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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 141 TPSPRLPHNLSLELVAVASPTRDPASLARGLCQVLAPPGVVASITFPEARPELRLLQFLAAATETPVLSVLRREVRAPLG 220
Cdd:cd06377   33 LPTGLLPYNLSLEVVVAAPWARDPASLTRSLCHSVVVQGVAALLAFPQSRGELLQLDFLSAALEIPVVSILRREFPRPLR 112

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 221 APTPFHLQLDWASPLETILDVLVSLVRAHAWEDIALVLCRVRDPSGLVTLWTSRASQAPKFVLDLSQLDS--GNDSLRAT 298
Cdd:cd06377  113 SQNPFHLQLDLQSSLESLEDVLVSLLQANSWEDVSLLLCQPWDPTSFLLLWQNNSQFHLGTVLNLSVLDEsdLQRSLQQH 192

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 299 LALLGTlegggtPVSAAVLLGCSTAHAHEVLEAAPPG----PQWLLGTPLPAEALPKTGLPPGVLVLGETGQPSLEAAVH 374
Cdd:cd06377  193 LESLKD------PSPAIVMFGCDAARARRVFEAAPPGglpeFHWLLGTPLPVEELPTEGLPPGLLALGETSRPSLEAYVQ 266

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 375 DMVELVARALSSMALMHPERALLPAAVNCEDLKTGGSESTARTLARFLSNTSFQGRTGAVWVAGSSQVHVSRHFKVWSLR 454
Cdd:cd06377  267 DAVELVARALSSAALVHPELALLPATVNCNDLKTGGSESSGQYLSRFLANTSFQGRTGTVWVTGSSQVHSERHFKVWSLR 346

                        330       340
                 ....*....|....*....|....*..
gi 568966813 455 RDPLGAPAWATVGSWQDGQLDFQPGAA 481
Cdd:cd06377  347 RDPLGAPTWATVGSWQDGKLDMEPGAW 373

Ligand-gated ion channel; This family includes the four transmembrane regions of the ionotropic glutamate receptors and NMDA receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813  654 HWSMWVGVFAALHLTALFLTLYEWRSPYGLTPRGRNRGTVFSYSSALNLCYAILFGRTvSSKTPKCPTGRFLMNLWAIFC 733
Cdd:pfam00060   1 SLEVWLGILVAFLIVGVVLFLLERFSPYEWRGPLETEENRFTLSNSLWFSFGALVQQG-HRENPRSLSGRIVVGVWWFFA 79

                          90       100
                  ....*....|....*....|....*....
gi 568966813  734 LLVLSSYTANLAAVMVGDKTFEELSGIHD 762
Cdd:pfam00060  80 LILLSSYTANLAAFLTVERMQSPIQSLED 108

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 141 TPSPRLPHNLSLELVAVASPTRDPASLARGLCQVLAPPGVVASITFPEARPELRLLQFLAAATETPVLSVLRREVRAPLG 220
Cdd:cd06377   33 LPTGLLPYNLSLEVVVAAPWARDPASLTRSLCHSVVVQGVAALLAFPQSRGELLQLDFLSAALEIPVVSILRREFPRPLR 112

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 221 APTPFHLQLDWASPLETILDVLVSLVRAHAWEDIALVLCRVRDPSGLVTLWTSRASQAPKFVLDLSQLDS--GNDSLRAT 298
Cdd:cd06377  113 SQNPFHLQLDLQSSLESLEDVLVSLLQANSWEDVSLLLCQPWDPTSFLLLWQNNSQFHLGTVLNLSVLDEsdLQRSLQQH 192

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 299 LALLGTlegggtPVSAAVLLGCSTAHAHEVLEAAPPG----PQWLLGTPLPAEALPKTGLPPGVLVLGETGQPSLEAAVH 374
Cdd:cd06377  193 LESLKD------PSPAIVMFGCDAARARRVFEAAPPGglpeFHWLLGTPLPVEELPTEGLPPGLLALGETSRPSLEAYVQ 266

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 375 DMVELVARALSSMALMHPERALLPAAVNCEDLKTGGSESTARTLARFLSNTSFQGRTGAVWVAGSSQVHVSRHFKVWSLR 454
Cdd:cd06377  267 DAVELVARALSSAALVHPELALLPATVNCNDLKTGGSESSGQYLSRFLANTSFQGRTGTVWVTGSSQVHSERHFKVWSLR 346

