGIVLEALAALGILLTLVLLVVFLLHRKTPIVKASNRSLSFLLLLGLLLLFLLAFLFIGKPTVT-CALRRFLFG 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063    666 LSSAMCYSALVTKTNRIARILAGSKKkictrkprFMSAWAQVIIASILISVQLTLVVTLIIMePPMPILSYPSIKEVYLI 745
Cdd:pfam00003   80 VGFTLCFSCLLAKTFRLVLIFRRRKP--------GPRGWQLLLLALGLLLVQVIILTEWLID-PPFPEKDNLSEGKIILE 150
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063    746 CNTSN----LGVVapVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSNYK------IITT 815
Cdd:pfam00003  151 CEGSTsiafLDFV--LAYVGLLLLAGFLLAFKTRKLPDNFNEAKFITFSMLLSVLIWVAFIPMYLYGNKGkgtwdpVALA 228
                          250
                   ....*....|....*....
gi 34328063    816 CFAVSLSVTVALGCMFTPK 834
Cdd:pfam00003  229 IFAILASGWVLLGLYFIPK 247
7tmC_mGluR3 cd15448
metabotropic glutamate receptor 3 in group 2, member of the class C family of ...
593-839 6.62e-72

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: 240.23  E-value: 6.62e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  593 SIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCY 672
Cdd:cd15448    3 AIGPVTIACLGFICTCMVITVFIKHNNTPLVKASGRELCYILLFGVFLSYCMTFFFIAKPSPVICTLRRLGLGTSFAVCY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  673 SALVTKTNRIARILAGSKKKicTRKPRFMSAWAQVIIASILISVQLTLVVTLIIMEPP-MPILSYPSIKE-VYLICNTSN 750
Cdd:cd15448   83 SALLTKTNCIARIFDGVKNG--AQRPKFISPSSQVFICLSLILVQIVVVSVWLILEAPgTRRYTLPEKREtVILKCNVKD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  751 LGVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYF--GSNYKIITT--CFAVSLSVTVA 826
Cdd:cd15448  161 SSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYvtSSDYRVQTTtmCISVSLSGFVV 240
                        250
                 ....*....|...
gi 34328063  827 LGCMFTPKMYIII 839
Cdd:cd15448  241 LGCLFAPKVHIIL 253
7tmC_mGluR6 cd15453
metabotropic glutamate receptor 6 in group 3, member of the class C family of ...
593-847 8.38e-71

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: 238.01  E-value: 8.38e-71
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  593 SIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCY 672
Cdd:cd15453    3 AAPPLLLAVLGILATTTVVITFVRFNNTPIVRASGRELSYVLLTGIFLIYAITFLMVAEPGAAVCAFRRLFLGLGTTLSY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  673 SALVTKTNRIARILAGSKKKICtrKPRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPILSY-------PSIKEVYLI 745
Cdd:cd15453   83 SALLTKTNRIYRIFEQGKRSVT--PPPFISPTSQLVITFSLTSLQVVGVIAWLGAQPPHSVIDYeeqrtvdPEQARGVLK 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  746 CNTSNLGVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFG---SNYKI----ITTCFA 818
Cdd:cd15453  161 CDMSDLSLIGCLGYSLLLMVTCTVYAIKARGVPETFNEAKPIGFTMYTTCIIWLAFVPIFFGtaqSAEKIyiqtTTLTVS 240
                        250       260
                 ....*....|....*....|....*....
gi 34328063  819 VSLSVTVALGCMFTPKMYIIIAKPERNVR 847
Cdd:cd15453  241 LSLSASVSLGMLYVPKTYVILFHPEQNVQ 269
7tmC_mGluR8 cd15454
metabotropic glutamate receptor 8 in group 3, member of the class C family of ...
588-847 3.96e-68

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: 231.83  E-value: 3.96e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  588 WSDIESIIAIafscLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLS 667
Cdd:cd15454    2 WAVVPVFVAI----LGIIATTFVIVTFVRYNDTPIVRASGRELSYVLLTGIFLCYAITFLMIATPDTGICSFRRVFLGLG 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  668 SAMCYSALVTKTNRIARILAGSKKKICTrkPRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPILSY-------PSIK 740
Cdd:cd15454   78 MCFSYAALLTKTNRIHRIFEQGKKSVTA--PKFISPASQLVITFSLISVQLLGVFVWFAVDPPHTIVDYgeqrtldPEKA 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  741 EVYLICNTSNLGVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSN-------YKII 813
Cdd:cd15454  156 RGVLKCDISDLSLICSLGYSILLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIIWLAFIPIFFGTAqsaermyIQTT 235
                        250       260       270
                 ....*....|....*....|....*....|....
gi 34328063  814 TTCFAVSLSVTVALGCMFTPKMYIIIAKPERNVR 847
Cdd:cd15454  236 TLTISMSLSASVSLGMLYMPKVYIIIFHPEQNVQ 269
7tmC_mGluR7 cd15451
metabotropic glutamate receptor 7 in group 3, member of the class C family of ...
593-847 2.91e-67

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: 229.14  E-value: 2.91e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  593 SIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCY 672
Cdd:cd15451    3 AVIPVFLAMLGIIATIFVMATFIRYNDTPIVRASGRELSYVLLTGIFLCYIITFLMIAKPDVAVCSFRRIFLGLGMCISY 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  673 SALVTKTNRIARILAGSKKKICTrkPRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPILSY-------PSIKEVYLI 745
Cdd:cd15451   83 AALLTKTNRIYRIFEQGKKSVTA--PRLISPTSQLAITSSLISVQLLGVLIWFAVDPPNIIIDYdeqktmnPEQARGVLK 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  746 CNTSNLGVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGS-----NYKIITTCFAVS 820
Cdd:cd15451  161 CDITDLQIICSLGYSILLMVTCTVYAIKTRGVPENFNEAKPIGFTMYTTCIVWLAFIPIFFGTaqsaeKLYIQTTTLTIS 240
                        250       260
                 ....*....|....*....|....*....
gi 34328063  821 --LSVTVALGCMFTPKMYIIIAKPERNVR 847
Cdd:cd15451  241 mnLSASVALGMLYMPKVYIIIFHPELNVQ 269
PBP1_pheromone_receptor cd06365
Ligand-binding domain of the V2R pheromone receptor, a member of the family C receptors within ...
46-513 5.04e-61

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: 216.74  E-value: 5.04e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   46 IIGALFSVHHQPPAEKV------PERKCGEIREQYgIQRVEAMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVALEqs 119
Cdd:cd06365    1 IIGGVFPIHTFSEGKKKdfkeppSPLLCFRFSIKY-YQHLLAFLFAIEEINKNPDLLPNITLGFHIYDSCSSERLALE-- 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  120 iefirdSLISIRDEkdglnrclpDGQTLP--PGRTKKPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTL 197
Cdd:cd06365   78 ------SSLSILSG---------NSEPIPnySCREQRKLVAFIGDLSSSTSVAMARILGLYKYPQISYGAFDPLLSDKVQ 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  198 YKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESGMDAFKELAAQEGLCIA-----------HSDKIYSNAG 266
Cdd:cd06365  143 FPSFYRTVPSDTSQSLAIVQLLKHFGWTWVGLIISDDDYGEQFSQDLKKEMEKNGICVAfvekiptnsslKRIIKYINQI 222
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  267 EKSfdrllrklrerlpKARVVVCFCEG---MTVRGLLSAMRRLGVVgefsLIGSDGWADRDEVIEGYEVEANGGITIKLQ 343
Cdd:cd06365  223 IKS-------------SANVIIIYGDTdslLELLFRLWEQLVTGKV----WITTSQWDISTLPFEFYLNLFNGTLGFSQH 285
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  344 SPEVRSFDDYFLKLRLDTNTRNPWFPEFWQHRFQCRLPghlLENPNFKKVCTGNESLEENYVQDSKMGF------VINAI 417
Cdd:cd06365  286 SGEIPGFKEFLQSVHPSKYPEDIFLKTLWESYFNCKWP---DQNCKSLQNCCGNESLETLDVHSFDMTMsrlsynVYNAV 362
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  418 YAMAHGLQNMHHALCPGYVGLCDAMKPIDGRKLLDFLIKSSFVGVSGEEVWFDEKGDAPGRYDIMNLQYTEANRYDYVHV 497
Cdd:cd06365  363 YAVAHALHEMLLCQPKTGPGNCSDRRNFQPWQLHHYLKKVQFTNPAGDEVNFDEKGDLPTKYDILNWQIFPNGTGTKVKV 442
                        490       500
                 ....*....|....*....|.
gi 34328063  498 GT--WHEGV---LNIDDYKIQ 513
Cdd:cd06365  443 GTfdPSAPSgqqLIINDSMIE 463
PBP1_taste_receptor cd06363
ligand-binding domain of the T1R taste receptor; Ligand-binding domain of the T1R taste ...
40-513 2.09e-49

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: 181.35  E-value: 2.09e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   40 RMDGDVIIGALFSVH-------HQPPaeKVPERKCGEIREqYGIQRVEAMFHTLDKINADPVLLPNITLGSEIRDSCwHS 112
Cdd:cd06363    2 RLPGDYLLGGLFPLHeltstlpHRPP--EPTDCSCDRFNL-HGYHLAQAMRFAVEEINNSSDLLPGVTLGYEIFDTC-SD 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  113 SVALEQSIEFI-RDSLISIRDEkdglnrclpdgqtLPPGRTKKPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSID 191
Cdd:cd06363   78 AVNFRPTLSFLsQNGSHDIEVQ-------------CNYTNYQPRVVAVIGPDSSELALTTAKLLGFFLMPQISYGASSEE 144
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  192 LSDKTLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESGMDAFKELAAQEGLCIAHSDKIYSNAGEKSfD 271
Cdd:cd06363  145 LSNKLLYPSFLRTVPSDKYQVEAMVQLLQEFGWNWVAFLGSDDEYGQDGLQLFSEKAANTGICVAYQGLIPTDTDPKP-K 223
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  272 RLLRKLRERLPKARVVVCFCEGMTVRGLLSAMRRLGVVGEFsLIGSDGWADRDEVIEGYEVEANG---GITIKLQSpeVR 348
Cdd:cd06363  224 YQDILKKINQTKVNVVVVFAPKQAAKAFFEEVIRQNLTGKV-WIASEAWSLNDTVTSLPGIQSIGtvlGFAIQTGT--LP 300
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  349 SFDDYflklrldtntrnpwfpefwqhrfqcrlpghllenpnfkkvctgneslEENYVQDskmgfVINAIYAMAHGLqnmH 428
Cdd:cd06363  301 GFQEF-----------------------------------------------IYAFAFS-----VYAAVYAVAHAL---H 325
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  429 HAL-CPGyvGLCDAMKPIDGRKLLDFLIKSSFVgVSGEEVWFDEKGDAPGRYDIMNLQYTEANrYDYVHVG--TWHEGVL 505
Cdd:cd06363  326 NLLgCNS--GACPKGRVVYPWQLLEELKKVNFT-LLNQTIRFDENGDPNFGYDIVQWIWNNSS-WTFEVVGsySTYPIQL 401

                 ....*...
gi 34328063  506 NIDDYKIQ 513
Cdd:cd06363  402 TINESKIK 409
7tmC_V2R_pheromone cd15283
vomeronasal type-2 pheromone receptors, member of the class C family of seven-transmembrane G ...
594-839 4.92e-43

