Guanylate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118263  251 KRKTLVLIGASGVGRSHIKNALLSQNPEKFVYPVPYTTRPPRKSEEDGKEYHFISTEEMTRNISANEFLEFGSYQGNMFG 330
Cdd:pfam00625   1 SRRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118263  331 TKFETVHQIHKQNKIAILDIEPQTLKIVRTAELSPFIVFI-APTDQGTQ-------TEALQQLQKDSEAIRSQYAHY-FD 401
Cdd:pfam00625  81 TSVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIkPPSLKVLQrrlkgrgKEQEEKINKRMAAAEQEFQHYeFD 160

                         170       180
                  ....*....|....*....|..
gi 262118263  402 LSLVNNGVDETLKKLQEAFDQA 423
Cdd:pfam00625 161 VIIVNDDLEEAYKKLKEALEAE 182

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 262118263 132 FMRAQFDYDPKKDNLIPCKEAGLKFATGDIIQIINKDDSNWWQGRVEGSSKESAGLIPSPEL 193
Cdd:cd12080    1 YMRAQFDYDPKKDNLIPCKEAGLKFQTGDIIQIINKDDSNWWQGRVEGSGEESAGLIPSPEL 62

Guanylate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118263  251 KRKTLVLIGASGVGRSHIKNALLSQNPEKFVYPVPYTTRPPRKSEEDGKEYHFISTEEMTRNISANEFLEFGSYQGNMFG 330
Cdd:pfam00625   1 SRRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118263  331 TKFETVHQIHKQNKIAILDIEPQTLKIVRTAELSPFIVFI-APTDQGTQ-------TEALQQLQKDSEAIRSQYAHY-FD 401
Cdd:pfam00625  81 TSVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIkPPSLKVLQrrlkgrgKEQEEKINKRMAAAEQEFQHYeFD 160

                         170       180
                  ....*....|....*....|..
gi 262118263  402 LSLVNNGVDETLKKLQEAFDQA 423
Cdd:pfam00625 161 VIIVNDDLEEAYKKLKEALEAE 182

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 262118263  40 RLIQFEKVTEEPMGITLKLNEKQSCTVARILHGGMIHRQGSLHVGDEILEINGTNVTNHSVDQLQKAMKETKGMISLKVI 119
Cdd:cd10830    1 RLVQFEKNTEEPMGITLKLNEKQSCIVARILHGGMIHRQGSLHVGDEILEINGKSVTNHSVDQLQKMLKETKGMVSLKVI 80

                 .
gi 262118263 120 P 120
Cdd:cd10830   81 P 81

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 262118263 255 LVLIGASGVGRSHIKNALLSQNPEKFVYPVPYTTRPPRKSEEDGKEYHFISTEEMTRNISANEFLEFGSYQGNMFGTKFE 334
Cdd:cd00071    2 IVLSGPSGVGKSTLLKRLLEEFDPNFGFSVSHTTRKPRPGEVDGVDYHFVSKEEFERLIENGEFLEWAEFHGNYYGTSKA 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 262118263 335 TVHQIHKQNKIAILDIEPQTLKIVRTAELSPFIVFIAPTD 374
Cdd:cd00071   82 AVEEALAEGKIVILEIDVQGARQVKKSYPDAVSIFILPPD 121

Guanylate kinase [Nucleotide transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118263 255 LVLIGASGVGRSHIKNALLSQNPEkFVYPVPYTTRPPRKSEEDGKEYHFISTEEMTRNISANEFLEFGSYQGNMFGTKFE 334
Cdd:COG0194    5 IVLSGPSGAGKTTLVKALLERDPD-LRFSVSATTRPPRPGEVDGVDYHFVSREEFERMIENGEFLEWAEVHGNYYGTPKA 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118263 335 TVHQIHKQNKIAILDIEPQTLKIVRtaELSP--FIVFIAPTDQ----------GTQTEALQQ--LQKDSEAIrsQYAHYF 400
Cdd:COG0194   84 EVEEALAAGKDVLLEIDVQGARQVK--KKFPdaVSIFILPPSLeelerrlrgrGTDSEEVIErrLAKAREEL--AHADEF 159

