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Conserved domains on  [gi|1907159703|ref|XP_036020613|]
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metabotropic glutamate receptor 3 isoform X1 [Mus musculus]

Protein Classification

G-protein coupled receptor( domain architecture ID 11570944)

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_groupII cd06375
ligand binding domain of the group II metabotropic glutamate receptor; Ligand binding domain ...
33-494 0e+00

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: 956.20  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  33 IKIEGDLVLGGLFPINEKGTGTEECGRINEDRGIQRLEAMLFAIDEINKDNYLLPGVKLGVHILDTCSRDTYALEQSLEF 112
Cdd:cd06375     1 IKLEGDLVLGGLFPVHEKGEGMEECGRINEDRGIQRLEAMLFAIDRINRDPHLLPGVRLGVHILDTCSRDTYALEQSLEF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 113 VRASLTKVDEAEYMCPD-GSYAIQENIPLLIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTV 191
Cdd:cd06375    81 VRASLTKVDDSEYMCPDdGSYAIQEDSPLPIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 192 PPDFYQAKAMAEILRYFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSNIRKSYDSVIRELLQKPNARV 271
Cdd:cd06375   161 PPDFYQAKAMAEILRFFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSADRKSFDGVIRELLQKPNARV 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 272 VVLFMRSDDSRELIAAASRVNASFTWVASDGWGAQESIVKGSEHVAYGAITLELASHPVRQFDRYFQSLNPYNNHRNPWF 351
Cdd:cd06375   241 VVLFTRSDDARELLAAAKRLNASFTWVASDGWGAQESIVKGSEDVAEGAITLELASHPIPDFDRYFQSLTPYNNHRNPWF 320
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 352 RDFWEQKFQCSLQNKRNHRQICDKHLAIDSSNYEQESKIMFVVNAVYAMAHALHKMQRTLCPNTTKLCDAMKILDGKKLY 431
Cdd:cd06375   321 RDFWEQKFQCSLQNKSQAASVSDKHLSIDSSNYEQESKIMFVVNAVYAMAHALHNMQRTLCPNTTRLCDAMRSLDGKKLY 400
                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907159703 432 KDYLLKINFTAPFnPNKGADSIVKFDTYGDGMGRYNVFNFQHIGGKYSYLKVGHWAETLYLDV 494
Cdd:cd06375   401 KDYLLNVSFTAPF-PPADAGSEVKFDAFGDGLGRYNIFNYQRAGGSYGYRYKGVGKWANSLDL 462
7tmC_mGluR3 cd15448
metabotropic glutamate receptor 3 in group 2, member of the class C family of ...
575-828 0e+00

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: 521.43  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 575 AWAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAI 654
Cdd:cd15448     1 AWAIGPVTIACLGFICTCMVITVFIKHNNTPLVKASGRELCYILLFGVFLSYCMTFFFIAKPSPVICTLRRLGLGTSFAV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGTRRYTLPEKRETVILKCNVKD 734
Cdd:cd15448    81 CYSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLSLILVQIVVVSVWLILEAPGTRRYTLPEKRETVILKCNVKD 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 735 SSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFVV 814
Cdd:cd15448   161 SSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFVV 240
                         250
                  ....*....|....
gi 1907159703 815 LGCLFAPKVHIVLF 828
Cdd:cd15448   241 LGCLFAPKVHIILF 254
NCD3G pfam07562
Nine Cysteines Domain of family 3 GPCR; This conserved sequence contains several ...
505-555 1.61e-17

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: 76.91  E-value: 1.61e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907159703 505 PTSQCSDPCAPNEMKNMQPGD-VCCWICIPCEPYEYL-VDEFTCMDCGPGQWP 555
Cdd:pfam07562   1 PSSVCSESCPPGQRKSQQGGApVCCWDCVPCPEGEISnTDSDTCKKCPEGQWP 53
 
Name Accession Description Interval E-value
PBP1_mGluR_groupII cd06375
ligand binding domain of the group II metabotropic glutamate receptor; Ligand binding domain ...
33-494 0e+00

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: 956.20  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  33 IKIEGDLVLGGLFPINEKGTGTEECGRINEDRGIQRLEAMLFAIDEINKDNYLLPGVKLGVHILDTCSRDTYALEQSLEF 112
Cdd:cd06375     1 IKLEGDLVLGGLFPVHEKGEGMEECGRINEDRGIQRLEAMLFAIDRINRDPHLLPGVRLGVHILDTCSRDTYALEQSLEF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 113 VRASLTKVDEAEYMCPD-GSYAIQENIPLLIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTV 191
Cdd:cd06375    81 VRASLTKVDDSEYMCPDdGSYAIQEDSPLPIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 192 PPDFYQAKAMAEILRYFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSNIRKSYDSVIRELLQKPNARV 271
Cdd:cd06375   161 PPDFYQAKAMAEILRFFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSADRKSFDGVIRELLQKPNARV 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 272 VVLFMRSDDSRELIAAASRVNASFTWVASDGWGAQESIVKGSEHVAYGAITLELASHPVRQFDRYFQSLNPYNNHRNPWF 351
Cdd:cd06375   241 VVLFTRSDDARELLAAAKRLNASFTWVASDGWGAQESIVKGSEDVAEGAITLELASHPIPDFDRYFQSLTPYNNHRNPWF 320
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 352 RDFWEQKFQCSLQNKRNHRQICDKHLAIDSSNYEQESKIMFVVNAVYAMAHALHKMQRTLCPNTTKLCDAMKILDGKKLY 431
Cdd:cd06375   321 RDFWEQKFQCSLQNKSQAASVSDKHLSIDSSNYEQESKIMFVVNAVYAMAHALHNMQRTLCPNTTRLCDAMRSLDGKKLY 400
                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907159703 432 KDYLLKINFTAPFnPNKGADSIVKFDTYGDGMGRYNVFNFQHIGGKYSYLKVGHWAETLYLDV 494
Cdd:cd06375   401 KDYLLNVSFTAPF-PPADAGSEVKFDAFGDGLGRYNIFNYQRAGGSYGYRYKGVGKWANSLDL 462
7tmC_mGluR3 cd15448
metabotropic glutamate receptor 3 in group 2, member of the class C family of ...
575-828 0e+00

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: 521.43  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 575 AWAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAI 654
Cdd:cd15448     1 AWAIGPVTIACLGFICTCMVITVFIKHNNTPLVKASGRELCYILLFGVFLSYCMTFFFIAKPSPVICTLRRLGLGTSFAV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGTRRYTLPEKRETVILKCNVKD 734
Cdd:cd15448    81 CYSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLSLILVQIVVVSVWLILEAPGTRRYTLPEKRETVILKCNVKD 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 735 SSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFVV 814
Cdd:cd15448   161 SSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFVV 240
                         250
                  ....*....|....
gi 1907159703 815 LGCLFAPKVHIVLF 828
Cdd:cd15448   241 LGCLFAPKVHIILF 254
ANF_receptor pfam01094
Receptor family ligand binding region; This family includes extracellular ligand binding ...
67-473 1.13e-91

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: 293.52  E-value: 1.13e-91
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  67 QRLEAMLFAIDEINKDNYLLPGVKLGVHILDTCSRDTYALEQSLEFVRASltkvdeaeymcpdgsyaiqenipllIAGVI 146
Cdd:pfam01094   1 LVLLAVRLAVEDINADPGLLPGTKLEYIILDTCCDPSLALAAALDLLKGE-------------------------VVAII 55
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 147 GGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDFYQAKAMAEILRYFNWTYVSTVASEGDYGETG 226
Cdd:pfam01094  56 GPSCSSVASAVASLANEWKVPLISYGSTSPALSDLNRYPTFLRTTPSDTSQADAIVDILKHFGWKRVALIYSDDDYGESG 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 227 IEAFEQEARLRNICIATAEKVGRSnirKSYDSVIRELLQ--KPNARVVVLFMRSDDSRELIAAASRVN---ASFTWVASD 301
Cdd:pfam01094 136 LQALEDALRERGIRVAYKAVIPPA---QDDDEIARKLLKevKSRARVIVVCCSSETARRLLKAARELGmmgEGYVWIATD 212
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 302 GWGAQESIVKGSEHVAYGAITlelashpvrqfdrYFQSLNPYnnhrNPWFRDFWEQKFQCSLQNKRNhrqicdkhlaids 381
Cdd:pfam01094 213 GLTTSLVILNPSTLEAAGGVL-------------GFRLHPPD----SPEFSEFFWEKLSDEKELYEN------------- 262
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 382 SNYEQESKIMFVVNAVYAMAHALHKMQRTLCPNTtkLCDAMKILDGKKLYKDYLLKINFTapfnpnkGADSIVKFDTYGD 461
Cdd:pfam01094 263 LGGLPVSYGALAYDAVYLLAHALHNLLRDDKPGR--ACGALGPWNGGQKLLRYLKNVNFT-------GLTGNVQFDENGD 333
                         410
                  ....*....|...
gi 1907159703 462 GM-GRYNVFNFQH 473
Cdd:pfam01094 334 RInPDYDILNLNG 346
7tm_3 pfam00003
7 transmembrane sweet-taste receptor of 3 GCPR; This is a domain of seven transmembrane ...
570-822 1.83e-76

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: 249.11  E-value: 1.83e-76
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 570 IRWEDAWAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSpVICALRRLGLG 649
Cdd:pfam00003   1 LDLSAPWGIVLEALAALGILLTLVLLVVFLLHRKTPIVKASNRSLSFLLLLGLLLLFLLAFLFIGKPT-VTCALRRFLFG 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 650 TSFAICYSALLTKTNCIARIFdgvkngAQRPKFISPSSQVFICLGLILVQIVMVSVWLILeTPGTRRYTLPEKRETVILK 729
Cdd:pfam00003  80 VGFTLCFSCLLAKTFRLVLIF------RRRKPGPRGWQLLLLALGLLLVQVIILTEWLID-PPFPEKDNLSEGKIILECE 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 730 CNVKDSSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYV-TSSDYRVQTTTM-CISV 807
Cdd:pfam00003 153 GSTSIAFLDFVLAYVGLLLLAGFLLAFKTRKLPDNFNEAKFITFSMLLSVLIWVAFIPMYLYgNKGKGTWDPVALaIFAI 232
                         250
                  ....*....|....*
gi 1907159703 808 SLSGFVVLGCLFAPK 822
Cdd:pfam00003 233 LASGWVLLGLYFIPK 247
LivK COG0683
ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid ...
36-299 1.77e-19

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: 90.38  E-value: 1.77e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  36 EGDLVLGGLFPInekgTGTeecgriNEDRGIQRLEAMLFAIDEINKDNYLLpGVKLGVHILDTCSRDTYALEQSLEFVRA 115
Cdd:COG0683     1 ADPIKIGVLLPL----TGP------YAALGQPIKNGAELAVEEINAAGGVL-GRKIELVVEDDASDPDTAVAAARKLIDQ 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 116 SltKVDeaeymcpdgsyaiqeniplliaGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDF 195
Cdd:COG0683    70 D--KVD----------------------AIVGPLSSGVALAVAPVAEEAGVPLISPSATAPALTGPECSPYVFRTAPSDA 125
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 196 YQAKAMAEILRY-FNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSNirKSYDSVIRELLQKpNARVVVL 274
Cdd:COG0683   126 QQAEALADYLAKkLGAKKVALLYDDYAYGQGLAAAFKAALKAAGGEVVGEEYYPPGT--TDFSAQLTKIKAA-GPDAVFL 202
                         250       260
                  ....*....|....*....|....*
gi 1907159703 275 FMRSDDSRELIAAASRVNASFTWVA 299
Cdd:COG0683   203 AGYGGDAALFIKQAREAGLKGPLNK 227
NCD3G pfam07562
Nine Cysteines Domain of family 3 GPCR; This conserved sequence contains several ...
505-555 1.61e-17

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: 76.91  E-value: 1.61e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907159703 505 PTSQCSDPCAPNEMKNMQPGD-VCCWICIPCEPYEYL-VDEFTCMDCGPGQWP 555
Cdd:pfam07562   1 PSSVCSESCPPGQRKSQQGGApVCCWDCVPCPEGEISnTDSDTCKKCPEGQWP 53
 
Name Accession Description Interval E-value
PBP1_mGluR_groupII cd06375
ligand binding domain of the group II metabotropic glutamate receptor; Ligand binding domain ...
33-494 0e+00

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: 956.20  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  33 IKIEGDLVLGGLFPINEKGTGTEECGRINEDRGIQRLEAMLFAIDEINKDNYLLPGVKLGVHILDTCSRDTYALEQSLEF 112
Cdd:cd06375     1 IKLEGDLVLGGLFPVHEKGEGMEECGRINEDRGIQRLEAMLFAIDRINRDPHLLPGVRLGVHILDTCSRDTYALEQSLEF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 113 VRASLTKVDEAEYMCPD-GSYAIQENIPLLIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTV 191
Cdd:cd06375    81 VRASLTKVDDSEYMCPDdGSYAIQEDSPLPIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTV 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 192 PPDFYQAKAMAEILRYFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSNIRKSYDSVIRELLQKPNARV 271
Cdd:cd06375   161 PPDFYQAKAMAEILRFFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSADRKSFDGVIRELLQKPNARV 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 272 VVLFMRSDDSRELIAAASRVNASFTWVASDGWGAQESIVKGSEHVAYGAITLELASHPVRQFDRYFQSLNPYNNHRNPWF 351
Cdd:cd06375   241 VVLFTRSDDARELLAAAKRLNASFTWVASDGWGAQESIVKGSEDVAEGAITLELASHPIPDFDRYFQSLTPYNNHRNPWF 320
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 352 RDFWEQKFQCSLQNKRNHRQICDKHLAIDSSNYEQESKIMFVVNAVYAMAHALHKMQRTLCPNTTKLCDAMKILDGKKLY 431
Cdd:cd06375   321 RDFWEQKFQCSLQNKSQAASVSDKHLSIDSSNYEQESKIMFVVNAVYAMAHALHNMQRTLCPNTTRLCDAMRSLDGKKLY 400
                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907159703 432 KDYLLKINFTAPFnPNKGADSIVKFDTYGDGMGRYNVFNFQHIGGKYSYLKVGHWAETLYLDV 494
Cdd:cd06375   401 KDYLLNVSFTAPF-PPADAGSEVKFDAFGDGLGRYNIFNYQRAGGSYGYRYKGVGKWANSLDL 462
PBP1_mGluR cd06362
ligand binding domain of metabotropic glutamate receptors (mGluR); Ligand binding domain of ...
37-495 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: 683.64  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  37 GDLVLGGLFPINEKGTGTEECGRINEDRGIQRLEAMLFAIDEINKDNYLLPGVKLGVHILDTCSRDTYALEQSLEFVRAS 116
Cdd:cd06362     1 GDINLGGLFPVHERSSSGECCGEIREERGIQRLEAMLFAIDEINSRPDLLPNITLGFVILDDCSSDTTALEQALHFIRDS 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 117 LTKVDEAEYMC--PDGSYAIQENIPLLIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPD 194
Cdd:cd06362    81 LLSQESAGFCQcsDDPPNLDESFQFYDVVGVIGAESSSVSIQVANLLRLFKIPQISYASTSDELSDKERYPYFLRTVPSD 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 195 FYQAKAMAEILRYFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSNIRKSYDSVIRELLQKPNARVVVL 274
Cdd:cd06362   161 SFQAKAIVDILLHFNWTYVSVVYSEGSYGEEGYKAFKKLARKAGICIAESERISQDSDEKDYDDVIQKLLQKKNARVVVL 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 275 FMRSDDSRELIAAASRVNAS--FTWVASDGWGAQESIVKGSEHVAYGAITLELASHPVRQFDRYFQSLNPYNNHRNPWFR 352
Cdd:cd06362   241 FADQEDIRGLLRAAKRLGASgrFIWLGSDGWGTNIDDLKGNEDVALGALTVQPYSEEVPRFDDYFKSLTPSNNTRNPWFR 320
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 353 DFWEQKFQCSLQNKRNHRQICDKHLAIDSSNYEQESKIMFVVNAVYAMAHALHKMQRTLCPNTTKLC-DAMKILDGKKLy 431
Cdd:cd06362   321 EFWQELFQCSFRPSRENSCNDDKLLINKSEGYKQESKVSFVIDAVYAFAHALHKMHKDLCPGDTGLCqDLMKCIDGSEL- 399
                         410       420       430       440       450       460
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907159703 432 KDYLLKINFTAPFNpnkgadSIVKFDTYGDGMGRYNVFNFQ-HIGGKYSYLKVGHWAE-TLYLDVD 495
Cdd:cd06362   400 LEYLLNVSFTGEAG------GEIRFDENGDGPGRYDIMNFQrNNDGSYEYVRVGVWDQyTQKLSLN 459
PBP1_mGluR_groupIII cd06376
ligand-binding domain of the group III metabotropic glutamate receptor; Ligand-binding domain ...
33-499 0e+00

