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 507834113 128 RMVGIRKTAGEHLGVTFRVEGGELVIARILHGGMVAQQGLLHVGDIIKEVNGQPVGSdPRALQELLRNASGSVILKILP 206
Cdd:cd10832    1 RMVGIRKNPGEPLGVTVRLEEGELVIARILHGGMIDRQGLLHVGDIIKEVNGVPVGS-PEQLQEMLKNASGSVTLKILP 78

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 507834113   57 LELVQEILRDLAQLAEQSSTAAELAHILQEPHFQSLLETHDSVASKTYETPP 108
Cdd:pfam02828   1 VELVLELLEDLQPLSEASEDLAELQKLLQSPHLQALLEAHDKVAQKVYEPPS 52

Guanylate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834113  338 RRKTLVLIGAQGVGRRSLKNKLIMWDPDRYGTTVPYTSRRPKDSEREGQGYSFVSRGEMEADVRAGRYLEHGEYEGNLYG 417
Cdd:pfam00625   1 SRRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834113  418 TRIDSIRGVVAAGKVCVLDVNPQAVKVLRTAEFVPYVVFIEAPDFETLRAMNRaalesgistkQLTEADLRRTVEESSRI 497
Cdd:pfam00625  81 TSVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPSLKVLQRRLK----------GRGKEQEEKINKRMAAA 150

                         170       180       190
                  ....*....|....*....|....*....|..
gi 507834113  498 QRGYGHY-FDLCLVNSNLERTFRELQTAMEKL 528
Cdd:pfam00625 151 EQEFQHYeFDVIIVNDDLEEAYKKLKEALEAE 182

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 507834113 218 FVKCHFDYDPARDSLIPCKEAGLRFNAGDLLQIVNQDDANWWQACHVEGGSAGLIPSQL 276
Cdd:cd12037    1 FVKCHFDYDPSSDSLIPCKEAGLKFRAGDLLQIVNQEDPNWWQACHVEGGSAGLIPSQL 59

Guanylate kinase [Nucleotide transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834113 342 LVLIGAQGVGRRSLKNKLIMWDPD-RYgtTVPYTSRRPKDSEREGQGYSFVSRGEMEADVRAGRYLEHGEYEGNLYGTRI 420
Cdd:COG0194    5 IVLSGPSGAGKTTLVKALLERDPDlRF--SVSATTRPPRPGEVDGVDYHFVSREEFERMIENGEFLEWAEVHGNYYGTPK 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834113 421 DSIRGVVAAGKVCVLDVNPQ-AVKVLRTAefvPYVV--FIEAPDFETL--RAMNRAalesgistkQLTEADLRRtveess 495
Cdd:COG0194   83 AEVEEALAAGKDVLLEIDVQgARQVKKKF---PDAVsiFILPPSLEELerRLRGRG---------TDSEEVIER------ 144

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 507834113 496 RIQR-----GYGHYFDLCLVNSNLERTFRELQTAM--EKLRTEPQ 533
Cdd:COG0194  145 RLAKareelAHADEFDYVVVNDDLDRAVEELKAIIraERLRRERQ 189

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 507834113   57 LELVQEILRDLAQLAEQSSTAAELAHILQEPHFQSLLETHDSVASKTYETPP 108
Cdd:pfam02828   1 VELVLELLEDLQPLSEASEDLAELQKLLQSPHLQALLEAHDKVAQKVYEPPS 52

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 507834113     2 QQVLDNLGSLPSATGAAElDLIFLRGIMESPIVRSLAKAHERLEETKLEAVRDN 55
Cdd:smart00569   1 QRLLELLEELQSLLSPSE-DLQELRRLLQSPHLQALLKIHDKVAETELDPPLPE 53

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 507834113    1 MQQVLDNLGSLPSATGAAElDLIFLRGIMESPIVRSLAKAHERLEETKLEAVR 53
Cdd:pfam02828   1 VELVLELLEDLQPLSEASE-DLAELQKLLQSPHLQALLEAHDKVAQKVYEPPS 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        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 507834113   217 VFVKCHFDYDPardslipCKEAGLRFNAGDLLQIVNQDDANWWQaCHVEGGSAGLIPSQLLE 278
Cdd:smart00326   3 PQVRALYDYTA-------QDPDELSFKKGDIITVLEKSDDGWWK-GRLGRGKEGLFPSNYVE 56

