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Conserved domains on  [gi|378548213|ref|NP_001243740|]
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metabotropic glutamate receptor 4 isoform 4 precursor [Homo sapiens]

Protein Classification

G-protein coupled receptor; G-protein-coupled receptor( domain architecture ID 11659899)

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| G-protein-coupled receptor (GPCR) containing an extracellular PBP1 (type 1 periplasmic-binding protein) ligand-binding domain, belongs to the class C GPCRs, which are mainly composed of metabotropic glutamate receptors (mGluRs), gamma-aminobutyric acid type B (GABA-B) receptors, Ca(2+)-sensing receptors (CaSR), taste receptors (T1R), and pheromone receptors (V2R)

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
Periplasmic_Binding_Protein_type1 super family cl10011
Type 1 periplasmic binding fold superfamily; Type 1 periplasmic binding fold superfamily. This ...
43-461 0e+00

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


The actual alignment was detected with superfamily member cd06376:

Pssm-ID: 471960 [Multi-domain]  Cd Length: 467  Bit Score: 805.95  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  43 IRIDGDITLGGLFPVHGRGSEGKPCGELKKEKGIHRLEAMLFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLTF 122
Cdd:cd06376    1 IRVEGDITLGGLFPVHARGLAGVPCGEIKKEKGIHRLEAMLYALDQINSDPDLLPNVTLGARILDTCSRDTYALEQSLTF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 123 VQALIEKDGTEVRCGSGGPPIITKPERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSD 202
Cdd:cd06376   81 VQALIQKDTSDVRCTNGDPPVFVKPEKVVGVIGASASSVSIMVANILRLFQIPQISYASTAPELSDDRRYDFFSRVVPPD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 203 TYQAQAMVDIVRALKWNYVSTVASEGSYGESGVEAFIQKSREDGGVCIAQSVKIPREPKAGEFDKIIRRLLETSNARAVI 282
Cdd:cd06376  161 SFQAQAMVDIVKALGWNYVSTLASEGNYGEKGVESFVQISREAGGVCIAQSEKIPRERRTGDFDKIIKRLLETPNARAVV 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 283 IFANEDDIRRVLEAARRANQTGHFFWMGSDSWGSKIAPVLHLEEVAEGAVTILPKRMSV----------------RD--- 343
Cdd:cd06376  241 IFADEDDIRRVLAAAKRANKTGHFLWVGSDSWGAKISPVLQQEDVAEGAITILPKRASIegfdayftsrtlennrRNvwf 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 344 ----------------------------RERIGQDSAYEQEGKVQFVIDAVYAMGHALHAMHRDLCPGRVGLCPRMDPVD 395
Cdd:cd06376  321 aefweenfnckltssgskkedtlrkctgQERIGRDSGYEQEGKVQFVVDAVYAMAHALHNMNKDLCPGYRGLCPEMEPAG 400
                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 378548213 396 GTQLLKYIRNVNFSGIAGNPVTFNENGDAPGRYDIYQYQLRN-DSAEYKVIGSWTDHLHLRIERMHW 461
Cdd:cd06376  401 GKKLLKYIRNVNFNGSAGTPVMFNKNGDAPGRYDIFQYQTTNgSNYGYRLIGQWTDELQLNIEDMQW 467
7tmC_mGluR4 cd15452
metabotropic glutamate receptor 4 in group 3, member of the class C family of ...
539-865 0e+00

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: 680.55  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15452    1 PWAVVPLLLAVLGIIATLFVVVTFVRYNDTPIVKASGRELSYVLLTGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSVVDFQDQRTLDPRFARGVLK 698
Cdd:cd15452   81 SYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLVITFSLISLQLLGVCVWFLVDPSHSVVDYEDQRTPDPQFARGVLK 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 699 CDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSADKLYIQTTTLTVS 778
Cdd:cd15452  161 CDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIIWLAFIPIFFGTSQSAEKMYIQTTTLTIS 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 779 VSLSASVSLGMLYMPKVYIILFHPEQNVPKRKRSLKAVVTAATMSNKFTQKGNFRPNGEAKSELCENLEAPALATKQTYV 858
Cdd:cd15452  241 VSLSASVSLGMLYMPKVYVILFHPEQNVPKRKRSLKAVVTAATMSNKFTQKGSFRPNGEAKSELCENLETQALATKQTYV 320

                 ....*..
gi 378548213 859 TYTNHAI 865
Cdd:cd15452  321 SYSNHAI 327
NCD3G pfam07562
Nine Cysteines Domain of family 3 GPCR; This conserved sequence contains several ...
469-519 1.49e-20

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: 85.38  E-value: 1.49e-20
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 378548213  469 PRSICSLPCQPGERKKTVKGMP-CCWHCEPCTGYQY-QVDRYTCKTCPYDMRP 519
Cdd:pfam07562   1 PSSVCSESCPPGQRKSQQGGAPvCCWDCVPCPEGEIsNTDSDTCKKCPEGQWP 53
 
Name Accession Description Interval E-value
PBP1_mGluR_groupIII cd06376
ligand-binding domain of the group III metabotropic glutamate receptor; Ligand-binding domain ...
43-461 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: 805.95  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  43 IRIDGDITLGGLFPVHGRGSEGKPCGELKKEKGIHRLEAMLFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLTF 122
Cdd:cd06376    1 IRVEGDITLGGLFPVHARGLAGVPCGEIKKEKGIHRLEAMLYALDQINSDPDLLPNVTLGARILDTCSRDTYALEQSLTF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 123 VQALIEKDGTEVRCGSGGPPIITKPERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSD 202
Cdd:cd06376   81 VQALIQKDTSDVRCTNGDPPVFVKPEKVVGVIGASASSVSIMVANILRLFQIPQISYASTAPELSDDRRYDFFSRVVPPD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 203 TYQAQAMVDIVRALKWNYVSTVASEGSYGESGVEAFIQKSREDGGVCIAQSVKIPREPKAGEFDKIIRRLLETSNARAVI 282
Cdd:cd06376  161 SFQAQAMVDIVKALGWNYVSTLASEGNYGEKGVESFVQISREAGGVCIAQSEKIPRERRTGDFDKIIKRLLETPNARAVV 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 283 IFANEDDIRRVLEAARRANQTGHFFWMGSDSWGSKIAPVLHLEEVAEGAVTILPKRMSV----------------RD--- 343
Cdd:cd06376  241 IFADEDDIRRVLAAAKRANKTGHFLWVGSDSWGAKISPVLQQEDVAEGAITILPKRASIegfdayftsrtlennrRNvwf 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 344 ----------------------------RERIGQDSAYEQEGKVQFVIDAVYAMGHALHAMHRDLCPGRVGLCPRMDPVD 395
Cdd:cd06376  321 aefweenfnckltssgskkedtlrkctgQERIGRDSGYEQEGKVQFVVDAVYAMAHALHNMNKDLCPGYRGLCPEMEPAG 400
                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 378548213 396 GTQLLKYIRNVNFSGIAGNPVTFNENGDAPGRYDIYQYQLRN-DSAEYKVIGSWTDHLHLRIERMHW 461
Cdd:cd06376  401 GKKLLKYIRNVNFNGSAGTPVMFNKNGDAPGRYDIFQYQTTNgSNYGYRLIGQWTDELQLNIEDMQW 467
7tmC_mGluR4 cd15452
metabotropic glutamate receptor 4 in group 3, member of the class C family of ...
539-865 0e+00

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: 680.55  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15452    1 PWAVVPLLLAVLGIIATLFVVVTFVRYNDTPIVKASGRELSYVLLTGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSVVDFQDQRTLDPRFARGVLK 698
Cdd:cd15452   81 SYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLVITFSLISLQLLGVCVWFLVDPSHSVVDYEDQRTPDPQFARGVLK 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 699 CDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSADKLYIQTTTLTVS 778
Cdd:cd15452  161 CDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIIWLAFIPIFFGTSQSAEKMYIQTTTLTIS 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 779 VSLSASVSLGMLYMPKVYIILFHPEQNVPKRKRSLKAVVTAATMSNKFTQKGNFRPNGEAKSELCENLEAPALATKQTYV 858
Cdd:cd15452  241 VSLSASVSLGMLYMPKVYVILFHPEQNVPKRKRSLKAVVTAATMSNKFTQKGSFRPNGEAKSELCENLETQALATKQTYV 320

                 ....*..
gi 378548213 859 TYTNHAI 865
Cdd:cd15452  321 SYSNHAI 327
ANF_receptor pfam01094
Receptor family ligand binding region; This family includes extracellular ligand binding ...
77-434 6.14e-107

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: 333.20  E-value: 6.14e-107
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213   77 HRLEAMLFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLTFVQALiekdgtevrcgsggppiitkperVVGVIGA 156
Cdd:pfam01094   1 LVLLAVRLAVEDINADPGLLPGTKLEYIILDTCCDPSLALAAALDLLKGE-----------------------VVAIIGP 57
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  157 SGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSDTYQAQAMVDIVRALKWNYVSTVASEGSYGESGVE 236
Cdd:pfam01094  58 SCSSVASAVASLANEWKVPLISYGSTSPALSDLNRYPTFLRTTPSDTSQADAIVDILKHFGWKRVALIYSDDDYGESGLQ 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  237 AFIQKSREDgGVCIAQSVKIPRepkAGEFDKIIRRLLE--TSNARAVIIFANEDDIRRVLEAARRANQTGHFF-WMGSDS 313
Cdd:pfam01094 138 ALEDALRER-GIRVAYKAVIPP---AQDDDEIARKLLKevKSRARVIVVCCSSETARRLLKAARELGMMGEGYvWIATDG 213
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  314 WGSKIAPVLH-LEEVAEGAVTILPKRMSVRD------RERIGQDSAYEQEGKVQFV-----IDAVYAMGHALHAMHRDLC 381
Cdd:pfam01094 214 LTTSLVILNPsTLEAAGGVLGFRLHPPDSPEfseffwEKLSDEKELYENLGGLPVSygalaYDAVYLLAHALHNLLRDDK 293
                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 378548213  382 PGRVglCPRMDPVD-GTQLLKYIRNVNFSGIAGNpVTFNENGDAP-GRYDIYQYQ 434
Cdd:pfam01094 294 PGRA--CGALGPWNgGQKLLRYLKNVNFTGLTGN-VQFDENGDRInPDYDILNLN 345
7tm_3 pfam00003
7 transmembrane sweet-taste receptor of 3 GCPR; This is a domain of seven transmembrane ...
534-774 2.06e-69

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


Pssm-ID: 459626 [Multi-domain]  Cd Length: 247  Bit Score: 229.85  E-value: 2.06e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  534 LEWGSPWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLgTCSLRRIFLG 613
Cdd:pfam00003   1 LDLSAPWGIVLEALAALGILLTLVLLVVFLLHRKTPIVKASNRSLSFLLLLGLLLLFLLAFLFIGKPTV-TCALRRFLFG 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  614 LGMSISYAALLTKTNRIYRIFEQGKRsvsaprFISPASQLAITFSLISLQLLgICVWFVVDPSHSVVDFQDQRTLdprfa 693
Cdd:pfam00003  80 VGFTLCFSCLLAKTFRLVLIFRRRKP------GPRGWQLLLLALGLLLVQVI-ILTEWLIDPPFPEKDNLSEGKI----- 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  694 rgVLKCDISDLS--LICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSADKLYIQ 771
Cdd:pfam00003 148 --ILECEGSTSIafLDFVLAYVGLLLLAGFLLAFKTRKLPDNFNEAKFITFSMLLSVLIWVAFIPMYLYGNKGKGTWDPV 225

                  ...
gi 378548213  772 TTT 774
Cdd:pfam00003 226 ALA 228
LivK COG0683
ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid ...
46-434 1.10e-27

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: 114.26  E-value: 1.10e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  46 DGDITLGGLFPVHGRGSEGkpcgelkkekGIHRLEAMLFALDRINNDPDLLPN-ITLgaRILDTCSrDThalEQSLTFVQ 124
Cdd:COG0683    1 ADPIKIGVLLPLTGPYAAL----------GQPIKNGAELAVEEINAAGGVLGRkIEL--VVEDDAS-DP---DTAVAAAR 64
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 125 ALIEKDGtevrcgsggppiitkperVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSDTY 204
Cdd:COG0683   65 KLIDQDK------------------VDAIVGPLSSGVALAVAPVAEEAGVPLISPSATAPALTGPECSPYVFRTAPSDAQ 126
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 205 QAQAMVD-IVRALKWNYVSTVASEGSYGESGVEAFIQKSREDGGVcIAQSVKIPrePKAGEFDKIIRRLLEtSNARAVII 283
Cdd:COG0683  127 QAEALADyLAKKLGAKKVALLYDDYAYGQGLAAAFKAALKAAGGE-VVGEEYYP--PGTTDFSAQLTKIKA-AGPDAVFL 202
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 284 FANEDDIRRVLEAARRANQTGHFFwmgsdswgskiapvlhleevaegavtilpKRMSVRDRERIGQD-SAYEQEGkvqfv 362
Cdd:COG0683  203 AGYGGDAALFIKQAREAGLKGPLN-----------------------------KAFVKAYKAKYGREpSSYAAAG----- 248
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 378548213 363 IDAVYAMGHALhamhrdlcpgrvglcPRMDPVDGTQLLKYIRNVNFSGIAGnPVTFNENGDAPGRYDIYQYQ 434
Cdd:COG0683  249 YDAALLLAEAI---------------EKAGSTDREAVRDALEGLKFDGVTG-PITFDPDGQGVQPVYIVQVK 304
NCD3G pfam07562
Nine Cysteines Domain of family 3 GPCR; This conserved sequence contains several ...
469-519 1.49e-20

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: 85.38  E-value: 1.49e-20
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 378548213  469 PRSICSLPCQPGERKKTVKGMP-CCWHCEPCTGYQY-QVDRYTCKTCPYDMRP 519
Cdd:pfam07562   1 PSSVCSESCPPGQRKSQQGGAPvCCWDCVPCPEGEIsNTDSDTCKKCPEGQWP 53
 
Name Accession Description Interval E-value
PBP1_mGluR_groupIII cd06376
ligand-binding domain of the group III metabotropic glutamate receptor; Ligand-binding domain ...
43-461 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: 805.95  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  43 IRIDGDITLGGLFPVHGRGSEGKPCGELKKEKGIHRLEAMLFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLTF 122
Cdd:cd06376    1 IRVEGDITLGGLFPVHARGLAGVPCGEIKKEKGIHRLEAMLYALDQINSDPDLLPNVTLGARILDTCSRDTYALEQSLTF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 123 VQALIEKDGTEVRCGSGGPPIITKPERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSD 202
Cdd:cd06376   81 VQALIQKDTSDVRCTNGDPPVFVKPEKVVGVIGASASSVSIMVANILRLFQIPQISYASTAPELSDDRRYDFFSRVVPPD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 203 TYQAQAMVDIVRALKWNYVSTVASEGSYGESGVEAFIQKSREDGGVCIAQSVKIPREPKAGEFDKIIRRLLETSNARAVI 282
Cdd:cd06376  161 SFQAQAMVDIVKALGWNYVSTLASEGNYGEKGVESFVQISREAGGVCIAQSEKIPRERRTGDFDKIIKRLLETPNARAVV 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 283 IFANEDDIRRVLEAARRANQTGHFFWMGSDSWGSKIAPVLHLEEVAEGAVTILPKRMSV----------------RD--- 343
Cdd:cd06376  241 IFADEDDIRRVLAAAKRANKTGHFLWVGSDSWGAKISPVLQQEDVAEGAITILPKRASIegfdayftsrtlennrRNvwf 320
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 344 ----------------------------RERIGQDSAYEQEGKVQFVIDAVYAMGHALHAMHRDLCPGRVGLCPRMDPVD 395
Cdd:cd06376  321 aefweenfnckltssgskkedtlrkctgQERIGRDSGYEQEGKVQFVVDAVYAMAHALHNMNKDLCPGYRGLCPEMEPAG 400
                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 378548213 396 GTQLLKYIRNVNFSGIAGNPVTFNENGDAPGRYDIYQYQLRN-DSAEYKVIGSWTDHLHLRIERMHW 461
Cdd:cd06376  401 GKKLLKYIRNVNFNGSAGTPVMFNKNGDAPGRYDIFQYQTTNgSNYGYRLIGQWTDELQLNIEDMQW 467
7tmC_mGluR4 cd15452
metabotropic glutamate receptor 4 in group 3, member of the class C family of ...
539-865 0e+00

