Formin Homology 2 Domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2032630020  637 HRRSETSHMSVKRLRWEQVENSE--GTIWGQLGEDSDYDKLsDMvkyLDLELHFGTQKPAKPVPGPE----PFRKKEVVE 710
Cdd:pfam02181    1 PKKTPKPKKKLKPLHWDKVRPSQdrGTVWDKLDDESFELDG-DL---SELEELFSAKAKTKKNKKSEdkssSKKKPKEVS 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2032630020  711 ILSHKKAYNTSILLAHLKLSPAELRQVLMSMEPRRLEPAHLAQLLLFAPDADEEQRYQAFREAPGRLSEPDQFVLQMLSV 790
Cdd:pfam02181   77 LLDPKRAQNIAILLRKLKLPPEEIIQAILEGDEDALDLELLENLLKMAPTKEELKKLKEYKGDPSELGRAEQFLLELSKI 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2032630020  791 PEYKTRLRSLHFQATLQEKTEEIRGSLECLRQASLELKNSRKLAKILEFVLAMGNYLNDGQPKTNkTTGFKINFLTELNS 870
Cdd:pfam02181  157 PRLEARLRALLFKSTFEEEIEELKPSLEALEAASEELRNSRKFKKLLELILALGNYMNDGTRRGQ-AKGFKLSSLLKLSD 235

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2032630020  871 TKTVDGKSTFLHILAKSLSQHFPELLGFAQDLPTVPLAAKVNQRALTSDLADLHGTISEIQDACQSISPSSE--DKFAMV 948
Cdd:pfam02181  236 TKSTDNKTTLLHYLVKIIREKFPEVLDFSSELSHVKKAAKVNLEQLEKDVKQLERGLKKLERELELSALDEHpdDKFREV 315

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2032630020  949 MSSFLETAQPALRALDGLQREAMEELGKALAFFGEDSKATTSEAFFGIFAEFMSKFE 1005
Cdd:pfam02181  316 LKEFLKSAEEKLDKLESLLREALELFKELVEYFGEDPKETSPEEFFKILRDFLKEFK 372

second harmonin_N_like domain (repeat 2) of L-delphilin, and related domains; This subgroup contains the second of two harmonin_N_like domains of an alternatively spliced longer variant of mouse delphilin (L-delphilin), and related domains. Delphilin is a postsynaptic density-95/discs-large/ZO-1 (PDZ) domain-containing scaffold protein which binds the glutamate receptor delta-2 (GRID2) subunit and the monocarboxylate transporter 2 at the cerebellar parallel fiber-Purkinje cell synapses. This harmonin_N_like domain in L-delphilin follows the second PDZ protein-binding domain, PDZ2; it is also found in the shorter C-terminal isoforms (S-delphilin/delphilin alpha and delphilin beta). It is a putative protein-binding module based on its sequence similarity to the N-terminal domain of harmonin. The first harmonin_N_like domain of L-delphilin belongs to a different subgroup and is missing from S-delphilin.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2032630020  206 IRVQGRTFSQQLEHLLTPPERYGVCRALESFFQHRNIDTLIVDVYPVLDTPAKQVLWQFIYQLLTYEEQELCQEKIACFL 285
Cdd:cd07355      1 IRVQGRTFKQQLEHLLTSKERYQLCRALERYFQHRNIDTLIVDVYPVLDTPAKQTLWQFILQLLTYEEQEYCQQKIALFL 80

