Guanylate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2557366340 284 RKTLVLIGAHGVGRSLIKNSLLSKYPEKFAYPAPHTTRPQKKDEENGKEYYFISNDEMTKGIVGNELLEYGSYQGHMFGT 363
Cdd:pfam00625   2 RRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYGT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2557366340 364 KIETIHKIHEQGKIAVLDVEPQTLKVLRTAEFAPLVIFIAPT--------NTGNQSEAVQNIQKESDSLLAAHRHF-FDE 434
Cdd:pfam00625  82 SVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPslkvlqrrLKGRGKEQEEKINKRMAAAEQEFQHYeFDV 161

                         170
                  ....*....|....*....
gi 2557366340 435 ILVNNDVDESVKGVEDAIE 453
Cdd:pfam00625 162 IIVNDDLEEAYKKLKEALE 180

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 2557366340 164 YMRAQFDYDPAKDELIPCKEAGLKFQTGDIIHIINKKDPNWWQGKVDSSSTDFAGLIPSPEL 225
Cdd:cd12080     1 YMRAQFDYDPKKDNLIPCKEAGLKFQTGDIIQIINKDDSNWWQGRVEGSGEESAGLIPSPEL 62

Guanylate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2557366340 284 RKTLVLIGAHGVGRSLIKNSLLSKYPEKFAYPAPHTTRPQKKDEENGKEYYFISNDEMTKGIVGNELLEYGSYQGHMFGT 363
Cdd:pfam00625   2 RRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYGT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2557366340 364 KIETIHKIHEQGKIAVLDVEPQTLKVLRTAEFAPLVIFIAPT--------NTGNQSEAVQNIQKESDSLLAAHRHF-FDE 434
Cdd:pfam00625  82 SVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPslkvlqrrLKGRGKEQEEKINKRMAAAEQEFQHYeFDV 161

                         170
                  ....*....|....*....
gi 2557366340 435 ILVNNDVDESVKGVEDAIE 453
Cdd:pfam00625 162 IIVNDDLEEAYKKLKEALE 180

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 2557366340  72 REVAFEKNPSEPLGVTLKLNEKQRCTVARILHGGMIHRQGSLHEGDEIAEINGKSVSNQSVDQLQKILKDTNGVVTLKII 151
Cdd:cd10830     1 RLVQFEKNTEEPMGITLKLNEKQSCIVARILHGGMIHRQGSLHVGDEILEINGKSVTNHSVDQLQKMLKETKGMVSLKVI 80

                  .
gi 2557366340 152 S 152
Cdd:cd10830    81 P 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 2557366340 287 LVLIGAHGVGRSLIKNSLLSKYPEKFAYPAPHTTRPQKKDEENGKEYYFISNDEMTKGIVGNELLEYGSYQGHMFGTKIE 366
Cdd:cd00071     2 IVLSGPSGVGKSTLLKRLLEEFDPNFGFSVSHTTRKPRPGEVDGVDYHFVSKEEFERLIENGEFLEWAEFHGNYYGTSKA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2557366340 367 TIHKIHEQGKIAVLDVEPQTLKVLRTAEFAPLVIFIAPTntgnqseavqniqkesdsllaahrhffDEILVNNDVDESVK 446
Cdd:cd00071    82 AVEEALAEGKIVILEIDVQGARQVKKSYPDAVSIFILPP---------------------------DYVIVNDDLEKAYE 134

                  ...
gi 2557366340 447 GVE 449
Cdd:cd00071   135 ELK 137

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 2557366340 287 LVLIGAHGVGRSLIKNSLLSKYPEkFAYPAPHTTRPQKKDEENGKEYYFISNDEMTKGIVGNELLEYGSYQGHMFGTKIE 366
Cdd:TIGR03263   3 IVISGPSGAGKSTLVKALLEEDPN-LKFSISATTRKPRPGEVDGVDYFFVSKEEFEEMIKAGEFLEWAEVHGNYYGTPKS 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2557366340 367 TIHKIHEQGKIAVLDVEPQTLKVLRTAEFAPLVIFIAPtntGNQSEAVQNIQK---ESDSLLA----------AHRHFFD 433
Cdd:TIGR03263  82 PVEEALAAGKDVLLEIDVQGARQVKKKFPDAVSIFILP---PSLEELERRLRKrgtDSEEVIErrlakakkeiAHADEFD 158