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: 564.43  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  33 IKIEGDLVLGGLFPINEKGTGTEECGRINEDRGIQRLEAMLFAIDEINKDNYLLPGVKLGVHILDTCSRDTYALEQSLEF 112
Cdd:cd06376     1 IRVEGDITLGGLFPVHARGLAGVPCGEIKKEKGIHRLEAMLYALDQINSDPDLLPNVTLGARILDTCSRDTYALEQSLTF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 113 VRASLTKvDEAEYMCPDGSYAIQENiPLLIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVP 192
Cdd:cd06376    81 VQALIQK-DTSDVRCTNGDPPVFVK-PEKVVGVIGASASSVSIMVANILRLFQIPQISYASTAPELSDDRRYDFFSRVVP 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 193 PDFYQAKAMAEILRYFNWTYVSTVASEGDYGETGIEAFEQEAR-LRNICIATAEKVGRSNIRKSYDSVIRELLQKPNARV 271
Cdd:cd06376   159 PDSFQAQAMVDIVKALGWNYVSTLASEGNYGEKGVESFVQISReAGGVCIAQSEKIPRERRTGDFDKIIKRLLETPNARA 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 272 VVLFMRSDDSRELIAAASRVNAS--FTWVASDGWGAQESIVKGSEHVAYGAITLELASHPVRQFDRYFQSLNPYNNHRNP 349
Cdd:cd06376   239 VVIFADEDDIRRVLAAAKRANKTghFLWVGSDSWGAKISPVLQQEDVAEGAITILPKRASIEGFDAYFTSRTLENNRRNV 318
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 350 WFRDFWEQKFQCSLQN----KRNHRQIC--DKHLAIDsSNYEQESKIMFVVNAVYAMAHALHKMQRTLCPNTTKLCDAMK 423
Cdd:cd06376   319 WFAEFWEENFNCKLTSsgskKEDTLRKCtgQERIGRD-SGYEQEGKVQFVVDAVYAMAHALHNMNKDLCPGYRGLCPEME 397
                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907159703 424 ILDGKKLYKdYLLKINFTAPfnpnkgADSIVKFDTYGDGMGRYNVFNFQ-HIGGKYSYLKVGHWAETLYLDVDSIHW 499
Cdd:cd06376   398 PAGGKKLLK-YIRNVNFNGS------AGTPVMFNKNGDAPGRYDIFQYQtTNGSNYGYRLIGQWTDELQLNIEDMQW 467
7tmC_mGluR3 cd15448
metabotropic glutamate receptor 3 in group 2, member of the class C family of ...
575-828 0e+00

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: 521.43  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 575 AWAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAI 654
Cdd:cd15448     1 AWAIGPVTIACLGFICTCMVITVFIKHNNTPLVKASGRELCYILLFGVFLSYCMTFFFIAKPSPVICTLRRLGLGTSFAV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGTRRYTLPEKRETVILKCNVKD 734
Cdd:cd15448    81 CYSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLSLILVQIVVVSVWLILEAPGTRRYTLPEKRETVILKCNVKD 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 735 SSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFVV 814
Cdd:cd15448   161 SSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFVV 240
                         250
                  ....*....|....
gi 1907159703 815 LGCLFAPKVHIVLF 828
Cdd:cd15448   241 LGCLFAPKVHIILF 254
7tmC_mGluR_group2 cd15284
metabotropic glutamate receptors in group 2, member of the class C family of ...
575-828 1.40e-179

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: 517.48  E-value: 1.40e-179
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 575 AWAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAI 654
Cdd:cd15284     1 AWAIGPVTIACLGFLCTLFVIGVFIKHNNTPLVKASGRELCYILLFGVFLCYCMTFIFIAKPSPAICTLRRLGLGTSFAV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGTRRYTLPEKRETVILKCNVKD 734
Cdd:cd15284    81 CYSALLTKTNRIARIFSGVKDGAQRPRFISPSSQVFICLALISVQLLVVSVWLLVEAPGTRRYTLPEKRETVILKCNVRD 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 735 SSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFVV 814
Cdd:cd15284   161 SSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFVV 240
                         250
                  ....*....|....
gi 1907159703 815 LGCLFAPKVHIVLF 828
Cdd:cd15284   241 LGCLFAPKVHIILF 254
PBP1_mGluR_groupI cd06374
ligand binding domain of the group I metabotropic glutamate receptor; Ligand binding domain of ...
30-486 3.52e-174

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: 512.27  E-value: 3.52e-174
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  30 RREIKIEGDLVLGGLFPINEKGTGTE----ECGRINEDRGIQRLEAMLFAIDEINKDNYLLPGVKLGVHILDTCSRDTYA 105
Cdd:cd06374     1 RLVARMPGDIIIGALFPVHHQPPLKKvfsrKCGEIREQYGIQRVEAMFRTLDKINKDPNLLPNITLGIEIRDSCWYSPVA 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 106 LEQSLEFVRASLTKVDEAE--YMCPDGSYAIQENIPLLIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSR 183
Cdd:cd06374    81 LEQSIEFIRDSVASVEDEKdtQNTPDPTPLSPPENRKPIVGVIGPGSSSVTIQVQNLLQLFHIPQIGYSATSIDLSDKSL 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 184 YDYFARTVPPDFYQAKAMAEILRYFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSNIRKSYDSVIREL 263
Cdd:cd06374   161 YKYFLRVVPSDYLQARAMLDIVKRYNWTYVSTVHTEGNYGESGIEAFKELAAEEGICIAHSDKIYSNAGEEEFDRLLRKL 240
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 264 LQKPN-ARVVVLFMRSDDSRELIAAASRVNAS--FTWVASDGWGAQESIVKGSEHVAYGAITLELASHPVRQFDRYFQSL 340
Cdd:cd06374   241 MNTPNkARVVVCFCEGETVRGLLKAMRRLNATghFLLIGSDGWADRKDVVEGYEDEAAGGITIKIHSPEVESFDEYYFNL 320
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 341 NPYNNHRNPWFRDFWEQKFQCSL----QNKRNHRQICDKHLAIDsSNYEQESKIMFVVNAVYAMAHALHKMQRTLCPNTT 416
Cdd:cd06374   321 KPETNSRNPWFREFWQHRFDCRLpghpDENPYFKKCCTGEESLL-GNYVQDSKLGFVINAIYAMAHALHRMQEDLCGGYS 399
                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907159703 417 K-LCDAMKILDGKKLyKDYLLKINFTAPFNpnkgadSIVKFDTYGDGMGRYNVFNFQHIG-GKYSYLKVGHW 486
Cdd:cd06374   400 VgLCPAMLPINGSLL-LDYLLNVSFVGVSG------DTIMFDENGDPPGRYDIMNFQKTGeGSYDYVQVGSW 464
7tmC_mGluRs_group2_3 cd15934
metabotropic glutamate receptors in group 2 and 3, member of the class C family of ...
575-828 2.19e-160

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: 468.25  E-value: 2.19e-160
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 575 AWAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAI 654
Cdd:cd15934     1 PWAIVPVVFALLGILATLFVIVVFIRYNDTPVVKASGRELSYVLLTGILLCYLMTFVLLAKPSVITCALRRLGLGLGFSI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGTRRYTlpEKRETVILKCNVKD 734
Cdd:cd15934    81 CYAALLTKTNRISRIFNSGKRSAKRPRFISPKSQLVICLGLISVQLIGVLVWLVVEPPGTRIDY--PRRDQVVLKCKISD 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 735 SSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFVV 814
Cdd:cd15934   159 SSLLISLVYNMLLIILCTVYAFKTRKIPENFNEAKFIGFTMYTTCIIWLAFVPIYFGTSNDFKIQTTTLCVSISLSASVA 238
                         250
                  ....*....|....
gi 1907159703 815 LGCLFAPKVHIVLF 828
Cdd:cd15934   239 LGCLFAPKVYIILF 252
7tmC_mGluR2 cd15447
metabotropic glutamate receptor 2 in group 2, member of the class C family of ...
575-828 2.08e-154

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: 452.85  E-value: 2.08e-154
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 575 AWAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAI 654
Cdd:cd15447     1 AWAIGPVTISCLGILSTLFVVGVFVKNNETPVVKASGRELCYILLLGVLLCYLMTFIFIAKPSTAVCTLRRLGLGTSFAV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGTRRYTLPEKRETVILKCNVKD 734
Cdd:cd15447    81 CYSALLTKTNRIARIFSGAKDGAQRPRFISPASQVAICLALISCQLLVVLIWLLVEAPGTRKETAPERRYVVTLKCNSRD 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 735 SSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFVV 814
Cdd:cd15447   161 SSMLISLTYNVLLIILCTLYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCISVSLSGSVV 240
                         250
                  ....*....|....
gi 1907159703 815 LGCLFAPKVHIVLF 828
Cdd:cd15447   241 LGCLFAPKLHIILF 254
7tmC_mGluRs cd15045
metabotropic glutamate receptors, member of the class C family of seven-transmembrane G ...
575-828 3.44e-138

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: 410.87  E-value: 3.44e-138
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 575 AWAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAI 654
Cdd:cd15045     1 PWAIGAMAFASLGILLTLFVLVVFVRYRDTPVVKASGRELSYVLLAGILLSYVMTFVLVAKPSTIVCGLQRFGLGLCFTV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGTRRYtLPEKRETVILKCNVKD 734
Cdd:cd15045    81 CYAAILTKTNRIARIFRLGKKSAKRPRFISPRSQLVITGLLVSVQVLVLAVWLILSPPRATHH-YPTRDKNVLVCSSALD 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 735 SSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFVV 814
Cdd:cd15045   160 ASYLIGLAYPILLIILCTVYAFKTRKIPEGFNEAKYIGFTMYTTCIIWLAFVPLYFTTASNIEVRITTLSVSISLSATVQ 239
                         250
                  ....*....|....
gi 1907159703 815 LGCLFAPKVHIVLF 828
Cdd:cd15045   240 LACLFAPKVYIILF 253
PBP1_GPCR_family_C-like cd06350
ligand-binding domain of membrane-bound glutamate receptors that mediate excitatory ...
40-486 3.60e-131

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: 396.67  E-value: 3.60e-131
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  40 VLGGLFPINEKGTGTEECGRINEDRGIQRLEAMLFAIDEINKDNYLLPGVKLGVHILDTCSRDTYALEQSLEFVRASLTK 119
Cdd:cd06350     1 IIGGLFPVHYRDDADFCCCGILNPRGVQLVEAMIYAIEEINNDSSLLPNVTLGYDIRDTCSSSSVALESSLEFLLDNGIK 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 120 VDEaeymcpdgSYAIQENIPLLIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDFYQAK 199
Cdd:cd06350    81 LLA--------NSNGQNIGPPNIVAVIGAASSSVSIAVANLLGLFKIPQISYASTSPELSDKIRYPYFLRTVPSDTLQAK 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 200 AMAEILRYFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSNIRKSYDSVIRELLQKPNARVVVLFMRSD 279
Cdd:cd06350   153 AIADLLKHFNWNYVSTVYSDDDYGRSGIEAFEREAKERGICIAQTIVIPENSTEDEIKRIIDKLKSSPNAKVVVLFLTES 232
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 280 DSRELIAAASRVNA-SFTWVASDGWGAQESIVKGSEHVAYGAITLELASHPVRQFDRYFQslnpynnhrnpwfrdfweqk 358
Cdd:cd06350   233 DARELLKEAKRRNLtGFTWIGSDGWGDSLVILEGYEDVLGGAIGVVPRSKEIPGFDDYLK-------------------- 292
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 359 fqcslqnkrnhrqicdkhlaidssnyeqeSKIMFVVNAVYAMahalhkmqrtlcpnttklcdamkildgkklykdyllki 438
Cdd:cd06350   293 -----------------------------SYAPYVIDAVYAT-------------------------------------- 305
                         410       420       430       440
                  ....*....|....*....|....*....|....*....|....*....
gi 1907159703 439 nftapfnpnkgadsiVKFDTYGDGMGRYNVFNFQHIG-GKYSYLKVGHW 486
Cdd:cd06350   306 ---------------VKFDENGDGNGGYDIVNLQRTGtGNYEYVEVGTW 339
7tmC_mGluR_group1 cd15285
metabotropic glutamate receptors in group 1, member of the class C family of ...
575-828 1.57e-109

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: 336.53  E-value: 1.57e-109
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 575 AWAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAI 654
Cdd:cd15285     1 TEAIVAMVFACVGILATLFVTVVFIRHNDTPVVKASTRELSYIILAGILLCYASTFALLAKPSTISCYLQRILPGLSFAM 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKNG--AQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGTrRYTLPEKREtVILKCNV 732
Cdd:cd15285    81 IYAALVTKTNRIARILAGSKKKilTRKPRFMSASAQVVITGILISVEVAIIVVMLILEPPDA-TLDYPTPKR-VRLICNT 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 733 KDSSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYvtSSDYRvqTTTMCISVSLSGF 812
Cdd:cd15285   159 STLGFVVPLGFDFLLILLCTLYAFKTRNLPENFNEAKFIGFTMYTTCVIWLAFLPIYF--GSDNK--EITLCFSVSLSAT 234
                         250
                  ....*....|....*.
gi 1907159703 813 VVLGCLFAPKVHIVLF 828
Cdd:cd15285   235 VALVFLFFPKVYIILF 250
PBP1_CaSR cd06364
ligand-binding domain of the CaSR calcium-sensing receptor, a member of the family C receptors ...
40-499 1.29e-97