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834113 123 PPDAVRMVGIRKTAGEHLGVTFRVEGGELVIARILHGGMVAQQGLlHVGDIIKEVNGQPV-GSDPRALQELLRNASGS-V 200
Cdd:COG0793   45 PEEYEDFQESTSGEFGGLGAELGEEDGKVVVVSVIPGSPAEKAGI-KPGDIILAIDGKSVaGLTLDDAVKLLRGKAGTkV 123

                 ....*.
gi 507834113 201 ILKILP 206
Cdd:COG0793  124 TLTIKR 129

Guanylate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834113  338 RRKTLVLIGAQGVGRRSLKNKLIMWDPDRYGTTVPYTSRRPKDSEREGQGYSFVSRGEMEADVRAGRYLEHGEYEGNLYG 417
Cdd:pfam00625   1 SRRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834113  418 TRIDSIRGVVAAGKVCVLDVNPQAVKVLRTAEFVPYVVFIEAPDFETLRAMNRaalesgistkQLTEADLRRTVEESSRI 497
Cdd:pfam00625  81 TSVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPSLKVLQRRLK----------GRGKEQEEKINKRMAAA 150

                         170       180       190
                  ....*....|....*....|....*....|..
gi 507834113  498 QRGYGHY-FDLCLVNSNLERTFRELQTAMEKL 528
Cdd:pfam00625 151 EQEFQHYeFDVIIVNDDLEEAYKKLKEALEAE 182

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 507834113 218 FVKCHFDYDPARDSLIPCKEAGLRFNAGDLLQIVNQDDANWWQACHVEGGSAGLIPSQL 276
Cdd:cd12037    1 FVKCHFDYDPSSDSLIPCKEAGLKFRAGDLLQIVNQEDPNWWQACHVEGGSAGLIPSQL 59

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 507834113 128 RMVGIRKTAGEHLGVTFRVEGGELVIARILHGGMVAQQGLLHVGDIIKEVNGQPV-GSDPRALQELLRNASGSVILKILP 206
Cdd:cd06726    1 RLVEFEKARDEPLGATIKMEEDSVIVARILHGGMAHRSGLLHVGDEILEINGIPVsGKTVDELQKLLSSLSGSVTFKLIP 80

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 507834113 218 FVKCHFDYDPARDSLIPCKEAGLRFNAGDLLQIVNQDDANWWQACHV-EGGSAGLIPSQLL 277
Cdd:cd12038    1 FVKCHFDYNPYNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQASHVkEGGSAGLIPSQFL 61

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 507834113 342 LVLIGAQGVGRRSLKNKLIMWDPDRYGTTVPYTSRRPKDSEREGQGYSFVSRGEMEADVRAGRYLEHGEYEGNLYGTRID 421
Cdd:cd00071    2 IVLSGPSGVGKSTLLKRLLEEFDPNFGFSVSHTTRKPRPGEVDGVDYHFVSKEEFERLIENGEFLEWAEFHGNYYGTSKA 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 507834113 422 SIRGVVAAGKVCVLDVNPQAVKVLRTAEFVPYVVFIEAPDF 462
Cdd:cd00071   82 AVEEALAEGKIVILEIDVQGARQVKKSYPDAVSIFILPPDY 122

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 507834113 218 FVKCHFDYDPARDSLIPCKEAGLRFNAGDLLQIVNQDDANWWQACHVEG--GSAGLIPSQLL 277
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 507834113 218 FVKCHFDYDPARDSLIPCKEAGLRFNAGDLLQIVNQDDANWWQACHVE--GGSAGLIPS 274
Cdd:cd12081    1 YVRAQFEYDPLKDDLIPCKQAGIRFRVGDILQIISKDDHNWWQAKLENskNGTAGLIPS 59

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 507834113 219 VKCHFDYDPARDSLIPCKEAGLRFNAGDLLQIVNQDDANWWQAcHVEGGS-----AGLIPSQ 275
Cdd:cd12036    2 VRAHFDYDPEDDPYIPCRELGLSFQKGDILHVISQEDPNWWQA-YREGEEdnqslAGLIPSK 62