                         170
                  ....*....|....*....
gi 2557366340 434 EILVNNDVDESVKGVEDAI 452
Cdd:TIGR03263 159 YVIVNDDLEKAVEELKSII 177

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2557366340  73 EVAFEKNPSEPLGVTLKLNEKQR---CTVARILHGGMIHRQGsLHEGDEIAEINGKSVSNQSVDQLQKILKDTNGVVTLK 149
Cdd:pfam00595   1 QVTLEKDGRGGLGFSLKGGSDQGdpgIFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLT 79

                  ..
gi 2557366340 150 II 151
Cdd:pfam00595  80 IL 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
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2557366340  164 YMRAQFDYDPAKDElipckeaGLKFQTGDIIHIINKKDPNWWQGKVDSSSTdfaGLIPS 222
Cdd:smart00326   4 QVRALYDYTAQDPD-------ELSFKKGDIITVLEKSDDGWWKGRLGRGKE---GLFPS 52

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2557366340  63 MNGRDATRMREvaFEKNPSEPLGVTLKLnEKQRCTVARILHGGMIHRQGsLHEGDEIAEINGKSVSNQSVDQLQKILKDT 142
Cdd:COG0793    43 LDPEEYEDFQE--STSGEFGGLGAELGE-EDGKVVVVSVIPGSPAEKAG-IKPGDIILAIDGKSVAGLTLDDAVKLLRGK 118

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2557366340 143 NG-VVTLKIISNQQSRPMACEMyMRAQFDYDPAKDELIP 180
Cdd:COG0793   119 AGtKVTLTIKRPGEGEPITVTL-TRAEIKLPSVEAKLLE 156

Guanylate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2557366340 284 RKTLVLIGAHGVGRSLIKNSLLSKYPEKFAYPAPHTTRPQKKDEENGKEYYFISNDEMTKGIVGNELLEYGSYQGHMFGT 363
Cdd:pfam00625   2 RRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYGT 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2557366340 364 KIETIHKIHEQGKIAVLDVEPQTLKVLRTAEFAPLVIFIAPT--------NTGNQSEAVQNIQKESDSLLAAHRHF-FDE 434
Cdd:pfam00625  82 SVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPslkvlqrrLKGRGKEQEEKINKRMAAAEQEFQHYeFDV 161

                         170
                  ....*....|....*....
gi 2557366340 435 ILVNNDVDESVKGVEDAIE 453
Cdd:pfam00625 162 IIVNDDLEEAYKKLKEALE 180

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 2557366340  72 REVAFEKNPSEPLGVTLKLNEKQRCTVARILHGGMIHRQGSLHEGDEIAEINGKSVSNQSVDQLQKILKDTNGVVTLKII 151
Cdd:cd10830     1 RLVQFEKNTEEPMGITLKLNEKQSCIVARILHGGMIHRQGSLHVGDEILEINGKSVTNHSVDQLQKMLKETKGMVSLKVI 80

                  .
gi 2557366340 152 S 152
Cdd:cd10830    81 P 81

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 2557366340 164 YMRAQFDYDPAKDELIPCKEAGLKFQTGDIIHIINKKDPNWWQGKVDSSSTDFAGLIPSPEL 225
Cdd:cd12080     1 YMRAQFDYDPKKDNLIPCKEAGLKFQTGDIIQIINKDDSNWWQGRVEGSGEESAGLIPSPEL 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 2557366340  72 REVAFEKNPSEPLGVTLKLNEKqRCTVARILHGGMIHRQGSLHEGDEIAEINGKSVSNQSVDQLQKILKDTNGVVTLKII 151
Cdd:cd06726     1 RLVEFEKARDEPLGATIKMEED-SVIVARILHGGMAHRSGLLHVGDEILEINGIPVSGKTVDELQKLLSSLSGSVTFKLI 79

