Guanylate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189  335 RRKTLVLIGAQGVGRRSLKNKLLVSDPHRYGTTTPYTSRKPKVDEKEGQMYLFMSRSEMETDIKCGRFLEHGEYDGNLYG 414
Cdd:pfam00625   1 SRRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189  415 TKIDSIHEVVDSGKICILDVNPQALKVLRTAEFLPYVVFIEAPNFEVLKDMNRSaieagvvtkqMTDSELKRTVDESERI 494
Cdd:pfam00625  81 TSVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPSLKVLQRRLKG----------RGKEQEEKINKRMAAA 150

                         170       180       190
                  ....*....|....*....|....*....|
gi 688579189  495 QRAYSHY-FDLSIVNDNLDGAYRSLRRALD 523
Cdd:pfam00625 151 EQEFQHYeFDVIIVNDDLEEAYKKLKEALE 180

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 688579189 239 FVKCHFDYDPSHDNLIPCKEAGLKFSSGDILQIFNQEDPNWWQACHLEGGSAGLIPSQL 297
Cdd:cd12037    1 FVKCHFDYDPSSDSLIPCKEAGLKFRAGDLLQIVNQEDPNWWQACHVEGGSAGLIPSQL 59

Guanylate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189  335 RRKTLVLIGAQGVGRRSLKNKLLVSDPHRYGTTTPYTSRKPKVDEKEGQMYLFMSRSEMETDIKCGRFLEHGEYDGNLYG 414
Cdd:pfam00625   1 SRRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189  415 TKIDSIHEVVDSGKICILDVNPQALKVLRTAEFLPYVVFIEAPNFEVLKDMNRSaieagvvtkqMTDSELKRTVDESERI 494
Cdd:pfam00625  81 TSVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPSLKVLQRRLKG----------RGKEQEEKINKRMAAA 150

                         170       180       190
                  ....*....|....*....|....*....|
gi 688579189  495 QRAYSHY-FDLSIVNDNLDGAYRSLRRALD 523
Cdd:pfam00625 151 EQEFQHYeFDVIIVNDDLEEAYKKLKEALE 180

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 688579189 149 RMVGIRKVSGEHLGVTFRVEGGELVIARILHGGMIDQQGLLHVGDIIKEVNGKEVGSdPKVLQNMLKESSGSVVLKILP 227
Cdd:cd10832    1 RMVGIRKNPGEPLGVTVRLEEGELVIARILHGGMIDRQGLLHVGDIIKEVNGVPVGS-PEQLQEMLKNASGSVTLKILP 78

guanylate kinase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189 337 KTLVLIGAQGVGRRSLKNKLLVSDPHRYGTTTPYTSRKPKVDEKEGQMYLFMSRSEMETDIKCGRFLEHGEYDGNLYGTK 416
Cdd:PLN02772 136 KPIVISGPSGVGKGTLISMLMKEFPSMFGFSVSHTTRAPREMEKDGVHYHFTERSVMEKEIKDGKFLEFASVHGNLYGTS 215

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189 417 IDSIHEVVDSGKICILDVNPQALKVLRTAEFLPYVVFIEAPNFEVLKDMNRSaieAGVVTKQMTDSELKRTvdESERIQR 496
Cdd:PLN02772 216 IEAVEVVTDSGKRCILDIDVQGARSVRASSLEAIFIFICPPSMEELEKRLRA---RGTETEEQIQKRLRNA--EAELEQG 290

                        170       180
                 ....*....|....*....|....*..
gi 688579189 497 AYSHYFDLSIVNDNLDGAYRSLRRALD 523
Cdd:PLN02772 291 KSSGIFDHILYNDNLEECYKNLKKLLG 317