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: 313.42  E-value: 1.29e-97
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  40 VLGGLFPINEKGTGTE----------ECGRINEdRGIQRLEAMLFAIDEINKDNYLLPGVKLGVHILDTCSRDTYALEQS 109
Cdd:cd06364     1 IIGGLFPIHFRPVSPDpdfttephspECEGFNF-RGFRWAQTMIFAIEEINNSPDLLPNITLGYRIYDSCATISKALRAA 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 110 LEFVraslTKVDE--AEYMCpdgsyaiqENIPLLIAgVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYF 187
Cdd:cd06364    80 LALV----NGQEEtnLDERC--------SGGPPVAA-VIGESGSTLSIAVARTLGLFYIPQVSYFASCACLSDKKQFPSF 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 188 ARTVPPDFYQAKAMAEILRYFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSNIRKSYDSVIrELLQKP 267
Cdd:cd06364   147 LRTIPSDYYQSRALAQLVKHFGWTWVGAIASDDDYGRNGIKAFLEEAEKLGICIAFSETIPRTYSQEKILRIV-EVIKKS 225
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 268 NARVVVLFMRSDDSRELIAAASRVNAS-FTWVASDGWgAQESIVKGSE--HVAYGAITLELASHPVRQFDRYFQSLNPYN 344
Cdd:cd06364   226 TAKVIVVFSSEGDLEPLIKELVRQNITgRQWIASEAW-ITSSLLATPEyfPVLGGTIGFAIRRGEIPGLKEFLLRVHPSK 304
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 345 NHRNPWFRDFWEQKFQCSLQNKRNHRQ------ICD--------KHLAIDSSNYEQESKimfVVNAVYAMAHALHKMQRt 410
Cdd:cd06364   305 SPSNPFVKEFWEETFNCSLSSSSKSNSssssrpPCTgsenlenvQNPYTDVSQLRISYN---VYKAVYAIAHALHDLLQ- 380
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 411 lC-----PNTTKLCDAMKILDGKKLYKdYLLKINFTAPFNPNkgadsiVKFDTYGDGMGRYNVFNFQHIG-GKYSYLKVG 484
Cdd:cd06364   381 -CepgkgPFSNGSCADIKKVEPWQLLY-YLKHVNFTTKFGEE------VYFDENGDPVASYDIINWQLSDdGTIQFVTVG 452
                         490       500
                  ....*....|....*....|.
gi 1907159703 485 HWAET------LYLDVDSIHW 499
Cdd:cd06364   453 YYDASapsgeeLVINESKILW 473
7tmC_mGluR_group3 cd15286
metabotropic glutamate receptors in group 3, member of the class C family of ...
575-835 1.65e-94

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: 297.87  E-value: 1.65e-94
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 575 AWAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAI 654
Cdd:cd15286     1 PWAAVPVALAVLGIIATLFVLVTFVRYNDTPIVRASGRELSYVLLTGIFLCYAITFLMVAEPGVGVCSLRRLFLGLGMSL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILETP------GTRRYTLPEKRETViL 728
Cdd:cd15286    81 SYAALLTKTNRIYRIFEQGKKSVTPPRFISPTSQLVITFSLISVQLLGVLAWFAVDPPhalidyEEGRTPDPEQARGV-L 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 729 KCNVKDSSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYR---VQTTTMCI 805
Cdd:cd15286   160 RCDMSDLSLICCLGYSLLLMVTCTVYAIKARGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTAQSAEklyIQTATLTV 239
                         250       260       270
                  ....*....|....*....|....*....|
gi 1907159703 806 SVSLSGFVVLGCLFAPKVHIVLFQPQKNVV 835
Cdd:cd15286   240 SMSLSASVSLGMLYMPKVYVILFHPEQNVQ 269
PBP1_ABC_transporter_GPCR_C-like cd04509
Family C of G-protein coupled receptors and their close homologs, the type 1 ...
40-325 2.30e-92

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: 293.83  E-value: 2.30e-92
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  40 VLGGLFPINEKGTGTEECGRINEDRGIQRLEAMLFAIDEINKDNYLLPGVKLGVHILDTCSRDTYALEQSLEFVRASLTK 119
Cdd:cd04509     1 KVGVLFAVHGKGPSGVPCGDIVAQYGIQRFEAMEQALDDINADPNLLPNNTLGIVIYDDCCDPKQALEQSNKFVNDLIQK 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 120 vDEAEYMCPDGSYAIQENiPLLIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDFYQAK 199
Cdd:cd04509    81 -DTSDVRCTNGEPPVFVK-PEGIKGVIGHLCSSVTIPVSNILELFGIPQITYAATAPELSDDRGYQLFLRVVPLDSDQAP 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 200 AMAEILRYFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSNIRKSYDSVIRELLQKPNARVVVLFMRSD 279
Cdd:cd04509   159 AMADIVKEKVWQYVSIVHDEGQYGEGGARAFQDGLKKGGLCIAFSDGITAGEKTKDFDRLVARLKKENNIRFVVYFGYHP 238
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 1907159703 280 DSRELIAAASR--VNASFTWVASDGWGAQESIVKGSEHVAYGAITLEL 325
Cdd:cd04509   239 EMGQILRAARRagLVGKFQFMGSDGWANVSLSLNIAEESAEGLITIKP 286
ANF_receptor pfam01094
Receptor family ligand binding region; This family includes extracellular ligand binding ...
67-473 1.13e-91

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: 293.52  E-value: 1.13e-91
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  67 QRLEAMLFAIDEINKDNYLLPGVKLGVHILDTCSRDTYALEQSLEFVRASltkvdeaeymcpdgsyaiqenipllIAGVI 146
Cdd:pfam01094   1 LVLLAVRLAVEDINADPGLLPGTKLEYIILDTCCDPSLALAAALDLLKGE-------------------------VVAII 55
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 147 GGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDFYQAKAMAEILRYFNWTYVSTVASEGDYGETG 226
Cdd:pfam01094  56 GPSCSSVASAVASLANEWKVPLISYGSTSPALSDLNRYPTFLRTTPSDTSQADAIVDILKHFGWKRVALIYSDDDYGESG 135
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 227 IEAFEQEARLRNICIATAEKVGRSnirKSYDSVIRELLQ--KPNARVVVLFMRSDDSRELIAAASRVN---ASFTWVASD 301
Cdd:pfam01094 136 LQALEDALRERGIRVAYKAVIPPA---QDDDEIARKLLKevKSRARVIVVCCSSETARRLLKAARELGmmgEGYVWIATD 212
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 302 GWGAQESIVKGSEHVAYGAITlelashpvrqfdrYFQSLNPYnnhrNPWFRDFWEQKFQCSLQNKRNhrqicdkhlaids 381
Cdd:pfam01094 213 GLTTSLVILNPSTLEAAGGVL-------------GFRLHPPD----SPEFSEFFWEKLSDEKELYEN------------- 262
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 382 SNYEQESKIMFVVNAVYAMAHALHKMQRTLCPNTtkLCDAMKILDGKKLYKDYLLKINFTapfnpnkGADSIVKFDTYGD 461
Cdd:pfam01094 263 LGGLPVSYGALAYDAVYLLAHALHNLLRDDKPGR--ACGALGPWNGGQKLLRYLKNVNFT-------GLTGNVQFDENGD 333
                         410
                  ....*....|...
gi 1907159703 462 GM-GRYNVFNFQH 473
Cdd:pfam01094 334 RInPDYDILNLNG 346
7tm_classC_mGluR-like cd13953
metabotropic glutamate receptor-like class C family of seven-transmembrane G protein-coupled ...
575-828 1.21e-88

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: 281.82  E-value: 1.21e-88
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 575 AWAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAI 654
Cdd:cd13953     1 PLAIVLLVLAALGLLLTIFIWVVFIRYRNTPVVKASNRELSYLLLFGILLCFLLAFLFLLPPSDVLCGLRRFLFGLSFTL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGTRRYTLPEKrETVILKCNVKD 734
Cdd:cd13953    81 VFSTLLVKTNRIYRIFKSGLRSSLRPKLLSNKSQLLLVLFLLLVQVAILIVWLILDPPKVEKVIDSDN-KVVELCCSTGN 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 735 SSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRvqTTTMCISVSLSGFVV 814
Cdd:cd13953   160 IGLILSLVYNILLLLICTYLAFKTRKLPDNFNEARYIGFSSLLSLVIWIAFIPTYFTTSGPYR--DAILSFGLLLNATVL 237
                         250
                  ....*....|....
gi 1907159703 815 LGCLFAPKVHIVLF 828
Cdd:cd13953   238 LLCLFLPKIYIILF 251
7tmC_mGluR6 cd15453
metabotropic glutamate receptor 6 in group 3, member of the class C family of ...
576-834 9.40e-88

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: 280.38  E-value: 9.40e-88
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 576 WAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAIC 655
Cdd:cd15453     2 WAAPPLLLAVLGILATTTVVITFVRFNNTPIVRASGRELSYVLLTGIFLIYAITFLMVAEPGAAVCAFRRLFLGLGTTLS 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 656 YSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGT------RRYTLPEKRETViLK 729
Cdd:cd15453    82 YSALLTKTNRIYRIFEQGKRSVTPPPFISPTSQLVITFSLTSLQVVGVIAWLGAQPPHSvidyeeQRTVDPEQARGV-LK 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 730 CNVKDSSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYR---VQTTTMCIS 806
Cdd:cd15453   161 CDMSDLSLIGCLGYSLLLMVTCTVYAIKARGVPETFNEAKPIGFTMYTTCIIWLAFVPIFFGTAQSAEkiyIQTTTLTVS 240
                         250       260
                  ....*....|....*....|....*...
gi 1907159703 807 VSLSGFVVLGCLFAPKVHIVLFQPQKNV 834
Cdd:cd15453   241 LSLSASVSLGMLYVPKTYVILFHPEQNV 268
7tmC_mGluR4 cd15452
metabotropic glutamate receptor 4 in group 3, member of the class C family of ...
576-834 2.32e-87

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: 281.10  E-value: 2.32e-87
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 576 WAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAIC 655
Cdd:cd15452     2 WAVVPLLLAVLGIIATLFVVVTFVRYNDTPIVKASGRELSYVLLTGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSIS 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 656 YSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGT------RRYTLPEKRETViLK 729
Cdd:cd15452    82 YAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLVITFSLISLQLLGVCVWFLVDPSHSvvdyedQRTPDPQFARGV-LK 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 730 CNVKDSSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYR---VQTTTMCIS 806
Cdd:cd15452   161 CDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIIWLAFIPIFFGTSQSAEkmyIQTTTLTIS 240
                         250       260
                  ....*....|....*....|....*...
gi 1907159703 807 VSLSGFVVLGCLFAPKVHIVLFQPQKNV 834
Cdd:cd15452   241 VSLSASVSLGMLYMPKVYVILFHPEQNV 268
7tmC_mGluR8 cd15454
metabotropic glutamate receptor 8 in group 3, member of the class C family of ...
575-834 1.07e-84

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: 273.43  E-value: 1.07e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 575 AWAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAI 654
Cdd:cd15454     1 PWAVVPVFVAILGIIATTFVIVTFVRYNDTPIVRASGRELSYVLLTGIFLCYAITFLMIATPDTGICSFRRVFLGLGMCF 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILETP------GTRRYTLPEKRETViL 728
Cdd:cd15454    81 SYAALLTKTNRIHRIFEQGKKSVTAPKFISPASQLVITFSLISVQLLGVFVWFAVDPPhtivdyGEQRTLDPEKARGV-L 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 729 KCNVKDSSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYR---VQTTTMCI 805
Cdd:cd15454   160 KCDISDLSLICSLGYSILLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIIWLAFIPIFFGTAQSAErmyIQTTTLTI 239
                         250       260
                  ....*....|....*....|....*....
gi 1907159703 806 SVSLSGFVVLGCLFAPKVHIVLFQPQKNV 834
Cdd:cd15454   240 SMSLSASVSLGMLYMPKVYIIIFHPEQNV 268
7tmC_mGluR7 cd15451
metabotropic glutamate receptor 7 in group 3, member of the class C family of ...
576-854 2.09e-78

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: 256.49  E-value: 2.09e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 576 WAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAIC 655
Cdd:cd15451     2 WAVIPVFLAMLGIIATIFVMATFIRYNDTPIVRASGRELSYVLLTGIFLCYIITFLMIAKPDVAVCSFRRIFLGLGMCIS 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 656 YSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGT-----RRYTLPEKRETVILKC 730
Cdd:cd15451    82 YAALLTKTNRIYRIFEQGKKSVTAPRLISPTSQLAITSSLISVQLLGVLIWFAVDPPNIiidydEQKTMNPEQARGVLKC 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 731 NVKDSSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYR---VQTTTMCISV 807
Cdd:cd15451   162 DITDLQIICSLGYSILLMVTCTVYAIKTRGVPENFNEAKPIGFTMYTTCIVWLAFIPIFFGTAQSAEklyIQTTTLTISM 241
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1907159703 808 SLSGFVVLGCLFAPKVHIVLFQPQKNVVTHRlhlNRFSVSGTATTYS 854
Cdd:cd15451   242 NLSASVALGMLYMPKVYIIIFHPELNVQKRK---RSFKAVVTAATMS 285
7tm_3 pfam00003
7 transmembrane sweet-taste receptor of 3 GCPR; This is a domain of seven transmembrane ...
570-822 1.83e-76

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: 249.11  E-value: 1.83e-76
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 570 IRWEDAWAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSpVICALRRLGLG 649
Cdd:pfam00003   1 LDLSAPWGIVLEALAALGILLTLVLLVVFLLHRKTPIVKASNRSLSFLLLLGLLLLFLLAFLFIGKPT-VTCALRRFLFG 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 650 TSFAICYSALLTKTNCIARIFdgvkngAQRPKFISPSSQVFICLGLILVQIVMVSVWLILeTPGTRRYTLPEKRETVILK 729
Cdd:pfam00003  80 VGFTLCFSCLLAKTFRLVLIF------RRRKPGPRGWQLLLLALGLLLVQVIILTEWLID-PPFPEKDNLSEGKIILECE 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 730 CNVKDSSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYV-TSSDYRVQTTTM-CISV 807
Cdd:pfam00003 153 GSTSIAFLDFVLAYVGLLLLAGFLLAFKTRKLPDNFNEAKFITFSMLLSVLIWVAFIPMYLYgNKGKGTWDPVALaIFAI 232
                         250
                  ....*....|....*
gi 1907159703 808 SLSGFVVLGCLFAPK 822
Cdd:pfam00003 233 LASGWVLLGLYFIPK 247
PBP1_pheromone_receptor cd06365
Ligand-binding domain of the V2R pheromone receptor, a member of the family C receptors within ...
40-499 7.57e-72

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: 244.09  E-value: 7.57e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  40 VLGGLFPINEKGTGTEE----------CGRINEdRGIQRLEAMLFAIDEINKDNYLLPGVKLGVHILDTCSRDTYALEQS 109
Cdd:cd06365     1 IIGGVFPIHTFSEGKKKdfkeppspllCFRFSI-KYYQHLLAFLFAIEEINKNPDLLPNITLGFHIYDSCSSERLALESS 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 110 LEFvrasLTKVDEA--EYMCpdgsyaiQENIPllIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYF 187
Cdd:cd06365    80 LSI----LSGNSEPipNYSC-------REQRK--LVAFIGDLSSSTSVAMARILGLYKYPQISYGAFDPLLSDKVQFPSF 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 188 ARTVPPDFYQAKAMAEILRYFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGrSNIRKSYDSVIRELLQKP 267
Cdd:cd06365   147 YRTVPSDTSQSLAIVQLLKHFGWTWVGLIISDDDYGEQFSQDLKKEMEKNGICVAFVEKIP-TNSSLKRIIKYINQIIKS 225
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 268 NARVVVLFmrSDDSrELIAAASRVNASF----TWVASDGWGAQESIVKGSEHVAYGAITLELASHPVRQFDRYFQSLNPY 343
Cdd:cd06365   226 SANVIIIY--GDTD-SLLELLFRLWEQLvtgkVWITTSQWDISTLPFEFYLNLFNGTLGFSQHSGEIPGFKEFLQSVHPS 302
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 344 NNHRNPWFRDFWEQKFQCSL--QNKRNHRQICDKH--LAIDSSNYEQEskiMF-----VVNAVYAMAHALHKMQRTLCPN 414
Cdd:cd06365   303 KYPEDIFLKTLWESYFNCKWpdQNCKSLQNCCGNEslETLDVHSFDMT---MSrlsynVYNAVYAVAHALHEMLLCQPKT 379
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 415 TTKLCDAMKILDGKKLYkDYLLKINFTAPFNPNkgadsiVKFDTYGDGMGRYNVFNFQHI-GGKYSYLKVGH---WA--- 487
Cdd:cd06365   380 GPGNCSDRRNFQPWQLH-HYLKKVQFTNPAGDE------VNFDEKGDLPTKYDILNWQIFpNGTGTKVKVGTfdpSApsg 452
                         490
                  ....*....|..
gi 1907159703 488 ETLYLDVDSIHW 499
Cdd:cd06365   453 QQLIINDSMIEW 464
7tmC_mGluR5 cd15450
metabotropic glutamate receptor 5 in group 1, member of the class C family of ...
578-827 1.06e-66

