Regulator of G-protein signaling 12 Phosphotyrosine-binding (PTB) PH-like fold; RGS12 functions as a GTPase-activating protein and a transcriptional repressor. It is thought to play a role in tumorigenesis. RGS12 specifically interacts with guanine nucleotide-binding protein G(i), alpha-1 subunit and guanine nucleotide-binding protein G(k) subunit alpha. RGS proteins are multi-functional, GTPase-accelerating proteins that promote GTP hydrolysis by the alpha subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signalling pathways. Upon activation by GPCRs, heterotrimeric G proteins exchange GDP for GTP, are released from the receptor, and dissociate into free, active GTP-bound alpha subunit and beta-gamma dimer, both of which activate downstream effectors. The response is terminated upon GTP hydrolysis by the alpha subunit, which can then bind the beta-gamma dimer and the receptor. RGS proteins markedly reduce the lifespan of GTP-bound alpha subunits by stabilizing the G protein transition state. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576 228 VAMIVGYLGSIELPSTSSNlESDSLQAIRGCMRRLRAEQKIHSLVTMKIMHDCVQLSTDKAGVVAEYPAEKLAFSAVCPD 307
Cdd:cd13162     1 VRMIVGYLGSIELPSTSSN-ESDSLQAIRGCVRRLRAEQKIHSLVLMKVMHDSVQLCDDRGGVLATYPAEKLAFSGVCPD 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462598576 308 DRRFFGLVTMQTNDDGSLAQEEEGALRTSCHVFMVDPDLFNHKIHQGIARRF 359
Cdd:cd13162    80 DRRFFGLVTMQSTDDQSEAQESEGSLRTSCHVFMVDPELFEHKIHQGIARRF 131

PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS12, and related domains. RGS12 downregulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. The RGS12 PDZ domain can bind selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the CXCR2 IL-8 receptor, and the alternative 3' exon form of RGS12. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462598576  21 RSVEVARGRAGYGFTLSGQAPCVLSCVMRGSPADFVGLRAGDQILAVNEINVKKASHEDVVKLIGKCSGVLHMVIA 96
Cdd:cd06710     1 RTVEIARGRAGYGFTISGQAPCVLSCVVRGSPADVAGLKAGDQILAVNGINVSKASHEDVVKLIGKCTGVLRLVIA 76

Regulator of G-protein signaling 12 Phosphotyrosine-binding (PTB) PH-like fold; RGS12 functions as a GTPase-activating protein and a transcriptional repressor. It is thought to play a role in tumorigenesis. RGS12 specifically interacts with guanine nucleotide-binding protein G(i), alpha-1 subunit and guanine nucleotide-binding protein G(k) subunit alpha. RGS proteins are multi-functional, GTPase-accelerating proteins that promote GTP hydrolysis by the alpha subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signalling pathways. Upon activation by GPCRs, heterotrimeric G proteins exchange GDP for GTP, are released from the receptor, and dissociate into free, active GTP-bound alpha subunit and beta-gamma dimer, both of which activate downstream effectors. The response is terminated upon GTP hydrolysis by the alpha subunit, which can then bind the beta-gamma dimer and the receptor. RGS proteins markedly reduce the lifespan of GTP-bound alpha subunits by stabilizing the G protein transition state. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576 228 VAMIVGYLGSIELPSTSSNlESDSLQAIRGCMRRLRAEQKIHSLVTMKIMHDCVQLSTDKAGVVAEYPAEKLAFSAVCPD 307
Cdd:cd13162     1 VRMIVGYLGSIELPSTSSN-ESDSLQAIRGCVRRLRAEQKIHSLVLMKVMHDSVQLCDDRGGVLATYPAEKLAFSGVCPD 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462598576 308 DRRFFGLVTMQTNDDGSLAQEEEGALRTSCHVFMVDPDLFNHKIHQGIARRF 359
Cdd:cd13162    80 DRRFFGLVTMQSTDDQSEAQESEGSLRTSCHVFMVDPELFEHKIHQGIARRF 131

PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS12, and related domains. RGS12 downregulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. The RGS12 PDZ domain can bind selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the CXCR2 IL-8 receptor, and the alternative 3' exon form of RGS12. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462598576  21 RSVEVARGRAGYGFTLSGQAPCVLSCVMRGSPADFVGLRAGDQILAVNEINVKKASHEDVVKLIGKCSGVLHMVIA 96
Cdd:cd06710     1 RTVEIARGRAGYGFTISGQAPCVLSCVVRGSPADVAGLKAGDQILAVNGINVSKASHEDVVKLIGKCTGVLRLVIA 76

Regulator of G protein signalling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576  715 SFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHvpAHDKKELSYRAREIFSKFLCSKATTPVNIDSQ--AQLAD 792
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKK--AEDDEERIAKAREIYDKFLSPNAPKEVNLDSDlrEKIEE 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 2462598576  793 DVLRA-PHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQEC 831
Cdd:smart00315  79 NLESEePPPDLFDEAQREVYELLEKDSFPRFLESDYYLRF 118

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576   19 RVRSVEVARGRAGYGFTLSG----QAPCVLSCVMRGSPADFVGLRAGDQILAVNEINVKKASHEDVVKLIGKCSGVLHMV 94
Cdd:smart00228   1 EPRLVELEKGGGGLGFSLVGgkdeGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLT 80

                   .
gi 2462598576   95 I 95
Cdd:smart00228  81 V 81

Unstructured region of RGS12; RGS12_us1 is a region of Regulator of G-protein signalling 12 proteins that is natively unstructured and lies N-terminal to other such regions in UniProt:E1BPP4. It is very glycine-rich, and the function is not known.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 2462598576 836 VEGRALPDSQQVPSSPASKHSLGSDHSSVSTPKKVS 871
Cdd:pfam16613   1 VEGRPLPDPQQVPSSPTSKHSVGSDRSNISTPKKLS 36

Phosphotyrosine interaction domain (PTB/PID);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576 232 VGYLGSIELPSTSSNLESDSLQAIRGCMRRLRAEQKIHSL-----------VTMKIMHDCVQLSTDKAG-VVAEYPAEKL 299
Cdd:pfam00640   3 VRYLGSVEVPEERAPDKNTRMQQAREAIRRVKAAKINKIRglsgetgpgtkVDLFISTDGLKLLNPDTQeLIHDHPLVSI 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2462598576 300 AFSAV-CPDDRRFFGLVTmqtnddgslaqeEEGAL-RTSCHVFMVD 343
Cdd:pfam00640  83 SFCADgDPDLMRYFAYIA------------RDKATnKFACHVFESE 116

Regulator of G-protein signaling 12 Phosphotyrosine-binding (PTB) PH-like fold; RGS12 functions as a GTPase-activating protein and a transcriptional repressor. It is thought to play a role in tumorigenesis. RGS12 specifically interacts with guanine nucleotide-binding protein G(i), alpha-1 subunit and guanine nucleotide-binding protein G(k) subunit alpha. RGS proteins are multi-functional, GTPase-accelerating proteins that promote GTP hydrolysis by the alpha subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off G protein-coupled receptor signalling pathways. Upon activation by GPCRs, heterotrimeric G proteins exchange GDP for GTP, are released from the receptor, and dissociate into free, active GTP-bound alpha subunit and beta-gamma dimer, both of which activate downstream effectors. The response is terminated upon GTP hydrolysis by the alpha subunit, which can then bind the beta-gamma dimer and the receptor. RGS proteins markedly reduce the lifespan of GTP-bound alpha subunits by stabilizing the G protein transition state. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576 228 VAMIVGYLGSIELPSTSSNlESDSLQAIRGCMRRLRAEQKIHSLVTMKIMHDCVQLSTDKAGVVAEYPAEKLAFSAVCPD 307
Cdd:cd13162     1 VRMIVGYLGSIELPSTSSN-ESDSLQAIRGCVRRLRAEQKIHSLVLMKVMHDSVQLCDDRGGVLATYPAEKLAFSGVCPD 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462598576 308 DRRFFGLVTMQTNDDGSLAQEEEGALRTSCHVFMVDPDLFNHKIHQGIARRF 359
Cdd:cd13162    80 DRRFFGLVTMQSTDDQSEAQESEGSLRTSCHVFMVDPELFEHKIHQGIARRF 131

