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 1720364019  68 KIVRLVKNKEPLGATIRRDEHSGAVVVARIMRGGAADRSGLVHVGDELREVNGIAVLHKRPDEISQILAQSQGSITLKII 147
Cdd:cd06799     1 KIVRLVKNNEPLGATIKRDEKTGAIVVARIMRGGAADRSGLIHVGDELREVNGISVEGKDPEEVIQILANSQGPITFKLI 80

                  .
gi 1720364019 148 P 148
Cdd:cd06799    81 P 81

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1720364019    3 LAEDVMEELQAA-SVHSDERELLQLLSTPHLRAVLMVHDTVAQKNFDPVLPP 53
Cdd:smart00569   2 RLLELLEELQSLlSPSEDLQELRRLLQSPHLQALLKIHDKVAETELDPPLPE 53

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 1720364019  68 KIVRLVKNKEPLGATIRRDEHSGAVVVARIMRGGAADRSGLVHVGDELREVNGIAVLHKRPDEISQILAQSQGSITLKII 147
Cdd:cd06799     1 KIVRLVKNNEPLGATIKRDEKTGAIVVARIMRGGAADRSGLIHVGDELREVNGISVEGKDPEEVIQILANSQGPITFKLI 80

                  .
gi 1720364019 148 P 148
Cdd:cd06799    81 P 81

Src Homology 3 domain of Membrane Protein, Palmitoylated 3 (or MAGUK p55 subfamily member 3); MPP3 is a scaffolding protein that colocalizes with MPP5 and CRB1 at the subdpical region adjacent to adherens junctions and may function in photoreceptor polarity. It interacts with some nectins and regulates their trafficking and processing. Nectins are cell-cell adhesion proteins involved in the establishment apical-basal polarity at cell adhesion sites. 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). 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 1720364019 162 FMRALFHYDPREDRAIPCQEAGLPFQRRQVLEVVSQDDPTWWQAKRVGDTNLRAGLIPSKQF 223
Cdd:cd12039     1 FMRALFDYNPYEDRAIPCQEAGLPFKRRDILEVVSQDDPTWWQAKRVGDTNLRAGLIPSKQF 62

guanylate kinase; Members of this family are the enzyme guanylate kinase, also called GMP kinase. This enzyme transfers a phosphate from ATP to GMP, yielding ADP and GDP. [Purines, pyrimidines, nucleosides, and nucleotides, Nucleotide and nucleoside interconversions]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720364019 318 RLVVLIGSLGAHLHELKQRVVAEDPQqFAVAVPHTTRPRKSHERDGVEYHFVSKQAFEADVHHNKFLEHGEYKENLYGTS 397
Cdd:TIGR03263   1 LLIVISGPSGAGKSTLVKALLEEDPN-LKFSISATTRKPRPGEVDGVDYFFVSKEEFEEMIKAGEFLEWAEVHGNYYGTP 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720364019 398 LEAIQAVMAKNKVCLVDVEPEALRHLRTPEFKPYVIFVKP----AIQER---RKTppvspDS-EDIASSLDEQQQEMAAS 469
Cdd:TIGR03263  80 KSPVEEALAAGKDVLLEIDVQGARQVKKKFPDAVSIFILPpsleELERRlrkRGT-----DSeEVIERRLAKAKKEIAHA 154

                         170       180       190
                  ....*....|....*....|....*....|..
gi 1720364019 470 AAFidqhyghliDTVLVRQDLQEACSQLRAVI 501
Cdd:TIGR03263 155 DEF---------DYVIVNDDLEKAVEELKSII 177

guanylate kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720364019 340 EDPQQFAVAVPHTTRPRKSHERDGVEYHFVSKQAFEADVHHNKFLEHGEYKENLYGTSLEAIQAVMAKNKVCLVDVE--- 416
Cdd:PRK00300   27 ERDPNLQLSVSATTRAPRPGEVDGVDYFFVSKEEFEEMIENGEFLEWAEVFGNYYGTPRSPVEEALAAGKDVLLEIDwqg 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720364019 417 --------PEALRhlrtpefkpyvIFVKP----AIQER---RKTppvspDSED-IASSLDEQQQEMAASAAFidqhyghl 480
Cdd:PRK00300  107 arqvkkkmPDAVS-----------IFILPpsleELERRlrgRGT-----DSEEvIARRLAKAREEIAHASEY-------- 162