                  .
gi 2557366340 152 S 152
Cdd:cd06726    80 P 80

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 2557366340 287 LVLIGAHGVGRSLIKNSLLSKYPEKFAYPAPHTTRPQKKDEENGKEYYFISNDEMTKGIVGNELLEYGSYQGHMFGTKIE 366
Cdd:cd00071     2 IVLSGPSGVGKSTLLKRLLEEFDPNFGFSVSHTTRKPRPGEVDGVDYHFVSKEEFERLIENGEFLEWAEFHGNYYGTSKA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2557366340 367 TIHKIHEQGKIAVLDVEPQTLKVLRTAEFAPLVIFIAPTntgnqseavqniqkesdsllaahrhffDEILVNNDVDESVK 446
Cdd:cd00071    82 AVEEALAEGKIVILEIDVQGARQVKKSYPDAVSIFILPP---------------------------DYVIVNDDLEKAYE 134

                  ...
gi 2557366340 447 GVE 449
Cdd:cd00071   135 ELK 137

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 2557366340  72 REVAFEKNPSEPLGVTLKLNEKQrCTVARILHGGMIHRQGSLHEGDEIAEINGKSVSNQsvDQLQKILKDTNGVVTLKII 151
Cdd:cd10832     1 RMVGIRKNPGEPLGVTVRLEEGE-LVIARILHGGMIDRQGLLHVGDIIKEVNGVPVGSP--EQLQEMLKNASGSVTLKIL 77

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 2557366340 287 LVLIGAHGVGRSLIKNSLLSKYPEkFAYPAPHTTRPQKKDEENGKEYYFISNDEMTKGIVGNELLEYGSYQGHMFGTKIE 366
Cdd:TIGR03263   3 IVISGPSGAGKSTLVKALLEEDPN-LKFSISATTRKPRPGEVDGVDYFFVSKEEFEEMIKAGEFLEWAEVHGNYYGTPKS 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2557366340 367 TIHKIHEQGKIAVLDVEPQTLKVLRTAEFAPLVIFIAPtntGNQSEAVQNIQK---ESDSLLA----------AHRHFFD 433
Cdd:TIGR03263  82 PVEEALAAGKDVLLEIDVQGARQVKKKFPDAVSIFILP---PSLEELERRLRKrgtDSEEVIErrlakakkeiAHADEFD 158

                         170
                  ....*....|....*....
gi 2557366340 434 EILVNNDVDESVKGVEDAI 452
Cdd:TIGR03263 159 YVIVNDDLEKAVEELKSII 177

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 2557366340 164 YMRAQFDYDPAKDELIPCKEAGLKFQTGDIIHIINKKDPNWWQG-KVDSSStdfAGLIPS 222
Cdd:cd12037     1 FVKCHFDYDPSSDSLIPCKEAGLKFRAGDLLQIVNQEDPNWWQAcHVEGGS---AGLIPS 57

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2557366340 164 YMRAQFDYDPAKDELIPCKEAGLKFQTGDIIHIINKKDPNWWQGKVDSSSTDFAGLIPS 222
Cdd:cd12033     1 FIKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKHEGDANPRAGLIPS 59

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2557366340  82 EPLGVTLKLNEKQRCT-VARILHGGMIHRQGSLHEGDEIAEINGKSVSNQSVDQLQKILKDTNGVVTLKII 151
Cdd:cd06799    10 EPLGATIKRDEKTGAIvVARIMRGGAADRSGLIHVGDELREVNGISVEGKDPEEVIQILANSQGPITFKLI 80