N-terminal protein-binding module of harmonin and similar domains, also known as HHD (harmonin homology domain); This domain is found in harmonin, and similar proteins such as delphilin, and whirlin. These are postsynaptic density-95/discs-large/ZO-1 (PDZ) domain-containing scaffold proteins. Harmonin and whirlin are organizers of the Usher protein network of the inner ear and the retina, delphilin is found at the cerebellar parallel fiber-Purkinje cell synapses. This domain is also found in CCM2 (also called malcavernin; C7orf22/chromosome 7 open reading frame 22; OSM). CCM2 along with CCM1 and CCM3 constitutes a set of proteins which when mutated are responsible for cerebral cavernous malformations, an autosomal dominant neurovascular disease characterized by cerebral hemorrhages and vascular malformations in the central nervous system. CCM2 plays many functional roles. CCM2 functions as a scaffold involved in small GTPase Rac-dependent p38 mitogen-activated protein kinase (MAPK) activation when the cell is under hyperosmotic stress. It associates with CCM1 in the signaling cascades that regulate vascular integrity and participates in HEG1 (the transmembrane receptor heart of glass 1) mediated endothelial cell junctions. CCM proteins also inhibit the activation of small GTPase RhoA and its downstream effector Rho kinase (ROCK) to limit vascular permeability. CCM2 mediates TrkA-dependent cell death via its N-terminal PTB domain in pediatric neuroblastic tumours; the C-terminal domain of malcavernin represented here has also been refered to as the Karet domain. Harmonin contains a single copy of this domain at its N-terminus which binds specifically to a short internal peptide fragment of the cadherin 23 cytoplasmic domain (a component of the Usher protein network). Whirlin contains two copies of this domain; the first of these has been assayed for interaction with the cytoplasmic domain of cadherin 23 and no interaction could be detected.

                           10
                   ....*....|....*...
gi 2032630020   12 RIFIPKKHRARFDEVVSQ 29
Cdd:cd07354     63 RYFIPNKHRARFDKLVSQ 80

Formin Homology 2 Domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2032630020  637 HRRSETSHMSVKRLRWEQVENSE--GTIWGQLGEDSDYDKLsDMvkyLDLELHFGTQKPAKPVPGPE----PFRKKEVVE 710
Cdd:pfam02181    1 PKKTPKPKKKLKPLHWDKVRPSQdrGTVWDKLDDESFELDG-DL---SELEELFSAKAKTKKNKKSEdkssSKKKPKEVS 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2032630020  711 ILSHKKAYNTSILLAHLKLSPAELRQVLMSMEPRRLEPAHLAQLLLFAPDADEEQRYQAFREAPGRLSEPDQFVLQMLSV 790
Cdd:pfam02181   77 LLDPKRAQNIAILLRKLKLPPEEIIQAILEGDEDALDLELLENLLKMAPTKEELKKLKEYKGDPSELGRAEQFLLELSKI 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2032630020  791 PEYKTRLRSLHFQATLQEKTEEIRGSLECLRQASLELKNSRKLAKILEFVLAMGNYLNDGQPKTNkTTGFKINFLTELNS 870
Cdd:pfam02181  157 PRLEARLRALLFKSTFEEEIEELKPSLEALEAASEELRNSRKFKKLLELILALGNYMNDGTRRGQ-AKGFKLSSLLKLSD 235

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2032630020  871 TKTVDGKSTFLHILAKSLSQHFPELLGFAQDLPTVPLAAKVNQRALTSDLADLHGTISEIQDACQSISPSSE--DKFAMV 948
Cdd:pfam02181  236 TKSTDNKTTLLHYLVKIIREKFPEVLDFSSELSHVKKAAKVNLEQLEKDVKQLERGLKKLERELELSALDEHpdDKFREV 315

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2032630020  949 MSSFLETAQPALRALDGLQREAMEELGKALAFFGEDSKATTSEAFFGIFAEFMSKFE 1005
Cdd:pfam02181  316 LKEFLKSAEEKLDKLESLLREALELFKELVEYFGEDPKETSPEEFFKILRDFLKEFK 372

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. 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 delphilin-like family PDZ2 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 2032630020   96 TVRVYKGNKSFGFTLRGHGPVWIESVLPGSPADNAALKSGDRILFLNGLDMRNCSHDKVVSMLQGSGAMPTLVVE 170
Cdd:cd06744      1 TVRVYRGNGSFGFTLRGHAPVYIESVDPGSAAERAGLKPGDRILFLNGLDVRNCSHDKVVSLLQGSGSMPTLVVE 75

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 2032630020    94 RRTVRVYKGNKSFGFTLRG----HGPVWIESVLPGSPADNAALKSGDRILFLNGLDMRNCSHDKVVSMLQGSGAMPTLVV 169
Cdd:smart00228    2 PRLVELEKGGGGLGFSLVGgkdeGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLTV 81

