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 1928577515  363 TGVLFNTVGL-DEKHSATTLLVGPRHGISHVIDLKTNLTTVLSEFSKISKIQLFRENQGVARVETSIMDAKPLVLLMEWP 441
Cdd:cd13183      1 GGRSFQATLMlQDRESEVTLLVGPRYGISHVINHKLNLLALLAEFSHISRIELLRESDKVSRVELHIHDVKPITLLMESP 80

                           90       100
                   ....*....|....*....|....*
gi 1928577515  442 EATNFACLIAGYCRLLLDSRKMVFS 466
Cdd:cd13183     81 DAKDLACLIAGYYRLLVDPRRSIFS 105

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 1928577515   148 VLKVFLENGQIKSFTFDGRTTVKDVMATLQDRLSLRSIEHFALVLEYTGPEQNHkFLilqdkQPLAYV-VQRTHYHGMKC 226
Cdd:smart00295    1 VLKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPDEDLRH-WL-----DPAKTLlDQDVKSEPLTL 74

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928577515   227 LFRISFFPKDPvELLRRDPAAFEYLYIQSRNDVIRERFGMEpkPEMLLGLAALHIYITVsatrPSQKITLKNVEKEWGLE 306
Cdd:smart00295   75 YFRVKFYPPDP-NQLKEDPTRLNLLYLQVRNDILEGRLPCP--EEEALLLAALALQAEF----GDYDEELHDLRGELSLK 147

                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1928577515   307 PFLPPSLLQGIKEKNLRKSLSQQLKAHqmhpssstKG-SAIQAKLQYLRILNELPTFtGVLF 367
Cdd:smart00295  148 RFLPKQLLDSRKLKEWRERIVELHKEL--------IGlSPEEAKLKYLELARKLPTY-GVEL 200

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 1928577515  363 TGVLFNTVGL-DEKHSATTLLVGPRHGISHVIDLKTNLTTVLSEFSKISKIQLFRENQGVARVETSIMDAKPLVLLMEWP 441
Cdd:cd13183      1 GGRSFQATLMlQDRESEVTLLVGPRYGISHVINHKLNLLALLAEFSHISRIELLRESDKVSRVELHIHDVKPITLLMESP 80

                           90       100
                   ....*....|....*....|....*
gi 1928577515  442 EATNFACLIAGYCRLLLDSRKMVFS 466
Cdd:cd13183     81 DAKDLACLIAGYYRLLVDPRRSIFS 105

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 1928577515   148 VLKVFLENGQIKSFTFDGRTTVKDVMATLQDRLSLRSIEHFALVLEYTGPEQNHkFLilqdkQPLAYV-VQRTHYHGMKC 226
Cdd:smart00295    1 VLKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIRESEYFGLQFEDPDEDLRH-WL-----DPAKTLlDQDVKSEPLTL 74

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928577515   227 LFRISFFPKDPvELLRRDPAAFEYLYIQSRNDVIRERFGMEpkPEMLLGLAALHIYITVsatrPSQKITLKNVEKEWGLE 306
Cdd:smart00295   75 YFRVKFYPPDP-NQLKEDPTRLNLLYLQVRNDILEGRLPCP--EEEALLLAALALQAEF----GDYDEELHDLRGELSLK 147

                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1928577515   307 PFLPPSLLQGIKEKNLRKSLSQQLKAHqmhpssstKG-SAIQAKLQYLRILNELPTFtGVLF 367
Cdd:smart00295  148 RFLPKQLLDSRKLKEWRERIVELHKEL--------IGlSPEEAKLKYLELARKLPTY-GVEL 200

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 1928577515  247 AFEYLYIQSRNDVIRERFgmEPKPEMLLGLAALHIYITVSATRPSQKitlknVEKEWGLEPFLPPSLLQGIKEKNLRKSL 326
Cdd:cd14473      1 TRYLLYLQVKRDILEGRL--PCSEETAALLAALALQAEYGDYDPSEH-----KPKYLSLKRFLPKQLLKQRKPEEWEKRI 73

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1928577515  327 SQQLKAHqmhpssstKG-SAIQAKLQYLRILNEL 359
Cdd:cd14473     74 VELHKKL--------RGlSPAEAKLKYLKIARKL 99

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928577515   21 QVTIHRDPIYGFGF-----VAGSERPVVVRSVRPGGPSE-DKLLAGDQIVAINEEDVSEAPRERFIELIRSAKESIVLTV 94
Cdd:pfam00595    1 QVTLEKDGRGGLGFslkggSDQGDPGIFVSEVLPGGAAEaGGLKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLTI 80