Regulator of G protein signaling (RGS) domain found in the R12 subfamily of proteins; The RGS (Regulator of G-protein Signaling) domain is an essential part of the R12 (Neuronal RGS) protein subfamily of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play a critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of G-protein signaling, controlled by RGS domain, accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP that results in reassociation of the alpha-subunit with the beta-gamma-dimer and thereby inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The R12 RGS subfamily includes RGS10, RGS12 and RGS14 all of which are highly selective for G-alpha-i1 over G-alpha-q.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576 716 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPahDKKELSYRAREIFSKFLCSKATTPVNIDSQAQLADDVL 795
Cdd:cd08706     1 FERLLQDPVGVKYFTEFLKKEFSEENILFWQACEKFKKIP--DKKQLVQEAREIYDTFLSSKASSPVNIDSQAQLAEEML 78

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2462598576 796 RAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 830
Cdd:cd08706    79 EEPHPDMFQKQQLQIFNLMKFDSYSRFLKSPLYQQ 113

PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS12, and related domains. RGS12 downregulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. The RGS12 PDZ domain can bind selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the CXCR2 IL-8 receptor, and the alternative 3' exon form of RGS12. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462598576  21 RSVEVARGRAGYGFTLSGQAPCVLSCVMRGSPADFVGLRAGDQILAVNEINVKKASHEDVVKLIGKCSGVLHMVIA 96
Cdd:cd06710     1 RTVEIARGRAGYGFTISGQAPCVLSCVVRGSPADVAGLKAGDQILAVNGINVSKASHEDVVKLIGKCTGVLRLVIA 76

Regulator of G protein signaling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576 715 SFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHvpAHDKKELSYRAREIFSKFLCSKATTPVNIDSQ--AQLAD 792
Cdd:pfam00615   1 SFDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKK--ADPDEERLKKAKEIYNEFLAPGSPKEINLDSDlrEEIRE 78

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462598576 793 DVLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQEC 831
Cdd:pfam00615  79 NLEKEPTRDLFDEAQAEVYELMEKDSYPRFLKSPLYLRL 117

Regulator of G protein signaling (RGS) domain found in the R7 subfamily of proteins; The RGS (Regulator of G-protein Signaling) domain is an essential part of the R7 (Neuronal RGS) protein subfamily of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The R7 subfamily includes RGS6, RGS7, RGS9, and RGS11, all of which, in humans, are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes. In addition, R7 proteins were found to bind many other proteins outside of the G protein signaling pathways including: m-opioid receptor, beta-arrestin, alpha-actinin-2, NMDAR, polycystin, spinophilin, guanylyl cyclase, among others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576 708 RVASWAVSFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPAHDKKElsyRAREIFSKFLCSKATTPVNIDSQ 787
Cdd:cd08705     1 RVKRWGFSFSELLKDPVGREQFLKFLEKEFSGENLRFWEACQDLKYGPQSQVPE---KVQEIYQEFLAPGAPSWINIDSK 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2462598576 788 -AQLADDVLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 830
Cdd:cd08705    78 tMEITLKNLKDPHRYTFDAAQEHIYMLMKKDSYPRFLRSDIYKE 121