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: 222.94  E-value: 1.06e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 578 IGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAICYS 657
Cdd:cd15450     4 IAAVVFACLGLLATLFVTVIFIIYRDTPVVKSSSRELCYIILAGICLGYLCTFCLIAKPKQIYCYLQRIGIGLSPAMSYS 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 658 ALLTKTNCIARIFDGVKNG--AQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGTrRYTLPEKREtVILKCNVKDS 735
Cdd:cd15450    84 ALVTKTNRIARILAGSKKKicTKKPRFMSACAQLVIAFILICIQLGIIVALFIMEPPDI-MHDYPSIRE-VYLICNTTNL 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 736 SMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYvtSSDYRvqTTTMCISVSLSGFVVL 815
Cdd:cd15450   162 GVVTPLGYNGLLILSCTFYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYF--GSNYK--IITMCFSVSLSATVAL 237
                         250
                  ....*....|..
gi 1907159703 816 GCLFAPKVHIVL 827
Cdd:cd15450   238 GCMFVPKVYIIL 249
PBP1_glutamate_receptors-like cd06269
ligand-binding domain of family C G-protein couples receptors (GPCRs), membrane bound guanylyl ...
41-399 6.62e-65

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: 221.14  E-value: 6.62e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  41 LGGLFPINEKGTGteecgrinedrGIQRLEAMLFAIDEINKDNYLLPGVKLGVHILDTCSRDTYALEQSLEFVRASLtkv 120
Cdd:cd06269     2 IGALLPVHDYLES-----------GAKVLPAFELALSDVNSRPDLLPKTTLGLAIRDSECNPTQALLSACDLLAAAK--- 67
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 121 deaeymcpdgsyaiqenipllIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDFYQAKA 200
Cdd:cd06269    68 ---------------------VVAILGPGCSASAAPVANLARHWDIPVLSYGATAPGLSDKSRYAYFLRTVPPDSKQADA 126
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 201 MAEILRYFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVgRSNIRKSYDSVIRELLQKPnARVVVLFMRSDD 280
Cdd:cd06269   127 MLALVRRLGWNKVVLIYSDDEYGEFGLEGLEELFQEKGGLITSRQSF-DENKDDDLTKLLRNLRDTE-ARVIILLASPDT 204
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 281 SRELIAAASR---VNASFTWVASDGWGAQESIVKGSEHVAY-GAITLELASHPVRQFDRYFQSLNpynnhrnpwfrdfwe 356
Cdd:cd06269   205 ARSLMLEAKRldmTSKDYVWFVIDGEASSSDEHGDEARQAAeGAITVTLIFPVVKEFLKFSMELK--------------- 269
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|...
gi 1907159703 357 qkfQCSLQNKRNHrqicdkhlaidSSNYEQESKIMFVVNAVYA 399
Cdd:cd06269   270 ---LKSSKRKQGL-----------NEEYELNNFAAFFYDAVLA 298
PBP1_GPC6A-like cd06361
ligand-binding domain of the promiscuous L-alpha-amino acid receptor GPRC6A which is a ...
40-502 2.78e-62

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: 216.08  E-value: 2.78e-62
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  40 VLGGLFPINEKGTGTEECGRINED--------RGIQRLEAMLFAIDEINKDNyLLPGVKLGVHILDTCSRDTYALEQSLE 111
Cdd:cd06361     1 IIGGLFPIHEKVLDLHDRPTKPQIfictgfdlRGFLQSLAMIHAIEMINNST-LLPGIKLGYEIYDTCSDVTKALQATLR 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 112 FVRA-----SLTKVDEAEYMCPdgsyaiqenipllIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDY 186
Cdd:cd06361    80 LLSKfnssnELLECDYTDYVPP-------------VKAVIGASYSEISIAVARLLNLQLIPQISYESSAPILSDKLRFPS 146
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 187 FARTVPPDFYQAKAMAEILRYFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKV----GRSNIRKSYDSVIRE 262
Cdd:cd06361   147 FLRTVPSDFHQTKAMAKLISHFGWNWVGIIYTDDDYGRSALESFIIQAEAENVCIAFKEVLpaylSDPTMNVRINDTIQT 226
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 263 LLQKPNARVVVLFMRSDDSRELIAAASRVNASFTWVASDGWGAQESI--VKGSEHVayGAIT-LELASHPVRQFDRYFQS 339
Cdd:cd06361   227 IQSSSQVNVVVLFLKPSLVKKLFKEVIERNISKIWIASDNWSTAREIlkMPNINKV--GKILgFTFKSGNISSFHNYLKN 304
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 340 LNPYNNhrnpwfrdfweqkfqcslqnkrnhrQIcdkhlaidssnyeqeskimfvvnAVYAMAHALHKM--QRTLCPNTT- 416
Cdd:cd06361   305 LLIYSI-------------------------QL-----------------------AVTAIANALRKLccERGCQDPTAf 336
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 417 ---KLCDAMKildgkklykdyllKINFTapfnpnKGADSIvKFDTYGDGMGRYNVFNFQHIGGKYSYLKVGHWaetlYLD 493
Cdd:cd06361   337 qpwELLKELK-------------KVTFT------DDGETY-HFDANGDLNTGYDLILWKEDNGHMTFTIVAEY----DLQ 392

                  ....*....
gi 1907159703 494 VDSIHWSRN 502
Cdd:cd06361   393 NDVFIFTNN 401
7tmC_mGluR1 cd15449
metabotropic glutamate receptor 1 in group 1, member of the class C family of ...
577-827 2.67e-60

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: 205.25  E-value: 2.67e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 577 AIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAICY 656
Cdd:cd15449     3 SIIAVAFSCLGILVTMFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAMCY 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 657 SALLTKTNCIARIFDGVKNG--AQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGTRRyTLPEKREtVILKCNVKD 734
Cdd:cd15449    83 SALVTKTNRIARILAGSKKKicTRKPRFMSAWAQVVIASILISVQLTLVVTLIIMEPPMPIL-SYPSIKE-VYLICNTSN 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 735 SSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYvtSSDYRVQTTtmCISVSLSGFVV 814
Cdd:cd15449   161 LGVVAPLGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYF--GSNYKIITT--CFAVSLSVTVA 236
                         250
                  ....*....|...
gi 1907159703 815 LGCLFAPKVHIVL 827
Cdd:cd15449   237 LGCMFTPKMYIII 249
PBP1_taste_receptor cd06363
ligand-binding domain of the T1R taste receptor; Ligand-binding domain of the T1R taste ...
34-505 9.24e-57

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: 201.38  E-value: 9.24e-57
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  34 KIEGDLVLGGLFPINE---------KGTGTEECGRINEDrGIQRLEAMLFAIDEINKDNYLLPGVKLGVHILDTCSrDTY 104
Cdd:cd06363     2 RLPGDYLLGGLFPLHEltstlphrpPEPTDCSCDRFNLH-GYHLAQAMRFAVEEINNSSDLLPGVTLGYEIFDTCS-DAV 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 105 ALEQSLEFVraSLTKVDEAEYMCPDGSYaiqenIPLLIAgVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRY 184
Cdd:cd06363    80 NFRPTLSFL--SQNGSHDIEVQCNYTNY-----QPRVVA-VIGPDSSELALTTAKLLGFFLMPQISYGASSEELSNKLLY 151
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 185 DYFARTVPPDFYQAKAMAEILRYFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSNIRKSYDSVIRELL 264
Cdd:cd06363   152 PSFLRTVPSDKYQVEAMVQLLQEFGWNWVAFLGSDDEYGQDGLQLFSEKAANTGICVAYQGLIPTDTDPKPKYQDILKKI 231
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 265 QKPNARVVVLFMRSDDSRELIAAASRVNAS-FTWVASDGWgAQESIVKGSEHVAYGAITLELAShPVRQFDRyfqslnpy 343
Cdd:cd06363   232 NQTKVNVVVVFAPKQAAKAFFEEVIRQNLTgKVWIASEAW-SLNDTVTSLPGIQSIGTVLGFAI-QTGTLPG-------- 301
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 344 nnhrnpwFRDFweqkfqcslqnkrnhrqicdkhlaIDSSNYEqeskimfVVNAVYAMAHALHKmqrTLCPNTTKlCDAMK 423
Cdd:cd06363   302 -------FQEF------------------------IYAFAFS-------VYAAVYAVAHALHN---LLGCNSGA-CPKGR 339
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 424 ILDGKKLYKDyLLKINFTApfnpnkgADSIVKFDTYGDGMGRYNVFNFQHIGGKYSYLKVG--HWAET-LYLDVDSIHWS 500
Cdd:cd06363   340 VVYPWQLLEE-LKKVNFTL-------LNQTIRFDENGDPNFGYDIVQWIWNNSSWTFEVVGsySTYPIqLTINESKIKWH 411

                  ....*
gi 1907159703 501 RNSVP 505
Cdd:cd06363   412 TKDSP 416
7tmC_V2R_pheromone cd15283
vomeronasal type-2 pheromone receptors, member of the class C family of seven-transmembrane G ...
578-828 1.43e-50

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: 178.24  E-value: 1.43e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 578 IGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAICYS 657
Cdd:cd15283     4 IALTVLSLLGSVLTAAVLVVFIKHRDTPIVKANNSELSYLLLLSLKLCFLCSLLFIGQPSTWTCMLRQTAFGISFVLCIS 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 658 ALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGTRRYTlPEKRETVILKCNvKDSSM 737
Cdd:cd15283    84 CILAKTIVVVAAFKATRPGSNIMKWFGPGQQRAIIFICTLVQVVICAIWLATSPPFPDKNM-HSEHGKIILECN-EGSVV 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 738 LIS--LTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFvvL 815
Cdd:cd15283   162 AFYcvLGYIGLLALVSFLLAFLARKLPDNFNEAKFITFSMLVFCAVWVAFVPAYISSPGKYMVAVEIFAILASSAGL--L 239
                         250
                  ....*....|...
gi 1907159703 816 GCLFAPKVHIVLF 828
Cdd:cd15283   240 GCIFAPKCYIILL 252
7tmC_V2R_AA_sensing_receptor-like cd15044
vomeronasal type-2 pheromone receptors, amino acid-sensing receptors and closely related ...
575-828 2.53e-45

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: 163.41  E-value: 2.53e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 575 AWAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAI 654
Cdd:cd15044     1 PLGILLVILSILGIIFVLVVGGVFVRYRNTPIVKANNRELSYLILLSLFLCFSSSLFFIGEPQDWTCKLRQTMFGVSFTL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKNGAQRpKFISPSSQVFICLGLILVQIVMVSVWLILETPGTRRYTLPEKREtVILKCNvKD 734
Cdd:cd15044    81 CISCILTKTLKVLLAFSADKPLTQK-FLMCLYLPILIVFTCTGIQVVICTVWLIFAPPTVEVNVSPLPRV-IILECN-EG 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 735 SSMLIS--LTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTmcISVSLSGF 812
Cdd:cd15044   158 SILAFGtmLGYIAFLAFLCFLFAFKARKLPDNYNEAKFITFGMLVFFIVWISFVPAYLSTKGKFVVAVEI--IAILASSY 235
                         250
                  ....*....|....*.
gi 1907159703 813 VVLGCLFAPKVHIVLF 828
Cdd:cd15044   236 GLLGCIFLPKCYVILL 251
7tmC_CaSR cd15282
calcium-sensing receptor, member of the class C of seven-transmembrane G protein-coupled ...
576-828 4.61e-41

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: 151.26  E-value: 4.61e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 576 WAIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAIC 655
Cdd:cd15282     2 FGIALTLFAVLGIFLTAFVLGVFIKFRNTPIVKATNRELSYLLLFSLICCFSSSLIFIGEPQDWTCRLRQPAFGISFVLC 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 656 YSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGTRRYTLPEKrETVILKCNVKDS 735
Cdd:cd15282    82 ISCILVKTNRVLLVFEAKIPTSLHRKWWGLNLQFLLVFLCTFVQIVICVIWLYTAPPSSYRNHELED-EIIFITCNEGSL 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 736 SMLISLT-YDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYrvQTTTMCISVSLSGFVV 814
Cdd:cd15282   161 MALGFLIgYTCLLAAICFFFAFKSRKLPENFNEAKFITFSMLIFFIVWISFIPAYASTYGKF--VSAVEVIAILASSFGL 238
                         250
                  ....*....|....
gi 1907159703 815 LGCLFAPKVHIVLF 828
Cdd:cd15282   239 LACIFFNKVYIILF 252
7tmC_V2R-like cd15280
vomeronasal type-2 receptor-like proteins, member of the class C family of seven-transmembrane ...
581-830 7.12e-39

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: 145.31  E-value: 7.12e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 581 VTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAICYSALL 660
Cdd:cd15280     7 IALSIFGALVVLAVTVVYIMHRHTPLVKANDRELSFLIQMSLVITFLTSILFIGKPENWSCMARQITLALGFSLCLSSIL 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 661 TKTNCI---ARIfdgvKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGTRRYTLPEKREtVILKCNVKDSSM 737
Cdd:cd15280    87 GKTISLflrYRA----SKSETRLDSMHPIYQKIIVLICVLIEVGICTAYLILEPPRMYKNTEVQNVK-IIFECNEGSIEF 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 738 LISL-TYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCISVslSGFVVLG 816
Cdd:cd15280   162 LCSIfGFDVFLALLCFLTAFVARKLPDNFNEGKFITFGMLVFFIVWISFVPAYLSTRGKFKVAVEIFAILA--SSFGLLG 239
                         250
                  ....*....|....
gi 1907159703 817 CLFAPKVHIVLFQP 830
Cdd:cd15280   240 CIFVPKCYIILLKP 253
PBP1_GABAb_receptor cd06366
ligand-binding domain of GABAb receptors, which are metabotropic transmembrane receptors for ...
41-500 1.06e-38

