FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM and PDZ domain-containing protein 4 (FRMPD4); FRMPD4, also termed PDZ domain-containing protein 10, or PSD-95-interacting regulator of spine morphogenesis (Preso), is a multiscaffolding protein that modulates both Homer1 and postsynaptic density protein 95 activity. It can associate with the tetratricopeptide repeat (TPR) motif-containing adaptor protein LGN. Moreover, FRMPD4 is asymmetrically distributed in the cytosol and nuclei of neural stem/progenitor cells in the adult brain, suggesting a significant role in cell differentiation via association with cell polarity machinery. FRMPD4 contains a WW domain, a PDZ domain, and a FERM domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain of the FERM domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569012072  198 FMPNVLKVYLENGQTKSFRFDCSTSIKDVILTLQEKLSIKGIEHFSLMLEQRIEGAGTKLLLLHEQETLTQVTQRPSSHK 277
Cdd:cd17170     1 FMPNVLKVYLENGQTKSFRFDCSTSIKDVILTLQEKLSIKCIEHFSLMLEQRTEGSGTKLLLLHEQETLTQVTQRPGSHK 80

                          90
                  ....*....|....
gi 569012072  278 MRCLFRISFVPKDP 291
Cdd:cd17170    81 MRCLFRISFVPKDP 94

PDZ domain of FERM and PDZ domain-containing protein 1 (FRMPD1), FRMPD3, FRMPD4, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of FRMPD1, FRMPD3, FRMPD4, and related domains. FRMPD1 (also known as FERM domain-containing protein 2, FRMD2), inhibits the malignant phenotype of lung cancer by activating the Hippo pathway via interaction with WWC3; the FRMPD1 PDZ domain binds WWC3. FRMPD3 is a target gene of the neuron-specific transcription factor NPAS4 that is involved in synaptic plasticity. FRMPD4 (also known as PDZ domain-containing protein 10, PDZD10, PDZK10, PSD-95-interacting regulator of spine morphogenesis, and Preso) regulates dendritic spine morphogenesis, and mGluR1/5 signaling; the FRMPD4 PDZ domain binds PAK-interacting exchange factor-beta (betaPix). 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 FRMPD1,3,4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569012072   75 KVEMRRDPVLGFGFVAGSEKPVVVRSVTPGGPSEGKLIPGDQIVMINDEAVSAAPRERVIDLVRSCKESILLTVI 149
Cdd:cd06769     1 TVEIQRDAVLGFGFVAGSERPVVVRSVTPGGPSEGKLLPGDQILKINNEPVEDLPRERVIDLIRECKDSIVLTVL 75

LGN tetratricopeptide repeat-binding domain found in FERM and PDZ domain-containing protein 4; FRMPD4, also called PDZ domain-containing protein 10 (PDZD10), PDZK10, or PSD-95-interacting regulator of spine morphogenesis (Preso), is a novel PSD-95-interacting FERM and PDZ domain protein that regulates dendritic spine morphogenesis. It acts as a positive regulator of dendritic spine morphogenesis and density. It is required for the maintenance of excitatory synaptic transmission. It binds phosphatidylinositol 4,5-bisphosphate. FRMPD4 contains WW, PDZ and FERM domains in the N-terminal region. This model corresponds to a conserved region in the C-terminal region of FRMPD4 that binds to tetratricopeptide (TPR) repeats present in the N-terminal domain of adaptor protein LGN. LGN plays a crucial role in mitotic spindle orientation and cell polarization via interaction with multiple targets including FRMPD4.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 569012072  970 PATDLPPKVVPSKQILHSDHMEMEPETMETKSVTDYFSKLHMGSVAYSC 1018
Cdd:cd21943     1 QETELQSKVVPSKQILHSDNIEMEPETMETKSLTDYFSKLHMGSLVYSC 49