                    .
gi 2032630020   170 E 170
Cdd:smart00228   82 L 82

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 2032630020  114 GPVWIESVLPGSPADNAALKSGDRILFLNGLDMRNCSHDKVVSMLQG 160
Cdd:COG0793     71 GKVVVVSVIPGSPAEKAGIKPGDIILAIDGKSVAGLTLDDAVKLLRG 117

first harmonin_N_like domain (repeat 1) of L-delphilin, and related domains; This subgroup contains the first of two harmonin_N_like domains of an alternatively spliced longer variant of mouse delphilin (L-delphilin, isoform 1), and related domains. Delphilin is a scaffold protein which binds the glutamate receptor delta-2 (GRID2) subunit and the monocarboxylate transporter 2 at the cerebellar parallel fiber-Purkinje cell synapses. The N-terminus of L-delphilin contains this harmonin_N_like domain preceded by a postsynaptic density-95/discs-large/ZO-1 (PDZ) protein-binding domain, PDZ1. L-delphilin, in common with the shorter C-terminal isoforms (S-delphilin/delphilin alpha and delphilin beta) has a second harmonin_N_like domain (not belonging to this subgroup) and a second PDZ domain, PDZ2. This first harmonin_N_like domain is a putative protein-binding module based on its sequence similarity to the N-terminal domain of harmonin.

                           10
                   ....*....|....*...
gi 2032630020   12 RIFIPKKHRARFDEVVSQ 29
Cdd:cd07354     63 RYFIPNKHRARFDKLVSQ 80

two-component system QseEF-associated lipoprotein QseG;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2032630020  717 AYNTSILLAHLKLSPAELRQVLMSMEPRRLE-PAHL------------AQLLLfapdADEEQRYQAFREAPGrlSEPDqf 783
Cdd:PRK10722   108 AFKQGILLADAKITPAERRQIVERLNAYSLQiPAQVrplyqlwrdgqaLQLAL----AEERQRYQKLQQSSD--SELD-- 179

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2032630020  784 vlqmlsvpeyktRLRSLhfQATLQEKTEEIRGSLECL----RQASlelknSRKlakilefvlAMGNYLNDGQPKTNKT 857
Cdd:PRK10722   180 ------------ALRQQ--QQRLQYQLELTTRKLENLtdieRQLS-----SRK---------QAGNFSPDTPEKPATS 229

Formin Homology 2 Domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2032630020  637 HRRSETSHMSVKRLRWEQVENSE--GTIWGQLGEDSDYDKLsDMvkyLDLELHFGTQKPAKPVPGPE----PFRKKEVVE 710
Cdd:pfam02181    1 PKKTPKPKKKLKPLHWDKVRPSQdrGTVWDKLDDESFELDG-DL---SELEELFSAKAKTKKNKKSEdkssSKKKPKEVS 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2032630020  711 ILSHKKAYNTSILLAHLKLSPAELRQVLMSMEPRRLEPAHLAQLLLFAPDADEEQRYQAFREAPGRLSEPDQFVLQMLSV 790
Cdd:pfam02181   77 LLDPKRAQNIAILLRKLKLPPEEIIQAILEGDEDALDLELLENLLKMAPTKEELKKLKEYKGDPSELGRAEQFLLELSKI 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2032630020  791 PEYKTRLRSLHFQATLQEKTEEIRGSLECLRQASLELKNSRKLAKILEFVLAMGNYLNDGQPKTNkTTGFKINFLTELNS 870
Cdd:pfam02181  157 PRLEARLRALLFKSTFEEEIEELKPSLEALEAASEELRNSRKFKKLLELILALGNYMNDGTRRGQ-AKGFKLSSLLKLSD 235

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2032630020  871 TKTVDGKSTFLHILAKSLSQHFPELLGFAQDLPTVPLAAKVNQRALTSDLADLHGTISEIQDACQSISPSSE--DKFAMV 948
Cdd:pfam02181  236 TKSTDNKTTLLHYLVKIIREKFPEVLDFSSELSHVKKAAKVNLEQLEKDVKQLERGLKKLERELELSALDEHpdDKFREV 315