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: 680.55  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15452    1 PWAVVPLLLAVLGIIATLFVVVTFVRYNDTPIVKASGRELSYVLLTGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSVVDFQDQRTLDPRFARGVLK 698
Cdd:cd15452   81 SYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLVITFSLISLQLLGVCVWFLVDPSHSVVDYEDQRTPDPQFARGVLK 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 699 CDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSADKLYIQTTTLTVS 778
Cdd:cd15452  161 CDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIIWLAFIPIFFGTSQSAEKMYIQTTTLTIS 240
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 779 VSLSASVSLGMLYMPKVYIILFHPEQNVPKRKRSLKAVVTAATMSNKFTQKGNFRPNGEAKSELCENLEAPALATKQTYV 858
Cdd:cd15452  241 VSLSASVSLGMLYMPKVYVILFHPEQNVPKRKRSLKAVVTAATMSNKFTQKGSFRPNGEAKSELCENLETQALATKQTYV 320

                 ....*..
gi 378548213 859 TYTNHAI 865
Cdd:cd15452  321 SYSNHAI 327
PBP1_mGluR cd06362
ligand binding domain of metabotropic glutamate receptors (mGluR); Ligand binding domain of ...
47-449 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: 556.52  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  47 GDITLGGLFPVHGRGSEGKPCGELKKEKGIHRLEAMLFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLTFVQAL 126
Cdd:cd06362    1 GDINLGGLFPVHERSSSGECCGEIREERGIQRLEAMLFAIDEINSRPDLLPNITLGFVILDDCSSDTTALEQALHFIRDS 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 127 IEKDGTEVRCGSGGPPII----TKPERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSD 202
Cdd:cd06362   81 LLSQESAGFCQCSDDPPNldesFQFYDVVGVIGAESSSVSIQVANLLRLFKIPQISYASTSDELSDKERYPYFLRTVPSD 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 203 TYQAQAMVDIVRALKWNYVSTVASEGSYGESGVEAFIQKSREDgGVCIAQSVKIPREPKAGEFDKIIRRLLETSNARAVI 282
Cdd:cd06362  161 SFQAKAIVDILLHFNWTYVSVVYSEGSYGEEGYKAFKKLARKA-GICIAESERISQDSDEKDYDDVIQKLLQKKNARVVV 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 283 IFANEDDIRRVLEAARRANQTGHFFWMGSDSWGSKIAPVLHLEEVAEGAVTILPKRMSVR-------------------- 342
Cdd:cd06362  240 LFADQEDIRGLLRAAKRLGASGRFIWLGSDGWGTNIDDLKGNEDVALGALTVQPYSEEVPrfddyfksltpsnntrnpwf 319
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 343 ----------------------DRERIGQDSAYEQEGKVQFVIDAVYAMGHALHAMHRDLCPGRVGLC-PRMDPVDGTQL 399
Cdd:cd06362  320 refwqelfqcsfrpsrenscndDKLLINKSEGYKQESKVSFVIDAVYAFAHALHKMHKDLCPGDTGLCqDLMKCIDGSEL 399
                        410       420       430       440       450
                 ....*....|....*....|....*....|....*....|....*....|.
gi 378548213 400 LKYIRNVNFSGIAGNPVTFNENGDAPGRYDIYQYQLRND-SAEYKVIGSWT 449
Cdd:cd06362  400 LEYLLNVSFTGEAGGEIRFDENGDGPGRYDIMNFQRNNDgSYEYVRVGVWD 450
7tmC_mGluR8 cd15454
metabotropic glutamate receptor 8 in group 3, member of the class C family of ...
539-847 0e+00

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: 533.44  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15454    1 PWAVVPVFVAILGIIATTFVIVTFVRYNDTPIVRASGRELSYVLLTGIFLCYAITFLMIATPDTGICSFRRVFLGLGMCF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSVVDFQDQRTLDPRFARGVLK 698
Cdd:cd15454   81 SYAALLTKTNRIHRIFEQGKKSVTAPKFISPASQLVITFSLISVQLLGVFVWFAVDPPHTIVDYGEQRTLDPEKARGVLK 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 699 CDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSADKLYIQTTTLTVS 778
Cdd:cd15454  161 CDISDLSLICSLGYSILLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIIWLAFIPIFFGTAQSAERMYIQTTTLTIS 240
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 378548213 779 VSLSASVSLGMLYMPKVYIILFHPEQNVPKRKRSLKAVVTAATMSNKFTQKGNFRPNGEAKSELCENLE 847
Cdd:cd15454  241 MSLSASVSLGMLYMPKVYIIIFHPEQNVQKRKRSFKAVVTAATMQSKLIQKGNDRPNGEVKTELCESLE 309
7tmC_mGluR_group3 cd15286
metabotropic glutamate receptors in group 3, member of the class C family of ...
539-809 1.09e-179

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: 517.82  E-value: 1.09e-179
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15286    1 PWAAVPVALAVLGIIATLFVLVTFVRYNDTPIVRASGRELSYVLLTGIFLCYAITFLMVAEPGVGVCSLRRLFLGLGMSL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSVVDFQDQRTLDPRFARGVLK 698
Cdd:cd15286   81 SYAALLTKTNRIYRIFEQGKKSVTPPRFISPTSQLVITFSLISVQLLGVLAWFAVDPPHALIDYEEGRTPDPEQARGVLR 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 699 CDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSADKLYIQTTTLTVS 778
Cdd:cd15286  161 CDMSDLSLICCLGYSLLLMVTCTVYAIKARGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTAQSAEKLYIQTATLTVS 240
                        250       260       270
                 ....*....|....*....|....*....|.
gi 378548213 779 VSLSASVSLGMLYMPKVYIILFHPEQNVPKR 809
Cdd:cd15286  241 MSLSASVSLGMLYMPKVYVILFHPEQNVQKR 271
7tmC_mGluR7 cd15451
metabotropic glutamate receptor 7 in group 3, member of the class C family of ...
539-845 1.56e-168

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: 490.69  E-value: 1.56e-168
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15451    1 PWAVIPVFLAMLGIIATIFVMATFIRYNDTPIVRASGRELSYVLLTGIFLCYIITFLMIAKPDVAVCSFRRIFLGLGMCI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSVVDFQDQRTLDPRFARGVLK 698
Cdd:cd15451   81 SYAALLTKTNRIYRIFEQGKKSVTAPRLISPTSQLAITSSLISVQLLGVLIWFAVDPPNIIIDYDEQKTMNPEQARGVLK 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 699 CDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSADKLYIQTTTLTVS 778
Cdd:cd15451  161 CDITDLQIICSLGYSILLMVTCTVYAIKTRGVPENFNEAKPIGFTMYTTCIVWLAFIPIFFGTAQSAEKLYIQTTTLTIS 240
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 378548213 779 VSLSASVSLGMLYMPKVYIILFHPEQNVPKRKRSLKAVVTAATMSNKFTQKGNFRPNGEAKSELCEN 845
Cdd:cd15451  241 MNLSASVALGMLYMPKVYIIIFHPELNVQKRKRSFKAVVTAATMSSRLSHKPSDRPNGEAKTELCEN 307
PBP1_mGluR_groupII cd06375
ligand binding domain of the group II metabotropic glutamate receptor; Ligand binding domain ...
43-454 1.21e-163

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: 484.33  E-value: 1.21e-163
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  43 IRIDGDITLGGLFPVHGRGSEGKPCGELKKEKGIHRLEAMLFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLTF 122
Cdd:cd06375    1 IKLEGDLVLGGLFPVHEKGEGMEECGRINEDRGIQRLEAMLFAIDRINRDPHLLPGVRLGVHILDTCSRDTYALEQSLEF 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 123 VQALIEK-DGTEVRCGSGGPPIITK--PERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVV 199
Cdd:cd06375   81 VRASLTKvDDSEYMCPDDGSYAIQEdsPLPIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTV 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 200 PSDTYQAQAMVDIVRALKWNYVSTVASEGSYGESGVEAFIQKSREDgGVCIAQSVKIPREPKAGEFDKIIRRLLETSNAR 279
Cdd:cd06375  161 PPDFYQAKAMAEILRFFNWTYVSTVASEGDYGETGIEAFEQEARLR-NICIATAEKVGRSADRKSFDGVIRELLQKPNAR 239
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 280 AVIIFANEDDIRRVLEAARRANQTghFFWMGSDSWGSKIAPVLHLEEVAEGAVTI------------------------- 334
Cdd:cd06375  240 VVVLFTRSDDARELLAAAKRLNAS--FTWVASDGWGAQESIVKGSEDVAEGAITLelashpipdfdryfqsltpynnhrn 317
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 335 --------------LPKRM---SVRDRERIGQDSAYEQEGKVQFVIDAVYAMGHALHAMHRDLCPGRVGLCPRMDPVDGT 397
Cdd:cd06375  318 pwfrdfweqkfqcsLQNKSqaaSVSDKHLSIDSSNYEQESKIMFVVNAVYAMAHALHNMQRTLCPNTTRLCDAMRSLDGK 397
                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 378548213 398 QLLK-YIRNVNF-----SGIAGNPVTFNENGDAPGRYDI--YQYQLRNDSAEYKVIGSWTDHLHL 454
Cdd:cd06375  398 KLYKdYLLNVSFtapfpPADAGSEVKFDAFGDGLGRYNIfnYQRAGGSYGYRYKGVGKWANSLDL 462
7tmC_mGluR6 cd15453
metabotropic glutamate receptor 6 in group 3, member of the class C family of ...
539-811 3.52e-158

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: 462.96  E-value: 3.52e-158
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15453    1 PWAAPPLLLAVLGILATTTVVITFVRFNNTPIVRASGRELSYVLLTGIFLIYAITFLMVAEPGAAVCAFRRLFLGLGTTL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSVVDFQDQRTLDPRFARGVLK 698
Cdd:cd15453   81 SYSALLTKTNRIYRIFEQGKRSVTPPPFISPTSQLVITFSLTSLQVVGVIAWLGAQPPHSVIDYEEQRTVDPEQARGVLK 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 699 CDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSADKLYIQTTTLTVS 778
Cdd:cd15453  161 CDMSDLSLIGCLGYSLLLMVTCTVYAIKARGVPETFNEAKPIGFTMYTTCIIWLAFVPIFFGTAQSAEKIYIQTTTLTVS 240
                        250       260       270
                 ....*....|....*....|....*....|...
gi 378548213 779 VSLSASVSLGMLYMPKVYIILFHPEQNVPKRKR 811
Cdd:cd15453  241 LSLSASVSLGMLYVPKTYVILFHPEQNVQKRKR 273
7tmC_mGluRs_group2_3 cd15934
metabotropic glutamate receptors in group 2 and 3, member of the class C family of ...
539-800 6.14e-149

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: 438.20  E-value: 6.14e-149
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15934    1 PWAIVPVVFALLGILATLFVIVVFIRYNDTPVVKASGRELSYVLLTGILLCYLMTFVLLAKPSVITCALRRLGLGLGFSI 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSVVDFQDQrtldprfARGVLK 698
Cdd:cd15934   81 CYAALLTKTNRISRIFNSGKRSAKRPRFISPKSQLVICLGLISVQLIGVLVWLVVEPPGTRIDYPRR-------DQVVLK 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 699 CDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQsadKLYIQTTTLTVS 778
Cdd:cd15934  154 CKISDSSLLISLVYNMLLIILCTVYAFKTRKIPENFNEAKFIGFTMYTTCIIWLAFVPIYFGTSN---DFKIQTTTLCVS 230
                        250       260
                 ....*....|....*....|..
gi 378548213 779 VSLSASVSLGMLYMPKVYIILF 800
Cdd:cd15934  231 ISLSASVALGCLFAPKVYIILF 252
PBP1_mGluR_groupI cd06374
ligand binding domain of the group I metabotropic glutamate receptor; Ligand binding domain of ...
40-458 8.60e-145

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: 436.39  E-value: 8.60e-145
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  40 MNSIRIDGDITLGGLFPVH----GRGSEGKPCGELKKEKGIHRLEAMLFALDRINNDPDLLPNITLGARILDTCSRDTHA 115
Cdd:cd06374    1 RLVARMPGDIIIGALFPVHhqppLKKVFSRKCGEIREQYGIQRVEAMFRTLDKINKDPNLLPNITLGIEIRDSCWYSPVA 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 116 LEQSLTFVQ-ALIEKDGTEVRCGSGGPPIITKPER---VVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSR 191
Cdd:cd06374   81 LEQSIEFIRdSVASVEDEKDTQNTPDPTPLSPPENrkpIVGVIGPGSSSVTIQVQNLLQLFHIPQIGYSATSIDLSDKSL 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 192 YDFFSRVVPSDTYQAQAMVDIVRALKWNYVSTVASEGSYGESGVEAFIQKSREDgGVCIAQSVKIPrePKAGE--FDKII 269
Cdd:cd06374  161 YKYFLRVVPSDYLQARAMLDIVKRYNWTYVSTVHTEGNYGESGIEAFKELAAEE-GICIAHSDKIY--SNAGEeeFDRLL 237
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 270 RRLLETSN-ARAVIIFANEDDIRRVLEAARRANQTGHFFWMGSDSWGSKIAPVLHLEEVAEGAVTILPKRMSVRD----- 343
Cdd:cd06374  238 RKLMNTPNkARVVVCFCEGETVRGLLKAMRRLNATGHFLLIGSDGWADRKDVVEGYEDEAAGGITIKIHSPEVESfdeyy 317
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 344 --------------RE--------RI---------------GQDS---AYEQEGKVQFVIDAVYAMGHALHAMHRDLCP- 382
Cdd:cd06374  318 fnlkpetnsrnpwfREfwqhrfdcRLpghpdenpyfkkcctGEESllgNYVQDSKLGFVINAIYAMAHALHRMQEDLCGg 397
                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 378548213 383 GRVGLCPRMDPVDGTQLLKYIRNVNFSGIAGNPVTFNENGDAPGRYDIYQYQ-LRNDSAEYKVIGSWtDHLHLRIER 458
Cdd:cd06374  398 YSVGLCPAMLPINGSLLLDYLLNVSFVGVSGDTIMFDENGDPPGRYDIMNFQkTGEGSYDYVQVGSW-KNGSLKMDD 473
PBP1_ABC_transporter_GPCR_C-like cd04509
Family C of G-protein coupled receptors and their close homologs, the type 1 ...
50-368 1.12e-135

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: 406.31  E-value: 1.12e-135
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  50 TLGGLFPVHGRGSEGKPCGELKKEKGIHRLEAMLFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLTFVQALIEK 129
Cdd:cd04509    1 KVGVLFAVHGKGPSGVPCGDIVAQYGIQRFEAMEQALDDINADPNLLPNNTLGIVIYDDCCDPKQALEQSNKFVNDLIQK 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 130 DGTEVRCGSGGPPIITKPERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSDTYQAQAM 209
Cdd:cd04509   81 DTSDVRCTNGEPPVFVKPEGIKGVIGHLCSSVTIPVSNILELFGIPQITYAATAPELSDDRGYQLFLRVVPLDSDQAPAM 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 210 VDIVRALKWNYVSTVASEGSYGESGVEAFIQKSREdGGVCIAQSVKIPREPKAGEFDKIIRRLLETSNARAVIIFANEDD 289
Cdd:cd04509  161 ADIVKEKVWQYVSIVHDEGQYGEGGARAFQDGLKK-GGLCIAFSDGITAGEKTKDFDRLVARLKKENNIRFVVYFGYHPE 239
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 378548213 290 IRRVLEAARRANQTGHFFWMGSDSWGSKIAPVLHLEEVAEGAVTILPkrmsvrdrerigqdsayeqegKVQFVIDAVYA 368
Cdd:cd04509  240 MGQILRAARRAGLVGKFQFMGSDGWANVSLSLNIAEESAEGLITIKP---------------------KVWFVIAALYA 297
PBP1_GPCR_family_C-like cd06350
ligand-binding domain of membrane-bound glutamate receptors that mediate excitatory ...
50-449 4.69e-128

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: 388.19  E-value: 4.69e-128
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  50 TLGGLFPVHGRGSEGKPCGELKKEKGIHRLEAMLFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLTFVqaliEK 129
Cdd:cd06350    1 IIGGLFPVHYRDDADFCCCGILNPRGVQLVEAMIYAIEEINNDSSLLPNVTLGYDIRDTCSSSSVALESSLEFL----LD 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 130 DGTEVRCGSggPPIITKPERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSDTYQAQAM 209
Cdd:cd06350   77 NGIKLLANS--NGQNIGPPNIVAVIGAASSSVSIAVANLLGLFKIPQISYASTSPELSDKIRYPYFLRTVPSDTLQAKAI 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 210 VDIVRALKWNYVSTVASEGSYGESGVEAFIQKSREDgGVCIAQSVKIPREPKAGEFDKIIRRLLETSNARAVIIFANEDD 289
Cdd:cd06350  155 ADLLKHFNWNYVSTVYSDDDYGRSGIEAFEREAKER-GICIAQTIVIPENSTEDEIKRIIDKLKSSPNAKVVVLFLTESD 233
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 290 IRRVLEAARRANQTGhFFWMGSDSWGSKIAPVLHLEEVAEGAVTILPKRMSVRDRERigqdsaYEQEgKVQFVIDAVYAM 369
Cdd:cd06350  234 ARELLKEAKRRNLTG-FTWIGSDGWGDSLVILEGYEDVLGGAIGVVPRSKEIPGFDD------YLKS-YAPYVIDAVYAT 305
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 370 ghalhamhrdlcpgrvglcprmdpvdgtqllkyirnvnfsgiagnpVTFNENGDAPGRYDIYQYQLRN-DSAEYKVIGSW 448
Cdd:cd06350  306 ----------------------------------------------VKFDENGDGNGGYDIVNLQRTGtGNYEYVEVGTW 339