                         170       180
                  ....*....|....*....|..
gi 1720364019 481 iDTVLVRQDLQEACSQLRAVIE 502
Cdd:PRK00300  163 -DYVIVNDDLDTALEELKAIIR 183

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1720364019    3 LAEDVMEELQAA-SVHSDERELLQLLSTPHLRAVLMVHDTVAQKNFDPVLPP 53
Cdd:smart00569   2 RLLELLEELQSLlSPSEDLQELRRLLQSPHLQALLKIHDKVAETELDPPLPE 53

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720364019  70 VRLVKNK-EPLGATIR--RDEHSGAVVVARIMRGGAADRSGLvHVGDELREVNGIAVLHKRPDEISQILAQSQGSITLKI 146
Cdd:pfam00595   2 VTLEKDGrGGLGFSLKggSDQGDPGIFVSEVLPGGAAEAGGL-KVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLTI 80

                  .
gi 1720364019 147 I 147
Cdd:pfam00595  81 L 81

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 1720364019  159 SKVFMRALFHYDPREDraipcQEagLPFQRRQVLEVVSQDDPTWWQAKRVgdtNLRAGLIPS 220
Cdd:smart00326   1 EGPQVRALYDYTAQDP-----DE--LSFKKGDIITVLEKSDDGWWKGRLG---RGKEGLFPS 52

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 1720364019  68 KIVRLVKNKEPLGATIRRDEHSGAVVVARIMRGGAADRSGLVHVGDELREVNGIAVLHKRPDEISQILAQSQGSITLKII 147
Cdd:cd06799     1 KIVRLVKNNEPLGATIKRDEKTGAIVVARIMRGGAADRSGLIHVGDELREVNGISVEGKDPEEVIQILANSQGPITFKLI 80

                  .
gi 1720364019 148 P 148
Cdd:cd06799    81 P 81

Src Homology 3 domain of Membrane Protein, Palmitoylated 3 (or MAGUK p55 subfamily member 3); MPP3 is a scaffolding protein that colocalizes with MPP5 and CRB1 at the subdpical region adjacent to adherens junctions and may function in photoreceptor polarity. It interacts with some nectins and regulates their trafficking and processing. Nectins are cell-cell adhesion proteins involved in the establishment apical-basal polarity at cell adhesion sites. 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). 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 1720364019 162 FMRALFHYDPREDRAIPCQEAGLPFQRRQVLEVVSQDDPTWWQAKRVGDTNLRAGLIPSKQF 223
Cdd:cd12039     1 FMRALFDYNPYEDRAIPCQEAGLPFKRRDILEVVSQDDPTWWQAKRVGDTNLRAGLIPSKQF 62

PDZ domain of membrane palmitoylated proteins (MPPs), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP1-7 (also known as MAGUK p55 subfamily members 1-7), and related domains. MPPs comprise a subfamily of a larger group of multidomain proteins, namely, membrane-associated guanylate kinases (MAGUKs). MPPs form diverse protein complexes at the cell membranes, which are involved in a wide range of cellular processes, including establishing proper cell structure, polarity and cell adhesion. MPPs have only one PDZ domain. 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 1720364019  68 KIVRLVKN-KEPLGATIRRDEhsGAVVVARIMRGGAADRSGLVHVGDELREVNGIAVLHKRPDEISQILAQSQGSITLKI 146
Cdd:cd06726     1 RLVEFEKArDEPLGATIKMEE--DSVIVARILHGGMAHRSGLLHVGDEILEINGIPVSGKTVDELQKLLSSLSGSVTFKL 78