Regulator of G protein signaling (RGS) domain found in the RGS11 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS11 protein, a member of R7 subfamily of the RGS protein family. RGS is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. Other members of the R7 subfamily (Neuronal RGS) include: RGS6, RGS7, and RGS9, all of which are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes such as vision and motor control. Additionally they have been implicated in many neurological conditions such as anxiety, schizophrenia, and drug dependence. RGS11 is expressed exclusively in retinal ON-bipolar neurons in which it forms complexes with G-beta-5 and R7AP (RGS7 anchor protein ) and plays crucial roles in processing the light responses of retinal neurons.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576 708 RVASWAVSFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHvpaHDKKELSYRAREIFSKFLCSKATTPVNIDSQ 787
Cdd:cd08740     2 RVERWGFSFRELLNDPVGRKEFLDFLEKEFSAENLSFWEACEELRY---GEQSKIPELVDSVYQQFLAPGATRWVNIDSK 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2462598576 788 A-QLADDVLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQEcILAE 835
Cdd:cd08740    79 TmERTLEGLKQPHRYVLDDAQMHIYMLMKKDSYPRFLKSDLYKN-LLAE 126

Regulator of G protein signaling (RGS) domain found in the RGS6 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS6 protein, a member of R7 subfamily of the RGS protein family. RGS is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). Other members of the R7 subfamily (Neuronal RGS) include: RGS7, RGS9, and RGS11, all of which are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes such as vision and motor control. Additionally they have been implicated in many neurological conditions such as anxiety, schizophrenia, and drug dependence. RGS6 exists in multiple splice isoforms with identical RGS domains, but possess complete or incomplete GGL domains and distinct N- and C-terminal domains. RGS6 interacts with SCG10, a neuronal growth-associated protein and therefore regulates neuronal differentiation. Another RGS6-binding protein is DMAP1, a component of the Dnmt1 complex involved in repression of newly replicated genes. Mutations of a critical residue required for interaction of RGS6 protein with G proteins did not affect the ability of RGS6 to interact with both SCG10 and DMAP1. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576 707 RRVASWAVSFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPAHDkkeLSYRAREIFSKFLCSKATTPVNIDS 786
Cdd:cd08737     1 QRVKRWGFSLDEVLKDPVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQD---VAKRVEEIWQEFLAPGAPSAINLDS 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2462598576 787 QA-QLADDVLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQECIL 833
Cdd:cd08737    78 HSyEKTSQNVKDPGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDLLL 125

Regulator of G protein signaling (RGS) domain found in the RZ protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RZ subfamily of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of G-protein signaling is controlled by RGS domains, which accelerate GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, which results in reassociation of the alpha-subunit with the beta-gamma-dimer and inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The RZ subfamily of RGS proteins includes RGS17, RGS19 (former GAIP), RGS20, and its splice variant Ret-RGS.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576 712 WAVSFERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHvpAHDKKELSYRAREIFSKFLCSKATTPVNIDSQA-QL 790
Cdd:cd08718     1 WAQSFDKLMKSPAGRNVFREFLRTEYSEENMLFWLACEELKK--EANKHVIEEKARLIYEDYISILSPKEVSLDSRVrEV 78

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462598576 791 ADDVLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQ 829
Cdd:cd08718    79 INRNMLEPSPHTFDDAQLQIYTLMHRDSYPRFLNSAIYK 117

Regulator of G protein signaling (RGS) domain found in the RGS16 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS16 protein. RGS16 is a member of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS16 is a member of the R4/RGS subfamily and interacts with neuronal G-alpha0. RGS16 expression is upregulated by IL-17 of the NF-kappaB signaling pathway in autoimmune B cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576 716 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVpaHDKKELSYRAREIFSKFLCSKATTPVNIDSQA-QLADDV 794
Cdd:cd08710     1 FDLLLNSKNGVAAFHAFLKTEFSEENLEFWLACEEFKKI--RSATKLASRAHHIFEEFIRSEAPKEVNIDHETrELTRTN 78

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2462598576 795 LRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 830
Cdd:cd08710    79 LQAATTSCFDVAQGKTRTLMEKDSYPRFLKSPAYRD 114