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: 157.44  E-value: 4.92e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  594 IIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCYS 673
Cdd:cd15283    4 IALTVLSLLGSVLTAAVLVVFIKHRDTPIVKANNSELSYLLLLSLKLCFLCSLLFIGQPSTWTCMLRQTAFGISFVLCIS 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  674 ALVTKTN------RIARILAGSKKKICTRKPRFMsawaqVIIASIlisVQLTLVVTLIIMEPPMPILSYPSIKE-VYLIC 746
Cdd:cd15283   84 CILAKTIvvvaafKATRPGSNIMKWFGPGQQRAI-----IFICTL---VQVVICAIWLATSPPFPDKNMHSEHGkIILEC 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  747 NT-SNLGVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGS--NYKIITTCFAVSLSV 823
Cdd:cd15283  156 NEgSVVAFYCVLGYIGLLALVSFLLAFLARKLPDNFNEAKFITFSMLVFCAVWVAFVPAYISSpgKYMVAVEIFAILASS 235
                        250
                 ....*....|....*.
gi 34328063  824 TVALGCMFTPKMYIII 839
Cdd:cd15283  236 AGLLGCIFAPKCYIIL 251
7tmC_V2R_AA_sensing_receptor-like cd15044
vomeronasal type-2 pheromone receptors, amino acid-sensing receptors and closely related ...
594-839 1.35e-42

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: 156.48  E-value: 1.35e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  594 IIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCYS 673
Cdd:cd15044    4 ILLVILSILGIIFVLVVGGVFVRYRNTPIVKANNRELSYLILLSLFLCFSSSLFFIGEPQDWTCKLRQTMFGVSFTLCIS 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  674 ALVTKTNRIarILAGSKKKICTRKpRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPILSYPSIKEVYLI-CNT-SNL 751
Cdd:cd15044   84 CILTKTLKV--LLAFSADKPLTQK-FLMCLYLPILIVFTCTGIQVVICTVWLIFAPPTVEVNVSPLPRVIILeCNEgSIL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  752 GVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGS--NYKIITTCFAVSLSVTVALGC 829
Cdd:cd15044  161 AFGTMLGYIAFLAFLCFLFAFKARKLPDNYNEAKFITFGMLVFFIVWISFVPAYLSTkgKFVVAVEIIAILASSYGLLGC 240
                        250
                 ....*....|
gi 34328063  830 MFTPKMYIII 839
Cdd:cd15044  241 IFLPKCYVIL 250
PBP1_GPC6A-like cd06361
ligand-binding domain of the promiscuous L-alpha-amino acid receptor GPRC6A which is a ...
46-353 6.24e-41

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: 155.99  E-value: 6.24e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   46 IIGALFSVHhqppaEKVPERKCGEIREQY---------GIQRVEAMFHTLDKINADPvLLPNITLGSEIRDSCWHSSVAL 116
Cdd:cd06361    1 IIGGLFPIH-----EKVLDLHDRPTKPQIfictgfdlrGFLQSLAMIHAIEMINNST-LLPGIKLGYEIYDTCSDVTKAL 74
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  117 EQSIEfirdsLISIRDEKDGLNRClpDGQTLPPgrtkkPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKT 196
Cdd:cd06361   75 QATLR-----LLSKFNSSNELLEC--DYTDYVP-----PVKAVIGASYSEISIAVARLLNLQLIPQISYESSAPILSDKL 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  197 LYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESGMDAFKELAAQEGLCIAHSDKIYSNAGEKSFDR---L 273
Cdd:cd06361  143 RFPSFLRTVPSDFHQTKAMAKLISHFGWNWVGIIYTDDDYGRSALESFIIQAEAENVCIAFKEVLPAYLSDPTMNVrinD 222
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  274 LRKLRERLPKARVVVCFCEGMTVRGLLSAMRRLGVvgEFSLIGSDGWADRDEVIEGYEVEANGGIT-IKLQSPEVRSFDD 352
Cdd:cd06361  223 TIQTIQSSSQVNVVVLFLKPSLVKKLFKEVIERNI--SKIWIASDNWSTAREILKMPNINKVGKILgFTFKSGNISSFHN 300

                 .
gi 34328063  353 Y 353
Cdd:cd06361  301 Y 301
7tmC_V2R-like cd15280
vomeronasal type-2 receptor-like proteins, member of the class C family of seven-transmembrane ...
594-842 3.99e-37

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: 140.69  E-value: 3.99e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  594 IIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCYS 673
Cdd:cd15280    4 ITLIALSIFGALVVLAVTVVYIMHRHTPLVKANDRELSFLIQMSLVITFLTSILFIGKPENWSCMARQITLALGFSLCLS 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  674 ALVTKTNRI--ARILAGSKKKICTRKPRFmsawaQVIIASILISVQLTLVVTLIIMEPPMPI--LSYPSIKeVYLICNTS 749
Cdd:cd15280   84 SILGKTISLflRYRASKSETRLDSMHPIY-----QKIIVLICVLIEVGICTAYLILEPPRMYknTEVQNVK-IIFECNEG 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  750 NLGVVAPV-GYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGS--NYKIITTCFAVSLSVTVA 826
Cdd:cd15280  158 SIEFLCSIfGFDVFLALLCFLTAFVARKLPDNFNEGKFITFGMLVFFIVWISFVPAYLSTrgKFKVAVEIFAILASSFGL 237
                        250
                 ....*....|....*.
gi 34328063  827 LGCMFTPKMYIIIAKP 842
Cdd:cd15280  238 LGCIFVPKCYIILLKP 253
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
592-834 4.23e-35

seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary model represents the seven-transmembrane (7TM) receptors, often referred to as G protein-coupled receptors (GPCRs), which transmit physiological signals from the outside of the cell to the inside via G proteins. GPCRs constitute the largest known superfamily of transmembrane receptors across the three kingdoms of life that respond to a wide variety of extracellular stimuli including peptides, lipids, neurotransmitters, amino acids, hormones, and sensory stimuli such as light, smell and taste. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. However, some 7TM receptors, such as the type 1 microbial rhodopsins, do not activate G proteins. Based on sequence similarity, GPCRs can be divided into six major classes: class A (the rhodopsin-like family), class B (the Methuselah-like, adhesion and secretin-like receptor family), class C (the metabotropic glutamate receptor family), class D (the fungal mating pheromone receptors), class E (the cAMP receptor family), and class F (the frizzled/smoothened receptor family). Nearly 800 human GPCR genes have been identified and are involved essentially in all major physiological processes. Approximately 40% of clinically marketed drugs mediate their effects through modulation of GPCR function for the treatment of a variety of human diseases including bacterial infections.


Pssm-ID: 410628 [Multi-domain]  Cd Length: 267  Bit Score: 135.25  E-value: 4.23e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  592 ESIIAIAFSCLGILVTLFVTLIFVLYRDTPvvkSSSRELCYIILAGIFLGYVCPFTLIAKPTTT--------SCYLQRLL 663
Cdd:cd14964    1 TTIILSLLTCLGLLGNLLVLLSLVRLRKRP---RSTRLLLASLAACDLLASLVVLVLFFLLGLTeassrpqaLCYLIYLL 77
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  664 VGLSSAMCYSALVTKTNRIARILAGSKKkictrKPRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPILSYPsIKEVY 743
Cdd:cd14964   78 WYGANLASIWTTLVLTYHRYFALCGPLK-----YTRLSSPGKTRVIILGCWGVSLLLSIPPLVGKGAIPRYNTL-TGSCY 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  744 LICNTSNLGVVAPVGYNGLLIMSCTYYAFK----------------TRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYF- 806
Cdd:cd14964  152 LICTTIYLTWGFLLVSFLLPLVAFLVIFSRivlrlrrrvrairsaaSLNTDKNLKATKSLLILVITFLLCWLPFSIVFIl 231
                        250       260       270
                 ....*....|....*....|....*....|....*.
gi 34328063  807 --------GSNYKIITTCFAVSLSVTVALGCMFTPK 834
Cdd:cd14964  232 halvaagqGLNLLSILANLLAVLASTLNPFIYCLGN 267
7tmC_GABA-B-like cd15047
gamma-aminobutyric acid type B receptor and related proteins, member of the class C family of ...
594-838 4.63e-35

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: 135.00  E-value: 4.63e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  594 IIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYV-CPFTLI--AKPTTTSCYLQRLLVGLSSAM 670
Cdd:cd15047    4 IVFTVLSGIGILLALVFLIFNIKFRKNRVIKMSSPLFNNLILLGCILCYIsVILFGLddSKPSSFLCTARPWLLSIGFTL 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  671 CYSALVTKTNRIARILAGSKKKICTRKPRFMsawaqVIIASILISVQLTLVVTLIIMEPPMPILSYPSIKE--------V 742
Cdd:cd15047   84 VFGALFAKTWRIYRIFTNKKLKRIVIKDKQL-----LKIVGILLLIDIIILILWTIVDPLKPTRVLVLSEIsddvkyeyV 158
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  743 YLICNTSNLGV--VAPVGYNGLLIMSCTYYAFKTRNVP-ANFNEAKYIAFTMYTTCIIWLAFVPIYFGS----NYKIITT 815
Cdd:cd15047  159 VHCCSSSNGIIwlGILLAYKGLLLLFGCFLAWKTRNVDiEEFNESKYIGISIYNVLFLSVIGVPLSFVLtdspDTSYLII 238
                        250       260
                 ....*....|....*....|...
gi 34328063  816 CFAVSLSVTVALGCMFTPKMYII 838
Cdd:cd15047  239 SAAILFCTTATLCLLFVPKFWLL 261
7tmC_CaSR cd15282
calcium-sensing receptor, member of the class C of seven-transmembrane G protein-coupled ...
595-839 9.15e-35

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: 133.92  E-value: 9.15e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  595 IAIA-FSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCYS 673
Cdd:cd15282    4 IALTlFAVLGIFLTAFVLGVFIKFRNTPIVKATNRELSYLLLFSLICCFSSSLIFIGEPQDWTCRLRQPAFGISFVLCIS 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  674 ALVTKTNRIARILagsKKKICTrkpRFMSAW----AQVIIASILISVQLTLVVTLIIMEPPMPILSYPSIKE-VYLICNT 748
Cdd:cd15282   84 CILVKTNRVLLVF---EAKIPT---SLHRKWwglnLQFLLVFLCTFVQIVICVIWLYTAPPSSYRNHELEDEiIFITCNE 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  749 SNLGVVAP-VGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSNYKIITT--CFAVSLSVTV 825
Cdd:cd15282  158 GSLMALGFlIGYTCLLAAICFFFAFKSRKLPENFNEAKFITFSMLIFFIVWISFIPAYASTYGKFVSAveVIAILASSFG 237
                        250
                 ....*....|....
gi 34328063  826 ALGCMFTPKMYIII 839
Cdd:cd15282  238 LLACIFFNKVYIIL 251
7tmC_GPRC6A cd15281
class C of seven-transmembrane G protein-coupled receptors, subtype 6A; GRPC6A (GPCR, class C, ...
593-839 3.35e-29

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: 117.57  E-value: 3.35e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  593 SIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCY 672
Cdd:cd15281    3 AIVLLILSALGVLLIFFISALFTKNLNTPVVKAGGGPLCYVILLSHFGSFISTVFFIGEPSDLTCKTRQTLFGISFTLCV 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  673 SALVTKTNRIarILAGS----KKKI--CTRKPrfmsawaqVIIASILISVQLTLVVTLIIMEPPMPILSYPSIKEVYLIC 746
Cdd:cd15281   83 SCILVKSLKI--LLAFSfdpkLQELlkCLYKP--------IMIVFICTGIQVIICTVWLVFYKPFVDKNFSLPESIILEC 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  747 NT-SNLGVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIY---FGSnYKIITTCFAVSLS 822
Cdd:cd15281  153 NEgSYVAFGLMLGYIALLAFICFIFAFKGRKLPENYNEAKFITFGMLIYFIAWITFIPIYattFGK-YVPAVEMIVILIS 231
                        250
                 ....*....|....*..
gi 34328063  823 VTVALGCMFTPKMYIII 839
Cdd:cd15281  232 NYGILSCTFLPKCYIIL 248
7tmC_TAS1R1 cd15289
type 1 taste receptor subtype 1, member of the class C of seven-transmembrane G ...
593-839 1.54e-28