                        170
                 ....*....|....*...
gi 262118263 401 DLSLVNNGVDETLKKLQE 418
Cdd:COG0194  160 DYVVVNDDLDRAVEELKA 177

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118263   41 LIQFEKVTEEPMGITLKLNEKQS---CTVARILHGGMIHRQGsLHVGDEILEINGTNVTNHSVDQLQKAMKETKGMISLK 117
Cdd:pfam00595   1 QVTLEKDGRGGLGFSLKGGSDQGdpgIFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLT 79

                  ..
gi 262118263  118 VI 119
Cdd:pfam00595  80 IL 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
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 262118263   132 FMRAQFDYDPKKDNlipckeaGLKFATGDIIQIINKDDSNWWQGRVEGSSKesaGLIPS 190
Cdd:smart00326   4 QVRALYDYTAQDPD-------ELSFKKGDIITVLEKSDDGWWKGRLGRGKE---GLFPS 52

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 262118263  65 TVARILHGGMIHRQGsLHVGDEILEINGTNVTNHSVDQLQKAMKETKG-MISLKVIPNQQSR 125
Cdd:COG0793   74 VVVSVIPGSPAEKAG-IKPGDIILAIDGKSVAGLTLDDAVKLLRGKAGtKVTLTIKRPGEGE 134

Guanylate kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118263  251 KRKTLVLIGASGVGRSHIKNALLSQNPEKFVYPVPYTTRPPRKSEEDGKEYHFISTEEMTRNISANEFLEFGSYQGNMFG 330
Cdd:pfam00625   1 SRRPVVLSGPSGVGKSHIKKALLSEYPDKFGYSVPHTTRPPRKGEVDGKDYYFVSKEEMERDISANEFLEYAQFSGNMYG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118263  331 TKFETVHQIHKQNKIAILDIEPQTLKIVRTAELSPFIVFI-APTDQGTQ-------TEALQQLQKDSEAIRSQYAHY-FD 401
Cdd:pfam00625  81 TSVETIEQIHEQGKIVILDVDPQGVKQLRKAELSPISVFIkPPSLKVLQrrlkgrgKEQEEKINKRMAAAEQEFQHYeFD 160

                         170       180
                  ....*....|....*....|..
gi 262118263  402 LSLVNNGVDETLKKLQEAFDQA 423
Cdd:pfam00625 161 VIIVNDDLEEAYKKLKEALEAE 182

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 262118263  40 RLIQFEKVTEEPMGITLKLNEKQSCTVARILHGGMIHRQGSLHVGDEILEINGTNVTNHSVDQLQKAMKETKGMISLKVI 119
Cdd:cd10830    1 RLVQFEKNTEEPMGITLKLNEKQSCIVARILHGGMIHRQGSLHVGDEILEINGKSVTNHSVDQLQKMLKETKGMVSLKVI 80

                 .
gi 262118263 120 P 120
Cdd:cd10830   81 P 81

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 262118263  40 RLIQFEKVTEEPMGITLKLNEKQSCTVARILHGGMIHRQGSLHVGDEILEINGTNVTNHSVDQLQKAMKETKGMISLKVI 119
Cdd:cd10831    1 RLVQFQKNTDEPMGITLKMNEDGRCIVARIMHGGMIHRQGTLHVGDEIREINGISVANQTVEQLQKMLREARGSITFKIV 80

                 .
gi 262118263 120 P 120
Cdd:cd10831   81 P 81

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 262118263 132 FMRAQFDYDPKKDNLIPCKEAGLKFATGDIIQIINKDDSNWWQGRVEGSSKESAGLIPSPEL 193
Cdd:cd12035    1 YVRAQFDYDPSKDDLIPCQQAGIAFKTGDILQIISKDDHNWWQARKPGASKEPAGLIPSPEL 62

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 262118263  255 LVLIGASGVGRSHIKNALLSQNPEkFVYPVPYTTRPPRKSEEDGKEYHFISTEEMTRNISANEFLEFGSYQGNMFGTKFE 334
Cdd:TIGR03263   3 IVISGPSGAGKSTLVKALLEEDPN-LKFSISATTRKPRPGEVDGVDYFFVSKEEFEEMIKAGEFLEWAEVHGNYYGTPKS 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118263  335 TVHQIHKQNKIAILDIEPQTLKIVRTAELSPFIVFIAPTDQgtqtEALQQ-LQK---DS-EAIRS---------QYAHYF 400
Cdd:TIGR03263  82 PVEEALAAGKDVLLEIDVQGARQVKKKFPDAVSIFILPPSL----EELERrLRKrgtDSeEVIERrlakakkeiAHADEF 157

