X11-like Phosphotyrosine-binding (PTB) domain; The function of the neuronal protein X11 is unknown to date. X11 has a PTB domain followed by two PDZ domains. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380 457 PEDLIDGIIFAANYLGSTQLLSDKTPSKNVRMMQAQEAVSRIKAPEGESQPMTEVDLFISTQRIKVLNADTQEPMMDHPL 536
Cdd:cd01208     1 PEDLIDGVIFGANYLGSTQLLSERNPSKNVRMAQAQEAVSRVKAPEGESQPSTEVDLFISTERIKVLNADTQETMMDHAL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380 537 RTISYIADIGNIVVLMARRRMPRSNSQENVEASHPSQDGKRQYKMICHVFESEDAQLIAQSIGQAFSVAYQEFLRANGIN 616
Cdd:cd01208    81 RTISYIADIGNIVVLMARRRMPRSSSQECVETTPPSQEGKRQYKMICHVFESEDAQLIAQSIGQAFSVAYQEFLRANGIN 160

                  .
gi 1720395380 617 P 617
Cdd:cd01208   161 P 161

PDZ domain 2 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, APBA3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of APBA1, APBA2, APBA3, and related domains. The APBA/X11/Mint protein family includes three members: neuron specific APBA1 (also known as X11alpha and Mint1) and APBA2 (also known as X11beta and Mint2), and the ubiquitously expressed APBA3 (also known as X12gamma and Mint3). They are involved in regulating neuronal signaling, trafficking, and plasticity. They contain two PDZ domains (PDZ1 and PDZ2) which bind a variety of proteins: Arf GTPases (APBA1 and APBA2 PDZ2) and neurexin (APBA1 and APBA2 PDZ1 and 2) which are involved in vesicle docking and exocytosis; alpha1B subunit of N-type Ca2+ channel (APBA1 PDZ1) that is involved in ion channels; KIF17 (APBA1 PDZ1) that is involved in transport and traffic; and Alzheimer's disease related proteins, APP (APBA3 PDZ2), CCS (APBA1 PDZ2), NF-kappa-B/p65 (APBA2 PDZ2), presenilin-1 (APBA1 and APBA2 PDZ1 and PDZ2). 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 APBA1,3-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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720395380 738 PVTTVLIRRPDLRYQLGFSVQNGIICSLMRGGIAERGGVRVGHRIIEINGQSVVATPHEKIVHILSNAVGEIHMKTMP 815
Cdd:cd06793     1 PVTTVLIRRPDLKYQLGFSVQNGIICSLLRGGIAERGGVRVGHRIIEINGQSVVATPHEKIVQLLSNSVGEIHMKTMP 78

X11-like Phosphotyrosine-binding (PTB) domain; The function of the neuronal protein X11 is unknown to date. X11 has a PTB domain followed by two PDZ domains. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380 457 PEDLIDGIIFAANYLGSTQLLSDKTPSKNVRMMQAQEAVSRIKAPEGESQPMTEVDLFISTQRIKVLNADTQEPMMDHPL 536
Cdd:cd01208     1 PEDLIDGVIFGANYLGSTQLLSERNPSKNVRMAQAQEAVSRVKAPEGESQPSTEVDLFISTERIKVLNADTQETMMDHAL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380 537 RTISYIADIGNIVVLMARRRMPRSNSQENVEASHPSQDGKRQYKMICHVFESEDAQLIAQSIGQAFSVAYQEFLRANGIN 616
Cdd:cd01208    81 RTISYIADIGNIVVLMARRRMPRSSSQECVETTPPSQEGKRQYKMICHVFESEDAQLIAQSIGQAFSVAYQEFLRANGIN 160

