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 167520410   432 RRVIIHRTAIGFGFAINGE----SPVFITTVVPGGPSDKglAGLLPRDIILKVNGTPCprGPRTHVVALVKNTPPGQPLE 507
Cdd:smart00228   3 RLVELEKGGGGLGFSLVGGkdegGGVVVSSVVPGSPAAK--AGLRVGDVILEVNGTSV--EGLTHLEAVDLLKKAGGKVT 78

                   ....*
gi 167520410   508 LVVCR 512
Cdd:smart00228  79 LTVLR 83

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410   14 MPELIPVPPTDFALATHAPDNSSSHAQVTSTSQRdpPDLPSVPASSQIEIGAQDPSPAATSSAQTPPCSTGVHVASPEAS 93
Cdd:PHA03247 2555 LPPAAPPAAPDRSVPPPRPAPRPSEPAVTSRARR--PDAPPQSARPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPSPS 2632

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410   94 SASLKPPLIEERPDQPSDIAHVQESAGAVRP--------LPTHDDSPPSVIEQSATQSRIQKQTATSDPvPLTSASPETR 165
Cdd:PHA03247 2633 PAANEPDPHPPPTVPPPERPRDDPAPGRVSRprrarrlgRAAQASSPPQRPRRRAARPTVGSLTSLADP-PPPPPTPEPA 2711

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410  166 PLNGSSG-PAPATSVELSGDHPVPSKDDVV----------VLRTRRGRQALALGDATlSASSTDRASilssfyfPPPPEF 234
Cdd:PHA03247 2712 PHALVSAtPLPPGPAAARQASPALPAAPAPpavpagpatpGGPARPARPPTTAGPPA-PAPPAAPAA-------GPPRRL 2783

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410  235 DE---SSSEVAPSSKPLQHSDSLPTSAKHDLSFGDSVESEASSMGPFSPTLRDLKTLPPPNMTSTPLRPEGGEAVGSSAD 311
Cdd:PHA03247 2784 TRpavASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVAPGGDVR 2863

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 167520410  312 RDALQQRRHNRPVIVYDLPVAAIPE---RRSLWGRVRSAFGSKRTR-PETPTSPSNTAPRHRPGRPA 374
Cdd:PHA03247 2864 RRPPSRSPAAKPAAPARPPVRRLARpavSRSTESFALPPDQPERPPqPQAPPPPQPQPQPPPPPQPQ 2930

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 167520410   432 RRVIIHRTAIGFGFAINGE----SPVFITTVVPGGPSDKglAGLLPRDIILKVNGTPCprGPRTHVVALVKNTPPGQPLE 507
Cdd:smart00228   3 RLVELEKGGGGLGFSLVGGkdegGGVVVSSVVPGSPAAK--AGLRVGDVILEVNGTSV--EGLTHLEAVDLLKKAGGKVT 78

                   ....*
gi 167520410   508 LVVCR 512
Cdd:smart00228  79 LTVLR 83

PDZ domain 2 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 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it 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 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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 167520410 434 VIIHRTAIGFGFAINGESPVFITTVVPGGPSDKglAGLLPRDIILKVNGTPCPRGPRTHVVALVKNTppGQPLELVVC 511
Cdd:cd06744    2 VRVYRGNGSFGFTLRGHAPVYIESVDPGSAAER--AGLKPGDRILFLNGLDVRNCSHDKVVSLLQGS--GSMPTLVVE 75

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410 636 YSGWLKKKTGAVVGAgdWKRRYFVLFGSRMAYFK-KATPNAKPCGVLELQQ-CRIQRTRETDMDNTFRVICKEFKNLLLA 713
Cdd:cd00821    1 KEGYLLKRGGGGLKS--WKKRWFVLFEGVLLYYKsKKDSSYKPKGSIPLSGiLEVEEVSPKERPHCFELVTPDGRTYYLQ 78

                 ....*
gi 167520410 714 APTQT 718
Cdd:cd00821   79 ADSEE 83

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410   14 MPELIPVPPTDFALATHAPDNSSSHAQVTSTSQRdpPDLPSVPASSQIEIGAQDPSPAATSSAQTPPCSTGVHVASPEAS 93
Cdd:PHA03247 2555 LPPAAPPAAPDRSVPPPRPAPRPSEPAVTSRARR--PDAPPQSARPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPSPS 2632

