FERM domain C-lobe of FERM and PDZ domain containing proteins 1, 3, and 4 (FRMPD1, 3, 4); The function of FRMPD1, FRMPD3, and FRMPD4 is unknown at present. These proteins contain an N-terminal PDZ (post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1) domain and a C-terminal FERM domain. PDZ (also known as DHR (Dlg homologous region) or GLGF (glycine-leucine-glycine-phenylalanine) domains) help anchor transmembrane proteins to the cytoskeleton and hold together signaling complexes. PDZ domains bind to a short region of the C-terminus of other specific proteins. The FERM domain is composed of three subdomains: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3), which form a clover leaf fold. The C-lobe/F3 within the FERM domain is part of the PH domain family. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158705786  397 GGKVFNATLMLQDRESYIALLVGAKYGISQIINSKLNIISTLAEFANISRVELTEESEKVSMVKVYLQDVKVLTLLLESS 476
Cdd:cd13183     1 GGRSFQATLMLQDRESEVTLLVGPRYGISHVINHKLNLLALLAEFSHISRIELLRESDKVSRVELHIHDVKPITLLMESP 80

                          90       100
                  ....*....|....*....|....
gi 158705786  477 SAKDLACLIAGYYRLFVDPANSVF 500
Cdd:cd13183    81 DAKDLACLIAGYYRLLVDPRRSIF 104

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 158705786   57 TVTLDKDvLLQNYGFHISETLPLTVVAVTAGGSAHGKLFPGDQILQMNNELAEDLSCERAADILRETEDALSITVV 132
Cdd:cd06769     1 TVEIQRD-AVLGFGFVAGSERPVVVRSVTPGGPSEGKLLPGDQILKINNEPVEDLPRERVIDLIRECKDSIVLTVL 75

FERM domain C-lobe of FERM and PDZ domain containing proteins 1, 3, and 4 (FRMPD1, 3, 4); The function of FRMPD1, FRMPD3, and FRMPD4 is unknown at present. These proteins contain an N-terminal PDZ (post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1) domain and a C-terminal FERM domain. PDZ (also known as DHR (Dlg homologous region) or GLGF (glycine-leucine-glycine-phenylalanine) domains) help anchor transmembrane proteins to the cytoskeleton and hold together signaling complexes. PDZ domains bind to a short region of the C-terminus of other specific proteins. The FERM domain is composed of three subdomains: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3), which form a clover leaf fold. The C-lobe/F3 within the FERM domain is part of the PH domain family. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158705786  397 GGKVFNATLMLQDRESYIALLVGAKYGISQIINSKLNIISTLAEFANISRVELTEESEKVSMVKVYLQDVKVLTLLLESS 476
Cdd:cd13183     1 GGRSFQATLMLQDRESEVTLLVGPRYGISHVINHKLNLLALLAEFSHISRIELLRESDKVSRVELHIHDVKPITLLMESP 80

                          90       100
                  ....*....|....*....|....
gi 158705786  477 SAKDLACLIAGYYRLFVDPANSVF 500
Cdd:cd13183    81 DAKDLACLIAGYYRLLVDPRRSIF 104

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 158705786   57 TVTLDKDvLLQNYGFHISETLPLTVVAVTAGGSAHGKLFPGDQILQMNNELAEDLSCERAADILRETEDALSITVV 132
Cdd:cd06769     1 TVEIQRD-AVLGFGFVAGSERPVVVRSVTPGGPSEGKLLPGDQILKINNEPVEDLPRERVIDLIRECKDSIVLTVL 75

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.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 158705786  901 ALGLLASLRETKSTNPASRIMEMEPETMETKSVIDSRV 938
Cdd:cd21942     1 SFGQLKSQRPTKNKNLSSELMEMEPDTMETKSVTDSVV 38

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 158705786     54 VRHTVTLDKDvlLQNYGFHIS----ETLPLTVVAVTAGGSAHGK-LFPGDQILQMNNELAEDLSCERAADILRETEDALS 128
Cdd:smart00228    1 EPRLVELEKG--GGGLGFSLVggkdEGGGVVVSSVVPGSPAAKAgLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVT 78

                    ....*
gi 158705786    129 ITVVR 133
Cdd:smart00228   79 LTVLR 83

N-terminal or F0 domain of Talin-head FERM; FERM_f0 forms a stable globular structure. The fold is an ubiquitin-like fold joined to the f1 domain in a novel fixed orientation by an extensive charged interface. It is required for maximal integrin-activation, by interacting with other FA components, No binding partner has yet been found for it.

