PDZ domain of membrane palmitoylated proteins 3 (MPP3), MPP4, and MPP7, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP3, MPP4, and MPP7, and related domains. MPP3 (also known as MAGUK p55 subfamily member 3, erythrocyte membrane protein p55, or EMP55), MPP4 (also known as MAGUK p55 subfamily member 4 or Discs large homolog 6), and MPP7 (also known as MAGUK p55 subfamily member 7) are membrane-associated guanylate kinase (MAGUK)-like proteins. MPP3 is part of a cell adhesion protein complex including tumor suppressor CADM1 and actin-binding protein 4.1B. Participation in the Crumbs cell polarity complex has also been demonstrated for MPP7 in epithelial cells, and for MPP3 and MPP4 in the retina. MPP4 is needed for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals. Binding partners of the MPP3 PDZ domain include nectin-3, serotonin 5-hydroxytryptamine, 5-HT(2C) receptor, and a cell adhesion protein, TSLC1 (tumor suppressor in lung cancer 1); fragments of MPP4 having the PDZ domain bind CRB (PDZ-SH3-GUK) and GABA transporter GAT1 (PDZ-SH3). 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 MPP1-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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613 147 RIVCLVKNKQPLGATIKRNEITGEIFVARVIHGGLADRSGLLHAGDRIIEVNGFPVDGMEPEQIIQVVqARSHGTIMFKV 226
Cdd:cd06799     1 KIVRLVKNNEPLGATIKRDEKTGAIVVARIMRGGAADRSGLIHVGDELREVNGISVEGKDPEEVIQIL-ANSQGPITFKL 79

                  ..
gi 2108652613 227 VP 228
Cdd:cd06799    80 IP 81

L27 domain; The L27 domain is found in receptor targeting proteins Lin-2 and Lin-7.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 2108652613  81 SGLSLQLLIDIRALPGCSEEAKELYRLLRQPHLQALLSAHDTVAQKDYE 129
Cdd:pfam02828   1 VELVLELLEDLQPLSEASEDLAELQKLLQSPHLQALLEAHDKVAQKVYE 49

Guanylate kinase homologues; Active enzymes catalyze ATP-dependent phosphorylation of GMP to GDP. Structure resembles that of adenylate kinase. So-called membrane-associated guanylate kinase homologues (MAGUKs) do not possess guanylate kinase activities; instead at least some possess protein-binding functions.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613  431 SGVGVNELRRRLIEINPNIFQGAVPYTTRAPRGYEESGREYYFTSREIFDNMVYNNRFLEYGEYKGNLYGTSIKSVRDVL 510
Cdd:smart00072   1 SGVGKGTLLAELIQEIPDAFERVVSHTTRPPRPGEVNGVDYHFVSKEEFEDDIKSGLFLEWGEYEGNYYGTSKETIRQVA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613  511 NSRKICVIDIEPNAIQAVRTHELRAYIIYVKPP---PLERLRETRQDSyittnyyvnrpyKDEDFQEMEEAARKIESHYw 587
Cdd:smart00072  81 EKGKHCLLDIDPQGVKQLRKAQLYPIVIFIAPPsseELERRLRQRGTE------------TSERIQKRLAAAQKEAQEY- 147

                          170       180
                   ....*....|....*....|....*..
gi 2108652613  588 QFFDHVIVNDELQDSCVQLLTAVRKAQ 614
Cdd:smart00072 148 HLFDYVIVNDDLEDAYEELKEILEAEQ 174