PDZ domain of membrane palmitoylated protein1 (MPP1), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP1, and related domains. MPP1 (also known as MAGUK p55 subfamily member 1, erythrocyte membrane protein p55, EMP55) is a membrane-associated guanylate kinase (MAGUK)-like protein which forms a complex with protein 4.1 and glycophorin C (GPC) at the cytoplasmic face of the plasma membrane; this complex is essential for cytoskeleton-membrane linkage in erythrocytes and many non-erythroid cells, and participates in the determination of membrane stability and cell shape. MPP1, by interacting with various scaffold proteins and cytoskeletal proteins in the postsynaptic density, also plays an important role in organizing synaptic and non-synaptic structures. MPP1 is also a component of the Crumbs protein complex in the mammalian retina and may link the Usher protein network and the Crumbs protein complex. The MPP1 PDZ domain binding partners include GPC, ABCC4, and CADM1/Necl-2/SynCAM1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834113 128 RMVGIRKTAGEHLGVTFRV-EGGELVIARILHGGMVAQQGLLHVGDIIKEVNGQPVGSDP-RALQELLRNASGSVILKIL 205
Cdd:cd10830    1 RLVQFEKNTEEPMGITLKLnEKQSCIVARILHGGMIHRQGSLHVGDEILEINGKSVTNHSvDQLQKMLKETKGMVSLKVI 80

                 .
gi 507834113 206 P 206
Cdd:cd10830   81 P 81

Src Homology 3 domain of Membrane Protein, Palmitoylated 3 (or MAGUK p55 subfamily member 3); MPP3 is a scaffolding protein that colocalizes with MPP5 and CRB1 at the subdpical region adjacent to adherens junctions and may function in photoreceptor polarity. It interacts with some nectins and regulates their trafficking and processing. Nectins are cell-cell adhesion proteins involved in the establishment apical-basal polarity at cell adhesion sites. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834113 218 FVKCHFDYDPARDSLIPCKEAGLRFNAGDLLQIVNQDDANWWQACHVEGGS--AGLIPSQ 275
Cdd:cd12039    1 FMRALFDYNPYEDRAIPCQEAGLPFKRRDILEVVSQDDPTWWQAKRVGDTNlrAGLIPSK 60

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 507834113 218 FVKCHFDYDPARDSLIPCKEAGLRFNAGDLLQIVNQDDANWWQACHVE--GGSAGLIPS 274
Cdd:cd12034    1 YVRAMVDYWPQQDPSIPCADAGLPFRKGDILQIVDQNDSLWWQARKLSdlAACAGLIPS 59

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 507834113    58 ELVQEILRDLAQLAEQSSTAAELAHILQEPHFQSLLETHDSVASKTYETPPP 109
Cdd:smart00569   1 QRLLELLEELQSLLSPSEDLQELRRLLQSPHLQALLKIHDKVAETELDPPLP 52

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 507834113 129 MVGIRKTAGEHLGvtFRVEGGE-----LVIARILHGGMVAQQGLLHVGDIIKEVNGQPV-GSDPRALQELLRNASGSVIL 202
Cdd:cd00136    1 TVTLEKDPGGGLG--FSIRGGKdggggIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLeGLTHEEAVELLKSAGGEVTL 78

                 ...
gi 507834113 203 KIL 205
Cdd:cd00136   79 TVR 81

guanylate kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834113 336 PFRRKTLVLIGAQGVGRRSLKNKLIMWDPDrYGTTVPYTSRRPKDSEREGQGYSFVSRGEMEADVRAGRYLEHGEYEGNL 415
Cdd:PRK14738  10 PAKPLLVVISGPSGVGKDAVLARMRERKLP-FHFVVTATTRPKRPGEIDGVDYHFVTPEEFREMISQNELLEWAEVYGNY 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834113 416 YGTRIDSIRGVVAAGKVCVLDVNPQAVKVLRtaEFVPYVVFI--EAPDFETL--RAMNR-----AALESGISTKQLteaD 486
Cdd:PRK14738  89 YGVPKAPVRQALASGRDVIVKVDVQGAASIK--RLVPEAVFIflAPPSMDELtrRLELRrtespEELERRLATAPL---E 163

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 507834113 487 LRRTVEessriqrgyghyFDLCLVNSN--LERTFRELQT--AMEKLRTEPQWV 535
Cdd:PRK14738 164 LEQLPE------------FDYVVVNPEdrLDEAVAQIMAiiSAEKSRVHPRRI 204