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2032630020  949 MSSFLETAQPALRALDGLQREAMEELGKALAFFGEDSKATTSEAFFGIFAEFMSKFE 1005
Cdd:pfam02181  316 LKEFLKSAEEKLDKLESLLREALELFKELVEYFGEDPKETSPEEFFKILRDFLKEFK 372

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. 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 delphilin-like family PDZ2 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 2032630020   96 TVRVYKGNKSFGFTLRGHGPVWIESVLPGSPADNAALKSGDRILFLNGLDMRNCSHDKVVSMLQGSGAMPTLVVE 170
Cdd:cd06744      1 TVRVYRGNGSFGFTLRGHAPVYIESVDPGSAAERAGLKPGDRILFLNGLDVRNCSHDKVVSLLQGSGSMPTLVVE 75

N-terminal protein-binding module of harmonin and similar domains, also known as HHD (harmonin homology domain); This domain is found in harmonin, and similar proteins such as delphilin, and whirlin. These are postsynaptic density-95/discs-large/ZO-1 (PDZ) domain-containing scaffold proteins. Harmonin and whirlin are organizers of the Usher protein network of the inner ear and the retina, delphilin is found at the cerebellar parallel fiber-Purkinje cell synapses. This domain is also found in CCM2 (also called malcavernin; C7orf22/chromosome 7 open reading frame 22; OSM). CCM2 along with CCM1 and CCM3 constitutes a set of proteins which when mutated are responsible for cerebral cavernous malformations, an autosomal dominant neurovascular disease characterized by cerebral hemorrhages and vascular malformations in the central nervous system. CCM2 plays many functional roles. CCM2 functions as a scaffold involved in small GTPase Rac-dependent p38 mitogen-activated protein kinase (MAPK) activation when the cell is under hyperosmotic stress. It associates with CCM1 in the signaling cascades that regulate vascular integrity and participates in HEG1 (the transmembrane receptor heart of glass 1) mediated endothelial cell junctions. CCM proteins also inhibit the activation of small GTPase RhoA and its downstream effector Rho kinase (ROCK) to limit vascular permeability. CCM2 mediates TrkA-dependent cell death via its N-terminal PTB domain in pediatric neuroblastic tumours; the C-terminal domain of malcavernin represented here has also been refered to as the Karet domain. Harmonin contains a single copy of this domain at its N-terminus which binds specifically to a short internal peptide fragment of the cadherin 23 cytoplasmic domain (a component of the Usher protein network). Whirlin contains two copies of this domain; the first of these has been assayed for interaction with the cytoplasmic domain of cadherin 23 and no interaction could be detected.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2032630020  206 IRVQGRTFSQQLEHLLTPPERYGVCRALESFFQHRNIDTLIVDVYPVLDTPAKQVLWQFIYQLLTYEEQELCQEKIAC 283
Cdd:cd07347      1 RRELARLFSEQADQLLTDQERAYVTQALSEYRKGRSVEALVADLFPVLDTPAKLSLLQGLRSLIPPKDQQRFDELVAQ 78

PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of rhophilin-1, rhophilin-2, and related domains. Rhophilin-1 (RHPN1, also known as GTP-Rho-binding protein 1) and rhophilin-2 (RHPN2, also known as GTP-Rho-binding protein 2) are Rho-GTP binding proteins involved in cytoskeletal dynamics. Rhophilin-2 inhibits RhoA's activity to induce F-actin stress fibers. 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 rhophilin-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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2032630020   95 RTVRVYKGNKSFGFTLRGHGPVWIESVLPGSPADNAALKSGDRILFLNGLDMRNCSHDKVVSMLQGSG 162
Cdd:cd06712      2 RTVHLTKEEGGFGFTLRGDSPVQVASVDPGSCAAEAGLKEGDYIVSVGGVDCKWSKHSEVVKLLKSAG 69

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 2032630020    94 RRTVRVYKGNKSFGFTLRG----HGPVWIESVLPGSPADNAALKSGDRILFLNGLDMRNCSHDKVVSMLQGSGAMPTLVV 169
Cdd:smart00228    2 PRLVELEKGGGGLGFSLVGgkdeGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLTV 81