                  .
gi 1720395380 617 P 617
Cdd:cd01208   161 P 161

PDZ domain 2 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, APBA3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of APBA1, APBA2, APBA3, and related domains. The APBA/X11/Mint protein family includes three members: neuron specific APBA1 (also known as X11alpha and Mint1) and APBA2 (also known as X11beta and Mint2), and the ubiquitously expressed APBA3 (also known as X12gamma and Mint3). They are involved in regulating neuronal signaling, trafficking, and plasticity. They contain two PDZ domains (PDZ1 and PDZ2) which bind a variety of proteins: Arf GTPases (APBA1 and APBA2 PDZ2) and neurexin (APBA1 and APBA2 PDZ1 and 2) which are involved in vesicle docking and exocytosis; alpha1B subunit of N-type Ca2+ channel (APBA1 PDZ1) that is involved in ion channels; KIF17 (APBA1 PDZ1) that is involved in transport and traffic; and Alzheimer's disease related proteins, APP (APBA3 PDZ2), CCS (APBA1 PDZ2), NF-kappa-B/p65 (APBA2 PDZ2), presenilin-1 (APBA1 and APBA2 PDZ1 and PDZ2). 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 APBA1,3-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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720395380 738 PVTTVLIRRPDLRYQLGFSVQNGIICSLMRGGIAERGGVRVGHRIIEINGQSVVATPHEKIVHILSNAVGEIHMKTMP 815
Cdd:cd06793     1 PVTTVLIRRPDLKYQLGFSVQNGIICSLLRGGIAERGGVRVGHRIIEINGQSVVATPHEKIVQLLSNSVGEIHMKTMP 78

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380  462 DGIIFAANYLGSTQLlsdktpSKNVRMMQAQEAVSRIKAP-EGESQPMTEVDLFISTQRIKVLNADTQEPMMDHPLRTIS 540
Cdd:smart00462   2 SGVSFRVKYLGSVEV------PEARGLQVVQEAIRKLRAAqGSEKKEPQKVILSISSRGVKLIDEDTKAVLHEHPLRRIS 75

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720395380  541 YIADI---GNIVVLMARrrmprsnsqenveasHPSQDgkrqyKMICHVFESED-AQLIAQSIGQAFSVAYQEFLRANGI 615
Cdd:smart00462  76 FCAVGpddLDVFGYIAR---------------DPGSS-----RFACHVFRCEKaAEDIALAIGQAFQLAYELKLKARSE 134

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380 650 DVFIEKQKGEILGVVIVESGWGSIlPTVIIANMMHGGPAEKSGkLNIGDQIMSINGTSLVGLPLSTCQSIIKGLKnqSRV 729
Cdd:pfam00595   1 QVTLEKDGRGGLGFSLKGGSDQGD-PGIFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENMTHEEAVLALKGSG--GKV 76

                  ....
gi 1720395380 730 KLNI 733
Cdd:pfam00595  77 TLTI 80

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 1720395380  741 TVLIRRPDLryQLGFSVQNG-------IICSLMRGGIAERGGVRVGHRIIEINGQSVVATPHEKIVHILSNAVGEIHMKT 813
Cdd:smart00228   4 LVELEKGGG--GLGFSLVGGkdegggvVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLTV 81

                   ..
gi 1720395380  814 MP 815
Cdd:smart00228  82 LR 83

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380 622 QKEYSDLLNTQDMYNDDL---------IH---FSKSEncKDVFIEKQKGEI--LGVVI-VESGwgsilpTVIIANMMHGG 686
Cdd:COG0793    11 RDNYVDEYDDRDLAEGALngmlgelgdPHsyyLDPEE--YEDFQESTSGEFggLGAELgEEDG------KVVVVSVIPGS 82

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720395380 687 PAEKSGkLNIGDQIMSINGTSLVGLPLSTCQSIIKGLKNqSRVKLNIVRCP---PVTTVLIRR 746
Cdd:COG0793    83 PAEKAG-IKPGDIILAIDGKSVAGLTLDDAVKLLRGKAG-TKVTLTIKRPGegePITVTLTRA 143