                        330       340
                 ....*....|....*....|....*..
gi 568966813 455 RDPLGAPAWATVGSWQDGQLDFQPGAA 481
Cdd:cd06377  347 RDPLGAPTWATVGSWQDGKLDMEPGAW 373

Ligand-gated ion channel; This family includes the four transmembrane regions of the ionotropic glutamate receptors and NMDA receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813  654 HWSMWVGVFAALHLTALFLTLYEWRSPYGLTPRGRNRGTVFSYSSALNLCYAILFGRTvSSKTPKCPTGRFLMNLWAIFC 733
Cdd:pfam00060   1 SLEVWLGILVAFLIVGVVLFLLERFSPYEWRGPLETEENRFTLSNSLWFSFGALVQQG-HRENPRSLSGRIVVGVWWFFA 79

                          90       100
                  ....*....|....*....|....*....
gi 568966813  734 LLVLSSYTANLAAVMVGDKTFEELSGIHD 762
Cdd:pfam00060  80 LILLSSYTANLAAFLTVERMQSPIQSLED 108

Ligated ion channel L-glutamate- and glycine-binding site; This region, sometimes called the S1 domain, is the luminal domain just upstream of the first, M1, transmembrane region of transmembrane ion-channel proteins, and it binds L-glutamate and glycine. It is found in association with Lig_chan.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 568966813   551 TLRRCCYGYCIDLLERLAEDLAFDFELYIVGDGKYGA-LRDGRWTGLVGDLL 601
Cdd:smart00918  11 GGNDRFEGYCIDLLKELAKKLGFTYEIILVPDGKYGArLPNGSWNGMVGELV 62

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 141 TPSPRLPHNLSLELVAVASPTRDPASLARGLCQVLAPPGVVASITFPEARPELRLLQFLAAATETPVLSVLRREVRAPLG 220
Cdd:cd06377   33 LPTGLLPYNLSLEVVVAAPWARDPASLTRSLCHSVVVQGVAALLAFPQSRGELLQLDFLSAALEIPVVSILRREFPRPLR 112

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 221 APTPFHLQLDWASPLETILDVLVSLVRAHAWEDIALVLCRVRDPSGLVTLWTSRASQAPKFVLDLSQLDS--GNDSLRAT 298
Cdd:cd06377  113 SQNPFHLQLDLQSSLESLEDVLVSLLQANSWEDVSLLLCQPWDPTSFLLLWQNNSQFHLGTVLNLSVLDEsdLQRSLQQH 192

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 299 LALLGTlegggtPVSAAVLLGCSTAHAHEVLEAAPPG----PQWLLGTPLPAEALPKTGLPPGVLVLGETGQPSLEAAVH 374
Cdd:cd06377  193 LESLKD------PSPAIVMFGCDAARARRVFEAAPPGglpeFHWLLGTPLPVEELPTEGLPPGLLALGETSRPSLEAYVQ 266

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 375 DMVELVARALSSMALMHPERALLPAAVNCEDLKTGGSESTARTLARFLSNTSFQGRTGAVWVAGSSQVHVSRHFKVWSLR 454
Cdd:cd06377  267 DAVELVARALSSAALVHPELALLPATVNCNDLKTGGSESSGQYLSRFLANTSFQGRTGTVWVTGSSQVHSERHFKVWSLR 346

                        330       340
                 ....*....|....*....|....*..
gi 568966813 455 RDPLGAPAWATVGSWQDGQLDFQPGAA 481
Cdd:cd06377  347 RDPLGAPTWATVGSWQDGKLDMEPGAW 373

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 144 PRLPHNLSLELVAvaSPTRDPASLARGLCQVLAPPgVVASITFPEARPE---LRLLQFLAAATETPVLSVLRREVRAPlG 220
Cdd:cd06367   30 FTLPVQLRVELVT--MPEPDPKSIITRICDLLSDS-KVQGVVFSDDTDQeaiAQILDFIAAQTLTPVLGLHGRSSMIM-A 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 221 APTPFHLQLDWASPLETILDVLVSLVRAHAWEDIALVLCRVRDPSGLVTLWTSRASQA-----PKFVLDLSqLDSGNDSL 295
Cdd:cd06367  106 DKSEHSMFLQFGPPIEQQASVMLNIMEEYDWYIVSLVTTYFPGYQDFVNKLRSTIENSgweleEVLQLDMS-LDDGDSKL 184