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: 115.60  E-value: 1.54e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  593 SIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCY 672
Cdd:cd15289    3 SWALLTALTLLLLLLAGTALLFALNLTTPVVKSAGGRTCFLMLGSLAAASCSLYCHFGEPTWLACLLKQPLFSLSFTVCL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  673 SALVTKTNRIARILagskkKICTRKPRFMSAWAQ-------VIIASiliSVQLTLVVTLIIMEPPMPILSYPSIKE-VYL 744
Cdd:cd15289   83 SCIAVRSFQIVCIF-----KLASKLPRFYETWAKnhgpelfILISS---AVQLLISLLWLVLNPPVPTKDYDRYPDlIVL 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  745 IC-NTSNLGVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVP---IYFGSnYKIITTCFAVS 820
Cdd:cd15289  155 ECsQTLSVGSFLELLYNCLLSISCFVFSYMGKDLPANYNEAKCITFSLLIYFISWISFFTtysIYRGK-YLMAINVLAIL 233
                        250
                 ....*....|....*....
gi 34328063  821 LSVTVALGCMFTPKMYIII 839
Cdd:cd15289  234 SSLLGIFGGYFLPKVYIIL 252
7tmC_TAS1R cd15046
type 1 taste receptors, member of the class C of seven-transmembrane G protein-coupled ...
593-839 8.56e-26

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: 107.61  E-value: 8.56e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  593 SIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCY 672
Cdd:cd15046    3 TVAVLLLAALGLLSTLAILVIFWRNFNTPVVRSAGGPMCFLMLTLLLVAYMSVPVYFGPPKVSTCLLRQALFPLCFTVCL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  673 SALVTKTNRIARILagskkKICTRKPRFMSAWA----QVIIASILISVQLTLVVTLIIMEPPMP---ILSYPSIKeVYLI 745
Cdd:cd15046   83 ACIAVRSFQIVCIF-----KMASRFPRAYSYWVkyhgPYVSIAFITVLKMVIVVIGMLATPPSPttdTDPDPKIT-IVSC 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  746 CNTSNLGVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSNYKIITTCF--AVSLSV 823
Cdd:cd15046  157 NPNYRNSSLFNTSLDLLLSVVCFSFSYMGKDLPTNYNEAKFITFSLTFYFTSWISFCTFMLAYSGVLVTIVDllATLLSL 236
                        250
                 ....*....|....*.
gi 34328063  824 TVALGCMFTPKMYIII 839
Cdd:cd15046  237 LAFSLGYFLPKCYIIL 252
PBP1_GABAb_receptor cd06366
ligand-binding domain of GABAb receptors, which are metabotropic transmembrane receptors for ...
86-501 5.18e-25

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: 109.26  E-value: 5.18e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   86 LDKINADPVLLPNITLGSEIRDSCWHSSVALEQSIEFIRdslisirdekdglnrclpdgqtlppgrTKKPIAGVIGPGSS 165
Cdd:cd06366   28 LEHINNRSDILPGYNLELIWNDTQCDPGLGLKALYDLLY---------------------------TPPPKVMLLGPGCS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  166 SVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESGMDAFK 245
Cdd:cd06366   81 SVTEPVAEASKYWNLVQLSYAATSPALSDRKRYPYFFRTVPSDTAFNPARIALLKHFGWKRVATIYQNDEVFSSTAEDLE 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  246 ELAAQEGLCIAHSDKIysnageKSFDRLLRKLRERLPKAR-VVVCFCEGMTvRGLLSAMRRLGVVGE---FSLIG--SDG 319
Cdd:cd06366  161 ELLEEANITIVATESF------SSEDPTDQLENLKEKDARiIIGLFYEDAA-RKVFCEAYKLGMYGPkyvWILPGwyDDN 233
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  320 WAD---------RDEVIEGYEveanGGITIKlqspevrsfddyFLKLR-LDTNTRNPWFPEFWQHRFQCRLPghllenpn 389
Cdd:cd06366  234 WWDvpdndvnctPEQMLEALE----GHFSTE------------LLPLNpDNTKTISGLTAQEFLKEYLERLS-------- 289
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  390 fKKVCTGNesleeNYVqdskmGFVINAIYAMAHGLQNMHHALCPGYVGLCDA--MKPIDGRKLLDFLIKSSFVGVSGeEV 467
Cdd:cd06366  290 -NSNYTGS-----PYA-----PFAYDAVWAIALALNKTIEKLAEYNKTLEDFtyNDKEMADLFLEAMNSTSFEGVSG-PV 357
                        410       420       430
                 ....*....|....*....|....*....|....
gi 34328063  468 WFDEKGDAPGRYDIMNLQYTEanrydYVHVGTWH 501
Cdd:cd06366  358 SFDSKGDRLGTVDIEQLQGGS-----YVKVGLYD 386
7tmC_TAS1R2 cd15288
type 1 taste receptor subtype 2, member of the class C of seven-transmembrane G ...
593-839 1.35e-22

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: 98.71  E-value: 1.35e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  593 SIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCY 672
Cdd:cd15288    3 TIVVALLAALGFLSTLAILVIFGRHFQTPVVRSAGGRMCFLMLAPLLVAYVNVPVYVGIPTVFTCLCRQTLFPLCFTVCI 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  673 SALVTKTNRIARILagskkKICTRKPRFMSAW----AQVIIASILISVQLTLVVTLIIMEPPMPILSY----PSIkeVYL 744
Cdd:cd15288   83 SCIAVRSFQIVCIF-----KMARRLPRAYSYWvkynGPYVFVALITLLKVVIVVINVLAHPTAPTTRAdpddPQV--MIL 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  745 ICNTS-NLGVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTM---YTTCIIWLAFVPIYFGsnykIITTCFAVS 820
Cdd:cd15288  156 QCNPNyRLALLFNTSLDLLLSVLGFCFAYMGKELPTNYNEAKFITLCMtfyFASSVFLCTFMSVYEG----VLVTIFDAL 231
                        250       260
                 ....*....|....*....|..
gi 34328063  821 LSVTVALGC---MFTPKMYIII 839
Cdd:cd15288  232 VTVINLLGIslgYFGPKCYMIL 253
PBP1_NPR_GC-like cd06352
ligand-binding domain of membrane guanylyl-cyclase receptors; Ligand-binding domain of ...
86-499 1.73e-21

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: 98.20  E-value: 1.73e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   86 LDKINADPVLLPNITLGSEIRDSCWHSSVALEQSIEFIRDSLISirdekdglnrclpdgqtlppgrtkkpiaGVIGPGSS 165
Cdd:cd06352   28 IERINSEGLLLPGFNFEFTYRDSCCDESEAVGAAADLIYKRNVD----------------------------VFIGPACS 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  166 SVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAV-HTEGNYGESGMDAF 244
Cdd:cd06352   80 AAADAVGRLATYWNIPIITWGAVSASFLDKSRYPTLTRTSPNSLSLAEALLALLKQFNWKRAAIIySDDDSKCFSIANDL 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  245 KELAAQEGLCIAHSDKIYSNAGEKSFDRLLRKLRErlpKARVVVCFCEGMTVRGLLSAMRRLGVV-GEFSLIGSD----- 318
Cdd:cd06352  160 EDALNQEDNLTISYYEFVEVNSDSDYSSILQEAKK---RARIIVLCFDSETVRQFMLAAHDLGMTnGEYVFIFIElfkdg 236
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  319 ---GWADRDEVIEGYEVEA----NGGITIKLQSPEVRSFDdyflklrldtntrnpwfpefwqhRFQCRLPGHLLENPNFk 391
Cdd:cd06352  237 fggNSTDGWERNDGRDEDAkqayESLLVISLSRPSNPEYD-----------------------NFSKEVKARAKEPPFY- 292
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  392 kvCTGNESLEENYvqdskmgFVI---NAIYAMAHGLQNMhhalcpgyvgLCDAMKPIDGRKLLDFLIKSSFVGVSGeEVW 468
Cdd:cd06352  293 --CYDASEEEVSP-------YAAalyDAVYLYALALNET----------LAEGGNYRNGTAIAQRMWNRTFQGITG-PVT 352
                        410       420       430
                 ....*....|....*....|....*....|.
gi 34328063  469 FDEKGDapgRYDIMNLQYTEANRYDYVHVGT 499
Cdd:cd06352  353 IDSNGD---RDPDYALLDLDPSTGKFVVVLT 380
7tmC_TAS1R2a-like cd15287
type 1 taste receptor subtype 2a and similar proteins, member of the class C of ...
591-839 4.16e-21

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: 93.98  E-value: 4.16e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  591 IESIIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAM 670
Cdd:cd15287    1 IVAILIMVGACVLVGLTLAVSVLFAINYNTPVVRSAGGPMCFLILGCLSLCSVSVFFYFGKPTVASCILRYFPFLLFYTV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  671 CYSALVTKTNRIARILagskkKICTRKPRFMSAW----AQVIIASILISVQLTLVVTLIIMEPPMP---ILSYPsiKEVY 743
Cdd:cd15287   81 CLACFVVRSFQIVCIF-----KIAAKFPKLHSWWvkyhGQWLLIAVAFVIQALLLITGFSFSPPKPyndTSWYP--DKII 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  744 LICNTSNLGVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIY--FGSNYKIITTCFAVSL 821
Cdd:cd15287  154 LSCDINLKATSMSLVLLLSLCCLCFIFSYMGKDLPKNYNEAKAITFCLLLLILTWIIFATEYmlYRGKYIQLLNALAVLS 233
                        250
                 ....*....|....*...
gi 34328063  822 SVTVALGCMFTPKMYIII 839
Cdd:cd15287  234 SLYSFLLWYFLPKCYIII 251
7tmC_GPR158-like cd15293
orphan GPR158 and similar proteins, member of the class C family of seven-transmembrane G ...
594-838 9.45e-20

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: 89.97  E-value: 9.45e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  594 IIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCYS 673
Cdd:cd15293    4 IAVLAVQAICILLCLVLALVVFRFRKVKVIKAASPILLELILFGALLLYFPVFILYFEPSVFRCILRPWFRHLGFAIVYG 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  674 ALVTKTNRIARILaGSKKkicTRKPRFMSAWAQVIIASILISVQLTLVVTLIIMEPPMPI-LSYPSIKEVYLICNTSNLG 752
Cdd:cd15293   84 ALILKTYRILVVF-RSRS---ARRVHLTDRDLLKRLGLIVLVVLGYLAAWTAVNPPNVEVgLTLTSSGLKFNVCSLDWWD 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  753 VVAPVGYngLLIMSCT-YYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYF------GSNYKIITTCFAVSLSVTV 825
Cdd:cd15293  160 YVMAIAE--LLFLLWGvYLCYAVRKAPSAFNESRYISLAIYNELLLSVIFNIIRFfllpslHPDLLFLLFFLHTQLTVTV 237
                        250
                 ....*....|...
gi 34328063  826 ALGCMFTPKMYII 838
Cdd:cd15293  238 TLLLIFGPKFYLV 250
PBP1_SAP_GC-like cd06370
Ligand-binding domain of membrane bound guanylyl cyclases; Ligand-binding domain of membrane ...
81-499 2.01e-19