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410   94 SASLKPPLIEERPDQPSDIAHVQESAGAVRP--------LPTHDDSPPSVIEQSATQSRIQKQTATSDPvPLTSASPETR 165
Cdd:PHA03247 2633 PAANEPDPHPPPTVPPPERPRDDPAPGRVSRprrarrlgRAAQASSPPQRPRRRAARPTVGSLTSLADP-PPPPPTPEPA 2711

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410  166 PLNGSSG-PAPATSVELSGDHPVPSKDDVV----------VLRTRRGRQALALGDATlSASSTDRASilssfyfPPPPEF 234
Cdd:PHA03247 2712 PHALVSAtPLPPGPAAARQASPALPAAPAPpavpagpatpGGPARPARPPTTAGPPA-PAPPAAPAA-------GPPRRL 2783

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410  235 DE---SSSEVAPSSKPLQHSDSLPTSAKHDLSFGDSVESEASSMGPFSPTLRDLKTLPPPNMTSTPLRPEGGEAVGSSAD 311
Cdd:PHA03247 2784 TRpavASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVAPGGDVR 2863

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 167520410  312 RDALQQRRHNRPVIVYDLPVAAIPE---RRSLWGRVRSAFGSKRTR-PETPTSPSNTAPRHRPGRPA 374
Cdd:PHA03247 2864 RRPPSRSPAAKPAAPARPPVRRLARpavSRSTESFALPPDQPERPPqPQAPPPPQPQPQPPPPPQPQ 2930

carboxyl-terminal processing protease; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410 404 YTLFLRaPVWFGRTQSATSAQ-TKLNLSarrviihrtaIGFGFAINGESP-VFITTVVPGGPSDKglAGLLPRDIILKVN 481
Cdd:PLN00049  64 FTRFLE-PEKFKSLRSGTKGAvTGVGLE----------VGYPTGSDGPPAgLVVVAPAPGGPAAR--AGIRPGDVILAID 130

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 167520410 482 GTPCpRGPRTHVVALVKNTPPGQPLELVVCRTPEQK 517
Cdd:PLN00049 131 GTST-EGLSLYEAADRLQGPEGSSVELTLRRGPETR 165

Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 viral late glycoprotein, also termed gp350/220. It is the most abundantly expressed glycoprotein in the viral envelope of the Herpesviruses and is the major antigen responsible for stimulating the production of neutralising antibodies in vivo.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410   17 LIPVP-PTDFALATHAPDNSSSHAQVTSTSQRDPPDLPSVPAssqieigaqdPSPAATSS--AQTPPCSTgvhVASPEAS 93
Cdd:pfam05109 488 VTPSPsPRDNGTESKAPDMTSPTSAVTTPTPNATSPTPAVTT----------PTPNATSPtlGKTSPTSA---VTTPTPN 554

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410   94 SASLKPPLIEERPDQPSDIAHVQESAGAVRPlPTHDDSPPSVIEQSATQSRIQKQTATSDPVPLTSASPETrplngssgp 173
Cdd:pfam05109 555 ATSPTPAVTTPTPNATIPTLGKTSPTSAVTT-PTPNATSPTVGETSPQANTTNHTLGGTSSTPVVTSPPKN--------- 624

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410  174 apATSVELSGDHPVPSKD-DVVVLRTRRGRQalalgdaTLSASSTDRASILSSFYFPPPPEFDESSSEVAPSSKPLQH-- 250
Cdd:pfam05109 625 --ATSAVTTGQHNITSSStSSMSLRPSSISE-------TLSPSTSDNSTSHMPLLTSAHPTGGENITQVTPASTSTHHvs 695

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 167520410  251 -SDSLPTSAKHDLSFGDSVESEASSMGPFSPTlrdlKTLPPPNMTStPLRPEG 302
Cdd:pfam05109 696 tSSPAPRPGTTSQASGPGNSSTSTKPGEVNVT----KGTPPKNATS-PQAPSG 743

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 167520410   432 RRVIIHRTAIGFGFAINGE----SPVFITTVVPGGPSDKglAGLLPRDIILKVNGTPCprGPRTHVVALVKNTPPGQPLE 507
Cdd:smart00228   3 RLVELEKGGGGLGFSLVGGkdegGGVVVSSVVPGSPAAK--AGLRVGDVILEVNGTSV--EGLTHLEAVDLLKKAGGKVT 78