                           10        20        30
                   ....*....|....*....|....*....|....
gi 158705786   183 LKVYL-ENGQTKAFKFEANTTVKDIILTVKEKLS 215
Cdd:pfam16511    3 LKISIvGSNVTKTMQFDPSTTVYDACRLIREKIP 36

FERM domain C-lobe of FERM and PDZ domain containing proteins 1, 3, and 4 (FRMPD1, 3, 4); The function of FRMPD1, FRMPD3, and FRMPD4 is unknown at present. These proteins contain an N-terminal PDZ (post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1) domain and a C-terminal FERM domain. PDZ (also known as DHR (Dlg homologous region) or GLGF (glycine-leucine-glycine-phenylalanine) domains) help anchor transmembrane proteins to the cytoskeleton and hold together signaling complexes. PDZ domains bind to a short region of the C-terminus of other specific proteins. The FERM domain is composed of three subdomains: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3), which form a clover leaf fold. The C-lobe/F3 within the FERM domain is part of the PH domain family. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158705786  397 GGKVFNATLMLQDRESYIALLVGAKYGISQIINSKLNIISTLAEFANISRVELTEESEKVSMVKVYLQDVKVLTLLLESS 476
Cdd:cd13183     1 GGRSFQATLMLQDRESEVTLLVGPRYGISHVINHKLNLLALLAEFSHISRIELLRESDKVSRVELHIHDVKPITLLMESP 80

                          90       100
                  ....*....|....*....|....
gi 158705786  477 SAKDLACLIAGYYRLFVDPANSVF 500
Cdd:cd13183    81 DAKDLACLIAGYYRLLVDPRRSIF 104

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 158705786  179 MPNVLKVYLENGQTKAFKFEANTTVKDIILTVKEKLSIRSIEYFALALEEQY--SISRLHLLHEEELVQQVVEREESQDS 256
Cdd:cd17170     2 MPNVLKVYLENGQTKSFRFDCSTSIKDVILTLQEKLSIKCIEHFSLMLEQRTegSGTKLLLLHEQETLTQVTQRPGSHKM 81

                          90
                  ....*....|...
gi 158705786  257 RCLFRVSFVPKDP 269
Cdd:cd17170    82 RCLFRISFVPKDP 94

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM and PDZ domain-containing protein 3 (FRMPD3); FRMPD3 is an uncharacterized FERM and PDZ domain-containing protein. 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 158705786  179 MPNVLKVYLENGQTKAFKFEANTTVKDIILTVKEKLSIRSIEYFALALE----EQYsiSRLHLLHEEELVQQVVEREESQ 254
Cdd:cd17169     1 IPNVLKVFLENGQIKSFTFDGRTTVKDVMLTLQDRLSLRHIEHFALVLEyggpEQN--HKFLLLQDKQPLAHVVQRTHYQ 78

                          90
                  ....*....|....*
gi 158705786  255 DSRCLFRVSFVPKDP 269
Cdd:cd17169    79 GMKCLFRICFFPKDP 93

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158705786   269 PLDLLKEDPVAFEYLYLQSCSDVLQERFAVEmkCNSALRLAALHIQERIYACAQPQKISlkyieKDWGIENFISPTLLRN 348
Cdd:pfam00373    1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCS--EEEALLLAALQLQAEFGDYQPSSHTS-----EYLSLESFLPKQLLRK 73

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 158705786   349 MKGKDIKKAISFHMKRNQNLleprqkqliSAAQLRLNYLQILGELKTYGGKVF 401
Cdd:pfam00373   74 MKSKELEKRVLEAHKNLRGL---------SAEEAKLKYLQIAQSLPTYGVEFF 117

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.