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: 91.92  E-value: 2.01e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063   81 AMFHTLDKINADPVLLPNITLGSEIRDSCWHSSVALEQSIEFIrdslisirdekdglnrclpdgqtlppgrtKKPIAGVI 160
Cdd:cd06370   25 AITLAVDDVNNDPNLLPGHTLSFVWNDTRCDELLSIRAMTELW-----------------------------KRGVSAFI 75
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  161 GPGSS------SVAIqvqnllqlFDIPQIAYSATSIDLSDKTLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEG 234
Cdd:cd06370   76 GPGCTcatearLAAA--------FNLPMISYKCADPEVSDKSLYPTFARTIPPDSQISKSVIALLKHFNWNKVSIVYENE 147
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  235 NYGESGMDAFKELAAQEGLCIAHsdkiysnagEKSFDRLLRKLRERLP-----------KARVVVCFCEGMTVRGLLSAM 303
Cdd:cd06370  148 TKWSKIADTIKELLELNNIEINH---------EEYFPDPYPYTTSHGNpfdkiveetkeKTRIYVFLGDYSLLREFMYYA 218
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  304 RRLGVV--GEFSLIGSD------GWADRDEVIEGYEVEANggitiklQSPEVRSFDDYFLKLRLdTNTRNPWFPEFWQhr 375
Cdd:cd06370  219 EDLGLLdnGDYVVIGVEldqydvDDPAKYPNFLSGDYTKN-------DTKEALEAFRSVLIVTP-SPPTNPEYEKFTK-- 288
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  376 fQCR----LPGHLLENPNFKKVcTGNESLEENYVQDSKMgfvinaIYAMAhglqnMHHALCPGYvglcdamKPIDGRKLL 451
Cdd:cd06370  289 -KVKeynkLPPFNFPNPEGIEK-TKEVPIYAAYLYDAVM------LYARA-----LNETLAEGG-------DPRDGTAII 348
                        410       420       430       440       450
                 ....*....|....*....|....*....|....*....|....*....|.
gi 34328063  452 DFLIKSSFVGVSGEEVWFDEKGDAPGRYDIMNLQY---TEANRYDYVHVGT 499
Cdd:cd06370  349 SKIRNRTYESIQGFDVYIDENGDAEGNYTLLALKPnkgTNDGSYGLHPVGT 399
NCD3G pfam07562
Nine Cysteines Domain of family 3 GPCR; This conserved sequence contains several ...
521-571 2.06e-19

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: 82.69  E-value: 2.06e-19
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 34328063    521 RSVCSEPCLKGQIKVIRKGEVSCCWICTACKENEFVQ-DEFTCRACDLGWWP 571
Cdd:pfam07562    2 SSVCSESCPPGQRKSQQGGAPVCCWDCVPCPEGEISNtDSDTCKKCPEGQWP 53
PBP1_ABC_ligand_binding-like cd06346
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
156-319 3.50e-17

type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems predicted to be involved in uptake of amino acids, peptides, or inorganic ions; This subgroup includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems that are predicted to be involved in uptake of amino acids, peptides, or inorganic ions. This subgroup has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP); however, its ligand specificity has not been determined experimentally.


Pssm-ID: 380569 [Multi-domain]  Cd Length: 314  Bit Score: 83.77  E-value: 3.50e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  156 IAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGN 235
Cdd:cd06346   68 VPAIVGAASSGVTLAVASVAVPNGVVQISPSSTSPALTTLEDKGYVFRTAPSDALQGVVLAQLAAERGFKKVAVIYVNND 147
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  236 YGESGMDAFKElaAQEGLCIAHSDKIYSNAGEKSFDRLLRKLRERLPKARVVVCFCEgmTVRGLLSAMRRLGVVGeFSLI 315
Cdd:cd06346  148 YGQGLADAFKK--AFEALGGTVTASVPYEPGQTSYRAELAQAAAGGPDALVLIGYPE--DGATILREALELGLDF-TPWI 222

                 ....
gi 34328063  316 GSDG 319
Cdd:cd06346  223 GTDG 226
7tmC_TAS1R3 cd15290
type 1 taste receptor subtype 3, member of the class C of seven-transmembrane G ...
596-839 5.75e-17

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: 82.03  E-value: 5.75e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  596 AIAFSCLGILVTLFVTLIFVLY---RDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCY 672
Cdd:cd15290    3 SLGLLLLGVLLLVLQCSVGVLFlkhRGTPLVQASGGPLSIFALLSLMGACLSLLLFLGQPSDVVCRLQQPLNALFLTVCL 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  673 SALVTKTNRIARI----LAGSKKKICTRKPRfmsAWAQVIIAsilISVQLTLVVTLIIMEPPMPILSYPSIK--EVYLIC 746
Cdd:cd15290   83 STILSISLQIFLVtefpKCAASHLHWLRGPG---SWLVVLIC---CLVQAGLCGWYVQDGPSLSEYDAKMTLfvEVFLRC 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  747 NT-SNLGVVAPVGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSNYK---IITTCFAVsLS 822
Cdd:cd15290  157 PVePWLGFGLMHGFNGALALISFMCTFMAQKPLKQYNLARDITFSTLIYCVTWVIFIPIYAGLQVKlrsIAQVGFIL-LS 235
                        250
                 ....*....|....*..
gi 34328063  823 VTVALGCMFTPKMYIII 839
Cdd:cd15290  236 NLGLLAAYYLPKCYLLL 252
LivK COG0683
ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid ...
156-308 1.61e-16

ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid transport and metabolism];


Pssm-ID: 440447 [Multi-domain]  Cd Length: 314  Bit Score: 81.90  E-value: 1.61e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  156 IAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYKYFLRVVPSDTLQARAMLD-IVKRYNWTYVSAVHTEG 234
Cdd:COG0683   72 VDAIVGPLSSGVALAVAPVAEEAGVPLISPSATAPALTGPECSPYVFRTAPSDAQQAEALADyLAKKLGAKKVALLYDDY 151
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 34328063  235 NYGESGMDAFKELAAQEGLCIAHSDKIysNAGEKSFDRLLRKLRERLPKArvVVCFCEGMTVRGLLSAMRRLGV 308
Cdd:COG0683  152 AYGQGLAAAFKAALKAAGGEVVGEEYY--PPGTTDFSAQLTKIKAAGPDA--VFLAGYGGDAALFIKQAREAGL 221
PBP1_ABC_transporter_LIVBP-like cd06268
periplasmic binding domain of ATP-binding cassette transporter-like systems that belong to the ...
156-357 1.09e-14

periplasmic binding domain of ATP-binding cassette transporter-like systems that belong to the type 1 periplasmic binding fold protein superfamily; Periplasmic binding domain of ATP-binding cassette transporter-like systems that belong to the type 1 periplasmic binding fold protein superfamily. They are mostly present in archaea and eubacteria, and are primarily involved in scavenging solutes from the environment. ABC-type transporters couple ATP hydrolysis with the uptake and efflux of a wide range of substrates across bacterial membranes, including amino acids, peptides, lipids and sterols, and various drugs. These systems are comprised of transmembrane domains, nucleotide binding domains, and in most bacterial uptake systems, periplasmic binding proteins (PBPs) which transfer the ligand to the extracellular gate of the transmembrane domains. These PBPs bind their substrates selectively and with high affinity. Members of this group include ABC-type Leucine-Isoleucine-Valine-Binding Proteins (LIVBP), which are homologous to the aliphatic amidase transcriptional repressor, AmiC, of Pseudomonas aeruginosa. The uncharacterized periplasmic components of various ABC-type transport systems are included in this group.


Pssm-ID: 380492 [Multi-domain]  Cd Length: 298  Bit Score: 76.21  E-value: 1.09e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  156 IAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKtLYKYFLRVVPSDTLQARAMLD-IVKRYNWTYVSAVHTEG 234
Cdd:cd06268   68 VLAVVGHYSSSVTLAAAPIYQEAGIPLISPGSTAPELTEG-GGPYVFRTVPSDAMQAAALADyLAKKLKGKKVAILYDDY 146
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  235 NYGESGMDAFKELAAQEGLCIAhsDKIYSNAGEKSFDRLLRKLRERLPKarVVVCFCEGMTVRGLLSAMRRLGVvgEFSL 314
Cdd:cd06268  147 DYGKSLADAFKKALKALGGEIV--AEEDFPLGTTDFSAQLTKIKAAGPD--VLFLAGYGADAANALKQARELGL--KLPI 220
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 34328063  315 IGSDGWADRDEVIEGYEVeANGGITI-----KLQSPEVRSFDDYFLKL 357
Cdd:cd06268  221 LGGDGLYSPELLKLGGEA-AEGVVVAvpwhpDSPDPPKQAFVKAYKKK 267
GluR_Homer-bdg pfam10606
Homer-binding domain of metabotropic glutamate receptor; This is the proline-rich region of ...
1149-1199 1.09e-14

Homer-binding domain of metabotropic glutamate receptor; This is the proline-rich region of metabotropic glutamate receptor proteins that binds Homer-related synaptic proteins. The Homer proteins form a physical tether linking mGluRs with the inositol trisphosphate receptors (IP3R) that appears to be due to the proline-rich "Homer ligand" (PPXXFr). Activation of PI turnover triggers intracellular calcium release. MGluR function is altered in the mouse model of human Fragile X syndrome mental retardation, a disorder caused by loss of function mutations in the Fragile X mental retardation gene Fmr1. Homer 3 (and to a lesser extent Homer 1b/c) has been shown to form a multimeric complex with mGlu1a and the IP3 receptor, indicating that Homers may play a role in the localization of receptors to their signalling partners.


Pssm-ID: 431390  Cd Length: 51  Bit Score: 69.41  E-value: 1.09e-14
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 34328063   1149 ALTPPSPFRDSVASGSSVPSSPVSESVLCTPPNVTYASVILRDYKQSSSTL 1199
Cdd:pfam10606    1 ALTPPSPFRDSVCSGSSSPGSPVSESMLCSPPSPTYTSLILRDYSQSSSTL 51
PBP1_ABC_LIVBP-like cd06342
type 1 periplasmic ligand-binding domain of ABC (Atpase Binding Cassette)-type active ...
156-319 1.76e-12

type 1 periplasmic ligand-binding domain of ABC (Atpase Binding Cassette)-type active transport systems involved in the transport of all three branched chain aliphatic amino acids (leucine, isoleucine and valine); This subgroup includes the type 1 periplasmic ligand-binding domain of ABC (Atpase Binding Cassette)-type active transport systems that are involved in the transport of all three branched chain aliphatic amino acids (leucine, isoleucine and valine). This subgroup also includes a leucine-specific binding protein (or LivK), which is very similar in sequence and structure to leucine-isoleucine-valine binding protein (LIVBP). ABC-type active transport systems are transmembrane proteins that function in the transport of diverse sets of substrates across extra- and intracellular membranes, including carbohydrates, amino acids, inorganic ions, dipeptides and oligopeptides, metabolic products, lipids and sterols, and heme, to name a few.


Pssm-ID: 380565 [Multi-domain]  Cd Length: 334  Bit Score: 69.86  E-value: 1.76e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  156 IAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTlYKYFLRVVPSDTLQARAMLD-IVKRYNWTYVSAVHTEG 234
Cdd:cd06342   67 VVAVIGHYNSGAAIAAAPIYAEAGIPMISPSATNPKLTEQG-YKNFFRVVGTDDQQGPAAADyAAKTLKAKRVAVIHDGT 145
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  235 NYGESGMDAFKELAAQEGLCIAHSDKIysNAGEKSFDRLLRKLRERLPKarvVVCFCeGMTVRG--LLSAMRRLGVvgEF 312
Cdd:cd06342  146 AYGKGLADAFKKALKALGGTVVGREGI--TPGTTDFSALLTKIKAANPD---AVYFG-GYYPEAglLLRQLREAGL--KA 217

                 ....*..
gi 34328063  313 SLIGSDG 319
Cdd:cd06342  218 PFMGGDG 224
PBP1_ABC_ligand_binding-like cd06335
type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type ...
153-369 1.25e-11

type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type active transport systems predicted to be involved in transport of amino acids, peptides, or inorganic ions; This subgroup includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type active transport systems that are predicted to be involved in transport of amino acids, peptides, or inorganic ions. Members of this group are sequence-similar to members of the family of ABC-type hydrophobic amino acid transporters, such as leucine-isoleucine-valine binding protein (LIVBP); however their ligand specificity has not been determined experimentally.