X11-like Phosphotyrosine-binding (PTB) domain; The function of the neuronal protein X11 is unknown to date. X11 has a PTB domain followed by two PDZ domains. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380 457 PEDLIDGIIFAANYLGSTQLLSDKTPSKNVRMMQAQEAVSRIKAPEGESQPMTEVDLFISTQRIKVLNADTQEPMMDHPL 536
Cdd:cd01208     1 PEDLIDGVIFGANYLGSTQLLSERNPSKNVRMAQAQEAVSRVKAPEGESQPSTEVDLFISTERIKVLNADTQETMMDHAL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380 537 RTISYIADIGNIVVLMARRRMPRSNSQENVEASHPSQDGKRQYKMICHVFESEDAQLIAQSIGQAFSVAYQEFLRANGIN 616
Cdd:cd01208    81 RTISYIADIGNIVVLMARRRMPRSSSQECVETTPPSQEGKRQYKMICHVFESEDAQLIAQSIGQAFSVAYQEFLRANGIN 160

                  .
gi 1720395380 617 P 617
Cdd:cd01208   161 P 161

PDZ domain 2 of amyloid-beta A4 precursor protein-binding family A member 1 (APBA1), APBA2, APBA3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of APBA1, APBA2, APBA3, and related domains. The APBA/X11/Mint protein family includes three members: neuron specific APBA1 (also known as X11alpha and Mint1) and APBA2 (also known as X11beta and Mint2), and the ubiquitously expressed APBA3 (also known as X12gamma and Mint3). They are involved in regulating neuronal signaling, trafficking, and plasticity. They contain two PDZ domains (PDZ1 and PDZ2) which bind a variety of proteins: Arf GTPases (APBA1 and APBA2 PDZ2) and neurexin (APBA1 and APBA2 PDZ1 and 2) which are involved in vesicle docking and exocytosis; alpha1B subunit of N-type Ca2+ channel (APBA1 PDZ1) that is involved in ion channels; KIF17 (APBA1 PDZ1) that is involved in transport and traffic; and Alzheimer's disease related proteins, APP (APBA3 PDZ2), CCS (APBA1 PDZ2), NF-kappa-B/p65 (APBA2 PDZ2), presenilin-1 (APBA1 and APBA2 PDZ1 and PDZ2). 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 APBA1,3-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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720395380 738 PVTTVLIRRPDLRYQLGFSVQNGIICSLMRGGIAERGGVRVGHRIIEINGQSVVATPHEKIVHILSNAVGEIHMKTMP 815
Cdd:cd06793     1 PVTTVLIRRPDLKYQLGFSVQNGIICSLLRGGIAERGGVRVGHRIIEINGQSVVATPHEKIVQLLSNSVGEIHMKTMP 78

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380  462 DGIIFAANYLGSTQLlsdktpSKNVRMMQAQEAVSRIKAP-EGESQPMTEVDLFISTQRIKVLNADTQEPMMDHPLRTIS 540
Cdd:smart00462   2 SGVSFRVKYLGSVEV------PEARGLQVVQEAIRKLRAAqGSEKKEPQKVILSISSRGVKLIDEDTKAVLHEHPLRRIS 75

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720395380  541 YIADI---GNIVVLMARrrmprsnsqenveasHPSQDgkrqyKMICHVFESED-AQLIAQSIGQAFSVAYQEFLRANGI 615
Cdd:smart00462  76 FCAVGpddLDVFGYIAR---------------DPGSS-----RFACHVFRCEKaAEDIALAIGQAFQLAYELKLKARSE 134

Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to bind peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380 464 IIFAANYLGSTQLLSDKTPsknvrMMQAQEAVSRIKAPEGESQPMTEVDLFISTQRIKVLNADTQEPMMDHPLRTISYIA 543
Cdd:cd00934     1 ASFQVKYLGSVEVGSSRGV-----DVVEEALKALAAALKSSKRKPGPVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCG 75

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720395380 544 DIG---NIVVLMARRrmprsnsqenveashpsqdgKRQYKMICHVFESED---AQLIAQSIGQAF 602
Cdd:cd00934    76 RDPdnpNVFAFIAGE--------------------EGGSGFRCHVFQCEDeeeAEEILQAIGQAF 120

