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 564346816 129 RILGIHKRAGEPLGVTFRVENNDLVIARILHGGMIDRQGLLHVGDIIKEVNGHEVGnNPKELQELLKNISGSVTLKILP 207
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 564346816   57 LELVNEILEDITPLISVDENVAELVGILKEPHFQSLLEAHDIVASKCYESPP 108
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 564346816   361 QGVGRRSLKNRFIVLNPARFGTTVPFTSRKPREDEKDGQAYKFVSRSEMEADIKAGKYLEHGEYEGNLYGTKIGSILDVV 440
Cdd:smart00072   1 SGVGKGTLLAELIQEIPDAFERVVSHTTRPPRPGEVNGVDYHFVSKEEFEDDIKSGLFLEWGEYEGNYYGTSKETIRQVA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564346816   441 QTGRTCILDVNPQALKVLRTSEFMPYVVFIAAPELETLRAMHKAVVDAgittkllTDSDLKKTVDESARIQRAYnHYFDL 520
Cdd:smart00072  81 EKGKHCLLDIDPQGVKQLRKAQLYPIVIFIAPPSSEELERRLRQRGTE-------TSERIQKRLAAAQKEAQEY-HLFDY 152

                          170       180
                   ....*....|....*....|..
gi 564346816   521 IIVNDNLDKAFENLQTAIEKLR 542
Cdd:smart00072 153 VIVNDDLEDAYEELKEILEAEQ 174

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 564346816 233 FVKCHFDYNPFNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQASHVKEGGSAGLIPSQFL 293
Cdd:cd12038    1 FVKCHFDYNPYNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQASHVKEGGSAGLIPSQFL 61

guanylate kinase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564346816 353 KTLVLIGAQGVGRRSLKNRFIVLNPARFGTTVPFTSRKPREDEKDGQAYKFVSRSEMEADIKAGKYLEHGEYEGNLYGTK 432
Cdd:PLN02772 136 KPIVISGPSGVGKGTLISMLMKEFPSMFGFSVSHTTRAPREMEKDGVHYHFTERSVMEKEIKDGKFLEFASVHGNLYGTS 215

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564346816 433 IGSILDVVQTGRTCILDVNPQALKVLRTSEFMPYVVFIAAPELETLRAMHKAvvdAGITTKlltDSDLKKTVDESARIQR 512
Cdd:PLN02772 216 IEAVEVVTDSGKRCILDIDVQGARSVRASSLEAIFIFICPPSMEELEKRLRA---RGTETE---EQIQKRLRNAEAELEQ 289

                        170       180
                 ....*....|....*....|....
gi 564346816 513 AYNHY-FDLIIVNDNLDKAFENLQ 535
Cdd:PLN02772 290 GKSSGiFDHILYNDNLEECYKNLK 313

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 564346816   57 LELVNEILEDITPLISVDENVAELVGILKEPHFQSLLEAHDIVASKCYESPP 108
Cdd:pfam02828   1 VELVLELLEDLQPLSEASEDLAELQKLLQSPHLQALLEAHDKVAQKVYEPPS 52

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564346816  133 IHKRAGEPLGVTFRVENND----LVIARILHGGMIDRQGLlHVGDIIKEVNGHEVGNNPKE-LQELLKNISGSVTLKIL 206
Cdd:pfam00595   4 LEKDGRGGLGFSLKGGSDQgdpgIFVSEVLPGGAAEAGGL-KVGDRILSINGQDVENMTHEeAVLALKGSGGKVTLTIL 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 564346816   232 VFVKCHFDYNPfndnlipCKEAGLKFSKGEILQIVNREDPNWWQAshVKEGGSAGLIPSQFLE 294
Cdd:smart00326   3 PQVRALYDYTA-------QDPDELSFKKGDIITVLEKSDDGWWKG--RLGRGKEGLFPSNYVE 56

Variant 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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564346816  233 FVKCHFDYNPfndnlipCKEAGLKFSKGEILQIVNREDPNWWQAShvkEGGSAGLIPSQFLEE 295
Cdd:pfam07653   1 YGRVIFDYVG-------TDKNGLTLKKGDVVKVLGKDNDGWWEGE---TGGRVGLVPSTAVEE 53