                 .
gi 378548213 449 T 449
Cdd:cd06350  340 D 340
7tmC_mGluRs cd15045
metabotropic glutamate receptors, member of the class C family of seven-transmembrane G ...
539-800 5.31e-119

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: 360.79  E-value: 5.31e-119
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15045    1 PWAIGAMAFASLGILLTLFVLVVFVRYRDTPVVKASGRELSYVLLAGILLSYVMTFVLVAKPSTIVCGLQRFGLGLCFTV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSVVDFQdqrtldPRFARGVLK 698
Cdd:cd15045   81 CYAAILTKTNRIARIFRLGKKSAKRPRFISPRSQLVITGLLVSVQVLVLAVWLILSPPRATHHYP------TRDKNVLVC 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 699 CDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSadkLYIQTTTLTVS 778
Cdd:cd15045  155 SSALDASYLIGLAYPILLIILCTVYAFKTRKIPEGFNEAKYIGFTMYTTCIIWLAFVPLYFTTASN---IEVRITTLSVS 231
                        250       260
                 ....*....|....*....|..
gi 378548213 779 VSLSASVSLGMLYMPKVYIILF 800
Cdd:cd15045  232 ISLSATVQLACLFAPKVYIILF 253
ANF_receptor pfam01094
Receptor family ligand binding region; This family includes extracellular ligand binding ...
77-434 6.14e-107

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: 333.20  E-value: 6.14e-107
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213   77 HRLEAMLFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLTFVQALiekdgtevrcgsggppiitkperVVGVIGA 156
Cdd:pfam01094   1 LVLLAVRLAVEDINADPGLLPGTKLEYIILDTCCDPSLALAAALDLLKGE-----------------------VVAIIGP 57
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  157 SGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSDTYQAQAMVDIVRALKWNYVSTVASEGSYGESGVE 236
Cdd:pfam01094  58 SCSSVASAVASLANEWKVPLISYGSTSPALSDLNRYPTFLRTTPSDTSQADAIVDILKHFGWKRVALIYSDDDYGESGLQ 137
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  237 AFIQKSREDgGVCIAQSVKIPRepkAGEFDKIIRRLLE--TSNARAVIIFANEDDIRRVLEAARRANQTGHFF-WMGSDS 313
Cdd:pfam01094 138 ALEDALRER-GIRVAYKAVIPP---AQDDDEIARKLLKevKSRARVIVVCCSSETARRLLKAARELGMMGEGYvWIATDG 213
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  314 WGSKIAPVLH-LEEVAEGAVTILPKRMSVRD------RERIGQDSAYEQEGKVQFV-----IDAVYAMGHALHAMHRDLC 381
Cdd:pfam01094 214 LTTSLVILNPsTLEAAGGVLGFRLHPPDSPEfseffwEKLSDEKELYENLGGLPVSygalaYDAVYLLAHALHNLLRDDK 293
                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 378548213  382 PGRVglCPRMDPVD-GTQLLKYIRNVNFSGIAGNpVTFNENGDAP-GRYDIYQYQ 434
Cdd:pfam01094 294 PGRA--CGALGPWNgGQKLLRYLKNVNFTGLTGN-VQFDENGDRInPDYDILNLN 345
7tmC_mGluR_group1 cd15285
metabotropic glutamate receptors in group 1, member of the class C family of ...
539-800 6.19e-94

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: 295.32  E-value: 6.19e-94
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15285    1 TEAIVAMVFACVGILATLFVTVVFIRHNDTPVVKASTRELSYIILAGILLCYASTFALLAKPSTISCYLQRILPGLSFAM 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSV--SAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSVVDFQDQRtldprfaRGV 696
Cdd:cd15285   81 IYAALVTKTNRIARILAGSKKKIltRKPRFMSASAQVVITGILISVEVAIIVVMLILEPPDATLDYPTPK-------RVR 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 697 LKCDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTsqsadklYIQTTTLT 776
Cdd:cd15285  154 LICNTSTLGFVVPLGFDFLLILLCTLYAFKTRNLPENFNEAKFIGFTMYTTCVIWLAFLPIYFGS-------DNKEITLC 226
                        250       260
                 ....*....|....*....|....
gi 378548213 777 VSVSLSASVSLGMLYMPKVYIILF 800
Cdd:cd15285  227 FSVSLSATVALVFLFFPKVYIILF 250
PBP1_glutamate_receptors-like cd06269
ligand-binding domain of family C G-protein couples receptors (GPCRs), membrane bound guanylyl ...
50-449 9.83e-88

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: 282.00  E-value: 9.83e-88
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  50 TLGGLFPVHGRgsegkpcgelkKEKGIHRLEAMLFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLTFVQAliek 129
Cdd:cd06269    1 TIGALLPVHDY-----------LESGAKVLPAFELALSDVNSRPDLLPKTTLGLAIRDSECNPTQALLSACDLLAA---- 65
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 130 dgtevrcgsggppiitkpERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSDTYQAQAM 209
Cdd:cd06269   66 ------------------AKVVAILGPGCSASAAPVANLARHWDIPVLSYGATAPGLSDKSRYAYFLRTVPPDSKQADAM 127
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 210 VDIVRALKWNYVSTVASEGSYGESGVEAFIQKSREdGGVCIAQSVKIPrEPKAGEFDKIIRRLLETSnARAVIIFANEDD 289
Cdd:cd06269  128 LALVRRLGWNKVVLIYSDDEYGEFGLEGLEELFQE-KGGLITSRQSFD-ENKDDDLTKLLRNLRDTE-ARVIILLASPDT 204
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 290 IRRVLEAARRANQTG-HFFWMGSDSWGSKIAPVLHLEEVA-EGAVTILPKRMSVRD-------------RERIGQDSAYE 354
Cdd:cd06269  205 ARSLMLEAKRLDMTSkDYVWFVIDGEASSSDEHGDEARQAaEGAITVTLIFPVVKEflkfsmelklkssKRKQGLNEEYE 284
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 355 QEGKVQFVIDAVYAmghalhamhrdlcpgrvglcprmdpvdgtqllkyirnvnfsgiagnpvtfnengDAPGRYDIYQYQ 434
Cdd:cd06269  285 LNNFAAFFYDAVLA------------------------------------------------------DRPGQFSIINLQ 310
                        410
                 ....*....|....*
gi 378548213 435 LRNDSAeYKVIGSWT 449
Cdd:cd06269  311 YTEAGD-YRKVGTWD 324
7tmC_mGluR2 cd15447
metabotropic glutamate receptor 2 in group 2, member of the class C family of ...
540-800 1.44e-87

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: 278.74  E-value: 1.44e-87
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 540 WAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSIS 619
Cdd:cd15447    2 WAIGPVTISCLGILSTLFVVGVFVKNNETPVVKASGRELCYILLLGVLLCYLMTFIFIAKPSTAVCTLRRLGLGTSFAVC 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 620 YAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSVVDFQDQRtldpRFARgVLKC 699
Cdd:cd15447   82 YSALLTKTNRIARIFSGAKDGAQRPRFISPASQVAICLALISCQLLVVLIWLLVEAPGTRKETAPER----RYVV-TLKC 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 700 DISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSadkLYIQTTTLTVSV 779
Cdd:cd15447  157 NSRDSSMLISLTYNVLLIILCTLYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSD---YRVQTTTMCISV 233
                        250       260
                 ....*....|....*....|.
gi 378548213 780 SLSASVSLGMLYMPKVYIILF 800
Cdd:cd15447  234 SLSGSVVLGCLFAPKLHIILF 254
7tmC_mGluR_group2 cd15284
metabotropic glutamate receptors in group 2, member of the class C family of ...
540-800 1.03e-85

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: 274.03  E-value: 1.03e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 540 WAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSIS 619
Cdd:cd15284    2 WAIGPVTIACLGFLCTLFVIGVFIKHNNTPLVKASGRELCYILLFGVFLCYCMTFIFIAKPSPAICTLRRLGLGTSFAVC 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 620 YAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSvvdfqDQRTLDPRFARGVLKC 699
Cdd:cd15284   82 YSALLTKTNRIARIFSGVKDGAQRPRFISPSSQVFICLALISVQLLVVSVWLLVEAPGT-----RRYTLPEKRETVILKC 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 700 DISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSadkLYIQTTTLTVSV 779
Cdd:cd15284  157 NVRDSSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSD---YRVQTTTMCISV 233
                        250       260
                 ....*....|....*....|.
gi 378548213 780 SLSASVSLGMLYMPKVYIILF 800
Cdd:cd15284  234 SLSGFVVLGCLFAPKVHIILF 254
PBP1_CaSR cd06364
ligand-binding domain of the CaSR calcium-sensing receptor, a member of the family C receptors ...
51-446 2.49e-80

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: 267.20  E-value: 2.49e-80
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  51 LGGLFPVHGR-GSEGKPCGELKKEKGIHRLE--------AMLFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLT 121
Cdd:cd06364    2 IGGLFPIHFRpVSPDPDFTTEPHSPECEGFNfrgfrwaqTMIFAIEEINNSPDLLPNITLGYRIYDSCATISKALRAALA 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 122 FVqALIEKDGTEVRCgSGGPPIItkpervvGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPS 201
Cdd:cd06364   82 LV-NGQEETNLDERC-SGGPPVA-------AVIGESGSTLSIAVARTLGLFYIPQVSYFASCACLSDKKQFPSFLRTIPS 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 202 DTYQAQAMVDIVRALKWNYVSTVASEGSYGESGVEAFIQKSrEDGGVCIAQSVKIPREPKAGEFDKIIRRlLETSNARAV 281
Cdd:cd06364  153 DYYQSRALAQLVKHFGWTWVGAIASDDDYGRNGIKAFLEEA-EKLGICIAFSETIPRTYSQEKILRIVEV-IKKSTAKVI 230
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 282 IIFANEDDIRRVLEAARRANQTGhFFWMGSDSWGSkiAPVLHLEE---VAEGAVTILPKRMSVRD-RE---RIGQDSAYE 354
Cdd:cd06364  231 VVFSSEGDLEPLIKELVRQNITG-RQWIASEAWIT--SSLLATPEyfpVLGGTIGFAIRRGEIPGlKEfllRVHPSKSPS 307
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 355 QEGKVQF-------------------------------------------------VIDAVYAMGHALHAMHRDLcPGR- 384
Cdd:cd06364  308 NPFVKEFweetfncslssssksnsssssrppctgsenlenvqnpytdvsqlrisynVYKAVYAIAHALHDLLQCE-PGKg 386
                        410       420       430       440       450       460
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 378548213 385 ---VGLCPRMDPVDGTQLLKYIRNVNFSGIAGNPVTFNENGDAPGRYDIYQYQL-RNDSAEYKVIG 446
Cdd:cd06364  387 pfsNGSCADIKKVEPWQLLYYLKHVNFTTKFGEEVYFDENGDPVASYDIINWQLsDDGTIQFVTVG 452
7tmC_mGluR3 cd15448
metabotropic glutamate receptor 3 in group 2, member of the class C family of ...
540-800 2.91e-79

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: 256.80  E-value: 2.91e-79
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 540 WAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSIS 619
Cdd:cd15448    2 WAIGPVTIACLGFICTCMVITVFIKHNNTPLVKASGRELCYILLFGVFLSYCMTFFFIAKPSPVICTLRRLGLGTSFAVC 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 620 YAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSvvdfqDQRTLDPRFARGVLKC 699
Cdd:cd15448   82 YSALLTKTNCIARIFDGVKNGAQRPKFISPSSQVFICLSLILVQIVVVSVWLILEAPGT-----RRYTLPEKRETVILKC 156
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 700 DISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSadkLYIQTTTLTVSV 779
Cdd:cd15448  157 NVKDSSMLISLTYDVVLVILCTVYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIFYVTSSD---YRVQTTTMCISV 233
                        250       260
                 ....*....|....*....|.
gi 378548213 780 SLSASVSLGMLYMPKVYIILF 800
Cdd:cd15448  234 SLSGFVVLGCLFAPKVHIILF 254
7tm_classC_mGluR-like cd13953
metabotropic glutamate receptor-like class C family of seven-transmembrane G protein-coupled ...
539-800 1.01e-73

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: 241.76  E-value: 1.01e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd13953    1 PLAIVLLVLAALGLLLTIFIWVVFIRYRNTPVVKASNRELSYLLLFGILLCFLLAFLFLLPPSDVLCGLRRFLFGLSFTL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSVvdfqdqRTLDPRFARGVLK 698
Cdd:cd13953   81 VFSTLLVKTNRIYRIFKSGLRSSLRPKLLSNKSQLLLVLFLLLVQVAILIVWLILDPPKVE------KVIDSDNKVVELC 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 699 CDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSqsadkLYIQTTTLTVS 778
Cdd:cd13953  155 CSTGNIGLILSLVYNILLLLICTYLAFKTRKLPDNFNEARYIGFSSLLSLVIWIAFIPTYFTTS-----GPYRDAILSFG 229
                        250       260
                 ....*....|....*....|..
gi 378548213 779 VSLSASVSLGMLYMPKVYIILF 800
Cdd:cd13953  230 LLLNATVLLLCLFLPKIYIILF 251
PBP1_taste_receptor cd06363
ligand-binding domain of the T1R taste receptor; Ligand-binding domain of the T1R taste ...
44-469 6.30e-72

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: 242.60  E-value: 6.30e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  44 RIDGDITLGGLFPVHGRGSEGKP---------CGELKKEkGIHRLEAMLFALDRINNDPDLLPNITLGARILDTCSrDTH 114
Cdd:cd06363    2 RLPGDYLLGGLFPLHELTSTLPHrppeptdcsCDRFNLH-GYHLAQAMRFAVEEINNSSDLLPGVTLGYEIFDTCS-DAV 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 115 ALEQSLTFVqALIEKDGTEVRCgsggpPIITKPERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDF 194
Cdd:cd06363   80 NFRPTLSFL-SQNGSHDIEVQC-----NYTNYQPRVVAVIGPDSSELALTTAKLLGFFLMPQISYGASSEELSNKLLYPS 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 195 FSRVVPSDTYQAQAMVDIVRALKWNYVSTVASEGSYGESGVEAFIQKSrEDGGVCIAQSVKIP-REPKAGEFDKIIRRLL 273
Cdd:cd06363  154 FLRTVPSDKYQVEAMVQLLQEFGWNWVAFLGSDDEYGQDGLQLFSEKA-ANTGICVAYQGLIPtDTDPKPKYQDILKKIN 232
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 274 ETsNARAVIIFANEDDIRRVLEAARRANQTGHfFWMGSDSWGskIAPVLH-LEEVAEGAVTIlpkRMSVRDRERIGQDsA 352
Cdd:cd06363  233 QT-KVNVVVVFAPKQAAKAFFEEVIRQNLTGK-VWIASEAWS--LNDTVTsLPGIQSIGTVL---GFAIQTGTLPGFQ-E 304
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 353 YEqEGKVQFVIDAVYAMGHALHamhrDLCPGRVGLCPRMDPVDGTQLLKYIRNVNFSgIAGNPVTFNENGDAPGRYDIYQ 432
Cdd:cd06363  305 FI-YAFAFSVYAAVYAVAHALH----NLLGCNSGACPKGRVVYPWQLLEELKKVNFT-LLNQTIRFDENGDPNFGYDIVQ 378
                        410       420       430       440
                 ....*....|....*....|....*....|....*....|
gi 378548213 433 YQLRNDSAEYKVIGSWTD---HLHLRIERMHWPGSGQQLP 469
Cdd:cd06363  379 WIWNNSSWTFEVVGSYSTypiQLTINESKIKWHTKDSPVP 418
7tm_3 pfam00003
7 transmembrane sweet-taste receptor of 3 GCPR; This is a domain of seven transmembrane ...
534-774 2.06e-69

