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 1723592924  179 MPNVLKVYLENGQTKAFKFEANTTVKDIILTVKEKLSIRSIEYFALALEEQYSISRLHLLHEEELIQQVVEREESQDSRC 258
Cdd:cd17168      1 MPNVLKVYLENGQTKAFKFESNTTVKDIILTLKEKLSIRSIEHFALVLEEQYSISKLYLLHEEELIEQVVEKRESHDYRC 80

                           90
                   ....*....|
gi 1723592924  259 LFRVCFVPKD 268
Cdd:cd17168     81 LFRVCFVPKD 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 1723592924   182 VLKVYLENGQTKAFKFEANTTVKDIILTVKEKLSIRSIEYFALALEEQYSISRLHLLHEEELIQQVVEREESQdsrCLFR 261
Cdd:smart00295    1 VLKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPDEDLRHWLDPAKTLLDQDVKSEPLT---LYFR 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1723592924   262 VCFVPKDPLDlLKEDPVAFEYLYLQSCSDVLQERFavemKC--NSALRLAALHIQeriyACAQPQKISLKYIEKDWGIEN 339
Cdd:smart00295   78 VKFYPPDPNQ-LKEDPTRLNLLYLQVRNDILEGRL----PCpeEEALLLAALALQ----AEFGDYDEELHDLRGELSLKR 148

                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1723592924   340 FISPTLLRNMKGKDIKKAI-SFHMK-RNQnlleprqkqliSAAQLRLNYLQILGELKTYGGKIF 401
Cdd:smart00295  149 FLPKQLLDSRKLKEWRERIvELHKElIGL-----------SPEEAKLKYLELARKLPTYGVELF 201

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 1723592924  901 ALGLLASLRETKSKNPASRIMEMEPETMETKSVIDSRV 938
Cdd:cd21942      1 SFGQLKSQRPTKNKNLSSELMEMEPDTMETKSVTDSVV 38

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 1723592924  179 MPNVLKVYLENGQTKAFKFEANTTVKDIILTVKEKLSIRSIEYFALALEEQYSISRLHLLHEEELIQQVVEREESQDSRC 258
Cdd:cd17168      1 MPNVLKVYLENGQTKAFKFESNTTVKDIILTLKEKLSIRSIEHFALVLEEQYSISKLYLLHEEELIEQVVEKRESHDYRC 80

                           90
                   ....*....|
gi 1723592924  259 LFRVCFVPKD 268
Cdd:cd17168     81 LFRVCFVPKD 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 1723592924   182 VLKVYLENGQTKAFKFEANTTVKDIILTVKEKLSIRSIEYFALALEEQYSISRLHLLHEEELIQQVVEREESQdsrCLFR 261
Cdd:smart00295    1 VLKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPDEDLRHWLDPAKTLLDQDVKSEPLT---LYFR 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1723592924   262 VCFVPKDPLDlLKEDPVAFEYLYLQSCSDVLQERFavemKC--NSALRLAALHIQeriyACAQPQKISLKYIEKDWGIEN 339
Cdd:smart00295   78 VKFYPPDPNQ-LKEDPTRLNLLYLQVRNDILEGRL----PCpeEEALLLAALALQ----AEFGDYDEELHDLRGELSLKR 148

                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1723592924   340 FISPTLLRNMKGKDIKKAI-SFHMK-RNQnlleprqkqliSAAQLRLNYLQILGELKTYGGKIF 401
Cdd:smart00295  149 FLPKQLLDSRKLKEWRERIvELHKElIGL-----------SPEEAKLKYLELARKLPTYGVELF 201

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1723592924  269 PLDLLKEDPVAFEYLYLQSCSDVLQERFAVEmkCNSALRLAALHIQERIYACAQPQKISlkyieKDWGIENFISPTLLRN 348
Cdd:pfam00373    1 DLELLLQDEVTRHLLYLQAKDDILEGRLPCS--EEEALLLAALQLQAEFGDYQPSSHTS-----EYLSLESFLPKQLLRK 73

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1723592924  349 MKGKDIKKAISFHMKRNQNLleprqkqliSAAQLRLNYLQILGELKTYGGKIF 401
Cdd:pfam00373   74 MKSKELEKRVLEAHKNLRGL---------SAEEAKLKYLQIAQSLPTYGVEFF 117