Regulator of G protein signaling (RGS) domain found in the RGS3 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS3 protein. RGS3 is a member of the R4/RGS subfamily of the RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes. RGS3 induces apoptosis when overexpressed and is involved in cell migration through interaction with the Ephrin receptor. RGS3 exits as several splice isoforms and interacts with neuroligin, estrogen receptor-alpha, and 14-3-3 outside of the GPCR pathways.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576 717 ERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVpaHDKKELSYRAREIFSKFLCSKATTPVNIDSQA-QLADDVL 795
Cdd:cd08713     2 EKLLLHKYGLAVFRAFLQTEFSEENLEFWLACEEYKKI--KSQSKMASRAKKIFAEYIAIQSCKEVNLDSYTrEHTKENL 79

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2462598576 796 RAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 830
Cdd:cd08713    80 QNPTRGCFDLAQKRIYGLMEKDSYPRFLRSDLYQD 114

Regulator of G protein signaling (RGS) domain found in the RGS5 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS5 protein. RGS5 is member of the R4/RGS subfamily of the RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. Two splice isoforms of RGS5 has been found: RGS5L (long) which is expressed in smooth muscle cells (pericytes) and heart and RGS5S (short) which is highly expressed in the ciliary body of the eye, kidney, brain, spleen, skeletal muscle, and small intestine. Outside of the GPCR pathway, RGS5 interacts with the 14-3-3 protein.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576 716 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPAHDKkeLSYRAREIFSKFLCSKATTPVNIDsqaQLADDV- 794
Cdd:cd08717     1 LDKLLQNSYGLASFKSFLKSEFSEENIEFWEACEDYKKTKSPLK--MATKAKKIYEEFIQTEAPKEVNID---HFTKDVt 75

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462598576 795 ---LRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 830
Cdd:cd08717    76 mknLVEPSSSSFDLAQKRIFALMEKDSLPRFVRSEFYQE 114

Regulator of G protein signaling (RGS) domain found in the RGS1 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS1 protein. RGS1 is a member of the R4/RGS subfamily of the RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS 1 is expressed predominantly in hematopoietic compartments, including T and B lymphocytes, and may play a major role in chemokine-mediated homing of lymphocytes to secondary lymphoid organs. In addition, RGS1 interacts with calmodulin and 14-3-3 protein outside of the GPCR pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576 716 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNhvpAHDKKELSYRAREIFSKFLCSKATTPVNIDSQAQ--LADD 793
Cdd:cd08715     1 LEKLLASQTGQNVFRSFLKSEFSEENIEFWLACEDYK---KTESDLLPCKAEEIYKEFVQSDAAKQINIDFRTResTAKK 77

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2462598576 794 vLRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLY 828
Cdd:cd08715    78 -IKAPTPTCFDEAQKVIYILMERDSYPRFLKSDIY 111

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576  228 VAMIVGYLGSIELPstssnlESDSLQAIRGCMRRLRA----EQKIHSLVTMKIMHDCVQLSTDKAG-VVAEYPAEKLAFS 302
Cdd:smart00462   4 VSFRVKYLGSVEVP------EARGLQVVQEAIRKLRAaqgsEKKEPQKVILSISSRGVKLIDEDTKaVLHEHPLRRISFC 77

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462598576  303 AVCPDDRRFFGLVTMQTNDDgslaqeeegalRTSCHVFMVDPdlfnHKIHQGIARRFGFECTADPDTNGCLE 374
Cdd:smart00462  78 AVGPDDLDVFGYIARDPGSS-----------RFACHVFRCEK----AAEDIALAIGQAFQLAYELKLKARSE 134

Regulator of G protein signaling (RGS) domain found in the RGS18 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS18 protein. RGS18 is a member of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS18 is a member of the R4/RGS subfamily and is expressed predominantly in osteoclasts where it acts as a negative regulator of the acidosis-induced osteoclastogenic OGR1/NFAT signaling pathway. RANKL (receptor activator of nuclear factor B ligand) stimulates osteoclastogenesis by inhibiting expression of RGS18.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576 716 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPAhdKKELSYRAREIFSKFLCSKATTPVNID-SQAQLADDV 794
Cdd:cd08712     1 FDKLLSHKDGLEAFTRFLKTEFSEENIEFWIACEDYKKSKT--PQQIHLKAKAIYEKFIQTDAPKEVNLDfHTKEVTTNS 78