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380 650 DVFIEKQKGEILGVVIVESGWGSIlPTVIIANMMHGGPAEKSGkLNIGDQIMSINGTSLVGLPLSTCQSIIKGLKnqSRV 729
Cdd:pfam00595   1 QVTLEKDGRGGLGFSLKGGSDQGD-PGIFVSEVLPGGAAEAGG-LKVGDRILSINGQDVENMTHEEAVLALKGSG--GKV 76

                  ....
gi 1720395380 730 KLNI 733
Cdd:pfam00595  77 TLTI 80

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380 743 LIRRPDLRYQLGFSVQNG--------IICSLMRGGIAERGGVRVGHRIIEINGQSVVATPHEKIVHILSNAVGEIHMKTM 814
Cdd:pfam00595   2 VTLEKDGRGGLGFSLKGGsdqgdpgiFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLTIL 81

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 1720395380  741 TVLIRRPDLryQLGFSVQNG-------IICSLMRGGIAERGGVRVGHRIIEINGQSVVATPHEKIVHILSNAVGEIHMKT 813
Cdd:smart00228   4 LVELEKGGG--GLGFSLVGGkdegggvVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLTV 81

                   ..
gi 1720395380  814 MP 815
Cdd:smart00228  82 LR 83

Cell death protein 6 homolog (CED-6/GULP1) Phosphotyrosine-binding (PTB) domain; CED6 (also known as GULP1: engulfment adaptor PTB domain containing 1) is an adaptor protein involved in the specific recognition and engulfment of apoptotic cells. CED6 has been shown to interact with the cytoplasmic tail of another protein involved in the engulfment of apoptotic cells, CED1. CED6 has a C-terminal PTB domain, which can bind to NPXY motifs. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380 457 PEDLIDG-IIFAANYLGSTQLlsDKtpSKNVRMmqAQEAVSRIK----APEGESQPMTEVDLFISTQRIKVLNADTQEPM 531
Cdd:cd01273     4 PEALIKGhVAYLVKFLGCTEV--EQ--PKGTEV--VKEAIRKLKfarqLKKSEGAKLPKVELQISIDGVKIQDPKTKVIM 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380 532 MDHPLRTISYIAD---IGNIVVLMARRrmPRSNSQEnveashpsqdgkrqykmiCHVFESED-AQLIAQSIGQAFSVAYQ 607
Cdd:cd01273    78 HQFPLHRISFCADdktDKRIFSFIAKD--SESEKHL------------------CFVFDSEKlAEEITLTIGQAFDLAYR 137

                  ....*..
gi 1720395380 608 EFLRANG 614
Cdd:cd01273   138 RFLESNG 144

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720395380 666 VESGWGS-ILPTVIIANMMHGGPAEKSGKLNIGDQIMSINGTSLVGLPLSTCQSIIKGLKNQSRVKLNIV--RCPPV 739
Cdd:cd06739    18 LEGGIDSpLGGKIVVSAVYEGGAADKHGGIVKGDQIMMVNGKSLTDVTLAEAEAALQRAMNSGGDWIDLViaVAPPK 94

PDZ domain 12 of multi-PDZ-domain protein 1 (MUPP1), PDZ domain 10 of protein-associated tight junction (PATJ, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 12 of MUPP1, PDZ domain 10 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 PDZ12 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 1720395380 651 VFIEKQKGEILGVVIVeSGWGSIL---PtVIIANMMHGGPAEKSGKLNIGDQIMSINGTSLVGLplsTCQSIIKGLKNQS 727
Cdd:cd06675     3 VEIKRGPQDSLGISIA-GGVGSPLgdvP-VFIAMIQPNGVAAQTGKLKVGDRIVSINGQSTDGL---THSEAVNLLKNAS 77

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
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gi 1720395380 761 IICSLMRGGIAERGGVRVGHRIIEINGQSVVATPHEKIV 799
Cdd:cd06768    26 FIREVDPGSPAERAGLKDGDRLVEVNGENVEGESHEQVV 64

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380 650 DVFIEKQKGEILGVVIVESGWGSILPTviIANMMHGGPAEKSGKLNIGDQIMSINGTSLVGLPLSTCQSIIK--GLknqs 727
Cdd:cd06734     3 DVTLTRRENEGFGFVIISSVNKKSGSK--IGRIIPGSPADRCGQLKVGDRILAVNGISILNLSHGDIVNLIKdsGL---- 76

                  ....*..
gi 1720395380 728 RVKLNIV 734
Cdd:cd06734    77 SVTLTIV 83

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.