                   .
gi 1928577515   95 L 95
Cdd:pfam00595   81 L 81

transcriptional regulator ICP4; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928577515  847 TGQSPAPTGARRKIPQSEVQVQGDRPYSLAVHPALSPQLSEQKNLSLLPPVPEDRGPGHSRAGLEMSLRSATPSLSEEQV 926
Cdd:PHA03307    72 PPGPGTEAPANESRSTPTWSLSTLAPASPAREGSPTPPGPSSPDPPPPTPPPASPPPSPAPDLSEMLRPVGSPGPPPAAS 151

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928577515  927 SELRENLPKEVrlspklildPKGNVTPAIISAALQQVVHSKslATPGTALATPSNRGERRLEASMGRPEVTMSRPEVSVM 1006
Cdd:PHA03307   152 PPAAGASPAAV---------ASDAASSRQAALPLSSPEETA--RAPSSPPAEPPPSTPPAAASPRPPRRSSPISASASSP 220

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928577515 1007 SSSVSKNLKFkmspGAPETTRNSQQQLGPEVSASPRASTGSRADNLHLSPPEDRFPVQSFPPKSYLSRVSRDSMGKQATG 1086
Cdd:PHA03307   221 APAPGRSAAD----DAGASSSDSSSSESSGCGWGPENECPLPRPAPITLPTRIWEASGWNGPSSRPGPASSSSSPRERSP 296

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928577515 1087 EVAGKGGPEGAKPPPNKQSVVSGQGDKGQLESLSKSSKLEETSLVPRAgypmalQSPSCQPRSHSPSCQPRGPSPSSQSR 1166
Cdd:PHA03307   297 SPSPSSPGSGPAPSSPRASSSSSSSRESSSSSTSSSSESSRGAAVSPG------PSPSRSPSPSRPPPPADPSSPRKRPR 370

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928577515 1167 GqSPSCQPRSQSPLRPL--ATSRQVSTMPSRKLETTLDGAHSASEGPTKPKSSRGPFRLR 1224
Cdd:PHA03307   371 P-SRAPSSPAASAGRPTrrRARAAVAGRARRRDATGRFPAGRPRPSPLDAGAASGAFYAR 429

PAB1-binding protein, interacts with poly(A)-binding protein [RNA processing and modification];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928577515  822 AAQAVLTAPYALGPPDPNPSPQPAVTGQSPAPTGARRKIPQSEVQVQGD-RPYSLAVHPALSPQLSEQKNLSL------- 893
Cdd:COG5180    121 GALPAPAAAAALPKAKVTREATSASAGVALAAALLQRSDPILAKDPDGDsASTLPPPAEKLDKVLTEPRDALKdspekld 200

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928577515  894 LPPVPED-----------RGPGHSRAGLEMSLRSATPSLSEEQVSELRENLPKEVRlspklildPKGNVTpaiisAALQQ 962
Cdd:COG5180    201 RPKVEVKdeaqeeppdltGGADHPRPEAASSPKVDPPSTSEARSRPATVDAQPEMR--------PPADAK-----ERRRA 267

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928577515  963 VVHSKSLATPGTALATpsnrgERRLEASMGRPEVTMSRPEVSVMSSSVSKNLK-FKMSPGAPETTRNSQQQLGPEVSASP 1041
Cdd:COG5180    268 AIGDTPAAEPPGLPVL-----EAGSEPQSDAPEAETARPIDVKGVASAPPATRpVRPPGGARDPGTPRPGQPTERPAGVP 342

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928577515 1042 RASTGSRADNLHLSPPEDRFPVQ---SFPPKSYLSRVSRDSMGKQATGEVAGKGGPEGAKPPPNKQSVVSGQGDKGQLES 1118
Cdd:COG5180    343 EAASDAGQPPSAYPPAEEAVPGKpleQGAPRPGSSGGDGAPFQPPNGAPQPGLGRRGAPGPPMGAGDLVQAALDGGGRET 422

                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1928577515 1119 LSKSS-KLEETSLVPRAGYPMALQSPSCQPRSHSPSCQPRGPS--PSSQSRGQSPSCQPRSQSPLRPLA 1184
Cdd:COG5180    423 ASLGGaAGGAGQGPKADFVPGDAESVSGPAGLADQAGAAASTAmaDFVAPVTDATPVDVADVLGVRPDA 491