                    .
gi 2032630020   170 E 170
Cdd:smart00228   82 L 82

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. 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 NHERF-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 2032630020   95 RTVRVYKGNKSFGFTLR------GHgpvWIESVLPGSPADNAALKSGDRILFLNGLDMRNCSHDKVVSMLQGSGAMPTLV 168
Cdd:cd06768      1 RLCHLVKGPEGYGFNLHaekgrpGH---FIREVDPGSPAERAGLKDGDRLVEVNGENVEGESHEQVVEKIKASGNQVTLL 77

                   .
gi 2032630020  169 V 169
Cdd:cd06768     78 V 78

PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGEF11, ARHGEF12, and related domains. This subfamily includes the GEFs (guanine exchange factors) ARHGEF11 (Rho guanine nucleotide exchange factor 11, known as PDZ-RhoGEF) and ARHGEF12 (Rho guanine nucleotide exchange factor 12, also known as leukemia-associated RhoGEF). GEFs activate Rho GTPases by promoting GTP binding. ARHGEF11/12 are regulators of G protein signaling (RGS) domain-containing GEFs; the RGS domain mediates their binding to and activation of Galpha (and Gq also in the case of ARHGEF12), in response to G-protein coupled receptor activation. ARHGEF11 and 12 are involved in serum-signaling, and regulate Yes-Associated Protein (YAP1)-dependent transcription. The ARHGEF12 PDZ domain binds plexin-B1 and the receptor tyrosine kinase insulin-like growth factor receptor (IGF-R1) beta-subunit. ARHGEF12 also interacts with glutamate receptor delta-1(GluD1), a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGEF11-12-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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2032630020   95 RTVRVYKGNKSFGFTLRGHGPVWIESVLPGSPADNAALKSGDRILFLNGLDMRNCSHDKVVSMLQGS 161
Cdd:cd23069      2 RCVVIQRDENGYGLTVSGDNPVFVQSVKEGGAAYRAGVQEGDRIIKVNGTLVTHSNHLEVVKLIKSG 68

PDZ domain 7 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 6 of PATJ (protein-associated tight junction) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 7 of MUPP1 and PDZ domain 6 of PATJ, and related domains. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, 9, and 13; consequently, MUPP1 PDZ7 and 8 align with PATJ PDZ6 and 7; and MUPP1 PDZ domains 10-12 align with PATJ PDZ domains 8-10. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ7 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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2032630020   95 RTVRVYK-GNKSFGFTLRG-------------HGPVWIESVLPGSPAD-NAALKSGDRILFLNGLDMRNCSHDKVVSMLQ 159
Cdd:cd06671      3 RRVELWRePGKSLGISIVGgrvmgsrlsngeeIRGIFIKHVLEDSPAGrNGTLKTGDRILEVNGVDLRNATHEEAVEAIR 82

                           90
                   ....*....|.
gi 2032630020  160 GSGAMPTLVVE 170
Cdd:cd06671     83 NAGNPVVFLVQ 93

PDZ domain of sorting nexin-27 (SNX27), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SNX27, and related domains. SNX27 is involved in retrograde transport from endosome to plasma membrane. The PDZ domain of SNX27 links cargo identification to retromer-mediated transport. SNX27 binds to the retromer complex (vacuolar protein sorting 26(VPS26)-VPS29-VPS35), via its PDZ domain binding to VPS26. The SNX27 PDZ domain also binds to cargo including the G-protein-coupled receptors (GPCRs): beta2-adrenergic receptor (beta2AR), beta1AR, parathyroid hormone receptor (PTHR), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), NMDA receptors, 5-hydroxytryptamine 4a receptors, frizzled receptors, and somatostatin receptor subtype 5 (SSTR5). Additional binding partners of the SNX27 PDZ domain include G protein-gated inwardly rectifying potassium (Kir3) channels, angiotensin-converting enzyme 2 (ACE2), and PTEN (phosphatase and tensin homolog deleted on chromosome 10); PTEN binding to SNX27 prevents SNX27's association with the retromer complex. SNX27 has been reported to be a host factor needed for efficient entry of an engineered SARS-CoV-2 variant, the spike protein of which contains a deletion at the S1/S2 subunit cleavage site; the PDZ domain of SNX27 binds angiotensin-converting enzyme 2 (ACE2), and may be involved in recycling ACE2 to the plasma membrane, thereby promoting viral entry. 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 SNX27-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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2032630020   95 RTVRVYKGNKSFGFTLRGH----GPV------------WIESVLPGSPADNAALKSGDRILFLNGLDMRNCSHDKVVSML 158
Cdd:cd23070      1 RVVTIVKSETGFGFNVRGQvsegGQLrsingelyaplqHVSAVLEGGAADKAGVRKGDRILEVNGVNVEGATHKQVVDLI 80