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 296 RATLALLgtleggGTPVSAAVLLGCSTAHAHEVLEAAPP------GPQWLLGTPLPAEALPKTGLPPGVLVLGETGQPSL 369
Cdd:cd06367  185 QAQLKKL------QSPEARVILLYCTKEEATYVFEVAASvgltgyGYTWLVGSLVAGTDTVPAEFPTGLISLSYDEWYNL 258

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 370 EAAVHDMVELVARALSSMALMHpeRALLPAAVNCEDLKTGGsESTARTLARFLSNTSFQGRTGAVWVagsSQVHVSRHFK 449
Cdd:cd06367  259 PARIRDGVAIVATAASEMLSEH--EQIPDPPSSCVNNQEIR-KYTGPMLKRYLINVTFEGRDLSFSE---DGYQMHPKLV 332

                        330       340
                 ....*....|....*....|..
gi 568966813 450 VWSLRRDplgaPAWATVGSWQD 471
Cdd:cd06367  333 IILLNNE----RKWERVGKWKD 350

The ligand-binding domain of the NR2 subunit of ionotropic NMDA (N-methyl-D-aspartate) glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily; This group contains the ligand-binding domain of the NR2 subunit of NMDA receptor family. The ionotropic N-methyl-d-asparate (NMDA) subtype of glutamate receptors serves critical functions in neuronal development, functioning, and degeneration in the mammalian central nervous system. The functional NMDA receptor is a heterotetramer composed of two NR1 and two NR2 (A, B, C, and D) or of NR3 (A and B) subunits. The receptor controls a cation channel that is highly permeable to monovalent ions and calcium and exhibits voltage-dependent inhibition by magnesium. Dual agonists, glutamate and glycine, are required for efficient activation of the NMDA receptor. Among NMDA receptor subtypes, the NR2B subunit containing receptors appear particularly important for pain perception; thus NR2B-selective antagonists may be useful in the treatment of chronic pain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 497 LRVVTLVEHPFVFTRESDedgqcPAGQLCLDPGTNDSARLDALFTALENGsvPRTLRRCCYGYCIDLLERLAEDLAFDFE 576
Cdd:cd13718    4 LKIVTLEEAPFVIVEPVD-----PLTGTCMRNTVPCRKQLNHENSTDADE--NRYVKKCCKGFCIDILKKLAKDVGFTYD 76

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 568966813 577 LYIVGDGKYGALRDGRWTGLVGDLLAGRAHMAVTSFSINSARSQVVDFTSPFFSTSLGIMVRTRDTAS 644
Cdd:cd13718   77 LYLVTNGKHGKKINGVWNGMIGEVVYKRADMAVGSLTINEERSEVVDFSVPFVETGISVMVARSNQVS 144

Ligand-gated ion channel; This family includes the four transmembrane regions of the ionotropic glutamate receptors and NMDA receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813  654 HWSMWVGVFAALHLTALFLTLYEWRSPYGLTPRGRNRGTVFSYSSALNLCYAILFGRTvSSKTPKCPTGRFLMNLWAIFC 733
Cdd:pfam00060   1 SLEVWLGILVAFLIVGVVLFLLERFSPYEWRGPLETEENRFTLSNSLWFSFGALVQQG-HRENPRSLSGRIVVGVWWFFA 79

                          90       100
                  ....*....|....*....|....*....
gi 568966813  734 LLVLSSYTANLAAVMVGDKTFEELSGIHD 762
Cdd:pfam00060  80 LILLSSYTANLAAFLTVERMQSPIQSLED 108

The ligand-binding domain of putative ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily; This group contains glutamate receptor domain GluR. These domains are found in the GluR proteins that have been shown to function as L-glutamate activated potassium channels, also known ionotropic glutamate receptors or iGluRs. In addition to two ligand binding core domains, iGluRs typically have a channel-like domain inserted in the middle of the GluR-like domain. Animal iGluRs mediate the ion flux in the synapses of the CNS and can be subdivided into several classes depending on the neurotransmitter specificity and ion conductance properties. Their plant homologs have been shown to function in light signal transduction and calcium homeostasis. The GluR proteins belong to the PBPII superfamily of periplasmic binding proteins that differ in size and ligand specificity, but have similar tertiary structures consisting of two globular subdomains connected by a flexible hinge. They have been shown to bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 494 RPKLRVVTLVEHPFVFTRESDEDGQcpagqlcldpgtndsarldalftalengsvprtlrrccYGYCIDLLERLAEDLAF 573
Cdd:cd13717    1 RRVYRIGTVESPPFVYRDRDGSPIW--------------------------------------EGYCIDLIEEISEILNF 42