                          10        20        30        40        50
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gi 1720395380 762 ICSLMRGGIAERGGVRVGHRIIEINGQSVVATPHEKIVHILSNAVGEIHMKTMP 815
Cdd:cd23070    40 VSAVLEGGAADKAGVRKGDRILEVNGVNVEGATHKQVVDLIKSGGDELTLTVIS 93

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

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gi 1720395380 655 KQKGEILGVvivesgwgSILPT----VIIANMMHGGPAEKSGKLNIGDQIMSINGTSLVGLPLSTCQSIIKGLKNqsRVK 730
Cdd:cd23066     6 KKAGKELGL--------SLSPNegigCTIADLLPGGYAEIDGKLQKGDIITKFNGDALSGLPFQVCYALFKGANG--KIS 75

                  ....*
gi 1720395380 731 LNIVR 735
Cdd:cd23066    76 LEVTR 80

PDZ domain 3 of the full-length isoform of whirlin, PDZ domain 1 of the short isoform of whirlin, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 3 of the full-length isoform of whirlin, PDZ domain 1 of the short isoform of whirlin, and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 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 whirlin 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 1720395380 648 CKDVFIEKQKGeILGVVIvESGWGS--ILPTVIiaNMMHGGPAEKSGKLNIGDQIMSINGTSLVGLPLSTC-QSIIKGLK 724
Cdd:cd06742     1 TLLVRIKKTKP-TLGIAI-EGGANTkqPLPRVI--NIQRGGSAHNCGGLKVGHVILEVNGTSLRGLEHREAaRLIAEAFK 76

                  ....
gi 1720395380 725 NQSR 728
Cdd:cd06742    77 NKSR 80

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720395380 622 QKEYSDLLNTQDMYNDDL---------IH---FSKSEncKDVFIEKQKGEI--LGVVI-VESGwgsilpTVIIANMMHGG 686
Cdd:COG0793    11 RDNYVDEYDDRDLAEGALngmlgelgdPHsyyLDPEE--YEDFQESTSGEFggLGAELgEEDG------KVVVVSVIPGS 82

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720395380 687 PAEKSGkLNIGDQIMSINGTSLVGLPLSTCQSIIKGLKNqSRVKLNIVRCP---PVTTVLIRR 746
Cdd:COG0793    83 PAEKAG-IKPGDIILAIDGKSVAGLTLDDAVKLLRGKAG-TKVTLTIKRPGegePITVTLTRA 143

PDZ domain of membrane palmitoylated proteins (MPPs), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MPP1-7 (also known as MAGUK p55 subfamily members 1-7), and related domains. MPPs comprise a subfamily of a larger group of multidomain proteins, namely, membrane-associated guanylate kinases (MAGUKs). MPPs form diverse protein complexes at the cell membranes, which are involved in a wide range of cellular processes, including establishing proper cell structure, polarity and cell adhesion. MPPs have only one PDZ domain. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MPP1-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1720395380 761 IICSLMRGGIAERGG-VRVGHRIIEINGQSVVATPHEKIVHILSNAVGEIHMKTMP 815
Cdd:cd06726    25 IVARILHGGMAHRSGlLHVGDEILEINGIPVSGKTVDELQKLLSSLSGSVTFKLIP 80