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


Pssm-ID: 459626 [Multi-domain]  Cd Length: 247  Bit Score: 229.85  E-value: 2.06e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  534 LEWGSPWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLgTCSLRRIFLG 613
Cdd:pfam00003   1 LDLSAPWGIVLEALAALGILLTLVLLVVFLLHRKTPIVKASNRSLSFLLLLGLLLLFLLAFLFIGKPTV-TCALRRFLFG 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  614 LGMSISYAALLTKTNRIYRIFEQGKRsvsaprFISPASQLAITFSLISLQLLgICVWFVVDPSHSVVDFQDQRTLdprfa 693
Cdd:pfam00003  80 VGFTLCFSCLLAKTFRLVLIFRRRKP------GPRGWQLLLLALGLLLVQVI-ILTEWLIDPPFPEKDNLSEGKI----- 147
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  694 rgVLKCDISDLS--LICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSADKLYIQ 771
Cdd:pfam00003 148 --ILECEGSTSIafLDFVLAYVGLLLLAGFLLAFKTRKLPDNFNEAKFITFSMLLSVLIWVAFIPMYLYGNKGKGTWDPV 225

                  ...
gi 378548213  772 TTT 774
Cdd:pfam00003 226 ALA 228
7tmC_mGluR5 cd15450
metabotropic glutamate receptor 5 in group 1, member of the class C family of ...
539-799 5.36e-61

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: 207.14  E-value: 5.36e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15450    1 PEPIAAVVFACLGLLATLFVTVIFIIYRDTPVVKSSSRELCYIILAGICLGYLCTFCLIAKPKQIYCYLQRIGIGLSPAM 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSV--SAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSVVDFQDQRTLDprfargv 696
Cdd:cd15450   81 SYSALVTKTNRIARILAGSKKKIctKKPRFMSACAQLVIAFILICIQLGIIVALFIMEPPDIMHDYPSIREVY------- 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 697 LKCDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSqsadklyIQTTTLT 776
Cdd:cd15450  154 LICNTTNLGVVTPLGYNGLLILSCTFYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSN-------YKIITMC 226
                        250       260
                 ....*....|....*....|...
gi 378548213 777 VSVSLSASVSLGMLYMPKVYIIL 799
Cdd:cd15450  227 FSVSLSATVALGCMFVPKVYIIL 249
7tmC_mGluR1 cd15449
metabotropic glutamate receptor 1 in group 1, member of the class C family of ...
539-799 4.91e-57

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: 196.39  E-value: 4.91e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15449    1 IESIIAVAFSCLGILVTMFVTLIFVLYRDTPVVKSSSRELCYIILAGIFLGYVCPFTLIAKPTTTSCYLQRLLVGLSSAM 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSVSA--PRFISPASQLAITFSLISLQLLGICVWFVVDPSHSVVDFqdqrtldPRFARGV 696
Cdd:cd15449   81 CYSALVTKTNRIARILAGSKKKICTrkPRFMSAWAQVVIASILISVQLTLVVTLIIMEPPMPILSY-------PSIKEVY 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 697 LKCDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSqsadklyIQTTTLT 776
Cdd:cd15449  154 LICNTSNLGVVAPLGYNGLLIMSCTYYAFKTRNVPANFNEAKYIAFTMYTTCIIWLAFVPIYFGSN-------YKIITTC 226
                        250       260
                 ....*....|....*....|...
gi 378548213 777 VSVSLSASVSLGMLYMPKVYIIL 799
Cdd:cd15449  227 FAVSLSVTVALGCMFTPKMYIII 249
PBP1_pheromone_receptor cd06365
Ligand-binding domain of the V2R pheromone receptor, a member of the family C receptors within ...
51-468 5.91e-57

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: 202.87  E-value: 5.91e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  51 LGGLFPVHgRGSEGKPCGELKKE----------KGIHRLEAMLFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSL 120
Cdd:cd06365    2 IGGVFPIH-TFSEGKKKDFKEPPspllcfrfsiKYYQHLLAFLFAIEEINKNPDLLPNITLGFHIYDSCSSERLALESSL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 121 TFVqaliekdgtevrcgSGGPPII-----TKPERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFF 195
Cdd:cd06365   81 SIL--------------SGNSEPIpnyscREQRKLVAFIGDLSSSTSVAMARILGLYKYPQISYGAFDPLLSDKVQFPSF 146
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 196 SRVVPSDTYQAQAMVDIVRALKWNYVSTVASEGSYGESGVEAF---IQKSredgGVCIAQSVKIPREPKAGEFDKIIRRl 272
Cdd:cd06365  147 YRTVPSDTSQSLAIVQLLKHFGWTWVGLIISDDDYGEQFSQDLkkeMEKN----GICVAFVEKIPTNSSLKRIIKYINQ- 221
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 273 LETSNARAVIIFANEDDIRRVLEAARRANQTGHfFWMGSDSWGSKIAPVLHLEEVAEGAVTIL----------------- 335
Cdd:cd06365  222 IIKSSANVIIIYGDTDSLLELLFRLWEQLVTGK-VWITTSQWDISTLPFEFYLNLFNGTLGFSqhsgeipgfkeflqsvh 300
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 336 ----PKRMSVRDRE---------RIGQDSAYEQEGKVQF------------------VIDAVYAMGHALHAMHRDLCPGR 384
Cdd:cd06365  301 pskyPEDIFLKTLWesyfnckwpDQNCKSLQNCCGNESLetldvhsfdmtmsrlsynVYNAVYAVAHALHEMLLCQPKTG 380
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 385 VGLCPRMDPVDGTQLLKYIRNVNFSGIAGNPVTFNENGDAPGRYDIYQYQLRNDSAEYKV-IGSWtdhlhlrierMHWPG 463
Cdd:cd06365  381 PGNCSDRRNFQPWQLHHYLKKVQFTNPAGDEVNFDEKGDLPTKYDILNWQIFPNGTGTKVkVGTF----------DPSAP 450

                 ....*
gi 378548213 464 SGQQL 468
Cdd:cd06365  451 SGQQL 455
PBP1_GPC6A-like cd06361
ligand-binding domain of the promiscuous L-alpha-amino acid receptor GPRC6A which is a ...
51-446 1.49e-56

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: 199.91  E-value: 1.49e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  51 LGGLFPVHG-------RGSEGKP--CGELKKeKGIHRLEAMLFALDRINNDPdLLPNITLGARILDTCSRDTHALEQSLT 121
Cdd:cd06361    2 IGGLFPIHEkvldlhdRPTKPQIfiCTGFDL-RGFLQSLAMIHAIEMINNST-LLPGIKLGYEIYDTCSDVTKALQATLR 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 122 FVQALIEKDGTeVRCGSGgppiiTKPERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPS 201
Cdd:cd06361   80 LLSKFNSSNEL-LECDYT-----DYVPPVKAVIGASYSEISIAVARLLNLQLIPQISYESSAPILSDKLRFPSFLRTVPS 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 202 DTYQAQAMVDIVRALKWNYVSTVASEGSYGESGVEAFIQKSrEDGGVCIAQSVKIPREPKAGEFDKIIRRLLET----SN 277
Cdd:cd06361  154 DFHQTKAMAKLISHFGWNWVGIIYTDDDYGRSALESFIIQA-EAENVCIAFKEVLPAYLSDPTMNVRINDTIQTiqssSQ 232
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 278 ARAVIIFANEDDIRRVLEAARRANQTGhfFWMGSDSWGS--KIAPVLHLEEVAEgavtILPkrMSVRDRERIGQDSaYEQ 355
Cdd:cd06361  233 VNVVVLFLKPSLVKKLFKEVIERNISK--IWIASDNWSTarEILKMPNINKVGK----ILG--FTFKSGNISSFHN-YLK 303
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 356 EGKVQFVIDAVYAMGHALHamhrDLCPGRVGLCPrmDPVDGTQLLKYIRNVNFSgIAGNPVTFNENGDAPGRYDIYQYQL 435
Cdd:cd06361  304 NLLIYSIQLAVTAIANALR----KLCCERGCQDP--TAFQPWELLKELKKVTFT-DDGETYHFDANGDLNTGYDLILWKE 376
                        410
                 ....*....|.
gi 378548213 436 RNDSAEYKVIG 446
Cdd:cd06361  377 DNGHMTFTIVA 387
PBP1_GABAb_receptor cd06366
ligand-binding domain of GABAb receptors, which are metabotropic transmembrane receptors for ...
50-463 2.82e-46

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: 170.89  E-value: 2.82e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  50 TLGGLFPVHGRGsegkpcgELKKEKGIhrLEAMLFALDRINNDPDLLPNITLGARILDT-CSRDtHAleqsltfVQALIE 128
Cdd:cd06366    1 YIGGLFPLSGSK-------GWWGGAGI--LPAAEMALEHINNRSDILPGYNLELIWNDTqCDPG-LG-------LKALYD 63
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 129 kdgtevrcgsggppIITKPERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSDTYQAQA 208
Cdd:cd06366   64 --------------LLYTPPPKVMLLGPGCSSVTEPVAEASKYWNLVQLSYAATSPALSDRKRYPYFFRTVPSDTAFNPA 129
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 209 MVDIVRALKWNYVSTVASEGSYGESGVEAFIqKSREDGGVCIAQSVKIPREPKAGEFDKIIRRlletsNARavIIFA--N 286
Cdd:cd06366  130 RIALLKHFGWKRVATIYQNDEVFSSTAEDLE-ELLEEANITIVATESFSSEDPTDQLENLKEK-----DAR--IIIGlfY 201
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 287 EDDIRRVLEAARRANQTGH---FFWMG--SDSWGSKIAPVL-----HLEEVAEGAVTILPKRMSVRDRERIG------QD 350
Cdd:cd06366  202 EDAARKVFCEAYKLGMYGPkyvWILPGwyDDNWWDVPDNDVnctpeQMLEALEGHFSTELLPLNPDNTKTISgltaqeFL 281
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 351 SAYEQEGKVQ---------FVIDAVYAMGHALHAMHRDLCPGRVGLC--PRMDPVDGTQLLKYIRNVNFSGIAGnPVTFN 419
Cdd:cd06366  282 KEYLERLSNSnytgspyapFAYDAVWAIALALNKTIEKLAEYNKTLEdfTYNDKEMADLFLEAMNSTSFEGVSG-PVSFD 360
                        410       420       430       440
                 ....*....|....*....|....*....|....*....|....*...
gi 378548213 420 ENGDAPGRYDIYQYQLRNdsaeYKVIGSW---TDHLHLRIER-MHWPG 463
Cdd:cd06366  361 SKGDRLGTVDIEQLQGGS----YVKVGLYdpnADSLLLLNESsIVWPG 404
7tmC_V2R_AA_sensing_receptor-like cd15044
vomeronasal type-2 pheromone receptors, amino acid-sensing receptors and closely related ...
539-800 1.91e-41

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: 152.24  E-value: 1.91e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15044    1 PLGILLVILSILGIIFVLVVGGVFVRYRNTPIVKANNRELSYLILLSLFLCFSSSLFFIGEPQDWTCKLRQTMFGVSFTL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEqGKRSVSAPRFISPASQLAITFSLISLQlLGIC-VWFVVDPSHSVVDfqdqrtLDPRFARGVL 697
Cdd:cd15044   81 CISCILTKTLKVLLAFS-ADKPLTQKFLMCLYLPILIVFTCTGIQ-VVICtVWLIFAPPTVEVN------VSPLPRVIIL 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 698 KCDI-SDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSadklyiqtTTLT 776
Cdd:cd15044  153 ECNEgSILAFGTMLGYIAFLAFLCFLFAFKARKLPDNYNEAKFITFGMLVFFIVWISFVPAYLSTKGK--------FVVA 224
                        250       260
                 ....*....|....*....|....*..
gi 378548213 777 VSVSLSASVSLGMLY---MPKVYIILF 800
Cdd:cd15044  225 VEIIAILASSYGLLGcifLPKCYVILL 251
7tmC_CaSR cd15282
calcium-sensing receptor, member of the class C of seven-transmembrane G protein-coupled ...
539-800 1.63e-35

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


Pssm-ID: 320409 [Multi-domain]  Cd Length: 252  Bit Score: 135.46  E-value: 1.63e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15282    1 PFGIALTLFAVLGIFLTAFVLGVFIKFRNTPIVKATNRELSYLLLFSLICCFSSSLIFIGEPQDWTCRLRQPAFGISFVL 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSvvdFQDQRTLDPRFargVLK 698
Cdd:cd15282   81 CISCILVKTNRVLLVFEAKIPTSLHRKWWGLNLQFLLVFLCTFVQIVICVIWLYTAPPSS---YRNHELEDEII---FIT 154
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 699 C-DISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGT----SQSADKLYIQTT 773
Cdd:cd15282  155 CnEGSLMALGFLIGYTCLLAAICFFFAFKSRKLPENFNEAKFITFSMLIFFIVWISFIPAYASTygkfVSAVEVIAILAS 234
                        250       260       270
                 ....*....|....*....|....*....|
gi 378548213 774 TLtvsvslsasvslGML---YMPKVYIILF 800
Cdd:cd15282  235 SF------------GLLaciFFNKVYIILF 252
7tmC_V2R_pheromone cd15283
vomeronasal type-2 pheromone receptors, member of the class C family of seven-transmembrane G ...
545-756 2.78e-35

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: 134.71  E-value: 2.78e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 545 LFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSISYAALL 624
Cdd:cd15283    7 TVLSLLGSVLTAAVLVVFIKHRDTPIVKANNSELSYLLLLSLKLCFLCSLLFIGQPSTWTCMLRQTAFGISFVLCISCIL 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 625 TKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSVVDFQDQRtldprfARGVLKCDI-SD 703
Cdd:cd15283   87 AKTIVVVAAFKATRPGSNIMKWFGPGQQRAIIFICTLVQVVICAIWLATSPPFPDKNMHSEH------GKIILECNEgSV 160
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 378548213 704 LSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIP 756
Cdd:cd15283  161 VAFYCVLGYIGLLALVSFLLAFLARKLPDNFNEAKFITFSMLVFCAVWVAFVP 213
7tmC_GABA-B-like cd15047
gamma-aminobutyric acid type B receptor and related proteins, member of the class C family of ...
545-798 3.54e-34

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: 131.91  E-value: 3.54e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 545 LFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMI---AEPDLGTCSLRRIFLGLGMSISYA 621
Cdd:cd15047    7 TVLSGIGILLALVFLIFNIKFRKNRVIKMSSPLFNNLILLGCILCYISVILFGlddSKPSSFLCTARPWLLSIGFTLVFG 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 622 ALLTKTNRIYRIFEQGKRSVSAprfISPASQLAITFSLISLQLLGICVWFVVDPSHSVVDFQDQRTLDPRFARGVLKCDI 701
Cdd:cd15047   87 ALFAKTWRIYRIFTNKKLKRIV---IKDKQLLKIVGILLLIDIIILILWTIVDPLKPTRVLVLSEISDDVKYEYVVHCCS 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 702 SDLS---LICLLGYSMLLMVTCTVYAIKTRGVP-ETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSADKLY-------I 770
Cdd:cd15047  164 SSNGiiwLGILLAYKGLLLLFGCFLAWKTRNVDiEEFNESKYIGISIYNVLFLSVIGVPLSFVLTDSPDTSYliisaaiL 243
                        250       260
                 ....*....|....*....|....*...
gi 378548213 771 QTTTLTvsvslsasvsLGMLYMPKVYII 798
Cdd:cd15047  244 FCTTAT----------LCLLFVPKFWLL 261
PBP1_ABC_ligand_binding-like cd06346
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
148-433 6.16e-33

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: 129.61  E-value: 6.16e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 148 ERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSDTYQAQAMVDIVRALKWNYVSTVASE 227
Cdd:cd06346   66 EGVPAIVGAASSGVTLAVASVAVPNGVVQISPSSTSPALTTLEDKGYVFRTAPSDALQGVVLAQLAAERGFKKVAVIYVN 145
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 228 GSYGESGVEAFIQKSREDGGVCIAqsvKIPREPKAGEFDKIIRRLLEtSNARAVIIFANEDDIRRVLEAARRANQTGHFF 307
Cdd:cd06346  146 NDYGQGLADAFKKAFEALGGTVTA---SVPYEPGQTSYRAELAQAAA-GGPDALVLIGYPEDGATILREALELGLDFTPW 221
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 308 WMGSDSWGSKIAPVLHlEEVAEGAVTILPKRMSVRDRERIgqDSAYEQEGKVQFVI------DAVYAMGHAlhamhrdlc 381
Cdd:cd06346  222 IGTDGLKSDDLVEAAG-AEALEGMLGTAPGSPGSPAYEAF--AAAYKAEYGDDPGPfaanayDAVMLLALA--------- 289
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 378548213 382 pgrvglcprmdpvdgtqllkyirnvnFSGIAGnPVTFNENGDAPGRYDIYQY 433
Cdd:cd06346  290 --------------------------YEGASG-PIDFDENGDVAGPYEIWKV 314
7tmC_V2R-like cd15280
vomeronasal type-2 receptor-like proteins, member of the class C family of seven-transmembrane ...
545-802 4.30e-29