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 564346816 141 LGVTFRVENNDLVIARILHGGMIDRQGLlHVGDIIKEVNGHEV-GNNPKELQELLKNISGS-VTLKILP 207
Cdd:COG0793   62 LGAELGEEDGKVVVVSVIPGSPAEKAGI-KPGDIILAIDGKSVaGLTLDDAVKLLRGKAGTkVTLTIKR 129

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 564346816   361 QGVGRRSLKNRFIVLNPARFGTTVPFTSRKPREDEKDGQAYKFVSRSEMEADIKAGKYLEHGEYEGNLYGTKIGSILDVV 440
Cdd:smart00072   1 SGVGKGTLLAELIQEIPDAFERVVSHTTRPPRPGEVNGVDYHFVSKEEFEDDIKSGLFLEWGEYEGNYYGTSKETIRQVA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564346816   441 QTGRTCILDVNPQALKVLRTSEFMPYVVFIAAPELETLRAMHKAVVDAgittkllTDSDLKKTVDESARIQRAYnHYFDL 520
Cdd:smart00072  81 EKGKHCLLDIDPQGVKQLRKAQLYPIVIFIAPPSSEELERRLRQRGTE-------TSERIQKRLAAAQKEAQEY-HLFDY 152

                          170       180
                   ....*....|....*....|..
gi 564346816   521 IIVNDNLDKAFENLQTAIEKLR 542
Cdd:smart00072 153 VIVNDDLEDAYEELKEILEAEQ 174

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 564346816 233 FVKCHFDYNPFNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQASHVKEGGSAGLIPSQFL 293
Cdd:cd12038    1 FVKCHFDYNPYNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQASHVKEGGSAGLIPSQFL 61

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 564346816 233 FVKCHFDYNPFNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQASHVkEGGSAGLIPSQF 292
Cdd:cd12037    1 FVKCHFDYDPSSDSLIPCKEAGLKFRAGDLLQIVNQEDPNWWQACHV-EGGSAGLIPSQL 59

guanylate kinase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564346816 353 KTLVLIGAQGVGRRSLKNRFIVLNPARFGTTVPFTSRKPREDEKDGQAYKFVSRSEMEADIKAGKYLEHGEYEGNLYGTK 432
Cdd:PLN02772 136 KPIVISGPSGVGKGTLISMLMKEFPSMFGFSVSHTTRAPREMEKDGVHYHFTERSVMEKEIKDGKFLEFASVHGNLYGTS 215

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564346816 433 IGSILDVVQTGRTCILDVNPQALKVLRTSEFMPYVVFIAAPELETLRAMHKAvvdAGITTKlltDSDLKKTVDESARIQR 512
Cdd:PLN02772 216 IEAVEVVTDSGKRCILDIDVQGARSVRASSLEAIFIFICPPSMEELEKRLRA---RGTETE---EQIQKRLRNAEAELEQ 289

                        170       180
                 ....*....|....*....|....
gi 564346816 513 AYNHY-FDLIIVNDNLDKAFENLQ 535
Cdd:PLN02772 290 GKSSGiFDHILYNDNLEECYKNLK 313

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 564346816 355 LVLIGAQGVGRRSLKNRFIVLNPARFGTTVPFTSRKPREDEKDGQAYKFVSRSEMEADIKAGKYLEHGEYEGNLYGTKIG 434
Cdd:cd00071    2 IVLSGPSGVGKSTLLKRLLEEFDPNFGFSVSHTTRKPRPGEVDGVDYHFVSKEEFERLIENGEFLEWAEFHGNYYGTSKA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564346816 435 SILDVVQTGRTCILDVNPQALKVLRTSEFMPYVVFIAAPeletlramhkavvdagittklltdsdlkktvdesariqray 514
Cdd:cd00071   82 AVEEALAEGKIVILEIDVQGARQVKKSYPDAVSIFILPP----------------------------------------- 120