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: 148.93  E-value: 1.06e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  41 LGGLFPINEKGTGteecgrineDRGIQRLEAMLFAIDEINKDNYLLPGVKLGVHILDT-CSRDtYALEQSLEFVRASLTK 119
Cdd:cd06366     2 IGGLFPLSGSKGW---------WGGAGILPAAEMALEHINNRSDILPGYNLELIWNDTqCDPG-LGLKALYDLLYTPPPK 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 120 VdeaeymcpdgsyaiqeniplliaGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDFYQAK 199
Cdd:cd06366    72 V-----------------------MLLGPGCSSVTEPVAEASKYWNLVQLSYAATSPALSDRKRYPYFFRTVPSDTAFNP 128
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 200 AMAEILRYFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSNIRksyDSVirELLQKPNARVVVLFMRSD 279
Cdd:cd06366   129 ARIALLKHFGWKRVATIYQNDEVFSSTAEDLEELLEEANITIVATESFSSEDPT---DQL--ENLKEKDARIIIGLFYED 203
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 280 DSRELIAAASRVN---ASFTW-----VASDGWGAQESIVKGSEH----VAYGAITLELASHP-----------VRQFDRY 336
Cdd:cd06366   204 AARKVFCEAYKLGmygPKYVWilpgwYDDNWWDVPDNDVNCTPEqmleALEGHFSTELLPLNpdntktisgltAQEFLKE 283
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 337 FQSLNPYNNHRnpwfrdfweqkfqcslqnkrnhrqicdkhlaidSSNYEqeskiMFVVNAVYAMAHALHKMQRTLCPNTT 416
Cdd:cd06366   284 YLERLSNSNYT---------------------------------GSPYA-----PFAYDAVWAIALALNKTIEKLAEYNK 325
                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 417 KLCDA-MKILDGKKLYKDYLLKINFTAPFNPnkgadsiVKFDTYGDGMGRYNVfnFQHIGGKysYLKVGHW----AETLY 491
Cdd:cd06366   326 TLEDFtYNDKEMADLFLEAMNSTSFEGVSGP-------VSFDSKGDRLGTVDI--EQLQGGS--YVKVGLYdpnaDSLLL 394

                  ....*....
gi 1907159703 492 LDVDSIHWS 500
Cdd:cd06366   395 LNESSIVWP 403
7tmC_GPRC6A cd15281
class C of seven-transmembrane G protein-coupled receptors, subtype 6A; GRPC6A (GPCR, class C, ...
577-828 3.64e-37

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: 139.91  E-value: 3.64e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 577 AIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAICY 656
Cdd:cd15281     3 AIVLLILSALGVLLIFFISALFTKNLNTPVVKAGGGPLCYVILLSHFGSFISTVFFIGEPSDLTCKTRQTLFGISFTLCV 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 657 SALLTKTNCIARIFD------GVKNGAQRPKFIspssqVFICLGlilVQIVMVSVWLILETPGTRR-YTLPekrETVILK 729
Cdd:cd15281    83 SCILVKSLKILLAFSfdpklqELLKCLYKPIMI-----VFICTG---IQVIICTVWLVFYKPFVDKnFSLP---ESIILE 151
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 730 CNVKDSSML-ISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYrVQTTTMcISVS 808
Cdd:cd15281   152 CNEGSYVAFgLMLGYIALLAFICFIFAFKGRKLPENYNEAKFITFGMLIYFIAWITFIPIYATTFGKY-VPAVEM-IVIL 229
                         250       260
                  ....*....|....*....|
gi 1907159703 809 LSGFVVLGCLFAPKVHIVLF 828
Cdd:cd15281   230 ISNYGILSCTFLPKCYIILY 249
7tmC_GABA-B-like cd15047
gamma-aminobutyric acid type B receptor and related proteins, member of the class C family of ...
578-826 3.30e-32

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: 126.14  E-value: 3.30e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 578 IGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFI---AKPSPVICALRRLGLGTSFAI 654
Cdd:cd15047     4 IVFTVLSGIGILLALVFLIFNIKFRKNRVIKMSSPLFNNLILLGCILCYISVILFGlddSKPSSFLCTARPWLLSIGFTL 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKNgaqRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGTRRYTLPEKR------ETVIL 728
Cdd:cd15047    84 VFGALFAKTWRIYRIFTNKKL---KRIVIKDKQLLKIVGILLLIDIIILILWTIVDPLKPTRVLVLSEIsddvkyEYVVH 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 729 KCNVKDSS--MLISLTYDVVLVILCTVYAFKTRKCP-ENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCI 805
Cdd:cd15047   161 CCSSSNGIiwLGILLAYKGLLLLFGCFLAWKTRNVDiEEFNESKYIGISIYNVLFLSVIGVPLSFVLTDSPDTSYLIISA 240
                         250       260
                  ....*....|....*....|.
gi 1907159703 806 SVSLSGFVVLGCLFAPKVHIV 826
Cdd:cd15047   241 AILFCTTATLCLLFVPKFWLL 261
7tmC_TAS1R1 cd15289
type 1 taste receptor subtype 1, member of the class C of seven-transmembrane G ...
580-828 5.37e-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: 113.67  E-value: 5.37e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 580 PVTIACLGFMCTCIVITV-----FIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAI 654
Cdd:cd15289     1 PVSWALLTALTLLLLLLAgtallFALNLTTPVVKSAGGRTCFLMLGSLAAASCSLYCHFGEPTWLACLLKQPLFSLSFTV 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFdgvKNGAQRPKFI-------SPSSQVFIClglILVQIVMVSVWLILETP-GTRRYTLpeKRETV 726
Cdd:cd15289    81 CLSCIAVRSFQIVCIF---KLASKLPRFYetwaknhGPELFILIS---SAVQLLISLLWLVLNPPvPTKDYDR--YPDLI 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 727 ILKC-NVKDSSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCI 805
Cdd:cd15289   153 VLECsQTLSVGSFLELLYNCLLSISCFVFSYMGKDLPANYNEAKCITFSLLIYFISWISFFTTYSIYRGKYLMAINVLAI 232
                         250       260
                  ....*....|....*....|...
gi 1907159703 806 SVSLSGfvVLGCLFAPKVHIVLF 828
Cdd:cd15289   233 LSSLLG--IFGGYFLPKVYIILL 253
Periplasmic_Binding_Protein_type1 cd01391
Type 1 periplasmic binding fold superfamily; Type 1 periplasmic binding fold superfamily. This ...
60-351 1.42e-27

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: 113.13  E-value: 1.42e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  60 INEDRGIQRLEAMLFAIDEINkdnyllpgvkLGVHILDTCSRDTYALEQSLEFVRasltkvdeaeymcpdgsyaiqENIp 139
Cdd:cd01391    12 IREQFGIQRVEAIFHTADKLG----------ASVEIRDSCWHGSVALEQSIEFIR---------------------DNI- 59
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 140 lliAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDFYQAKAMAEILRYFNWTYVSTVASE 219
Cdd:cd01391    60 ---AGVIGPGSSSVAIVIQNLAQLFDIPQLALDATSQDLSDKTLYKYFLSVVFSDTLGARLGLDIVKRKNWTYVAAIHGE 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 220 GD-YGETGIEAFEQEARLRNICIATAEKVGRSNIRKSYDSVIRELLQKPNARVVVLFmRSDDSRELIAAA--SRVNASFT 296
Cdd:cd01391   137 GLnSGELRMAGFKELAKQEGICIVASDKADWNAGEKGFDRALRKLREGLKARVIVCA-NDMTARGVLSAMrrLGLVGDVS 215
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907159703 297 WVASDGWGAQESIVKGSEHVAYGAITLELASHPVRQFDRYFQSLNpyNNHRNPWF 351
Cdd:cd01391   216 VIGSDGWADRDEVGYEVEANGLTTIKQQKMGFGITAIKAMADGSQ--NMHEEVWF 268
7tmC_TAS1R cd15046
type 1 taste receptors, member of the class C of seven-transmembrane G protein-coupled ...
584-828 1.45e-24

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: 103.76  E-value: 1.45e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 584 ACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAICYSALLTKT 663
Cdd:cd15046    10 AALGLLSTLAILVIFWRNFNTPVVRSAGGPMCFLMLTLLLVAYMSVPVYFGPPKVSTCLLRQALFPLCFTVCLACIAVRS 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 664 NCIARIFdgvKNGAQRP-------KFISPSSQVFICLGLILVQIVmvsVWLILETPGTRRYTLPEKRETVILKCNVKDSS 736
Cdd:cd15046    90 FQIVCIF---KMASRFPraysywvKYHGPYVSIAFITVLKMVIVV---IGMLATPPSPTTDTDPDPKITIVSCNPNYRNS 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 737 MLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLpIFYVTSSDYRVQTTTMCISVsLSGFVVLG 816
Cdd:cd15046   164 SLFNTSLDLLLSVVCFSFSYMGKDLPTNYNEAKFITFSLTFYFTSWISFC-TFMLAYSGVLVTIVDLLATL-LSLLAFSL 241
                         250
                  ....*....|..
gi 1907159703 817 CLFAPKVHIVLF 828
Cdd:cd15046   242 GYFLPKCYIILF 253
PBP1_ABC_ligand_binding-like cd06346
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
142-302 5.01e-22

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: 97.63  E-value: 5.01e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 142 IAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDFYQAKAMAEILRYFNWTYVSTVASEGD 221
Cdd:cd06346    68 VPAIVGAASSGVTLAVASVAVPNGVVQISPSSTSPALTTLEDKGYVFRTAPSDALQGVVLAQLAAERGFKKVAVIYVNND 147
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 222 YGeTGI-EAFEQ--EARLRNIciatAEKVGRSNIRKSYDSVIRELLQ-KPNARVVVLFMrsDDSRELIAAASRVNASFT- 296
Cdd:cd06346   148 YG-QGLaDAFKKafEALGGTV----TASVPYEPGQTSYRAELAQAAAgGPDALVLIGYP--EDGATILREALELGLDFTp 220

                  ....*.
gi 1907159703 297 WVASDG 302
Cdd:cd06346   221 WIGTDG 226
PBP1_SAP_GC-like cd06370
Ligand-binding domain of membrane bound guanylyl cyclases; Ligand-binding domain of membrane ...
71-485 6.78e-21

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: 96.16  E-value: 6.78e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  71 AMLFAIDEINKDNYLLPGVKLGVHILDTCSRDTYALEQSLEFvrasltkvdeaeymcpdgsyaIQENIplliAGVIG-GS 149
Cdd:cd06370    25 AITLAVDDVNNDPNLLPGHTLSFVWNDTRCDELLSIRAMTEL---------------------WKRGV----SAFIGpGC 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 150 YSSVSIQVANLLRLfqiPQISYASTSAKLSDKSRYDYFARTVPPDFYQAKAMAEILRYFNWTYVSTVASEGDYGETGIEA 229
Cdd:cd06370    80 TCATEARLAAAFNL---PMISYKCADPEVSDKSLYPTFARTIPPDSQISKSVIALLKHFNWNKVSIVYENETKWSKIADT 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 230 FEQEARLRNICIATAEK-----VGRSNIRKSYDSVIRELLQKpnARVVVLFMRSDDSRELIAAAS--RVNAS----FTWV 298
Cdd:cd06370   157 IKELLELNNIEINHEEYfpdpyPYTTSHGNPFDKIVEETKEK--TRIYVFLGDYSLLREFMYYAEdlGLLDNgdyvVIGV 234
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 299 ASDgwgaqesIVKGSEHVAY-GAITLELASHPVRQFDRYFQSL--NPYNNHRNPWFRDFWEQkfqcslQNKRNHRQicdk 375
Cdd:cd06370   235 ELD-------QYDVDDPAKYpNFLSGDYTKNDTKEALEAFRSVliVTPSPPTNPEYEKFTKK------VKEYNKLP---- 297
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 376 hlAIDSSNYEQESKIMFVV-------NAVYAMAHALHKMQR--TLCPNTTKLCDamKILDGKklYKDYLlkinftapfnp 446
Cdd:cd06370   298 --PFNFPNPEGIEKTKEVPiyaaylyDAVMLYARALNETLAegGDPRDGTAIIS--KIRNRT--YESIQ----------- 360
                         410       420       430       440
                  ....*....|....*....|....*....|....*....|...
gi 1907159703 447 nkGADsiVKFDTYGDGMGRYNVFNFQHIG----GKYSYLKVGH 485
Cdd:cd06370   361 --GFD--VYIDENGDAEGNYTLLALKPNKgtndGSYGLHPVGT 399
PBP1_NPR_GC-like cd06352
ligand-binding domain of membrane guanylyl-cyclase receptors; Ligand-binding domain of ...
75-301 1.37e-20

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: 95.11  E-value: 1.37e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  75 AIDEINKDNYLLPGVKLGVHILDTCSRDTYALEQSLEFVRASltKVDeaeymcpdgsyaiqeniplliaGVIGGSYSSVS 154
Cdd:cd06352    27 AIERINSEGLLLPGFNFEFTYRDSCCDESEAVGAAADLIYKR--NVD----------------------VFIGPACSAAA 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 155 IQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDFYQAKAMAEILRYFNWTYVSTVAS-EGDYGETGIEAFEQE 233
Cdd:cd06352    83 DAVGRLATYWNIPIITWGAVSASFLDKSRYPTLTRTSPNSLSLAEALLALLKQFNWKRAAIIYSdDDSKCFSIANDLEDA 162
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907159703 234 ARLRNICIATAEKVGRSNIRKSYDSVIRELlqKPNARVVVLFMRSDDSRELIAAASR---VNASFTWVASD 301
Cdd:cd06352   163 LNQEDNLTISYYEFVEVNSDSDYSSILQEA--KKRARIIVLCFDSETVRQFMLAAHDlgmTNGEYVFIFIE 231
PBP1_ABC_transporter_LIVBP-like cd06268
periplasmic binding domain of ATP-binding cassette transporter-like systems that belong to the ...
63-314 1.37e-19

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: 90.08  E-value: 1.37e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  63 DRGIQRLEAMLFAIDEINKdNYLLPGVKLGVHILDtcsrDTYALEQSLEFVRAsLTKVDEaeymcpdgsyaiqenipllI 142
Cdd:cd06268    14 DYGEEILRGVALAVEEINA-AGGINGRKLELVIAD----DQGDPETAVAVARK-LVDDDK-------------------V 68
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 143 AGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSrYDYFARTVPPDFYQAKAMAE-ILRYFNWTYVSTVASEGD 221
Cdd:cd06268    69 LAVVGHYSSSVTLAAAPIYQEAGIPLISPGSTAPELTEGG-GPYVFRTVPSDAMQAAALADyLAKKLKGKKVAILYDDYD 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 222 YGETGIEAFEQEARLRNICIATAEKVGRSNirKSYDSVIRELLQKpNARVVVLFMRSDDSRELIAAASRVNASFTWVASD 301
Cdd:cd06268   148 YGKSLADAFKKALKALGGEIVAEEDFPLGT--TDFSAQLTKIKAA-GPDVLFLAGYGADAANALKQARELGLKLPILGGD 224
                         250
                  ....*....|...
gi 1907159703 302 GWGAQESIVKGSE 314
Cdd:cd06268   225 GLYSPELLKLGGE 237
7tmC_TAS1R2 cd15288
type 1 taste receptor subtype 2, member of the class C of seven-transmembrane G ...
581-828 1.58e-19