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2557366340 164 YMRAQFDYDPAKDELIPCKEAGLKFQTGDIIHIINKKDPNWWQGKVDSSSTDFAGLIPS 222
Cdd:cd12039     1 FMRALFDYNPYEDRAIPCQEAGLPFKRRDILEVVSQDDPTWWQAKRVGDTNLRAGLIPS 59

Src Homology 3 domain of Membrane Protein, Palmitoylated 4 (or MAGUK p55 subfamily member 4); MPP4, also called Disks Large homolog 6 (DLG6) or Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 5 protein (ALS2CR5), is a retina-specific scaffolding protein that plays a role in organizing presynaptic protein complexes in the photoreceptor synapse, where it localizes to the plasma membrane. It is required in the proper localization of calcium ATPases and for maintenance of calcium homeostasis. MPP4 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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2557366340 164 YMRAQFDYDPAKDELIPCKEAGLKFQTGDIIHIINKKDPNWWQGKVDSSSTDFAGLIPS 222
Cdd:cd12034     1 YVRAMVDYWPQQDPSIPCADAGLPFRKGDILQIVDQNDSLWWQARKLSDLAACAGLIPS 59

Src Homology 3 domain of Disks large homolog proteins; The DLG-like proteins are scaffolding proteins that cluster at synapses and are also called PSD (postsynaptic density)-95 proteins or SAPs (synapse-associated proteins). They play important roles in synaptic development and plasticity, cell polarity, migration and proliferation. They are members 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. DLG-like proteins contain three PDZ domains and varying N-terminal regions. All DLG proteins exist as alternatively-spliced isoforms. Vertebrates contain four DLG proteins from different genes, called DLG1-4. DLG4 and DLG2 are found predominantly at postsynaptic sites and they mediate surface ion channel and receptor clustering. DLG3 is found axons and some presynaptic terminals. DLG1 interacts with AMPA-type glutamate receptors and is critical in their maturation and delivery to synapses. 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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2557366340 164 YMRAQFDYDPAKDELIPCKeaGLKFQTGDIIHIINKKDPNWWQGK--VDSSSTDFAGLIPS 222
Cdd:cd11861     1 YVRALFDYDPSRDSGLPSQ--GLSFKFGDILHVTNASDDEWWQARrvTPNGEEEEVGVIPS 59

guanylate kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2557366340 285 KTLVLIGAHGVGRSLIKNSLLSKYPEkFAYPAPHTTRPQKKDEENGKEYYFISNDEMTKGIVGNELLEYGSYQGHMFGTK 364
Cdd:PRK14737    5 KLFIISSVAGGGKSTIIQALLEEHPD-FLFSISCTTRAPRPGDEEGKTYFFLTIEEFKKGIADGEFLEWAEVHDNYYGTP 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2557366340 365 IETIHKIHEQGKIAVLDVEPQTLKVLRTAEFAPLV-IFIAPTN------------TGNQSEAVQNIQKESDSLLAAHRhf 431
Cdd:PRK14737   84 KAFIEDAFKEGRSAIMDIDVQGAKIIKEKFPERIVtIFIEPPSeeeweerlihrgTDSEESIEKRIENGIIELDEANE-- 161

                         170       180
                  ....*....|....*....|.
gi 2557366340 432 FDEILVNNDVDESVKGVEDAI 452
Cdd:PRK14737  162 FDYKIINDDLEDAIADLEAII 182

PDZ domain 5 of inactivation no after potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ45 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. 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 INAD-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 2557366340  73 EVAFEKNPSEPLGVTLKLNEKQRCTVARILHGGMIHRQGSLHEGDEIAEINGKSVSNQSVDQLQKILKDTNGVVTLKI 150
Cdd:cd23066     1 EVELMKKAGKELGLSLSPNEGIGCTIADLLPGGYAEIDGKLQKGDIITKFNGDALSGLPFQVCYALFKGANGKISLEV 78

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
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 2557366340  164 YMRAQFDYDPAKDElipckeaGLKFQTGDIIHIINKKDPNWWQGKVDSSSTdfaGLIPS 222
Cdd:smart00326   4 QVRALYDYTAQDPD-------ELSFKKGDIITVLEKSDDGWWKGRLGRGKE---GLFPS 52