PDZ domain of membrane palmitoylated proteins 3 (MPP3), MPP4, and MPP7, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP3, MPP4, and MPP7, and related domains. MPP3 (also known as MAGUK p55 subfamily member 3, erythrocyte membrane protein p55, or EMP55), MPP4 (also known as MAGUK p55 subfamily member 4 or Discs large homolog 6), and MPP7 (also known as MAGUK p55 subfamily member 7) are membrane-associated guanylate kinase (MAGUK)-like proteins. MPP3 is part of a cell adhesion protein complex including tumor suppressor CADM1 and actin-binding protein 4.1B. Participation in the Crumbs cell polarity complex has also been demonstrated for MPP7 in epithelial cells, and for MPP3 and MPP4 in the retina. MPP4 is needed for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals. Binding partners of the MPP3 PDZ domain include nectin-3, serotonin 5-hydroxytryptamine, 5-HT(2C) receptor, and a cell adhesion protein, TSLC1 (tumor suppressor in lung cancer 1); fragments of MPP4 having the PDZ domain bind CRB (PDZ-SH3-GUK) and GABA transporter GAT1 (PDZ-SH3). 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 MPP1-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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613 147 RIVCLVKNKQPLGATIKRNEITGEIFVARVIHGGLADRSGLLHAGDRIIEVNGFPVDGMEPEQIIQVVqARSHGTIMFKV 226
Cdd:cd06799     1 KIVRLVKNNEPLGATIKRDEKTGAIVVARIMRGGAADRSGLIHVGDELREVNGISVEGKDPEEVIQIL-ANSQGPITFKL 79

                  ..
gi 2108652613 227 VP 228
Cdd:cd06799    80 IP 81

Guanosine monophosphate kinase (GMPK, EC 2.7.4.8), also known as guanylate kinase (GKase), catalyzes the reversible phosphoryl transfer from adenosine triphosphate (ATP) to guanosine monophosphate (GMP) to yield adenosine diphosphate (ADP) and guanosine diphosphate (GDP). It plays an essential role in the biosynthesis of guanosine triphosphate (GTP). This enzyme is also important for the activation of some antiviral and anticancer agents, such as acyclovir, ganciclovir, carbovir, and thiopurines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613 424 LIALLGPSGVGVNELRRRLIEINPNIFQGAVPYTTRAPRGYEESGREYYFTSREIFDNMVYNNRFLEYGEYKGNLYGTSI 503
Cdd:cd00071     1 LIVLSGPSGVGKSTLLKRLLEEFDPNFGFSVSHTTRKPRPGEVDGVDYHFVSKEEFERLIENGEFLEWAEFHGNYYGTSK 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2108652613 504 KSVRDVLNSRKICVIDIEPNAIQAVRTHELRAYIIYVKPP 543
Cdd:cd00071    81 AAVEEALAEGKIVILEIDVQGARQVKKSYPDAVSIFILPP 120

guanylate kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613 423 RLIALLGPSGVGVNELRRRLIEINPNIfQGAVPYTTRAPRGYEESGREYYFTSREIFDNMVYNNRFLEYGEYKGNLYGTS 502
Cdd:PRK00300    6 LLIVLSGPSGAGKSTLVKALLERDPNL-QLSVSATTRAPRPGEVDGVDYFFVSKEEFEEMIENGEFLEWAEVFGNYYGTP 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613 503 IKSVRDVLNSRKICVIDIE-----------PNAIQavrthelrayiIYVKPPPLE----RLRETRQDSyittnyyvnrpy 567
Cdd:PRK00300   85 RSPVEEALAAGKDVLLEIDwqgarqvkkkmPDAVS-----------IFILPPSLEelerRLRGRGTDS------------ 141

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 2108652613 568 kDEDFQE-MEEAarKIESHYWQFFDHVIVNDELQDSCVQLLTAVR 611
Cdd:PRK00300  142 -EEVIARrLAKA--REEIAHASEYDYVIVNDDLDTALEELKAIIR 183

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 2108652613  146 TRIVCLVKNKQPLGATIKRNEITGE-IFVARVIHGGLADRSGLlHAGDRIIEVNGFPVDGMEPEQIIQVVQaRSHGTIMF 224
Cdd:smart00228   2 PRLVELEKGGGGLGFSLVGGKDEGGgVVVSSVVPGSPAAKAGL-RVGDVILEVNGTSVEGLTHLEAVDLLK-KAGGKVTL 79

                   ....
gi 2108652613  225 KVVP 228
Cdd:smart00228  80 TVLR 83

domain in receptor targeting proteins Lin-2 and Lin-7;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2108652613   83 LSLQLLIDIRALPGCSEEAKELYRLLRQPHLQALLSAHDTVAQKDYE 129
Cdd:smart00569   2 RLLELLEELQSLLSPSEDLQELRRLLQSPHLQALLKIHDKVAETELD 48