Pssm-ID: 380558 [Multi-domain]  Cd Length: 348  Bit Score: 67.63  E-value: 1.25e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  153 KKPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYK--YFLRVVPSDTLQARAMLDIVKRYNWTYVSAV 230
Cdd:cd06335   65 KEKVVAIIGPTNSGVALATIPILQEAKIPLIIPVATGTAITKPPAKPrnYIFRVAASDTLQADFLVDYAVKKGFKKIAIL 144
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  231 HTEGNYGESGMDAFKELAAQEGLCIAHSDKIysNAGEKsfDRLLRKLRERLPKARVVVCFCEGMTVRGLLSAMRRLGVvg 310
Cdd:cd06335  145 HDTTGYGQGGLKDVEAALKKRGITPVATESF--KIGDT--DMTPQLLKAKDAGADVILVYGLGPDLAQILKAMEKLGW-- 218
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 34328063  311 EFSLIGSDGWADRdEVIEGYEVEANGGITIK-----LQSPEVRSFDDYFLKLRLDTNTRNPWFP 369
Cdd:cd06335  219 KVPLVGSWGLSMP-NFIELAGPLAEGTIMTQtfiedYLTPRAKKFIDAYKKKYGTDRIPSPVSA 281
PBP1_ABC_HAAT-like cd06344
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
156-350 2.19e-11

type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems predicted to be involved in uptake of hydrophobic amino acids or peptides; This subgroup includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems that are predicted to be involved in the uptake of hydrophobic amino acids or peptides. This subgroup has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP); however, its ligand specificity has not been determined experimentally.


Pssm-ID: 380567 [Multi-domain]  Cd Length: 332  Bit Score: 66.48  E-value: 2.19e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  156 IAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTlYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGN 235
Cdd:cd06344   66 VVAVIGHRSSYVAIPASIIYERAGLLMLSPGATAPKLTQHG-FKYIFRNIPSDEDIARQLARYAARQGYKRIVIYYDDDS 144
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  236 YGESGMDAFKELAAQEGLCIAHSdKIYSnAGEKSFDRLLRKLRErlpkarvvVCFCEGMTVRG-------LLSAMRRLGV 308
Cdd:cd06344  145 YGKGLANAFEEEARELGITIVDR-RSYS-SDEEDFRRLLSKWKA--------LDFFDAIFLAGsmpegaeFIKQARELGI 214
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 34328063  309 vgEFSLIGSDGWaDRDEVIEGYEVEANGGITI-----KLQSPEVRSF 350
Cdd:cd06344  215 --KVPIIGGDGL-DSPELIEIAGKAAEGVVVAtvfdpDDPRPEVRAF 258
7tmC_GABA-B-R1 cd15291
gamma-aminobutyric acid type B receptor subunit 1, member of the class C family of ...
597-839 3.03e-11

gamma-aminobutyric acid type B receptor subunit 1, member of the class C family of seven-transmembrane G protein-coupled receptors; The type B receptor for gamma-aminobutyric acid, GABA-B, is activated by its endogenous ligand GABA, the principal inhibitory neurotransmitter. The functional GABA-B receptor is an obligatory heterodimer composed of two related subunits, GABA-B1, which is primarily involved in GABA ligand binding, and GABA-B2, which is responsible for both G-protein coupling and trafficking of the heterodimer to the plasma membrane. Activation of GABA-B couples to G(i/o)-type G proteins, which in turn modulate three major downstream effectors: adenylate cyclase, voltage-sensitive Ca2+ channels, and inwardly-rectifying K+ channels. Consequently, GABA-B receptor produces slow and sustained inhibitory responses by decreased neurotransmitter release via inhibition of Ca2+ channels and by postsynaptic hyperpolarization via the activation of K+ channels through the G-protein beta-gamma dimer. The GABA-B is expressed in both pre- and postsynaptic sites of glutamatergic and GABAergic neurons in the brain where it regulates synaptic activity. Thus, the GABA-B receptor agonist, baclofen, is used to treat muscle tightness and cramping caused by spasticity in multiple sclerosis patients. Moreover, GABA-B antagonists improves cognitive performance in mammals, while GABA-B agonists suppress cognitive behavior. In most of the class C family members, the extracellular Venus-flytrap domain in the N-terminus is connected to the seven-transmembrane (7TM) via a cysteine-rich domain (CRD). However, in the GABA-B receptor, the CRD is absent in both subunits and the Venus-flytrap ligand-binding domain is directly connected to the 7TM via a 10-15 amino acids linker, suggesting that GABA-B receptor may utilize a different activation mechanism.


Pssm-ID: 320418  Cd Length: 274  Bit Score: 65.43  E-value: 3.03e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  597 IAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTL------IAKPTTTS-CYLQRLLVGLSSA 669
Cdd:cd15291    7 CLLASLGIFAAVFLLIFNIYNRHRRYIQLSQPHCNNVMLVGCILCLASVFLLgldgrhVSRSHFPLvCQARLWLLCLGFT 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  670 MCYSALVTKTNRIARILAGSKKKICTRKPrfMSAWAQVIIASILISVQL------TLVVTLIIMEPPMPILSYPSIKEVY 743
Cdd:cd15291   87 LAYGSMFTKVWRVHRLTTKKKEKKETRKT--LEPWKLYAVVGILLVVDViilaiwQIVDPLHRTIEEFPLEEPKDTDEDV 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  744 LI------CNTSN----LGVVApvGYNGLLIMSCTYYAFKTRNVPANF-NEAKYIAFTMYTTCIIWLAFVPI--YFGS-- 808
Cdd:cd15291  165 KIlpqlehCSSKKqntwLGIVY--GYKGLLLLFGLFLAYETRNVKVEKiNDSRFVGMSIYNVVVLCLITAPVtmIISSqq 242
                        250       260       270
                 ....*....|....*....|....*....|...
gi 34328063  809 --NYKIITtcFAVSLSVTVALGCMFTPKMYIII 839
Cdd:cd15291  243 daSFAFVS--LAILFSSYITLVLIFVPKIRELI 273
PBP1_GABAb_receptor_plant cd19990
periplasmic ligand-binding domain of Arabidopsis thaliana glutamate receptors and its close ...
152-500 6.41e-11

periplasmic ligand-binding domain of Arabidopsis thaliana glutamate receptors and its close homologs in other plants; This group includes the ligand-binding domain of Arabidopsis thaliana glutamate receptors, which have sequence similarity with animal ionotropic glutamate receptor and its close homologs in other plants. The ligand-binding domain of GABAb receptors 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: 380645 [Multi-domain]  Cd Length: 373  Bit Score: 65.71  E-value: 6.41e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  152 TKKPIAGVIGPGSSSVA---IQVQNLLQlfdIPQIAYSATSIDLSDKTlYKYFLRVVPSDTLQARAMLDIVKRYNWTYVS 228
Cdd:cd19990   61 KNKKVEAIIGPQTSEEAsfvAELGNKAQ---VPIISFSATSPTLSSLR-WPFFIRMTHNDSSQMKAIAAIVQSYGWRRVV 136
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  229 AVHTEGNYGESGM----DAFKELAAQeglcIAHSDKIYSNAGEKSFDRLLRKLRERlpKARV-VVCFCEGMTVRgLLSAM 303
Cdd:cd19990  137 LIYEDDDYGSGIIpylsDALQEVGSR----IEYRVALPPSSPEDSIEEELIKLKSM--QSRVfVVHMSSLLASR-LFQEA 209
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  304 RRLGVVGE-FSLIGSDGWAD-----RDEVIEGYEveanGGITIKLQSPEVRSFDDYFLKlrldtntrnpwfpefWQHRFQ 377
Cdd:cd19990  210 KKLGMMEKgYVWIVTDGITNlldslDSSTISSMQ----GVIGIKTYIPESSEFQDFKAR---------------FRKKFR 270
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  378 crlpghlLENPNFKKVCTGNESLeenYVQDskmgfvinAIYAMAHGlqnMHHALCPGYVglcdAMKPIDGRKLLDFLIKS 457
Cdd:cd19990  271 -------SEYPEEENAEPNIYAL---RAYD--------AIWALAHA---VEKLNSSGGN----ISVSDSGKKLLEEILST 325
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....
gi 34328063  458 SFVGVSGeEVWFDEKGDAPG-RYDIMNLqyteaNRYDYVHVGTW 500
Cdd:cd19990  326 KFKGLSG-EVQFVDGQLAPPpAFEIVNV-----IGKGYRELGFW 363
PBP1_ABC_HAAT-like cd19986
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
154-270 1.13e-10

type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems predicted to be involved in uptake of amino acids or peptides; This subgroup includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems that are predicted to be involved in the uptake of amino acids or peptides. This subgroup has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP); however, its ligand specificity has not been determined experimentally.


Pssm-ID: 380641 [Multi-domain]  Cd Length: 297  Bit Score: 64.18  E-value: 1.13e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  154 KPIAGVIGPGSSSVAIQVQNLLQLFDIPQIaYSATSIDLSDKTlYKYFLRVVPSDTLQARAMLD-IVKRYNWTYVSAVHT 232
Cdd:cd19986   66 DKVVAVIGPHYSTQVLAVSPLVKEAKIPVI-TGGTSPKLTEQG-NPYMFRIRPSDSVSAKALAKyAVEELGAKKIAILYD 143
                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 34328063  233 EGNYGESGMDAFKELAAQEGLCIAHSDKIysNAGEKSF 270
Cdd:cd19986  144 NDDFGTGGADVVTAALKALGLEPVAVESY--NTGDKDF 179
PBP1_ABC_ligand_binding-like cd19984
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
159-358 4.63e-10

type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems predicted to be involved in uptake of amino acids, peptides, or inorganic ions; This subgroup includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems that are predicted to be involved in uptake of amino acids, peptides, or inorganic ions. This subgroup has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP); however, its ligand specificity has not been determined experimentally.


Pssm-ID: 380639 [Multi-domain]  Cd Length: 296  Bit Score: 62.24  E-value: 4.63e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  159 VIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDktLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGE 238
Cdd:cd19984   71 IIGGVCSSETLAIAPIAEQNKVVLISPGASSPEITK--AGDYIFRNYPSDAYQGKVLAEFAYNKLYKKVAILYENNDYGV 148
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  239 SGMDAFKELAAQEGLCIAHSDKIysNAGEKSFDRLLRKLRERLPKARVVVCFCEGMTVrgLLSAMRRLGVVGEFslIGSD 318
Cdd:cd19984  149 GLKDVFKKEFEELGGKIVASESF--EQGETDFRTQLTKIKAANPDAIFLPGYPKEGGL--ILKQAKELGIKAPI--LGSD 222
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 34328063  319 GWADrDEVIEGYEVEANGGITIKLQSPEVRSFDDYFLKLR 358
Cdd:cd19984  223 GFED-PELLEIAGEAAEGVIFTYPAFDDSSEKKQKFFFYR 261
PBP1_ABC_RPA1789-like cd06333
type 1 periplasmic binding-protein component (CouP) of an ABC system (CouPSTU; RPA1789, ...
159-256 1.44e-09

type 1 periplasmic binding-protein component (CouP) of an ABC system (CouPSTU; RPA1789, RPA1791-1793), involved in active transport of lignin-derived aromatic substrates, and its close homologs; This group includes RPA1789 (CouP) from Rhodopseudomonas palustris and its close homologs in other bacteria. RPA1789 (CouP) is the periplasmic binding-protein component of an ABC system (CouPSTU; RPA1789, RPA1791-1793) that is involved in the active transport of lignin-derived aromatic substrates. Members of this group has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP).