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 1928577515  363 TGVLFNTVGL-DEKHSATTLLVGPRHGISHVIDLKTNLTTVLSEFSKISKIQLFRENQGVARVETSIMDAKPLVLLMEWP 441
Cdd:cd13183      1 GGRSFQATLMlQDRESEVTLLVGPRYGISHVINHKLNLLALLAEFSHISRIELLRESDKVSRVELHIHDVKPITLLMESP 80

                           90       100
                   ....*....|....*....|....*
gi 1928577515  442 EATNFACLIAGYCRLLLDSRKMVFS 466
Cdd:cd13183     81 DAKDLACLIAGYYRLLVDPRRSIFS 105

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 1928577515   21 QVTIHRDPIYGFGFVAGSERPVVVRSVRPGGPSEDKLLAGDQIVAINEEDVSEAPRERFIELIRSAKESIVLTVL 95
Cdd:cd06769      1 TVEIQRDAVLGFGFVAGSERPVVVRSVTPGGPSEGKLLPGDQILKINNEPVEDLPRERVIDLIRECKDSIVLTVL 75

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 1928577515  144 LIPNVLKVFLENGQIKSFTFDGRTTVKDVMATLQDRLSLRSIEHFALVLEYTGPEQNHKFLILQDKQPLAYVVQRTHYHG 223
Cdd:cd17170      1 FMPNVLKVYLENGQTKSFRFDCSTSIKDVILTLQEKLSIKCIEHFSLMLEQRTEGSGTKLLLLHEQETLTQVTQRPGSHK 80

                           90
                   ....*....|....
gi 1928577515  224 MKCLFRISFFPKDP 237
Cdd:cd17170     81 MRCLFRISFVPKDP 94

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1928577515  237 PVELLRRDPAAFEYLYIQSRNDVIRERFgmEPKPEMLLGLAALHIYITVSATRPSQKItlknvEKEWGLEPFLPPSLLQG 316
Cdd:pfam00373    1 DLELLLQDEVTRHLLYLQAKDDILEGRL--PCSEEEALLLAALQLQAEFGDYQPSSHT-----SEYLSLESFLPKQLLRK 73

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1928577515  317 IKEKNLRKSLSQQLKAHQ-MhpssstkgSAIQAKLQYLRILNELPTFTGVLF 367
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 1928577515  247 AFEYLYIQSRNDVIRERFgmEPKPEMLLGLAALHIYITVSATRPSQKitlknVEKEWGLEPFLPPSLLQGIKEKNLRKSL 326
Cdd:cd14473      1 TRYLLYLQVKRDILEGRL--PCSEETAALLAALALQAEYGDYDPSEH-----KPKYLSLKRFLPKQLLKQRKPEEWEKRI 73

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1928577515  327 SQQLKAHqmhpssstKG-SAIQAKLQYLRILNEL 359
Cdd:cd14473     74 VELHKKL--------RGlSPAEAKLKYLKIARKL 99

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 1928577515   21 QVTIHRDPiYGFGFvAGSERP----VVVRSVRPGGPS--EDKLLAGDQIVAINEEDVSEAPRERFIELIRSAKESIVLTV 94
Cdd:cd10817      1 HVELPKDQ-GGLGI-AISEEDtengIVIKSLTEGGPAakDGRLKVGDQILAVDDESVVGCPYEKAISLLKTAKGTVKLTV 78

PDZ domain of ARHGEF11, ARHGEF12, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ARHGEF11, ARHGEF12, and related domains. This subfamily includes the GEFs (guanine exchange factors) ARHGEF11 (Rho guanine nucleotide exchange factor 11, known as PDZ-RhoGEF) and ARHGEF12 (Rho guanine nucleotide exchange factor 12, also known as leukemia-associated RhoGEF). GEFs activate Rho GTPases by promoting GTP binding. ARHGEF11/12 are regulators of G protein signaling (RGS) domain-containing GEFs; the RGS domain mediates their binding to and activation of Galpha (and Gq also in the case of ARHGEF12), in response to G-protein coupled receptor activation. ARHGEF11 and 12 are involved in serum-signaling, and regulate Yes-Associated Protein (YAP1)-dependent transcription. The ARHGEF12 PDZ domain binds plexin-B1 and the receptor tyrosine kinase insulin-like growth factor receptor (IGF-R1) beta-subunit. ARHGEF12 also interacts with glutamate receptor delta-1(GluD1), a postsynaptic organizer of inhibitory synapses in cortical pyramidal neurons. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ARHGEF11-12-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 1928577515   20 RQVTIHRDPiYGFGFVAGSERPVVVRSVRPGGPSEDK-LLAGDQIVAINEEDVSEAPRERFIELIRSAkESIVLTVL 95
Cdd:cd23069      2 RCVVIQRDE-NGYGLTVSGDNPVFVQSVKEGGAAYRAgVQEGDRIIKVNGTLVTHSNHLEVVKLIKSG-SYVALTLL 76