                         170       180
                  ....*....|....*....|
gi 262118263  401 DLSLVNNGVDETLKKLQEAF 420
Cdd:TIGR03263 158 DYVIVNDDLEKAVEELKSII 177

Guanylate kinase [Nucleotide transport and metabolism];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118263 255 LVLIGASGVGRSHIKNALLSQNPEkFVYPVPYTTRPPRKSEEDGKEYHFISTEEMTRNISANEFLEFGSYQGNMFGTKFE 334
Cdd:COG0194    5 IVLSGPSGAGKTTLVKALLERDPD-LRFSVSATTRPPRPGEVDGVDYHFVSREEFERMIENGEFLEWAEVHGNYYGTPKA 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118263 335 TVHQIHKQNKIAILDIEPQTLKIVRtaELSP--FIVFIAPTDQ----------GTQTEALQQ--LQKDSEAIrsQYAHYF 400
Cdd:COG0194   84 EVEEALAAGKDVLLEIDVQGARQVK--KKFPdaVSIFILPPSLeelerrlrgrGTDSEEVIErrLAKAREEL--AHADEF 159

                        170
                 ....*....|....*...
gi 262118263 401 DLSLVNNGVDETLKKLQE 418
Cdd:COG0194  160 DYVVVNDDLDRAVEELKA 177

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 262118263 132 FMRAQFDYDPKKDNLIPCKEAGLKFATGDIIQIINKDDSNWWQGRVEGSSKESAGLIPSPEL 193
Cdd:cd12081    1 YVRAQFEYDPLKDDLIPCKQAGIRFRVGDILQIISKDDHNWWQAKLENSKNGTAGLIPSPEL 62

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118263  40 RLIQFEKVTEEPMGITLKLNEKQsCTVARILHGGMIHRQGSLHVGDEILEINGTNVtnHSVDQLQKAMKETKGMISLKVI 119
Cdd:cd10832    1 RMVGIRKNPGEPLGVTVRLEEGE-LVIARILHGGMIDRQGLLHVGDIIKEVNGVPV--GSPEQLQEMLKNASGSVTLKIL 77

                 .
gi 262118263 120 P 120
Cdd:cd10832   78 P 78

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 262118263 132 FMRAQFDYDPKKDNLIPCKEAGLKFATGDIIQIINKDDSNWWQGRVEGSSKESAGLIPS 190
Cdd:cd12033    1 FIKALFDYNPNEDKAIPCKEAGLSFKKGDILQIMSQDDATWWQAKHEGDANPRAGLIPS 59

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118263   41 LIQFEKVTEEPMGITLKLNEKQS---CTVARILHGGMIHRQGsLHVGDEILEINGTNVTNHSVDQLQKAMKETKGMISLK 117
Cdd:pfam00595   1 QVTLEKDGRGGLGFSLKGGSDQGdpgIFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLT 79

                  ..
gi 262118263  118 VI 119
Cdd:pfam00595  80 IL 81

guanylate kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118263 253 KTLVLIGASGVGRSHIKNALLSQNPEkFVYPVPYTTRPPRKSEEDGKEYHFISTEEMTRNISANEFLEFGSYQGNMFGTK 332
Cdd:PRK14737   5 KLFIISSVAGGGKSTIIQALLEEHPD-FLFSISCTTRAPRPGDEEGKTYFFLTIEEFKKGIADGEFLEWAEVHDNYYGTP 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262118263 333 FETVHQIHKQNKIAILDIEPQTLKIVRtaELSP---FIVFIAPTDQGTQTEALQQLQKDSEA----------IRSQYAHY 399
Cdd:PRK14737  84 KAFIEDAFKEGRSAIMDIDVQGAKIIK--EKFPeriVTIFIEPPSEEEWEERLIHRGTDSEEsiekriengiIELDEANE 161

                        170       180
                 ....*....|....*....|....*...
gi 262118263 400 FDLSLVNNGVDETLKKLQEAFdqaCSSP 427
Cdd:PRK14737 162 FDYKIINDDLEDAIADLEAII---CGKK 186

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 262118263 132 FMRAQFDYDPKKDNLIPCKEAGLKFATGDIIQIINKDDSNWWQGR--VEGSskeSAGLIPS 190
Cdd:cd12038    1 FVKCHFDYNPYNDNLIPCKEAGLKFSKGEILQIVNREDPNWWQAShvKEGG---SAGLIPS 58