Guanylate kinase [Nucleotide transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189 339 LVLIGAQGVGRRSLKNKLLVSDPH-RYGTTtpYTSRKPKVDEKEGQMYLFMSRSEMETDIKCGRFLEHGEYDGNLYGTKI 417
Cdd:COG0194    5 IVLSGPSGAGKTTLVKALLERDPDlRFSVS--ATTRPPRPGEVDGVDYHFVSREEFERMIENGEFLEWAEVHGNYYGTPK 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189 418 DSIHEVVDSGKICILDVNPQ-ALKVLRTaefLPYVV--FIEAPNFEVLKD--MNRsaieagvvtKQMTDSELKRtvdese 492
Cdd:COG0194   83 AEVEEALAAGKDVLLEIDVQgARQVKKK---FPDAVsiFILPPSLEELERrlRGR---------GTDSEEVIER------ 144

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 688579189 493 RIQRAYS-----HYFDLSIVNDNLDGAYRSLRRAL--DRLNTDQQ 530
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 688579189   76 VELVQDILRDLNTLSPDSPAAHELICILKEPHFQSLLETHDSVASKSYETPP 127
Cdd:pfam02828   1 VELVLELLEDLQPLSEASEDLAELQKLLQSPHLQALLEAHDKVAQKVYEPPS 52

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 688579189   239 FVKCHFDYDPSHDNlipckeaGLKFSSGDILQIFNQEDPNWWQaCHLEGGSAGLIPSQLLE 299
Cdd:smart00326   4 QVRALYDYTAQDPD-------ELSFKKGDIITVLEKSDDGWWK-GRLGRGKEGLFPSNYVE 56

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189  153 IRKVSGEHLGvtFRVEGG------ELVIARILHGGMIDQQGLlHVGDIIKEVNGKEVGSDPKV-LQNMLKESSGSVVLKI 225
Cdd:pfam00595   4 LEKDGRGGLG--FSLKGGsdqgdpGIFVSEVLPGGAAEAGGL-KVGDRILSINGQDVENMTHEeAVLALKGSGGKVTLTI 80

                  .
gi 688579189  226 L 226
Cdd:pfam00595  81 L 81

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189 144 PPDAVRMVGIRKVSGEHLGVTFRVEGGELVIARILHGGMIDQQGLlHVGDIIKEVNGKEV-GSDPKVLQNMLKESSGS-V 221
Cdd:COG0793   45 PEEYEDFQESTSGEFGGLGAELGEEDGKVVVVSVIPGSPAEKAGI-KPGDIILAIDGKSVaGLTLDDAVKLLRGKAGTkV 123

                 ....*.
gi 688579189 222 VLKILP 227
Cdd:COG0793  124 TLTIKR 129

Guanylate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189  335 RRKTLVLIGAQGVGRRSLKNKLLVSDPHRYGTTTPYTSRKPKVDEKEGQMYLFMSRSEMETDIKCGRFLEHGEYDGNLYG 414
Cdd:pfam00625   1 SRRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189  415 TKIDSIHEVVDSGKICILDVNPQALKVLRTAEFLPYVVFIEAPNFEVLKDMNRSaieagvvtkqMTDSELKRTVDESERI 494
Cdd:pfam00625  81 TSVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIKPPSLKVLQRRLKG----------RGKEQEEKINKRMAAA 150

                         170       180       190
                  ....*....|....*....|....*....|
gi 688579189  495 QRAYSHY-FDLSIVNDNLDGAYRSLRRALD 523
Cdd:pfam00625 151 EQEFQHYeFDVIIVNDDLEEAYKKLKEALE 180

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 688579189 149 RMVGIRKVSGEHLGVTFRVEGGELVIARILHGGMIDQQGLLHVGDIIKEVNGKEVGSdPKVLQNMLKESSGSVVLKILP 227
Cdd:cd10832    1 RMVGIRKNPGEPLGVTVRLEEGELVIARILHGGMIDRQGLLHVGDIIKEVNGVPVGS-PEQLQEMLKNASGSVTLKILP 78