Pssm-ID: 380556 [Multi-domain]  Cd Length: 342  Bit Score: 61.02  E-value: 1.44e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  159 VIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTlyKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGE 238
Cdd:cd06333   71 IIGPSTTGESLAVAPIAEEAKVPLISLAGAAAIVEPVR--KWVFKTPQSDSLVAEAILDYMKKKGIKKVALLGDSDAYGQ 148
                         90
                 ....*....|....*...
gi 34328063  239 SGMDAFKELAAQEGLCIA 256
Cdd:cd06333  149 SGRAALKKLAPEYGIEIV 166
7tmC_GABA-B-R2 cd15294
gamma-aminobutyric acid type B receptor subunit 2, member of the class C family of ...
594-835 7.32e-09

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


Pssm-ID: 320421  Cd Length: 270  Bit Score: 58.21  E-value: 7.32e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  594 IIAIAFSCLGILVTLFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTS-------CYLQR--LLV 664
Cdd:cd15294    4 SILSSLTIIGIILASAFLAFNIKFRNHRYIKMSSPYMNNLIILGCMLTYASVILLGLDGSLVSektfetlCTARTwiLCV 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  665 GLSSAmcYSALVTKTNRIARILAGSK--KKICTRKPRFMsawaqviIASILISVQLTLVVTLIIMEPP------MPILSY 736
Cdd:cd15294   84 GFTLA--FGAMFSKTWRVHSIFTNVKlnKKAIKDYKLFI-------IVGVLLLIDICILITWQIVDPFyrtvkeLEPEPD 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  737 PSIKEVYLI-----CNTSNLGVVAPV--GYNGLLIMSCTYYAFKTRNV--PAnFNEAKYIAFTMYTTCIIWLAFVPIYF- 806
Cdd:cd15294  155 PAGDDILIRpeleyCESTHMTIFLGIiyAYKGLLMVFGCFLAWETRNVsiPA-LNDSKYIGMSVYNVVIMCVIGAAVSFi 233
                        250       260       270
                 ....*....|....*....|....*....|..
gi 34328063  807 ---GSNYKIITTCFAVSLSVTVALGCMFTPKM 835
Cdd:cd15294  234 lrdQPNVQFCIISLFIIFCTTITLCLVFVPKL 265
PBP1_ABC_HAAT-like cd19988
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
159-270 7.90e-07

type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems predicted to be involved in uptake of amino acids or peptides; This subgroup includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems that are predicted to be involved in the uptake of amino acids or peptides. This subgroup has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP); however, its ligand specificity has not been determined experimentally.


Pssm-ID: 380643 [Multi-domain]  Cd Length: 302  Bit Score: 52.28  E-value: 7.90e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  159 VIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDkTLYKYFLRVVPSDTLQARAMLD-IVKRYNWTYVSAVHTEGNYG 237
Cdd:cd19988   71 IIGSINSSCTLAAIRVALKAGVPQINPGSSAPTITE-SGNPWVFRCTPDDRQQAYALVDyAFEKLKVTKIAVLYVNDDYG 149
                         90       100       110
                 ....*....|....*....|....*....|...
gi 34328063  238 ESGMDAFKELAAQEGLCIAHSDkiYSNAGEKSF 270
Cdd:cd19988  150 RGGIDAFKDAAKKYGIEVVVEE--SYNRGDKDF 180
PBP1_ABC_ligand_binding-like cd19980
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
159-270 6.45e-06

type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems predicted to be involved in uptake of amino acids, peptides, or inorganic ions; This subgroup includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems that are predicted to be involved in uptake of amino acids, peptides, or inorganic ions. This subgroup has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP); however, its ligand specificity has not been determined experimentally.


Pssm-ID: 380635 [Multi-domain]  Cd Length: 334  Bit Score: 49.53  E-value: 6.45e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  159 VIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSdKTLYKYFLRVVPSDTLQARAMLD-IVKRYNWTYVSAVHTEGNYG 237
Cdd:cd19980   71 IIGAWCSSVTLAVMPVAERAKVPLVVEISSAPKIT-EGGNPYVFRLNPTNSMLAKAFAKyLADKGKPKKVAFLAENDDYG 149
                         90       100       110
                 ....*....|....*....|....*....|...
gi 34328063  238 ESGMDAFKELAAQEGLCIAHSDkiYSNAGEKSF 270
Cdd:cd19980  150 RGAAEAFKKALKAKGVKVVATE--YFDQGQTDF 180
PBP1_ABC_HAAT-like cd06349
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
156-270 7.22e-06

type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems predicted to be involved in uptake of amino acids or peptides; This subgroup includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems that are predicted to be involved in the uptake of amino acids or peptides. This subgroup has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP); however, its ligand specificity has not been determined experimentally.


Pssm-ID: 380572 [Multi-domain]  Cd Length: 338  Bit Score: 49.49  E-value: 7.22e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  156 IAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSdkTLYKYFLRVVPSDTLQARAMLD-IVKRYNWTYVSAVHTEG 234
Cdd:cd06349   68 VVAVIGDFSSSCSMAAAPIYEEAGLVQISPTASHPDFT--KGGDYVFRNSPTQAVEAPFLADyAVKKLGAKKIAIIYLNT 145
                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 34328063  235 NYGESGMDAFKELAAQEGLCIAHSDKIysNAGEKSF 270
Cdd:cd06349  146 DWGVSAADAFKKAAKALGGEIVATEAY--LPGTKDF 179
PBP1_ABC_ligand_binding-like cd06340
type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type ...
156-263 4.45e-05

type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type active transport systems predicted to be involved in transport of amino acids, peptides, or inorganic ions; This subgroup includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type active transport systems that are predicted to be involved in transport of amino acids, peptides, or inorganic ions. This subgroup has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP); however, their ligand specificity has not been determined experimentally.


Pssm-ID: 380563 [Multi-domain]  Cd Length: 352  Bit Score: 47.17  E-value: 4.45e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  156 IAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTlYKYFLRVVPSDTLQARAMLDIVKRYNWTY------VSA 229
Cdd:cd06340   71 VVAIIGAYSSSVTLAASQVAERYGVPFVTASAVADEITERG-FKYVFRTAPTASQFAEDAVDFLKELAKKKgkkikkVAI 149
                         90       100       110
                 ....*....|....*....|....*....|....
gi 34328063  230 VHTEGNYGESGMDAFKELAAQEGLCIAhSDKIYS 263
Cdd:cd06340  150 IYEDSAFGTSVAKGLKKAAKKAGLEVV-LDEPYP 182
PBP1_ABC_ligand_binding-like cd19982
type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type ...
152-253 5.64e-05

type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type active transport systems predicted to be involved in transport of amino acids, peptides, or inorganic ions; This subgroup includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type active transport systems that are predicted to be involved in transport of amino acids, peptides, or inorganic ions. This subgroup has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP); however, their ligand specificity has not been determined experimentally.


Pssm-ID: 380637 [Multi-domain]  Cd Length: 302  Bit Score: 46.51  E-value: 5.64e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  152 TKKPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSiDLSDKTLYKYFLRVVPSDTLQARAMLDIVKRY-NWTYVSAV 230
Cdd:cd19982   64 SQDKVPLIVGGYSSGITLPVAAVAERQKIPLLVPTAAD-DDITKPGYKYVFRLNPPASIYAKALFDFFKELvKPKTIAIL 142
                         90       100
                 ....*....|....*....|...
gi 34328063  231 HTEGNYGESGMDAFKELAAQEGL 253
Cdd:cd19982  143 YENTAFGTSVAKAARRFAKKRGI 165
PBP1_ABC_LivK_ligand_binding-like cd06347
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
156-215 6.93e-05

type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems predicted to be involved in uptake of amino acids, peptides, or inorganic ions; This subgroup includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems that are predicted to be involved in uptake of amino acids, peptides, or inorganic ions. This subgroup has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP); however, its ligand specificity has not been determined experimentally.


Pssm-ID: 380570 [Multi-domain]  Cd Length: 334  Bit Score: 46.38  E-value: 6.93e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  156 IAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKtlYKYFLRVVPSDTLQARAM 215
Cdd:cd06347   68 VVAIIGPVTSSIALAAAPIAQKAKIPMITPSATNPLVTKG--GDYIFRACFTDPFQGAAL 125
PBP1_iGluR_NMDA_NR1 cd06379
N-terminal leucine-isoleucine-valine-binding protein (LIVBP)-like domain of the NR1, an ...
180-271 2.01e-04

N-terminal leucine-isoleucine-valine-binding protein (LIVBP)-like domain of the NR1, an essential channel-forming subunit of the NMDA receptor; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the NR1, an essential channel-forming subunit of the NMDA receptor. The ionotropic N-methyl-D-asparate (NMDA) subtype of glutamate receptor serves critical functions in neuronal development, functioning, and degeneration in the mammalian central nervous system. The functional NMDA receptor is a heterotetramer ccomposed of two NR1 and two NR2 (A, B, C, and D) or of NR3 (A and B) subunits. The receptor controls a cation channel that is highly permeable to monovalent ions and calcium and exhibits voltage-dependent inhibition by magnesium. Dual agonists, glutamate and glycine, are required for efficient activation of the NMDA receptor. When co-expressed with NR1, the NR3 subunits form receptors that are activated by glycine alone and therefore can be classified as excitatory glycine receptors. NR1/NR3 receptors are calcium-impermeable and unaffected by ligands acting at the NR2 glutamate-binding site


Pssm-ID: 380602  Cd Length: 364  Bit Score: 45.02  E-value: 2.01e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  180 IPQIAYSATSIDLSDKTLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNYGESGMDAFKELAAQEGLCIAhsD 259
Cdd:cd06379   92 IPVIGISARDSAFSDKNIHVSFLRTVPPYSHQADVWAEMLRHFEWKQVIVIHSDDQDGRALLGRLETLAETKDIKIE--K 169
                         90
                 ....*....|..
gi 34328063  260 KIYSNAGEKSFD 271
Cdd:cd06379  170 VIEFEPGEKNFT 181
PBP1_ABC_HAAT-like cd19983
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
156-390 3.05e-04

type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems predicted to be involved in uptake of hydrophobic amino acids or peptides; This subgroup includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems that are predicted to be involved in the uptake of hydrophobic amino acids or peptides. This subgroup has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP); however, its ligand specificity has not been determined experimentally.


Pssm-ID: 380638 [Multi-domain]  Cd Length: 303  Bit Score: 44.11  E-value: 3.05e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  156 IAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTlyKYFLRVVPSDTLQARAMLD-IVKRYNWTYVSAVHTEG 234
Cdd:cd19983   67 VVAIIGHMTSAMTVAVLPVINEAKVLMISPTVSTPELSGKD--DYFFRVTPTTRESAQALARyAYNRGGLRRVAVIYDLS 144
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  235 N--YGESGMDAFKELAAQEGLCIAhSDKIYSNAGEKSFDRLLRKLRERLPKARVVVCfcegmtvRGLLSAM-----RRLG 307
Cdd:cd19983  145 NraYSESWLDNFRSEFEALGGRIV-AEIPFSSGADVDFSDLARRLLASKPDGLLLVA-------SAVDTAMlaqqiRKLG 216
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  308 VvgEFSLIGSdGWADRDEVIE--GYEVEangGITIklqspeVRSFDDYflklrlDTNTRNPWFPEFWQHRFQcrlpghll 385
Cdd:cd19983  217 S--KIPLFSS-AWAATEELLElgGKAVE---GMLF------SQAYDRN------SSNPRYLAFKEAYEERFG-------- 270

                 ....*
gi 34328063  386 ENPNF 390
Cdd:cd19983  271 REPSF 275
PBP1_iGluR_Kainate cd06382
N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the kainate ...
156-225 3.27e-04

N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the kainate receptors; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the kainate receptors, non-NMDA ionotropic receptors which respond to the neurotransmitter glutamate. While this N-terminal domain belongs to the periplasmic-binding fold type 1 superfamily, the glutamate-binding domain of the iGluR is structurally homologous to the periplasmic-binding fold type 2. The LIVBP-like domain of iGluRs is thought to play a role in the initial assembly of iGluR subunits, but it is not well understood how this domain is arranged and functions in intact iGluR. Kainate receptors have five subunits, GluR5, GluR6, GluR7, KA1 and KA2, which are structurally similar to AMPA and NMDA subunits of ionotropic glutamate receptors. KA1 and KA2 subunits can only form functional receptors with one of the GluR5-7 subunits. Moreover, GluR5-7 can also form functional homomeric receptor channels activated by kainate and glutamate when expressed in heterologous systems. Kainate receptors are involved in excitatory neurotransmission by activating postsynaptic receptors and in inhibitory neurotransmission by modulating release of the inhibitory neurotransmitter GABA through a presynaptic mechanism. Kainate receptors are closely related to AMAP receptors. In contrast of AMPA receptors, kainate receptors play only a minor role in signaling at synapses and their function is not well defined.