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM and PDZ domain-containing protein 4 (FRMPD4); FRMPD4, also termed PDZ domain-containing protein 10, or PSD-95-interacting regulator of spine morphogenesis (Preso), is a multiscaffolding protein that modulates both Homer1 and postsynaptic density protein 95 activity. It can associate with the tetratricopeptide repeat (TPR) motif-containing adaptor protein LGN. Moreover, FRMPD4 is asymmetrically distributed in the cytosol and nuclei of neural stem/progenitor cells in the adult brain, suggesting a significant role in cell differentiation via association with cell polarity machinery. FRMPD4 contains a WW domain, a PDZ domain, and a FERM domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain of the FERM domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569012072  198 FMPNVLKVYLENGQTKSFRFDCSTSIKDVILTLQEKLSIKGIEHFSLMLEQRIEGAGTKLLLLHEQETLTQVTQRPSSHK 277
Cdd:cd17170     1 FMPNVLKVYLENGQTKSFRFDCSTSIKDVILTLQEKLSIKCIEHFSLMLEQRTEGSGTKLLLLHEQETLTQVTQRPGSHK 80

                          90
                  ....*....|....
gi 569012072  278 MRCLFRISFVPKDP 291
Cdd:cd17170    81 MRCLFRISFVPKDP 94

PDZ domain of FERM and PDZ domain-containing protein 1 (FRMPD1), FRMPD3, FRMPD4, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of FRMPD1, FRMPD3, FRMPD4, and related domains. FRMPD1 (also known as FERM domain-containing protein 2, FRMD2), inhibits the malignant phenotype of lung cancer by activating the Hippo pathway via interaction with WWC3; the FRMPD1 PDZ domain binds WWC3. FRMPD3 is a target gene of the neuron-specific transcription factor NPAS4 that is involved in synaptic plasticity. FRMPD4 (also known as PDZ domain-containing protein 10, PDZD10, PDZK10, PSD-95-interacting regulator of spine morphogenesis, and Preso) regulates dendritic spine morphogenesis, and mGluR1/5 signaling; the FRMPD4 PDZ domain binds PAK-interacting exchange factor-beta (betaPix). 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 FRMPD1,3,4-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569012072   75 KVEMRRDPVLGFGFVAGSEKPVVVRSVTPGGPSEGKLIPGDQIVMINDEAVSAAPRERVIDLVRSCKESILLTVI 149
Cdd:cd06769     1 TVEIQRDAVLGFGFVAGSERPVVVRSVTPGGPSEGKLLPGDQILKINNEPVEDLPRERVIDLIRECKDSIVLTVL 75

LGN tetratricopeptide repeat-binding domain found in FERM and PDZ domain-containing protein 4; FRMPD4, also called PDZ domain-containing protein 10 (PDZD10), PDZK10, or PSD-95-interacting regulator of spine morphogenesis (Preso), is a novel PSD-95-interacting FERM and PDZ domain protein that regulates dendritic spine morphogenesis. It acts as a positive regulator of dendritic spine morphogenesis and density. It is required for the maintenance of excitatory synaptic transmission. It binds phosphatidylinositol 4,5-bisphosphate. FRMPD4 contains WW, PDZ and FERM domains in the N-terminal region. This model corresponds to a conserved region in the C-terminal region of FRMPD4 that binds to tetratricopeptide (TPR) repeats present in the N-terminal domain of adaptor protein LGN. LGN plays a crucial role in mitotic spindle orientation and cell polarization via interaction with multiple targets including FRMPD4.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 569012072  970 PATDLPPKVVPSKQILHSDHMEMEPETMETKSVTDYFSKLHMGSVAYSC 1018
Cdd:cd21943     1 QETELQSKVVPSKQILHSDNIEMEPETMETKSLTDYFSKLHMGSLVYSC 49

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 569012072     73 PRKVEMRRDP-VLGFGFVAGSE--KPVVVRSVTPGGPSEGK-LIPGDQIVMINDEAVSAAPRERVIDLVRSCKESILLTV 148
Cdd:smart00228    2 PRLVELEKGGgGLGFSLVGGKDegGGVVVSSVVPGSPAAKAgLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLTV 81

                    ...
gi 569012072    149 IQP 151
Cdd:smart00228   82 LRG 84

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569012072    75 KVEMRRDPVLGFGF-----VAGSEKPVVVRSVTPGGPSE-GKLIPGDQIVMINDEAVSAAPRERVIDLVRSCKESILLTV 148
Cdd:pfam00595    1 QVTLEKDGRGGLGFslkggSDQGDPGIFVSEVLPGGAAEaGGLKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLTI 80

