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 767959719 138 KIIRLVKNREPLGATIKKDEQTGAIIVARIMRGGAADRSGLIHVGDELREVNGIPVEDKRPEEIIQILAQSQGAITFKII 217
Cdd:cd06799    1 KIVRLVKNNEPLGATIKRDEKTGAIVVARIMRGGAADRSGLIHVGDELREVNGISVEGKDPEEVIQILANSQGPITFKLI 80

                 .
gi 767959719 218 P 218
Cdd:cd06799   81 P 81

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 767959719 232 FIKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKHEADANPRAGLIPSKH 292
Cdd:cd12033    1 FIKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKHEGDANPRAGLIPSKH 61

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

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 767959719   89 NSEIRELLKLLSKPNVKALLSVHDTVAQKNYDPVL 123
Cdd:pfam02828  18 SEDLAELQKLLQSPHLQALLEAHDKVAQKVYEPPS 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 767959719 138 KIIRLVKNREPLGATIKKDEQTGAIIVARIMRGGAADRSGLIHVGDELREVNGIPVEDKRPEEIIQILAQSQGAITFKII 217
Cdd:cd06799    1 KIVRLVKNNEPLGATIKRDEKTGAIVVARIMRGGAADRSGLIHVGDELREVNGISVEGKDPEEVIQILANSQGPITFKLI 80

                 .
gi 767959719 218 P 218
Cdd:cd06799   81 P 81

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 767959719 232 FIKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKHEADANPRAGLIPSKH 292
Cdd:cd12033    1 FIKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKHEGDANPRAGLIPSKH 61

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 767959719  386 RKLLISDTQHYGVTVPHTTRARRSQESDGVEYIFISKHLFETDVQNNKFIEYGEYKNNYYGTSIDSVRSVLAKNKVCLLD 465
Cdd:TIGR03263  17 VKALLEEDPNLKFSISATTRKPRPGEVDGVDYFFVSKEEFEEMIKAGEFLEWAEVHGNYYGTPKSPVEEALAAGKDVLLE 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767959719  466 VQPHTVKHLRTLEFKPYVIFIKPPSIERLREtRknakiISSRDDQgaakpfTEEDFQEMIKSAQiMESQYGHLFDKIIIN 545
Cdd:TIGR03263  97 IDVQGARQVKKKFPDAVSIFILPPSLEELER-R-----LRKRGTD------SEEVIERRLAKAK-KEIAHADEFDYVIVN 163

                         170
                  ....*....|.
gi 767959719  546 DDLTVAFNELK 556
Cdd:TIGR03263 164 DDLEKAVEELK 174

guanylate kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767959719 386 RKLLISDTQHYGVTVPHTTRARRSQESDGVEYIFISKHLFETDVQNNKFIEYGEYKNNYYGTSIDSVRSVLAKNKVCLL- 464
Cdd:PRK00300  22 VKALLERDPNLQLSVSATTRAPRPGEVDGVDYFFVSKEEFEEMIENGEFLEWAEVFGNYYGTPRSPVEEALAAGKDVLLe 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767959719 465 -DVQ---------PHTVKhlrtlefkpyvIFIKPPSIERLREtRknakiISSRD-DqgaakpfTEEDFQEMIKSAQImES 533
Cdd:PRK00300 102 iDWQgarqvkkkmPDAVS-----------IFILPPSLEELER-R-----LRGRGtD-------SEEVIARRLAKARE-EI 156

                        170       180
                 ....*....|....*....|....
gi 767959719 534 QYGHLFDKIIINDDLTVAFNELKT 557
Cdd:PRK00300 157 AHASEYDYVIVNDDLDTALEELKA 180

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 767959719   137 VKIIRLVKNREPLGATIKK-DEQTGAIIVARIMRGGAADRSGLiHVGDELREVNGIPVEDKRPEEIIQILAQSQGAITFK 215
Cdd:smart00228   2 PRLVELEKGGGGLGFSLVGgKDEGGGVVVSSVVPGSPAAKAGL-RVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLT 80