                           90
                   ....*....|.
gi 2032630020  159 QGSGAMPTLVV 169
Cdd:cd23070     81 KSGGDELTLTV 91

PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of harmonin isoforms a, b, and c, 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 PDZ1 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.

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gi 2032630020   94 RRTVRVYK-GNKSFGFTLRG---HGP-VWIESVLPGSPADNAALKSGDRILFLNGLDMRNCSHDKVVSMLQG 160
Cdd:cd06737      2 LRLVRLDRrGPESLGFSVRGgleHGCgLFVSHVSPGSQADNKGLRVGDEIVRINGYSISQCTHEEVINLIKT 73

PDZ domain 1 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 1 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 PDZ1 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.

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gi 2032630020   96 TVRVYKGNKSFGFTLRG--HGPVW--IESVLPGSPAD-NAALKSGDRILFLNGLDMRNCSHDKVVSMLQG 160
Cdd:cd06731      3 RTSLKKSARGFGFTIIGgdEPDEFlqIKSVVPDGPAAlDGKLRTGDVLVSVNDTCVLGYTHADVVKLFQS 72

PDZ domain 3 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of Drosophila Dlg1, human Dlg1, 2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197; SAP-97), Dlg2 (also known as channel-associated protein of synapse-110; postsynaptic density protein 93, PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95; synapse-associated protein 90, SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling, regulating surface expression of NMDA receptors in dorsal horn neurons of the spinal cord; it interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. The Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development; postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. 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 Dlg-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.

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gi 2032630020   95 RTVRVYKGNKSFGFTLRG---HGPVWIESVLPGSPAD-NAALKSGDRILFLNGLDMRNCSHDKVVSMLQGSGAMPTLVVE 170
Cdd:cd06795      3 RKIVLHKGSTGLGFNIVGgedGEGIFISFILAGGPADlSGELRRGDQILSVNGVDLRNATHEQAAAALKNAGQTVTIIAQ 82

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.

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gi 2032630020  103 NKSFGFTL-----RGHGPVwIESVLPGSPADNAA-LKSGDRILFLNGLDMRNCSHDKVVSMLQGSGAMPTLVV 169
Cdd:cd06734     11 NEGFGFVIissvnKKSGSK-IGRIIPGSPADRCGqLKVGDRILAVNGISILNLSHGDIVNLIKDSGLSVTLTI 82

PDZ domain of PDZ domain-containing protein 11, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZD11, and related domains. PDZD11 (also known as ATPase-interacting PDZ protein, plasma membrane calcium ATPase-interacting single-PDZ protein, PMCA-interacting single-PDZ protein, PISP) is involved in the dynamic assembly of apical junctions (AJs). It is recruited by PLEKHA7 to AJs to promote the efficient junctional recruitment and stabilization of nectins, and the efficient early phases of assembly of AJs in epithelial cells. The PDZD11 PDZ domain binds nectin-1 and nectin-3. PDZD11 also binds to a PDZ binding motif located in the C-terminal tail of the human sodium-dependent multivitamin transporter, to the cytoplasmic tail of the Menkes copper ATPase ATP7A, and to the cytoplasmic tail of all plasma membrane Ca2+-ATPase b-splice variants. 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 PDZD11-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.