FERM domain B-lobe; The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). 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, the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the pleckstrin homology (PH) and phosphotyrosine binding (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 1723592924  279 AFEYLYLQSCSDVLQERFAVemKCNSALRLAALHIQeRIYACAQPQKISLKYIekdwGIENFISPTLLRNMKGKDIKKAI 358
Cdd:cd14473      1 TRYLLYLQVKRDILEGRLPC--SEETAALLAALALQ-AEYGDYDPSEHKPKYL----SLKRFLPKQLLKQRKPEEWEKRI 73

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1723592924  359 SFHMKRNQNLleprqkqliSAAQLRLNYLQILGEL 393
Cdd:cd14473     74 VELHKKLRGL---------SPAEAKLKYLKIARKL 99

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

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1723592924   58 VTLDKDVLLQNYGFHISETLPltvvavtaGGSAH-GKLFPGDQILQMNKELAEDLSCERAVDILRETEDALSITV 131
Cdd:pfam00595   14 FSLKGGSDQGDPGIFVSEVLP--------GGAAEaGGLKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLTI 80

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 1723592924  179 MPNVLKVYLENGQTKAFKFEANTTVKDIILTVKEKLSIRSIEYFALALEEQYSISRLHLLHEEELIQQVVEREESQDSRC 258
Cdd:cd17168      1 MPNVLKVYLENGQTKAFKFESNTTVKDIILTLKEKLSIRSIEHFALVLEEQYSISKLYLLHEEELIEQVVEKRESHDYRC 80

                           90
                   ....*....|
gi 1723592924  259 LFRVCFVPKD 268
Cdd:cd17168     81 LFRVCFVPKD 90

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 1723592924  179 MPNVLKVYLENGQTKAFKFEANTTVKDIILTVKEKLSIRSIEYFALALEEQ--YSISRLHLLHEEELIQQVVEREESQDS 256
Cdd:cd17088      1 MPNVLKVYLENGQTKSFKYDQSTTVKDVLLSLQEKLGIKSMEHFSLVLEYVksPRTNKLSLLQPDESLAQVAARPGSHHL 80

                           90
                   ....*....|
gi 1723592924  257 RCLFRVCFVP 266
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 1723592924   182 VLKVYLENGQTKAFKFEANTTVKDIILTVKEKLSIRSIEYFALALEEQYSISRLHLLHEEELIQQVVEREESQdsrCLFR 261
Cdd:smart00295    1 VLKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPDEDLRHWLDPAKTLLDQDVKSEPLT---LYFR 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1723592924   262 VCFVPKDPLDlLKEDPVAFEYLYLQSCSDVLQERFavemKC--NSALRLAALHIQeriyACAQPQKISLKYIEKDWGIEN 339
Cdd:smart00295   78 VKFYPPDPNQ-LKEDPTRLNLLYLQVRNDILEGRL----PCpeEEALLLAALALQ----AEFGDYDEELHDLRGELSLKR 148

                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1723592924   340 FISPTLLRNMKGKDIKKAI-SFHMK-RNQnlleprqkqliSAAQLRLNYLQILGELKTYGGKIF 401
Cdd:smart00295  149 FLPKQLLDSRKLKEWRERIvELHKElIGL-----------SPEEAKLKYLELARKLPTYGVELF 201

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 1723592924   57 TVTLDKDvLLQNYGFHISETLPLTVVAVTAGGSAHGKLFPGDQILQMNKELAEDLSCERAVDILRETEDALSITVV 132
Cdd:cd06769      1 TVEIQRD-AVLGFGFVAGSERPVVVRSVTPGGPSEGKLLPGDQILKINNEPVEDLPRERVIDLIRECKDSIVLTVL 75

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1723592924   57 TVTLDKDvLLQNYGFHIS----ETLPLTVVAVTAGGSAH--GKLFPGDQILQMNKELAEDLSCERAVDILRETEDALSIT 130
Cdd:cd00136      1 TVTLEKD-PGGGLGFSIRggkdGGGGIFVSRVEPGGPAArdGRLRVGDRILEVNGVSLEGLTHEEAVELLKSAGGEVTLT 79