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: 116.81  E-value: 4.30e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 545 LFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSISYAALL 624
Cdd:cd15280    7 IALSIFGALVVLAVTVVYIMHRHTPLVKANDRELSFLIQMSLVITFLTSILFIGKPENWSCMARQITLALGFSLCLSSIL 86
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 625 TKTnriYRIFEQGKRSVSAPRFIS--PASQLAITFSLISLQLLGICVWFVVDPSHSVVDFQDQRTldprfaRGVLKCDIS 702
Cdd:cd15280   87 GKT---ISLFLRYRASKSETRLDSmhPIYQKIIVLICVLIEVGICTAYLILEPPRMYKNTEVQNV------KIIFECNEG 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 703 DLSLIC-LLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTsQSADKLYIQTTTLtvsvSL 781
Cdd:cd15280  158 SIEFLCsIFGFDVFLALLCFLTAFVARKLPDNFNEGKFITFGMLVFFIVWISFVPAYLST-RGKFKVAVEIFAI----LA 232
                        250       260
                 ....*....|....*....|.
gi 378548213 782 SASVSLGMLYMPKVYIILFHP 802
Cdd:cd15280  233 SSFGLLGCIFVPKCYIILLKP 253
LivK COG0683
ABC-type branched-chain amino acid transport system, periplasmic component [Amino acid ...
46-434 1.10e-27

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: 114.26  E-value: 1.10e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  46 DGDITLGGLFPVHGRGSEGkpcgelkkekGIHRLEAMLFALDRINNDPDLLPN-ITLgaRILDTCSrDThalEQSLTFVQ 124
Cdd:COG0683    1 ADPIKIGVLLPLTGPYAAL----------GQPIKNGAELAVEEINAAGGVLGRkIEL--VVEDDAS-DP---DTAVAAAR 64
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 125 ALIEKDGtevrcgsggppiitkperVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSDTY 204
Cdd:COG0683   65 KLIDQDK------------------VDAIVGPLSSGVALAVAPVAEEAGVPLISPSATAPALTGPECSPYVFRTAPSDAQ 126
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 205 QAQAMVD-IVRALKWNYVSTVASEGSYGESGVEAFIQKSREDGGVcIAQSVKIPrePKAGEFDKIIRRLLEtSNARAVII 283
Cdd:COG0683  127 QAEALADyLAKKLGAKKVALLYDDYAYGQGLAAAFKAALKAAGGE-VVGEEYYP--PGTTDFSAQLTKIKA-AGPDAVFL 202
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 284 FANEDDIRRVLEAARRANQTGHFFwmgsdswgskiapvlhleevaegavtilpKRMSVRDRERIGQD-SAYEQEGkvqfv 362
Cdd:COG0683  203 AGYGGDAALFIKQAREAGLKGPLN-----------------------------KAFVKAYKAKYGREpSSYAAAG----- 248
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 378548213 363 IDAVYAMGHALhamhrdlcpgrvglcPRMDPVDGTQLLKYIRNVNFSGIAGnPVTFNENGDAPGRYDIYQYQ 434
Cdd:COG0683  249 YDAALLLAEAI---------------EKAGSTDREAVRDALEGLKFDGVTG-PITFDPDGQGVQPVYIVQVK 304
Periplasmic_Binding_Protein_type1 cd01391
Type 1 periplasmic binding fold superfamily; Type 1 periplasmic binding fold superfamily. This ...
77-403 6.05e-26

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: 108.51  E-value: 6.05e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  77 HRLEAMLFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLTFVQaliekdgtevrcgsggppiitkpERVVGVIGA 156
Cdd:cd01391    9 LHQIREQFGIQRVEAIFHTADKLGASVEIRDSCWHGSVALEQSIEFIR-----------------------DNIAGVIGP 65
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 157 SGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSDTYQAQAMVDIVRALKWNYVSTVASEGS-YGESGV 235
Cdd:cd01391   66 GSSSVAIVIQNLAQLFDIPQLALDATSQDLSDKTLYKYFLSVVFSDTLGARLGLDIVKRKNWTYVAAIHGEGLnSGELRM 145
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 236 EAFiQKSREDGGVCIAQSVKIPREPKAGEFDKIIRRLLETSNARAVIIFaNEDDIRRVLEAARRANQTGHFFWMGSDSWG 315
Cdd:cd01391  146 AGF-KELAKQEGICIVASDKADWNAGEKGFDRALRKLREGLKARVIVCA-NDMTARGVLSAMRRLGLVGDVSVIGSDGWA 223
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 316 SkiAPVLHLEEVAEGAVTILPKRMSvrdrerigqdsayeqegkvqFVIDAVYAMGHALHAMHRDLcpgrvglcprMDPVD 395
Cdd:cd01391  224 D--RDEVGYEVEANGLTTIKQQKMG--------------------FGITAIKAMADGSQNMHEEV----------WFDEK 271

                 ....*...
gi 378548213 396 GTQLLKYI 403
Cdd:cd01391  272 GDALGRYI 279
7tmC_GPRC6A cd15281
class C of seven-transmembrane G protein-coupled receptors, subtype 6A; GRPC6A (GPCR, class C, ...
541-800 1.07e-25

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: 106.78  E-value: 1.07e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 541 AVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSISY 620
Cdd:cd15281    3 AIVLLILSALGVLLIFFISALFTKNLNTPVVKAGGGPLCYVILLSHFGSFISTVFFIGEPSDLTCKTRQTLFGISFTLCV 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 621 AALLTKTNRIYRIFEQGKRsvsAPRFISPASQ-LAITFSLISLQLLGICVWFVVDPSHSVVDFQDQRTLdprfargVLKC 699
Cdd:cd15281   83 SCILVKSLKILLAFSFDPK---LQELLKCLYKpIMIVFICTGIQVIICTVWLVFYKPFVDKNFSLPESI-------ILEC 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 700 DI-SDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSqsadKLYIQTTTLTvs 778
Cdd:cd15281  153 NEgSYVAFGLMLGYIALLAFICFIFAFKGRKLPENYNEAKFITFGMLIYFIAWITFIPIYATTF----GKYVPAVEMI-- 226
                        250       260
                 ....*....|....*....|....*
gi 378548213 779 vsLSASVSLGMLY---MPKVYIILF 800
Cdd:cd15281  227 --VILISNYGILSctfLPKCYIILY 249
PBP1_NPR_GC-like cd06352
ligand-binding domain of membrane guanylyl-cyclase receptors; Ligand-binding domain of ...
85-445 2.67e-23

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: 103.20  E-value: 2.67e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  85 ALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLTFVQAliekdgtevrcgsggppiitkpERVVGVIGASGSSVSIM 164
Cdd:cd06352   27 AIERINSEGLLLPGFNFEFTYRDSCCDESEAVGAAADLIYK----------------------RNVDVFIGPACSAAADA 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 165 VANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSDTYQAQAMVDIVRALKWNYVSTVAS-EGSYGESGVEAFIQKSR 243
Cdd:cd06352   85 VGRLATYWNIPIITWGAVSASFLDKSRYPTLTRTSPNSLSLAEALLALLKQFNWKRAAIIYSdDDSKCFSIANDLEDALN 164
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 244 EDGGVCIAQSVKIPREPKAgEFDKIIRRLLetSNARAVIIFANEDDIRRVLEAARRANQTG----HFF-------WMGSD 312
Cdd:cd06352  165 QEDNLTISYYEFVEVNSDS-DYSSILQEAK--KRARIIVLCFDSETVRQFMLAAHDLGMTNgeyvFIFielfkdgFGGNS 241
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 313 SWGS-------KIAPvlhleEVAEGAVTILPKRMSVRD--------RERIGQDSAYEQEGKVQFVI-------DAVYAMG 370
Cdd:cd06352  242 TDGWerndgrdEDAK-----QAYESLLVISLSRPSNPEydnfskevKARAKEPPFYCYDASEEEVSpyaaalyDAVYLYA 316
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 378548213 371 HALHAMHRDlcpgrvglcpRMDPVDGTQLLKYIRNVNFSGIAGnPVTFNENGDapgRYDIYQ-YQLRNDSAEYKVI 445
Cdd:cd06352  317 LALNETLAE----------GGNYRNGTAIAQRMWNRTFQGITG-PVTIDSNGD---RDPDYAlLDLDPSTGKFVVV 378
PBP1_ABC_transporter_LIVBP-like cd06268
periplasmic binding domain of ATP-binding cassette transporter-like systems that belong to the ...
79-379 4.03e-23

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: 100.48  E-value: 4.03e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  79 LEAMLFALDRINNDPDLLpNITLGARILDtcsrDTHALEQSLTFVQALIEKDGtevrcgsggppiitkperVVGVIGASG 158
Cdd:cd06268   20 LRGVALAVEEINAAGGIN-GRKLELVIAD----DQGDPETAVAVARKLVDDDK------------------VLAVVGHYS 76
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 159 SSVSIMVANILRLFKIPQISYASTAPDLSDNSrYDFFSRVVPSDTYQAQAMVD-IVRALKWNYVSTVASEGSYGESGVEA 237
Cdd:cd06268   77 SSVTLAAAPIYQEAGIPLISPGSTAPELTEGG-GPYVFRTVPSDAMQAAALADyLAKKLKGKKVAILYDDYDYGKSLADA 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 238 FIQKSREDGGVcIAQSVKIPrePKAGEFDKIIRRLLEtSNARAVIIFANEDDIRRVLEAARRANQTGHFFwmGSDSWGSK 317
Cdd:cd06268  156 FKKALKALGGE-IVAEEDFP--LGTTDFSAQLTKIKA-AGPDVLFLAGYGADAANALKQARELGLKLPIL--GGDGLYSP 229
                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 378548213 318 IAPVLhLEEVAEGAVTILPKRMSVRDRERIGQDSAYEQEGKVQfvIDAVYAMGH-ALHAMHRD 379
Cdd:cd06268  230 ELLKL-GGEAAEGVVVAVPWHPDSPDPPKQAFVKAYKKKYGGP--PSWRAATAYdATQALAGD 289
PBP1_ABC_LIVBP-like cd06342
type 1 periplasmic ligand-binding domain of ABC (Atpase Binding Cassette)-type active ...
150-433 2.44e-22

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: 99.14  E-value: 2.44e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 150 VVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNsRYDFFSRVVPSDTYQAQAMVD-IVRALKwnyVSTVA--S 226
Cdd:cd06342   67 VVAVIGHYNSGAAIAAAPIYAEAGIPMISPSATNPKLTEQ-GYKNFFRVVGTDDQQGPAAADyAAKTLK---AKRVAviH 142
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 227 EGS-YGESGVEAFIQKSREDGGVcIAQSVKIPrePKAGEFDKIIRRLLEtSNARAVIIFANEDDIRRVLEAARRANQTGH 305
Cdd:cd06342  143 DGTaYGKGLADAFKKALKALGGT-VVGREGIT--PGTTDFSALLTKIKA-ANPDAVYFGGYYPEAGLLLRQLREAGLKAP 218
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 306 FfwMGSDswGS------KIApvlhlEEVAEGAVTILP----------KRMSVRDRERIGQDS------AYeqegkvqfvi 363
Cdd:cd06342  219 F--MGGD--GIvspdfiKAA-----GDAAEGVYATTPgappeklpaaKAFLKAYKAKFGEPPgayaayAY---------- 279
                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 378548213 364 DAVYAMGHALhamhrdlcpGRVGlcprmdPVDGTQLLKYIRNVNFSGIAGnPVTFNENGD-APGRYDIYQY 433
Cdd:cd06342  280 DAAQVLLAAI---------EKAG------STDRAAVAAALRATDFDGVTG-TISFDAKGDlTGPAFTVYQV 334
PBP1_SAP_GC-like cd06370
Ligand-binding domain of membrane bound guanylyl cyclases; Ligand-binding domain of membrane ...
81-435 6.65e-22

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: 98.86  E-value: 6.65e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  81 AMLFALDRINNDPDLLPNITLGARILDTCSRDthalEQSLTFVqaliekdgTEVRCgsggppiitkpERVVGVIGASGS- 159
Cdd:cd06370   25 AITLAVDDVNNDPNLLPGHTLSFVWNDTRCDE----LLSIRAM--------TELWK-----------RGVSAFIGPGCTc 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 160 SVSIMVANILRLfkiPQISYASTAPDLSDNSRYDFFSRVVPSDTYQAQAMVDIVRALKWNYVSTVASEGSYGESGVEAfI 239
Cdd:cd06370   82 ATEARLAAAFNL---PMISYKCADPEVSDKSLYPTFARTIPPDSQISKSVIALLKHFNWNKVSIVYENETKWSKIADT-I 157
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 240 QKSREDGGVCIAQSVKIPREP-----KAGEFDKIIRRLLETsnARAVIIFANEDDIRRVLEAA--RRANQTGHFFWMGSD 312
Cdd:cd06370  158 KELLELNNIEINHEEYFPDPYpyttsHGNPFDKIVEETKEK--TRIYVFLGDYSLLREFMYYAedLGLLDNGDYVVIGVE 235
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 313 ----------------SWGSKIAPVLHLEEVAEGAVTILPKRMSVRD--------RERIGQ----DSAYEQEGKVQFVI- 363
Cdd:cd06370  236 ldqydvddpakypnflSGDYTKNDTKEALEAFRSVLIVTPSPPTNPEyekftkkvKEYNKLppfnFPNPEGIEKTKEVPi 315
                        330       340       350       360       370       380       390
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 378548213 364 ------DAVYAMGHALHAMHRDlcpgrvglcpRMDPVDGTQLLKYIRNVNFSGIAGNPVTFNENGDAPGRYDIYQYQL 435
Cdd:cd06370  316 yaaylyDAVMLYARALNETLAE----------GGDPRDGTAIISKIRNRTYESIQGFDVYIDENGDAEGNYTLLALKP 383
NCD3G pfam07562
Nine Cysteines Domain of family 3 GPCR; This conserved sequence contains several ...
469-519 1.49e-20

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: 85.38  E-value: 1.49e-20
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 378548213  469 PRSICSLPCQPGERKKTVKGMP-CCWHCEPCTGYQY-QVDRYTCKTCPYDMRP 519
Cdd:pfam07562   1 PSSVCSESCPPGQRKSQQGGAPvCCWDCVPCPEGEIsNTDSDTCKKCPEGQWP 53
7tmC_GPR158-like cd15293
orphan GPR158 and similar proteins, member of the class C family of seven-transmembrane G ...
545-799 1.66e-19

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: 88.81  E-value: 1.66e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 545 LFLAVVGIAATLFVVITFV--RYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSISYAA 622
Cdd:cd15293    5 AVLAVQAICILLCLVLALVvfRFRKVKVIKAASPILLELILFGALLLYFPVFILYFEPSVFRCILRPWFRHLGFAIVYGA 84
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 623 LLTKTNRIYRIFeqgkRSVSAPRFISPASQLAITFSLISLQLLG-ICVWFVVDPSHSVVDFqDQRTLDPRFARgvlkCDI 701
Cdd:cd15293   85 LILKTYRILVVF----RSRSARRVHLTDRDLLKRLGLIVLVVLGyLAAWTAVNPPNVEVGL-TLTSSGLKFNV----CSL 155
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 702 sDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAF--IPIFFGTSQSADKLYI--------- 770
Cdd:cd15293  156 -DWWDYVMAIAELLFLLWGVYLCYAVRKAPSAFNESRYISLAIYNELLLSVIFniIRFFLLPSLHPDLLFLlfflhtqlt 234
                        250       260
                 ....*....|....*....|....*....
gi 378548213 771 QTTTLtvsvslsasvslGMLYMPKVYIIL 799
Cdd:cd15293  235 VTVTL------------LLIFGPKFYLVL 251
PBP1_GABAb_receptor_plant cd19990
periplasmic ligand-binding domain of Arabidopsis thaliana glutamate receptors and its close ...
146-449 1.67e-19

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: 91.52  E-value: 1.67e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 146 KPERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSdNSRYDFFSRVVPSDTYQAQAMVDIVRALKWNYVSTVA 225
Cdd:cd19990   61 KNKKVEAIIGPQTSEEASFVAELGNKAQVPIISFSATSPTLS-SLRWPFFIRMTHNDSSQMKAIAAIVQSYGWRRVVLIY 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 226 SEGSYGeSGVEAFIQKSREDGGVCIAQSVKIPrePKAGEfDKIIRRL--LETSNARAVIIFANEDDIRRVLEAARRANQT 303
Cdd:cd19990  140 EDDDYG-SGIIPYLSDALQEVGSRIEYRVALP--PSSPE-DSIEEELikLKSMQSRVFVVHMSSLLASRLFQEAKKLGMM 215
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 304 GH-FFWMGSDSWGSkIAPVLHLEEVA--EGAVTILP--------KRMSVRDRERIGQDsaYEQEGKVQFVI------DAV 366
Cdd:cd19990  216 EKgYVWIVTDGITN-LLDSLDSSTISsmQGVIGIKTyipessefQDFKARFRKKFRSE--YPEEENAEPNIyalrayDAI 292
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 367 YAMGHALHAMHRDLCPGRVglcprmdPVDGTQLLKYIRNVNFSGIAGnPVTFNENGDAPGRydiyQYQLRNDSAE-YKVI 445
Cdd:cd19990  293 WALAHAVEKLNSSGGNISV-------SDSGKKLLEEILSTKFKGLSG-EVQFVDGQLAPPP----AFEIVNVIGKgYREL 360

