Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  694 LLQLSTVEVATQLSMRNFELFRNIEPTEYIDDLFKLKSKT--SCANLKKFEEVINQETFWVASEILRETNQLKRMKIIKH 771
Cdd:cd00155      1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNihLSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  772 FIKIALHCRECKNFNSMFAIISGLNLAPVARLRTTWEKLPNKYEKLFQDLQDLFDPSRNMAKYRNVLSGQNLQPPVIPLF 851
Cdd:cd00155     81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVGPNPPCVPFL 160

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720405454  852 PVIKKDLTFLHEGNDSKVD-GLVNFEKLRMIAKEIRHVGRMASV--NMDPALMFRTRKKKWRSLGSLSQGS 919
Cdd:cd00155    161 GVYLKDLTFLHEGNPDFLEgNLVNFEKRRKIAEILREIRQLQSNsyELNRDEDILAFLWKLLELILNEDEL 231

Ras-associating (RA) domain found in PDZ domain-containing guanine nucleotide exchange factor 1 (PDZ-GEF1) and similar proteins; PDZ-GEF1, also termed Rap guanine nucleotide exchange factor 2, or cyclic nucleotide ras GEF (CNrasGEF), or neural RAP guanine nucleotide exchange protein (nRap GEP), or Ras/Rap1-associating GEF-1 (RA-GEF-1), is a Rap-specific guanine nucleotide exchange factor (GEF) that has a PSD-95/DlgA/ZO-1 (PDZ) domain, a RA domain and a region related to a cyclic nucleotide binding domain (RCBD). The RA domain of PDZ-GEF interacts with Rap1 and also contributes to the membrane localization of PDZ-GEF. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and involve in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  589 QVLRVFKADQQSRYIMISKDTTAKEVVIQAIREFAVTAT--PEQYSLCEVSVTPEGVIKQRRLPDQLSKLADRIQLSGRY 666
Cdd:cd01785      1 QVLKVYRADQSSKYILIHKETTAREVVMLALREFGITDDenSDNYSLCEVTVTPEGLIKQRRLPDQLSNLANRISLNGRY 80

                   ....*
gi 1720405454  667 YLKNN 671
Cdd:cd01785     81 YLKNN 85

Cyclic nucleotide-monophosphate binding domain; Catabolite gene activator protein (CAP) is a prokaryotic homologue of eukaryotic cNMP-binding domains, present in ion channels, and cNMP-dependent kinases.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454   117 FANMTMSVRRELCAVMvFAVVERAGTIVLNDGEELDSWSVILNGSVEVTY--PDGKAEILCM---GNSFGVSPTMDkeYM 191
Cdd:smart00100    2 FKNLDAEELRELADAL-EPVRYPAGEVIIRQGDVGDSFYIIVSGEVEVYKvlEDGEEQIVGTlgpGDFFGELALLT--NS 78

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|.
gi 1720405454   192 KGVMRTKVDDCQFVCIAQQDYCRILNQVEKNMQKVEEEGEI 232
Cdd:smart00100   79 RRAASAAAVALELATLLRIDFRDFLQLLPELPQLLLELLLE 119

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  694 LLQLSTVEVATQLSMRNFELFRNIEPTEYIDDLFKLKSKT--SCANLKKFEEVINQETFWVASEILRETNQLKRMKIIKH 771
Cdd:cd00155      1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNihLSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  772 FIKIALHCRECKNFNSMFAIISGLNLAPVARLRTTWEKLPNKYEKLFQDLQDLFDPSRNMAKYRNVLSGQNLQPPVIPLF 851
Cdd:cd00155     81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVGPNPPCVPFL 160

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720405454  852 PVIKKDLTFLHEGNDSKVD-GLVNFEKLRMIAKEIRHVGRMASV--NMDPALMFRTRKKKWRSLGSLSQGS 919
Cdd:cd00155    161 GVYLKDLTFLHEGNPDFLEgNLVNFEKRRKIAEILREIRQLQSNsyELNRDEDILAFLWKLLELILNEDEL 231

RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  701 EVATQLSMRNFELFRNIEPTEYIDDLF-KLKSKTSCANLKKFEEVINQETFWVASEILRETNQLKRMKIIKHFIKIALHC 779
Cdd:pfam00617    1 ELARQLTLIEFELFRKIKPRELLGSAWsKKDKKENSPNIEAMIARFNKLSNWVASEILSEEDLKKRAKVIKKFIKIAEHC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  780 RECKNFNSMFAIISGLNLAPVARLRTTWEKLPNKYEKLFQDLQDLFDPSRNMAKYRNVLsgQNLQPPVIPLFPVIKKDLT 859
Cdd:pfam00617   81 RELNNFNSLMAILSGLNSSPISRLKKTWELVSKKYKKTLEELEKLMSPSRNFKNYREAL--SSASPPCIPFLGLYLTDLT 158

                          170       180
                   ....*....|....*....|.
gi 1720405454  860 FLHEGNDSKV-DGLVNFEKLR 879
Cdd:pfam00617  159 FIEEGNPDFLeGGLINFEKRR 179

Ras-associating (RA) domain found in PDZ domain-containing guanine nucleotide exchange factor 1 (PDZ-GEF1) and similar proteins; PDZ-GEF1, also termed Rap guanine nucleotide exchange factor 2, or cyclic nucleotide ras GEF (CNrasGEF), or neural RAP guanine nucleotide exchange protein (nRap GEP), or Ras/Rap1-associating GEF-1 (RA-GEF-1), is a Rap-specific guanine nucleotide exchange factor (GEF) that has a PSD-95/DlgA/ZO-1 (PDZ) domain, a RA domain and a region related to a cyclic nucleotide binding domain (RCBD). The RA domain of PDZ-GEF interacts with Rap1 and also contributes to the membrane localization of PDZ-GEF. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and involve in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  589 QVLRVFKADQQSRYIMISKDTTAKEVVIQAIREFAVTAT--PEQYSLCEVSVTPEGVIKQRRLPDQLSKLADRIQLSGRY 666
Cdd:cd01785      1 QVLKVYRADQSSKYILIHKETTAREVVMLALREFGITDDenSDNYSLCEVTVTPEGLIKQRRLPDQLSNLANRISLNGRY 80

                   ....*
gi 1720405454  667 YLKNN 671
Cdd:cd01785     81 YLKNN 85

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately N-terminal to the RasGef (Cdc25-like) domain. REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  256 TSERLTMHLVEEHSVVDPTFIEDFLLTYRTFLsSPMEVGKKLLEWFNDP----------------SLRDKVTRVVLLWVN 319
Cdd:cd06224      1 TLEALIEHLTSTFDMPDPSFVSTFLLTYRSFT-TPTELLEKLIERYEIAppenleyndwdkkkskPIRLRVLNVLRTWVE 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1720405454  320 NHFNDFEGDPAMTRFLEEFENNLEREKMGGHLRLLNIACAAK 361
Cdd:cd06224     80 NYPYDFFDDEELLELLEEFLNRLVQEGALLQELKKLLRKLLK 121

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.)

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454   589 QVLRVFKAD---QQSRYIMISKDTTAKEVVIQAIREFAVTATPEQYSLCEV-SVTPEGVIKQRRLPDQLSKLADRIQLSG 664
Cdd:smart00314    3 FVLRVYVDDlpgGTYKTLRVSSRTTARDVIQQLLEKFHLTDDPEEYVLVEVlPDGKERVLPDDENPLQLQKLWPRRGPNL 82

                    ....*..
gi 1720405454   665 RYYLKNN 671
Cdd:smart00314   83 RFVLRKR 89

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 1720405454   363 KRRLMTLTKpsREAPLPFILLGGSEKGFGIFVDSVDSCSKATEAGLKRGDQILEVNGQNFENIQLSKAMEILRNN-THLS 441
Cdd:smart00228    1 EPRLVELEK--GGGGLGFSLVGGKDEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAgGKVT 78

