Guanylate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140201 340 QRKTLILIGAQGVGRRSLKNRLVVLHPTRFGTTVPHTSRRPRNDERDGQSYRFVTRLEMETDIKLGRYLEHGEYDGNLYG 419
Cdd:pfam00625   1 SRRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140201 420 TKIDSIHEVVNTGRTCILDVNPQALKLLKTPEFMPYVVFIAAPEFDTLKDMHKavvdaGLTTKQladvdLKKTVDESARI 499
Cdd:pfam00625  81 TSVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPSLKVLQRRLK-----GRGKEQ-----EEKINKRMAAA 150

                         170       180       190
                  ....*....|....*....|....*....|..
gi 1207140201 500 LRAYRHY-FDLIIVNDNLDCAFEKLQSSVEEL 530
Cdd:pfam00625 151 EQEFQHYeFDVIIVNDDLEEAYKKLKEALEAE 182

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 1207140201 223 YVKPHFDYNPASDNLIPCREAGLAFKRGDILQIVNREDPNWWQACHLAE--GGTGLIPSQ 280
Cdd:cd11862     1 FVRALFDYDPEEDPLIPCKEAGLSFKKGDILQIVNQDDPNWWQARKVGDpnGRAGLIPSQ 60

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207140201    6 QQVLDNLGELPSTTGAKDiDLIFLKGIMESPIVRSLAKAHERLEDVKLEAVQEN 59
Cdd:smart00569   1 QRLLELLEELQSLLSPSE-DLQELRRLLQSPHLQALLKIHDKVAETELDPPLPE 53

Guanylate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140201 340 QRKTLILIGAQGVGRRSLKNRLVVLHPTRFGTTVPHTSRRPRNDERDGQSYRFVTRLEMETDIKLGRYLEHGEYDGNLYG 419
Cdd:pfam00625   1 SRRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140201 420 TKIDSIHEVVNTGRTCILDVNPQALKLLKTPEFMPYVVFIAAPEFDTLKDMHKavvdaGLTTKQladvdLKKTVDESARI 499
Cdd:pfam00625  81 TSVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPSLKVLQRRLK-----GRGKEQ-----EEKINKRMAAA 150

                         170       180       190
                  ....*....|....*....|....*....|..
gi 1207140201 500 LRAYRHY-FDLIIVNDNLDCAFEKLQSSVEEL 530
Cdd:pfam00625 151 EQEFQHYeFDVIIVNDDLEEAYKKLKEALEAE 182

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 1207140201 133 RMIGIRKKAGEPLGVTFRMDKGDLVIARILHGGLIDRQGLLHVGDIIKEVNGKDVGtNPTELQEMLKECSGGITLKILP 211
Cdd:cd10832     1 RMVGIRKNPGEPLGVTVRLEEGELVIARILHGGMIDRQGLLHVGDIIKEVNGVPVG-SPEQLQEMLKNASGSVTLKILP 78

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 1207140201 344 LILIGAQGVGRRSLKNRLVVLHPTRFGTTVPHTSRRPRNDERDGQSYRFVTRLEMETDIKLGRYLEHGEYDGNLYGTKID 423
Cdd:cd00071     2 IVLSGPSGVGKSTLLKRLLEEFDPNFGFSVSHTTRKPRPGEVDGVDYHFVSKEEFERLIENGEFLEWAEFHGNYYGTSKA 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1207140201 424 SIHEVVNTGRTCILDVNPQALKLLKTPEFMPYVVFIAAPEF 464
Cdd:cd00071    82 AVEEALAEGKIVILEIDVQGARQVKKSYPDAVSIFILPPDY 122

Guanylate kinase [Nucleotide transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140201 344 LILIGAQGVGRRSLKNRLVVLHPtRFGTTVPHTSRRPRNDERDGQSYRFVTRLEMETDIKLGRYLEHGEYDGNLYGTKID 423
Cdd:COG0194     5 IVLSGPSGAGKTTLVKALLERDP-DLRFSVSATTRPPRPGEVDGVDYHFVSREEFERMIENGEFLEWAEVHGNYYGTPKA 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140201 424 SIHEVVNTGRTCILDVNPQ-ALKLLKTpefMPYVV--FIAAPEFDTLKD-MHK------AVVDAGLTTkqlADVDLkktv 493
Cdd:COG0194    84 EVEEALAAGKDVLLEIDVQgARQVKKK---FPDAVsiFILPPSLEELERrLRGrgtdseEVIERRLAK---AREEL---- 153