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 574 DFELYIVGDGKYGALRD-GRWTGLVGDLLAGRAHMAVTSFSINSARSQVVDFTSPFF-STSLGIMVRTRDTASPIGAFMW 651
Cdd:cd13717   43 DYEIVEPEDGKFGTMDEnGEWNGLIGDLVRKEADIALAALSVMAEREEVVDFTVPYYdLVGITILMKKPERPTSLFKFLT 122

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 652 PLHWSMWvgvfaalhltaLFLTLYE--WRSPYGLTPRGrnrgtvfsyssalnlcyailfgrtvSSKTPKCPTGRFLMNLW 729
Cdd:cd13717  123 VLELEVW-----------REFTLKEslWFCLTSLTPQG-------------------------GGEAPKNLSGRLLVATW 166

                        250       260       270
                 ....*....|....*....|....*....|....*
gi 568966813 730 AIFCLLVLSSYTANLAAVMVGDK------TFEELS 758
Cdd:cd13717  167 WLFVFIIIASYTANLAAFLTVSRlqtpveSLDDLA 201

The ligand-binding domain of ionotropic glutamate receptor family, a member of the periplasmic binding protein type II superfamily; This subfamily represents the ligand binding of ionotropic glutamate receptors. iGluRs are heterotetrameric ion channels that comprises of three functionally distinct subtypes based on their pharmacology and structural similarities: AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid), NMDA (N-methyl-D-aspartate), and kainate receptors. All three types of channels are also activated by the physiological neurotransmitter, glutamate. iGluRs are concentrated at postsynaptic sites, where they exert a variety of different functions. While this ligand-binding domain of iGluRs is structurally homologous to the periplasmic binding fold type II superfamily, the N-terminal leucine/isoleucine/valine-binding protein (LIVBP)-like domain belongs to the periplasmic-binding fold type I.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 497 LRVVTLVEHPFVFTRESDEDGqcpagqlcldpgtndsarldalftalengsvprTLRRCCYGYCIDLLERLAEDLAFDFE 576
Cdd:cd00998    3 LKVVVPLEPPFVMFVTGSNAV---------------------------------TGNGRFEGYCIDLLKELSQSLGFTYE 49

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568966813 577 LYIVGDGKYGALRDGRWTGLVGDLLAGRAHMAVTSFSINSARSQVVDFTSPFFSTSLGIMVRTR 640
Cdd:cd00998   50 YYLVPDGKFGAPVNGSWNGMVGEVVRGEADLAVGPITITSERSVVIDFTQPFMTSGIGIMIPIR 113

Kainate receptor of the type 2 periplasmic-binding fold superfamily; This group contains glutamate receptor domain GluR. These domains are found in the GluR proteins that have been shown to function as L-glutamate activated potassium channels, also known ionotropic glutamate receptors or iGluRs. In addition to two ligand binding core domains, iGluRs typically have a channel-like domain inserted in the middle of the GluR-like domain. Animal iGluRs mediate the ion flux in the synapses of the CNS and can be subdivided into several classes depending on the neurotransmitter specificity and ion conductance properties. Their plant homologs have been shown to function in light signal transduction and calcium homeostasis. The GluR proteins belong to the PBPII superfamily of periplasmic binding proteins that differ in size and ligand specificity, but have similar tertiary structures consisting of two globular subdomains connected by a flexible hinge. They have been shown to bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 497 LRVVTLVEHPFVFTRESDE--DGqcpagqlcldpgtNDsarldaLFtalengsvprtlrrccYGYCIDLLERLAEDLAFD 574
Cdd:cd13714    4 LIVTTILEEPYVMLKESAKplTG-------------ND------RF----------------EGFCIDLLKELAKILGFN 48

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568966813 575 FELYIVGDGKYGALRD--GRWTGLVGDLLAGRAHMAVTSFSINSARSQVVDFTSPFFstSLGI 635
Cdd:cd13714   49 YTIRLVPDGKYGSYDPetGEWNGMVRELIDGRADLAVADLTITYERESVVDFTKPFM--NLGI 109