Pssm-ID: 380605  Cd Length: 335  Bit Score: 44.14  E-value: 3.27e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  156 IAGVIGPGSSSVAIQVQNLLQLFDIPQIaysATSIDLSDKTLYKYFLRVVPSDTLQARAMLDIVKRYNWT 225
Cdd:cd06382   62 VAAIFGPSSPSSSDIVQSICDALEIPHI---ETRWDPKESNRDTFTINLYPDPDALSKAYADLVKSLNWK 128
7tmC_RAIG3_GPRC5C cd15277
retinoic acid-inducible orphan G-protein-coupled receptor 3; class C family of ...
594-812 3.33e-04

retinoic acid-inducible orphan G-protein-coupled receptor 3; class C family of seven-transmembrane G protein-coupled receptors, group 5, member C; Retinoic acid-inducible G-protein-coupled receptors (RAIGs), also referred to as GPCR class C group 5, are a group consisting of four orphan receptors RAIG1 (GPRC5A), RAIG2 (GPRC5B), RAIG3 (GPRC5C), and RAIG4 (GPRC5D). Unlike other members of the class C GPCRs which contain a large N-terminal extracellular domain, RAIGs have a shorter N-terminus. Thus, it is unlikely that RAIGs bind an agonist at its N-terminus domain. Instead, the agonists may bind to the seven-transmembrane domain of these receptors. In addition, RAIG2 and RAIG3 contain a cleavable signal peptide whereas RAIG1 and RAIG4 do not. Although their expression is induced by retinoic acid (vitamin A analog), their biological function is not clearly understood. To date, no ligand is known for the members of RAIG family. Three receptor types (RAIG1-3) are found in vertebrates, while RAIG4 is only present in mammals. They show distinct tissue distribution with RAIG1 being primarily expressed in the lung, RAIG2 in the brain and placenta, RAIG3 in the brain, kidney and liver, and RAIG4 in the skin. The specific function of RAIG3 is unknown; however, this protein may play a role in mediating the effects of retinoic acid on embryogenesis, differentiation, and tumorigenesis through interaction with a G-protein signaling cascade.


Pssm-ID: 320404  Cd Length: 250  Bit Score: 43.96  E-value: 3.33e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  594 IIAIAFSCLGILVTLFVTLIFVlyRDTPVV----KSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSA 669
Cdd:cd15277    4 IVLEAVAGAGVVTSFVLTIVLV--ASLPFVqdkkKKSLLGTQVFFLLGTLGLFCLVFAFIVGPNFATCASRRFLFGVLFA 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  670 MCYSALVTKTNRIaRILAgskkkictRKPRFMSAWAQVIIASILISVQLT-----LVVTLIIME-PPMPILSYPsikevy 743
Cdd:cd15277   82 ICFSCLLAHAVRL-NFLA--------RRNRGPRGWVIFLLALGLWLVEVIintewLIITIVRGNaGSAPVLGDP------ 146
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34328063  744 liCNTSNLGVVAPVGYNGLLIMSCTYYAFktrnvPANF-------NEAKYIAFTMYTTCIIWLAFVPIYFGSNYKI 812
Cdd:cd15277  147 --CNIANQDFVMALIYVMFLLLAAFITAW-----PALCgkykhwrKHGAFILVTGFLSVAIWVAWIVMYVYGNQKV 215
PBP1_ABC_HAAT-like cd19985
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
158-323 3.57e-04

type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems predicted to be involved in uptake of hydrophobic amino acids or peptides; This subgroup includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems that are predicted to be involved in the uptake of hydrophobic amino acids or peptides. This subgroup has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP); however, its ligand specificity has not been determined experimentally.


Pssm-ID: 380640 [Multi-domain]  Cd Length: 321  Bit Score: 44.19  E-value: 3.57e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  158 GVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLsdkTLY-KYFLRVVPSDTLQ-------ARAMLDiVKRynwtyVSA 229
Cdd:cd19985   69 AVIGHYYSSASIAAGKIYKKAGIPAITPSATADAV---TRDnPWYFRVIFNDSLQgrflanyAKKVLK-KDK-----VSI 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  230 VHTEGNYGESGMDAFKELAAQEGLCIAHSDKIYSNAGEKSFDRLLRKLRERLPKARVVVCFCEGMTVRG--LLSAMRRLG 307
Cdd:cd19985  140 IYEEDSYGKSLASVFEATARALGLKVLKKWSFDTDSSQLDQNLDQIVDELKKAPDEPGVIFLATHADEGakLIKKLRDAG 219
                        170
                 ....*....|....*.
gi 34328063  308 VvgEFSLIGSDGWADR 323
Cdd:cd19985  220 L--KAPIIGPDSLASE 233
PBP1_ABC_ligand_binding-like cd06345
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
152-253 5.31e-04

type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems predicted to be involved in uptake of amino acids, peptides, or inorganic ions; This subgroup includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems that are predicted to be involved in uptake of amino acids, peptides, or inorganic ions. This subgroup has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP); however, its ligand specificity has not been determined experimentally.


Pssm-ID: 380568 [Multi-domain]  Cd Length: 356  Bit Score: 43.79  E-value: 5.31e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  152 TKKPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTL-----YKYFLRVVPSDTLQARAMLD-----IVKR 221
Cdd:cd06345   61 TEDKVDAIVGGFRSEVVLAAMEVAAEYKVPFIVTGAASPAITKKVKkdyekYKYVFRVGPNNSYLGATVAEflkdlLVEK 140
                         90       100       110
                 ....*....|....*....|....*....|..
gi 34328063  222 YNWTYVSAVHTEGNYGESGMDAFKELAAQEGL 253
Cdd:cd06345  141 LGFKKVAILAEDAAWGRGIAEALKKLLPEAGL 172
PBP1_SBP-like cd19989
periplasmic substrate-binding domain of active transport proteins; Periplasmic ...
159-252 7.85e-04

periplasmic substrate-binding domain of active transport proteins; Periplasmic substrate-binding domain of active transport proteins found in bacteria and Archaea. Members of this group are initial receptors in the process of active transport across cellular membrane, but their substrate specificities are not known in detail. However, they closely resemble the group of AmiC and active transport systems for short-chain amides and urea (FmdDEF), and thus are likely to exhibit a ligand-binding mode similar to that of the amide sensor protein AmiC from Pseudomonas aeruginosa. Moreover, this binding domain has high sequence identity to the family of hydrophobic amino acid transporters (HAAT), and thus it may also be involved in transport of amino acids.


Pssm-ID: 380644 [Multi-domain]  Cd Length: 299  Bit Score: 43.03  E-value: 7.85e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  159 VIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYKYFLRVVPSDTLQARAMLD-IVKRY--NWTYVSAVHTegn 235
Cdd:cd19989   71 LTGAVSSAVALAVAPKAAELKVPYLVTVAADDELTGENCNRYTFRVNTSDRMIARALAPwLAENGgkKWYIVYADYA--- 147
                         90
                 ....*....|....*..
gi 34328063  236 YGESGMDAFKELAAQEG 252
Cdd:cd19989  148 WGQSSAEAFKEAIEELG 164
PBP1_iGluR_NMDA_NR3 cd06377
N-terminal leucine-isoleucine-valine-binding protein (LIVBP)-like domain of the NR3 subunit of ...
402-508 8.20e-04

N-terminal leucine-isoleucine-valine-binding protein (LIVBP)-like domain of the NR3 subunit of NMDA receptor family; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the NR3 subunit of NMDA receptor family. The ionotropic N-methyl-D-asparate (NMDA) subtype of glutamate receptor serves critical functions in neuronal development, functioning, and degeneration in the mammalian central nervous system. The functional NMDA receptor is a heterotetramer composed of two NR1 and two NR2 (A, B, C, and D) or of NR3 (A and B) subunits. The receptor controls a cation channel that is highly permeable to monovalent ions and calcium and exhibits voltage-dependent inhibition by magnesium. Dual agonists, glutamate and glycine, are required for efficient activation of the NMDA receptor. Among NMDA receptor subtypes, the NR2B subunit containing receptors appear particularly important for pain perception; thus NR2B-selective antagonists may be useful in the treatment of chronic pain.


Pssm-ID: 380600 [Multi-domain]  Cd Length: 373  Bit Score: 43.19  E-value: 8.20e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  402 ENYVQDSkMGFVINAIYAMAHGLQNmhHALCPGYVGlCDAMKPID----GRKLLDFLIKSSFVGVSGeEVWFDEKG--DA 475
Cdd:cd06377  262 EAYVQDA-VELVARALSSAALVHPE--LALLPATVN-CNDLKTGGsessGQYLSRFLANTSFQGRTG-TVWVTGSSqvHS 336
                         90       100       110
                 ....*....|....*....|....*....|...
gi 34328063  476 PGRYDIMNLQYTEANRYDYVHVGTWHEGVLNID 508
Cdd:cd06377  337 ERHFKVWSLRRDPLGAPTWATVGSWQDGKLDME 369
7tmC_RAIG2_GPRC5B cd15278
retinoic acid-inducible orphan G-protein-coupled receptor 2; class C family of ...
591-812 8.44e-04

retinoic acid-inducible orphan G-protein-coupled receptor 2; class C family of seven-transmembrane G protein-coupled receptors, group 5, member B; Retinoic acid-inducible G-protein-coupled receptors (RAIGs), also referred to as GPCR class C group 5, are a group consisting of four orphan receptors RAIG1 (GPRC5A), RAIG2 (GPRC5B), RAIG3 (GPRC5C), and RAIG4 (GPRC5D). Unlike other members of the class C GPCRs which contain a large N-terminal extracellular domain, RAIGs have a shorter N-terminus. Thus, it is unlikely that RAIGs bind an agonist at its N-terminus domain. Instead, the agonists may bind to the seven-transmembrane domain of these receptors. In addition, RAIG2 and RAIG3 contain a cleavable signal peptide whereas RAIG1 and RAIG4 do not. Although their expression is induced by retinoic acid (vitamin A analog), their biological function is not clearly understood. To date, no ligand is known for the members of RAIG family. Three receptor types (RAIG1-3) are found in vertebrates, while RAIG4 is only present in mammals. They show distinct tissue distribution with RAIG1 being primarily expressed in the lung, RAIG2 in the brain and placenta, RAIG3 in the brain, kidney and liver, and RAIG4 in the skin. RAIG2 (GPRC5B), a mammalian Boss (Bride of sevenless) homolog, has been shown to activate obesity-associated inflammatory signaling in adipocytes, and that the GPRC5B knockout mice have been shown to be resistance to high-fat diet-induced obesity and insulin resistance.


