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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207119214 139 RMISIQKKAGEPLGVTFRVEEGDLVIARVLHGSMIDRQGMLHAGDVIREVNGREVGkDPMALQHMLRDCNGSITLKILP 217
Cdd:cd10832     1 RMVGIRKNPGEPLGVTVRLEEGELVIARILHGGMIDRQGLLHVGDIIKEVNGVPVG-SPEQLQEMLKNASGSVTLKILP 78

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1207119214  68 VELVSEILSDMSSLIIRDESAAELSNILKEPHFQSLLEAHDKVASKSYEAPP 119
Cdd:pfam02828   1 VELVLELLEDLQPLSEASEDLAELQKLLQSPHLQALLEAHDKVAQKVYEPPS 52

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207119214  357 QGVGRRSLKNRLIVLNPLRYGTTVPFTSRRPRDDEKDGQSYCFVSREEMEMDIKASRYLEHGEYDGNLYGTKMDSIHEVV 436
Cdd:smart00072   1 SGVGKGTLLAELIQEIPDAFERVVSHTTRPPRPGEVNGVDYHFVSKEEFEDDIKSGLFLEWGEYEGNYYGTSKETIRQVA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207119214  437 RAGRTCILDVNPQALKVLKTSEFMPFVVFIAAPELDTLRAMHKAvvdagittkLLTETD--LKKTVDESARIKRAYnHYF 514
Cdd:smart00072  81 EKGKHCLLDIDPQGVKQLRKAQLYPIVIFIAPPSSEELERRLRQ---------RGTETSerIQKRLAAAQKEAQEY-HLF 150

                          170       180
                   ....*....|....*....|..
gi 1207119214  515 DLTIVNDNLDKAFEKLQAAVEQ 536
Cdd:smart00072 151 DYVIVNDDLEDAYEELKEILEA 172

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 1207119214 229 YLKPHFNYNPNTDNLIPCREAGLAFSKGDILHIVNKEDPNWWQACNIN--GGHTGLIPSQ 286
Cdd:cd11862     1 FVRALFDYDPEEDPLIPCKEAGLSFKKGDILQIVNQDDPNWWQARKVGdpNGRAGLIPSQ 60

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 1207119214 351 LVLIGAQGVGRRSLKNRLIVLNPLRYGTTVPFTSRRPRDDEKDGQSYCFVSREEMEMDIKASRYLEHGEYDGNLYGTKMD 430
Cdd:cd00071     2 IVLSGPSGVGKSTLLKRLLEEFDPNFGFSVSHTTRKPRPGEVDGVDYHFVSKEEFERLIENGEFLEWAEFHGNYYGTSKA 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207119214 431 SIHEVVRAGRTCILDVNPQALKVLKTSEFMPFVVFIAAPeldtlramhkavvdagittklltetdlkktvdesarikray 510
Cdd:cd00071    82 AVEEALAEGKIVILEIDVQGARQVKKSYPDAVSIFILPP----------------------------------------- 120

                         170       180
                  ....*....|....*....|
gi 1207119214 511 nhyfDLTIVNDNLDKAFEKL 530
Cdd:cd00071   121 ----DYVIVNDDLEKAYEEL 136

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1207119214  68 VELVSEILSDMSSLIIRDESAAELSNILKEPHFQSLLEAHDKVASKSYEAPP 119
Cdd:pfam02828   1 VELVLELLEDLQPLSEASEDLAELQKLLQSPHLQALLEAHDKVAQKVYEPPS 52

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
                   ....*....|....*....|....*....|....*....|....*
gi 1207119214  245 PCREAGLAFSKGDILHIVNKEDPNWWQACNiNGGHTGLIPSQFLE 289
Cdd:smart00326  13 AQDPDELSFKKGDIITVLEKSDDGWWKGRL-GRGKEGLFPSNYVE 56

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207119214   13 QQVLDNLKELPPSTGAKDiDLIFLRGIMESPIVRSLAKAHERLEDVKLEAVQSN 66
Cdd:smart00569   1 QRLLELLEELQSLLSPSE-DLQELRRLLQSPHLQALLKIHDKVAETELDPPLPE 53

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 1207119214  138 VRMISIQKKaGEPLGVTF---RVEEGDLVIARVLHGSMIDRQGmLHAGDVIREVNGREV-GKDPMALQHMLRDCNGSITL 213
Cdd:smart00228   2 PRLVELEKG-GGGLGFSLvggKDEGGGVVVSSVVPGSPAAKAG-LRVGDVILEVNGTSVeGLTHLEAVDLLKKAGGKVTL 79