                    ....
gi 1720405454   442 ITVK 445
Cdd:smart00228   79 LTVL 82

effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO sensor. In all cases binding of the effector leads to conformational changes and the ability to activate transcription. Cyclic nucleotide-binding domain similar to CAP are also present in cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) and vertebrate cyclic nucleotide-gated ion-channels. Cyclic nucleotide-monophosphate binding domain; proteins that bind cyclic nucleotides (cAMP or cGMP) share a structural domain of about 120 residues; the best studied is the prokaryotic catabolite gene activator, CAP, where such a domain is known to be composed of three alpha-helices and a distinctive eight-stranded, antiparallel beta-barrel structure; three conserved glycine residues are thought to be essential for maintenance of the structural integrity of the beta-barrel; CooA is a homodimeric transcription factor that belongs to CAP family; cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) contain two tandem copies of the cyclic nucleotide-binding domain; cAPK's are composed of two different subunits, a catalytic chain and a regulatory chain, which contains both copies of the domain; cGPK's are single chain enzymes that include the two copies of the domain in their N-terminal section; also found in vertebrate cyclic nucleotide-gated ion-channels

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  116 AFANMTMSVRRELCAVMVFAVVErAGTIVLNDGEELDSWSVILNGSVEVTY--PDGKAEILCM---GNSFGVSPTMDKEY 190
Cdd:cd00038      1 LFSGLDDEELEELADALEERRFP-AGEVIIRQGDPADSLYIVLSGSVEVYKldEDGREQIVGFlgpGDLFGELALLGNGP 79

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1720405454  191 MKGVMRTKvDDCQFVCIAQQDYCRILNQVEKNMQKV 226
Cdd:cd00038     80 RSATVRAL-TDSELLVLPRSDFRRLLQEYPELARRL 114

EBNA-3A; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454 1342 VPVTTEEAKPVPMPAHIAVT-PSTTKGlIARKEGRYREPP--PTPP-GYVGIPIADFPeGPCHPARKPPDYNVALQRSRM 1417
Cdd:PHA03379   536 VPTVALERPVCPAPPLIAMQgPGETSG-IVRVRERWRPAPwtPNPPrSPSQMSVRDRL-ARLRAEAQPYQASVEVQPPQL 613

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1720405454 1418 VARPTEAPAPGQTPPAAAASrPGSKPQWHKPSDADPRLAPFQPQGF 1463
Cdd:PHA03379   614 TQVSPQQPMEYPLEPEQQMF-PGSPFSQVADVMRAGGVPAMQPQYF 658

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

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720405454  391 GIFVDSVDSCSKATEAGLKRGDQILEVNGQNFENI-QLSKAM-----------EILRNNTHLSITVK 445
Cdd:COG0265    202 GVLVARVEPGSPAAKAGLRPGDVILAVDGKPVTSArDLQRLLaslkpgdtvtlTVLRGGKELTVTVT 268

Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  694 LLQLSTVEVATQLSMRNFELFRNIEPTEYIDDLFKLKSKT--SCANLKKFEEVINQETFWVASEILRETNQLKRMKIIKH 771
Cdd:cd00155      1 FLSLDPKELAEQLTLLDFELFRKIEPFELLGSLWSKKDKNihLSPNLERFIERFNNLSNWVASEILLCTNPKKRARLLSK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  772 FIKIALHCRECKNFNSMFAIISGLNLAPVARLRTTWEKLPNKYEKLFQDLQDLFDPSRNMAKYRNVLSGQNLQPPVIPLF 851
Cdd:cd00155     81 FIQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEVLSSKLKKLFEELEELVDPSRNFKNYRKLLKSVGPNPPCVPFL 160

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720405454  852 PVIKKDLTFLHEGNDSKVD-GLVNFEKLRMIAKEIRHVGRMASV--NMDPALMFRTRKKKWRSLGSLSQGS 919
Cdd:cd00155    161 GVYLKDLTFLHEGNPDFLEgNLVNFEKRRKIAEILREIRQLQSNsyELNRDEDILAFLWKLLELILNEDEL 231

RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  701 EVATQLSMRNFELFRNIEPTEYIDDLF-KLKSKTSCANLKKFEEVINQETFWVASEILRETNQLKRMKIIKHFIKIALHC 779
Cdd:pfam00617    1 ELARQLTLIEFELFRKIKPRELLGSAWsKKDKKENSPNIEAMIARFNKLSNWVASEILSEEDLKKRAKVIKKFIKIAEHC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  780 RECKNFNSMFAIISGLNLAPVARLRTTWEKLPNKYEKLFQDLQDLFDPSRNMAKYRNVLsgQNLQPPVIPLFPVIKKDLT 859
Cdd:pfam00617   81 RELNNFNSLMAILSGLNSSPISRLKKTWELVSKKYKKTLEELEKLMSPSRNFKNYREAL--SSASPPCIPFLGLYLTDLT 158

                          170       180
                   ....*....|....*....|.
gi 1720405454  860 FLHEGNDSKV-DGLVNFEKLR 879
Cdd:pfam00617  159 FIEEGNPDFLeGGLINFEKRR 179

Ras-associating (RA) domain found in PDZ domain-containing guanine nucleotide exchange factor 1 (PDZ-GEF1) and similar proteins; PDZ-GEF1, also termed Rap guanine nucleotide exchange factor 2, or cyclic nucleotide ras GEF (CNrasGEF), or neural RAP guanine nucleotide exchange protein (nRap GEP), or Ras/Rap1-associating GEF-1 (RA-GEF-1), is a Rap-specific guanine nucleotide exchange factor (GEF) that has a PSD-95/DlgA/ZO-1 (PDZ) domain, a RA domain and a region related to a cyclic nucleotide binding domain (RCBD). The RA domain of PDZ-GEF interacts with Rap1 and also contributes to the membrane localization of PDZ-GEF. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and involve in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Ub is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair in eukaryotes.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  589 QVLRVFKADQQSRYIMISKDTTAKEVVIQAIREFAVTAT--PEQYSLCEVSVTPEGVIKQRRLPDQLSKLADRIQLSGRY 666
Cdd:cd01785      1 QVLKVYRADQSSKYILIHKETTAREVVMLALREFGITDDenSDNYSLCEVTVTPEGLIKQRRLPDQLSNLANRISLNGRY 80

                   ....*
gi 1720405454  667 YLKNN 671
Cdd:cd01785     81 YLKNN 85

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal domain (RasGef_N), also called REM domain (Ras exchanger motif). This domain is common in nucleotide exchange factors for Ras-like small GTPases and is typically found immediately N-terminal to the RasGef (Cdc25-like) domain. REM contacts the GTPase and is assumed to participate in the catalytic activity of the exchange factor. Proteins with the REM domain include Sos1 and Sos2, which relay signals from tyrosine-kinase mediated signalling to Ras, RasGRP1-4, RasGRF1,2, CNrasGEF, and RAP-specific nucleotide exchange factors, to name a few.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  256 TSERLTMHLVEEHSVVDPTFIEDFLLTYRTFLsSPMEVGKKLLEWFNDP----------------SLRDKVTRVVLLWVN 319
Cdd:cd06224      1 TLEALIEHLTSTFDMPDPSFVSTFLLTYRSFT-TPTELLEKLIERYEIAppenleyndwdkkkskPIRLRVLNVLRTWVE 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1720405454  320 NHFNDFEGDPAMTRFLEEFENNLEREKMGGHLRLLNIACAAK 361
Cdd:cd06224     80 NYPYDFFDDEELLELLEEFLNRLVQEGALLQELKKLLRKLLK 121

PDZ domain 2 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of the full-length isoform of whirlin and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 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 whirlin 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720405454  384 GGSEKGFGIFVDSVDSCSKATEAGLKRGDQILEVNGQNFENIQLSKAMEILRNNTHLSITVK 445
Cdd:cd06741     20 GGAEYGLGIYVTGVDPGSVAENAGLKVGDQILEVNGRSFLDITHDEAVKILKSSKHLIMTVK 81