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 2108652613 158 LGATIKRNEitGEIFVARVIHGGLADRSGLlHAGDRIIEVNGFPVDGMEPEQIIQ 212
Cdd:COG0793    62 LGAELGEED--GKVVVVSVIPGSPAEKAGI-KPGDIILAIDGKSVAGLTLDDAVK 113

SH3 domain; SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organization. First described in the Src cytoplasmic tyrosine kinase. The structure is a partly opened beta barrel.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2108652613 243 RAMADYSPQQDPTIpcadagmSFRKGDILEIVDQTDALWWQAKKLPSDTscaGLIPS 299
Cdd:pfam00018   1 VALYDYTAQEPDEL-------SFKKGDIIIVLEKSEDGWWKGRNKGGKE---GLIPS 47

Guanylate kinase homologues; Active enzymes catalyze ATP-dependent phosphorylation of GMP to GDP. Structure resembles that of adenylate kinase. So-called membrane-associated guanylate kinase homologues (MAGUKs) do not possess guanylate kinase activities; instead at least some possess protein-binding functions.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613  431 SGVGVNELRRRLIEINPNIFQGAVPYTTRAPRGYEESGREYYFTSREIFDNMVYNNRFLEYGEYKGNLYGTSIKSVRDVL 510
Cdd:smart00072   1 SGVGKGTLLAELIQEIPDAFERVVSHTTRPPRPGEVNGVDYHFVSKEEFEDDIKSGLFLEWGEYEGNYYGTSKETIRQVA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613  511 NSRKICVIDIEPNAIQAVRTHELRAYIIYVKPP---PLERLRETRQDSyittnyyvnrpyKDEDFQEMEEAARKIESHYw 587
Cdd:smart00072  81 EKGKHCLLDIDPQGVKQLRKAQLYPIVIFIAPPsseELERRLRQRGTE------------TSERIQKRLAAAQKEAQEY- 147

                          170       180
                   ....*....|....*....|....*..
gi 2108652613  588 QFFDHVIVNDELQDSCVQLLTAVRKAQ 614
Cdd:smart00072 148 HLFDYVIVNDDLEDAYEELKEILEAEQ 174

PDZ domain of membrane palmitoylated proteins 3 (MPP3), MPP4, and MPP7, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP3, MPP4, and MPP7, and related domains. MPP3 (also known as MAGUK p55 subfamily member 3, erythrocyte membrane protein p55, or EMP55), MPP4 (also known as MAGUK p55 subfamily member 4 or Discs large homolog 6), and MPP7 (also known as MAGUK p55 subfamily member 7) are membrane-associated guanylate kinase (MAGUK)-like proteins. MPP3 is part of a cell adhesion protein complex including tumor suppressor CADM1 and actin-binding protein 4.1B. Participation in the Crumbs cell polarity complex has also been demonstrated for MPP7 in epithelial cells, and for MPP3 and MPP4 in the retina. MPP4 is needed for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals. Binding partners of the MPP3 PDZ domain include nectin-3, serotonin 5-hydroxytryptamine, 5-HT(2C) receptor, and a cell adhesion protein, TSLC1 (tumor suppressor in lung cancer 1); fragments of MPP4 having the PDZ domain bind CRB (PDZ-SH3-GUK) and GABA transporter GAT1 (PDZ-SH3). 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 MPP1-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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613 147 RIVCLVKNKQPLGATIKRNEITGEIFVARVIHGGLADRSGLLHAGDRIIEVNGFPVDGMEPEQIIQVVqARSHGTIMFKV 226
Cdd:cd06799     1 KIVRLVKNNEPLGATIKRDEKTGAIVVARIMRGGAADRSGLIHVGDELREVNGISVEGKDPEEVIQIL-ANSQGPITFKL 79