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 262118263 132 FMRAQFDYDPKKDNLIPCKEAGLKFATGDIIQIINKDDSNWWQGRVEGSSKESAGLIPS 190
Cdd:cd12034    1 YVRAMVDYWPQQDPSIPCADAGLPFRKGDILQIVDQNDSLWWQARKLSDLAACAGLIPS 59

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 262118263  40 RLIQFEKvTEEPMGITLKlNEKQSCTVARILHGGMIHRQGSLHVGDEILEINGTNVTNHSVDQLQKAMKETKGMISLKVI 119
Cdd:cd06798    1 KIVRIEK-TREPLGATVR-NEGDSVIISRIVKGGAAEKSGLLHEGDEILEINGIEIRGKDVNEVCDLLADMHGTLTFLLI 78

                 .
gi 262118263 120 P 120
Cdd:cd06798   79 P 79

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 262118263    38 KVRLIQFEKvTEEPMGITLK--LNEKQSCTVARILHGGMIHRQGsLHVGDEILEINGTNVTNHSVDQLQKAMKETKGMIS 115
Cdd:smart00228   1 EPRLVELEK-GGGGLGFSLVggKDEGGGVVVSSVVPGSPAAKAG-LRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVT 78

                   ....*.
gi 262118263   116 LKVIPN 121
Cdd:smart00228  79 LTVLRG 84

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 262118263 131 MFMRAQFDYDPKKDNLIPCKeaGLKFATGDIIQIINKDDSNWWQGR---VEGSSKEsAGLIPS 190
Cdd:cd12032    6 LYVRAMFDYEKSKDSGLPSQ--GLSFRYGDILHVINASDDEWWQARrvtPDGDSEE-MGVIPS 65

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 262118263 132 FMRAQFDYDPKKDNlipckeaGLKFATGDIIQIINKDDSNWWQGRVEGSSKesaGLIPS 190
Cdd:cd00174    1 YARALYDYEAQDDD-------ELSFKKGDIITVLEKDDDGWWEGELNGGRE---GLFPA 49

PDZ domain 3 of harmonin isoforms a and b, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of harmonin isoforms a and b, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. 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 harmonin family PDZ3 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 262118263  37 RKVRLIQFEKvtEEPMGITLK------LNEKqsCTVARILHGGMIHRQGSLHVGDEILEINGTNVTNHSVDQ----LQKA 106
Cdd:cd06739    1 RQVRLLRIKK--NGPLDLALEggidspLGGK--IVVSAVYEGGAADKHGGIVKGDQIMMVNGKSLTDVTLAEaeaaLQRA 76

                         90
                 ....*....|..
gi 262118263 107 MKETKGMISLKV 118
Cdd:cd06739   77 MNSGGDWIDLVI 88

PDZ domain 3 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. 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 GRIP family PDZ3 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 262118263  41 LIQFEKVTEEPMGITL---KLNEKQSCTVARILHGGMIHRQGSLHVGDEILEINGTNVTNHSVDQLQKAMKET-KGMISL 116
Cdd:cd06684    4 LVEIEKTPGSSLGITLstsTHRNKQVIVIDSIKPASIADRCGALHVGDHILSIDGTSVEHCSLAEATQLLASNsGDQVKL 83

                 ....
gi 262118263 117 KVIP 120
Cdd:cd06684   84 EILP 87

Src Homology 3 domain of Sdc25/Cdc25 guanine nucleotide exchange factors; This subfamily is composed of the Saccharomyces cerevisiae guanine nucleotide exchange factors (GEFs) Sdc25 and Cdc25, and similar proteins. These GEFs regulate Ras by stimulating the GDP/GTP exchange on Ras. Cdc25 is involved in the Ras/PKA pathway that plays an important role in the regulation of metabolism, stress responses, and proliferation, depending on available nutrients and conditions. Proteins in this subfamily contain an N-terminal SH3 domain as well as REM (Ras exchanger motif) and RasGEF domains at the C-terminus. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 262118263 134 RAQFDYDPKKDNLipckeagLKFATGDIIQIINKDDSNWWQGRVEGSSKE 183
Cdd:cd11883    3 VALYDFTPKSKNQ-------LSFKAGDIIYVLNKDPSGWWDGVIISSSGK 45