PDZ domain of PDZ domain-containing protein 11, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZD11, and related domains. PDZD11 (also known as ATPase-interacting PDZ protein, plasma membrane calcium ATPase-interacting single-PDZ protein, PMCA-interacting single-PDZ protein, PISP) is involved in the dynamic assembly of apical junctions (AJs). It is recruited by PLEKHA7 to AJs to promote the efficient junctional recruitment and stabilization of nectins, and the efficient early phases of assembly of AJs in epithelial cells. The PDZD11 PDZ domain binds nectin-1 and nectin-3. PDZD11 also binds to a PDZ binding motif located in the C-terminal tail of the human sodium-dependent multivitamin transporter, to the cytoplasmic tail of the Menkes copper ATPase ATP7A, and to the cytoplasmic tail of all plasma membrane Ca2+-ATPase b-splice variants. 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 PDZD11-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 1720405454  365 RLMTLTKPSREaPLPFILLGGSEKGFGIFVDSVDSCSKATEAGLKRGDQILEVNGQNFENIQLSKAMEILRNNTHLSITV 444
Cdd:cd06752      1 RTVVLKRPPGE-QLGFNIRGGKASGLGIFISKVIPDSDAHRLGLKEGDQILSVNGVDFEDIEHSEAVKVLKTAREIQMRV 79

                   .
gi 1720405454  445 K 445
Cdd:cd06752     80 R 80

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

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  368 TLTKPSREaPLPFILLGGSEKGFGIFVDSVDSCSKATEAG-LKRGDQILEVNGQNFENIQLSKAMEILRNNT-HLSITVK 445
Cdd:cd00136      3 TLEKDPGG-GLGFSIRGGKDGGGGIFVSRVEPGGPAARDGrLRVGDRILEVNGVSLEGLTHEEAVELLKSAGgEVTLTVR 81

Cyclic nucleotide-monophosphate binding domain; Catabolite gene activator protein (CAP) is a prokaryotic homologue of eukaryotic cNMP-binding domains, present in ion channels, and cNMP-dependent kinases.

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                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454   117 FANMTMSVRRELCAVMvFAVVERAGTIVLNDGEELDSWSVILNGSVEVTY--PDGKAEILCM---GNSFGVSPTMDkeYM 191
Cdd:smart00100    2 FKNLDAEELRELADAL-EPVRYPAGEVIIRQGDVGDSFYIIVSGEVEVYKvlEDGEEQIVGTlgpGDFFGELALLT--NS 78

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|.
gi 1720405454   192 KGVMRTKVDDCQFVCIAQQDYCRILNQVEKNMQKVEEEGEI 232
Cdd:smart00100   79 RRAASAAAVALELATLLRIDFRDFLQLLPELPQLLLELLLE 119

PDZ domain 1 of the full-length isoform of whirlin and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of the full-length isoform of whirlin and related domains. Whirlin is an essential protein for developmental pathways in photoreceptor cells of the retina and hair cells of the inner ear. The full-length whirlin isoform has two harmonin N-like domains, three PDZ domains, a proline-rich region, and a PDZ-binding motif. Whirlin isoforms may form different complexes at the periciliary membrane complex (PMC) in photoreceptors, and the stereociliary tip and base in inner ear hair cells. It interacts with ADGRV1 and usherin at the PMC; with SANS and RpgrORF15 at the connecting cilium in photoreceptors; with EPS8, MYO15A, p55, and CASK proteins at the stereociliary tip of inner ear hair cells; and with ADGRV1, usherin, and PDZD7 at the stereociliary base in inner ear hair cells. Mutations in the gene encoding whirlin (WHRN; also known as USH2D and DFNB31), have been found to cause either USH2 subtype (USH2D) or autosomal recessive non-syndromic deafness type 31 (DFNB31). Whirlin is the key protein in the USH2 complex (whirlin, usherin and GPR98) which recruits other USH2 causative proteins at the periciliary membrane in photoreceptors and the ankle link of the stereocilia in hair cells. Whirlin's interaction with espin, another stereociliary protein, may be important for the architecture of the USH2 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 whirlin family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  364 RRLMTLTKPSREAPLPFILLGGSEKGFGIFVDSVDSCSKATEAGLKRGDQILEVNGQNFENIQLSKAMEILRNNTHLSIT 443
Cdd:cd06740      1 VRQVTLKRSKSHEGLGFSIRGGAEHGVGIYVSLVEPGSLAEKEGLRVGDQILRVNDVSFEKVTHAEAVKILRVSKKLVLS 80