                 ....
gi 378548213 446 GSWT 449
Cdd:cd19990  361 GFWS 364
7tmC_TAS1R3 cd15290
type 1 taste receptor subtype 3, member of the class C of seven-transmembrane G ...
539-800 1.89e-17

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


Pssm-ID: 320417 [Multi-domain]  Cd Length: 253  Bit Score: 82.80  E-value: 1.89e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15290    1 PESLGLLLLGVLLLVLQCSVGVLFLKHRGTPLVQASGGPLSIFALLSLMGACLSLLLFLGQPSDVVCRLQQPLNALFLTV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSVSAPRFIS-PASQLAITfsLISLQLLGICVWFVVD-PSHSVVDFqdQRTLdprFARGV 696
Cdd:cd15290   81 CLSTILSISLQIFLVTEFPKCAASHLHWLRgPGSWLVVL--ICCLVQAGLCGWYVQDgPSLSEYDA--KMTL---FVEVF 153
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 697 LKCDI-SDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSADKLYIQTTTL 775
Cdd:cd15290  154 LRCPVePWLGFGLMHGFNGALALISFMCTFMAQKPLKQYNLARDITFSTLIYCVTWVIFIPIYAGLQVKLRSIAQVGFIL 233
                        250       260
                 ....*....|....*....|....*...
gi 378548213 776 TvsvslsasVSLGML---YMPKVYIILF 800
Cdd:cd15290  234 L--------SNLGLLaayYLPKCYLLLR 253
PBP1_ABC_LivK_ligand_binding-like cd06347
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
75-424 6.69e-17

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


Pssm-ID: 380570 [Multi-domain]  Cd Length: 334  Bit Score: 82.98  E-value: 6.69e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  75 GIHRLEAMLFALDRINNDPDLLP-NITLgaRILDTCSRDThaleQSLTFVQALIEKDGtevrcgsggppiitkperVVGV 153
Cdd:cd06347   16 GQPALNGAELAVDEINAAGGILGkKIEL--IVYDNKSDPT----EAANAAQKLIDEDK------------------VVAI 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 154 IGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFfsRVVPSDTYQAQAMVD-IVRALKWNYVSTVASEGS-YG 231
Cdd:cd06347   72 IGPVTSSIALAAAPIAQKAKIPMITPSATNPLVTKGGDYIF--RACFTDPFQGAALAKfAYEELGAKKAAVLYDVSSdYS 149
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 232 ESGVEAFIQKSREDGGVcIAQSVKIPREPKagEFDKIIRRLLEtSNARAVIIFANEDDIRRVLEAARRANQTGHFfwMGS 311
Cdd:cd06347  150 KGLAKAFKEAFEKLGGE-IVAEETYTSGDT--DFSAQLTKIKA-ANPDVIFLPGYYEEAALIIKQARELGITAPI--LGG 223
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 312 DSWGSKIapvlhLEEVAEGAV--TILPKRMSVRDRERIGQD--SAYEQE-GKvqfVIDAVYAMGH-----ALHAMHrdlc 381
Cdd:cd06347  224 DGWDSPE-----LLELGGDAVegVYFTTHFSPDDPSPEVQEfvKAYKAKyGE---PPNAFAALGYdavmlLADAIK---- 291
                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....
gi 378548213 382 pgrvglcpRMDPVDGTQLLKYIRN-VNFSGIAGNpVTFNENGDA 424
Cdd:cd06347  292 --------RAGSTDPEAIRDALAKtKDFEGVTGT-ITFDPNGNP 326
PBP1_ABC_ligand_binding-like cd19984
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
150-337 3.86e-16

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: 79.96  E-value: 3.86e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 150 VVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSryDFFSRVVPSDTYQAQAMVDIVRALKWNYVSTVASEGS 229
Cdd:cd19984   68 VKAIIGGVCSSETLAIAPIAEQNKVVLISPGASSPEITKAG--DYIFRNYPSDAYQGKVLAEFAYNKLYKKVAILYENND 145
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 230 YGESGVEAFIQKSREDGG-VCIAQSVkiprEPKAGEFDKIIRRLLEtSNARAVIIFANEDDIRRVLEAARRANQTGHFFw 308
Cdd:cd19984  146 YGVGLKDVFKKEFEELGGkIVASESF----EQGETDFRTQLTKIKA-ANPDAIFLPGYPKEGGLILKQAKELGIKAPIL- 219
                        170       180       190
                 ....*....|....*....|....*....|...
gi 378548213 309 mGSDSWGS----KIAPvlhleEVAEGAVTILPK 337
Cdd:cd19984  220 -GSDGFEDpellEIAG-----EAAEGVIFTYPA 246
7tmC_TAS1R cd15046
type 1 taste receptors, member of the class C of seven-transmembrane G protein-coupled ...
539-800 6.65e-16

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: 78.34  E-value: 6.65e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15046    1 APTVAVLLLAALGLLSTLAILVIFWRNFNTPVVRSAGGPMCFLMLTLLLVAYMSVPVYFGPPKVSTCLLRQALFPLCFTV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSVSA----PRFISPASQLAITFSLISlqllgicvwFVVDPSHSVVDFQDQRTLDPRFAR 694
Cdd:cd15046   81 CLACIAVRSFQIVCIFKMASRFPRAysywVKYHGPYVSIAFITVLKM---------VIVVIGMLATPPSPTTDTDPDPKI 151
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 695 GVLKCDISDL-SLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLafipIFFGTSQSADKLYIQTT 773
Cdd:cd15046  152 TIVSCNPNYRnSSLFNTSLDLLLSVVCFSFSYMGKDLPTNYNEAKFITFSLTFYFTSWI----SFCTFMLAYSGVLVTIV 227
                        250       260
                 ....*....|....*....|....*..
gi 378548213 774 TLTVSVSLSASVSLGMlYMPKVYIILF 800
Cdd:cd15046  228 DLLATLLSLLAFSLGY-FLPKCYIILF 253
PBP1_iGluR_NMDA_NR1 cd06379
N-terminal leucine-isoleucine-valine-binding protein (LIVBP)-like domain of the NR1, an ...
156-463 3.87e-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: 78.15  E-value: 3.87e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 156 ASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSDTYQAQAMVDIVRALKWNYVSTVASEGSYGESGV 235
Cdd:cd06379   74 TPSDLSPTSVSYTAGFYRIPVIGISARDSAFSDKNIHVSFLRTVPPYSHQADVWAEMLRHFEWKQVIVIHSDDQDGRALL 153
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 236 EAFiQKSREDGGVCIAQSVKIprEPKAGEFDKIIRRLLETSnARAVIIFANEDDIRRVLEAARRANQTGH-FFWMGSDS- 313
Cdd:cd06379  154 GRL-ETLAETKDIKIEKVIEF--EPGEKNFTSLLEEMKELQ-SRVILLYASEDDAEIIFRDAAMLNMTGAgYVWIVTEQa 229
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 314 WGSKIAP--VLHLeevaegavtilpkrmsvrdreRIGQdsAYEQEGKVQfviDAVYAMGHALHAMHRDlcpGRVGLCP-- 389
Cdd:cd06379  230 LAASNVPdgVLGL---------------------QLIH--GKNESAHIR---DSVSVVAQAIRELFRS---SENITDPpv 280
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 390 --RMDPVD---GTQLLKYIRNVNFSGIAGNPVTFNENGDAPG-RYDIYQYQLRNdsaEYKVIGSW-------TDHLHLRI 456
Cdd:cd06379  281 dcRDDTNIwksGQKFFRVLKSVKLSDGRTGRVEFNDKGDRIGaEYDIINVQNPR---KLVQVGIYvgsqrptKSLLSLND 357

                 ....*..
gi 378548213 457 ERMHWPG 463
Cdd:cd06379  358 RKIIWPG 364
PBP1_ABC_ligand_binding-like cd19980
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
143-333 1.08e-13

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: 73.03  E-value: 1.08e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 143 IITKpERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSdNSRYDFFSRVVPSDTYQAQAMVD-IVRALKWNYV 221
Cdd:cd19980   62 LITD-DKVPAIIGAWCSSVTLAVMPVAERAKVPLVVEISSAPKIT-EGGNPYVFRLNPTNSMLAKAFAKyLADKGKPKKV 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 222 STVASEGSYGESGVEAFiQKSREDGGVCIAQSVKIPREpkAGEFDKIIRRlLETSNARAVIIFANEDDIRRVLEAARRAN 301
Cdd:cd19980  140 AFLAENDDYGRGAAEAF-KKALKAKGVKVVATEYFDQG--QTDFTTQLTK-LKAANPDAIFVVAETEDGALILKQARELG 215
                        170       180       190
                 ....*....|....*....|....*....|..
gi 378548213 302 QTGHffWMGSDSWGSKIAPVLhLEEVAEGAVT 333
Cdd:cd19980  216 LKQQ--LVGTGGTTSPDLIKL-AGDAAEGVYG 244
PBP1_ABC_HAAT-like cd19985
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
148-317 1.17e-12

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: 70.00  E-value: 1.17e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 148 ERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFfsRVVPSDTYQAQAMVDIVRA-LKWNYVSTVAS 226
Cdd:cd19985   65 DKALAVIGHYYSSASIAAGKIYKKAGIPAITPSATADAVTRDNPWYF--RVIFNDSLQGRFLANYAKKvLKKDKVSIIYE 142
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 227 EGSYGESGVEAFIQKSREDGG-VCIAQSVKIPREPKAGEFDKIIRRLLETSNARAVIIFA-NEDDIRRVLEAARRANQTG 304
Cdd:cd19985  143 EDSYGKSLASVFEATARALGLkVLKKWSFDTDSSQLDQNLDQIVDELKKAPDEPGVIFLAtHADEGAKLIKKLRDAGLKA 222
                        170
                 ....*....|...
gi 378548213 305 HFfwMGSDSWGSK 317
Cdd:cd19985  223 PI--IGPDSLASE 233
7tmC_GABA-B-R1 cd15291
gamma-aminobutyric acid type B receptor subunit 1, member of the class C family of ...
546-795 3.56e-12

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: 67.75  E-value: 3.56e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 546 FLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGT-------CSLRRIFLGLGMSI 618
Cdd:cd15291    8 LLASLGIFAAVFLLIFNIYNRHRRYIQLSQPHCNNVMLVGCILCLASVFLLGLDGRHVSrshfplvCQARLWLLCLGFTL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSVSAPRFISPASQLAITFSLISLQLLGICVWFVVDPSHSVVD-FQDQrtlDPRFArgvl 697
Cdd:cd15291   88 AYGSMFTKVWRVHRLTTKKKEKKETRKTLEPWKLYAVVGILLVVDVIILAIWQIVDPLHRTIEeFPLE---EPKDT---- 160
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 698 KCDISDLSLI--C-----------LLGYSMLLMVTCTVYAIKTRGV-PETFNEAKPIGFTMYTTCIVWLAFIPI--FFGT 761
Cdd:cd15291  161 DEDVKILPQLehCsskkqntwlgiVYGYKGLLLLFGLFLAYETRNVkVEKINDSRFVGMSIYNVVVLCLITAPVtmIISS 240
                        250       260       270
                 ....*....|....*....|....*....|....
gi 378548213 762 SQSADKLYIQTTTLtvsvsLSASVSLGMLYMPKV 795
Cdd:cd15291  241 QQDASFAFVSLAIL-----FSSYITLVLIFVPKI 269
PBP1_ABC_HAAT-like cd06344
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
150-427 7.17e-12

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: 67.64  E-value: 7.17e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 150 VVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNS-RYDFfsRVVPSDTYQAQAMVDIVRALKWNYVSTVASEG 228
Cdd:cd06344   66 VVAVIGHRSSYVAIPASIIYERAGLLMLSPGATAPKLTQHGfKYIF--RNIPSDEDIARQLARYAARQGYKRIVIYYDDD 143
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 229 SYGESGVEAFIQKSREDGGVCIAQSVKIPREpkaGEFDKIIRRLLETSNARAVIIFANEDDIRRVLEAARRANQTGHFFw 308
Cdd:cd06344  144 SYGKGLANAFEEEARELGITIVDRRSYSSDE---EDFRRLLSKWKALDFFDAIFLAGSMPEGAEFIKQARELGIKVPII- 219
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 309 mGSDSWGSkiapvLHLEEVAEGAV--TILP-------KRMSVRD-----RERIGQD------SAYeqegkvqfviDAVYA 368
Cdd:cd06344  220 -GGDGLDS-----PELIEIAGKAAegVVVAtvfdpddPRPEVRAfveafRKKYGREpdvwaaQGY----------DAVKL 283
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 378548213 369 MGHALHAMHRDlcpgrvglcprmDPVDGTQLLKYIRnvNFSGIAGnPVTFNENGDAPGR 427
Cdd:cd06344  284 LAEAIEKAGST------------VPAKIASALRFLE--NWEGVTG-TYSFDANGDVVGK 327
PBP1_iGluR_AMPA cd06380
N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the AMPA receptor; ...
81-451 2.86e-11

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: 66.15  E-value: 2.86e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  81 AMLFALDRINNDPDLLPNITLGARILDTCSRDTHALEQSLtfvqaliekdgtevrCG--SGGppiitkperVVGVIG-AS 157
Cdd:cd06380   16 AFRYAIDRHNSNNNNRFRLFPLTERIDITNADSFSVSRAI---------------CSqlSRG---------VFAIFGsSD 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 158 GSSVSIMVAnILRLFKIPQISYASTAPDLSDNSRYDFFSRvvPSdtYqAQAMVDIVRALKWN---YVStvasEGSYGESG 234
Cdd:cd06380   72 ASSLNTIQS-YSDTFHMPYITPSFPKNEPSDSNPFELSLR--PS--Y-IEAIVDLIRHYGWKkvvYLY----DSDEGLLR 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 235 VEAFIQKSREDGGVCI-AQSVKIPREpkAGEFDKIIRRLLETSNARAVIIFANEDDIRRVLEAARRA--NQTG-HFFWMG 310
Cdd:cd06380  142 LQQLYDYLKEKSNISVrVRRVRNVND--AYEFLRTLRELDREKEDKRIVLDLSSERYQKILEQIVEDgmNRRNyHYLLAN 219
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 311 SDswgskIAPvLHLEEVAEGAVTIL------PKRMSVRD-RERIGQDSAYEQEG--------KVQFVIDAVYAMGHALHA 375
Cdd:cd06380  220 LD-----FLD-LDLERFLHGGVNITgfqlvdTNNKTVKDfLQRWKKLDPREYPGagtdtipyEAALAVDAVLVIAEAFQS 293
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 376 M-------HRDLCPGRVGL-------CPRMDPV---DGTQLLKYIRNVNFSGIAGNpVTFNENGdapGR--Y--DIYQYQ 434
Cdd:cd06380  294 LlrqnddiFRFTFHGELYNngskgidCDPNPPLpweHGKAIMKALKKVRFEGLTGN-VQFDDFG---QRknYtlDVIELT 369
                        410
                 ....*....|....*..
gi 378548213 435 LRNDSAEykvIGSWTDH 451
Cdd:cd06380  370 SNRGLRK---IGTWSEG 383
7tmC_TAS1R1 cd15289
type 1 taste receptor subtype 1, member of the class C of seven-transmembrane G ...
539-800 4.35e-11

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: 63.98  E-value: 4.35e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 539 PWAVLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSI 618
Cdd:cd15289    1 PVSWALLTALTLLLLLLAGTALLFALNLTTPVVKSAGGRTCFLMLGSLAAASCSLYCHFGEPTWLACLLKQPLFSLSFTV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFeqgKRSVSAPRFISPASQL--AITFSLIS--LQLLGICVWFVVDPSHSVVDFQdqrtldpRFAR 694
Cdd:cd15289   81 CLSCIAVRSFQIVCIF---KLASKLPRFYETWAKNhgPELFILISsaVQLLISLLWLVLNPPVPTKDYD-------RYPD 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 695 G-VLKCD--ISDLSLICLLgYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTMYTTCIVWLAF---IPIFFGTSQSADKL 768
Cdd:cd15289  151 LiVLECSqtLSVGSFLELL-YNCLLSISCFVFSYMGKDLPANYNEAKCITFSLLIYFISWISFfttYSIYRGKYLMAINV 229
                        250       260       270
                 ....*....|....*....|....*....|..
gi 378548213 769 YIQTTTLtvsvslsaSVSLGMLYMPKVYIILF 800
Cdd:cd15289  230 LAILSSL--------LGIFGGYFLPKVYIILL 253
7tmC_TAS1R2a-like cd15287
type 1 taste receptor subtype 2a and similar proteins, member of the class C of ...
541-800 7.04e-11