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2462598576 795 LRAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLY 828
Cdd:cd08712    79 IEQPTLTSFDAAQSRVYQLMEQDSYPRFLKSDIY 112

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576   19 RVRSVEVARGRAGYGFTLSG----QAPCVLSCVMRGSPADFVGLRAGDQILAVNEINVKKASHEDVVKLIGKCSGVLHMV 94
Cdd:smart00228   1 EPRLVELEKGGGGLGFSLVGgkdeGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLT 80

                   .
gi 2462598576   95 I 95
Cdd:smart00228  81 V 81

Regulator of G protein signaling (RGS) domain found in the RGS13 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS13 protein. RGS13 is member of the R4/RGS subfamily of the RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS13 is predominantly expressed in T and B lymphocytes and in mast cells, and plays a role in adaptive immune responses. RGS13 also found in Rgs13, which is also expressed in dendritic cells and in neuroendocrine cells of the thymus, gastrointestinal, and respiratory tracts. Outside of the GPCR pathway, RGS5 interacts with the PIP3 protein.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576 716 FERLLQDPVGVRYFSDFLRKEFSEENILFWQACEYFNHVPAHDKKelSYRAREIFSKFLCSKATTPVNIDSQAQLAddVL 795
Cdd:cd08716     1 FENLMATKYGPIIYATYLKTEHSDENIEFWLACETYKKIASQRKR--ISMARKLFASYIQPQAPREINIDSPTRKA--II 76

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2462598576 796 R---APHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 830
Cdd:cd08716    77 RniqEPTQSCFDEAQRIVYMHMERDSYPRFLESKFYQK 114

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This SHANK-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged as beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta- strand F.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462598576  20 VRSVEVARGRAGYGFTLSG--------------QAPCV--LSCVMRGSPADFVGLRAGDQILAVNEINVKKASHEDVVKL 83
Cdd:cd06746     6 PRTVVLQKGDKGFGFVLRGakavgpileftptpAFPALqyLESVDPGGVADKAGLKKGDFLLEINGEDVVKASHEQVVNL 85

                          90
                  ....*....|..
gi 2462598576  84 IGKCSGVLHMVI 95
Cdd:cd06746    86 IRQSGNTLVLKV 97

PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of rhophilin-1, rhophilin-2, and related domains. Rhophilin-1 (RHPN1, also known as GTP-Rho-binding protein 1) and rhophilin-2 (RHPN2, also known as GTP-Rho-binding protein 2) are Rho-GTP binding proteins involved in cytoskeletal dynamics. Rhophilin-2 inhibits RhoA's activity to induce F-actin stress fibers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This rhophilin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462598576  21 RSVEVARGRAGYGFTLSGQAPCVLSCVMRGSPADFVGLRAGDQILAVNEINVKKASHEDVVKLI 84
Cdd:cd06712     2 RTVHLTKEEGGFGFTLRGDSPVQVASVDPGSCAAEAGLKEGDYIVSVGGVDCKWSKHSEVVKLL 65

Unstructured region of RGS12; RGS12_us1 is a region of Regulator of G-protein signalling 12 proteins that is natively unstructured and lies N-terminal to other such regions in UniProt:E1BPP4. It is very glycine-rich, and the function is not known.