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gi 2032630020   95 RTVRVYK-GNKSFGFTLRG----HGPVWIESVLPGSPADNAALKSGDRILFLNGLDMRNCSHDKVVSMLQGS 161
Cdd:cd06752      1 RTVVLKRpPGEQLGFNIRGgkasGLGIFISKVIPDSDAHRLGLKEGDQILSVNGVDFEDIEHSEAVKVLKTA 72

PDZ domain of regulator of G-protein signaling 3 (RGS3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS3, and related domains. RGS3 down-regulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. It downregulates G-protein-mediated release of inositol phosphates and activation of MAP kinases. In Eph/ephrin signaling, RGS3 binds via its PDZ domain to the cytoplasmic C terminus of Eph receptor tyrosine kinase EphB. 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 RGS3-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.

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gi 2032630020   97 VRVYKGNKSFGFTLRGHGPVWIESVLPGSPADNAALKSGDRILFLNGLdmrNCSHDKVVSM 157
Cdd:cd06711      3 ITIQRGKDGFGFTICDDSPVRVQAVDPGGPAEQAGLQQGDTVLQINGQ---PVERSKCVEL 60

circularly permuted PDZ domain of C-terminal processing peptidase (CPP), a serine protease, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of CPP (also known as tail-specific protease, PRC protein, Protease Re, and Photosystem II D1 protein processing peptidase), and related domains. CPP belongs to the peptidase S41A family. It cleaves a C-terminal 11 residue peptide from the precursor form of penicillin-binding protein 3, and may have a role in protecting bacterium from thermal and osmotic stresses. In the plant chloroplast, the enzyme removes the C-terminal extension of the D1 polypeptide of photosystem II. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This CPP-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

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gi 2032630020  108 FTLRGHGPVWIESVLPGSPADNAALKSGDRILFLNGLDMRNCSHDKVVSMLQG 160
Cdd:cd06782      8 IGKDDDGYLVVVSPIPGGPAEKAGIKPGDVIVAVDGESVRGMSLDEVVKLLRG 60

PDZ domain of tyrosine-protein phosphatase non-receptor type 3 (PTPN3), tyrosine-protein phosphatase non-receptor type 4 (PTNP4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PTPN3, PTPN4 and related domains. PTPN3 (also known as protein-tyrosine phosphatase H1, PTP-H1) has a tumor-suppressive or a tumor-promoting role in many cancers. It serves as a specific phosphatase for the MAP kinase p38gamma; the two interact via their PDZ domains and cooperate to promote Ras-induced oncogenesis. Interaction partners of the PTPN3 PDZ domain include p38gamma and human papillomavirus E6 oncoprotein. PTPN4 (also known as protein-tyrosine phosphatase MEG1) plays a role in immunity, learning, synaptic plasticity or cell homeostasis. p38gamma is also an interaction partner of the PTPN4 PDZ domain: PTPN4 regulates neuronal cell homeostasis by protecting neurons against apoptosis; binding of the C terminus of p38gamma to the PDZ domain of PTPN4, antagonizes the catalytic autoinhibition of PTPN4, leading to cell apoptosis. Other interaction partners of the PTPN4 PDZ domain include glutamate receptor subunit GluN2A, and RABV strain G protein, among others. 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 PTPN3-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.

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gi 2032630020  106 FGFTLRG---HG-PVWIESVLPGSPADNA--ALKSGDRILFLNGLDMRNCSHDKVVSMLQGS 161
Cdd:cd06706     16 FGFNVKGgvdQKmPVIVSRVAPGTPADLCipRLNEGDQVLLINGRDISEHTHDQVVMFIKAS 77

PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. 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 PTPN13 family PDZ1 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.

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gi 2032630020  116 VWIESVLPGSPAD-NAALKSGDRILFLNGLDMRNCSHDKVVSMLQGSGAMPTLVVEE 171
Cdd:cd23072     32 IFISSITPGGPADlDGRLKPGDRLISVNDVSLEGLSHDAAVEILQNAPEDVTLVVSQ 88

PDZ domain 3 of Drosophila Scribble, human Scribble homolog, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila Scribble (also known as LAP4), human Scribble homolog (also known as hScrib, LAP4, CriB1, ScrB1 and Vartul), and related domains. They belong to the LAP family, which describes proteins that contain either one or four PDZ domains and 16 LRRs (leucine-rich repeats) and function in controlling cell shape, size and subcellular protein localization. In Drosophila, the Scribble complex, comprising Scribble, discs large, and lethal giant larvae, plays a role in apico-basal cell polarity, in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Mammalian Scribble is important in many aspects of cancer development. Scribble and its homologs can be downregulated or overexpressed in cancer; they have a role in cancer beyond their function in loss 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 Scribble-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.