                  ..
gi 1720364019 147 IP 148
Cdd:cd06726    79 IP 80

Src Homology 3 domain of Membrane Protein, Palmitoylated 7 (or MAGUK p55 subfamily member 7); MPP7 is a scaffolding protein that binds to DLG1 and promotes tight junction formation and epithelial cell polarity. Mutations in the MPP7 gene may be associated with the pathogenesis of diabetes and extreme bone mineral density. 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). 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 1720364019 162 FMRALFHYDPREDRAIPCQEAGLPFQRRQVLEVVSQDDPTWWQAKRVGDTNLRAGLIPSKQ 222
Cdd:cd12033     1 FIKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKHEGDANPRAGLIPSKH 61

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 1720364019  68 KIVRLVKNKEPLGATIRRDehSGAVVVARIMRGGAADRSGLVHVGDELREVNGIAVLHKRPDEISQILAQSQGSITLKII 147
Cdd:cd06798     1 KIVRIEKTREPLGATVRNE--GDSVIISRIVKGGAAEKSGLLHEGDEILEINGIEIRGKDVNEVCDLLADMHGTLTFLLI 78

                  .
gi 1720364019 148 P 148
Cdd:cd06798    79 P 79

guanylate kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720364019 340 EDPQQFAVAVPHTTRPRKSHERDGVEYHFVSKQAFEADVHHNKFLEHGEYKENLYGTSLEAIQAVMAKNKVCLVDVE--- 416
Cdd:PRK00300   27 ERDPNLQLSVSATTRAPRPGEVDGVDYFFVSKEEFEEMIENGEFLEWAEVFGNYYGTPRSPVEEALAAGKDVLLEIDwqg 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720364019 417 --------PEALRhlrtpefkpyvIFVKP----AIQER---RKTppvspDSED-IASSLDEQQQEMAASAAFidqhyghl 480
Cdd:PRK00300  107 arqvkkkmPDAVS-----------IFILPpsleELERRlrgRGT-----DSEEvIARRLAKAREEIAHASEY-------- 162

                         170       180
                  ....*....|....*....|..
gi 1720364019 481 iDTVLVRQDLQEACSQLRAVIE 502
Cdd:PRK00300  163 -DYVIVNDDLDTALEELKAIIR 183

guanylate kinase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720364019 288 EAKVPTGAESQVLLTYEEVARYQHQPGERPRLVVLIGSLGAHLHELKQRVVAEDPQQFAVAVPHTTRPRKSHERDGVEYH 367
Cdd:PLN02772  106 EVDTPFVREQKKLLGTEVVAWSKGVRGNAEKPIVISGPSGVGKGTLISMLMKEFPSMFGFSVSHTTRAPREMEKDGVHYH 185

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720364019 368 FVSKQAFEADVHHNKFLEHGEYKENLYGTSLEAIQAVMAKNKVCLVDVEPEALRHLRTPEFKPYVIFVKPAIQ---ERRK 444
Cdd:PLN02772  186 FTERSVMEKEIKDGKFLEFASVHGNLYGTSIEAVEVVTDSGKRCILDIDVQGARSVRASSLEAIFIFICPPSMeelEKRL 265

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1720364019 445 TPPVSPDSEDIASSLDEQQQEMAASaafidqHYGHLIDTVLVRQDLQEACSQLR 498
Cdd:PLN02772  266 RARGTETEEQIQKRLRNAEAELEQG------KSSGIFDHILYNDNLEECYKNLK 313