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: 63.55  E-value: 7.04e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 541 AVLPLFLAVVGIAATLFVVITF-VRYNdTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSIS 619
Cdd:cd15287    3 AILIMVGACVLVGLTLAVSVLFaINYN-TPVVRSAGGPMCFLILGCLSLCSVSVFFYFGKPTVASCILRYFPFLLFYTVC 81
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 620 YAALLTKTNRIYRIFeqgKRSVSAPRFIS-----PASQLAITFSLIsLQLLGICVWFVVDPSHSVVD---FQDQRtldpr 691
Cdd:cd15287   82 LACFVVRSFQIVCIF---KIAAKFPKLHSwwvkyHGQWLLIAVAFV-IQALLLITGFSFSPPKPYNDtswYPDKI----- 152
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 692 fargVLKCDISDLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFtmyttCIVWLAFIPIFFGTSQSADK-LYI 770
Cdd:cd15287  153 ----ILSCDINLKATSMSLVLLLSLCCLCFIFSYMGKDLPKNYNEAKAITF-----CLLLLILTWIIFATEYMLYRgKYI 223
                        250       260       270
                 ....*....|....*....|....*....|.
gi 378548213 771 QttTLTVSVSLSASVSLGMLY-MPKVYIILF 800
Cdd:cd15287  224 Q--LLNALAVLSSLYSFLLWYfLPKCYIIIF 252
PBP1_ABC_ligand_binding-like cd06335
type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type ...
111-301 1.89e-10

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


Pssm-ID: 380558 [Multi-domain]  Cd Length: 348  Bit Score: 63.40  E-value: 1.89e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 111 RDTHA-LEQSLTFVQALIEKdgtevrcgsggppiitkpERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDN 189
Cdd:cd06335   46 RDDEAnPTKAVQNAQELIDK------------------EKVVAIIGPTNSGVALATIPILQEAKIPLIIPVATGTAITKP 107
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 190 SRYDF---FsRVVPSDTYQAQAMVDIVRALKWNYVSTVASEGSYGESGVEAfIQKSREDGGVCIAQSVKIprepKAGEFD 266
Cdd:cd06335  108 PAKPRnyiF-RVAASDTLQADFLVDYAVKKGFKKIAILHDTTGYGQGGLKD-VEAALKKRGITPVATESF----KIGDTD 181
                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 378548213 267 --KIIRRlLETSNARAVIIFANEDDIRRVLEAARRAN 301
Cdd:cd06335  182 mtPQLLK-AKDAGADVILVYGLGPDLAQILKAMEKLG 217
PBP1_ABC_RPA1789-like cd06333
type 1 periplasmic binding-protein component (CouP) of an ABC system (CouPSTU; RPA1789, ...
75-285 2.17e-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: 63.34  E-value: 2.17e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  75 GIHRLEAMLFALDRINNDPDLLP-NITLgaRILDTCSRDThaleQSLTFVQALIEKDGtevrcgsggppiitkperVVGV 153
Cdd:cd06333   16 GIPERNAVELLVEQINAAGGINGrKLEL--IVYDDESDPT----KAVTNARKLIEEDK------------------VDAI 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 154 IGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFfsRVVPSDTYQAQAMVDIVRALKWNYVSTVASEGSYGES 233
Cdd:cd06333   72 IGPSTTGESLAVAPIAEEAKVPLISLAGAAAIVEPVRKWVF--KTPQSDSLVAEAILDYMKKKGIKKVALLGDSDAYGQS 149
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 378548213 234 GVEAFiQKSREDGGVCIAQSVKIPREPK--AGEFDKIIrrlleTSNARAVIIFA 285
Cdd:cd06333  150 GRAAL-KKLAPEYGIEIVADERFARTDTdmTAQLTKIR-----AAKPDAVLVWA 197
PBP1_ABC_HAAT-like cd19988
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
75-356 3.39e-10

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


Pssm-ID: 380643 [Multi-domain]  Cd Length: 302  Bit Score: 62.29  E-value: 3.39e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  75 GIHRLEAMLFALDRINNdpdllPNITLGARIlDTCSRDTHAL-EQSLTFVQALIEKDGtevrcgsggppiitkperVVGV 153
Cdd:cd19988   16 GQAMLQGAELAVEEINA-----AGGILGIPI-ELVVEDDEGLpAASVSAAKKLIYQDK------------------VWAI 71
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 154 IGASGSSVSIMVANILRLFKIPQISYASTAPDLSdNSRYDFFSRVVPSDTYQAQAMVD-IVRALKWNYVSTVASEGSYGE 232
Cdd:cd19988   72 IGSINSSCTLAAIRVALKAGVPQINPGSSAPTIT-ESGNPWVFRCTPDDRQQAYALVDyAFEKLKVTKIAVLYVNDDYGR 150
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 233 SGVEAFIQKSREDGGVCIAQSVKIPrepkaGEFD---KIIRrlLETSNARAVIIFANEDDIRRVLEAARRANQTGHFFwm 309
Cdd:cd19988  151 GGIDAFKDAAKKYGIEVVVEESYNR-----GDKDfspQLEK--IKDSGAQAIVMWGQYTEGALIAKQARELGLKQPLF-- 221
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 378548213 310 GSDSWGS----KIAPvlhleEVAEGAVTILPKRMSVRDRERIGQDSAYEQE 356
Cdd:cd19988  222 GSDGLVTpkfiELAG-----DAAEGAIATTPFLPDSDDPKVSAFVEKYKKR 267
7tmC_TAS1R2 cd15288
type 1 taste receptor subtype 2, member of the class C of seven-transmembrane G ...
542-744 3.85e-10

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: 61.34  E-value: 3.85e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 542 VLPLFLAVVGIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLGMSISYA 621
Cdd:cd15288    4 IVVALLAALGFLSTLAILVIFGRHFQTPVVRSAGGRMCFLMLAPLLVAYVNVPVYVGIPTVFTCLCRQTLFPLCFTVCIS 83
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 622 ALLTKTNRIYRIFEQGKRSVSA----PRFISPASQLAITfslISLQLLGICVWFVVDPSHSVVDFQDQrtlDPRFArgVL 697
Cdd:cd15288   84 CIAVRSFQIVCIFKMARRLPRAysywVKYNGPYVFVALI---TLLKVVIVVINVLAHPTAPTTRADPD---DPQVM--IL 155
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 378548213 698 KCDIS-DLSLICLLGYSMLLMVTCTVYAIKTRGVPETFNEAKPIGFTM 744
Cdd:cd15288  156 QCNPNyRLALLFNTSLDLLLSVLGFCFAYMGKELPTNYNEAKFITLCM 203
PBP1_ABC_HAAT-like cd19981
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
75-285 6.76e-10

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


Pssm-ID: 380636 [Multi-domain]  Cd Length: 297  Bit Score: 61.15  E-value: 6.76e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  75 GIHRLEAMLFALDRINNdpdllpNITLGARIL------DTCSRDthaleQSLTFVQALIEKDgtevrcgsggppiitkpe 148
Cdd:cd19981   16 GKSALHGAELAVEQINA------AGGINGKKVelvvydDQASPK-----QAVNIAQKLIEQD------------------ 66
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 149 RVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSryDFFSRVVPSDTYQAQAMVD-IVRALKWNYVSTVASE 227
Cdd:cd19981   67 KVVAVVSGSYSGPTRAAAPIFQEAKVPMVSAYAVHPDITKAG--DYVFRVAFLGPVQGRAGAEyAVKDLGAKKVAILTID 144
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 378548213 228 GSYGESGVEAFIQKSREDGGVCIAqsvKIPREPKAGEFDKIIRRLletSNARAVIIFA 285
Cdd:cd19981  145 NDFGKSLAAGFKEEAKKLGAEIVS---EYAYALGDRDFRPILTKI---KSANPDAIYA 196
PBP1_ABC_HAAT-like cd06349
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
148-432 5.36e-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 or peptides; This subgroup includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type active transport systems that are predicted to be involved in the uptake of amino acids or peptides. This subgroup has high sequence similarity to members of the family of hydrophobic amino acid transporters (HAAT), such as leucine-isoleucine-valine binding protein (LIVBP); however, its ligand specificity has not been determined experimentally.


Pssm-ID: 380572 [Multi-domain]  Cd Length: 338  Bit Score: 58.73  E-value: 5.36e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 148 ERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFfsRVVPSDTYQAQAMVD-IVRALKWNYVSTVAS 226
Cdd:cd06349   66 DKVVAVIGDFSSSCSMAAAPIYEEAGLVQISPTASHPDFTKGGDYVF--RNSPTQAVEAPFLADyAVKKLGAKKIAIIYL 143
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 227 EGSYGESGVEAFIQKSREDGGVCIAQSVKIPREPkagEFDKIIRRLLETsNARAVIIFANEDDIRRVLEAARRANQTGHF 306
Cdd:cd06349  144 NTDWGVSAADAFKKAAKALGGEIVATEAYLPGTK---DFSAQITKIKNA-NPDAIYLAAYYNDAALIAKQARQLGWDVQI 219
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 307 FwmGSDSWGSKIAPVLhLEEVAEGAVTILPkRMSVRDRERIgQD--SAYEQE-GKV--QFVI---DAVYAMGHALhamhr 378
Cdd:cd06349  220 F--GSSSLYSPEFIEL-AGDAAEGVYLSSP-FFPESPDPEV-KEfvKAYKAKyGEDpdDFAArayDAVNILAEAI----- 289
                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 378548213 379 dlcpGRVGlcprmdpVDGTQLLKYIRNV-NFSGIAGnPVTFNENGDAPGRYDIYQ 432
Cdd:cd06349  290 ----EKAG-------TDREAIRDALANIkDFSGLTG-TITFDENGDVLKSLTILV 332
7tm_GPCRs cd14964
seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary ...
545-766 7.25e-09

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: 57.82  E-value: 7.25e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 545 LFLAVVGIAATLFVVITFVRYNDTPivkASGRELSYVLLAGIFLCYATTFLMIAEPDL--------GTCSLRRIFLGLGM 616
Cdd:cd14964    6 SLLTCLGLLGNLLVLLSLVRLRKRP---RSTRLLLASLAACDLLASLVVLVLFFLLGLteassrpqALCYLIYLLWYGAN 82
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 617 SISYAALLTKTNRIYRIfeqGKRSVSAPRFISPASQLAITFSLISLQLL-------GICVWFV-VDPSHSVVDFQDQRTL 688
Cdd:cd14964   83 LASIWTTLVLTYHRYFA---LCGPLKYTRLSSPGKTRVIILGCWGVSLLlsipplvGKGAIPRyNTLTGSCYLICTTIYL 159
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 689 dprfarGVLKCDISDLSLICLLGYSMLLMV---TCTVYAIKTRGVPET---FNEAKPIGFTMYTTCIVWLAFIPIFFGTS 762
Cdd:cd14964  160 ------TWGFLLVSFLLPLVAFLVIFSRIVlrlRRRVRAIRSAASLNTdknLKATKSLLILVITFLLCWLPFSIVFILHA 233

                 ....
gi 378548213 763 QSAD 766
Cdd:cd14964  234 LVAA 237
PBP1_iGluR_NMDA cd06367
N-terminal leucine-isoleucine-valine-binding protein (LIVBP)-like domain of the ionotropic ...
187-452 2.67e-08

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: 56.86  E-value: 2.67e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 187 SDNSRYDFFSRVVPSDTYQAQAMVDIVRALKWNYVSTVASEgSYGESGVEAFIQKSREDGGVCIAQSVKIprEPKAGEFD 266
Cdd:cd06367  105 ADKSEHSMFLQFGPPIEQQASVMLNIMEEYDWYIVSLVTTY-FPGYQDFVNKLRSTIENSGWELEEVLQL--DMSLDDGD 181
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 267 KIIRRLL---ETSNARAVIIFANEDDIRRVLEAARRANQTGH-FFWMgsdsWGSKIAPV-LHLEEVAEGAVTilpkrmsv 341
Cdd:cd06367  182 SKLQAQLkklQSPEARVILLYCTKEEATYVFEVAASVGLTGYgYTWL----VGSLVAGTdTVPAEFPTGLIS-------- 249
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 342 rdrerIGQDSAYEQEGKVQfviDAVYAMGHALHAM---HRDLCPGRVGlCPRMDPV---DGTQLLKYIRNVNFSGIAGnp 415
Cdd:cd06367  250 -----LSYDEWYNLPARIR---DGVAIVATAASEMlseHEQIPDPPSS-CVNNQEIrkyTGPMLKRYLINVTFEGRDL-- 318
                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 378548213 416 vTFNENGDAPGR-YDIyqYQLRNDSAEYKViGSWTDHL 452
Cdd:cd06367  319 -SFSEDGYQMHPkLVI--ILLNNERKWERV-GKWKDSS 352
PBP1_ABC_HAAT-like cd19983
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
148-286 6.15e-07

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: 52.20  E-value: 6.15e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 148 ERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSryDFFSRVVPSDTYQAQAMVDivRALKWNYVSTVA-- 225
Cdd:cd19983   65 GGVVAIIGHMTSAMTVAVLPVINEAKVLMISPTVSTPELSGKD--DYFFRVTPTTRESAQALAR--YAYNRGGLRRVAvi 140
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 378548213 226 ---SEGSYGESGVEAFIQKSREDGGVCIAqsvKIPREPKA-GEFDKIIRRLLEtSNARAVIIFAN 286
Cdd:cd19983  141 ydlSNRAYSESWLDNFRSEFEALGGRIVA---EIPFSSGAdVDFSDLARRLLA-SKPDGLLLVAS 201
PBP1_ABC_HAAT-like cd19986
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
150-365 6.63e-07

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


Pssm-ID: 380641 [Multi-domain]  Cd Length: 297  Bit Score: 51.86  E-value: 6.63e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 150 VVGVIGASGSSVSIMVANILRLFKIPQIsYASTAPDLSDNsRYDFFSRVVPSDTYQAQAMVD-IVRALKWNYVSTVASEG 228
Cdd:cd19986   68 VVAVIGPHYSTQVLAVSPLVKEAKIPVI-TGGTSPKLTEQ-GNPYMFRIRPSDSVSAKALAKyAVEELGAKKIAILYDND 145
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 229 SYGESGVEAfIQKSREDGGVCIAQSVKIPREPKagEFDKIIRRLLEtSNARAVIIFANEDDirrVLEAARRANQTG-HFF 307
Cdd:cd19986  146 DFGTGGADV-VTAALKALGLEPVAVESYNTGDK--DFTAQLLKLKN-SGADVIIAWGHDAE---AALIARQIRQLGlDVP 218
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 378548213 308 WMGSDSWGSkiAPVLHLE-EVAEGavtilpkRMSVRDrerigqDSAYEQEGKVQFVIDA 365
Cdd:cd19986  219 VIGSSSFAT--PTVLLLAgEALEG-------IYSVTD------FVPSDPDPKVQAFVKK 262
7tmC_GPR156 cd15292
orphan GPR156, member of the class C family of seven-transmembrane G protein-coupled receptors; ...
551-676 9.23e-07

orphan GPR156, member of the class C family of seven-transmembrane G protein-coupled receptors; This subgroup represents orphan GPR156 that is 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: 320419  Cd Length: 268  Bit Score: 51.28  E-value: 9.23e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 551 GIAATLFVVITFVRYNDTPIVKASGRELSYVLLAGIFLCYATTFLM-IAEPDLGTCSL---RRIFLGLGMSISYAALLTK 626
Cdd:cd15292   13 GILLALFFLAFTIRFRNNRIVKMSSPNLNVVTLLGSILTYTSGFLFgIQEPGTSMETIfqvRIWLLCIGTSLVFGPILGK 92
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 378548213 627 TNRIYRIFEQgkrSVSAPRFISPASQL-AITFSLISLQLLGICVWFVVDPS 676
Cdd:cd15292   93 SWRLYRVFTQ---RVPDKRVIIKDIQLlGLVAGLIFADVLLLLTWVLTDPV 140
Peripla_BP_6 pfam13458
Periplasmic binding protein; This family includes a diverse range of periplasmic binding ...
49-434 1.52e-06

Periplasmic binding protein; This family includes a diverse range of periplasmic binding proteins.