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gi 2032630020  116 VWIESVLPGSPADNAALKSGDRILFLNGLDMRNCSHDKVVSMLQGSGAMPTLVV 169
Cdd:cd06702     34 IFISKVIPDGAAAKSGLRIGDRILSVNGKDLRHATHQEAVSALLSPGQEIKLLV 87

PDZ domain of densin, erbin, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of densin, erbin, and related domains. Densin (also known as leucine-rich repeat-containing protein 7, LRRC7, densin-180, protein LAP1) and erbin (also known as densin-180-like protein, Erbb2-interacting protein, protein LAP2) belong to the LAP (leucine-rich repeat and PDZ domain) family of scaffolding proteins that play roles in the maintenance of cell shape and apical-basal polarity. Densin and erbin are components of the excitatory postsynaptic compartment and are regulators of dendritic morphology and postsynaptic structure. The densin PDZ domain binds CaV1.3 alpha1 subunit, delta-catenin, and MAGUIN-1. Binding partners of the erbin PDZ domain include ErbB receptor tyrosine kinase ErbB2, HTLV-1 Tax1, Cav1.3 Ca2+channels, and constituents of the cadherin:catenin cell adhesion complex, in particular delta-catenin, p0071 and ARVCF. The erbin PDZ domain binds Smad3, a transductor of the TGFbeta pathway, possibly by a novel interface of binding. Erbin and two other LAP proteins (scribble and lano) redundantly regulate epithelial polarity and apical adhesion complex. 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 densin and erbin-like family 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.

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gi 2032630020   96 TVRVYKgNKSFGFTLRG----HG-P-------VWIESVLPGSPADNAaLKSGDRILFLNGLDMRNCSHDKVVSMLQGSGA 163
Cdd:cd06749      2 RVRIEK-NPGLGFSISGgigsQGnPfrpdddgIFVTKVQPDGPASKL-LQPGDKILEVNGYDFVNIEHGQAVSLLKSFQN 79

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gi 2032630020  164 MPTLVVE 170
Cdd:cd06749     80 TVDLVVE 86

PDZ domain 4 of human Ligand of Numb protein X 1 (LNX1) and LNX2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of LNX1 (also known as PDZ domain-containing RING finger protein 2, PDZRN2)and LNX2 (also known as PDZ domain-containing RING finger protein 1, PDZRN1), and related domains. LNX1 and LNX2 are Ring (Really Interesting New Gene) finger and PDZ domain-containing E3 ubiquitin ligases that bind to the cell fate determinant protein NUMB and mediate its ubiquitination. LNX1 can ubiquitinate a number of other ligands including PPFIA1, KLHL11, KIF7 and ERC2. LNX1 and LNX2 each have four PDZ domains. 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 LNX family PDZ4 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.

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gi 2032630020  103 NKSFGFTLRG-----HG--PVWIESVLPGSPADNAA-LKSGDRILFLNGLDMRNCSHDKVVSMLQ 159
Cdd:cd06680     10 SGSLGFSIVGgyeesHGnqPFFVKSIVPGTPAYNDGrLKCGDIILAVNGVSTVGMSHAALVPLLK 74

PDZ domain 4 of protein tyrosine phosphatase non-receptor type 13 (PTPN13), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 4 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)] and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. 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 PTPN13 family PDZ4 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.

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gi 2032630020  103 NKSFGFTLRG---HGPVWIESVLPGSPADNAALKSGDRILFLNGLDMRNCSHDKVVSMLQGSGAMPTLVV 169
Cdd:cd06696     13 KGSLGFTVTKgkdDNGCYIHDIVQDPAKSDGRLRPGDRLIMVNGVDVTNMSHTEAVSLLRAAPKEVTLVL 82