                         170       180       190
                  ....*....|....*....|....*....|..
gi 1207140201 494 desarilrAYRHYFDLIIVNDNLDCAFEKLQS 525
Cdd:COG0194   154 --------AHADEFDYVVVNDDLDRAVEELKA 177

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1207140201   62 ELVTDILGDISGLSVRDDSAAELSKILQEPHFQSLLEAHDMVASKCYEAPAPP 114
Cdd:smart00569   1 QRLLELLEELQSLLSPSEDLQELRRLLQSPHLQALLKIHDKVAETELDPPLPE 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207140201  140 KAGEPLGVTFRMDKGD---LVIARILHGGLIDRQGLlHVGDIIKEVNGKDV-GTNPTELQEMLKECSGGITLKILP 211
Cdd:smart00228   9 KGGGGLGFSLVGGKDEgggVVVSSVVPGSPAAKAGL-RVGDVILEVNGTSVeGLTHLEAVDLLKKAGGKVTLTVLR 83

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207140201    6 QQVLDNLGELPSTTGAKDiDLIFLKGIMESPIVRSLAKAHERLEDVKLEAVQEN 59
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
                  ....*....|....*....|....*....|....*....|....*.
gi 1207140201   5 MQQVLDNLGELPSTTGAKDiDLIFLKGIMESPIVRSLAKAHERLED 50
Cdd:pfam02828   1 VELVLELLEDLQPLSEASE-DLAELQKLLQSPHLQALLEAHDKVAQ 45

Guanylate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140201 340 QRKTLILIGAQGVGRRSLKNRLVVLHPTRFGTTVPHTSRRPRNDERDGQSYRFVTRLEMETDIKLGRYLEHGEYDGNLYG 419
Cdd:pfam00625   1 SRRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140201 420 TKIDSIHEVVNTGRTCILDVNPQALKLLKTPEFMPYVVFIAAPEFDTLKDMHKavvdaGLTTKQladvdLKKTVDESARI 499
Cdd:pfam00625  81 TSVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPSLKVLQRRLK-----GRGKEQ-----EEKINKRMAAA 150

                         170       180       190
                  ....*....|....*....|....*....|..
gi 1207140201 500 LRAYRHY-FDLIIVNDNLDCAFEKLQSSVEEL 530
Cdd:pfam00625 151 EQEFQHYeFDVIIVNDDLEEAYKKLKEALEAE 182

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 1207140201 133 RMIGIRKKAGEPLGVTFRMDKGDLVIARILHGGLIDRQGLLHVGDIIKEVNGKDVGtNPTELQEMLKECSGGITLKILP 211
Cdd:cd10832     1 RMVGIRKNPGEPLGVTVRLEEGELVIARILHGGMIDRQGLLHVGDIIKEVNGVPVG-SPEQLQEMLKNASGSVTLKILP 78

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 1207140201 223 YVKPHFDYNPASDNLIPCREAGLAFKRGDILQIVNREDPNWWQACHLAEGGTGLIPSQF 281
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 1207140201 223 YVKPHFDYNPASDNLIPCREAGLAFKRGDILQIVNREDPNWWQACHLAEGGT-GLIPSQFL 282
Cdd:cd12038     1 FVKCHFDYNPYNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQASHVKEGGSaGLIPSQFL 61

Guanylate kinase [Nucleotide transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140201 344 LILIGAQGVGRRSLKNRLVVLHPtRFGTTVPHTSRRPRNDERDGQSYRFVTRLEMETDIKLGRYLEHGEYDGNLYGTKID 423
Cdd:COG0194     5 IVLSGPSGAGKTTLVKALLERDP-DLRFSVSATTRPPRPGEVDGVDYHFVSREEFERMIENGEFLEWAEVHGNYYGTPKA 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140201 424 SIHEVVNTGRTCILDVNPQ-ALKLLKTpefMPYVV--FIAAPEFDTLKD-MHK------AVVDAGLTTkqlADVDLkktv 493
Cdd:COG0194    84 EVEEALAAGKDVLLEIDVQgARQVKKK---FPDAVsiFILPPSLEELERrLRGrgtdseEVIERRLAK---AREEL---- 153

                         170       180       190
                  ....*....|....*....|....*....|..
gi 1207140201 494 desarilrAYRHYFDLIIVNDNLDCAFEKLQS 525
Cdd:COG0194   154 --------AHADEFDYVVVNDDLDRAVEELKA 177