                   ..
gi 1720405454  444 VK 445
Cdd:cd06740     81 VR 82

PDZ domain 2 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family 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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720405454  381 ILLGGSEKGfGIFVDSVDSCSKATEAGLKRGDQILEVNGQNFENIQLSKAMEILRNNTHLSITVK 445
Cdd:cd06738     19 ISSGPTQKP-GIFISNVKPGSLAEEVGLEVGDQIVEVNGTSFTNVDHKEAVMALKSSRHLTITVR 82

effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO sensor. In all cases binding of the effector leads to conformational changes and the ability to activate transcription. Cyclic nucleotide-binding domain similar to CAP are also present in cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) and vertebrate cyclic nucleotide-gated ion-channels. Cyclic nucleotide-monophosphate binding domain; proteins that bind cyclic nucleotides (cAMP or cGMP) share a structural domain of about 120 residues; the best studied is the prokaryotic catabolite gene activator, CAP, where such a domain is known to be composed of three alpha-helices and a distinctive eight-stranded, antiparallel beta-barrel structure; three conserved glycine residues are thought to be essential for maintenance of the structural integrity of the beta-barrel; CooA is a homodimeric transcription factor that belongs to CAP family; cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) contain two tandem copies of the cyclic nucleotide-binding domain; cAPK's are composed of two different subunits, a catalytic chain and a regulatory chain, which contains both copies of the domain; cGPK's are single chain enzymes that include the two copies of the domain in their N-terminal section; also found in vertebrate cyclic nucleotide-gated ion-channels

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  116 AFANMTMSVRRELCAVMVFAVVErAGTIVLNDGEELDSWSVILNGSVEVTY--PDGKAEILCM---GNSFGVSPTMDKEY 190
Cdd:cd00038      1 LFSGLDDEELEELADALEERRFP-AGEVIIRQGDPADSLYIVLSGSVEVYKldEDGREQIVGFlgpGDLFGELALLGNGP 79

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1720405454  191 MKGVMRTKvDDCQFVCIAQQDYCRILNQVEKNMQKV 226
Cdd:cd00038     80 RSATVRAL-TDSELLVLPRSDFRRLLQEYPELARRL 114

PDZ domain 1 of harmonin isoforms a, b, and c, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of harmonin isoforms a, b, and c, and related domains. Harmonin (also known as Usher Type 1C, PDZ-73 and AIE-75) is a key organizer of the Usher (USH) protein interactome. USH syndrome is the leading cause of hereditary sensory deaf-blindness in humans; three clinically distinct types of USH have been identified, type 1 to 3. The gene encoding harmonin (USH1C) is the causative gene for the USH type 1C phenotype. There are at least 10 alternatively spliced isoforms of harmonin, which are divided into three subclasses (a, b, and c). All isoforms contain the first two PDZ domains and the first coiled-coil domain. The a and b isoforms all have a third PDZ domain. The different PDZ domains are responsible for interactions with all known Usher syndrome type 1 proteins, and most Usher syndrome type 2 proteins. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This harmonin family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  363 KRRLMTLTKPSREaPLPFILLGGSEKGFGIFVDSVDSCSKATEAGLKRGDQILEVNGQNFENIQLSKAMEILRNNTHLSI 442
Cdd:cd06737      1 KLRLVRLDRRGPE-SLGFSVRGGLEHGCGLFVSHVSPGSQADNKGLRVGDEIVRINGYSISQCTHEEVINLIKTKKTVSL 79