PDZ domain of Ras-associating and dilute domain-containing protein (Radil) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Radil (also known as protein KIAA1849) and related domains. Radil is required for cell adhesion and migration of neural crest precursors during development. Radil is a component of a Rasip1-Radil-ARHGAP29 complex at endothelial cell-cell junctions. Rap1, via its effectors Radil and Rasip1 and their binding partner ArhGAP29, controls the endothelial barrier by decreasing Rho-mediated radial tension on cell-cell junctions. ArhGAP29 binds the Radil PDZ domain. The Radil PDZ domain also binds kinesin family protein 14 (KIF14); KIF14 negatively regulates Rap1-mediated inside-out integrin activation by tethering Radil on microtubules. 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 Radil-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
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gi 1720395380 649 KDVF-IEKQKGEI-LGVVIVESGWGSIL-PTVIIANMMHGGPAEKSGKLNIGDQIMSINGTSLVGLPLSTCQSIIKG 722
Cdd:cd06690     1 EDVFvVELERGPKgLGLGLIDGLHTPLRsPGIYIRTLVPDSPAARDGRLRLGDRILAVNGTSLVGADYQSAMDLIRT 77

PDZ domain of protein Lin-7 and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Lin-7 (also known as LIN-7 or LIN7), and related domains. Lin-7 targets and organize protein complexes to epithelial and synaptic plasma membranes. There are three mammalian Lin-7 homologs: Lin-7A (protein lin-7 homolog A, also known as mammalian lin-seven protein 1 (MALS-1), vertebrate lin-7 homolog 1 (Veli-1), tax interaction protein 33); Lin-7B (also known as MALS-2, Veli-2); and Lin-7C (also known as MALS-3, Veli-3). Lin-7 is involved in localization of the Let-23 growth factor receptor to the basolateral membrane of epithelial cells, in tight junction localization of insulin receptor substrate p53 (IRSp53), in retaining gamma-aminobutyric (GABA) transporter (BGT-1) at the basolateral surface of epithelial cells, and in regulating recruitment of neurotransmitter receptors to the postsynaptic density (PSD). The Lin7 PDZ domain binds Let-23, BGT and beta-catenin, and NMDA (N-methyl-D-aspartate) receptor NR2B. Lin-7 also binds to the PDZ binding motif located in the C-terminal tail of Rhotekin, an effector protein for small GTPase Rho. 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 Lin-7-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 1720395380 753 LGFSVQNG-------IICSLMRGGIAER-GGVRVGHRIIEINGQSVVATPHEKIVHILSNAVGEI 809
Cdd:cd06796    14 LGFNVMGGkeqnspiYISRIIPGGVADRhGGLKRGDQLLSVNGVSVEGEHHEKAVELLKAAQGSV 78

PDZ1 domain of human syntaxin-binding protein 4 (STXBP4), PDZ2 domain of Gallus gallus uncharacterized STXBP4 isoform X1, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of human syntaxin-binding protein 4 (STXBP4), PDZ2 domain of Gallus gallus uncharacterized STXBP4 isoform X1, and related domains. Human STXBP4 (also known as Synip) includes a single PDZ domain, a coiled-coil domain, and a WW domain (named for its two conserved tryptophans); Gallus gallus STXBP4 isoform X1 contains 2 PDZ domains (PDZ1 and PDZ2). Human STXBP4 plays a role in the translocation of transport vesicles from the cytoplasm to the plasma membrane: insulin induces the dissociation of the STXBP4 and STX4 complex liberating STX4 to interact with Vamp2, and to form the SNARE complex thereby promoting vesicle fusion. It may also play a role in the regulation of insulin release by pancreatic beta cells after stimulation by glucose. Human STXBP4 is also known to physically associate with a prominent isoform of TP63 (deltaNp63alpha 9) whose overexpression promotes squamous cell carcinoma development, and in doing so prevents degradation of this isoform by the Cdc20-APC/C complex, Itch, and RACK1. 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 STXBP4-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 1720395380 675 PTVIIANMMHGGPAEKSGKLNIGDQIMSINGTSLVGLPLSTCQSIIKGLK 724
Cdd:cd06698    27 PMVFIQEVIPGGDCYKDGRLRPGDQLVSINKESLIGVTLEEAKSILTRAK 76

