canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 525313685    3 LGVSAE--QPAGGAE-GFHLHgDVEPSSPAALAGLRPYTDYVVGSD-QILQESEDFFTLIESHEGKPLKLMVYNSKSDSC 78
Cdd:pfam04495  28 LGLSLRwcSFAKALEnVWHVL-DVHENSPAAKAGLQPYSDYIIGTPkGLLKGEDDLYTLVEDHEDRPLRLYVYNSETDTV 106

                          90       100       110
                  ....*....|....*....|....*....|..
gi 525313685   79 REVTVTPNAAWGGEGSLGCGIGYGYLHRIPTQ 110
Cdd:pfam04495 107 REVTITPNRNWGGEGALGCGLGYGLLHRIPVV 138

GRASP55/65 PDZ-like domain; GRASP55 (Golgi re-assembly stacking protein of 55 kDa) and GRASP65 (a 65 kDa) protein are highly homologous. GRASP55 is a component of the Golgi stacking machinery. GRASP65, an N-ethylmaleimide- sensitive membrane protein required for the stacking of Golgi cisternae in a cell-free system. This region appears to be related to the PDZ domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 525313685    3 LGVSAE--QPAGGAE-GFHLHgDVEPSSPAALAGLRPYTDYVVGSD-QILQESEDFFTLIESHEGKPLKLMVYNSKSDSC 78
Cdd:pfam04495  28 LGLSLRwcSFAKALEnVWHVL-DVHENSPAAKAGLQPYSDYIIGTPkGLLKGEDDLYTLVEDHEDRPLRLYVYNSETDTV 106

                          90       100       110
                  ....*....|....*....|....*....|..
gi 525313685   79 REVTVTPNAAWGGEGSLGCGIGYGYLHRIPTQ 110
Cdd:pfam04495 107 REVTITPNRNWGGEGALGCGLGYGLLHRIPVV 138

circularly permuted PDZ domains of Escherichia coli Regulator of sigma-E protease (RseP) and related domains; Permuted PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ResP (also known as Site-2 protease RseP, and YaeL), and related domains. RseP is involved in the regulation of an extracytoplasmic stress response through the cleavage of membrane-spanning anti-stress-response transcription factor (anti-sigmE) protein RseA; it cleaves the peptide bond between the critical alanine and cysteine in the transmembrane region of RseA, releasing the cytoplasmic domain of RseA with its associated sigmaE. RseP contains two tandem-arranged periplasmic PDZ domains (PDZ-N/PDZ1 and PDZ-C/PDZ2) which act to negatively regulate protease action on intact RseA; they serve as a size-exclusion filter which prevents the access of an intact RseA into the active site of RseP. PDZ domains usually bind in 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 beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This RseP family PDZ domain is a circularly permuted PDZ domain which places both beta-strands A and B at the C-terminus. Another permutation exists in the PDZ superfamily which places beta-strand A at the C-terminus.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 525313685  21 GDVEPSSPAALAGLRPyTDYVV-GSDQILQESEDFFTLIESHEGKPLKLMVynSKSDSCREVTVTP 85
Cdd:cd23081    4 GEVVANSPAAEAGLKP-GDRILkIDGQKVRTWEDIVRIVRENPGKPLTLKI--ERDGKILTVTVTP 66

GRASP55/65 PDZ-like domain; GRASP55 (Golgi re-assembly stacking protein of 55 kDa) and GRASP65 (a 65 kDa) protein are highly homologous. GRASP55 is a component of the Golgi stacking machinery. GRASP65, an N-ethylmaleimide- sensitive membrane protein required for the stacking of Golgi cisternae in a cell-free system. This region appears to be related to the PDZ domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 525313685    3 LGVSAE--QPAGGAE-GFHLHgDVEPSSPAALAGLRPYTDYVVGSD-QILQESEDFFTLIESHEGKPLKLMVYNSKSDSC 78
Cdd:pfam04495  28 LGLSLRwcSFAKALEnVWHVL-DVHENSPAAKAGLQPYSDYIIGTPkGLLKGEDDLYTLVEDHEDRPLRLYVYNSETDTV 106

                          90       100       110
                  ....*....|....*....|....*....|..
gi 525313685   79 REVTVTPNAAWGGEGSLGCGIGYGYLHRIPTQ 110
Cdd:pfam04495 107 REVTITPNRNWGGEGALGCGLGYGLLHRIPVV 138

GRASP55/65 PDZ-like domain; GRASP55 (Golgi re-assembly stacking protein of 55 kDa) and GRASP65 (a 65 kDa) protein are highly homologous. GRASP55 is a component of the Golgi stacking machinery. GRASP65, an N-ethylmaleimide- sensitive membrane protein required for the stacking of Golgi cisternae in a cell-free system. This region appears to be related to the PDZ domain.

                          10        20        30
                  ....*....|....*....|....*....|..
gi 525313685   68 LMVYNSKSDSCREVTVTPNAAWGGEGSLGCGI 99
Cdd:pfam04495   1 LTVYNAKGQKIRDVYIVPSNTWGGQGLLGLSL 32

circularly permuted PDZ domains of Escherichia coli Regulator of sigma-E protease (RseP) and related domains; Permuted PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ResP (also known as Site-2 protease RseP, and YaeL), and related domains. RseP is involved in the regulation of an extracytoplasmic stress response through the cleavage of membrane-spanning anti-stress-response transcription factor (anti-sigmE) protein RseA; it cleaves the peptide bond between the critical alanine and cysteine in the transmembrane region of RseA, releasing the cytoplasmic domain of RseA with its associated sigmaE. RseP contains two tandem-arranged periplasmic PDZ domains (PDZ-N/PDZ1 and PDZ-C/PDZ2) which act to negatively regulate protease action on intact RseA; they serve as a size-exclusion filter which prevents the access of an intact RseA into the active site of RseP. PDZ domains usually bind in 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 beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This RseP family PDZ domain is a circularly permuted PDZ domain which places both beta-strands A and B at the C-terminus. Another permutation exists in the PDZ superfamily which places beta-strand A at the C-terminus.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 525313685  21 GDVEPSSPAALAGLRPyTDYVV-GSDQILQESEDFFTLIESHEGKPLKLMVynSKSDSCREVTVTP 85
Cdd:cd23081    4 GEVVANSPAAEAGLKP-GDRILkIDGQKVRTWEDIVRIVRENPGKPLTLKI--ERDGKILTVTVTP 66

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
                 ....*....|....*....|....*....|....*..
gi 525313685  16 GFHLH----------GDVEPSSPAALAGLRPYtDYVV 42
Cdd:cd06768   13 GFNLHaekgrpghfiREVDPGSPAERAGLKDG-DRLV 48