                   ....
gi 1207119214  214 KILP 217
Cdd:smart00228  80 TVLR 83

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207119214 133 MPADTVRMISIQKK-AGEPLGVTFRVEEGDLVIARVLHGSMIDRQGmLHAGDVIREVNGREV-GKDPMALQHMLRDCNGS 210
Cdd:COG0793    43 LDPEEYEDFQESTSgEFGGLGAELGEEDGKVVVVSVIPGSPAEKAG-IKPGDIILAIDGKSVaGLTLDDAVKLLRGKAGT 121

                          90
                  ....*....|....
gi 1207119214 211 -ITLKILPSYKDTP 223
Cdd:COG0793   122 kVTLTIKRPGEGEP 135

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207119214  357 QGVGRRSLKNRLIVLNPLRYGTTVPFTSRRPRDDEKDGQSYCFVSREEMEMDIKASRYLEHGEYDGNLYGTKMDSIHEVV 436
Cdd:smart00072   1 SGVGKGTLLAELIQEIPDAFERVVSHTTRPPRPGEVNGVDYHFVSKEEFEDDIKSGLFLEWGEYEGNYYGTSKETIRQVA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207119214  437 RAGRTCILDVNPQALKVLKTSEFMPFVVFIAAPELDTLRAMHKAvvdagittkLLTETD--LKKTVDESARIKRAYnHYF 514
Cdd:smart00072  81 EKGKHCLLDIDPQGVKQLRKAQLYPIVIFIAPPSSEELERRLRQ---------RGTETSerIQKRLAAAQKEAQEY-HLF 150

                          170       180
                   ....*....|....*....|..
gi 1207119214  515 DLTIVNDNLDKAFEKLQAAVEQ 536
Cdd:smart00072 151 DYVIVNDDLEDAYEELKEILEA 172

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 1207119214 229 YLKPHFNYNPNTDNLIPCREAGLAFSKGDILHIVNKEDPNWWQACNIN--GGHTGLIPSQ 286
Cdd:cd11862     1 FVRALFDYDPEEDPLIPCKEAGLSFKKGDILQIVNQDDPNWWQARKVGdpNGRAGLIPSQ 60

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207119214 229 YLKPHFNYNPNTDNLIPCREAGLAFSKGDILHIVNKEDPNWWQACNINGGHTGLIPSQF 287
Cdd:cd12037     1 FVKCHFDYDPSSDSLIPCKEAGLKFRAGDLLQIVNQEDPNWWQACHVEGGSAGLIPSQL 59

Src Homology 3 domain of Membrane Protein, Palmitoylated 6 (or MAGUK p55 subfamily member 6); MPP6, also called Veli-associated MAGUK 1 (VAM-1) or PALS2, is a scaffolding protein that binds to Veli-1, a homolog of Caenorhabditis Lin-7. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207119214 229 YLKPHFNYNPNTDNLIPCREAGLAFSKGDILHIVNKEDPNWWQACNIN-GGHTGLIPSQFL 288
Cdd:cd12038     1 FVKCHFDYNPYNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQASHVKeGGSAGLIPSQFL 61

guanylate kinase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207119214 349 KTLVLIGAQGVGRRSLKNRLIVLNPLRYGTTVPFTSRRPRDDEKDGQSYCFVSREEMEMDIKASRYLEHGEYDGNLYGTK 428
Cdd:PLN02772  136 KPIVISGPSGVGKGTLISMLMKEFPSMFGFSVSHTTRAPREMEKDGVHYHFTERSVMEKEIKDGKFLEFASVHGNLYGTS 215

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207119214 429 MDSIHEVVRAGRTCILDVNPQALKVLKTSEFMPFVVFIAAPELDTLRAMHKAvvdAGITTKlltETDLKKTVDESARIKR 508
Cdd:PLN02772  216 IEAVEVVTDSGKRCILDIDVQGARSVRASSLEAIFIFICPPSMEELEKRLRA---RGTETE---EQIQKRLRNAEAELEQ 289

                         170       180
                  ....*....|....*....|....
gi 1207119214 509 AYNHY-FDLTIVNDNLDKAFEKLQ 531
Cdd:PLN02772  290 GKSSGiFDHILYNDNLEECYKNLK 313