Src Homology 3 domain of Membrane Protein, Palmitoylated 5 (or MAGUK p55 subfamily member 5); MPP5, also called PALS1 (Protein associated with Lin7) or Nagie oko protein in zebrafish or Stardust in Drosophila, is a scaffolding protein which associates with Crumbs homolog 1 (CRB1), CRB2, or CRB3 through its PDZ domain and with PALS1-associated tight junction protein (PATJ) or multi-PDZ domain protein 1 (MUPP1) through its L27 domain. The resulting tri-protein complexes are core proteins of the Crumb complex, which localizes at tight junctions or subapical regions, and is involved in the maintenance of apical-basal polarity in epithelial cells and the morphogenesis and function of photoreceptor cells. MPP5 is critical for the proper stratification of the retina and is also expressed in T lymphocytes where it is important for TCR-mediated activation of NFkB. Drosophila Stardust exists in several isoforms, some of which show opposing functions in photoreceptor cells, which suggests that the relative ratio of different Crumbs complexes regulates photoreceptor homeostasis. MPP5 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720364019 163 MRALFHYDPREDRAIPCQEAGLPFQRRQVLEVVSQDDPTWWQAKRVGDTNLR--AGLIPSKQ 222
Cdd:cd12036     2 VRAHFDYDPEDDPYIPCRELGLSFQKGDILHVISQEDPNWWQAYREGEEDNQslAGLIPSKS 63

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 1720364019 162 FMRALFHYDPREDRAIPCQEAGLPFQRRQVLEVVSQDDPTWWQAKRVGDTNLRAGLIPSKQF 223
Cdd:cd12080     1 YMRAQFDYDPKKDNLIPCKEAGLKFQTGDIIQIINKDDSNWWQGRVEGSGEESAGLIPSPEL 62

Src Homology 3 domain of Calcium/calmodulin-dependent Serine protein Kinase; CASK is a scaffolding protein that is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. CASK interacts with many different binding partners including parkin, neurexin, syndecans, calcium channel proteins, caskin, among others, to perform specific functions in different subcellular locations. Disruption of the CASK gene in mice results in neonatal lethality while mutations in the human gene have been associated with X-linked mental retardation. Drosophila CASK is associated with both pre- and postsynaptic membranes and is crucial in synaptic transmission and vesicle cycling. CASK contains an N-terminal calmodulin-dependent kinase (CaMK)-like domain, 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720364019 162 FMRALFHYDPREDRAIPCQEAGLPFQRRQVLEVVSQDDPTWWQAKRVGDTNLRAGLIPSKQF 223
Cdd:cd12081     1 YVRAQFEYDPLKDDLIPCKQAGIRFRVGDILQIISKDDHNWWQAKLENSKNGTAGLIPSPEL 62

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720364019 162 FMRALFHYDPREDRAIPCQEAGLPFQRRQVLEVVSQDDPTWWQAKRV-GDTnlrAGLIPSK 221
Cdd:cd12037     1 FVKCHFDYDPSSDSLIPCKEAGLKFRAGDLLQIVNQEDPNWWQACHVeGGS---AGLIPSQ 58

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 1720364019   67 VKIVRLVKNKEPLGATIR-RDEHSGAVVVARIMRGGAADRSGLvHVGDELREVNGIAVLHKRPDEISQILAQSQGSITLK 145
Cdd:smart00228   2 PRLVELEKGGGGLGFSLVgGKDEGGGVVVSSVVPGSPAAKAGL-RVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLT 80

                   ...
gi 1720364019  146 IIP 148
Cdd:smart00228  81 VLR 83

Src Homology 3 domain of Membrane Protein, Palmitoylated 6 (or MAGUK p55 subfamily member 6); MPP6, also called Veli-associated MAGUK 1 (VAM-1) or PALS2, is a scaffolding protein that binds to Veli-1, a homolog of Caenorhabditis Lin-7. 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720364019 162 FMRALFHYDPREDRAIPCQEAGLPFQRRQVLEVVSQDDPTWWQAKRVGDTNlRAGLIPSK 221
Cdd:cd12038     1 FVKCHFDYNPYNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQASHVKEGG-SAGLIPSQ 59