                   ..
gi 1723592924  131 VV 132
Cdd:cd00136     80 VR 81

FERM domain B-lobe; The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). 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, the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the pleckstrin homology (PH) and phosphotyrosine binding (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 1723592924  279 AFEYLYLQSCSDVLQERFAVemKCNSALRLAALHIQeRIYACAQPQKISLKYIekdwGIENFISPTLLRNMKGKDIKKAI 358
Cdd:cd14473      1 TRYLLYLQVKRDILEGRLPC--SEETAALLAALALQ-AEYGDYDPSEHKPKYL----SLKRFLPKQLLKQRKPEEWEKRI 73

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1723592924  359 SFHMKRNQNLleprqkqliSAAQLRLNYLQILGEL 393
Cdd:cd14473     74 VELHKKLRGL---------SPAEAKLKYLKIARKL 99

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 1723592924  902 LGLLASLRETKSKNPASR-IMEMEPETMETKSVIDSR 937
Cdd:cd21928      1 LGEDAPLGLQASGDRSSYsLMEMEPETMETKSVTDSV 37

PDZ domain 7 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 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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1723592924   56 HTVTLDKDVLLQNYGFHISETL---PLTVVAVTAGGSA-HGKLFPGDQILQMNKELAEDLSCERAVDILRETEDALSITV 131
Cdd:cd06685      4 HKVTLYKDSDTEDFGFSVSDGLyekGVYVNAIRPGGPAdLSGLQPYDRILQVNHVRTRDFDCCLVVPLIAESGDKLELVV 83

                   ..
gi 1723592924  132 VR 133
Cdd:cd06685     84 SR 85

PDZ domain 13 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 13 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 PDZ13 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 PDZ13 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 1723592924   57 TVTLDKDVllQNYGFHI-------SETLPLTVVAVTAGGSAH--GKLFPGDQILQMNKELAEDLSCERAVDILRETEDAL 127
Cdd:cd06676      1 TITLERGS--DGLGFSIvggfgspHGDLPIYVKTVFEKGAAAedGRLKRGDQILAVNGESLEGVTHEEAVNILKKTKGTV 78

                   ....*
gi 1723592924  128 SITVV 132
Cdd:cd06676     79 TLTVL 83

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 1723592924   56 HTVTLDKDvllQNYGF-----------HISETLPLTVVA-VTAGGSAHGKLFPGDQILQMNKELAEDLSCERAVDILRET 123
Cdd:cd06727      1 HTVTLHRA---PGFGFgiavsggrdnpHFQSGDTSIVISdVLKGGPAEGKLQENDRVVSVNGVSMENVEHSFAVQILRKC 77

                           90
                   ....*....|
gi 1723592924  124 EDALSITVVR 133
Cdd:cd06727     78 GKTANITVKR 87

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

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gi 1723592924   58 VTLDKDVLLQNYGFHISETLPltvvavtaGGSAH-GKLFPGDQILQMNKELAEDLSCERAVDILRETEDALSITV 131
Cdd:pfam00595   14 FSLKGGSDQGDPGIFVSEVLP--------GGAAEaGGLKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLTI 80

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 1723592924   57 TVTLDKDvllQNYGFHIS------------ETLPLTVVAVTAGGSAHGKLFPGDQILQMNKELAEDLSCERAVDILRETE 124
Cdd:cd06749      2 RVRIEKN---PGLGFSISggigsqgnpfrpDDDGIFVTKVQPDGPASKLLQPGDKILEVNGYDFVNIEHGQAVSLLKSFQ 78

                   ....*....
gi 1723592924  125 DALSITVVR 133
Cdd:cd06749     79 NTVDLVVER 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.