                  ..
gi 2108652613 227 VP 228
Cdd:cd06799    80 IP 81

Guanosine monophosphate kinase (GMPK, EC 2.7.4.8), also known as guanylate kinase (GKase), catalyzes the reversible phosphoryl transfer from adenosine triphosphate (ATP) to guanosine monophosphate (GMP) to yield adenosine diphosphate (ADP) and guanosine diphosphate (GDP). It plays an essential role in the biosynthesis of guanosine triphosphate (GTP). This enzyme is also important for the activation of some antiviral and anticancer agents, such as acyclovir, ganciclovir, carbovir, and thiopurines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613 424 LIALLGPSGVGVNELRRRLIEINPNIFQGAVPYTTRAPRGYEESGREYYFTSREIFDNMVYNNRFLEYGEYKGNLYGTSI 503
Cdd:cd00071     1 LIVLSGPSGVGKSTLLKRLLEEFDPNFGFSVSHTTRKPRPGEVDGVDYHFVSKEEFERLIENGEFLEWAEFHGNYYGTSK 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2108652613 504 KSVRDVLNSRKICVIDIEPNAIQAVRTHELRAYIIYVKPP 543
Cdd:cd00071    81 AAVEEALAEGKIVILEIDVQGARQVKKSYPDAVSIFILPP 120

guanylate kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613 423 RLIALLGPSGVGVNELRRRLIEINPNIfQGAVPYTTRAPRGYEESGREYYFTSREIFDNMVYNNRFLEYGEYKGNLYGTS 502
Cdd:PRK00300    6 LLIVLSGPSGAGKSTLVKALLERDPNL-QLSVSATTRAPRPGEVDGVDYFFVSKEEFEEMIENGEFLEWAEVFGNYYGTP 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613 503 IKSVRDVLNSRKICVIDIE-----------PNAIQavrthelrayiIYVKPPPLE----RLRETRQDSyittnyyvnrpy 567
Cdd:PRK00300   85 RSPVEEALAAGKDVLLEIDwqgarqvkkkmPDAVS-----------IFILPPSLEelerRLRGRGTDS------------ 141

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 2108652613 568 kDEDFQE-MEEAarKIESHYWQFFDHVIVNDELQDSCVQLLTAVR 611
Cdd:PRK00300  142 -EEVIARrLAKA--REEIAHASEYDYVIVNDDLDTALEELKAIIR 183

Src Homology 3 domain of Membrane Protein, Palmitoylated (or MAGUK p55 subfamily member) proteins; The MPP/p55 subfamily of MAGUK (membrane-associated guanylate kinase) proteins includes at least eight vertebrate members (MPP1-7 and CASK), four Drosophila proteins (Stardust, Varicose, CASK and Skiff), and other similar proteins; they all contain one each of the core of three domains characteristic of MAGUK proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, most members except for MPP1 contain N-terminal L27 domains and some also contain a Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. CASK has an additional calmodulin-dependent kinase (CaMK)-like domain at the N-terminus. Members of this subfamily are scaffolding proteins that play important roles in regulating and establishing cell polarity, cell adhesion, and synaptic targeting and transmission, among others. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2108652613 241 YVRAMADYSPQQDPTIPCADAGMSFRKGDILEIVDQTDALWWQAKKLPSDTSCAGLIPS 299
Cdd:cd11862     1 FVRALFDYDPEEDPLIPCKEAGLSFKKGDILQIVNQDDPNWWQARKVGDPNGRAGLIPS 59

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1)-like proteins; This subfamily includes MPP1, CASK (Calcium/calmodulin-dependent Serine protein Kinase), Caenorhabditis elegans lin-2, and similar proteins. MPP1 and CASK are scaffolding proteins from the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). In addition, they also have the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. CASK and lin-2 also contain an N-terminal calmodulin-dependent kinase (CaMK)-like domain and two L27 domains. MPP1 is ubiquitously-expressed and plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. CASK is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2108652613 241 YVRAMADYSPQQDPTIPCADAGMSFRKGDILEIVDQTDALWWQAKKLPSDTSCAGLIPSTNL 302
Cdd:cd12035     1 YVRAQFDYDPSKDDLIPCQQAGIAFKTGDILQIISKDDHNWWQARKPGASKEPAGLIPSPEL 62