                   ....*
gi 767959719   216 IIPGS 220
Cdd:smart00228  81 VLRGG 85

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767959719  146 REPLGATIK--KDEQTGAIIVARIMRGGAADRSGlIHVGDELREVNGIPVEDKRPEEIIQILAQSQGAITFKII 217
Cdd:pfam00595   9 RGGLGFSLKggSDQGDPGIFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLTIL 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 767959719   229 GKMFIKALFDYNPnedkaipCKEAGLSFKKGDILQIMSQDDATWWQAKHEadaNPRAGLIPSKHFQ 294
Cdd:smart00326   1 EGPQVRALYDYTA-------QDPDELSFKKGDIITVLEKSDDGWWKGRLG---RGKEGLFPSNYVE 56

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

                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 767959719    89 NSEIRELLKLLSKPNVKALLSVHDTVAQKNYDPVLPP 125
Cdd:smart00569  17 SEDLQELRRLLQSPHLQALLKIHDKVAETELDPPLPE 53

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767959719 149 LGATIKKDEqtGAIIVARIMRGGAADRSGlIHVGDELREVNGIPVEDKRPEEIIQILAQSQG-AITFKIIPGSKEET 224
Cdd:COG0793   62 LGAELGEED--GKVVVVSVIPGSPAEKAG-IKPGDIILAIDGKSVAGLTLDDAVKLLRGKAGtKVTLTIKRPGEGEP 135

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 767959719 138 KIIRLVKNREPLGATIKKDEQTGAIIVARIMRGGAADRSGLIHVGDELREVNGIPVEDKRPEEIIQILAQSQGAITFKII 217
Cdd:cd06799    1 KIVRLVKNNEPLGATIKRDEKTGAIVVARIMRGGAADRSGLIHVGDELREVNGISVEGKDPEEVIQILANSQGPITFKLI 80

                 .
gi 767959719 218 P 218
Cdd:cd06799   81 P 81

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 767959719 232 FIKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKHEADANPRAGLIPSKH 292
Cdd:cd12033    1 FIKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKHEGDANPRAGLIPSKH 61

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767959719 232 FIKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKHEADANPRAGLIPSKH 292
Cdd:cd11862    1 FVRALFDYDPEEDPLIPCKEAGLSFKKGDILQIVNQDDPNWWQARKVGDPNGRAGLIPSQD 61

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 767959719 138 KIIRLVKNR-EPLGATIKKDEqtGAIIVARIMRGGAADRSGLIHVGDELREVNGIPVEDKRPEEIIQILAQSQGAITFKI 216
Cdd:cd06726    1 RLVEFEKARdEPLGATIKMEE--DSVIVARILHGGMAHRSGLLHVGDEILEINGIPVSGKTVDELQKLLSSLSGSVTFKL 78

                 ..
gi 767959719 217 IP 218
Cdd:cd06726   79 IP 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767959719 232 FIKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKHEADANPRAGLIPSKHF 293
Cdd:cd12039    1 FMRALFDYNPYEDRAIPCQEAGLPFKRRDILEVVSQDDPTWWQAKRVGDTNLRAGLIPSKQF 62

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 767959719 384 LKRKLLISDTQHYGVTVPHTTRARRSQESDGVEYIFISKHLFETDVQNNKFIEYGEYKNNYYGTSIDSVRSVLAKNKVCL 463
Cdd:cd00071   15 LLKRLLEEFDPNFGFSVSHTTRKPRPGEVDGVDYHFVSKEEFERLIENGEFLEWAEFHGNYYGTSKAAVEEALAEGKIVI 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767959719 464 LDVQPHTVKHLRTLEFKPYVIFIKPPsierlretrknakiissrddqgaakpfteedfqemiksaqimesqyghlfDKII 543
Cdd:cd00071   95 LEIDVQGARQVKKSYPDAVSIFILPP--------------------------------------------------DYVI 124

                        170
                 ....*....|...
gi 767959719 544 INDDLTVAFNELK 556
Cdd:cd00071  125 VNDDLEKAYEELK 137

guanylate kinase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767959719 396 YGVTVPHTTRARRSQESDGVEYIFISKHLFETDVQNNKFIEYGEYKNNYYGTSIDSVRSVLAKNKVCLLDVQPHTVKHLR 475
Cdd:PLN02772 163 FGFSVSHTTRAPREMEKDGVHYHFTERSVMEKEIKDGKFLEFASVHGNLYGTSIEAVEVVTDSGKRCILDIDVQGARSVR 242