                   ....*
gi 167520410   508 LVVCR 512
Cdd:smart00228  79 LTVLR 83

PDZ domain 2 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 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it 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 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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 167520410 434 VIIHRTAIGFGFAINGESPVFITTVVPGGPSDKglAGLLPRDIILKVNGTPCPRGPRTHVVALVKNTppGQPLELVVC 511
Cdd:cd06744    2 VRVYRGNGSFGFTLRGHAPVYIESVDPGSAAER--AGLKPGDRILFLNGLDVRNCSHDKVVSLLQGS--GSMPTLVVE 75

PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of rhophilin-1, rhophilin-2, and related domains. Rhophilin-1 (RHPN1, also known as GTP-Rho-binding protein 1) and rhophilin-2 (RHPN2, also known as GTP-Rho-binding protein 2) are Rho-GTP binding proteins involved in cytoskeletal dynamics. Rhophilin-2 inhibits RhoA's activity to induce F-actin stress fibers. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This rhophilin-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 167520410 432 RRVIIHRTAIGFGFAINGESPVFITTVVPGGPSDkgLAGLLPRDIILKVNGTPCPRGPRTHVVALVKNTpPGQPLELVV 510
Cdd:cd06712    2 RTVHLTKEEGGFGFTLRGDSPVQVASVDPGSCAA--EAGLKEGDYIVSVGGVDCKWSKHSEVVKLLKSA-GEEGLELQV 77

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 167520410 433 RVIIHRTAI-GFGFAINGESPVFITTVVPGGPSDkglAGLLPRDIILKVNGTPCPRGPRTHVVALVK 498
Cdd:cd06769    1 TVEIQRDAVlGFGFVAGSERPVVVRSVTPGGPSE---GKLLPGDQILKINNEPVEDLPRERVIDLIR 64

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 167520410 432 RRVIIHRTAIGFGFAINGESPVFITTVVPGGPSDKglAGLLPRDIILKVNGTPCPRGPRTHVVALV 497
Cdd:cd06710    1 RTVEIARGRAGYGFTISGQAPCVLSCVVRGSPADV--AGLKAGDQILAVNGINVSKASHEDVVKLI 64

PDZ domain of regulator of G-protein signaling 3 (RGS3), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of RGS3, and related domains. RGS3 down-regulates GPCR signal transduction by increasing the GTPase activity of G-protein alpha subunits, thereby driving G-proteins into their inactive GDP-bound form. It downregulates G-protein-mediated release of inositol phosphates and activation of MAP kinases. In Eph/ephrin signaling, RGS3 binds via its PDZ domain to the cytoplasmic C terminus of Eph receptor tyrosine kinase EphB. 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 RGS3-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 167520410 432 RRVIIHRTAIGFGFAINGESPVFITTVVPGGPSDKglAGLLPRDIILKVNGTPCPRGPRTHVVALVKNTP 501
Cdd:cd06711    1 LQITIQRGKDGFGFTICDDSPVRVQAVDPGGPAEQ--AGLQQGDTVLQINGQPVERSKCVELAHAIRNCP 68

PDZ domain 1 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 1 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 PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as beta-strands A, -B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410 433 RVIIHRTAIGFGFAI-NGESP-VF--ITTVVPGGPSDkgLAG-LLPRDIILKVNGTpCPRGpRTH--VVALVKNTPPGQP 505
Cdd:cd06731    3 RTSLKKSARGFGFTIiGGDEPdEFlqIKSVVPDGPAA--LDGkLRTGDVLVSVNDT-CVLG-YTHadVVKLFQSIPIGQS 78

                 ....*..
gi 167520410 506 LELVVCR 512
Cdd:cd06731   79 VNLEVCR 85

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 167520410 637 SGWLKKKTG--AVVGAGDWKRRYFVLFGSRMAYFKKATPNAKPCGVLELQQCR 687
Cdd:cd13296    2 SGWLTKKGGgsSTLSRRNWKSRWFVLRDTVLKYYENDQEGEKLLGTIDIRSAK 54