Pssm-ID: 433225 [Multi-domain]  Cd Length: 342  Bit Score: 51.12  E-value: 1.52e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213   49 ITLGGLFPVHGRGSE-GKPCgelkkekgihrLEAMLFALDRINNDPDLLpnitlGARIlDTCSRDTH-ALEQSLTFVQAL 126
Cdd:pfam13458   2 IKIGVLTPLSGPYASsGKSS-----------RAGARAAIEEINAAGGVN-----GRKI-ELVVADDQgDPDVAAAAARRL 64
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  127 IEKDGtevrcgsggppiitkperVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDlsDNSRYDFFSRVVPSDtyQA 206
Cdd:pfam13458  65 VDQDG------------------VDAIVGGVSSAVALAVAEVLAKKGVPVIGPAALTGE--KCSPYVFSLGPTYSA--QA 122
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  207 QAMVD-IVRALKWNYVSTVASEGSYGESGVEAfIQKSREDGGVCIAQSVKIPrePKAGEFDKIIRRlLETSNARAVIIFA 285
Cdd:pfam13458 123 TALGRyLAKELGGKKVALIGADYAFGRALAAA-AKAAAKAAGGEVVGEVRYP--LGTTDFSSQVLQ-IKASGADAVLLAN 198
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  286 NEDDIRRVLEAARRAN-QTGHFFWMGSDSWGSKIAPVlhLEEVAEGAVTILP----------KRMSVRDRERIGQDSAye 354
Cdd:pfam13458 199 AGADTVNLLKQAREAGlDAKGIKLVGLGGDEPDLKAL--GGDAAEGVYATVPffpdldnpatRAFVAAFAAKYGEAPP-- 274
                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  355 qegkVQFVIDAVYAMGHALHAMhrdlcpgrvglcPRMDPVDGTQLLKYIRNVNFSGIAGNPVTFNENGDAPGRYDIYQYQ 434
Cdd:pfam13458 275 ----TQFAAGGYIAADLLLAAL------------EAAGSPTREAVIAALRALPYDGPFGPVGFRAEDHQAVHCMYLVQVK 338
7tmC_GABA-B-R2 cd15294
gamma-aminobutyric acid type B receptor subunit 2, member of the class C family of ...
547-770 1.90e-06

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: 50.50  E-value: 1.90e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 547 LAVVGIA-ATLFVVITFvRYNDTPIVKASGRELSYVLLAGIFLCYATTFL------MIAEPDLGT-CSLRRIFLGLGMSI 618
Cdd:cd15294    9 LTIIGIIlASAFLAFNI-KFRNHRYIKMSSPYMNNLIILGCMLTYASVILlgldgsLVSEKTFETlCTARTWILCVGFTL 87
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 619 SYAALLTKTNRIYRIFEQGKRSVSAprfISPASQLAITFSLISLQLLGICVWFVVDPSHSVVDfQDQRTLDPRfARGVL- 697
Cdd:cd15294   88 AFGAMFSKTWRVHSIFTNVKLNKKA---IKDYKLFIIVGVLLLIDICILITWQIVDPFYRTVK-ELEPEPDPA-GDDILi 162
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 698 -----KCDISDLS--LICLLGYSMLLMVTCTVYAIKTRGVP-ETFNEAKPIGFTMYTTCIVWLAFIPIFFGTSQSADKLY 769
Cdd:cd15294  163 rpeleYCESTHMTifLGIIYAYKGLLMVFGCFLAWETRNVSiPALNDSKYIGMSVYNVVIMCVIGAAVSFILRDQPNVQF 242

                 .
gi 378548213 770 I 770
Cdd:cd15294  243 C 243
PBP1_iGluR_Kainate cd06382
N-terminal leucine-isoleucine-valine binding protein (LIVBP)-like domain of the kainate ...
81-458 1.91e-06

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: 50.68  E-value: 1.91e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  81 AMLFALDRINNDpDLLPNITLGARILDTCSRDTHALEQsltFVQALIEKdGtevrcgsggppiitkperVVGVIGASGSS 160
Cdd:cd06382   16 AFKYAVDRINRE-RTLPNTKLVPDIERVPRDDSFEASK---KVCELLEE-G------------------VAAIFGPSSPS 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 161 VSIMVANILRLFKIPQIsyaSTAPDLSDNSRYDFFSRVVPSDTYQAQAMVDIVRALKWNYVsTVASEGSYGesgveafIQ 240
Cdd:cd06382   73 SSDIVQSICDALEIPHI---ETRWDPKESNRDTFTINLYPDPDALSKAYADLVKSLNWKSF-TILYEDDEG-------LI 141
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 241 KSREdggvciaqsvkIPREPKAGEFDKIIRRLLETSNARAVI--IFANED-------DIRRVLEAARRANQTG------H 305
Cdd:cd06382  142 RLQE-----------LLKLPKPKDIPITVRQLDPGDDYRPVLkeIKKSGEtriildcSPDRLVDVLKQAQQVGmlteyyH 210
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 306 FFWMGSDswgskiAPVLHLEEVAEGAVTIL------PKRMSVRD-------RERIGQDSAYEQEG---KVQFVIDAVYAM 369
Cdd:cd06382  211 YILTNLD------LHTLDLEPFKYSGANITgfrlvdPENPEVKNvlkdwskREKEGFNKDIGPGQittETALMYDAVNLF 284
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 370 GHALHamhrdlcpgrvglcprmdpvdgtqllkyirnvnfSGIAGnPVTFNENGdapGRYD--IYQYQLRNDSaeYKVIGS 447
Cdd:cd06382  285 ANALK----------------------------------EGLTG-PIKFDEEG---QRTDfkLDILELTEGG--LVKVGT 324
                        410
                 ....*....|.
gi 378548213 448 WTDHLHLRIER 458
Cdd:cd06382  325 WNPTDGLNITR 335
PBP1_ABC_ligand_binding-like cd06343
type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type ...
118-334 1.54e-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: 47.95  E-value: 1.54e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 118 QSLTFVQALIEKDGtevrcgsggppiitkperVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSr 197
Cdd:cd06343   61 RAVAAVRKLVEQDK------------------VFAIVGGLGTPTNLAVRPYLNEAGVPQLFPATGASALSPPPKPYTFG- 121
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 198 VVPSDTYQAQAMVD-IVRALKWNYVSTVASEGSYGESGVEAFiQKSREDGGVCIAQSVkiPREPKAGEFDKIIRRLLEtS 276
Cdd:cd06343  122 VQPSYEDEGRILADyIVETLPAAKVAVLYQNDDFGKDGLEGL-KEALKAYGLEVVAEE--TYEPGDTDFSSQVLKLKA-A 197
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 378548213 277 NARAVIIFANEDDIRRVLEAARRANQTGHffWMGSDSWGSKIAPVLHLEEVAEGAVTI 334
Cdd:cd06343  198 GADVVVLGTLPKEAAAALKEAAKLGWKPT--FLGSSVSADPTTLAKAGGDAAEGVYSA 253
PBP1_YraM_LppC_lipoprotein-like cd06339
periplasmic binding component of lipoprotein LppC, an immunodominant antigen; This subgroup ...
79-282 5.09e-05

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


Pssm-ID: 380562 [Multi-domain]  Cd Length: 331  Bit Score: 46.49  E-value: 5.09e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  79 LEAMLFALDRINN-DPDLLPnitlgarildtcsRDTHALEQSLTFVQALIEkdgtevrcgsggppiitkpERVVGVIG-A 156
Cdd:cd06339   20 RDGIELALFDAGGsRPELRV-------------YDTGGPEGAAAAYQQAVA-------------------EGADLIIGpL 67
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 157 SGSSVSImVANILRLFKIPQISYASTAPDLSDNSRYDF-FSrvvPSDtyQAQAMVDIVRALKWNYVSTVASEGSYGESGV 235
Cdd:cd06339   68 LKSSVAA-LAAAAQALGVPVLALNNDESATAGPGLFQFgLS---PED--EARQAARYAVQQGLRRFAVLAPDNAYGQRVA 141
                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 378548213 236 EAFIQKSREDGGVcIAQSVKIPrePKAGEFDKIIRRLLETSNARAVI 282
Cdd:cd06339  142 NAFREAWQALGGT-VVAVESYD--PDETDFSAAIRRLLGVDQSEARI 185
PBP1_ABC_ligand_binding-like cd06340
type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type ...
144-241 7.70e-05

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


Pssm-ID: 380563 [Multi-domain]  Cd Length: 352  Bit Score: 46.01  E-value: 7.70e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 144 ITKpERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDnsR-YDFFSRVVPSDTYQAQAMVDIVRAL------ 216
Cdd:cd06340   66 ITQ-EGVVAIIGAYSSSVTLAASQVAERYGVPFVTASAVADEITE--RgFKYVFRTAPTASQFAEDAVDFLKELakkkgk 142
                         90       100
                 ....*....|....*....|....*...
gi 378548213 217 KWNYVSTVASEGSYGES---GVEAFIQK 241
Cdd:cd06340  143 KIKKVAIIYEDSAFGTSvakGLKKAAKK 170
PBP1_ABC_ligand_binding-like cd06326
periplasmic ligand-binding domain of uncharacterized ABC-type transport systems predicted to ...
148-307 9.58e-05

periplasmic ligand-binding domain of uncharacterized ABC-type transport systems predicted to be involved in uptake of amino acids, peptides, or inorganic ions; This group includes the type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type transport systems that are predicted to be involved in the 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); its ligand specificity has not been determined experimentally, however.


Pssm-ID: 380549 [Multi-domain]  Cd Length: 339  Bit Score: 45.61  E-value: 9.58e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 148 ERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDL-SDNSRYDFFSRvvPSDTYQAQAMVDIVRALKWNYVSTVAS 226
Cdd:cd06326   67 DKVVALFGYVGTANVEAVLPLLEEAGVPLVGPLTGADSLrEPGNPYVFHVR--ASYADEVEKIVRHLATLGLKRIAVVYQ 144
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 227 EGSYGESGVEAfIQKSREDGGVCIAQSVKIPREpkAGEFDKIIRRLLEtSNARAVIIFANEDDIRRVLEAARRANQTGHF 306
Cdd:cd06326  145 DDPFGKEGLAA-AEAALAARGLEPVATAAVARN--AADVAAAAAALAA-AKPQAVVLIAAGKAAAAFIKALRAAGGAAQF 220

                 .
gi 378548213 307 F 307
Cdd:cd06326  221 Y 221
PBP1_ABC_HAAT-like cd06348
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
75-424 5.38e-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: 380571 [Multi-domain]  Cd Length: 342  Bit Score: 42.99  E-value: 5.38e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  75 GIHRLEAMLFALDRINNDPdLLPNITLGARILDTCSRDthalEQSLTFVQALIEKDgtevrcgsggppiitkpeRVVGVI 154
Cdd:cd06348   16 GQSQKNGAQLAVEEINAAG-GVGGVKIELIVEDTAGDP----EQAINAFQKLINQD------------------KVLAIL 72
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 155 GASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFfsrvVPSDTYQAQAMVDIVRALKWNYVSTVA----SEGSY 230
Cdd:cd06348   73 GPTLSSEAFAADPIAQQAKVPVVGISNTAPGITDIGPYIF----RNSLPEDKVIPPTVKAAKKKYGIKKVAvlydQDDAF 148
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 231 GESGVEAFiQKSREDGGVCIAQSVKIPRepkaGEFD------KIIRrlletSNARAVIIFANEDDIRRVLEAARRANQTG 304
Cdd:cd06348  149 TVSGTKVF-PAALKKNGVEVLDTETFQT----GDTDfsaqltKIKA-----LNPDAIVISALAQEGALIVKQARELGLKG 218
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 305 HFfwMGSDSWGS-KIAPVlhLEEVAEGAVTILP----------KRMSVRDRERIGQD------SAYeqegkvqfviDAVY 367
Cdd:cd06348  219 PI--VGGNGFNSpDLIKL--AGKAAEGVIVGSAwspdnpdpknQAFVAAYKEKYGKEpdqfaaQAY----------DAAY 284
                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 378548213 368 AMGHALHAMhrDLCPGRVGLcpRmdpvdgTQLLKYIRNVNFSGIAGnPVTFNENGDA 424
Cdd:cd06348  285 ILAEAIKKA--GSTTDRADL--R------DALARILIAKDFEGPLG-PFSFDADRDG 330
7tmC_RAIG_GPRC5 cd15043
retinoic acid-inducible orphan G-protein-coupled receptors; class C family of ...
540-773 6.05e-04

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: 42.55  E-value: 6.05e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 540 WAVLPLFLAVVGIAATLFVVITFVRYndTPIVKASGRE----LSYVLLAGIFLCYATTFLMIAEPDLGTCSLRRIFLGLG 615
Cdd:cd15043    2 WGIVLEAVAGAGVVTTVALMLILPIL--LPFVQDSNKRsmlgTQFLFLLGTLGLFGLTFAFIIGLDGSTCPTRRFLFGVL 79
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 616 MSISYAALLTKTNRIYRIFEQGKrsvsAPRFISPASqLAITFSLIslQLLGICVWFVVdpshSVVdfqdqRTLDPRFARg 695
Cdd:cd15043   80 FAICFSCLLAHAVSLTKLVRGRK----GPSGWVILG-LALGLSLV--QVIIAIEWLVL----TMN-----RTNVNVFSE- 142
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 696 vLKCDISDLSLICLLGYSMLLMVTCTVYAIKTrgVPETFNEAKPIG----FTMYTTCIVWLAFIPIF-FGTSQSADKLYI 770
Cdd:cd15043  143 -LSCARRNMDFVMALIYVMFLLALTFLMASFT--LCGSFKRWKRHGafilLTMLLSVAIWVAWITMYmLGNVLQFDRRWD 219

                 ...
gi 378548213 771 QTT 773
Cdd:cd15043  220 DPT 222
PBP1_ABC_ligand_binding-like cd06345
type 1 periplasmic ligand-binding domain of uncharacterized ABC (Atpase Binding Cassette)-type ...
75-284 7.86e-04

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


Pssm-ID: 380568 [Multi-domain]  Cd Length: 356  Bit Score: 42.64  E-value: 7.86e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213  75 GIHRLEAMLFALDRINNDPDLLPnitlgaRILDTCSRDTHAL-EQSLTFVQALIEKDGtevrcgsggppiitkperVVGV 153
Cdd:cd06345   13 GEAMERGAELAVEEINAAGGILG------RKVELVVADTQGKpEDGVAAAERLITEDK------------------VDAI 68
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 154 IGASGSSVSIMVANILRLFKIPQISYASTAPDL-----SDNSRYDFFSRVVPSDTYQAQAMVD-----IVRALKWNYVST 223
Cdd:cd06345   69 VGGFRSEVVLAAMEVAAEYKVPFIVTGAASPAItkkvkKDYEKYKYVFRVGPNNSYLGATVAEflkdlLVEKLGFKKVAI 148
                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 378548213 224 VASEGSYGESGVEAFIQKSREDGgvciAQSVKIPREPK-AGEFDKIIRRlLETSNARAVIIF 284
Cdd:cd06345  149 LAEDAAWGRGIAEALKKLLPEAG----LEVVGVERFPTgTTDFTPILSK-IKASGADVIVTI 205
PBP1_ABC_ligand_binding-like cd19982
type 1 periplasmic ligand-binding domain of uncharacterized ABC (ATPase Binding Cassette)-type ...
150-246 1.32e-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: 41.88  E-value: 1.32e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 150 VVGVIGASGSSVSIMVANILRLFKIPQISYASTApDLSDNSRYDFFSRVVPSDTYQAQAMVDIVRALKwnYVSTVA---S 226
Cdd:cd19982   68 VPLIVGGYSSGITLPVAAVAERQKIPLLVPTAAD-DDITKPGYKYVFRLNPPASIYAKALFDFFKELV--KPKTIAilyE 144
                         90       100
                 ....*....|....*....|
gi 378548213 227 EGSYGESGVEAFIQKSREDG 246
Cdd:cd19982  145 NTAFGTSVAKAARRFAKKRG 164
PBP1_As_SBP-like cd06330
periplasmic substrate-binding domain of active transport proteins; Periplasmic ...
148-285 2.11e-03

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: 41.39  E-value: 2.11e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 378548213 148 ERVVGVIGASGSSVSIMVANILRLFKIPQISYASTAPDLSDNSRYDFFSRVVPSDTYQAQAMVDIVRALKWNY--VSTVA 225
Cdd:cd06330   66 EGVDFLIGTISSGVALAVAPVAEELKVLFIATDAATDRLTEENFNPYVFRTSPNTYMDAVAAALYAAKKPPDVkrWAGIG 145
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 378548213 226 SEGSYGESGVEAFIQKSREdggvcIAQSVKIPRE--PKAGEFD--KIIRRLLetsNARAVIIFA 285
Cdd:cd06330  146 PDYEYGRDSWAAFKAALKK-----LKPDVEVVGElwPKLGATDytAYITALL---AAKPDGVFS 201
 
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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