                   .
gi 569012072   149 I 149
Cdd:pfam00595   81 L 81

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569012072   36 WEMMTNRDGRDYFINHMTQAipFDDP--RFdscqiIPP--APRKVEMRRDPVLGFGFVAGSEK-PVVVRSVTPGGPSE-G 109
Cdd:COG0793    15 VDEYDDRDLAEGALNGMLGE--LGDPhsYY-----LDPeeYEDFQESTSGEFGGLGAELGEEDgKVVVVSVIPGSPAEkA 87

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569012072  110 KLIPGDQIVMINDEAVSAAPRERVIDLVRSCK-ESILLTVIQpyPSPKSAFISAAKKARLKSNPVKVRFSEEVI 182
Cdd:COG0793    88 GIKPGDIILAIDGKSVAGLTLDDAVKLLRGKAgTKVTLTIKR--PGEGEPITVTLTRAEIKLPSVEAKLLEGKI 159

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM and PDZ domain-containing protein 4 (FRMPD4); FRMPD4, also termed PDZ domain-containing protein 10, or PSD-95-interacting regulator of spine morphogenesis (Preso), is a multiscaffolding protein that modulates both Homer1 and postsynaptic density protein 95 activity. It can associate with the tetratricopeptide repeat (TPR) motif-containing adaptor protein LGN. Moreover, FRMPD4 is asymmetrically distributed in the cytosol and nuclei of neural stem/progenitor cells in the adult brain, suggesting a significant role in cell differentiation via association with cell polarity machinery. FRMPD4 contains a WW domain, a PDZ domain, and a FERM domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain of the FERM domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569012072  198 FMPNVLKVYLENGQTKSFRFDCSTSIKDVILTLQEKLSIKGIEHFSLMLEQRIEGAGTKLLLLHEQETLTQVTQRPSSHK 277
Cdd:cd17170     1 FMPNVLKVYLENGQTKSFRFDCSTSIKDVILTLQEKLSIKCIEHFSLMLEQRTEGSGTKLLLLHEQETLTQVTQRPGSHK 80

                          90
                  ....*....|....
gi 569012072  278 MRCLFRISFVPKDP 291
Cdd:cd17170    81 MRCLFRISFVPKDP 94

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM and PDZ domain-containing proteins FRMPD1, FRMPD3, FRMPD4, and similar proteins; This family includes FERM and PDZ domain-containing proteins FRMPD1, FRMPD3, and FRMPD4, which all contain a PDZ domain and a FERM domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain of the FERM domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). FRMPD1, also termed FERM domain-containing protein 2, is an activator of G-protein signaling 3 (AGS3)-binding protein that regulates the subcellular location of AGS3 and its interaction with G-proteins. FRMPD4, also termed PDZ domain-containing protein 10, or PSD-95-interacting regulator of spine morphogenesis (Preso), is a multiscaffolding protein that modulates both Homer1 and post-synaptic density protein 95 activity. Both FRMPD1 and FRMPD4 can associate with the tetratricopeptide repeat (TPR) motif-containing adaptor protein LGN. The biological role of FRMPD3 remains unclear.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569012072  199 MPNVLKVYLENGQTKSFRFDCSTSIKDVILTLQEKLSIKGIEHFSLMLEQRIEGAGTKLLLLHEQETLTQVTQRPSSHKM 278
Cdd:cd17088     1 MPNVLKVYLENGQTKSFKYDQSTTVKDVLLSLQEKLGIKSMEHFSLVLEYVKSPRTNKLSLLQPDESLAQVAARPGSHHL 80

                          90
                  ....*....|
gi 569012072  279 RCLFRISFVP 288
Cdd:cd17088    81 RCLFRISFVP 90

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569012072    202 VLKVYLENGQTKSFRFDCSTSIKDVILTLQEKLSIKGIEHFSLMLEQRIEGAgtKLLLLHEQETLTQVTQrpsSHKMRCL 281
Cdd:smart00295    1 VLKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPDEDL--RHWLDPAKTLLDQDVK---SEPLTLY 75

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569012072    282 FRISFVPKDPIDlLRRDPVAFEYLYVQSCNDVVQERFgpELKYDIALRLAALQMYIatvtTKQTQKISLKYIEKEWGLET 361
Cdd:smart00295   76 FRVKFYPPDPNQ-LKEDPTRLNLLYLQVRNDILEGRL--PCPEEEALLLAALALQA----EFGDYDEELHDLRGELSLKR 148