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410 432 RRVIIHRTAIGFGFAING---ESPVFITTVVPGGPSDkgLAGLLPR-DIILKVNGTPCPRGPRTHVVALVKNTppGQPLE 507
Cdd:cd06795    3 RKIVLHKGSTGLGFNIVGgedGEGIFISFILAGGPAD--LSGELRRgDQILSVNGVDLRNATHEQAAAALKNA--GQTVT 78

                 ....*....
gi 167520410 508 LVVCRTPEQ 516
Cdd:cd06795   79 IIAQYKPEE 87

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410   14 MPELIPVPPTDFALATHAPDNSSSHAQVTSTSQRdpPDLPSVPASSQIEIGAQDPSPAATSSAQTPPCSTGVHVASPEAS 93
Cdd:PHA03247 2555 LPPAAPPAAPDRSVPPPRPAPRPSEPAVTSRARR--PDAPPQSARPRAPVDDRGDPRGPAPPSPLPPDTHAPDPPPPSPS 2632

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410   94 SASLKPPLIEERPDQPSDIAHVQESAGAVRP--------LPTHDDSPPSVIEQSATQSRIQKQTATSDPvPLTSASPETR 165
Cdd:PHA03247 2633 PAANEPDPHPPPTVPPPERPRDDPAPGRVSRprrarrlgRAAQASSPPQRPRRRAARPTVGSLTSLADP-PPPPPTPEPA 2711

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410  166 PLNGSSG-PAPATSVELSGDHPVPSKDDVV----------VLRTRRGRQALALGDATlSASSTDRASilssfyfPPPPEF 234
Cdd:PHA03247 2712 PHALVSAtPLPPGPAAARQASPALPAAPAPpavpagpatpGGPARPARPPTTAGPPA-PAPPAAPAA-------GPPRRL 2783

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410  235 DE---SSSEVAPSSKPLQHSDSLPTSAKHDLSFGDSVESEASSMGPFSPTLRDLKTLPPPNMTSTPLRPEGGEAVGSSAD 311
Cdd:PHA03247 2784 TRpavASLSESRESLPSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVAPGGDVR 2863

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 167520410  312 RDALQQRRHNRPVIVYDLPVAAIPE---RRSLWGRVRSAFGSKRTR-PETPTSPSNTAPRHRPGRPA 374
Cdd:PHA03247 2864 RRPPSRSPAAKPAAPARPPVRRLARpavSRSTESFALPPDQPERPPqPQAPPPPQPQPQPPPPPQPQ 2930

Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410 453 VFITTVVPGGPSDKglAGLLPRDIILKVNGTPCpRGPRThVVALVKNTPPGQPLELVVCR 512
Cdd:COG0265  203 VLVARVEPGSPAAK--AGLRPGDVILAVDGKPV-TSARD-LQRLLASLKPGDTVTLTVLR 258

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 167520410 637 SGWLKKKTGAVvgaGDWKRRYFVLFGSRMAYFKKATpNAKPCGVLELQQCRI 688
Cdd:cd13263    6 SGWLKKQGSIV---KNWQQRWFVLRGDQLYYYKDED-DTKPQGTIPLPGNKV 53