PDZ domain of membrane palmitoylated protein 6 (MPP6), MPP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP6, MPP2, and related domains. MPP6 (also known as MAGUK p55 subfamily member, Protein associated with Lin-7, 2 (PALS2), Veli-associated MAGUK 1, and VAM-1) is a membrane-associated guanylate kinase (MAGUK)-like protein. MPP6 is a regulator of Lin-7 expression and localization. MPP6 is also known to bind cell-adhesion protein, nectin-like molecule-2 (Necl-2), and localize to the basolateral plasma membrane in mammalian epithelial cells. MPP2 (also known as MAGUK p55 subfamily member 2) is a postsynaptic protein that links SynCAM1 cell adhesion molecules to core components of the postsynaptic density. Other members of this family include the Drosophila Vari protein, an essential basolateral septate junction protein which interacts with the cell-adhesion protein neurexin IV. 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 MPP6-MPP2-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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613 147 RIVCLVKNK-QPLGATIKRNEitGEIFVARVIHGGLADRSGLLHAGDRIIEVNGFPVDGmePEQiIQVVQARSHGTIMFK 225
Cdd:cd10832     1 RMVGIRKNPgEPLGVTVRLEE--GELVIARILHGGMIDRQGLLHVGDIIKEVNGVPVGS--PEQ-LQEMLKNASGSVTLK 75

                  ...
gi 2108652613 226 VVP 228
Cdd:cd10832    76 ILP 78

PDZ domain of membrane palmitoylated protein 5 (MPP5), Drosophila Stardust, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP5, Drosophila Stardust, and related domains. MPP5 (also known as MAGUK p55 subfamily member 1, protein associated with Lin-7 1 or PALS1) and Drosophila Stardust are membrane-associated guanylate kinase (MAGUK)-like proteins that serve as signaling and scaffolding proteins, linking different proteins critical to the formation and maintenance of tight junctions (TJ) and apical-basal polarity. Apical-basal polarity determinants cluster in complexes; in particular, the Crumbs complex (Crb, MPP5, and PATJ) and the PAR/aPKC-complex (PAR-3, PAR-6, aPKC) determine the apical plasma membrane domain. Within the Crumbs complex, Crb is stabilized in the plasma membrane by MPP5, which in turn recruits PATJ and Lin-7 to the complex. MPP5 also links the Crumbs complex with the PAR/aPKC-complex. The Drosophila homolog of the Crumbs complex is the (CRB)-Stardust (Sdt)-Discs Lost (Dlt) complex. MPP5 also acts as an interaction partner for SARS-CoV envelope protein E, which results in delayed formation of TJs and dysregulation of cell polarity. 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 MPP5-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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613 147 RIVCLVKNKQPLGATIkRNEiTGEIFVARVIHGGLADRSGLLHAGDRIIEVNGFPVDGMEPEQIIQVVqARSHGTIMFKV 226
Cdd:cd06798     1 KIVRIEKTREPLGATV-RNE-GDSVIISRIVKGGAAEKSGLLHEGDEILEINGIEIRGKDVNEVCDLL-ADMHGTLTFLL 77

                  ..
gi 2108652613 227 VP 228
Cdd:cd06798    78 IP 79

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1); MPP1, also called 55 kDa erythrocyte membrane protein (p55), is a ubiquitously-expressed scaffolding protein that plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. It was originally identified as an erythrocyte protein that stabilizes the actin cytoskeleton to the plasma membrane by forming a complex with 4.1R protein and glycophorin C. MPP1 is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains the three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2108652613 241 YVRAMADYSPQQDPTIPCADAGMSFRKGDILEIVDQTDALWWQAKKLPSDTSCAGLIPSTNL 302
Cdd:cd12080     1 YMRAQFDYDPKKDNLIPCKEAGLKFQTGDIIQIINKDDSNWWQGRVEGSGEESAGLIPSPEL 62

guanylate kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613 423 RLIALLGPSGVGVNELRRRLIEINPNiFQGAVPYTTRAPRGYEESGREYYFTSREIFDNMVYNNRFLEYGEYKGNLYGTS 502
Cdd:PRK14738   14 LLVVISGPSGVGKDAVLARMRERKLP-FHFVVTATTRPKRPGEIDGVDYHFVTPEEFREMISQNELLEWAEVYGNYYGVP 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613 503 IKSVRDVLNSRKICVIDIEPNAIQAVRTHELRAYIIYVKPPPLE----RLRETRQDSyittnyyvnrpyKDEDFQEMEEA 578
Cdd:PRK14738   93 KAPVRQALASGRDVIVKVDVQGAASIKRLVPEAVFIFLAPPSMDeltrRLELRRTES------------PEELERRLATA 160

                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 2108652613 579 ARKIESHYwqFFDHVIVN--DELqDSCVQLLTAVRKAQ 614
Cdd:PRK14738  161 PLELEQLP--EFDYVVVNpeDRL-DEAVAQIMAIISAE 195