PDZ domain 1 of Zonula Occludens-1 (ZO-1), homologs ZO-2 and ZO-3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of ZO-1, -2, -3 and related domains. Zonula occludens proteins (ZO-1, ZO-2, ZO-3) are multi-PDZ domain proteins involved in the maintenance and biogenesis of multi-protein networks at the cytoplasmic surface of intercellular contacts in epithelial and endothelial cells. They have three N-terminal PDZ domains, PDZ1-3, followed by a Src homology-3 (SH3) domain and a guanylate kinase (GuK)-like domain. Among protein-protein interactions for all ZO proteins is the binding of the first PDZ domain (PDZ1) to the C-termini of claudins, and the homo- and hetero-dimerization of ZO-proteins via their second PDZ domain (PDZ2), which takes place by symmetrical domain swapping of the first two beta-strands of PDZ2. At the cell level, ZO-1 and ZO-2 are involved in polarity maintenance, gene transcription, cell proliferation, and tumor cell metastasis. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This ZO family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

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gi 1928577515   22 VTIHRDPIYGFGFV--AGSERP--------VVVRSVRPGGPSEDKLLAGDQIVAINEEDVSEAPRERFIELIRSAKESIV 91
Cdd:cd06727      3 VTLHRAPGFGFGIAvsGGRDNPhfqsgdtsIVISDVLKGGPAEGKLQENDRVVSVNGVSMENVEHSFAVQILRKCGKTAN 82

                   ...
gi 1928577515   92 LTV 94
Cdd:cd06727     83 ITV 85

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 1928577515   21 QVTIHRDPIYGFGFV------------AGSERPVVVRSVRPGGPSED---KLLAGDQIVAINEEDVSEAPRERFIELIRS 85
Cdd:cd06747      1 EITLKRQPTGDFGFSlrrgtivergpdDGQELKRTVHFAEPGAGTKNlatGLLPGDRLIEVNGVNVENASRDEIIEMIRK 80

                   ....*....
gi 1928577515   86 AKESIVLTV 94
Cdd:cd06747     81 SGDTVTLKV 89

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 1928577515   22 VTIHRDPIYGFGFVAGSERPVVVRS----VRPGGPSE--DKLLAGDQIVAINEEDVSEAPRERFIELIRSAKESIVLTVL 95
Cdd:cd06734      4 VTLTRRENEGFGFVIISSVNKKSGSkigrIIPGSPADrcGQLKVGDRILAVNGISILNLSHGDIVNLIKDSGLSVTLTIV 83

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.

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gi 1928577515   20 RQVTIHRDPIyGFGFVAGSERPVVVRSVRPGGPSEDK-LLAGDQIVAINEEDVSEAPRERFIELIRSAKESIVLTV 94
Cdd:cd06710      1 RTVEIARGRA-GYGFTISGQAPCVLSCVVRGSPADVAgLKAGDQILAVNGINVSKASHEDVVKLIGKCTGVLRLVI 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 1928577515   20 RQVTIHRDPiYGFGFVAGSERPV---VVRSVRPGGPSED-KLLAGDQIVAINEEDVSEAPRERFIELIRSAKESIVLTVL 95
Cdd:cd06768      1 RLCHLVKGP-EGYGFNLHAEKGRpghFIREVDPGSPAERaGLKDGDRLVEVNGENVEGESHEQVVEKIKASGNQVTLLVV 79

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 1928577515   22 VTIHRDPIY---GFGFVAGSERP---VVVRSVRPGGP-SED-KLLAGDQIVAINEEDVSEAPRERFIELIRSAKESIVLT 93
Cdd:cd06677      6 IEIHRSDPYeelGISIVGGNDTPlinIVIQEVYRDGViARDgRLLPGDQILEVNGVDISNVTHSQARSVLRQPCPVLRLT 85