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 1207119214 139 RMISIQKKAGEPLGVTFRV-EEGDLVIARVLHGSMIDRQGMLHAGDVIREVNGREV-GKDPMALQHMLRDCNGSITLKIL 216
Cdd:cd10831     1 RLVQFQKNTDEPMGITLKMnEDGRCIVARIMHGGMIHRQGTLHVGDEIREINGISVaNQTVEQLQKMLREARGSITFKIV 80

                  .
gi 1207119214 217 P 217
Cdd:cd10831    81 P 81

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 1207119214 138 VRMIsiqkKAGEPLGVTFRVEE--GDLVIARVLHGSMIDRQGMLHAGDVIREVNGREV-GKDPMALQHMLRDCNGSITLK 214
Cdd:cd06799     3 VRLV----KNNEPLGATIKRDEktGAIVVARIMRGGAADRSGLIHVGDELREVNGISVeGKDPEEVIQILANSQGPITFK 78

                  ...
gi 1207119214 215 ILP 217
Cdd:cd06799    79 LIP 81

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207119214 229 YLKPHFNYNPNTDNLIPCREAGLAFSKGDILHIVNKEDPNWWQACNING--GHTGLIPSQFL 288
Cdd:cd12035     1 YVRAQFDYDPSKDDLIPCQQAGIAFKTGDILQIISKDDHNWWQARKPGAskEPAGLIPSPEL 62

Src Homology 3 domain of Calcium/calmodulin-dependent Serine protein Kinase; CASK is a scaffolding protein that is highly expressed in the mammalian nervous system and plays roles in synaptic protein targeting, neural development, and gene expression regulation. CASK interacts with many different binding partners including parkin, neurexin, syndecans, calcium channel proteins, caskin, among others, to perform specific functions in different subcellular locations. Disruption of the CASK gene in mice results in neonatal lethality while mutations in the human gene have been associated with X-linked mental retardation. Drosophila CASK is associated with both pre- and postsynaptic membranes and is crucial in synaptic transmission and vesicle cycling. CASK contains an N-terminal calmodulin-dependent kinase (CaMK)-like domain, two L27 domains, followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207119214 229 YLKPHFNYNPNTDNLIPCREAGLAFSKGDILHIVNKEDPNWWQACNIN--GGHTGLIPS 285
Cdd:cd12081     1 YVRAQFEYDPLKDDLIPCKQAGIRFRVGDILQIISKDDHNWWQAKLENskNGTAGLIPS 59

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1207119214  68 VELVSEILSDMSSLIIRDESAAELSNILKEPHFQSLLEAHDKVASKSYEAPP 119
Cdd:pfam02828   1 VELVLELLEDLQPLSEASEDLAELQKLLQSPHLQALLEAHDKVAQKVYEPPS 52

guanylate kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207119214 351 LVLIGAQGVGRRSLKNRLIVLN-PLRYGTTVpfTSRRPRDDEKDGQSYCFVSREEMEMDIKASRYLEHGEYDGNLYGTKM 429
Cdd:PRK14738   16 VVISGPSGVGKDAVLARMRERKlPFHFVVTA--TTRPKRPGEIDGVDYHFVTPEEFREMISQNELLEWAEVYGNYYGVPK 93

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207119214 430 DSIHEVVRAGRTCILDVNPQALKVLKtsEFMPFVVFI--AAPELDTL--RAMHKavvdagittklLTE--TDLKKTVDES 503
Cdd:PRK14738   94 APVRQALASGRDVIVKVDVQGAASIK--RLVPEAVFIflAPPSMDELtrRLELR-----------RTEspEELERRLATA 160

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1207119214 504 AR-IKRAYNhyFDLTIVN--DNLDKAFEKLQA--AVEQLTTQPQWV 544
Cdd:PRK14738  161 PLeLEQLPE--FDYVVVNpeDRLDEAVAQIMAiiSAEKSRVHPRRI 204