PDZ domain of signal-induced proliferation-associated protein 1 (SIPA1), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SIPA1, and related domains. The Rap-GTPase activating protein SIPA1 (also known as GTPase-activating protein Spa-1, p130 SPA1) is a metastasis promoter; a polymorphism in a region of the Sipa1 gene encoding the PDZ domain is associated with metastasis. The SIPA1 PDZ domain binds ribosomal RNA processing 1 homolog B (Rrp1b). SIPA1 also forms a complex with water channel aquaporin-2 (AQP2) and plays a role in trafficking of AQP2, targeted positioning of which strictly regulates body water homeostasis; the SIPA1 PDZ domain binds AQP2. Rrp1b or AQP2 binding inhibits the RapGAP activity of SIPA1. 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 SIPA1-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 1720395380 752 QLGFSVQ-NGIICSLMRGGIAERGGVRVGHRIIEINGQSVVATPHEKIVHILSNAV 806
Cdd:cd06745    11 QLGFHVNyEGFVTEVERFGFAWQAGLRQGSRLVEICKVPVATLTHEQMIDLLRTSV 66

Tensin-related Phosphotyrosine-binding (PTB) domain; Tensin plays critical roles in renal function, muscle regeneration, and cell migration. It binds to actin filaments and interacts with the cytoplasmic tails of beta-integrin via its PTB domain, allowing tensin to link actin filaments to integrin receptors. Tensin functions as a platform for assembly and disassembly of signaling complexes at focal adhesions by recruiting tyrosine-phosphorylated signaling molecules, and also by providing interaction sites for other proteins. In addition to its PTB domain, it contains a C-terminal SH2 domain. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.

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gi 1720395380 511 VDLFISTQRIKVLNADTQEPMMDHPLRTISYIAdignivvlmARrrmpRSNSQENVEASHPSQDGKRQYkmiCHVF---E 587
Cdd:cd13157    43 VILSVSLSGIKICSEDGKVVLMAHALRRVSYST---------CR----PAHAQFAFVARNPGGPTNRQY---CHVFvtrS 106

                          90
                  ....*....|....*....
gi 1720395380 588 SEDAQLIAQSIGQAFSVAY 606
Cdd:cd13157   107 PREAQELNLLLCRAFQLAY 125

PDZ domain 5 of multi-PDZ-domain protein 1 (MUPP1), 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 5 of MUPP1 and 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 PDZ5 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 1720395380 647 NCKDVFIEKQKGEilgvviveSGWG-SIL---------PTVI-IANMMHGGPAEKSGKLNIGDQIMSINGTSLVGLPLST 715
Cdd:cd06669     5 SDEVTVIELEKGD--------RGLGfSILdyqdpldpsETVIvIRSLVPGGVAEQDGRLLPGDRLVFVNDVSLENASLDE 76

                          90       100
                  ....*....|....*....|...
gi 1720395380 716 CQSIIKGLKnQSRVKLNIVRCPP 738
Cdd:cd06669    77 AVQALKSAP-PGTVRIGVAKPLP 98

PDZ domain 4 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 4 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 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 1720395380 742 VLIRRPDlrYQLGFSVQNGI----------------ICSLMRGGIAERGG-VRVGHRIIEINGQSVVATPHEKIVHILSN 804
Cdd:cd06701     8 TIVKEPG--EKLGISIRGGAkghagnpldptdegifISKINPDGAAARDGrLKVGQRILEVNGQSLLGATHQEAVRILRS 85

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gi 1720395380 805 AVGEIHM 811
Cdd:cd06701    86 VGDTLTL 92