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 688579189 239 FVKCHFDYDPSHDNLIPCKEAGLKFSSGDILQIFNQEDPNWWQACHLE--GGSAGLIPSQ 296
Cdd:cd11862    1 FVRALFDYDPEEDPLIPCKEAGLSFKKGDILQIVNQDDPNWWQARKVGdpNGRAGLIPSQ 60

guanylate kinase; Members of this family are the enzyme guanylate kinase, also called GMP kinase. This enzyme transfers a phosphate from ATP to GMP, yielding ADP and GDP. [Purines, pyrimidines, nucleosides, and nucleotides, Nucleotide and nucleoside interconversions]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189  339 LVLIGAQGVGRRSLKNKLLVSDPHRYGTTTpYTSRKPKVDEKEGQMYLFMSRSEMETDIKCGRFLEHGEYDGNLYGTKID 418
Cdd:TIGR03263   3 IVISGPSGAGKSTLVKALLEEDPNLKFSIS-ATTRKPRPGEVDGVDYFFVSKEEFEEMIKAGEFLEWAEVHGNYYGTPKS 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189  419 SIHEVVDSGKICILDVNPQ-ALKVLRTaeFLPYV-VFIEAPNFEVLKdmNRsaieagvVTKQMTDSE--LKRtvdeseRI 494
Cdd:TIGR03263  82 PVEEALAAGKDVLLEIDVQgARQVKKK--FPDAVsIFILPPSLEELE--RR-------LRKRGTDSEevIER------RL 144

                         170       180       190
                  ....*....|....*....|....*....|...
gi 688579189  495 QRA-----YSHYFDLSIVNDNLDGAYRSLRRAL 522
Cdd:TIGR03263 145 AKAkkeiaHADEFDYVIVNDDLEKAVEELKSII 177

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 688579189 149 RMVGIRKVSGEHLGVTFRVEGGELVIARILHGGMIDQQGLLHVGDIIKEVNGKEV-GSDPKVLQNMLKESSGSVVLKILP 227
Cdd:cd06726    1 RLVEFEKARDEPLGATIKMEEDSVIVARILHGGMAHRSGLLHVGDEILEINGIPVsGKTVDELQKLLSSLSGSVTFKLIP 80

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189 239 FVKCHFDYDPSHDNLIPCKEAGLKFSSGDILQIFNQEDPNWWQAcHLEG---GSAGLIPS 295
Cdd:cd12080    1 YMRAQFDYDPKKDNLIPCKEAGLKFQTGDIIQIINKDDSNWWQG-RVEGsgeESAGLIPS 59

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 688579189 339 LVLIGAQGVGRRSLKNKLLVSDPHRYGTTTPYTSRKPKVDEKEGQMYLFMSRSEMETDIKCGRFLEHGEYDGNLYGTKID 418
Cdd:cd00071    2 IVLSGPSGVGKSTLLKRLLEEFDPNFGFSVSHTTRKPRPGEVDGVDYHFVSKEEFERLIENGEFLEWAEFHGNYYGTSKA 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 688579189 419 SIHEVVDSGKICILDVNPQALKVLRTAEFLPYVVFIEAPNFEVLKD 464
Cdd:cd00071   82 AVEEALAEGKIVILEIDVQGARQVKKSYPDAVSIFILPPDYVIVND 127

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 688579189 239 FVKCHFDYDPSHDNLIPCKEAGLKFSSGDILQIFNQEDPNWWQACHlEGGS---AGLIPSQ 296
Cdd:cd12033    1 FIKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKH-EGDAnprAGLIPSK 60

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 688579189 149 RMVGIRKVSGEHLGVTFRV-EGGELVIARILHGGMIDQQGLLHVGDIIKEVNGKEV-GSDPKVLQNMLKESSGSVVLKIL 226
Cdd:cd10831    1 RLVQFQKNTDEPMGITLKMnEDGRCIVARIMHGGMIHRQGTLHVGDEIREINGISVaNQTVEQLQKMLREARGSITFKIV 80