The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtype GluR1 of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily; This group contains the ligand-binding domain of the AMPA receptor subunit GluR1, a member of non-NMDA (N-methyl-D-aspartate) type iGluRs which are ligand-gated ion channels that mediate excitatory synaptic transmission in the central nervous system. While this ligand-binding domain is structurally homologous to the periplasmic-binding fold type II superfamily, the N-terminal domain of AMPA receptors belongs to the periplasmic-binding fold type I. The AMPA receptors are the most commonly found receptor in the nervous system and sensitive to the artificial glutamate analog, AMPA. They consist of four types of subunits (GluR1, GluR2, GluR3, and GluR4) which combine to form a tetramer and play an important role in mediating the rapid excitatory synaptic current.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 558 GYCIDLLERLAEDLAFDFELYIVGDGKYGAlRDGR---WTGLVGDLLAGRAHMAVTSFSINSARSQVVDFTSPFFstSLG 634
Cdd:cd13729   32 GYCVELAAEIAKHVGYSYKLEIVSDGKYGA-RDPEtkmWNGMVGELVYGKADVAVAPLTITLVREEVIDFSKPFM--SLG 108

                         90
                 ....*....|..
gi 568966813 635 IMVRTRDTASPI 646
Cdd:cd13729  109 ISIMIKKPTSPI 120

The ligand-binding domain of the delta family of ionotropic glutamate receptors, a member of the type 2 periplasmic-binding fold protein superfamily; This subfamily represents the ligand-binding domain of an orphan family of delta receptors, GluRdelta1 and GluRdelta2. While this ligand-binding domain is structurally homologous to the periplasmic-binding fold type II superfamily, the N-terminal domain of iGluRs belongs to the periplasmic-binding fold type I. Although the delta receptors are members of the ionotropic glutamate receptor family, they cannot be activated by AMPA, kainate, NMDA, glutamate, or any other ligands. Phylogenetical analysis shows that both GluRdelta1 and GluRalpha2 are more homologous to non-NMDA receptors. GluRdelta2 was shown to function as an AMPA-like receptor by mutation analysis. Moreover, targeted disruption of GluRdelta2 gene caused motor coordination impairment, Purkinje cell maturation, and long-term depression of synaptic transmission. It has been suggested that GluRdelta2 is the receptor for cerebellin 1, a glycoprotein of the Clq, and the tumor necrosis factor family which is secreted from cerebellar granule cells. Furthermore, recent studies have shown that the orphan GluRdelta1 plays an essential role in high-frequency hearing and ionic homeostasis in the basal cochlea and that the locus encoding GluRdelta1 may be involved in congenial or acquired high-frequency hearing loss in humans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 497 LRVVTLVEHPFVFTRESdedgqcPAGQlcldpgtndsarldalftalengsvPRTLRrccyGYCIDLLERLAEDLAFDFE 576
Cdd:cd13716    4 LRVVTVLEEPFVMVSEN------VLGK-------------------------PKKYQ----GFSIDVLDALANYLGFKYE 48

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568966813 577 LYIVGDGKYGA-LRDGRWTGLVGDLLAGRAHMAVTSFSINSARSQVVDFTSPFFSTSLGIMVRtrdTASPIGAF 649
Cdd:cd13716   49 IYVAPDHKYGSqQEDGTWNGLIGELVFKRADIGISALTITPERENVVDFTTRYMDYSVGVLLR---KAESIQSL 119

GluR6 subtype of kainate receptor, type 2 periplasmic-binding fold superfamily; This group contains glutamate receptor domain GluR. These domains are found in the GluR proteins that have been shown to function as L-glutamate activated potassium channels, also known ionotropic glutamate receptors or iGluRs. In addition to two ligand binding core domains, iGluRs typically have a channel-like domain inserted in the middle of the GluR-like domain. Animal iGluRs mediate the ion flux in the synapses of the CNS and can be subdivided into several classes depending on the neurotransmitter specificity and ion conductance properties. Their plant homologs have been shown to function in light signal transduction and calcium homeostasis. The GluR proteins belong to the PBPII superfamily of periplasmic binding proteins that differ in size and ligand specificity, but have similar tertiary structures consisting of two globular subdomains connected by a flexible hinge. They have been shown to bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 497 LRVVTLVEHPFVFTRESDEDgqcpagqlcldpgTNDSARLDalftalengsvprtlrrccyGYCIDLLERLAEDLAFDFE 576
Cdd:cd13721    4 LIVTTILEEPYVLFKKSDKP-------------LYGNDRFE--------------------GYCIDLLRELSTILGFTYE 50