Src Homology 3 domain of Membrane Protein, Palmitoylated 1 (or MAGUK p55 subfamily member 1); MPP1, also called 55 kDa erythrocyte membrane protein (p55), is a ubiquitously-expressed scaffolding protein that plays roles in regulating neutrophil polarity, cell shape, hair cell development, and neural development and patterning of the retina. It was originally identified as an erythrocyte protein that stabilizes the actin cytoskeleton to the plasma membrane by forming a complex with 4.1R protein and glycophorin C. MPP1 is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains the three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207140201 223 YVKPHFDYNPASDNLIPCREAGLAFKRGDILQIVNREDPNWWQA--CHLAEGGTGLIPS 279
Cdd:cd12080     1 YMRAQFDYDPKKDNLIPCKEAGLKFQTGDIIQIINKDDSNWWQGrvEGSGEESAGLIPS 59

PDZ domain of peripheral plasma membrane protein CASK, Caenorhabditis Lin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CASK, Caenorhabditis elegans Lin-2, and related domains. CASK and Lin-2 are membrane-associated guanylate kinase (MAGUK)-like proteins. CASK (also known as Calcium/calmodulin-dependent protein kinase, CAKI, and Camguk) has a role in synaptic transmembrane protein anchoring and ion channel trafficking. CASK may regulate transmembrane proteins that bind calcium, calmodulin, or nucleotides; it regulates the Drosophila ether a go-go (eag) potassium channel, and also regulates autophosphorylation of CaMKII. CASK binding partners include the transcription factor TBR1, and cell-surface proteins, including amyloid precursor protein, neurexins, and syndecans. Lin-2, as a component of the CLin-10-Lin-2-Lin-7 complex, plays a role in controlling the basolateral localization of the EGF receptor Let-23; this complex also associates with the neuron-specific motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor 2B along microtubules. CASK may also function in targeting or scaffolding of the protein parkin which is selectively truncated by a Parkinson's disease-causing mutation; the C-terminus of parkin functions as a class II PDZ-binding motif that binds CASK. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP6-MPP2-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140201 133 RMIGIRKKAGEPLGVTFRM-DKGDLVIARILHGGLIDRQGLLHVGDIIKEVNGKDVGTNPTE-LQEMLKECSGGITLKIL 210
Cdd:cd10831     1 RLVQFQKNTDEPMGITLKMnEDGRCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEqLQKMLREARGSITFKIV 80

                  .
gi 1207140201 211 P 211
Cdd:cd10831    81 P 81

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 1207140201 133 RMIGIRKKAGEPLGVTFRM-DKGDLVIARILHGGLIDRQGLLHVGDIIKEVNGKDVgTNPT--ELQEMLKECSGGITLKI 209
Cdd:cd10830     1 RLVQFEKNTEEPMGITLKLnEKQSCIVARILHGGMIHRQGSLHVGDEILEINGKSV-TNHSvdQLQKMLKETKGMVSLKV 79

                  ..
gi 1207140201 210 LP 211
Cdd:cd10830    80 IP 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 1207140201 223 YVKPHFDYNPASDNLIPCREAGLAFKRGDILQIVNREDPNWWQACHLAEGG--TGLIPSQ 280
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 1207140201 223 YVKPHFDYNPASDNLIPCREAGLAFKRGDILQIVNREDPNWWQA--CHLAEGGTGLIPS 279
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 1207140201  61 VELVTDILGDISGLSVRDDSAAELSKILQEPHFQSLLEAHDMVASKCYEAPA 112
Cdd:pfam02828   1 VELVLELLEDLQPLSEASEDLAELQKLLQSPHLQALLEAHDKVAQKVYEPPS 52

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207140201 140 KAGEPLGVTFRMDKGDLVIARILHGGLIDRQGLLHVGDIIKEVNGKDV-GTNPTELQEMLKECSGGITLKILP 211
Cdd:cd06798     7 KTREPLGATVRNEGDSVIISRIVKGGAAEKSGLLHEGDEILEINGIEIrGKDVNEVCDLLADMHGTLTFLLIP 79

guanylate kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140201 344 LILIGAQGVGRRSLKNRLVVLHPTrFGTTVPHTSRRPRNDERDGQSYRFVTRLEMETDIKLGRYLEHGEYDGNLYGTKID 423
Cdd:PRK14738   16 VVISGPSGVGKDAVLARMRERKLP-FHFVVTATTRPKRPGEIDGVDYHFVTPEEFREMISQNELLEWAEVYGNYYGVPKA 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207140201 424 SIHEVVNTGRTCILDVNPQALKLLKtpEFMPYVVFI--AAPEFDTLkdMHKavvdagLTTKQLADVD-LKKTVDESARIL 500
Cdd:PRK14738   95 PVRQALASGRDVIVKVDVQGAASIK--RLVPEAVFIflAPPSMDEL--TRR------LELRRTESPEeLERRLATAPLEL 164