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: 89.08  E-value: 1.58e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 581 VTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAICYSALL 660
Cdd:cd15288     7 ALLAALGFLSTLAILVIFGRHFQTPVVRSAGGRMCFLMLAPLLVAYVNVPVYVGIPTVFTCLCRQTLFPLCFTVCISCIA 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 661 TKTNCIARIFdgvKNGAQRPKFIS-----PSSQVFICLGLIL-VQIVMVSVWLILETPGTRryTLPEKRETVILKCNVK- 733
Cdd:cd15288    87 VRSFQIVCIF---KMARRLPRAYSywvkyNGPYVFVALITLLkVVIVVINVLAHPTAPTTR--ADPDDPQVMILQCNPNy 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 734 DSSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTM--YTTCIIWLAFLPIFY----VTSSDYRVqTTTMCISV 807
Cdd:cd15288   162 RLALLFNTSLDLLLSVLGFCFAYMGKELPTNYNEAKFITLCMtfYFASSVFLCTFMSVYegvlVTIFDALV-TVINLLGI 240
                         250       260
                  ....*....|....*....|.
gi 1907159703 808 SLsGFvvlgclFAPKVHIVLF 828
Cdd:cd15288   241 SL-GY------FGPKCYMILF 254
LivK COG0683
ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid ...
36-299 1.77e-19

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: 90.38  E-value: 1.77e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  36 EGDLVLGGLFPInekgTGTeecgriNEDRGIQRLEAMLFAIDEINKDNYLLpGVKLGVHILDTCSRDTYALEQSLEFVRA 115
Cdd:COG0683     1 ADPIKIGVLLPL----TGP------YAALGQPIKNGAELAVEEINAAGGVL-GRKIELVVEDDASDPDTAVAAARKLIDQ 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 116 SltKVDeaeymcpdgsyaiqeniplliaGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDF 195
Cdd:COG0683    70 D--KVD----------------------AIVGPLSSGVALAVAPVAEEAGVPLISPSATAPALTGPECSPYVFRTAPSDA 125
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 196 YQAKAMAEILRY-FNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSNirKSYDSVIRELLQKpNARVVVL 274
Cdd:COG0683   126 QQAEALADYLAKkLGAKKVALLYDDYAYGQGLAAAFKAALKAAGGEVVGEEYYPPGT--TDFSAQLTKIKAA-GPDAVFL 202
                         250       260
                  ....*....|....*....|....*
gi 1907159703 275 FMRSDDSRELIAAASRVNASFTWVA 299
Cdd:COG0683   203 AGYGGDAALFIKQAREAGLKGPLNK 227
7tmC_TAS1R3 cd15290
type 1 taste receptor subtype 3, member of the class C of seven-transmembrane G ...
577-828 3.24e-19

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: 88.19  E-value: 3.24e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 577 AIGPVTIACLGFMCTCIVITVFIKHNNTPLVKASGRELCY---ILLFGVSLSYCMtffFIAKPSPVICALRRLGLGTSFA 653
Cdd:cd15290     3 SLGLLLLGVLLLVLQCSVGVLFLKHRGTPLVQASGGPLSIfalLSLMGACLSLLL---FLGQPSDVVCRLQQPLNALFLT 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 654 ICYSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQiVMVSVWLILETPGTRRY----TLPEKretVILK 729
Cdd:cd15290    80 VCLSTILSISLQIFLVTEFPKCAASHLHWLRGPGSWLVVLICCLVQ-AGLCGWYVQDGPSLSEYdakmTLFVE---VFLR 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 730 CNVKD-SSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIfYVTSSDYRVQTTTMCISVs 808
Cdd:cd15290   156 CPVEPwLGFGLMHGFNGALALISFMCTFMAQKPLKQYNLARDITFSTLIYCVTWVIFIPI-YAGLQVKLRSIAQVGFIL- 233
                         250       260
                  ....*....|....*....|
gi 1907159703 809 LSGFVVLGCLFAPKVHIVLF 828
Cdd:cd15290   234 LSNLGLLAAYYLPKCYLLLR 253
7tmC_GPR158-like cd15293
orphan GPR158 and similar proteins, member of the class C family of seven-transmembrane G ...
580-827 1.12e-18

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: 86.50  E-value: 1.12e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 580 PVTIACLgFMCTCIVITVFI-KHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRR----LGlgtsFAI 654
Cdd:cd15293     6 VLAVQAI-CILLCLVLALVVfRFRKVKVIKAASPILLELILFGALLLYFPVFILYFEPSVFRCILRPwfrhLG----FAI 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKngAQRPKFisPSSQVFICLGLI-LVQIVMVSVWLI--LETPGTRRYTLPEKRETVILKCN 731
Cdd:cd15293    81 VYGALILKTYRILVVFRSRS--ARRVHL--TDRDLLKRLGLIvLVVLGYLAAWTAvnPPNVEVGLTLTSSGLKFNVCSLD 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 732 VKDSSMLIsltydVVLVILCT--VYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSS----DY-------RV 798
Cdd:cd15293   157 WWDYVMAI-----AELLFLLWgvYLCYAVRKAPSAFNESRYISLAIYNELLLSVIFNIIRFFLLPslhpDLlfllfflHT 231
                         250       260
                  ....*....|....*....|....*....
gi 1907159703 799 QTTTmcisvslsgFVVLGCLFAPKVHIVL 827
Cdd:cd15293   232 QLTV---------TVTLLLIFGPKFYLVL 251
NCD3G pfam07562
Nine Cysteines Domain of family 3 GPCR; This conserved sequence contains several ...
505-555 1.61e-17

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: 76.91  E-value: 1.61e-17
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907159703 505 PTSQCSDPCAPNEMKNMQPGD-VCCWICIPCEPYEYL-VDEFTCMDCGPGQWP 555
Cdd:pfam07562   1 PSSVCSESCPPGQRKSQQGGApVCCWDCVPCPEGEISnTDSDTCKKCPEGQWP 53
7tmC_TAS1R2a-like cd15287
type 1 taste receptor subtype 2a and similar proteins, member of the class C of ...
584-828 1.26e-15

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: 77.42  E-value: 1.26e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 584 ACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGTSFAICYSALLTKT 663
Cdd:cd15287    10 ACVLVGLTLAVSVLFAINYNTPVVRSAGGPMCFLILGCLSLCSVSVFFYFGKPTVASCILRYFPFLLFYTVCLACFVVRS 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 664 NCIARIFdgvKNGAQRPKFIS----PSSQVFICLGLILVQIVMVSVWLILETPGTRRYTLPEKRETVILKC-NVKDSSMl 738
Cdd:cd15287    90 FQIVCIF---KIAAKFPKLHSwwvkYHGQWLLIAVAFVIQALLLITGFSFSPPKPYNDTSWYPDKIILSCDiNLKATSM- 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 739 iSLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTTTMCISVSLSGFvvLGCL 818
Cdd:cd15287   166 -SLVLLLSLCCLCFIFSYMGKDLPKNYNEAKAITFCLLLLILTWIIFATEYMLYRGKYIQLLNALAVLSSLYSF--LLWY 242
                         250
                  ....*....|
gi 1907159703 819 FAPKVHIVLF 828
Cdd:cd15287   243 FLPKCYIIIF 252
PBP1_iGluR_NMDA_NR1 cd06379
N-terminal leucine-isoleucine-valine-binding protein (LIVBP)-like domain of the NR1, an ...
75-300 9.27e-15

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: 76.99  E-value: 9.27e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  75 AIDEINKDNYLLPGVKLGvhildtcsRDTYALEQSLEfvrasLTKVDEAEYMCPDGSYAIQENIPLLiagviGGSYSSVS 154
Cdd:cd06379    21 AVNEVNAHSHLPRKITLN--------ATSITLDPNPI-----RTALSVCEDLIASQVYAVIVSHPPT-----PSDLSPTS 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 155 iqVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDFYQAKAMAEILRYFNWTYVSTVASEGDYGETGIEAFEQEA 234
Cdd:cd06379    83 --VSYTAGFYRIPVIGISARDSAFSDKNIHVSFLRTVPPYSHQADVWAEMLRHFEWKQVIVIHSDDQDGRALLGRLETLA 160
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907159703 235 RLRNIciaTAEKV-----GRSNIRKSYDSvIRELlqkpNARVVVLFMRSDDSRELIAAASRVN---ASFTWVAS 300
Cdd:cd06379   161 ETKDI---KIEKViefepGEKNFTSLLEE-MKEL----QSRVILLYASEDDAEIIFRDAAMLNmtgAGYVWIVT 226
7tmC_GABA-B-R1 cd15291
gamma-aminobutyric acid type B receptor subunit 1, member of the class C family of ...
582-823 2.92e-13

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: 70.83  E-value: 2.92e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 582 TIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFF------FIAKPS-PVICALRRLGLGTSFAI 654
Cdd:cd15291     8 LLASLGIFAAVFLLIFNIYNRHRRYIQLSQPHCNNVMLVGCILCLASVFLlgldgrHVSRSHfPLVCQARLWLLCLGFTL 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLGLILVQIVMVSVWLI------------LETPgtRRYTLPEK 722
Cdd:cd15291    88 AYGSMFTKVWRVHRLTTKKKEKKETRKTLEPWKLYAVVGILLVVDVIILAIWQIvdplhrtieefpLEEP--KDTDEDVK 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 723 RETVILKCNVKDSSMLISLTYDV--VLVILCTVYAFKTRKC-PENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQ 799
Cdd:cd15291   166 ILPQLEHCSSKKQNTWLGIVYGYkgLLLLFGLFLAYETRNVkVEKINDSRFVGMSIYNVVVLCLITAPVTMIISSQQDAS 245
                         250       260
                  ....*....|....*....|....
gi 1907159703 800 TTTMCISVSLSGFVVLGCLFAPKV 823
Cdd:cd15291   246 FAFVSLAILFSSYITLVLIFVPKI 269
PBP1_ABC_LIVBP-like cd06342
type 1 periplasmic ligand-binding domain of ABC (Atpase Binding Cassette)-type active ...
61-302 1.82e-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: 69.48  E-value: 1.82e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  61 NEDRGIQRLEAMLFAIDEINKDNyLLPGVKLGVHILDTCSRDTYAleqslefvrasltkVDEAEYMCPDGsyaiqenipl 140
Cdd:cd06342    12 NAALGQDIRNGAELAVDEINAKG-GGLGFKIELVAQDDACDPAQA--------------VAAAQKLVADG---------- 66
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 141 lIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKsRYDYFARTVPPDFYQAKAMAE-ILRYFNWTYVSTVASE 219
Cdd:cd06342    67 -VVAVIGHYNSGAAIAAAPIYAEAGIPMISPSATNPKLTEQ-GYKNFFRVVGTDDQQGPAAADyAAKTLKAKRVAVIHDG 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 220 GDYGETGIEAFEQEARLRNICIATAEKVGRSNirKSYDSVIRELLQKpNARVVVLFMRSDDSRELIAAASRVNASFTWVA 299
Cdd:cd06342   145 TAYGKGLADAFKKALKALGGTVVGREGITPGT--TDFSALLTKIKAA-NPDAVYFGGYYPEAGLLLRQLREAGLKAPFMG 221

                  ...
gi 1907159703 300 SDG 302
Cdd:cd06342   222 GDG 224
PBP1_GABAb_receptor_plant cd19990
periplasmic ligand-binding domain of Arabidopsis thaliana glutamate receptors and its close ...
145-302 1.89e-12

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: 69.95  E-value: 1.89e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 145 VIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSdKSRYDYFARTVPPDFYQAKAMAEILRYFNWTYVSTVASEGDYGE 224
Cdd:cd19990    68 IIGPQTSEEASFVAELGNKAQVPIISFSATSPTLS-SLRWPFFIRMTHNDSSQMKAIAAIVQSYGWRRVVLIYEDDDYGS 146
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 225 TGIEAFEQEarLRNICIATAEKVGRSNIrkSYDSVIRELLQK---PNARVVVLFMRSDDSRELIAAASRVN---ASFTWV 298
Cdd:cd19990   147 GIIPYLSDA--LQEVGSRIEYRVALPPS--SPEDSIEEELIKlksMQSRVFVVHMSSLLASRLFQEAKKLGmmeKGYVWI 222

                  ....
gi 1907159703 299 ASDG 302
Cdd:cd19990   223 VTDG 226
7tmC_RAIG_GPRC5 cd15043
retinoic acid-inducible orphan G-protein-coupled receptors; class C family of ...
575-827 2.20e-12

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: 67.98  E-value: 2.20e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 575 AWAIGPVTIACLG------FMCTCIVITVFIKHNNtplvKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGL 648
Cdd:cd15043     1 AWGIVLEAVAGAGvvttvaLMLILPILLPFVQDSN----KRSMLGTQFLFLLGTLGLFGLTFAFIIGLDGSTCPTRRFLF 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 649 GTSFAICYSALLTKTNCIARIFDGVKngaqrpkfiSPSSQVF--ICLGLILVQIVMVSVWLILETPGTRRYTLPEkretv 726
Cdd:cd15043    77 GVLFAICFSCLLAHAVSLTKLVRGRK---------GPSGWVIlgLALGLSLVQVIIAIEWLVLTMNRTNVNVFSE----- 142
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 727 iLKCNVKDSSMLISLTYDVVLVILCTVYA-------FKTRKcpenfNEAKFIGFTMYTTCIIWLAFLPIFY---VTSSDY 796
Cdd:cd15043   143 -LSCARRNMDFVMALIYVMFLLALTFLMAsftlcgsFKRWK-----RHGAFILLTMLLSVAIWVAWITMYMlgnVLQFDR 216
                         250       260       270
                  ....*....|....*....|....*....|.
gi 1907159703 797 RVQTTTMCISVSLSGFVVLGCLFAPKVHIVL 827
Cdd:cd15043   217 RWDDPTLAIALAANGWVFVLFYVIPEFWLLT 247
7tmC_RAIG3_GPRC5C cd15277
retinoic acid-inducible orphan G-protein-coupled receptor 3; class C family of ...
575-786 1.51e-10

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: 62.44  E-value: 1.51e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 575 AWAIGPVTIACLGFMCTCIVITVFIKhnNTPLV----KASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLGT 650
Cdd:cd15277     1 AWGIVLEAVAGAGVVTSFVLTIVLVA--SLPFVqdkkKKSLLGTQVFFLLGTLGLFCLVFAFIVGPNFATCASRRFLFGV 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 651 SFAICYSALLTKTncIARIFDGVKNGAQRPKFIspssqVFICLGLILVQIVMVSVWLI---LETPGTRRYTLPEkretvi 727
Cdd:cd15277    79 LFAICFSCLLAHA--VRLNFLARRNRGPRGWVI-----FLLALGLWLVEVIINTEWLIitiVRGNAGSAPVLGD------ 145
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907159703 728 lKCNVKDSSMLISLTYDVVLVILCTVYAFKT--------RKcpenfnEAKFIGFTMYTTCIIWLAFL 786
Cdd:cd15277   146 -PCNIANQDFVMALIYVMFLLLAAFITAWPAlcgkykhwRK------HGAFILVTGFLSVAIWVAWI 205
7tmC_RAIG2_GPRC5B cd15278
retinoic acid-inducible orphan G-protein-coupled receptor 2; class C family of ...
576-827 2.73e-10

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: 61.75  E-value: 2.73e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 576 WAIGPVTIACLGFMCTCIVITV------FIKHNNtplvKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGLG 649
Cdd:cd15278     2 WGIVVEAVAGAGVLITLLLMLIllvrlpFIKEKE----KKSPVGPHFLFLLGTLGLFGLTFAFIIQEDETICSLRRFLWG 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 650 TSFAICYSALLTKTNCIARIfdgVKNGAqrpkfiSPS--SQVFICLGLILVQIVMVSVWLILETPGTRRytlpekretvi 727
Cdd:cd15278    78 VLFALCFSCLLAQGWRLRRL---VRHGK------GPSgwHLTGLALCLMLVQVIIAVEWLILTVLRDGR----------- 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 728 LKCNVKDSSMLISLTYDVVLVILCTVYAF-----KTRKCPENfneAKFIGFTMYTTCIIWLAFLpIFYVTSSDYRVQT-- 800
Cdd:cd15278   138 PACQYEPMDFVMALIYVMVLLVATLGLALftlcgKFQKWKKN---GICLLITCFLSVLIWVAWM-TMYLYGNDELGRSdd 213
                         250       260       270
                  ....*....|....*....|....*....|
gi 1907159703 801 ---TTMCISVSLSGFVVLGCLFAPKVHIVL 827
Cdd:cd15278   214 wndPTLAIALVASGWVFLIFHAIPEVHCTL 243
7tmC_GABA-B-R2 cd15294
gamma-aminobutyric acid type B receptor subunit 2, member of the class C family of ...
582-823 5.96e-10