PDZ domain 1 of inactivation-no-after-potential D (INAD), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of INAD, and related domains. INAD assembles key enzymes of the Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. It contains 5 PDZ domains arranged in tandem (PDZ1-PDZ5) which independently bind various proteins. INAD PDZ2 binds eye-specific protein kinase C, INAD PDZ3 binds transient receptor potential (TRP) channel, and INAD PDZ4,5 tandem binds NORPA (phospholipase Cbeta, PLCbeta). Mutations of the inaD gene that lead to disruption of each of these interactions impair fly photo signal transduction. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This INAD-like family 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 1720395380 651 VFIEKQKGEILGVVIV----ESGWGSILPTVIIANMMHGGPAEKSGKLNIGDQIMSINGTSLVGlplSTCQSIIKGLKN- 725
Cdd:cd23063     2 VVIEKTEKKSFGICIVrgevKVSPNTKTTGIFIKGIIPDSPAHKCGRLKVGDRILSVNGNDVRN---STEQAAIDLIKEa 78

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gi 1720395380 726 QSRVKLNI 733
Cdd:cd23063    79 DFKIVLEI 86

PDZ domain 2 of tyrosine kinase PTPN13, FERM and PDZ domain-containing protein 2 (FRMPD2), and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of human PTPN13, and related domains. PTPN13, also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1), negatively regulates FAS-mediated apoptosis and NGFR-mediated pro-apoptotic signaling, and may also regulate phosphoinositide 3-kinase (PI3K) signaling. It contains 5 PDZ domains; interaction partners of its second PDZ domain (PDZ2) include the Fas receptor (TNFRSF6) and thyroid receptor-interacting protein 6 (TRIP6). The second PDZ (PDZ2) domain, but not PDZ1 or PDZ3, of FRMPD2 binds to GluN2A and GluN2B, two subunits of N-methyl-d-aspartic acid (NMDA) receptors. Other binding partners of the FRMPDZ2 PDZ2 domain include NOD2, and catenin family members, delta catenin (CTNND2), armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) and p0071 (also known as plakophilin 4; PKP4). 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-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.

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gi 1720395380 753 LGFSVQNGI----------ICSLMRGGIAERGG-VRVGHRIIEINGQSVVATPHEKIVHILSNA 805
Cdd:cd06792    14 LGISVTGGIntsvrhggiyVKSLVPGGAAEQDGrIQKGDRLLEVNGVSLEGVTHKQAVECLKNA 77

PDZ domain 7 of PDZ domain containing 2 (PDZD2), PDZ domain 4 of human pro-interleukin-16 (isoform 1, 1332 AA), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 7 of PDZD2, also known as KIAA0300, PIN-1, PAPIN, activated in prostate cancer (AIPC) and PDZ domain-containing protein 3 (PDZK3). PDZD2 has seven PDZ domains. PDZD2 is expressed at exceptionally high levels in the pancreas and certain cancer tissues, such as prostate cancer. It promotes the proliferation of insulinoma cells and is upregulated during prostate tumorigenesis. In osteosarcoma (OS), the microRNA miR-363 acts as a tumor suppressor by inhibiting PDZD2. This family include the PDZ domain of the secreted mature form of human interleukin-16 (IL-16); this is the fourth PDZ domain (PDZ4) of human pro-interleukin-16 (isoform 1, also known as nPro-Il-16). Precursor IL-16 is cleaved to produce pro-IL-16 and C-terminal mature IL-16. Pro-IL-16 functions as a regulator of T cell growth; mature IL-16 is a CD4 ligand that induces chemotaxis and CD25 expression in CD4+ T cells. IL-16 bioactivity has been closely associated with the progression of several different cancers 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 PDZD2-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 1720395380 666 VESGWGSIL---PtVIIANMMHGGPAEKSGKLNIGDQIMSINGTSLVGL 711
Cdd:cd06763    17 LEGGKGSPLgdrP-LTIKRIFKGGAAEQSGVLQVGDEILQINGTSLQGL 64

PDZ domain 1 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins, and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. 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 ZO 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 1720395380 675 PTVIIANMMHGGPAEksGKLNIGDQIMSINGTSLVGLPLSTCQSIIK 721
Cdd:cd06727    31 TSIVISDVLKGGPAE--GKLQENDRVVSVNGVSMENVEHSFAVQILR 75