Pssm-ID: 320405  Cd Length: 244  Bit Score: 42.49  E-value: 8.44e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  591 IESIIAIAFSCLGILVTLFVTLIFV--LYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSS 668
Cdd:cd15278    1 IWGIVVEAVAGAGVLITLLLMLILLvrLPFIKEKEKKSPVGPHFLFLLGTLGLFGLTFAFIIQEDETICSLRRFLWGVLF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  669 AMCYSALVTKTNRIARILagskkkictRKPRFMSAWAQVIIASILISVQLTLVVTLIIMEppmpilsypSIKEVYLICNT 748
Cdd:cd15278   81 ALCFSCLLAQGWRLRRLV---------RHGKGPSGWHLTGLALCLMLVQVIIAVEWLILT---------VLRDGRPACQY 142
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 34328063  749 SNLGVVAPVGYNGLLIMSCTYYAF-----KTRNVPANfneAKYIAFTMYTTCIIWLAFVPIYFGSNYKI 812
Cdd:cd15278  143 EPMDFVMALIYVMVLLVATLGLALftlcgKFQKWKKN---GICLLITCFLSVLIWVAWMTMYLYGNDEL 208
PBP1_As_SBP-like cd06330
periplasmic substrate-binding domain of active transport proteins; Periplasmic ...
159-246 8.80e-04

periplasmic substrate-binding domain of active transport proteins; Periplasmic substrate-binding domain of active transport proteins found in bacteria and Archaea that is predicted to be involved in the efflux of toxic compounds. Members of this subgroup include proteins from Herminiimonas arsenicoxydans, which is resistant to arsenic (As) and various heavy metals such as cadmium and zinc. Moreover, they show significant sequence similarity to the cluster of AmiC and active transport systems for short-chain amides and urea (FmdDEF), and thus are likely to exhibit a ligand-binding mode similar to that of the amide sensor protein AmiC from Pseudomonas aeruginosa.


Pssm-ID: 380553 [Multi-domain]  Cd Length: 342  Bit Score: 42.93  E-value: 8.80e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  159 VIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYKYFLRVVPSDTLQARAMLDIVKRYNWTYVSAVHTEGNY-- 236
Cdd:cd06330   71 LIGTISSGVALAVAPVAEELKVLFIATDAATDRLTEENFNPYVFRTSPNTYMDAVAAALYAAKKPPDVKRWAGIGPDYey 150
                         90
                 ....*....|
gi 34328063  237 GESGMDAFKE 246
Cdd:cd06330  151 GRDSWAAFKA 160
7tmC_Boss cd15042
Bride of sevenless, member of the class C family of seven-transmembrane G protein-coupled ...
602-839 9.68e-04

Bride of sevenless, member of the class C family of seven-transmembrane G protein-coupled receptors; Bride of Sevenless (Boss) is a putative Drosophila melanogaster G protein-coupled receptor that functions as a glucose-responding receptor to regulate energy metabolism. Boss is expressed predominantly in the fly's fat body, a nutrient-sensing tissue functionally analogous to the mammalian liver and adipose tissues, and in photoreceptor cells. Boss, which is expressed on the surface of R8 photoreceptor cell, binds and activates the Sevenless receptor tyrosine kinase on the neighboring R7 precursor cell. Activation of Sevenless results in phosphorylation of the Sevenless, triggering a signaling transduction cascade through Ras pathway that ultimately leads to the differentiation of the R7 precursor into a fully functional R7 photoreceptor, the last of eight photoreceptors to differentiate in each ommatidium of the developing Drosophila eye. In the absence of either of Sevenless or Boss, the R7 precursor fails to differentiate as a photoreceptor and instead develops into a non-neuronal cone cell. Moreover, Boss mutants in Drosophila showed elevated food intake, but reduced stored triglyceride levels, suggesting that Boss may play a role in regulating energy homeostasis in nutrient sensing tissues. Furthermore, GPRC5B, a mammalian Boss homolog, activates obesity-associated inflammatory signaling in adipocytes, and that the GPRC5B knockout mice showed resistance to high-fat diet-induced obesity and insulin resistance.


Pssm-ID: 320170  Cd Length: 238  Bit Score: 42.41  E-value: 9.68e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  602 LGILVTLfVTLIFVLYRDT--PVVKSSSRELCYIILAGIF-LGYVCPFTL--IAKPTTTSCYLQRLLVGLSSAMCYSALV 676
Cdd:cd15042   12 LGILFCC-AILVFIVVRVTtkDVLEGNPVLTILLLLALIFtFLSFLPFSMedDYFGKNSLCAVRILLTTLAFGFTFSLML 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  677 TKtnriARILAGSKKKICtrkprFMS---AWAQVIIASILISVQLTLVVTLIImeppmpiLSYPSIKEVYlicntSNLGV 753
Cdd:cd15042   91 SR----ALFLALSTGEGG-----FLShvnGYLQSVMCLFSFGVQVAMSVQYFV-------LNHANSAVIY-----RGLWF 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  754 VAPVGYNGLLIMS---CTYYAFKTRNvpaNFNEAKYIAFTMYTTCIIWLAFVP--IYFGSNYKIITTCFAVSLSVTVALG 828
Cdd:cd15042  150 IALLGYDIFLLIAlfvLCPFIFRSQR---NYREGKYFFGASIGLLVIWVIWLPcfLLMGPEWRDAVISFGLVATAYAILV 226
                        250
                 ....*....|.
gi 34328063  829 CMFTPKMYIII 839
Cdd:cd15042  227 GILVPRTYLMT 237
PBP1_YraM_LppC_lipoprotein-like cd06339
periplasmic binding component of lipoprotein LppC, an immunodominant antigen; This subgroup ...
159-252 1.69e-03

periplasmic binding component of lipoprotein LppC, an immunodominant antigen; This subgroup includes periplasmic binding component of lipoprotein LppC, an immunodominant antigen, whose molecular function is not characterized. Members of this subgroup are predicted to be involved in transport of lipid compounds, and they are sequence similar to the family of ABC-type hydrophobic amino acid transporters (HAAT).


Pssm-ID: 380562 [Multi-domain]  Cd Length: 331  Bit Score: 41.87  E-value: 1.69e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  159 VIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSDKTLYKYFLRvvPSDtlQARAMLDIVKRYNWTYVSAVHTEGNYGE 238
Cdd:cd06339   63 IIGPLLKSSVAALAAAAQALGVPVLALNNDESATAGPGLFQFGLS--PED--EARQAARYAVQQGLRRFAVLAPDNAYGQ 138
                         90
                 ....*....|....
gi 34328063  239 SGMDAFKELAAQEG 252
Cdd:cd06339  139 RVANAFREAWQALG 152
PBP1_ABC_HAAT-like cd19981
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
152-356 2.09e-03

type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems predicted to be involved in uptake of amino acids or peptides; This subgroup includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems that are predicted to be involved in the uptake of amino acids or peptides. This subgroup has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP); however, its ligand specificity has not been determined experimentally.


Pssm-ID: 380636 [Multi-domain]  Cd Length: 297  Bit Score: 41.51  E-value: 2.09e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  152 TKKPIAGVIGPGSSSVAIQVQNLLQLFDIPQIAYSATSIDLSdKTlYKYFLRVVPSDTLQARAMLD-IVKRYNWTYVSAV 230
Cdd:cd19981   64 EQDKVVAVVSGSYSGPTRAAAPIFQEAKVPMVSAYAVHPDIT-KA-GDYVFRVAFLGPVQGRAGAEyAVKDLGAKKVAIL 141
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  231 HTEGNYGESGMDAFKELAAQEGLCIAhSDKIYSnAGEKSFDRLLRKLRERLPKARVVVCFceGMTVRGLLSAMRRLGVvg 310
Cdd:cd19981  142 TIDNDFGKSLAAGFKEEAKKLGAEIV-SEYAYA-LGDRDFRPILTKIKSANPDAIYASGY--YAEAAPIVKQARELGI-- 215
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 34328063  311 EFSLIGSDGwADRDEVIEGYEVEANGG-ITIKLQSPEVRSFDDYFLK 356
Cdd:cd19981  216 KVPIIGQEG-YDSPKFIEIAGSAAEGViITTSLNRDSDRPITQKFIK 261
7tmC_RAIG_GPRC5 cd15043
retinoic acid-inducible orphan G-protein-coupled receptors; class C family of ...
594-809 4.78e-03

retinoic acid-inducible orphan G-protein-coupled receptors; class C family of seven-transmembrane G protein-coupled receptors, group 5; Retinoic acid-inducible G-protein-coupled receptors (RAIGs), also referred to as GPCR class C group 5, are a group consisting of four orphan receptors RAIG1 (GPRC5A), RAIG2 (GPRC5B), RAIG3 (GPRC5C), and RAIG4 (GPRC5D). Unlike other members of the class C GPCRs which contain a large N-terminal extracellular domain, RAIGs have a shorter N-terminus. Thus, it is unlikely that RAIGs bind an agonist at its N-terminus domain. Instead, agonists may bind to the seven-transmembrane domain of these receptors. In addition, RAIG2 and RAIG3 contain a cleavable signal peptide whereas RAIG1 and RAIG4 do not. Although their expression is induced by retinoic acid (vitamin A analog), their biological function is not clearly understood. To date, no ligand is known for the members of RAIG family. Three receptor types (RAIG1-3) are found in vertebrates, while RAIG4 is only present in mammals. They show distinct tissue distribution with RAIG1 being primarily expressed in the lung, RAIG2 in the brain and placenta, RAIG3 in the brain, kidney and liver, and RAIG4 in the skin. RAIG1 is evolutionarily conserved from mammals to fish. RAIG1 has been to shown to act as a tumor suppressor in non-small cell lung carcinoma as well as oral squamous cell carcinoma, but it could also act as an oncogene in breast cancer, colorectal cancer, and pancreatic cancer. Studies have shown that overexpression of RAIG1 decreases intracellular cAMP levels. Moreover, knocking out RAIG1 induces the activation of the NF-kB and STAT3 signaling pathways leading to cell proliferation and resistance to apoptosis. RAIG2 (GPRC5B), a mammalian Boss (Bride of sevenless) homolog, activates obesity-associated inflammatory signaling in adipocytes, and GPRC5B knockout mice show resistance to high-fat diet-induced obesity and insulin resistance. The specific functions of RAIG3 and RAIG4 are unknown; however, they may play roles in mediating the effects of retinoic acid on embryogenesis, differentiation, and tumorigenesis through interactions with G-protein signaling pathways.


Pssm-ID: 320171  Cd Length: 248  Bit Score: 40.24  E-value: 4.78e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  594 IIAIAFSCLGILVTLFVTLIFVLYrdTPVVKSSSRE----LCYIILAGIfLGYVC-PFTLIAKPTTTSCYLQRLLVGLSS 668
Cdd:cd15043    4 IVLEAVAGAGVVTTVALMLILPIL--LPFVQDSNKRsmlgTQFLFLLGT-LGLFGlTFAFIIGLDGSTCPTRRFLFGVLF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34328063  669 AMCYSALVTKTNRIARILagskkkictRKPRFMSAWAQVIIASILISVQLTLVVTLIIMEppmpILSYPSIKEVYLICNT 748
Cdd:cd15043   81 AICFSCLLAHAVSLTKLV---------RGRKGPSGWVILGLALGLSLVQVIIAIEWLVLT----MNRTNVNVFSELSCAR 147
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 34328063  749 SNLGVVAPVGYNGLLIMSCTYYAFKTrnVPANFNEAK----YIAFTMYTTCIIWLAFVPIYFGSN 809
Cdd:cd15043  148 RNMDFVMALIYVMFLLALTFLMASFT--LCGSFKRWKrhgaFILLTMLLSVAIWVAWITMYMLGN 210
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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