                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 569012072    362 FLPSAVLQSMKEKNIKKALSHLVKanqnlvpPGKKLSALQAKVHYLKFLSDLRLYGGRVF 421
Cdd:smart00295  149 FLPKQLLDSRKLKEWRERIVELHK-------ELIGLSPEEAKLKYLELARKLPTYGVELF 201

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM and PDZ domain-containing protein 1 (FRMPD1); FRMPD1, also termed FERM domain-containing protein 2, is an activator of G-protein signaling 3 (AGS3)-binding protein that regulates the subcellular location of AGS3 and its interaction with G-proteins. It also binds to the tetratricopeptide repeat (TPR) motif-containing adaptor protein LGN. FRMPD1 contains a PDZ domain and a FERM domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to the F1 sub-domain of the FERM domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569012072  199 MPNVLKVYLENGQTKSFRFDCSTSIKDVILTLQEKLSIKGIEHFSLMLEQRIEGAgtKLLLLHEQETLTQVTQRPSSHKM 278
Cdd:cd17168     1 MPNVLKVYLENGQTKAFKFESNTTVKDIILTLKEKLSIRSIEHFALVLEEQYSIS--KLYLLHEEELIEQVVEKRESHDY 78

                          90
                  ....*....|..
gi 569012072  279 RCLFRISFVPKD 290
Cdd:cd17168    79 RCLFRVCFVPKD 90

FERM central domain; This domain is the central structural domain of the FERM domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569012072   291 PIDLLRRDPVAFEYLYVQSCNDVVQERFGPELkyDIALRLAALQMYIATVTTKQTQKISlkyieKEWGLETFLPSAVLQS 370
Cdd:pfam00373    1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCSE--EEALLLAALQLQAEFGDYQPSSHTS-----EYLSLESFLPKQLLRK 73

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 569012072   371 MKEKNIKKALSHLVKANQNlvppgkkLSALQAKVHYLKFLSDLRLYGGRVF 421
Cdd:pfam00373   74 MKSKELEKRVLEAHKNLRG-------LSAEEAKLKYLQIAQSLPTYGVEFF 117

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 569012072     73 PRKVEMRRDP-VLGFGFVAGSE--KPVVVRSVTPGGPSEGK-LIPGDQIVMINDEAVSAAPRERVIDLVRSCKESILLTV 148
Cdd:smart00228    2 PRLVELEKGGgGLGFSLVGGKDegGGVVVSSVVPGSPAAKAgLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLTV 81

                    ...
gi 569012072    149 IQP 151
Cdd:smart00228   82 LRG 84

PDZ domain 9 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 9 of MUPP1. 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. PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, PDZ9, and PDZ13. This MuPP1-like PDZ9 domain is therefore absent from PATJ. 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). 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 PDZ9 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 569012072   76 VEMRRDPV-LGFGFVAGSEKP-VVVRSVTPGGPS--EGKLIPGDQIVMINDEAVSAAPRERVIDLVRSCKESILLTV 148
Cdd:cd10817     2 VELPKDQGgLGIAISEEDTENgIVIKSLTEGGPAakDGRLKVGDQILAVDDESVVGCPYEKAISLLKTAKGTVKLTV 78

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569012072   76 VEMRRDPVLGFGF-VAGSEKP------VVVRSVTPGGPSE--GKLIPGDQIVMINDEAVSAAPRERVIDLVRSCKESILL 146
Cdd:cd23072     5 VNLKKDAKYGLGFqIVGGEKSgrldlgIFISSITPGGPADldGRLKPGDRLISVNDVSLEGLSHDAAVEILQNAPEDVTL 84

                  ....*
gi 569012072  147 TVIQP 151
Cdd:cd23072    85 VVSQP 89

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569012072   73 PRKVEMRRDPVlGFGFVAGSEKPVVVRSVTPGGP-SEGKLIPGDQIVMINDEAVSAAPRERVIDLVRSC-KESILLTVI 149
Cdd:cd06712     1 PRTVHLTKEEG-GFGFTLRGDSPVQVASVDPGSCaAEAGLKEGDYIVSVGGVDCKWSKHSEVVKLLKSAgEEGLELQVV 78