                 .
gi 688579189 227 P 227
Cdd:cd10831   81 P 81

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189 239 FVKCHFDYDPSHDNLIPCKEAGLKFSSGDILQIFNQEDPNWWQAcHLE---GGSAGLIPS 295
Cdd:cd12081    1 YVRAQFEYDPLKDDLIPCKQAGIRFRVGDILQIISKDDHNWWQA-KLEnskNGTAGLIPS 59

PDZ domain of membrane palmitoylated proteins 3 (MPP3), MPP4, and MPP7, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP3, MPP4, and MPP7, and related domains. MPP3 (also known as MAGUK p55 subfamily member 3, erythrocyte membrane protein p55, or EMP55), MPP4 (also known as MAGUK p55 subfamily member 4 or Discs large homolog 6), and MPP7 (also known as MAGUK p55 subfamily member 7) are membrane-associated guanylate kinase (MAGUK)-like proteins. MPP3 is part of a cell adhesion protein complex including tumor suppressor CADM1 and actin-binding protein 4.1B. Participation in the Crumbs cell polarity complex has also been demonstrated for MPP7 in epithelial cells, and for MPP3 and MPP4 in the retina. MPP4 is needed for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals. Binding partners of the MPP3 PDZ domain include nectin-3, serotonin 5-hydroxytryptamine, 5-HT(2C) receptor, and a cell adhesion protein, TSLC1 (tumor suppressor in lung cancer 1); fragments of MPP4 having the PDZ domain bind CRB (PDZ-SH3-GUK) and GABA transporter GAT1 (PDZ-SH3). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189 148 VRMVGirkvSGEHLGVTFRV--EGGELVIARILHGGMIDQQGLLHVGDIIKEVNGKEV-GSDPKVLQNMLKESSGSVVLK 224
Cdd:cd06799    3 VRLVK----NNEPLGATIKRdeKTGAIVVARIMRGGAADRSGLIHVGDELREVNGISVeGKDPEEVIQILANSQGPITFK 78

                 ...
gi 688579189 225 ILP 227
Cdd:cd06799   79 LIP 81

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 688579189   76 VELVQDILRDLNTLSPDSPAAHELICILKEPHFQSLLETHDSVASKSYETPP 127
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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189 149 RMVGIRKvSGEHLGVTFRVEGGELVIARILHGGMIDQQGLLHVGDIIKEVNGKEV-GSDPKVLQNMLKESSGSVVLKILP 227
Cdd:cd06798    1 KIVRIEK-TREPLGATVRNEGDSVIISRIVKGGAAEKSGLLHEGDEILEINGIEIrGKDVNEVCDLLADMHGTLTFLLIP 79

Src Homology 3 domain of Disks large homolog proteins; The DLG-like proteins are scaffolding proteins that cluster at synapses and are also called PSD (postsynaptic density)-95 proteins or SAPs (synapse-associated proteins). They play important roles in synaptic development and plasticity, cell polarity, migration and proliferation. They are members of the MAGUK (membrane-associated guanylate kinase) protein family, which is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. DLG-like proteins contain three PDZ domains and varying N-terminal regions. All DLG proteins exist as alternatively-spliced isoforms. Vertebrates contain four DLG proteins from different genes, called DLG1-4. DLG4 and DLG2 are found predominantly at postsynaptic sites and they mediate surface ion channel and receptor clustering. DLG3 is found axons and some presynaptic terminals. DLG1 interacts with AMPA-type glutamate receptors and is critical in their maturation and delivery to synapses. The SH3 domain of DLG4 binds and clusters the kainate subgroup of glutamate receptors via two proline-rich sequences in their C-terminal tail. It also binds AKAP79/150 (A-kinase anchoring protein). SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 688579189 239 FVKCHFDYDPSHDNLIPCKeaGLKFSSGDILQIFNQEDPNWWQACHL----EGGSAGLIPS 295
Cdd:cd11861    1 YVRALFDYDPSRDSGLPSQ--GLSFKFGDILHVTNASDDEWWQARRVtpngEEEEVGVIPS 59