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568966813 577 LYIVGDGKYGALRD--GRWTGLVGDLLAGRAHMAVTSFSINSARSQVVDFTSPFFSTSLGIMVR 638
Cdd:cd13721   51 IRLVEDGKYGAQDDvnGQWNGMVRELIDHKADLAVAPLAITYVREKVIDFSKPFMTLGISILYR 114

The ligand-binding domain of an orphan ionotropic glutamate receptor delta-1, a member of the type 2 periplasmic-binding fold protein superfamily; This group contains the ligand-binding domain of the delta1 receptor of an orphan glutamate receptor family. While this ligand-binding domain is structurally homologous to the periplasmic-binding fold type II superfamily, the N-terminal domain of delta receptors belongs to the periplasmic-binding fold type I. Although the delta receptors are a member of the ionotropic glutamate receptor family, they cannot be activated by AMPA, kainate, NMDA, glutamate, or any other ligands. Phylogenetical analysis shows that both GluRdelta1 and GluRdelta2 are more homologous to non-NMDA receptors. GluRdelta2 was shown to function as an AMPA-like receptor by mutation analysis. Moreover, targeted disruption of GluRdelta2 gene caused motor coordination impairment, Purkinje cell maturation, and long-term depression of synaptic transmission. It has been suggested that GluRdelta2 is the receptor for cerebellin 1, a glycoprotein of the Clq, and the tumor necrosis factor family which is secreted from cerebellar granule cells. Furthermore, recent studies have shown that the orphan GluRdelta1 plays an essential role in high-frequency hearing and ionic homeostasis in the basal cochlea and that the locus encoding GluRdelta1 may be involved in congenial or acquired high-frequency hearing loss in humans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 497 LRVVTLVEHPFVFTRESdedgqcPAGQlcldpgtndsarldalftalengsvPRTLRrccyGYCIDLLERLAEDLAFDFE 576
Cdd:cd13730    4 LKVVTVLEEPFVMVAEN------ILGQ-------------------------PKRYK----GFSIDVLDALAKALGFKYE 48

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568966813 577 LYIVGDGKYGA-LRDGRWTGLVGDLLAGRAHMAVTSFSINSARSQVVDFTSPFFSTSLGIMVR 638
Cdd:cd13730   49 IYQAPDGKYGHqLHNTSWNGMIGELISKRADLAISAITITPERESVVDFSKRYMDYSVGILIK 111

The ligand-binding domain of an orphan ionotropic glutamate receptor delta-2, a member of the type 2 periplasmic-binding fold protein superfamily; This group contains the ligand-binding domain of the delta-2 receptor of an orphan glutamate receptor family. While this ligand-binding domain is structurally homologous to the periplasmic-binding fold type II superfamily, the N-terminal domain of delta receptors belongs to the periplasmic-binding fold type I. Although the delta receptors are a member of the ionotropic glutamate receptor family, they cannot be activated by AMPA, kainate, NMDA, glutamate, or any other ligands. Phylogenetical analysis shows that both GluRdelta1 and GluRalpha2 are more homologous to non-NMDA receptors. GluRdelta2 was shown to function as an AMPA-like receptor by mutation analysis. Moreover, targeted disruption of GluRdelta2 gene caused motor coordination impairment, Purkinje cell maturation, and long-term depression of synaptic transmission. It has been suggested that GluRdelta2 is the receptor for cerebellin 1, a glycoprotein of the Clq, and the tumor necrosis factor family which is secreted from cerebellar granule cells. Furthermore, recent studies have shown that the orphan GluRdelta1 plays an essential role in high-frequency hearing and ionic homeostasis in the basal cochlea and that the locus encoding GluRdelta1 may be involved in congenial or acquired high-frequency hearing loss in humans.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 497 LRVVTLVEHPFVFTRESdedgqcPAGQlcldpgtndsarldalftalengsvPRTLRrccyGYCIDLLERLAEDLAFDFE 576
Cdd:cd13731    4 LRVVTVLEEPFVMVSEN------VLGK-------------------------PKKYQ----GFSIDVLDALSNYLGFNYE 48

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568966813 577 LYIVGDGKYGALR-DGRWTGLVGDLLAGRAHMAVTSFSINSARSQVVDFTSPFFSTSLGIMVR 638
Cdd:cd13731   49 IYVAPDHKYGSPQeDGTWNGLVGELVFKRADIGISALTITPDRENVVDFTTRYMDYSVGVLLR 111