PDZ domain of membrane palmitoylated protein 5 (MPP5), Drosophila Stardust, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP5, Drosophila Stardust, and related domains. MPP5 (also known as MAGUK p55 subfamily member 1, protein associated with Lin-7 1 or PALS1) and Drosophila Stardust are membrane-associated guanylate kinase (MAGUK)-like proteins that serve as signaling and scaffolding proteins, linking different proteins critical to the formation and maintenance of tight junctions (TJ) and apical-basal polarity. Apical-basal polarity determinants cluster in complexes; in particular, the Crumbs complex (Crb, MPP5, and PATJ) and the PAR/aPKC-complex (PAR-3, PAR-6, aPKC) determine the apical plasma membrane domain. Within the Crumbs complex, Crb is stabilized in the plasma membrane by MPP5, which in turn recruits PATJ and Lin-7 to the complex. MPP5 also links the Crumbs complex with the PAR/aPKC-complex. The Drosophila homolog of the Crumbs complex is the (CRB)-Stardust (Sdt)-Discs Lost (Dlt) complex. MPP5 also acts as an interaction partner for SARS-CoV envelope protein E, which results in delayed formation of TJs and dysregulation of cell polarity. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP5-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

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gi 1207119214 139 RMISIQKkAGEPLGVTFRVEEGDLVIARVLHGSMIDRQGMLHAGDVIREVNGREV-GKDPMALQHMLRDCNGSITLKILP 217
Cdd:cd06798     1 KIVRIEK-TREPLGATVRNEGDSVIISRIVKGGAAEKSGLLHEGDEILEINGIEIrGKDVNEVCDLLADMHGTLTFLLIP 79

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.

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gi 1207119214 229 YLKPHFNYNPNTDNLIPCReaGLAFSKGDILHIVNKEDPNWWQACNIN-GGHT---GLIPS 285
Cdd:cd11861     1 YVRALFDYDPSRDSGLPSQ--GLSFKFGDILHVTNASDDEWWQARRVTpNGEEeevGVIPS 59

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.

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gi 1207119214 140 MISIQKKAGEPLGVTFRVEEGD---LVIARVLHGSMIDRQGMLHAGDVIREVNGREV-GKDPMALQHMLRDCNGSITLKI 215
Cdd:cd00136     1 TVTLEKDPGGGLGFSIRGGKDGgggIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLeGLTHEEAVELLKSAGGEVTLTV 80

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gi 1207119214 216 L 216
Cdd:cd00136    81 R 81

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

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gi 1207119214 141 ISIQKKAGEPLGVTFRVEEGD----LVIARVLHGSMIDRQGmLHAGDVIREVNGREVGK-DPMALQHMLRDCNGSITLKI 215
Cdd:pfam00595   2 VTLEKDGRGGLGFSLKGGSDQgdpgIFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENmTHEEAVLALKGSGGKVTLTI 80

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gi 1207119214 216 L 216
Cdd:pfam00595  81 L 81

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.

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gi 1207119214 228 VYlKPHFNYNPNTDNlipcreaGLAFSKGDILHIVNKEDPNWWQA-CninGGHTGLIPSQFLEE 290
Cdd:cd11772     1 VF-RALYDYEAQHPD-------ELSFEEGDLLYISDKSDPNWWKAtC---GGKTGLIPSNYVEE 53

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.

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gi 1207119214 251 LAFSKGDILHIVNKEDPNWWQACNiNGGHTGLIPS 285
Cdd:pfam00018  14 LSFKKGDIIIVLEKSEDGWWKGRN-KGGKEGLIPS 47

Src Homology 3 domain superfamily; Src Homology 3 (SH3) domains are protein interaction domains that bind proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. Thus, they are referred to as proline-recognition domains (PRDs). SH3 domains are less selective and show more diverse specificity compared to other PRDs. They have been shown to bind peptide sequences that lack the PxxP motif; examples include the PxxDY motif of Eps8 and the RKxxYxxY sequence in SKAP55. SH3 domain containing proteins 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, among others. Many members of this superfamily are adaptor proteins that associate with a number of protein partners, facilitating complex formation and signal transduction.

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gi 1207119214 234 FNYNPNTDNlipcreaGLAFSKGDILHIVNKEDPNWWQACNiNGGHTGLIPSQF 287
Cdd:cd00174     6 YDYEAQDDD-------ELSFKKGDIITVLEKDDDGWWEGEL-NGGREGLFPANY 51

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207119214 228 VYLKPHFNYNPNTDNLIPCReaGLAFSKGDILHIVNKEDPNWWQACNIN----GGHTGLIPSQ 286
Cdd:cd12029     3 LYVRALFDYDRTRDSCLPSQ--GLSFSYGDILHVINASDDEWWQARLVTphgeSEQIGVIPSK 63