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1720364019   1 MALAEDVMEELQAASVHS-DERELLQLLSTPHLRAVLMVHDTVAQKNFDPVL 51
Cdd:pfam02828   1 VELVLELLEDLQPLSEASeDLAELQKLLQSPHLQALLEAHDKVAQKVYEPPS 52

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
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720364019  93 VVARIMRGGAADRSGLVHVGDELREVNGIAVLHKRPDEISQILAQSQGSITLKIIP 148
Cdd:cd06734    29 KIGRIIPGSPADRCGQLKVGDRILAVNGISILNLSHGDIVNLIKDSGLSVTLTIVP 84

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720364019  70 VRLVKNK-EPLGATIR--RDEHSGAVVVARIMRGGAADRSGLvHVGDELREVNGIAVLHKRPDEISQILAQSQGSITLKI 146
Cdd:pfam00595   2 VTLEKDGrGGLGFSLKggSDQGDPGIFVSEVLPGGAAEAGGL-KVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLTI 80

                  .
gi 1720364019 147 I 147
Cdd:pfam00595  81 L 81

guanylate kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720364019 317 PRLVVLIGSLGAHLHELKQRVVAEDPQqFAVAVPHTTRPRKSHERDGVEYHFVSKQAFEADVHHNKFLEHGEYKENLYGT 396
Cdd:PRK14737    4 PKLFIISSVAGGGKSTIIQALLEEHPD-FLFSISCTTRAPRPGDEEGKTYFFLTIEEFKKGIADGEFLEWAEVHDNYYGT 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720364019 397 SLEAIQAVMAKNKVCLVDVEPEALRHLRT--PEfKPYVIFVKP---AIQERRKTPPVSPDSEDIASSLDEQQQEMAASAA 471
Cdd:PRK14737   83 PKAFIEDAFKEGRSAIMDIDVQGAKIIKEkfPE-RIVTIFIEPpseEEWEERLIHRGTDSEESIEKRIENGIIELDEANE 161

                         170       180       190
                  ....*....|....*....|....*....|
gi 1720364019 472 FidqhyghliDTVLVRQDLQEACSQLRAVI 501
Cdd:PRK14737  162 F---------DYKIINDDLEDAIADLEAII 182

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 1720364019 161 VFMRALFHYDPREDRAIPCQeaGLPFQRRQVLEVVSQDDPTWWQAKRV---GDTNlRAGLIPSKQFQERR 227
Cdd:cd12032     6 LYVRAMFDYEKSKDSGLPSQ--GLSFRYGDILHVINASDDEWWQARRVtpdGDSE-EMGVIPSKRRVERK 72

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720364019  79 LGATIRRDEhsGAVVVARIMRGGAADRSGLvHVGDELREVNGIAVLHKRPDEISQILAQSQGS-ITLKIIPATQEE 153
Cdd:COG0793    62 LGAELGEED--GKVVVVSVIPGSPAEKAGI-KPGDIILAIDGKSVAGLTLDDAVKLLRGKAGTkVTLTIKRPGEGE 134

PDZ domain 3 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. 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 Dlg5-like family PDZ3 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 1720364019  74 KNKEPLGATIRRDEHSGaVVVARIMRGGAADRSGLVhVGDELREVNGIAVLHKRPDEISQILAQSQGSITLKI 146
Cdd:cd06767    10 KGSEPLGISIVSGENGG-IFVSSVTEGSLAHQAGLE-YGDQLLEVNGINLRNATEQQAALILRQCGDTITMLV 80

circularly permuted PDZ domain of C-terminal processing peptidase (CPP), a serine protease, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CPP (also known as tail-specific protease, PRC protein, Protease Re, and Photosystem II D1 protein processing peptidase), and related domains. CPP belongs to the peptidase S41A family. It cleaves a C-terminal 11 residue peptide from the precursor form of penicillin-binding protein 3, and may have a role in protecting bacterium from thermal and osmotic stresses. In the plant chloroplast, the enzyme removes the C-terminal extension of the D1 polypeptide of photosystem II. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This CPP-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.