                   ..
gi 1928577515   94 VL 95
Cdd:cd06677     86 VL 87

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

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gi 1928577515   14 LPAETLRQVTIH-RDPIYGFGFVAGSE-RPVVVRSVRPGGPSED-KLLAGDQIVAINEEDVSEAPRERFIELIRSAKESI 90
Cdd:COG0793     43 LDPEEYEDFQEStSGEFGGLGAELGEEdGKVVVVSVIPGSPAEKaGIKPGDIILAIDGKSVAGLTLDDAVKLLRGKAGTK 122

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1928577515   91 V-LTVLhtHQSPKSAFISAAKKAKLRSNPVKVRFSE 125
Cdd:COG0793    123 VtLTIK--RPGEGEPITVTLTRAEIKLPSVEAKLLE 156

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 1928577515   31 GFGFVAGSER--PVVVRSVRPGGPSE--DKLLAGDQIVAINEEDVSEAPRERFIELIRSAKESIVLTVLHT 97
Cdd:cd06796     15 GFNVMGGKEQnsPIYISRIIPGGVADrhGGLKRGDQLLSVNGVSVEGEHHEKAVELLKAAQGSVKLVVRYT 85

PDZ domain 5 of Danio rerio tyrosine-protein 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 5 of Danio rerio Ptpn13, and related domains. Protein-tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosyl residues in proteins that are phosphorylated by protein tyrosine kinases (PTKs). Danio rerio Ptpn13 is a classical non-receptor-like PTP. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13-like family 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 1928577515   21 QVTIHRDPIYGFGF--VAGSE-RPVVVRSVRPGGPS--EDKLLAGDQIVAINEEDVSEAPRERFIELIRSAKESIVLTV 94
Cdd:cd23060      1 QIELEKPANGGLGFslVGGEGgSGIFVKSISPGGVAdrDGRLQVGDRLLQVNGESVIGLSHSKAVNILRKAKGTVQLTV 79

PDZ domain 2 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 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 1928577515   21 QVTIHRDPiYGFGFV----AGSE----RPVVVRSVRPGGPS--EDKLLAGDQIVAINEEDVSEAPRERFIELIRSAKESI 90
Cdd:cd06681      4 EVTLEKEG-NSFGFVirggAHEDrnksRPLTVTHVRPGGPAdrEGTIKPGDRLLSVDGISLHGATHAEAMSILKQCGQEA 82

                   ....
gi 1928577515   91 VLTV 94
Cdd:cd06681     83 TLLI 86

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.

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gi 1928577515   32 FGFVAGSERPVVVRSVRPGGPSEDK-LLAGDQIVAINEEDVSEAPRERFIELIRSAKES 89
Cdd:cd06743     11 FGFSIGGSGPCYILSVEEGSSAHAAgLQPGDQILELDGQDVSSLSCEAIIALARRCPSV 69

PDZ domain 3 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 3 of Drosophila Dlg1, human Dlg1, 2, and 4 and related domains. Dlg1 (also known as synapse-associated protein Dlg197; SAP-97), Dlg2 (also known as channel-associated protein of synapse-110; postsynaptic density protein 93, PSD-93), Dlg4 (also known as postsynaptic density protein 95, PSD-95; synapse-associated protein 90, 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, regulating surface expression of NMDA receptors in dorsal horn neurons of the spinal cord; it interacts with NMDA receptor subunits and with Shaker-type K+ channel subunits to cluster into a channel complex. The 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 PDZ3 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

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gi 1928577515   20 RQVTIHRDPI-YGFGFVAGSE-RPVVVRSVRPGGPSED--KLLAGDQIVAINEEDVSEAPRERFIELIRSAKESIVLTVL 95
Cdd:cd06795      3 RKIVLHKGSTgLGFNIVGGEDgEGIFISFILAGGPADLsgELRRGDQILSVNGVDLRNATHEQAAAALKNAGQTVTIIAQ 82

                   .
gi 1928577515   96 H 96
Cdd:cd06795     83 Y 83

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

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gi 1928577515   21 QVTIHRDPIYGFGF------VAGSERPVV----VRSVRPGGPSE--DKLLAGDQIVAINEEDVSEAPRERFIELIRSAKE 88
Cdd:cd23063      1 MVVIEKTEKKSFGIcivrgeVKVSPNTKTtgifIKGIIPDSPAHkcGRLKVGDRILSVNGNDVRNSTEQAAIDLIKEADF 80