PDZ domain of peripheral plasma membrane protein CASK, Caenorhabditis Lin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CASK, Caenorhabditis elegans Lin-2, and related domains. CASK and Lin-2 are membrane-associated guanylate kinase (MAGUK)-like proteins. CASK (also known as Calcium/calmodulin-dependent protein kinase, CAKI, and Camguk) has a role in synaptic transmembrane protein anchoring and ion channel trafficking. CASK may regulate transmembrane proteins that bind calcium, calmodulin, or nucleotides; it regulates the Drosophila ether a go-go (eag) potassium channel, and also regulates autophosphorylation of CaMKII. CASK binding partners include the transcription factor TBR1, and cell-surface proteins, including amyloid precursor protein, neurexins, and syndecans. Lin-2, as a component of the CLin-10-Lin-2-Lin-7 complex, plays a role in controlling the basolateral localization of the EGF receptor Let-23; this complex also associates with the neuron-specific motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor 2B along microtubules. CASK may also function in targeting or scaffolding of the protein parkin which is selectively truncated by a Parkinson's disease-causing mutation; the C-terminus of parkin functions as a class II PDZ-binding motif that binds CASK. 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 MPP6-MPP2-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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613 147 RIVCLVKN-KQPLGATIKRNEiTGEIFVARVIHGGLADRSGLLHAGDRIIEVNGFPVDGMEPEQiIQVVQARSHGTIMFK 225
Cdd:cd10831     1 RLVQFQKNtDEPMGITLKMNE-DGRCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQ-LQKMLREARGSITFK 78

                  ...
gi 2108652613 226 VVP 228
Cdd:cd10831    79 IVP 81

Src Homology 3 domain of Membrane Protein, Palmitoylated 2 (or MAGUK p55 subfamily member 2); MPP2 is a scaffolding protein that interacts with the non-receptor tyrosine kinase c-Src in epithelial cells to negatively regulate its activity and morphological function. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2108652613 241 YVRAMADYSPQQDPTIPCADAGMSFRKGDILEIVDQTDALWWQAKKLPSDTscAGLIPS 299
Cdd:cd12037     1 FVKCHFDYDPSSDSLIPCKEAGLKFRAGDLLQIVNQEDPNWWQACHVEGGS--AGLIPS 57

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 2108652613  146 TRIVCLVKNKQPLGATIKRNEITGE-IFVARVIHGGLADRSGLlHAGDRIIEVNGFPVDGMEPEQIIQVVQaRSHGTIMF 224
Cdd:smart00228   2 PRLVELEKGGGGLGFSLVGGKDEGGgVVVSSVVPGSPAAKAGL-RVGDVILEVNGTSVEGLTHLEAVDLLK-KAGGKVTL 79

                   ....
gi 2108652613  225 KVVP 228
Cdd:smart00228  80 TVLR 83

PDZ domain of membrane palmitoylated protein1 (MPP1), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP1, and related domains. MPP1 (also known as MAGUK p55 subfamily member 1, erythrocyte membrane protein p55, EMP55) is a membrane-associated guanylate kinase (MAGUK)-like protein which forms a complex with protein 4.1 and glycophorin C (GPC) at the cytoplasmic face of the plasma membrane; this complex is essential for cytoskeleton-membrane linkage in erythrocytes and many non-erythroid cells, and participates in the determination of membrane stability and cell shape. MPP1, by interacting with various scaffold proteins and cytoskeletal proteins in the postsynaptic density, also plays an important role in organizing synaptic and non-synaptic structures. MPP1 is also a component of the Crumbs protein complex in the mammalian retina and may link the Usher protein network and the Crumbs protein complex. The MPP1 PDZ domain binding partners include GPC, ABCC4, and CADM1/Necl-2/SynCAM1. 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 MPP1-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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613 147 RIVCLVKN-KQPLGATIKRNEiTGEIFVARVIHGGLADRSGLLHAGDRIIEVNGFPVDGMEPEQiIQVVQARSHGTIMFK 225
Cdd:cd10830     1 RLVQFEKNtEEPMGITLKLNE-KQSCIVARILHGGMIHRQGSLHVGDEILEINGKSVTNHSVDQ-LQKMLKETKGMVSLK 78