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767959719 476 TLEFKPYVIFIKPPSIERLrETRknakiISSRDDQgaakpfTEEDFQEMIKSA--QIMESQYGHLFDKIIINDDLTVAFN 553
Cdd:PLN02772 243 ASSLEAIFIFICPPSMEEL-EKR-----LRARGTE------TEEQIQKRLRNAeaELEQGKSSGIFDHILYNDNLEECYK 310

                 ...
gi 767959719 554 ELK 556
Cdd:PLN02772 311 NLK 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 767959719 233 IKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQA--KHEADANPRAGLIPSKH 292
Cdd:cd12036    2 VRAHFDYDPEDDPYIPCRELGLSFQKGDILHVISQEDPNWWQAyrEGEEDNQSLAGLIPSKS 63

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 767959719 232 FIKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKHEADANPRAGLIPS 290
Cdd:cd12081    1 YVRAQFEYDPLKDDLIPCKQAGIRFRVGDILQIISKDDHNWWQAKLENSKNGTAGLIPS 59

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 767959719 138 KIIRLVKN-REPLGATIKKDEQtGAIIVARIMRGGAADRSGLIHVGDELREVNGIPVEDKRPEEIIQILAQSQGAITFKI 216
Cdd:cd10831    1 RLVQFQKNtDEPMGITLKMNED-GRCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREARGSITFKI 79

                 ..
gi 767959719 217 IP 218
Cdd:cd10831   80 VP 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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767959719 232 FIKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKHEADANprAGLIPSK 291
Cdd:cd12037    1 FVKCHFDYDPSSDSLIPCKEAGLKFRAGDLLQIVNQEDPNWWQACHVEGGS--AGLIPSQ 58

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains 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 767959719 140 IRLVKNR-EPLGATIK--KDEQTGaIIVARIMRGGAADRSGLIHVGDELREVNGIPVEDKRPEEIIQILAQSQGAITFKI 216
Cdd:cd00136    2 VTLEKDPgGGLGFSIRggKDGGGG-IFVSRVEPGGPAARDGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAGGEVTLTV 80

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 767959719 232 FIKALFDYNPNEDKAIPCKeaGLSFKKGDILQIMSQDDATWWQAKHEADAN--PRAGLIPSK 291
Cdd:cd11861    1 YVRALFDYDPSRDSGLPSQ--GLSFKFGDILHVTNASDDEWWQARRVTPNGeeEEVGVIPSK 60

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 767959719    16 ELLAALPAQLQPHVDSQEDLTFLWDMFGEKSLHSLVKIHEKLHYYEKQSPVPI 68
Cdd:smart00569   1 QRLLELLEELQSLLSPSEDLQELRRLLQSPHLQALLKIHDKVAETELDPPLPE 53

guanylate kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767959719 403 TTRARRSQESDGVEYIFISKHLFETDVQNNKFIEYGEYKNNYYGTSIDSVRSVLAKNKVCLLDVQPHTVKHLRTLEFKPY 482
Cdd:PRK14737  38 TTRAPRPGDEEGKTYFFLTIEEFKKGIADGEFLEWAEVHDNYYGTPKAFIEDAFKEGRSAIMDIDVQGAKIIKEKFPERI 117

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767959719 483 V-IFIKPPS----IERLRETRKNakiissrddqgaakpfTEEDFQEMIKSAqIMESQYGHLFDKIIINDDLTVAFNELK 556
Cdd:PRK14737 118 VtIFIEPPSeeewEERLIHRGTD----------------SEESIEKRIENG-IIELDEANEFDYKIINDDLEDAIADLE 179

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 767959719   15 YELLAALPAQLQPHVDSQEDLTFLWDMFGEKSLHSLVKIHEKLHYYEKQSP 65
Cdd:pfam02828   1 VELVLELLEDLQPLSEASEDLAELQKLLQSPHLQALLEAHDKVAQKVYEPP 51