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 158705786  901 ALGLLASLRETKSTNPASRIMEMEPETMETKSVIDSRV 938
Cdd:cd21942     1 SFGQLKSQRPTKNKNLSSELMEMEPDTMETKSVTDSVV 38

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain and F1 sub-domain, found in FERM (Four.1/Ezrin/Radixin/Moesin) family proteins; FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain is present at the N-terminus of a large and diverse group of proteins that mediate linkage of the cytoskeleton to the plasma membrane. FERM-containing proteins are ubiquitous components of the cytocortex and are involved in cell transport, cell structure and signaling functions. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N), which is structurally similar to ubiquitin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158705786  182 VLKVYLENGQTKAFKFEANTTVKDIILTVKEKLSIRSIEYFALALEEQYSISRLhLLHEEELVQQVVEReesQDSRCLFR 261
Cdd:cd01765     2 SCRVRLLDGTELTLEVSKKATGQELFDKVCEKLNLLEKDYFGLFYEDNDGQKHW-LDLDKKISKQLKRS---GPYQFYFR 77

                  ...
gi 158705786  262 VSF 264
Cdd:cd01765    78 VKF 80

LGN tetratricopeptide repeat-binding domain found in FERM and PDZ domain-containing proteins FRMPD1, FRMPD4, and similar proteins; The family includes FRMPD1, FRMPD4, and similar proteins. 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). 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-containing 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. This model corresponds to a conserved region in FRMPD1 and 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 FRMPD1 and FRMPD4.

                          10        20        30
                  ....*....|....*....|....*....|....*..
gi 158705786  902 LGLLASLRETKSTNPASR-IMEMEPETMETKSVIDSR 937
Cdd:cd21928     1 LGEDAPLGLQASGDRSSYsLMEMEPETMETKSVTDSV 37

PDZ domain 1 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family 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
                  ....*....|....*....|....*....|....*....|....*...
gi 158705786   69 YGFHISETLPLTVVAVTAGGSAH-GKLFPGDQILQMNNELAEDLSCER 115
Cdd:cd06743    11 FGFSIGGSGPCYILSVEEGSSAHaAGLQPGDQILELDGQDVSSLSCEA 58

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158705786   57 TVTLDKDvlLQNYGFHISE--TLPLTVV-AVTAGGSA--HGKLFPGDQILQMNNELAEDLSCERAADILRETEDALSITV 131
Cdd:cd10817     1 HVELPKD--QGGLGIAISEedTENGIVIkSLTEGGPAakDGRLKVGDQILAVDDESVVGCPYEKAISLLKTAKGTVKLTV 78

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158705786   56 HTVTLDKDvllQNYGF-----------HISETLPLTVVA-VTAGGSAHGKLFPGDQILQMNNELAEDLSCERAADILRET 123
Cdd:cd06727     1 HTVTLHRA---PGFGFgiavsggrdnpHFQSGDTSIVISdVLKGGPAEGKLQENDRVVSVNGVSMENVEHSFAVQILRKC 77

                          90
                  ....*....|
gi 158705786  124 EDALSITVVR 133
Cdd:cd06727    78 GKTANITVKR 87

PDZ domain of PDZ-LIM family proteins, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZ-LIM family proteins including PDLIM1-7, and related domains. PDZ-LIM family proteins (also known as Zasp PDZ domain proteins) are involved in the rearrangement of the actin cytoskeleton; they mediate association with the cytoskeleton through alpha-actinin as well as with other proteins involved in signal transduction pathways. Members of this family include PDLIM1 (also known as C-terminal LIM domain protein 1, elfin, LIM domain protein CLP-36), PDLIM2 (also known as PDZ-LIM protein mystique), PDLIM3 (also known as actinin-associated LIM protein, alpha-actinin-2-associated LIM protein, ALP), PDLIM4 (also known as LIM protein RIL, Reversion-induced LIM protein), PDLIM5 (also known as enigma homolog, ENH, enigma-like PDZ and LIM domains protein), PDLIM6 (also known as LIM domain-binding protein 3, ZASP, Cypher, Oracle), and PDLIM7 (also known as PDZ and LIM domain protein 7, LIM mineralization protein, LMP; protein enigma). PDLIM1 has been shown to negatively regulate NF-kappaB-mediated signaling in the cytoplasm. PDLIM7 negatively regulates p53 through binding murine double minute 2 (MDM2). The PDZ domains of PDZ-LIM family proteins PDLIM1, 2, 3, 5, 6, 7 have been shown to bind actin. Other PDZ-LIM family PDZ domain binding partners include thyroid receptor interacting protein-6 (PDLIM4-PDZ), the LIM domain of PDLIM4 (PDLIM4-PDZ), tropomyosin (PDLIM7-PDZ), myotilin and calsarcin 1 (PDLIM6-PDZ), and proteins from the myotilin and FATZ (calsarcin/myozenin) families (PDLIM1, 3, 4, 6 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 PDLIM-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 158705786   78 PLTVVAVTAGGSAH-GKLFPGDQILQMNNELAEDLSCERAADILRETEDALSITVVR 133
Cdd:cd06753    23 PLTISRVTPGGKAAqANLRPGDVILAINGESTEGMTHLEAQNKIKAATGSLSLTLER 79