                         170       180
                  ....*....|....*....|....*..
gi 1207140201 501 RAYRHyFDLIIVN--DNLDCAFEKLQS 525
Cdd:PRK14738  165 EQLPE-FDYVVVNpeDRLDEAVAQIMA 190

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 1207140201 134 MIGIRKKAGEPLGVTFR---MDKGDLVIARILHGGLIDRQGLLHVGDIIKEVNGKDV-GTNPTELQEMLKECSGGITLKI 209
Cdd:cd00136     1 TVTLEKDPGGGLGFSIRggkDGGGGIFVSRVEPGGPAARDGRLRVGDRILEVNGVSLeGLTHEEAVELLKSAGGEVTLTV 80

                  .
gi 1207140201 210 L 210
Cdd:cd00136    81 R 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 1207140201  220 PQVYVKPHFDYNPASDNlipcreaGLAFKRGDILQIVNREDPNWWQaCHLAEGGTGLIPSQFLE 283
Cdd:smart00326   1 EGPQVRALYDYTAQDPD-------ELSFKKGDIITVLEKSDDGWWK-GRLGRGKEGLFPSNYVE 56

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207140201  140 KAGEPLGVTFRMDKGD---LVIARILHGGLIDRQGLlHVGDIIKEVNGKDV-GTNPTELQEMLKECSGGITLKILP 211
Cdd:smart00228   9 KGGGGLGFSLVGGKDEgggVVVSSVVPGSPAAKAGL-RVGDVILEVNGTSVeGLTHLEAVDLLKKAGGKVTLTVLR 83

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
                  ....*....|....*....|....*....|....*..
gi 1207140201 245 LAFKRGDILQIVNREDPNWWQACHLAEGGTGLIPSQF 281
Cdd:cd11845    16 LSFKKGDRLQILDDSDGDWWLARHLSTGKEGYIPSNY 52

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 1207140201 222 VYVKPHFDYNPASDNLIPCReaGLAFKRGDILQIVNREDPNWWQACHLAEGG----TGLIPSQ 280
Cdd:cd12031     3 LYVRALFDYDKTKDSGLPSQ--GLNFKFGDILHVVNASDDEWWQARQVTADGeseeIGVIPSK 63

PDZ domain 5 of inactivation no after potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 5 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ45 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This INAD-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207140201 139 KKAGEPLGVTFRMDKG-DLVIARILHGGLIDRQGLLHVGDIIKEVNGKDVGTNPTE-LQEMLKECSGGITLKI 209
Cdd:cd23066     6 KKAGKELGLSLSPNEGiGCTIADLLPGGYAEIDGKLQKGDIITKFNGDALSGLPFQvCYALFKGANGKISLEV 78

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 1207140201 223 YVKPHFDYNPasdnlipCREAGLAFKRGDILQIVNREDPNWWQAchLAEGGTGLIPSQFLEE 284
Cdd:pfam07653   1 YGRVIFDYVG-------TDKNGLTLKKGDVVKVLGKDNDGWWEG--ETGGRVGLVPSTAVEE 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1207140201 228 FDYNPASDNlipcrEagLAFKRGDILQIVNREDPNWWQAChLAEGGTGLIPS 279
Cdd:pfam00018   4 YDYTAQEPD-----E--LSFKKGDIIIVLEKSEDGWWKGR-NKGGKEGLIPS 47

N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins; CRK adaptor proteins consists of SH2 and SH3 domains, which bind tyrosine-phosphorylated peptides and proline-rich motifs, respectively. They function downstream of protein tyrosine kinases in many signaling pathways started by various extracellular signals, including growth and differentiation factors. Cellular CRK (c-CRK) contains a single SH2 domain, followed by N-terminal and C-terminal SH3 domains. It is involved in the regulation of many cellular processes including cell growth, motility, adhesion, and apoptosis. CRK has been implicated in the malignancy of various human cancers. The N-terminal SH3 domain of CRK binds a number of target proteins including DOCK180, C3G, SOS, and cABL. The CRK family includes two alternatively spliced protein forms, CRKI and CRKII, that are expressed by the CRK gene, and the CRK-like (CRKL) protein, which is expressed by a distinct gene (CRKL). 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 1207140201 223 YVKPHFDYnPASDnlipcrEAGLAFKRGDILQIVNREDPNWWQACHlAEGGTGLIPSQFLEE 284
Cdd:cd11758     2 YVRALFDF-PGND------DEDLPFKKGEILTVIRKPEEQWWNARN-SEGKTGMIPVPYVEK 55