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2557366340 163 MYMRAQFDYDPAKDELIPCKeaGLKFQTGDIIHIINKKDPNWWQGK--VDSSSTDFAGLIPS 222
Cdd:cd12032     6 LYVRAMFDYEKSKDSGLPSQ--GLSFRYGDILHVINASDDEWWQARrvTPDGDSEEMGVIPS 65

PDZ domain 6 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. 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 GRIP family PDZ6 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 2557366340  83 PLGVTLKLNEK--QRCTVARILHGGMIHRQGSLHEGDEIAEINGKSVSNQSVDQLQKILKDTNGVVTLKI 150
Cdd:cd06683    14 PLGITISGTEEpfDPIVISGLTEGGLAERTGAIHVGDRILAINGESLRGKPLSEAIHLLQNAGDTVTLKI 83

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically 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 2557366340 164 YMRAQFDYDPAKDelipckeAGLKFQTGDIIHIINKKDPNWWQGKVDSSStdfaGLIPS 222
Cdd:cd11949     1 YVQALFDFDPQED-------GELGFRRGDFIEVMDNSDPNWWKGACHGQT----GMFPR 48

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 2557366340 166 RAQFDYDPAKDElipckEagLKFQTGDIIHIINKKDPNWWQGKVDSSSTdfaGLIPS 222
Cdd:pfam00018   1 VALYDYTAQEPD-----E--LSFKKGDIIIVLEKSEDGWWKGRNKGGKE---GLIPS 47

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2557366340 164 YMRAQFDYDPAKDelipCK--EAGLKFQTGDIIHIINKKDPNWWQGK--VDSSSTDFAGLIPS 222
Cdd:cd12030     3 YIRALFDYDKTKD----CGflSQALSFRFGDVLHVIDAGDEEWWQARrvHSDSETEEIGFIPS 61

PDZ domain 1 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, APBA3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of APBA1, APBA2, APBA3, and related domains. The APBA/X11/Mint protein family includes three members: neuron specific APBA1 (also known as X11alpha and Mint1) and APBA2 (also known as X11beta and Mint2), and the ubiquitously expressed APBA3 (also known as (X12gamma and Mint3). They are involved in regulating neuronal signaling, trafficking and plasticity. They contain two PDZ domains (PDZ1 and PDZ2) which bind a variety of proteins: Arf GTPases (APBA1 and APBA2 PDZ2) and neurexin (APBA1 and APBA2 PDZ1 and 2), which are involved in vesicle docking and exocytosis; alpha1B subunit of N-type Ca2+ channel (APBA1 PDZ1) that is involved in ion channels; KIF17 (APBA1 PDZ1) that is involved in transport and traffic; and Alzheimer's disease related proteins such as APP (APBA3 PDZ2), CCS (APBA1 PDZ2), NF-kappa-B/p65 (APBA2 PDZ2), presenilin-1 (APBA1 and APBA2 PDZ1 and PDZ2). 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 APBA1,2,3-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 2557366340  72 REVAFEKNPSEPLGVTLKlnEKQR------CTVARILHGGMIHRQGSLHEGDEIAEINGKSVSNQSVDQLQKILKDTNG- 144
Cdd:cd06720     1 KEVVVEKQKGEILGVVIV--ESGWgsllptVVVANMMPGGPAARSGKLNIGDQIMSINGTSLVGLPLSTCQAIIKNLKNq 78

                  ....*...
gi 2557366340 145 -VVTLKII 151
Cdd:cd06720    79 tKVKLTVV 86

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. 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 2557366340 166 RAQFDYDPAK-DELipckeaglKFQTGDIIHIINKKDPNWWQGKVDSSStdfaGLIPS 222
Cdd:cd11772     3 RALYDYEAQHpDEL--------SFEEGDLLYISDKSDPNWWKATCGGKT----GLIPS 48