PDZ domain 3 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. 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 Dlg5-like family PDZ3 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 262118263  40 RLIQFEKvTEEPMGITLKLNEKQSCTVARIlHGGMIHRQGSLHVGDEILEINGTNVTNHSVDQLQKAMKETKGMISLKV 118
Cdd:cd06767    4 RHVSIEK-GSEPLGISIVSGENGGIFVSSV-TEGSLAHQAGLEYGDQLLEVNGINLRNATEQQAALILRQCGDTITMLV 80

PDZ domain 4 of membrane-associated guanylate kinase inverted 1 (MAGI-1), MAGI-2, and MAGI-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of MAGI1, 2, 3 (MAGI is also known as Membrane-associated guanylate kinase, WW and PDZ domain-containing protein) and related domains. MAGI proteins have been implicated in the control of cell migration and invasion through altering the activity of phosphatase and tensin homolog (PTEN) and modulating Akt signaling. Four MAGI proteins have been identified (MAGI1-3 and MAGIX). MAGI1-3 have 6 PDZ domains and bind to the C-terminus of PTEN via their PDZ2 domain. MAGIX has a single PDZ domain that is related to MAGI1-3 PDZ domain 5. Other binding partners for MAGI1 include JAM4, C-terminal tail of high risk HPV-18 E6, megalin, TRAF6, Kir4.1 (basolateral K+ channel subunit), and cadherin 23; for MAGI2, include DASM1, dendrin, axin, beta- and delta-catenin, neuroligin, hyperpolarization-activated cation channels, beta1-adrenergic receptors, NMDA receptor, and TARPs; and for MAGI3 includes LPA2. 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 MAGI family PDZ4 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 262118263  54 ITLKLNEKQSCTVARILHGGMIHRQGSLHVGDEILEINGTNVTNHSVDQLQKAMKETKGMISLKVIP 120
Cdd:cd06734   18 IISSVNKKSGSKIGRIIPGSPADRCGQLKVGDRILAVNGISILNLSHGDIVNLIKDSGLSVTLTIVP 84

Src homology 3 domain of Myosins Ie, If, and similar proteins; Myosins Ie (MyoIe) and If (MyoIf) are nonmuscle, unconventional, long tailed, class I myosins containing an N-terminal motor domain and a myosin tail with TH1, TH2, and SH3 domains. MyoIe interacts with the endocytic proteins, dynamin and synaptojanin-1, through its SH3 domain; it may play a role in clathrin-dependent endocytosis. In the kidney, MyoIe is critical for podocyte function and normal glomerular filtration. Mutations in MyoIe is associated with focal segmental glomerulosclerosis, a disease characterized by massive proteinuria and progression to end-stage kidney disease. MyoIf is predominantly expressed in the immune system; it plays a role in immune cell motility and innate immunity. Mutations in MyoIf may be associated with the loss of hearing. The MyoIf gene has also been found to be fused to the MLL (Mixed lineage leukemia) gene in infant acute myeloid leukemias (AML). 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 262118263 134 RAQFDYDPKKDNlipckeaGLKFATGDIIQIINKDDSNWWQGRVEGssKEsaGLIPS 190
Cdd:cd11827    3 KALYAYDAQDTD-------ELSFNEGDIIEILKEDPSGWWTGRLRG--KE--GLFPG 48

PDZ domain of partitioning defective 6 (Par6), Drosophila Rho GTPase-activating protein 100F (RhoGAP100F), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Par6 (also known as PAR6 or Par-6), RhoGAP100F, and related domains. Par6 is part of a conserved machinery that directs metazoan cell polarity, a process necessary for the function of diverse cell types. Par6 forms a cell polarity-regulatory complex with atypical protein kinase C (aPKC) and Par3. Par6 can also directly associate with PALS1 (proteins associated with Lin7, also known as Stardust) providing a link between the Par3/aPKC/Par6 complex and the PALS1-PATJ (protein-associated TJ) complex. Binding partners of the Par6-PDZ domain include Par3, PALS1/Stardust; leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2), human crumbs (CRB3) involve in the morphogenesis of the tight junctions in mammalian epithelial cells, and PAR-6 co-operates with the Par6 semi-CRIB domain to bind CDC42. CDC42 regulates the Par6 PDZ domain through an allosteric CRIB-PDZ transition. Drosophila RhoGAP100F, also known as synapse defective protein 1 homolog (syd-1 homolog), is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound form. The RhoGAP100F-PDZ domain binds the neurexin C terminus to control synapse formation at the Drosophila neuromuscular junction. 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 Par6-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.