PDZ domains of the Na+/H+ exchange regulatory cofactor (NHERF) family (NHERF1-4), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the Na+/H+ exchange regulatory cofactor (NHERF) family of multi-PDZ-domain-containing scaffolding proteins (NHERF1-4), and related domains. The NHERF family includes NHERF1 (also known as EBP50), NHERF2 (also known as E3KARP; TKA-1; SIP-1), NHERF3 (also known as CAP70; CLAMP; Napi-Cap-1; PDZD1) and NHERF4 (also known as IKEPP; PDZK2; Napi-Cap-2). NHERF1 and NHERF2 have tandem PDZ domains (PDZ1-2); NHERF3 and NHERF4 have four PDZ domains (PDZ1-4). NHERFs are involved in the regulation of multiple receptors or transporters, such as type II sodium-phosphate cotransporter (Npt2a), purinergic P2Y1 receptor P2Y1R, the beta2-adrenergic receptor (beta2-AR), parathyroid hormone receptor type 1 (PTHR), the lysophosphatidic acid receptors (LPARs), sodium-hydrogen exchanger 3 (NHE3), and cystic fibrosis transmembrane conductance regulator (CFTR). NHERF-PDZ1 domain interaction partners include Npt2a, purinergic P2Y1 receptor, beta2-AR, CFTR, PTHR, NH3, G-protein-coupled receptor kinase 6 (GRK6A), platelet-derived growth factor receptor (PDGFR), B1 subunit of the H+ATPase, cholesterol, receptor for activated C-kinase RACK1, aquaporin 9, among others. The NHERF PDZ2 domain interacts with fewer proteins: NHERF1 PDZ2 binds Npt2a, PTHR, beta-catenin, aquaporin 9, and RACK1; NHERF2 PDZ2 binds LPA2, P2Y1R, and NHE3, cGMP-dependent protein kinase type II (cGKII). NHERF4 PDZ1 and PDZ4 bind the epithelial Ca(2+) channels TRPV5 and TRPV6. NHERF2/NHERF3 heterodimerization is mediated by PDZ domains of NHERF2 and the C-terminal PDZ domain recognition motif of NHERF3. NHERF4 regulates several transporters mediating influx of xenobiotics and nutrients in the small intestine. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This NHERF-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410 432 RRVIIHRTAIGFGF---AINGESPVFITTVVPGGPSDKglAGLLPRDIILKVNGTPCprGPRTH--VVALVKNTppGQPL 506
Cdd:cd06768    1 RLCHLVKGPEGYGFnlhAEKGRPGHFIREVDPGSPAER--AGLKDGDRLVEVNGENV--EGESHeqVVEKIKAS--GNQV 74

                 ....*
gi 167520410 507 ELVVC 511
Cdd:cd06768   75 TLLVV 79

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410 442 GFGFAINGES-PVFITTVVPGGPSDKglAGLLPRDIILKVNGTPCPRGPRTHVVALVKNtPPGQPLELVVCRTPEQKRKR 520
Cdd:COG0793   61 GLGAELGEEDgKVVVVSVIPGSPAEK--AGIKPGDIILAIDGKSVAGLTLDDAVKLLRG-KAGTKVTLTIKRPGEGEPIT 137

                 .
gi 167520410 521 F 521
Cdd:COG0793  138 V 138

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 167520410 443 FGFAING---ESPVFITTVVPGGPSDkgLAGLLPRDIILKVNGTpcprgpRTH------VVALVKNTppGQPLELVVCR 512
Cdd:cd06685   17 FGFSVSDglyEKGVYVNAIRPGGPAD--LSGLQPYDRILQVNHV------RTRdfdcclVVPLIAES--GDKLELVVSR 85

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. 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 C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410 637 SGWLKKKTGAVvgaGDWKRRYFVLFGSRMAYFKkaTPN---AKPCGVLEL-QQCRIQRTREtdmDNTFRVICKEfKNLLL 712
Cdd:cd13282    2 AGYLTKLGGKV---KTWKRRWFVLKNGELFYYK--SPNdviRKPQGQIALdGSCEIARAEG---AQTFEIVTEK-RTYYL 72

                 ....*.
gi 167520410 713 AAPTQT 718
Cdd:cd13282   73 TADSEN 78

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 167520410 638 GWLKKKTGAVVGagDWKRRYFVLFGSRMAYFKKATPNAKPCGVLELQQCRIQRTRETDMDNTFRVICKEfKNLLLAA 714
Cdd:cd13250    3 GYLFKRSSNAFK--TWKRRWFSLQNGQLYYQKRDKKDEPTVMVEDLRLCTVKPTEDSDRRFCFEVISPT-KSYMLQA 76

Membrane-associated protease RseP, regulator of RpoE activity [Posttranslational modification, protein turnover, chaperones, Transcription];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 167520410 439 TAIGFGFAINGESPVFITTVVPGGPSDKglAGLLPRDIILKVNGTPCPRGprTHVVALVKNTpPGQPLELVVCR 512
Cdd:COG0750  116 AVLFMTVGVPVLTPPVVGEVVPGSPAAK--AGLQPGDRIVAINGQPVTSW--DDLVDIIRAS-PGKPLTLTVER 184