                  ...
gi 2108652613 226 VVP 228
Cdd:cd10830    79 VIP 81

Src Homology 3 domain of Disks Large homolog 2; DLG2, also called postsynaptic density-93 (PSD93) or Channel-associated protein of synapse-110 (chapsyn 110), is a scaffolding protein that clusters at synapses and plays an important role in synaptic development and plasticity. The DLG2 delta isoform binds inwardly rectifying potassium Kir2 channels, which determine resting membrane potential in neurons. It regulates the spatial and temporal distribution of Kir2 channels within neuronal membranes. DLG2 is a member of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. DLG2 contains three PDZ domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2108652613 240 LYVRAMADYSPQQDPTIPcaDAGMSFRKGDILEIVDQTDALWWQAKK--LPSDTSCAGLIPSTNLLKRKQR 308
Cdd:cd12032     6 LYVRAMFDYEKSKDSGLP--SQGLSFRYGDILHVINASDDEWWQARRvtPDGDSEEMGVIPSKRRVERKER 74

PDZ domain; PDZ domains are found in diverse signaling proteins.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2108652613 156 QPLGATIKRNE--ITGEIFVARVIHGGLADRSGLlHAGDRIIEVNGFPVDGMEPEQIIQVVQaRSHGTIMFKV 226
Cdd:pfam00595  10 GGLGFSLKGGSdqGDPGIFVSEVLPGGAAEAGGL-KVGDRILSINGQDVENMTHEEAVLALK-GSGGKVTLTI 80

PDZ domain of partitioning defective 6 (Par6), Drosophila Rho GTPase-activating protein 100F (RhoGAP100F), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Par6 (also known as PAR6 or Par-6), RhoGAP100F, and related domains. Par6 is part of a conserved machinery that directs metazoan cell polarity, a process necessary for the function of diverse cell types. Par6 forms a cell polarity-regulatory complex with atypical protein kinase C (aPKC) and Par3. Par6 can also directly associate with PALS1 (proteins associated with Lin7, also known as Stardust) providing a link between the Par3/aPKC/Par6 complex and the PALS1-PATJ (protein-associated TJ) complex. Binding partners of the Par6-PDZ domain include Par3, PALS1/Stardust; leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2), human crumbs (CRB3) involve in the morphogenesis of the tight junctions in mammalian epithelial cells, and PAR-6 co-operates with the Par6 semi-CRIB domain to bind CDC42. CDC42 regulates the Par6 PDZ domain through an allosteric CRIB-PDZ transition. Drosophila RhoGAP100F, also known as synapse defective protein 1 homolog (syd-1 homolog), is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound form. The RhoGAP100F-PDZ domain binds the neurexin C terminus to control synapse formation at the Drosophila neuromuscular junction. 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 Par6-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 2108652613 147 RIVCLVK-NKQPLGATIKR-NEI---TGeIFVARVIHGGLADRSGLLHAGDRIIEVNGFPVDGMEPEQIIQVVQARS 218
Cdd:cd06718     1 RRVELIKpPGKPLGFYIRDgNGVervPG-IFISRLVLGSLADSTGLLAVGDEILEVNGVEVTGKSLDDVTDMMVAPT 76

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2108652613  241 YVRAMADYSPQQDPTIpcadagmSFRKGDILEIVDQTDALWWQAKKlpsDTSCAGLIPST 300
Cdd:smart00326   4 QVRALYDYTAQDPDEL-------SFKKGDIITVLEKSDDGWWKGRL---GRGKEGLFPSN 53

Src Homology 3 domain of Disks Large homolog 4; DLG4, also called postsynaptic density-95 (PSD95) or synapse-associated protein 90 (SAP90), is a scaffolding protein that clusters at synapses and plays an important role in synaptic development and plasticity. It is responsible for the membrane clustering and retention of many transporters and receptors such as potassium channels and PMCA4b, a P-type ion transport ATPase, among others. DLG4 is a member of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. DLG4 contains three PDZ domains. The SH3 domain of DLG4 binds and clusters the kainate subgroup of glutamate receptors via two proline-rich sequences in their C-terminal tail. It also binds AKAP79/150 (A-kinase anchoring protein). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.