PDZ domain of afadin (AFDN), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of afadin (AFDN, also known as ALL1-fused gene from chromosome 6 protein (AF6) and MLLT4), and related domains. AFDN belongs to the adhesion system, probably together with the E-cadherin-catenin system, that plays a role in the organization of homotypic, interneuronal, and heterotypic cell-cell adherens junctions. The AFDN PDZ domain interaction partners include poliovirus receptor-related protein PRR2/nectin, the junctional adhesion molecule (JAM), the breakpoint-cluster-region protein (BCR), connexin36 (Cx36), and a subset of Eph-related receptor tyrosine kinases; it can also bind low molecular weight ligands, in competition with a natural peptide ligand. Other AFDN-binding proteins have been identified. 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 AFDN 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 158705786   81 VVAVTAGGSAH--GKLFPGDQILQMNNELAEDLSCERAADILRETEDALSITV 131
Cdd:cd06789    34 IKSVVKGGAADldGRLQAGDQLLSVDGHSLVGLSQERAAELMTKTGSVVTLEV 86

PDZ domain 5 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 5 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, and belongs to this MAGI1,2,3-like family. 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 PDZ5 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 158705786   55 RHTVTLDKDVllQNYGFHIS-----ETLPLTVVAVTAGGSAH--GKLFPGDQILQMNNELAEDLSCERAADILRETEDAL 127
Cdd:cd06735     1 YYSVELERGP--KGFGFSIRggreyNNMPLYVLRLAEDGPAQrdGRLRVGDQILEINGESTQGMTHAQAIELIRSGGSVV 78

                  ....*.
gi 158705786  128 SITVVR 133
Cdd:cd06735    79 RLLLRR 84

PDZ domain of Rap guanine nucleotide exchange factor 2 and Rap guanine nucleotide exchange factor 6, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Rap guanine nucleotide exchange factor 2 (RapGEF2, also named RA-GEF-1, PDZ-GEF1, CNrasGEF and nRapGEP) and Rap guanine nucleotide exchange factor 6 (RapGEF6, also named RA-GEF-2 and PDZ-GEF2). RapGEF2 and RapGEF6 constitute a subfamily of guanine nucleotide exchange factors (GEFs) for RAP small GTPases that is characterized by the possession of the PDZ and Ras/Rap-associating domains. They activate Rap small GTPases, by catalyzing the release of GDP from the inactive GDP-bound forms, thereby accelerating GTP loading to yield the active GTP-bound forms. The PDZ domain of RapGEF6 (also known as PDZ-GEF2) binds junctional adhesion molecule A (JAM-A). 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 RapGEF2 and RapGEF6 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 158705786   97 GDQILQMNNELAEDLSCERAADILRETEDaLSITV 131
Cdd:cd06755    47 GDQILEVNGQNFENITLKKALEILRNNTH-LSITV 80

PDZ domain 1 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 1 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 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 158705786   73 ISETLPLTVVAVTaggsahGKLFPGDQILQMNNELAEDLSCERAADILRETEDALSITVVR 133
Cdd:cd06677    34 IQEVYRDGVIARD------GRLLPGDQILEVNGVDISNVTHSQARSVLRQPCPVLRLTVLR 88