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: 60.90  E-value: 5.96e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 582 TIACLGFMCTCIVITVFIKHNNTPLVKASGRELCYILLFGVSLSYCMTFFF-----IAKPS--PVICALRRLGLGTSFAI 654
Cdd:cd15294     8 SLTIIGIILASAFLAFNIKFRNHRYIKMSSPYMNNLIILGCMLTYASVILLgldgsLVSEKtfETLCTARTWILCVGFTL 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKngaqRPKFISPSSQVFICLG-LILVQIVMVSVWLIL-----ETPGTRRYTLPEKRETVIL 728
Cdd:cd15294    88 AFGAMFSKTWRVHSIFTNVK----LNKKAIKDYKLFIIVGvLLLIDICILITWQIVdpfyrTVKELEPEPDPAGDDILIR 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 729 ----KCNVKDSSMLISLTYDV--VLVILCTVYAFKTRKCP-ENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQTT 801
Cdd:cd15294   164 peleYCESTHMTIFLGIIYAYkgLLMVFGCFLAWETRNVSiPALNDSKYIGMSVYNVVIMCVIGAAVSFILRDQPNVQFC 243
                         250       260
                  ....*....|....*....|..
gi 1907159703 802 TMCISVSLSGFVVLGCLFAPKV 823
Cdd:cd15294   244 IISLFIIFCTTITLCLVFVPKL 265
PBP1_ABC_RPA1789-like cd06333
type 1 periplasmic binding-protein component (CouP) of an ABC system (CouPSTU; RPA1789, ...
65-250 7.62e-10

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: 61.41  E-value: 7.62e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  65 GIQRLEAMLFAIDEINKDNYLLpGVKLGVHILDTCSRDTyaleQSLEFVRASLT--KVDeaeymcpdgsyaiqeniplli 142
Cdd:cd06333    16 GIPERNAVELLVEQINAAGGIN-GRKLELIVYDDESDPT----KAVTNARKLIEedKVD--------------------- 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 143 aGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYfaRTVPPDFYQAKAMAEILRYFNWTYVSTVASEGDY 222
Cdd:cd06333    70 -AIIGPSTTGESLAVAPIAEEAKVPLISLAGAAAIVEPVRKWVF--KTPQSDSLVAEAILDYMKKKGIKKVALLGDSDAY 146
                         170       180
                  ....*....|....*....|....*...
gi 1907159703 223 GETGIEAFEQEARLRNICIATAEKVGRS 250
Cdd:cd06333   147 GQSGRAALKKLAPEYGIEIVADERFART 174
PBP1_ABC_HAAT-like cd06344
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
69-307 1.39e-09

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: 60.70  E-value: 1.39e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  69 LEAMLFAIDEINKDNYLLpGVKLGVHILDtcsrDtyaleqslefvRASLTK-VDEAeymcpdgsYAIQENIPllIAGVIG 147
Cdd:cd06344    18 LEGVELAVEEINAAGGVL-GRKIRLVEYD----D-----------EASVDKgLAIA--------QRFADNPD--VVAVIG 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 148 GSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKsRYDYFARTVPPDFYQAKAMAEILRYFNWTYVSTVASEGDYGETGI 227
Cdd:cd06344    72 HRSSYVAIPASIIYERAGLLMLSPGATAPKLTQH-GFKYIFRNIPSDEDIARQLARYAARQGYKRIVIYYDDDSYGKGLA 150
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 228 EAFEQEARLRNICIATAEKVGRSNirKSYDSVIRELLQKPNARVVVLFMRSDDSRELIAAASRVNASFTWVASDGWGAQE 307
Cdd:cd06344   151 NAFEEEARELGITIVDRRSYSSDE--EDFRRLLSKWKALDFFDAIFLAGSMPEGAEFIKQARELGIKVPIIGGDGLDSPE 228
PBP1_ABC_ligand_binding-like cd19984
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
145-309 1.78e-09

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: 59.92  E-value: 1.78e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 145 VIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSryDYFARTVPPDFYQAKAMAEILRYFNWTYVSTVASEGDYGE 224
Cdd:cd19984    71 IIGGVCSSETLAIAPIAEQNKVVLISPGASSPEITKAG--DYIFRNYPSDAYQGKVLAEFAYNKLYKKVAILYENNDYGV 148
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 225 TGIEAFEQEARLRNICIATAEKVGRSNirKSYDSVIRELLQKpNARVVVLFMRSDDSRELIAAASRVNASFTWVASDGWG 304
Cdd:cd19984   149 GLKDVFKKEFEELGGKIVASESFEQGE--TDFRTQLTKIKAA-NPDAIFLPGYPKEGGLILKQAKELGIKAPILGSDGFE 225

                  ....*
gi 1907159703 305 AQESI 309
Cdd:cd19984   226 DPELL 230
PBP1_ABC_HAAT-like cd19985
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
144-306 6.26e-09

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: 58.44  E-value: 6.26e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 144 GVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYdYFaRTVPPDFYQAKAMAEILRYF-NWTYVSTVASEGDY 222
Cdd:cd19985    69 AVIGHYYSSASIAAGKIYKKAGIPAITPSATADAVTRDNPW-YF-RVIFNDSLQGRFLANYAKKVlKKDKVSIIYEEDSY 146
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 223 GETGIEAFEQEARLRNICIATAEKVGR--SNIRKSYDSVIRELLQKP-NARVVVLFMRSDDSRELIAAASRVNASFTWVA 299
Cdd:cd19985   147 GKSLASVFEATARALGLKVLKKWSFDTdsSQLDQNLDQIVDELKKAPdEPGVIFLATHADEGAKLIKKLRDAGLKAPIIG 226

                  ....*..
gi 1907159703 300 SDGWGAQ 306
Cdd:cd19985   227 PDSLASE 233
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
583-822 4.40e-08

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: 55.51  E-value: 4.40e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 583 IACLGFMCTCIVITVFIKHNNTPlvkASGRELCYILLFGVSLSYCMTFFFIAKPSP--------VICALRRLGLGTSFAI 654
Cdd:cd14964     8 LTCLGLLGNLLVLLSLVRLRKRP---RSTRLLLASLAACDLLASLVVLVLFFLLGLteassrpqALCYLIYLLWYGANLA 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 655 CYSALLTKTNCIARIFDGVKNgaqRPKFISPSSQVFICLGLILVQIVMVSVWLILETPGTRRYTLpekRETVILKCNVKD 734
Cdd:cd14964    85 SIWTTLVLTYHRYFALCGPLK---YTRLSSPGKTRVIILGCWGVSLLLSIPPLVGKGAIPRYNTL---TGSCYLICTTIY 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 735 SSMLISLTYDVVLVILCTVYAFKTRK----------------CPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRV 798
Cdd:cd14964   159 LTWGFLLVSFLLPLVAFLVIFSRIVLrlrrrvrairsaaslnTDKNLKATKSLLILVITFLLCWLPFSIVFILHALVAAG 238
                         250       260
                  ....*....|....*....|....*....
gi 1907159703 799 Q-----TTTMCISVSLSGFVVLGCLFAPK 822
Cdd:cd14964   239 QglnllSILANLLAVLASTLNPFIYCLGN 267
PBP1_GC_G-like cd06372
Ligand-binding domain of membrane guanylyl cyclase G; This group includes the ligand-binding ...
166-486 1.76e-07

Ligand-binding domain of membrane guanylyl cyclase G; This group includes the ligand-binding domain of membrane guanylyl cyclase G (GC-G) which is a sperm surface receptor and might function, similar to its sea urchin counterpart, in the early signaling event that regulates the Ca2+ influx/efflux and subsequent motility response in sperm. GC-G appears to be a pseudogene in human. Furthermore, in contrast to the other orphan receptor GCs, GC-G has a broad tissue distribution in rat, including lung, intestine, kidney, and skeletal muscle.


Pssm-ID: 380595 [Multi-domain]  Cd Length: 390  Bit Score: 54.42  E-value: 1.76e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 166 IPQISYASTSAKLSDKSRYDYFARTVPPDFYQAKAMAEILRYFNWTYV-----STVASEGDYGETGIEAFEQEARLRNIC 240
Cdd:cd06372    93 IPMFGFVGQSPKLDDRDVYDTYVKLVPPLQRIGEVLVKTLQFFGWTHVamfggSSATSTWDKVDELWKSVENQLKFNFNV 172
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 241 IATaekvgrsnIRksYDSVIRELLQK------PNARVVVLFMRSDDSRELIAAAsrvnasftwvasdgwgAQESIVKGsE 314
Cdd:cd06372   173 TAK--------VK--YDTSNPDLLQEnlryisSVARVIVLICSSEDARSILLEA----------------EKLGLMDG-E 225
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 315 HVAYGAITLE-------LASHPVRQFDRYFQS-----LNPYNNHRNPWFRDFWEQK-----FQCSLqnkrnhrqicdkhl 377
Cdd:cd06372   226 YVFFLLQQFEdsfwkevLNDEKNQVFLKAYEMvfliaQSSYGTYGYSDFRKQVHQKlrrapFYSSI-------------- 291
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 378 aidSSNYEQESKIMFVVNAVYAMAHALHKMQRtlcpnttklcDAMKILDGKKLYKDYLLKINFTApfnpnKGADSIVKFD 457
Cdd:cd06372   292 ---SSEDQVSPYSAYLHDAVLLYAMGLKEMLK----------DGKDPRDGRALLQTLRGYNQTTF-----YGITGLVYLD 353
                         330       340
                  ....*....|....*....|....*....
gi 1907159703 458 TYGDGMGRYNVFNFQHIGGKYSYLKVGHW 486
Cdd:cd06372   354 VQGERHMDYSVYDLQKSGNQSLFVPVLHY 382
PBP1_ABC_LivK_ligand_binding-like cd06347
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
65-312 3.10e-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, 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: 53.32  E-value: 3.10e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  65 GIQRLEAMLFAIDEINKDNYLLpGVKLGVHILDTCSRDTyaleqslEFVRASLTKVDEaeymcpDGsyaiqenipllIAG 144
Cdd:cd06347    16 GQPALNGAELAVDEINAAGGIL-GKKIELIVYDNKSDPT-------EAANAAQKLIDE------DK-----------VVA 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 145 VIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYdYFaRTVPPDFYQAKAMAE-ILRYFNWTYVSTVASEG-DY 222
Cdd:cd06347    71 IIGPVTSSIALAAAPIAQKAKIPMITPSATNPLVTKGGDY-IF-RACFTDPFQGAALAKfAYEELGAKKAAVLYDVSsDY 148
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 223 GETGIEAFEQEARLRNICIATAEKVGRSNirKSYDSVIRELLQKpNARVVVLfmrSDDSRE--LIAAASR---VNASFtw 297
Cdd:cd06347   149 SKGLAKAFKEAFEKLGGEIVAEETYTSGD--TDFSAQLTKIKAA-NPDVIFL---PGYYEEaaLIIKQARelgITAPI-- 220
                         250
                  ....*....|....*
gi 1907159703 298 VASDGWGAQESIVKG 312
Cdd:cd06347   221 LGGDGWDSPELLELG 235
PBP1_ABC_ligand_binding-like cd19980
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
65-359 3.94e-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, 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: 53.00  E-value: 3.94e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  65 GIQRLEAMLFAIDEINKDNYLLpGVKLGVHILDTCSRDtyalEQSLEFVRAsLTKVDEaeymcpdgsyaiqenipllIAG 144
Cdd:cd19980    16 GQQVLNGAKLAVEEINAKGGVL-GRKLELVVEDDKCPP----AEGVAAAKK-LITDDK-------------------VPA 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 145 VIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSdKSRYDYFARTVPPDFYQAKAMAEILRYF-NWTYVSTVASEGDYG 223
Cdd:cd19980    71 IIGAWCSSVTLAVMPVAERAKVPLVVEISSAPKIT-EGGNPYVFRLNPTNSMLAKAFAKYLADKgKPKKVAFLAENDDYG 149
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 224 ETGIEAFEQEARLRNICIATAEKVGR---------SNIRKSydsvirellqkpNARVVVLFMRSDDSRELIAAASRVNAS 294
Cdd:cd19980   150 RGAAEAFKKALKAKGVKVVATEYFDQgqtdfttqlTKLKAA------------NPDAIFVVAETEDGALILKQARELGLK 217
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907159703 295 FTWVASDGWGAQESIVKGSEhVAYGAITLelashpvrqfDRYFqslnpynnhrnPWFRDFWEQKF 359
Cdd:cd19980   218 QQLVGTGGTTSPDLIKLAGD-AAEGVYGA----------SIYA-----------PTADNPANKAF 260
PBP1_iGluR_NMDA cd06367
N-terminal leucine-isoleucine-valine-binding protein (LIVBP)-like domain of the ionotropic ...
166-298 3.93e-06

N-terminal leucine-isoleucine-valine-binding protein (LIVBP)-like domain of the ionotropic N-methyl-D-asparate (NMDA) subtype of glutamate receptors; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the ionotropic N-methyl-D-asparate (NMDA) subtype of glutamate receptors. 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. The function of the NMDA subtype receptor serves critical functions in neuronal development, functioning, and degeneration in the mammalian central nervous system. The functional NMDA receptor is a heterotetramer comprising two NR1 and two NR2 (A, B, C, and D) or 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: 380590 [Multi-domain]  Cd Length: 357  Bit Score: 49.93  E-value: 3.93e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 166 IPQISYASTSAK-LSDKSRYDYFARTVPPDFYQAKAMAEILRYFNWTYVSTVASEgdygETGIEAFEQ--EARLRNICIA 242
Cdd:cd06367    91 TPVLGLHGRSSMiMADKSEHSMFLQFGPPIEQQASVMLNIMEEYDWYIVSLVTTY----FPGYQDFVNklRSTIENSGWE 166
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907159703 243 TAEKVGRSNIRKSYDSVIRELL---QKPNARVVVLFMRSDDSRELIAAASRVN---ASFTWV 298
Cdd:cd06367   167 LEEVLQLDMSLDDGDSKLQAQLkklQSPEARVILLYCTKEEATYVFEVAASVGltgYGYTWL 228
PBP1_NPR-like cd06373
Ligand binding domain of natriuretic peptide receptor (NPR) family; Ligand binding domain of ...
69-292 8.29e-06

Ligand binding domain of natriuretic peptide receptor (NPR) family; Ligand binding domain of natriuretic peptide receptor (NPR) family which consists of three different subtypes: type A natriuretic peptide receptor (NPR-A, or GC-A), type B natriuretic peptide receptors (NPR-B, or GC-B), and type C natriuretic peptide receptor (NPR-C). There are three types of natriuretic peptide (NP) ligands specific to the receptors: atrial NP (ANP), brain or B-type NP (BNP), and C-type NP (CNP). The NP family is thought to have arisen through gene duplication during evolution and plays an essential role in cardiovascular and body fluid homeostasis. ANP and BNP bind mainly to NPR-A, while CNP binds specifically to NPR-B. Both NPR-A and NPR-B have guanylyl cyclase catalytic activity and produces intracellular secondary messenger cGMP in response to peptide-ligand binding. Consequently, the NPR-A activation results in vasodilation and inhibition of vascular smooth muscle cell proliferation. NPR-C acts as the receptor for all the three members of NP family, and functions as a clearance receptor. Unlike NPR-A and -B, NPR-C lacks an intracellular guanylyl cyclase domain and is thought to exert biological actions by sequestration of released natriuretic peptides and/or inhibition of adenylyl cyclase.