PDZ domain of regulator of G-protein signaling 12 (RGS12), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS12, and related domains. RGS12 downregulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. The RGS12 PDZ domain can bind selectively to C-terminal (A/S)-T-X-(L/V) motifs as found within both the CXCR2 IL-8 receptor, and the alternative 3' exon form of RGS12. 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 RGS12-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569012072   74 RKVEMRRDPVlGFGFVAGSEKPVVVRSVTPGGPSE--GkLIPGDQIVMINDEAVSAAPRERVIDLVRSCKESILLTV 148
Cdd:cd06710     1 RTVEIARGRA-GYGFTISGQAPCVLSCVVRGSPADvaG-LKAGDQILAVNGINVSKASHEDVVKLIGKCTGVLRLVI 75

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569012072   74 RKVEMRRDPvLGFGFVAGSEKPV---VVRSVTPGGPSE-GKLIPGDQIVMINDEAVSAAPRERVIDLVRSCKESILLTVI 149
Cdd:cd06768     1 RLCHLVKGP-EGYGFNLHAEKGRpghFIREVDPGSPAErAGLKDGDRLVEVNGENVEGESHEQVVEKIKASGNQVTLLVV 79

PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13),FERM and PDZ domain-containing protein 2 (FRMPD2), 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)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), 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. FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 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 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 569012072   76 VEMRRDPVLGFGFV-AGSEKP------VVVRSVTPGGPSE--GKLIPGDQIVMINDEAVSAAPRERVIDLVRSCKESILL 146
Cdd:cd06694     5 VTLKKDPQKGLGFTiVGGENSgsldlgIFVKSIIPGGPADkdGRIKPGDRIIAINGQSLEGKTHHAAVEIIQNAPDKVEL 84

                  ....*...
gi 569012072  147 TVIQPYPS 154
Cdd:cd06694    85 IISQPKSV 92

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 569012072   73 PRKVEM-RRDPVLGFGFVAGSEK--PVVVRSVTPGGPSE--GKLIPGDQIVMINDEAVSAAPRERVIDLVRSCKESILLT 147
Cdd:cd06796     2 PRVVELpKTEEGLGFNVMGGKEQnsPIYISRIIPGGVADrhGGLKRGDQLLSVNGVSVEGEHHEKAVELLKAAQGSVKLV 81

                  .
gi 569012072  148 V 148
Cdd:cd06796    82 V 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 569012072   73 PRKVEMRRDPVLGFGFVAGSEKPVVVRS----VTPGGPSE--GKLIPGDQIVMINDEAVSAAPRERVIDLVRSCKESILL 146
Cdd:cd06734     1 PYDVTLTRRENEGFGFVIISSVNKKSGSkigrIIPGSPADrcGQLKVGDRILAVNGISILNLSHGDIVNLIKDSGLSVTL 80

                  ....
gi 569012072  147 TVIQ 150
Cdd:cd06734    81 TIVP 84

PDZ domain of syntrophins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of syntrophins (including alpha-1-syntrophin, beta-1-syntrophin, beta-2-syntrophin, gamma-1-syntrophin, and gamma-2-syntrophin), and related domains. Syntrophins play a role in recruiting various signaling molecules into signaling complexes and help provide appropriate spatiotemporal regulation of signaling pathways. They function in cytoskeletal organization and maintenance; as components of the dystrophin-glycoprotein complex (DGC), they help maintain structural integrity of skeletal muscle fibers. They link voltage-gated sodium channels to the actin cytoskeleton and the extracellular matrix, and control the localization and activity of the actin reorganizing proteins such as PI3K, PI(3,4)P2 and TAPP1. Through association with various cytoskeletal proteins within the cells, they are involved in processes such as regulation of focal adhesions, myogenesis, calcium homeostasis, and cell migration. They also have roles in synapse formation and in the organization of utrophin, acetylcholine receptor, and acetylcholinesterase at the neuromuscular synapse. 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 syntrophin-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 569012072   74 RKVEMRRDPVLGFGFV--AGSEK--PVVVRSVTPGGPSE--GKLIPGDQIVMINDEAVSAAPRERVIDLVRSCKESILLT 147
Cdd:cd06801     1 RTVRVVKQDVGGLGISikGGAEHkmPILISKIFKGQAADqtGQLFVGDAILSVNGENLEDATHDEAVQALKNAGDEVTLT 80