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gi 1723592924   78 PLTVVAVTAGGSAH-GKLFPGDQILQMNKELAEDLSCERAVDILRETEDALSITVVR 133
Cdd:cd06753     23 PLTISRVTPGGKAAqANLRPGDVILAINGESTEGMTHLEAQNKIKAATGSLSLTLER 79

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
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gi 1723592924  921 MEMEPETMETKSVID 935
Cdd:cd21943     21 IEMEPETMETKSLTD 35

PDZ domain of segment polarity protein dishevelled homolog DVL1, DVL2, DVL3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of DVL1-3, and related domains. The dishevelleds (DVL1, 2 and 3 in humans) act downstream of Frizzled (FZD) receptors in both the canonical and non-canonical WNT signaling pathway; they bind the cytoplasmic C-terminus of frizzled family members and transduce the Wnt signal to down-stream effectors. They bind to several proteins known to modulate Wnt signaling. Binding partners of the DVL1 PDZ domain include nucleoredoxin (NXN), Van Gogh-like (VANGL1), Wnt receptor RYK, Dapper 1 (DACT1), Frizzled7 (FZD7), transmembrane protein 88 (TMEM88), Daple (dishevelled-associating protein with a high frequency of leucines), also known as Ccdc88c), and cysteine-rich protein Idax. The DVL2 PDZ domain has been shown to bind the nuclear export signal sequence of the DVL2 protein. 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 DVL-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 1723592924   70 GFHISETLPLTVVAvtaggsAHGKLFPGDQILQMNKELAEDLSCERAVDILRE 122
Cdd:cd06717     27 GIYVGSIMKGGAVA------ADGRIEPGDMILQVNDISFENMSNDDAVRVLRE 73

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 1723592924   67 QNYGFHISETLPltvvavtaGGSA--HGKLFPGDQILQMNKELAEDLSCERAVDILRETEDALSITV 131
Cdd:cd06796     24 QNSPIYISRIIP--------GGVAdrHGGLKRGDQLLSVNGVSVEGEHHEKAVELLKAAQGSVKLVV 82

PDZ domain 2 of human discs large homolog 1 (Dlg1), Dlg2, and Dlg4, Drosophila disc large (Dlg), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Drosophila Dlg1, human Dlg1,2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197 or SAP-97), Dlg2 (also known as channel-associated protein of synapse-110, postsynaptic density protein 93, or PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95, synapse-associated protein 90, or SAP-90) each have 3 PDZ domains and belong to the membrane-associated guanylate kinase family. Dlg1 regulates antigen receptor signaling and cell polarity in lymphocytes, B-cell proliferation and antibody production, and TGFalpha bioavailability; its PDZ3 domain binds pro-TGFalpha, and its PDZ2 domain binds the TACE metalloprotease responsible for cleaving pro-TGFalpha to a soluble form. Dlg2 is involved in N-methyl-D-aspartate (NMDA) receptor signaling. It regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord, and it also interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. Dlg4 PDZ1 domain binds NMDA receptors, and its PDZ2 domain binds neuronal nitric oxide synthase (nNOS), forming a complex in neurons. The Drosophila Scribble complex (Scribble, Dlg, and lethal giant larvae) plays a role in apico-basal cell polarity, and in other forms of polarity, including regulation of the actin cytoskeleton, cell signaling and vesicular trafficking, and in tumor development. Postsynaptic targeting of Drosophila DLG requires interactions mediated by the first two PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Dlg-like family 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 1723592924   81 VVAVTAGGSAH--GKLFPGDQILQMNKELAEDLSCERAVDILRETEDALSITVV 132
Cdd:cd06724     32 VTKIIEGGAAQkdGRLQVGDKLLAVNDVSLEEVTHEEAVAALKNTSDVVYLKVA 85

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 1723592924   81 VVAVTAGGSAH--GKLFPGDQILQMNKELAEDLSCERAVDILRETEDALSITVVR 133
Cdd:cd06673     32 IHEVYEDGAAAkdGRLWAGDQILEVNGEDLRKATHDEAINVLRQTPQKVRLLVYR 86

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.

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gi 1723592924  183 LKVYL-ENGQTKAFKFEANTTVKDIILTVKEKLS 215
Cdd:pfam16511    3 LKISIvGSNVTKTMQFDPSTTVYDACRLIREKIP 36

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 1723592924   67 QNYGFHISETL--PLTVV-AVTAGGSAH-GKLFPGDQILQMNKELAEDLSCERAVDILRETEDALSITVV 132
Cdd:cd06768     10 EGYGFNLHAEKgrPGHFIrEVDPGSPAErAGLKDGDRLVEVNGENVEGESHEQVVEKIKASGNQVTLLVV 79