Pssm-ID: 380596 [Multi-domain]  Cd Length: 394  Bit Score: 49.19  E-value: 8.29e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  69 LEAMLFAIDEInKDNYLLPGVKLGVHILDT-CSrDTYALEQSLEFvrasltkvdeaeyMCPDGSYAIqeniplliagvIG 147
Cdd:cd06373    20 LPAIELALRRV-ERRGFLPGWRFQVHYRDTkCS-DTLAPLAAVDL-------------YCAKKVDVF-----------LG 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 148 GSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDFYQAKAMAEILRYFNWTYVSTVASEGDYGETGI 227
Cdd:cd06373    74 PVCEYALAPVARYAGHWNVPVLTAGGLAAGFDDKTEYPLLTRMGGSYVKLGEFVLTLLRHFGWRRVALLYHDNLRRKAGN 153
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907159703 228 EA--FEQEArlrnicIATAEKVGRSNIRKSYDSV------IRELLQK--PNARVVVLFMRSDDSRELIAAASRVN 292
Cdd:cd06373   154 SNcyFTLEG------IFNALTGERDSIHKSFDEFdetkddFEILLKRvsNSARIVILCASPDTVREIMLAAHELG 222
PBP1_As_SBP-like cd06330
periplasmic substrate-binding domain of active transport proteins; Periplasmic ...
65-232 1.08e-05

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: 48.33  E-value: 1.08e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  65 GIQRLEAMLFAIDEINKDNYLLpGVKLGVHILDTCSRDTYALEQSLEFVRasltkvdeaeymcpdgsyaiQENIPLLIAG 144
Cdd:cd06330    16 GEPARNGAELAVEEINAAGGIL-GRKIELVVRDDKGKPDEAVRAARELVL--------------------QEGVDFLIGT 74
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 145 VIggsySSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDFYQAKAMAEIL--RYFNWTYVSTVASEGDY 222
Cdd:cd06330    75 IS----SGVALAVAPVAEELKVLFIATDAATDRLTEENFNPYVFRTSPNTYMDAVAAALYAakKPPDVKRWAGIGPDYEY 150
                         170
                  ....*....|
gi 1907159703 223 GETGIEAFEQ 232
Cdd:cd06330   151 GRDSWAAFKA 160
7tmC_Boss cd15042
Bride of sevenless, member of the class C family of seven-transmembrane G protein-coupled ...
575-827 1.17e-05

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: 47.80  E-value: 1.17e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 575 AWAIGPVTIACLGFMcTCIVITVFIKHNNTPLVKASGRELCYILL-------FGVSLSYCMTFFFIAKPSpvICALRRLG 647
Cdd:cd15042     1 VWVPAFLTAAILGIL-FCCAILVFIVVRVTTKDVLEGNPVLTILLllaliftFLSFLPFSMEDDYFGKNS--LCAVRILL 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 648 LGTSFAICYSALLTKTNCIARIFDGVKngaqrpkFISPSS---QVFICLGLILVQIVMVSVWLILETpgtrrytlpeKRE 724
Cdd:cd15042    78 TTLAFGFTFSLMLSRALFLALSTGEGG-------FLSHVNgylQSVMCLFSFGVQVAMSVQYFVLNH----------ANS 140
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 725 TVILKCNVkdssMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRvqTTTMC 804
Cdd:cd15042   141 AVIYRGLW----FIALLGYDIFLLIALFVLCPFIFRSQRNYREGKYFFGASIGLLVIWVIWLPCFLLMGPEWR--DAVIS 214
                         250       260
                  ....*....|....*....|...
gi 1907159703 805 ISVSLSGFVVLGCLFAPKVHIVL 827
Cdd:cd15042   215 FGLVATAYAILVGILVPRTYLMT 237
PBP1_ABC_HAAT-like cd19986
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
70-203 2.15e-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 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: 47.24  E-value: 2.15e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  70 EAMLFAIDEINKDNYLLpGVKLGVHILDTCSRDTYALEqslefvraSLTKVdeaeymcpdgsyaIQENIPlliAGVIGGS 149
Cdd:cd19986    21 NGAQLALEEINAAGGVL-GRPLELVVEDDQGTNTGAVN--------AVNKL-------------ISDDKV---VAVIGPH 75
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907159703 150 YSSVSIQVANLLRLFQIPQIsYASTSAKLSDKsRYDYFARTVPPDFYQAKAMAE 203
Cdd:cd19986    76 YSTQVLAVSPLVKEAKIPVI-TGGTSPKLTEQ-GNPYMFRIRPSDSVSAKALAK 127
PBP1_ABC_HAAT-like cd19983
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
140-360 3.03e-05

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: 46.81  E-value: 3.03e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 140 LLIAG----VIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSryDYFARTVPPDFYQAKAMAeilRY-FNWTYVS 214
Cdd:cd19983    61 ELIAGgvvaIIGHMTSAMTVAVLPVINEAKVLMISPTVSTPELSGKD--DYFFRVTPTTRESAQALA---RYaYNRGGLR 135
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 215 TVASEGD-----YGETGIEAFEQEarlrniciatAEKVG---------RSNIRKSYDSVIRELLQ-KPNArvvVLFMRSD 279
Cdd:cd19983   136 RVAVIYDlsnraYSESWLDNFRSE----------FEALGgrivaeipfSSGADVDFSDLARRLLAsKPDG---LLLVASA 202
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 280 DSRELIAAASRVNASFTWVASDGWGAQESIVKGSEHVAYGaITLELAshpvrqFDRyfqslnpynNHRNPWFRDFwEQKF 359
Cdd:cd19983   203 VDTAMLAQQIRKLGSKIPLFSSAWAATEELLELGGKAVEG-MLFSQA------YDR---------NSSNPRYLAF-KEAY 265

                  .
gi 1907159703 360 Q 360
Cdd:cd19983   266 E 266
PBP1_ABC_ligand_binding-like cd06343
type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type ...
135-356 3.03e-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: 380566 [Multi-domain]  Cd Length: 355  Bit Score: 47.18  E-value: 3.03e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 135 QENIpLLIAGVIGgsySSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFArTVPPDFYQAKAMAE-ILRYFNWTYV 213
Cdd:cd06343    72 QDKV-FAIVGGLG---TPTNLAVRPYLNEAGVPQLFPATGASALSPPPKPYTFG-VQPSYEDEGRILADyIVETLPAAKV 146
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 214 STVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSNIrkSYDSVIRELLQKpNARVVVLFMRSDDSRELIAAASRVNA 293
Cdd:cd06343   147 AVLYQNDDFGKDGLEGLKEALKAYGLEVVAEETYEPGDT--DFSSQVLKLKAA-GADVVVLGTLPKEAAAALKEAAKLGW 223
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907159703 294 SFTWVASDGWGAQESIVKGSEHVAYGAITlelashpvrqfdryFQSLNPYNNHRNPWFRDFWE 356
Cdd:cd06343   224 KPTFLGSSVSADPTTLAKAGGDAAEGVYS--------------ASYLKDPTDADDPAVKEFRE 272
7tmC_RAIG1_4_GPRC5A_D cd15279
retinoic acid-inducible orphan G-protein-coupled receptors 1 and 4; class C family of ...
575-815 1.66e-04

retinoic acid-inducible orphan G-protein-coupled receptors 1 and 4; class C family of seven-transmembrane G protein-coupled receptors, group 5, member A and D; 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. 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. The specific function of RAIG4 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: 320406  Cd Length: 248  Bit Score: 44.37  E-value: 1.66e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 575 AWAIGPVTIACLG------FMCTCIVITVFIKHNNtplvKASGRELCYILLFGVSLSYCMTFFFIAKPSPVICALRRLGL 648
Cdd:cd15279     1 AWGIVLETLAAAGivvtiaLILALLFLMCKVQDSN----KRKMLPTQFLFLLGVLGIFGLTFAFIIELNGQTGPTRFFLF 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 649 GTSFAICYSALLTKTNCIARIFDGVKNgaqrpkfISPSSQVFICLGLILVQIVMVSVWLIL-----ETPGTRRYTLPEKR 723
Cdd:cd15279    77 GVLFAICFSCLLAHASNLVKLVRGRKP-------FSWLVILLLAVGFSLVQVVIAIEYIVLtmvrtNVNVFSEMTAPQLN 149
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 724 ET-VILKCNVkdsSMLISLTYDVVLVILCTVYAFKTRkcpenfnEAKFIGFTMYTTCIIWLAFLPIFYVTSSDYRVQT-- 800
Cdd:cd15279   150 EDfVLLLIYV---LFLMALTFLVSKFTFCGSCKGWKR-------HGAHIFVTMLFSIAIWVAWITMLLRGNPFQRNRQwd 219
                         250
                  ....*....|....*.
gi 1907159703 801 -TTMCISVSLSGFVVL 815
Cdd:cd15279   220 dPVLSIALVANGWVFL 235
PBP1_ABC_HAAT-like cd19981
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
65-234 4.88e-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 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: 43.05  E-value: 4.88e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  65 GIQRLEAMLFAIDEINKDNYLLpGVKLG-VHILDTCSRDtyaleQSLEFVRaSLTKVDEaeymcpdgsyaiqenipllIA 143
Cdd:cd19981    16 GKSALHGAELAVEQINAAGGIN-GKKVElVVYDDQASPK-----QAVNIAQ-KLIEQDK-------------------VV 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 144 GVIGGSYSSVSIQVANLLRLFQIPQIS-YASTSAKLSDKsryDYFARTVPPDFYQAKAMAEIL-RYFNWTYVSTVASEGD 221
Cdd:cd19981    70 AVVSGSYSGPTRAAAPIFQEAKVPMVSaYAVHPDITKAG---DYVFRVAFLGPVQGRAGAEYAvKDLGAKKVAILTIDND 146
                         170
                  ....*....|...
gi 1907159703 222 YGETGIEAFEQEA 234
Cdd:cd19981   147 FGKSLAAGFKEEA 159
PBP1_iGluR_AMPA cd06380
N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the AMPA receptor; ...
61-409 5.86e-04

N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the AMPA receptor; N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor, a member of the glutamate-receptor ion channels (iGluRs). AMPA receptors are the major mediators of excitatory synaptic transmission in the central nervous system. 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. AMPA receptors consist of four types of subunits (GluR1, GluR2, GluR3, and GluR4) which combine to form a tetramer and play an important roles in mediating the rapid excitatory synaptic current.


Pssm-ID: 380603 [Multi-domain]  Cd Length: 390  Bit Score: 43.04  E-value: 5.86e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  61 NEDRGIQRleAMLFAIDEINKDNYLLPGVKLGVHILDTCSRDTYALEQSL--EFVRasltkvdeaeymcpdGSYAIqeni 138
Cdd:cd06380     8 SGEDQVQT--AFRYAIDRHNSNNNNRFRLFPLTERIDITNADSFSVSRAIcsQLSR---------------GVFAI---- 66
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 139 plliagVIGGSYSSVSIqVANLLRLFQIPQISYASTSAKLSDKSRYDYFARtvpPDFyqAKAMAEILRYFNW---TYVst 215
Cdd:cd06380    67 ------FGSSDASSLNT-IQSYSDTFHMPYITPSFPKNEPSDSNPFELSLR---PSY--IEAIVDLIRHYGWkkvVYL-- 132
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 216 vaSEGDYGETGIEAFEQEARLRNICIATAEKVGRSNIRKSYDSVIRELLQKPNARVVVLFMRSDDSRELIAAasrvnasf 295
Cdd:cd06380   133 --YDSDEGLLRLQQLYDYLKEKSNISVRVRRVRNVNDAYEFLRTLRELDREKEDKRIVLDLSSERYQKILEQ-------- 202
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 296 twVASDGwgaqesIVKGSEHvaYGAITLELASHPVRQFDRY------FQSLNPynNHRNPW-FRDFWEQKFQcSLQNKRN 368
Cdd:cd06380   203 --IVEDG------MNRRNYH--YLLANLDFLDLDLERFLHGgvnitgFQLVDT--NNKTVKdFLQRWKKLDP-REYPGAG 269
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|..
gi 1907159703 369 HRQI-CDKHLAIDssnyeqeskimfvvnAVYAMAHALHKMQR 409
Cdd:cd06380   270 TDTIpYEAALAVD---------------AVLVIAEAFQSLLR 296
PBP1_ABC_HAAT-like cd19988
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
145-248 8.54e-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 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: 42.26  E-value: 8.54e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 145 VIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDkSRYDYFARTVPPDFYQAKAMAE-ILRYFNWTYVSTVASEGDYG 223
Cdd:cd19988    71 IIGSINSSCTLAAIRVALKAGVPQINPGSSAPTITE-SGNPWVFRCTPDDRQQAYALVDyAFEKLKVTKIAVLYVNDDYG 149
                          90       100
                  ....*....|....*....|....*
gi 1907159703 224 ETGIEAFeqearlrnicIATAEKVG 248
Cdd:cd19988   150 RGGIDAF----------KDAAKKYG 164
PBP1_iGluR_Kainate cd06382
N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the kainate ...
71-273 9.65e-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: 42.21  E-value: 9.65e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703  71 AMLFAIDEINKDNyLLPGVKLGVHILDTCSRDTYALEQslefvrasltkvdeaeYMCPdgsyAIQENipllIAGVIGGSY 150
Cdd:cd06382    16 AFKYAVDRINRER-TLPNTKLVPDIERVPRDDSFEASK----------------KVCE----LLEEG----VAAIFGPSS 70
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 151 SSVSIQVANLLRLFQIPQISYAStSAKLSDKSRYdyfarTV----PPDFYqAKAMAEILRYFNWTYVsTVASEGDYGETG 226
Cdd:cd06382    71 PSSSDIVQSICDALEIPHIETRW-DPKESNRDTF-----TInlypDPDAL-SKAYADLVKSLNWKSF-TILYEDDEGLIR 142
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1907159703 227 IEAFEQEARLRNICIaTAEKVGRSNirkSYDSVIRELLQKPNARVVV 273
Cdd:cd06382   143 LQELLKLPKPKDIPI-TVRQLDPGD---DYRPVLKEIKKSGETRIIL 185
PBP1_ABC_ligand_binding-like cd19982
type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type ...
142-246 2.19e-03

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: 41.11  E-value: 2.19e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907159703 142 IAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSdKSRYDYFARTVPPDFYQAKAMAEILRY-FNWTYVSTVASEG 220
Cdd:cd19982    68 VPLIVGGYSSGITLPVAAVAERQKIPLLVPTAADDDIT-KPGYKYVFRLNPPASIYAKALFDFFKElVKPKTIAILYENT 146
                          90       100
                  ....*....|....*....|....*.
gi 1907159703 221 DYGETGIEAFEQEARLRNICIATAEK 246
Cdd:cd19982   147 AFGTSVAKAARRFAKKRGIEVVADES 172
 
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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