                        170       180
                 ....*....|....*....|
gi 564346816 515 nhyfDLIIVNDNLDKAFENL 534
Cdd:cd00071  121 ----DYVIVNDDLEKAYEEL 136

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 564346816 233 FVKCHFDYNPFNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQAShvKEG---GSAGLIPSQFL 293
Cdd:cd12035    1 YVRAQFDYDPSKDDLIPCQQAGIAFKTGDILQIISKDDHNWWQAR--KPGaskEPAGLIPSPEL 62

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 564346816 129 RILGIHKRAGEPLGVTFRV-ENNDLVIARILHGGMIDRQGLLHVGDIIKEVNGHEVGNNPKE-LQELLKNISGSVTLKIL 206
Cdd:cd10831    1 RLVQFQKNTDEPMGITLKMnEDGRCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEqLQKMLREARGSITFKIV 80

                 .
gi 564346816 207 P 207
Cdd:cd10831   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 564346816 233 FVKCHFDYNPFNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQASHVKEGG-SAGLIPSQ 291
Cdd:cd12033    1 FIKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKHEGDANpRAGLIPSK 60

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 564346816 233 FVKCHFDYNPFNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQASHVKE-GGSAGLIPS 290
Cdd:cd12081    1 YVRAQFEYDPLKDDLIPCKQAGIRFRVGDILQIISKDDHNWWQAKLENSkNGTAGLIPS 59

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 564346816 233 FVKCHFDYNPFNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQASHVKEGG-SAGLIPS-QF 292
Cdd:cd12039    1 FMRALFDYNPYEDRAIPCQEAGLPFKRRDILEVVSQDDPTWWQAKRVGDTNlRAGLIPSkQF 62

guanylate kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564346816 355 LVLIGAQGVGRRSLKNRFIVLNPArFGTTVPFTSRKPREDEKDGQAYKFVSRSEMEADIKAGKYLEHGEYEGNLYGTKIG 434
Cdd:PRK14738  16 VVISGPSGVGKDAVLARMRERKLP-FHFVVTATTRPKRPGEIDGVDYHFVTPEEFREMISQNELLEWAEVYGNYYGVPKA 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564346816 435 SILDVVQTGRTCILDVNPQALKVLRtsEFMPYVVFI--AAPELETL--RAMHKavvdagittklLTDS--DLKKTVDESA 508
Cdd:PRK14738  95 PVRQALASGRDVIVKVDVQGAASIK--RLVPEAVFIflAPPSMDELtrRLELR-----------RTESpeELERRLATAP 161

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 564346816 509 R-IQRAYNhyFDLIIVN--DNLDKAFENLQTAI--EKLRTEPQWV 548
Cdd:PRK14738 162 LeLEQLPE--FDYVVVNpeDRLDEAVAQIMAIIsaEKSRVHPRRI 204

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 564346816 233 FVKCHFDYNPFNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQASHVKEGGS-AGLIPS 290
Cdd:cd12034    1 YVRAMVDYWPQQDPSIPCADAGLPFRKGDILQIVDQNDSLWWQARKLSDLAAcAGLIPS 59

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 564346816    58 ELVNEILEDITPLISVDENVAELVGILKEPHFQSLLEAHDIVASKCYESPPS 109
Cdd:smart00569   1 QRLLELLEELQSLLSPSEDLQELRRLLQSPHLQALLKIHDKVAETELDPPLP 52

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 564346816 233 FVKCHFDYNPFNDNLIPCKeaGLKFSKGEILQIVNREDPNWWQASHVKEGGSA---GLIPS 290
Cdd:cd11861    1 YVRALFDYDPSRDSGLPSQ--GLSFKFGDILHVTNASDDEWWQARRVTPNGEEeevGVIPS 59

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 564346816     2 QQVLENLTELPSSTGAEEiDLIFLKGIMENPIVKSLAKAHERLEDSKLEAVSDN 55
Cdd:smart00569   1 QRLLELLEELQSLLSPSE-DLQELRRLLQSPHLQALLKIHDKVAETELDPPLPE 53