Src Homology 3 domain of Disks Large homolog 1; DLG1, also called synapse-associated protein 97 (SAP97), is a scaffolding protein that clusters at synapses and plays an important role in synaptic development and plasticity. DLG1 plays roles in regulating cell polarity, proliferation, migration, and cycle progression. It interacts with AMPA-type glutamate receptors and is critical in their maturation and delivery to synapses. It also interacts with PKCalpha and promotes wound healing. DLG1 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. DLG1 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 507834113 215 RQVFVKCHFDYDPARDSLIPCKeaGLRFNAGDLLQIVNQDDANWWQACHV----EGGSAGLIPSQ 275
Cdd:cd12031    1 RSLYVRALFDYDKTKDSGLPSQ--GLNFKFGDILHVVNASDDEWWQARQVtadgESEEIGVIPSK 63

Src Homology 3 domain of Disks Large homolog 2; DLG2, also called postsynaptic density-93 (PSD93) or Channel-associated protein of synapse-110 (chapsyn 110), is a scaffolding protein that clusters at synapses and plays an important role in synaptic development and plasticity. The DLG2 delta isoform binds inwardly rectifying potassium Kir2 channels, which determine resting membrane potential in neurons. It regulates the spatial and temporal distribution of Kir2 channels within neuronal membranes. DLG2 is a member of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. DLG2 contains three PDZ domains. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 507834113 215 RQVFVKCHFDYDPARDSLIPCKeaGLRFNAGDLLQIVNQDDANWWQACHV--EGGSA--GLIPSQLLEEKRK 282
Cdd:cd12032    4 RSLYVRAMFDYEKSKDSGLPSQ--GLSFRYGDILHVINASDDEWWQARRVtpDGDSEemGVIPSKRRVERKE 73

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 507834113    1 MQQVLDNLGSLPSATGAAElDLIFLRGIMESPIVRSLAKAHERLEETKLEAVR 53
Cdd:pfam02828   1 VELVLELLEDLQPLSEASE-DLAELQKLLQSPHLQALLEAHDKVAQKVYEPPS 52

Src Homology 3 domain of metazoan osteoclast stimulating factor 1; OSTF1, also named OSF or SH3P2, is a signaling protein containing SH3 and ankyrin-repeat domains. It acts through a Src-related pathway to enhance the formation of osteoclasts and bone resorption. It also acts as a negative regulator of cell motility. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 507834113 218 FVKCHFDYDPARDslipcKEagLRFNAGDLLQIVNQDDANWWQA-ChveGGSAGLIPSQLLEE 279
Cdd:cd11772    1 VFRALYDYEAQHP-----DE--LSFEEGDLLYISDKSDPNWWKAtC---GGKTGLIPSNYVEE 53

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 507834113  132 IRKTAGEHLGvtFRVEGG------ELVIARILHGGMvAQQGLLHVGDIIKEVNGQPVGSDPR-ALQELLRNASGSVILKI 204
Cdd:pfam00595   4 LEKDGRGGLG--FSLKGGsdqgdpGIFVSEVLPGGA-AEAGGLKVGDRILSINGQDVENMTHeEAVLALKGSGGKVTLTI 80

                  .
gi 507834113  205 L 205
Cdd:pfam00595  81 L 81

Src homology 3 domain of Src kinase-like Protein Tyrosine Kinases; Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, Yes, and Brk. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). However, Brk lacks the N-terminal myristoylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells, and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, Lyn, and Brk show a limited expression pattern. This subfamily also includes Drosophila Src42A, Src oncogene at 42A (also known as Dsrc41) which accumulates at sites of cell-cell or cell-matrix adhesion, and participates in Drosphila development and wound healing. It has been shown to promote tube elongation in the tracheal system, is essential for proper cell-cell matching during dorsal closure, and regulates cell-cell contacts in developing Drosophila eyes. The SH3 domain of Src kinases contributes to substrate recruitment by binding adaptor proteins/substrates, and regulation of kinase activity through an intramolecular interaction. 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 507834113 223 FDYDpARDslipckEAGLRFNAGDLLQIVNQDDANWWQACHVEGGSAGLIPS 274
Cdd:cd11845    6 YDYE-ART------DDDLSFKKGDRLQILDDSDGDWWLARHLSTGKEGYIPS 50