circularly permuted PDZ domain of high-temperature requirement factor A (HtrA) family serine proteases and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of HtrA family serine proteases including human HtrA1, HtrA2 (mitochondrial), HtrA3, and HtrA4, and related domains. These proteases are key enzymes associated with pregnancy. Their diverse biological functions include cell growth proliferation, migration and apoptosis. They are also implicated in disorders including Alzheimer's, Parkinson's, arthritis and cancer. HtrA1 (also known as high-temperature requirement A serine peptidase 1, L56, and serine protease 11) substrates include extracellular matrix proteins, proteoglycans, and insulin-like growth factor (IGF)-binding proteins. HtrA1 also inhibits signaling by members of the transforming growth factor beta (TGF-beta) family. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping of beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2); arranged as A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This HtrA-like PDZ domain is a circularly permuted PDZ domain which places beta-strand A on the C-terminus. Another permutation exists in the PDZ superfamily which places both beta-strands A and B on the C-terminus.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410 453 VFITTVVPGGPSDKGlaGLLPRDIILKVNGTPCPRGprTHVVALVKNtppGQPLELVVCR 512
Cdd:cd06785   33 VYVHKVIPGSPAQRA--GLKDGDVIISINGKPVKSS--SDVYEAVKS---GSSLLVVVRR 85

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410 433 RVIIHRTAiGFGFAING------------ESPVFITTVVPGGPSDKglaGLLPRDIILKVNGTPCPRGPRTHVVALVKNT 500
Cdd:cd06749    2 RVRIEKNP-GLGFSISGgigsqgnpfrpdDDGIFVTKVQPDGPASK---LLQPGDKILEVNGYDFVNIEHGQAVSLLKSF 77

                         90
                 ....*....|..
gi 167520410 501 ppGQPLELVVCR 512
Cdd:cd06749   78 --QNTVDLVVER 87

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and, with the exception of CNK3, a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from mammals, chickens, amphibians, fish, and crustacea. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410 626 RRL--RDIGESDYSGWL--KKKTGAVVGAgDWKRRYFVLFGSRMaYFKKATPNAKPCGVLELQQCRIQRTRETDMDNTFR 701
Cdd:cd01260    3 RRVscKDLGRGDCQGWLwkKKEAKSFFGQ-KWKKYWFVLKGSSL-YWYSNQQDEKAEGFINLPDFKIERASECKKKYAFK 80

                         90
                 ....*....|...
gi 167520410 702 VICKEFKNLLLAA 714
Cdd:cd01260   81 ACHPKIKTFYFAA 93

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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 167520410 432 RRVIIHRTAIGFGFAING----ESPVFITTVVPGGPSDKglAGLLPR-DIILKVNGTPCPRGPRTHVVALVKN 499
Cdd:cd06796    3 RVVELPKTEEGLGFNVMGgkeqNSPIYISRIIPGGVADR--HGGLKRgDQLLSVNGVSVEGEHHEKAVELLKA 73

transcriptional regulator ICP4; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410    5 TETTALESQMPELIPVPPTDFALATHAPDNSSSHAQVTSTSQRDPPDLPSVPASSQIEIGAQDPSPAATSSAQTPPCSTG 84
Cdd:PHA03307   87 TPTWSLSTLAPASPAREGSPTPPGPSSPDPPPPTPPPASPPPSPAPDLSEMLRPVGSPGPPPAASPPAAGASPAAVASDA 166

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410   85 VH-------VASPEASSASLKPPLIEERPDQPsdiahvqesagavRPLPTHDDSPPSVIEQSatqsriqkqtATSDPVPL 157
Cdd:PHA03307  167 ASsrqaalpLSSPEETARAPSSPPAEPPPSTP-------------PAAASPRPPRRSSPISA----------SASSPAPA 223

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410  158 TSASPETRPLNGSSGPAPATSVELS----GDHPVPSkDDVVVLRTRRGRQALALGDATLSASSTDRASIlssfyfppppe 233
Cdd:PHA03307  224 PGRSAADDAGASSSDSSSSESSGCGwgpeNECPLPR-PAPITLPTRIWEASGWNGPSSRPGPASSSSSP----------- 291

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167520410  234 fDESSSEVAPSSkplQHSDSLPTSAKHDLSFGDSVESEASSMGPFSPTLRDLKTLPPPNMTSTPLRPEGgeavGSSADRD 313
Cdd:PHA03307  292 -RERSPSPSPSS---PGSGPAPSSPRASSSSSSSRESSSSSTSSSSESSRGAAVSPGPSPSRSPSPSRP----PPPADPS 363