guanylate kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189 333 PFRRKTLVLIGAQGVGRRSLKNKL-LVSDPHRYGTTTpyTSRKPKVDEKEGQMYLFMSRSEMETDIKCGRFLEHGEYDGN 411
Cdd:PRK14738  10 PAKPLLVVISGPSGVGKDAVLARMrERKLPFHFVVTA--TTRPKRPGEIDGVDYHFVTPEEFREMISQNELLEWAEVYGN 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189 412 LYGTKIDSIHEVVDSGKICILDVNPQALKVLRtaEFLPYVVFI--EAPNFEVLkdMNRsaieagvVTKQMTDS--ELKRT 487
Cdd:PRK14738  88 YYGVPKAPVRQALASGRDVIVKVDVQGAASIK--RLVPEAVFIflAPPSMDEL--TRR-------LELRRTESpeELERR 156

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 688579189 488 VDESER-IQRAYShyFDLSIVN--DNLDGAYRSLR 519
Cdd:PRK14738 157 LATAPLeLEQLPE--FDYVVVNpeDRLDEAVAQIM 189

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 688579189   148 VRMVGIRKVSGEhLGVTF---RVEGGELVIARILHGGMIDQQGLlHVGDIIKEVNGKEV-GSDPKVLQNMLKESSGSVVL 223
Cdd:smart00228   2 PRLVELEKGGGG-LGFSLvggKDEGGGVVVSSVVPGSPAAKAGL-RVGDVILEVNGTSVeGLTHLEAVDLLKKAGGKVTL 79

                   ....
gi 688579189   224 KILP 227
Cdd:smart00228  80 TVLR 83

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 688579189 236 RQAFVKCHFDYDPSHDNLIPCKeaGLKFSSGDILQIFNQEDPNWWQA--CHLEGGSA--GLIPSQLLEEKRK 303
Cdd:cd12032    4 RSLYVRAMFDYEKSKDSGLPSQ--GLSFRYGDILHVINASDDEWWQArrVTPDGDSEemGVIPSKRRVERKE 73

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 688579189   239 FVKCHFDYDPSHDNlipckeaGLKFSSGDILQIFNQEDPNWWQaCHLEGGSAGLIPSQLLE 299
Cdd:smart00326   4 QVRALYDYTAQDPD-------ELSFKKGDIITVLEKSDDGWWK-GRLGRGKEGLFPSNYVE 56

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 688579189  153 IRKVSGEHLGvtFRVEGG------ELVIARILHGGMIDQQGLlHVGDIIKEVNGKEVGSDPKV-LQNMLKESSGSVVLKI 225
Cdd:pfam00595   4 LEKDGRGGLG--FSLKGGsdqgdpGIFVSEVLPGGAAEAGGL-KVGDRILSINGQDVENMTHEeAVLALKGSGGKVTLTI 80

                  .
gi 688579189  226 L 226
Cdd:pfam00595  81 L 81

C-terminal Src homology 3 domain of Growth factor receptor-bound protein 2; GRB2 is a critical signaling molecule that regulates the Ras pathway by linking tyrosine kinases to the Ras guanine nucleotide releasing protein Sos (son of sevenless), which converts Ras to the active GTP-bound state. It is ubiquitously expressed in all tissues throughout development and is important in cell cycle progression, motility, morphogenesis, and angiogenesis. In lymphocytes, GRB2 is associated with antigen receptor signaling components. GRB2 contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRB2 binds to Gab2 (Grb2-associated binder 2) through epitopes containing RxxK motifs, as well as to the proline-rich C-terminus of FGRF2. SH3 domains are protein interaction domains that typically bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 688579189 239 FVKCHFDYDPSHDNlipckeaGLKFSSGDILQIFNQEDPNWWQ-ACHlegGSAGLIPS 295
Cdd:cd11949    1 YVQALFDFDPQEDG-------ELGFRRGDFIEVMDNSDPNWWKgACH---GQTGMFPR 48