PDZ domain of protein Lin-7 and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Lin-7 (also known as LIN-7 or LIN7), and related domains. Lin-7 targets and organize protein complexes to epithelial and synaptic plasma membranes. There are three mammalian Lin-7 homologs: Lin-7A (protein lin-7 homolog A, also known as mammalian lin-seven protein 1 (MALS-1), vertebrate lin-7 homolog 1 (Veli-1), tax interaction protein 33); Lin-7B (also known as MALS-2, Veli-2); and Lin-7C (also known as MALS-3, Veli-3). Lin-7 is involved in localization of the Let-23 growth factor receptor to the basolateral membrane of epithelial cells, in tight junction localization of insulin receptor substrate p53 (IRSp53), in retaining gamma-aminobutyric (GABA) transporter (BGT-1) at the basolateral surface of epithelial cells, and in regulating recruitment of neurotransmitter receptors to the postsynaptic density (PSD). The Lin7 PDZ domain binds Let-23, BGT and beta-catenin, and NMDA (N-methyl-D-aspartate) receptor NR2B. Lin-7 also binds to the PDZ binding motif located in the C-terminal tail of Rhotekin, an effector protein for small GTPase Rho. 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 Lin-7-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 767959719 138 KIIRLVKNREPLGATIKK-DEQTGAIIVARIMRGGAADRSGLIHVGDELREVNGIPVEDKRPEEIIQILAQSQGAIT 213
Cdd:cd06796    3 RVVELPKTEEGLGFNVMGgKEQNSPIYISRIIPGGVADRHGGLKRGDQLLSVNGVSVEGEHHEKAVELLKAAQGSVK 79

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 767959719   229 GKMFIKALFDYNPnedkaipCKEAGLSFKKGDILQIMSQDDATWWQAKHEadaNPRAGLIPSKHFQ 294
Cdd:smart00326   1 EGPQVRALYDYTA-------QDPDELSFKKGDIITVLEKSDDGWWKGRLG---RGKEGLFPSNYVE 56

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 767959719 164 VARIMRGGAADRSGLIHVGDELREVNGIPVEDKRPEEIIQILAQSQGAITFKIIP 218
Cdd:cd06734   30 IGRIIPGSPADRCGQLKVGDRILAVNGISILNLSHGDIVNLIKDSGLSVTLTIVP 84

Src Homology 3 domain of Disks Large homolog 3; DLG3, also called synapse-associated protein 102 (SAP102), is a scaffolding protein that clusters at synapses and plays an important role in synaptic development and plasticity. Mutations in DLG3 cause midgestational embryonic lethality in mice and may be associated with nonsyndromic X-linked mental retardation in humans. It interacts with the NEDD4 (neural precursor cell-expressed developmentally downregulated 4) family of ubiquitin ligases and promotes apical tight junction formation. DLG3 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. DLG3 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 767959719 231 MFIKALFDYNPNEDKAIPCKeaGLSFKKGDILQIMSQDDATWWQAK--HEADANPRAGLIPSK 291
Cdd:cd12029    3 LYVRALFDYDRTRDSCLPSQ--GLSFSYGDILHVINASDDEWWQARlvTPHGESEQIGVIPSK 63

PDZ domain 2 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss 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 Scribble-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767959719 150 GATIKKDEQTGaIIVARIMRGGAADRSGLIHVGDELREVNGIPVEDKRPEEIIQILAQSQGAIT 213
Cdd:cd06703   23 GSTPFRDGDEG-IFISRITEGGAADRDGKLQVGDRVLSINGVDVTEARHDQAVALLTSSSPTIT 85

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767959719 232 FIKALFDYNPNEDKAipckeagLSFKKGDILQIMSQDDATWWQAKheadANPRAGLIPSKHFQ 294
Cdd:cd11949    1 YVQALFDFDPQEDGE-------LGFRRGDFIEVMDNSDPNWWKGA----CHGQTGMFPRNYVT 52

PDZ domain 4 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 PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767959719 163 IVARIMRGGAADRSGLIHVGDELREVNGIPVEDKRPEEIIQILAQSQGAITFKI 216
Cdd:cd06686   39 LISFIEPDSPAERCGVLQVGDRVLSINGIPTEDRTLEEANQLLRDSASKVTLEI 92