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 2462598576 836 VEGRALPDSQQVPSSPASKHSLGSDHSSVSTPKKVS 871
Cdd:pfam16613   1 VEGRPLPDPQQVPSSPTSKHSVGSDRSNISTPKKLS 36

PDZ domain of regulator of G-protein signaling 3 (RGS3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS3, and related domains. RGS3 down-regulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. It downregulates G-protein-mediated release of inositol phosphates and activation of MAP kinases. In Eph/ephrin signaling, RGS3 binds via its PDZ domain to the cytoplasmic C terminus of Eph receptor tyrosine kinase EphB. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RGS3-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2462598576  23 VEVARGRAGYGFTLSGQAPCVLSCVMRGSPADFVGLRAGDQILAVNEINVKKASHEDVVKLIGKCSG 89
Cdd:cd06711     3 ITIQRGKDGFGFTICDDSPVRVQAVDPGGPAEQAGLQQGDTVLQINGQPVERSKCVELAHAIRNCPS 69

PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGEF11, ARHGEF12, and related domains. This subfamily includes the GEFs (guanine exchange factors) ARHGEF11 (Rho guanine nucleotide exchange factor 11, known as PDZ-RhoGEF) and ARHGEF12 (Rho guanine nucleotide exchange factor 12, also known as leukemia-associated RhoGEF). GEFs activate Rho GTPases by promoting GTP binding. ARHGEF11/12 are regulators of G protein signaling (RGS) domain-containing GEFs; the RGS domain mediates their binding to and activation of Galpha (and Gq also in the case of ARHGEF12), in response to G-protein coupled receptor activation. ARHGEF11 and 12 are involved in serum-signaling, and regulate Yes-Associated Protein (YAP1)-dependent transcription. The ARHGEF12 PDZ domain binds plexin-B1 and the receptor tyrosine kinase insulin-like growth factor receptor (IGF-R1) beta-subunit. ARHGEF12 also interacts with glutamate receptor delta-1(GluD1), a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGEF11-12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462598576  21 RSVEVARGRAGYGFTLSGQAPCVLSCVMRGSPADFVGLRAGDQILAVNEINVKKASHEDVVKLI 84
Cdd:cd23069     2 RCVVIQRDENGYGLTVSGDNPVFVQSVKEGGAAYRAGVQEGDRIIKVNGTLVTHSNHLEVVKLI 65

PDZ domain of FERM and PDZ domain-containing protein 1 (FRMPD1), FRMPD3, FRMPD4, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of FRMPD1, FRMPD3, FRMPD4, and related domains. FRMPD1 (also known as FERM domain-containing protein 2, FRMD2), inhibits the malignant phenotype of lung cancer by activating the Hippo pathway via interaction with WWC3; the FRMPD1 PDZ domain binds WWC3. FRMPD3 is a target gene of the neuron-specific transcription factor NPAS4 that is involved in synaptic plasticity. FRMPD4 (also known as PDZ domain-containing protein 10, PDZD10, PDZK10, PSD-95-interacting regulator of spine morphogenesis, and Preso) regulates dendritic spine morphogenesis, and mGluR1/5 signaling; the FRMPD4 PDZ domain binds PAK-interacting exchange factor-beta (betaPix). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This FRMPD1,3,4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2462598576  31 GYGFTLSGQAPCVLSCVMRGSPADfvG-LRAGDQILAVNEINVKKASHEDVVKLIGKC 87
Cdd:cd06769    11 GFGFVAGSERPVVVRSVTPGGPSE--GkLLPGDQILKINNEPVEDLPRERVIDLIREC 66

PDZ domain 4 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MAGI family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2462598576  31 GYGFTL----SGQAPCVLSCVMRGSPADFVG-LRAGDQILAVNEINVKKASHEDVVKLIgKCSG 89
Cdd:cd06734    13 GFGFVIissvNKKSGSKIGRIIPGSPADRCGqLKVGDRILAVNGISILNLSHGDIVNLI-KDSG 75

PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2462598576  27 RGRAGYGFTLSGQAP----CVLSCVMRGSPADFVGLRAGDQILAVNEINVKKASHEDVVKLI 84
Cdd:cd06737    10 RGPESLGFSVRGGLEhgcgLFVSHVSPGSQADNKGLRVGDEIVRINGYSISQCTHEEVINLI 71