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 564346816 230 RQVFVKCHFDYNPFNDNLIPCKeaGLKFSKGEILQIVNREDPNWWQASHVKEGGSA---GLIPSQ 291
Cdd:cd12029    1 RSLYVRALFDYDRTRDSCLPSQ--GLSFSYGDILHVINASDDEWWQARLVTPHGESeqiGVIPSK 63

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 564346816   128 IRILGIHKRAGEPLGVTFRVENND---LVIARILHGGMIDRQGLlHVGDIIKEVNGHEVGNNP-KELQELLKNISGSVTL 203
Cdd:smart00228   1 EPRLVELEKGGGGLGFSLVGGKDEgggVVVSSVVPGSPAAKAGL-RVGDVILEVNGTSVEGLThLEAVDLLKKAGGKVTL 79

                   ....
gi 564346816   204 KILP 207
Cdd:smart00228  80 TVLR 83

PDZ domain 11 of MUPP1 of multi-PDZ-domain protein 1 (MUPP1), domain 9 of PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 11 of MUPP1, PDZ domain 9 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. 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 MUPP1-like family PDZ11 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 564346816 133 IHKRAGEPLGVTFRVENND--LVIARILHGGMIDRQGLLHVGDIIKEVNGHEVGNNPKE-LQELLKNISGSVTLKI 205
Cdd:cd06674    8 LQKKPGRGLGLSIVGKRNDtgVFVSDIVKGGAADADGRLMQGDQILSVNGEDVRNASQEaAAALLKCAQGKVRLEV 83

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 564346816    1 MQQVLENLTELPSSTGAEEiDLIFLKGIMENPIVKSLAKAHERLEDSKLEAVS 53
Cdd:pfam02828   1 VELVLELLEDLQPLSEASE-DLAELQKLLQSPHLQALLEAHDKVAQKVYEPPS 52

Fifth Src homology 3 domain (or SH3E) of Intersectin-1; Intersectin-1 (ITSN1) is an adaptor protein that functions in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. It plays a role in clathrin-coated pit (CCP) formation. It binds to many proteins through its multidomain structure and facilitate the assembly of multimeric complexes. ITSN1 localizes in membranous organelles, CCPs, the Golgi complex, and may be involved in the cell membrane trafficking system. It exists in alternatively spliced short and long isoforms. The short isoform contains two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoform, in addition, contains RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. 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 564346816 238 FDYNPFNDNLIPckeaglkFSKGEILQIVNREDPNWWQAshvKEGGSAGLIPSQFLE 294
Cdd:cd11995    7 YDYTAQNDDELA-------FSKGQIINVLNKEDPDWWKG---ELNGQVGLFPSNYVK 53

Fifth Src homology 3 domain (or SH3E) of Intersectin; Intersectins (ITSNs) are adaptor proteins that function in exo- and endocytosis, actin cytoskeletal reorganization, and signal transduction. They are essential for initiating clathrin-coated pit formation. They bind to many proteins through their multidomain structure and facilitate the assembly of multimeric complexes. Vertebrates contain two ITSN proteins, ITSN1 and ITSN2, which exist in alternatively spliced short and long isoforms. The short isoforms contain two Eps15 homology domains (EH1 and EH2), a coiled-coil region and five SH3 domains (SH3A-E), while the long isoforms, in addition, contain RhoGEF (also called Dbl-homologous or DH), Pleckstrin homology (PH) and C2 domains. ITSN1 and ITSN2 are both widely expressed, with variations depending on tissue type and stage of development. The fifth SH3 domain (or SH3E) of ITSN1 has been shown to bind many protein partners including SGIP1, Sos1, dynamin1/2, CIN85, c-Cbl, SHIP2, N-WASP, and synaptojanin-1, among others. 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 564346816 238 FDYNPFNDNlipckeaGLKFSKGEILQIVNREDPNWWQAshvKEGGSAGLIPSQFLEE 295
Cdd:cd11840    6 FPYTAQNED-------ELSFQKGDIINVLSKDDPDWWRG---ELNGQTGLFPSNYVEP 53