                  .
gi 569012072  148 V 148
Cdd:cd06801    81 V 81

FERM domain C-lobe of Focal Adhesion Kinase 1 and 2; FAK1 (also called FRNK/Focal adhesion kinase-related nonkinase; p125FAK/pp125FAK;PTK2/Protein-tyrosine kinase 2 protein tyrosine kinase 2 (PTK2) is a non-receptor tyrosine kinase that localizes to focal adhesions in adherent cells. It has been implicated in diverse cellular roles including cell locomotion, mitogen response and cell survival. The N-terminal region of FAK1 contains a FERM domain, a linker, a kinase domain, and a C-terminal FRNK (FAK-related-non-kinase) domain. Three subdomains of FERM: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3), form a cloverleaf fold, similar to those of known FERM structures despite the low sequence conservation. The C-lobe/F3 within the FERM domain is part of the PH domain family. The phosphoinositide-binding site found in ERM family proteins is not present in the FERM domain of FAK1. The adjacent Src SH3 and SH2 binding sites in the linker of FAK1 associates with the F3 and F1 lobes and are thought to be involved in regulation. The FERM domain of FAK1 can inhibit enzymatic activity and repress FAK signaling. In an inactive state of FAK1, the FERM domain is thought to interact with the catalytic domain of FAK1 to repress its activity. Upon activation this interaction is disrupted and its kinase activity restored. The FRNK domain is thought to function as a negative regulator of kinase activity. The C-lobe/F3 is the third structural domain within the FERM domain. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569012072  420 VFKATLVQAEKRSeVTLLVGPRYGISHVINTKTNLVaLLADFSHVNRIEMFTEEESLVRVELHvLDVK----PITLLMES 495
Cdd:cd13190     4 IFKCALGSGWSIP-VDLVIGPEVGISYLTDKGSAPT-HLADFEQIQSIQTSKSEDKDGKALLQ-LKIAgasePLSITCSS 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 569012072  496 SD-AMNLACLTAGYYRLLVDSRRSIFNMANK 525
Cdd:cd13190    81 LAtAESLADLIDGYCRLVNQTDSSLIIRPEK 111

PDZ domain of MYO18A protein, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MYO18 protein and related domains. MYO18 (also known as myosin XVIIIA, KIAA0216, MysPDZ), a member of the myosin superfamily, is involved in regulating cell protrusion and migration, and Golgi trafficking and morphology, and is required for myoblast adhesion and muscle integrity. The MYO18A/MRCK/LRAP35a complex regulates actomyosin retrograde flow in cell protrusion and migration; the PtdIns(4)P/GOLPH3/MYO18A/F-actin complex is a hub for signals that regulate Golgi trafficking function. The MYO18A PDZ domain binds p190Rho-guanine nucleotide exchange factor (p190RhoGEF), Golgin45, and leucine repeat adaptor protein 1 (Lurap1, also known as Lrap35a). 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 MYO18-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 569012072   75 KVEMRRDPVLGFGFV---------AGSEKPVVVRSVTPGGPSEGK------LIPGDQIVMINDEAVSAAPRERVIDLVRS 139
Cdd:cd06747     1 EITLKRQPTGDFGFSlrrgtiverGPDDGQELKRTVHFAEPGAGTknlatgLLPGDRLIEVNGVNVENASRDEIIEMIRK 80

                  ....*....
gi 569012072  140 CKESILLTV 148
Cdd:cd06747    81 SGDTVTLKV 89

LGN tetratricopeptide repeat-binding domain found in FERM and PDZ domain-containing protein 1; FERM and PDZ domain-containing protein 1 (FRMPD1), also called FERM domain-containing protein 2 (FRMD2), stabilizes membrane-bound GPSM1, and thereby promotes its interaction with GNAI1. It also acts as a regulatory binding partner of Activator of G-protein Signaling 3 (AGS3). This model corresponds to a conserved region in FRMPD1 that binds to tetratricopeptide (TPR) repeats present in the N-terminal domain of adaptor protein LGN. LGN plays a crucial role in mitotic spindle orientation and cell polarization via interaction with multiple targets including FRMPD1.