The ligand-binding domain of the AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid) subtype GluR3 of ionotropic glutamate receptors, a member of the type 2 periplasmic binding fold protein superfamily; This group contains the ligand-binding domain of the AMPA receptor subunit GluR3, a member of non-NMDA (N-methyl-D-aspartate) type iGluRs which are ligand-gated ion channels that mediate excitatory synaptic transmission in the central nervous system. While this ligand-binding domain is structurally homologous to the periplasmic-binding fold type II superfamily, the N-terminal domain of AMPA receptors belongs to the periplasmic-binding fold type I. The AMPA receptors are the most commonly found receptor in the nervous system and sensitive to the artificial glutamate analog, AMPA. They consist of four types of subunits (GluR1, GluR2, GluR3, and GluR4) which combine to form a tetramer and play an important role in mediating the rapid excitatory synaptic current

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 558 GYCIDLLERLAEDLAFDFELYIVGDGKYGAlRDGR---WTGLVGDLLAGRAHMAVTSFSINSARSQVVDFTSPFFSTSLG 634
Cdd:cd13728   32 GYCVDLAYEIAKHVRIKYKLSIVGDGKYGA-RDPEtkiWNGMVGELVYGRADIAVAPLTITLVREEVIDFSKPFMSLGIS 110

                 ....
gi 568966813 635 IMVR 638
Cdd:cd13728  111 IMIK 114

Bacterial extracellular solute-binding proteins, family 3; This is a sensor domain found in solute-binding protein family 3 members from Gram-positive bacteria, Gram-negative bacteria and archaea. It can also be found in the N-terminal of the membrane-bound lytic murein transglycosylase F (MltF) protein. This domain recognizes Nicotinate, quidalnate, pyridine-2,5-dicarboxylate and salicylate (Matilla et. al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813  558 GYCIDLLERLAEDLAFDFELyivgdgkygalRDGRWTGLVGDLLAGRAHMAVTSFSINSARSQVVDFTSPFFSTSLGIMV 637
Cdd:pfam00497  23 GFDVDLAKAIAKRLGVKVEF-----------VPVSWDGLIPALQSGKVDLIIAGMTITPERAKQVDFSDPYYYSGQVILV 91

                          90
                  ....*....|..
gi 568966813  638 RTRDTASPIGAF 649
Cdd:pfam00497  92 RKKDSSKSIKSL 103

ABC-type amino acid transport/signal transduction system, periplasmic component/domain [Amino acid transport and metabolism, Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 558 GYCIDLLERLAEDLAFDFELYIVgdgkygalrdgRWTGLVGDLLAGRAHMAVTSFSINSARSQVVDFTSPFFSTSLGIMV 637
Cdd:COG0834   23 GFDVDLARAIAKRLGLKVEFVPV-----------PWDRLIPALQSGKVDLIIAGMTITPEREKQVDFSDPYYTSGQVLLV 91

                 .
gi 568966813 638 R 638
Cdd:COG0834   92 R 92

Glutamine binding domain of ABC-type transporter; the type 2 periplasmic binding protein fold; This periplasmic substrate-binding component serves as an initial receptor in the ABC transport of glutamine in bacteria and eukaryota. GlnH belongs to the type 2 periplasmic-binding fold protein (PBP2) superfamily, whose members are involved in chemotaxis and uptake of nutrients and other small molecules from the extracellular space as a primary receptor. PBP2 typically comprises of two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two receptor cytoplasmically-located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 558 GYCIDLLERLAEDLAFDFELyivgdgkygalRDGRWTGLVGDLLAGRAHMAVTSFSINSARSQVVDFTSPFFSTSLGIMV 637
Cdd:cd00994   23 GFDIDLWEAIAKEAGFKYEL-----------QPMDFKGIIPALQTGRIDIAIAGITITEERKKVVDFSDPYYDSGLAVMV 91