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 158705786   57 TVTLDKDvllQNYGFHIS------------ETLPLTVVAVTAGGSAHGKLFPGDQILQMNNELAEDLSCERAADILRETE 124
Cdd:cd06749     2 RVRIEKN---PGLGFSISggigsqgnpfrpDDDGIFVTKVQPDGPASKLLQPGDKILEVNGYDFVNIEHGQAVSLLKSFQ 78

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gi 158705786  125 DALSITVVR 133
Cdd:cd06749    79 NTVDLVVER 87

PDZ domain 10 of multi-PDZ-domain protein 1 (MUPP1), domain 8 of PATJ (protein-associated tight junction) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 10 of MUPP1, PDZ domain 8 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 PDZ10 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 158705786   81 VVAVTAGGSAH--GKLFPGDQILQMNNELAEDLSCERAADILRETEDALSITVVR 133
Cdd:cd06673    32 IHEVYEDGAAAkdGRLWAGDQILEVNGEDLRKATHDEAINVLRQTPQKVRLLVYR 86

PDZ domain 5 of glutamate receptor-interacting protein 1 (GRIP1) and GRIP2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) binding proteins GRIP1 (ABP/GRIP2) and GRIP2, and related domains. GRIP1 and GRIP2 each have 7 PDZ domains. The interaction of GRIP1 and GRIP2 with GluA2/3 (AMPAR subunit) regulates AMPAR trafficking and synaptic targeting. GRIP1 has an essential role in regulating AMPAR trafficking during synaptic plasticity and learning and memory. GRIP1 and GRIP2 interact with a variety of other proteins associated with protein trafficking and internalization, for example GRIP1 also interacts with KIF5 (also known as kinesin 1), EphB receptors, scaffold protein liprin-alpha, and the rasGEF GRASP-1. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This GRIP family domain PDZ5 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 158705786   78 PLTVVAVTAGGSAH--GKLFPGDQILQMNNELAEDLSCERAADILRETED 125
Cdd:cd06682    28 PLIISDVKKGSVAHrtGTLEPGDKLLAIDNIRLDNCSMEDAAQILQQAED 77

PDZ domain 2 of multi-PDZ-domain protein 1 (MUPP1) and PATJ (protein-associated tight junction) and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 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 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 158705786   70 GFHI--SETLPLTVVAVTAGGSAH--GKLFPGDQILQMNNELAEDLSCERAADILRETEDALSITVVR 133
Cdd:cd06667    13 GFGIvgGKSTGVVVKTILPGGVADrdGRLRSGDHILQIGDTNLRGMGSEQVAQVLRQCGSHVRLVVAR 80

PDZ domain 2 of Discs Large 5 (Dlg5) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Drosophila and mammalian Dlg5, and related domains. Dlg5 is a scaffold protein with multiple conserved functions that are independent of each other in regulating growth, cell polarity, and cell adhesion. It has a coiled-coil domain, 4 PDZ domains and a MAGUK domain (an SH3 domain next to a non-catalytically active guanylate kinase domain). Deregulation of Dlg5 has been implicated in the malignancy of several cancer types. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg5-like family PSZ2 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 158705786   70 GFHISETLPLTVVAvtaggsAHGKLFPGDQILQMNNELAEDLSCERAADILRETEDALSITVVRCTS 136
Cdd:cd06765    17 GVFISRIVPGSPAA------KEGSLTVGDRIIAINGIALDNKSLSECEALLRSCRDSLSLSLMKVFP 77

PDZ domain 2 of Zonula Occludens-1 (ZO-1), ZO-2 and ZO-3, and related domains; form domain-swapping dimers; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 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 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 158705786   57 TVTLDKDVLLQNYGFHISETLPLTVVAVTAGGSAHGKLFPGDQILQMNNELAEDLSCERAADILRETEDALSITVVR 133
Cdd:cd06728     2 KVTLTKSRKNDEYGLRLGSRIFVKEITPDSLAAKDGNLQEGDIILKINGTPVENLSLSEAKKLIEKSKDKLQLVVLR 78