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                  ....*....|....*....|....*....|
gi 569012072  975 PPKVVPSKQiLHSDHMEMEPETMETKSVTD 1004
Cdd:cd21942     7 SQRPTKNKN-LSSELMEMEPDTMETKSVTD 35

PDZ domain 3 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 3 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 PDZ3 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 569012072   76 VEMRRDPvLGFGF--VAGSE--KPVVVRSVTPGGPSE--GKLIPGDQIVMINDEAVSAAPRERVIDLV 137
Cdd:cd06733     4 VFLRRQE-TGFGFriLGGTEegSQVSIGAIVPGGAADldGRLRTGDELLSVDGVNVVGASHHKVVDLM 70

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 569012072   76 VEMRRDPVLGFGF-VAGS---EKPVVVRSVTPGGPSeGKLIP----GDQIVMINDEAVSAAPRERVIDLVRSCKES---- 143
Cdd:cd06706     6 IRMKPDENGRFGFnVKGGvdqKMPVIVSRVAPGTPA-DLCIPrlneGDQVLLINGRDISEHTHDQVVMFIKASRERhsge 84

                  ....*
gi 569012072  144 ILLTV 148
Cdd:cd06706    85 LVLLV 89

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 569012072   84 LGFGFVAGSE-----KPVVVRSVTPGGPSE--GKLIPGDQIVMINDEAVSAAPRERVIDLVRSCKESILLTVIqPYPS 154
Cdd:cd06680    13 LGFSIVGGYEeshgnQPFFVKSIVPGTPAYndGRLKCGDIILAVNGVSTVGMSHAALVPLLKEQRGRVTLTVV-SWPG 89

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. 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 SHANK-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 569012072   71 PAPRKVEMRRDPvLGFGFVAGSEKPVV----------------VRSVTPGGPSE--GkLIPGDQIVMINDEAVSAAPRER 132
Cdd:cd06746     4 IDPRTVVLQKGD-KGFGFVLRGAKAVGpileftptpafpalqyLESVDPGGVADkaG-LKKGDFLLEINGEDVVKASHEQ 81

                          90
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gi 569012072  133 VIDLVRSCKESILLTVIQP 151
Cdd:cd06746    82 VVNLIRQSGNTLVLKVVTV 100

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 569012072   91 GSEKPVVVRSVTPGGPSE-GKLIPGDQIVMINDEAVSAAPRERVIDLVR 138
Cdd:cd06782    11 DDDGYLVVVSPIPGGPAEkAGIKPGDVIVAVDGESVRGMSLDEVVKLLR 59

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 569012072   85 GFGF--------VAGSEKPVVVRSVTPGGPSE--GKLIPGDQIVMIN---------DEAVSA---APRERV 133
Cdd:cd06669    19 GLGFsildyqdpLDPSETVIVIRSLVPGGVAEqdGRLLPGDRLVFVNdvslenaslDEAVQAlksAPPGTV 89

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 569012072   73 PRKVEMRRDP--VLGFGFVAGS-----------EKPVVVRSVTPGGPS--EGKLIPGDQIVMINDEAVSAAPRERVIDLV 137
Cdd:cd06671     2 PRRVELWREPgkSLGISIVGGRvmgsrlsngeeIRGIFIKHVLEDSPAgrNGTLKTGDRILEVNGVDLRNATHEEAVEAI 81

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gi 569012072  138 RSC 140
Cdd:cd06671    82 RNA 84

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 569012072   76 VEMRRDPVLGFGFVAG----------SEKPVVVRSVTPGGPSEGKLIPGDQIVMINDEAVSAAPRERVIDLVRSCKESIL 145
Cdd:cd06749     3 VRIEKNPGLGFSISGGigsqgnpfrpDDDGIFVTKVQPDGPASKLLQPGDKILEVNGYDFVNIEHGQAVSLLKSFQNTVD 82

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gi 569012072  146 LTV 148
Cdd:cd06749    83 LVV 85

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 569012072   84 LGFGFVAGSEKPV--VVRSVTPGGPSEGK-LIPGDQIVMINDEAVSAAPRERVIDLVRScKESILLTV 148
Cdd:cd06737    15 LGFSVRGGLEHGCglFVSHVSPGSQADNKgLRVGDEIVRINGYSISQCTHEEVINLIKT-KKTVSLKV 81