                 ....*.
gi 568966813 638 RTRDTA 643
Cdd:cd00994   92 KADNNS 97

Substrate-binding domain of putative amino acid-binding protein; the type 2 periplasmic-binding protein fold; This putative amino acid-binding protein belongs to the type 2 periplasmic-binding fold protein (PBP2) superfamily, whose members are involved in chemotaxis and uptake of nutrients and other small molecules from the extracellular space as a primary receptor. PBP2 typically comprises of two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two receptor cytoplasmically-located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 538 ALFTALENGSVprtlrrccYGYCIDLLERLAEDLAFDFElYIvgdgkygalrDGRWTGLVGDLLAGRAHMAVTSFSINSA 617
Cdd:cd13625   16 APFEFVENGKI--------VGFDRDLLDEMAKKLGVKVE-QQ----------DLPWSGILPGLLAGKFDMVATSVTITKE 76

                         90       100
                 ....*....|....*....|....*
gi 568966813 618 RSQVVDFTSPFFSTSLGIMVRTRDT 642
Cdd:cd13625   77 RAKRFAFTLPIAEATAALLKRAGDD 101

Bacterial GluR0 ligand-binding domain; the type 2 periplasmic binding protein fold; Glutamate receptor domain GluR0. These domains are found in the GluR0 proteins that have been shown to function as prokaryotic L-glutamate activated potassium channels, also known ionotropic glutamate receptors or iGluRs. In addition to two ligand binding core domains, iGluRs typically have a channel-like domain inserted in the middle of the GluR-like domain. The GluR0 proteins belong to the PBP2 superfamily of periplasmic binding proteins that differ in size and ligand specificity, but have similar tertiary structures consisting of two globular subdomains connected by a flexible hinge. They have been shown to bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 558 GYCIDLLERLAEDLAFDFELYivgdgkygalrdgrWTGLVGDLLA----GRAHMAVTSFSINSARSQVVDFTSPFFSTSL 633
Cdd:cd00997   25 GFSIDLWRAIAERLGWETEYV--------------RVDSVSALLAavaeGEADIAIAAISITAEREAEFDFSQPIFESGL 90

                 ....*
gi 568966813 634 GIMVR 638
Cdd:cd00997   91 QILVP 95

The periplasmic sensor domain of histidine kinase receptors; the type 2 periplasmic binding fold protein; This subfamily includes the periplasmic sensor domain of the histidine kinase receptors (HisK) which are elements of the two-component signal transduction systems commonly found in bacteria and lower eukaryotes. Typically, the two-component system consists of a membrane-spanning histidine kinase sensor and a cytoplasmic response regulator. The two-component systems serve as a stimulus-response coupling mechanism to enable microorganisms to sense and respond to changes in environmental conditions. Extracellular stimuli such as small molecule ligands and ions are detected by the N-terminal periplasmic sensing domain of the sensor kinase receptor, which regulate the catalytic activity of the cytoplasmic kinase domain and promote ATP-dependent autophosphorylation of a conserved histidine residue. The phosphate is then transferred to a conserved aspartate in the response regulator through a phospho-transfer mechanism, and the activity of the response regulator is in turn regulated. The sensor domain belongs to the type 2 periplasmic-binding fold protein (PBP2) superfamily, whose members are involved in chemotaxis and uptake of nutrients and other small molecules from the extracellular space through their function as an initial high-affinity binding component. PBP2 typically comprises of two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568966813 557 YGYCIDLLERLAEDLAFDFELYIvgdgkygalrdGRWTGLVGDLLAGRAHMaVTSFSINSARSQVVDFTSPFFSTSLGIM 636
Cdd:cd13704   25 TGFNVDLLRAIAEEMGLKVEIRL-----------GPWSEVLQALENGEIDV-LIGMAYSEERAKLFDFSDPYLEVSVSIF 92

                 ...
gi 568966813 637 VRT 639
Cdd:cd13704   93 VRK 95

Substrate binding domain of ABC-type histidine/lysine/arginine/ornithine transporter-like; the type 2 periplasmic-binding protein fold; This group includes uncharacterized periplasmic substrate-binding protein similar to HisJ and LAO proteins which serve as initial receptors in the ABC transport of histidine-, arginine, and lysine-arginine-ornithine amino acids. This group belongs to the type 2 periplasmic-binding fold protein (PBP2) superfamily, whose members are involved in chemotaxis and uptake of nutrients and other small molecules from the extracellular space as a primary receptor. PBP2 typically comprises of two globular subdomains connected by a flexible hinge and bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two receptor cytoplasmically-located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 568966813 593 WTGLVGDLLAGRAHMAVTSFSINSARSQVVDFTSPFFSTSLGIMV 637
Cdd:cd13702   50 WDGIIPALQAKKFDAIIASMSITPERKKQVDFTDPYYTNPLVFVA 94