                   ....
gi 1720405454  443 TVKT 446
Cdd:cd06737     80 KVRH 83

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.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720405454  367 MTLTKPSREApLPFILLGGsEKGFGIFVDSVDSCSKATEAG-LKRGDQILEVNGQNFENIQLSKAMEILR 435
Cdd:cd23060      2 IELEKPANGG-LGFSLVGG-EGGSGIFVKSISPGGVADRDGrLQVGDRLLQVNGESVIGLSHSKAVNILR 69

PDZ domain of synaptopodin 2 (SYNPO2), synaptopodin 2-like protein (SYNPO2L), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SYNPO2, SYNPO2L, and related domains. SYNPO2 (also known as genethonin-2, myopodin) is a cytoskeleton adaptor protein. It participates in chaperone-assisted selective autophagy (CASA), a mechanism for the disposal of misfolded and damaged proteins and provides a link between the CASA chaperone complex and a membrane-tethering and fusion machinery that generates autophagosome membranes. The SYNPO2 PPxY motif binds CASA cochaperone BCL2-associated athanogene 3 (BAG3) and the SYNPO2 PDZ domain binds vacuolar protein sorting 18 homolog (VPS18). There are three isoforms of SYNPO2, which possess an amino-terminal PDZ domain (SYNPO2a, b, c); the short isoform SYNPO2d, lacks the PDZ domain. 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 SYNPO2-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 1720405454  376 APLPFILLGGSEKGFGIFVDSVDSCSKATEAGLKRGDQILEVNGQNFENIQLSKAMEILRNNTH-LSITVK 445
Cdd:cd10820      8 APWGFRLQGGSEQKKPLQVAKIRKKSKAALAGLCEGDELLSINGKPCADLSHSEAMDLIDSSGDtLQLLIK 78

PDZ domain 1 of protein tyrosine phosphatase non-receptor type 13 (PTPN13),FERM and PDZ domain-containing protein 2 (FRMPD2), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of PTPN13 [also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1)], FRMPD2 (also known as PDZ domain-containing protein 4; PDZ domain-containing protein 5C), and related domains. PTPN13 regulates negative apoptotic signaling and mediates phosphoinositide 3-kinase (PI3K) signaling. PTPN13 has five PDZ domains. Proteins known to interact with PTPN13 PDZ domains include: PLEKHA1 and PLEKHA2 via PTPN13-PDZ domain 1, Fas receptor and thyroid receptor-interacting protein 6 via PTPN13-PDZ domain 2, nerve growth factor receptor and protein kinase N2 via PTPN13-PDZ domain 3, PDZ and LIM domain 4 (PDLIM4) via PTPN13-PDZ domains 2 and 4, and brain calpain-2 via PTPN13-PDZ domains 3, 4 and 5. Calpain-2-mediated PTPN13 fragments may be involved in abnormal tau aggregation and increased risk for Alzheimer's disease. FRMPD2 is localized in the basolateral membranes of polarized epithelial cells and is associated with tight junction formation and immune response; it contains 3 PDZ domains. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PTPN13 family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720405454  366 LMTLTKPSREApLPFILLGGSEKG---FGIFVDSVDSCSKATEAG-LKRGDQILEVNGQNFENIQLSKAMEILRNNT 438
Cdd:cd06694      4 IVTLKKDPQKG-LGFTIVGGENSGsldLGIFVKSIIPGGPADKDGrIKPGDRIIAINGQSLEGKTHHAAVEIIQNAP 79

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 1720405454  365 RLMTLTKPsrEAPLPFILLGGSEKGFGIFVDSVDSCSKA-TEAGLKRGDQILEVNGQNFENIQLSKAMEILRN 436
Cdd:cd06796      3 RVVELPKT--EEGLGFNVMGGKEQNSPIYISRIIPGGVAdRHGGLKRGDQLLSVNGVSVEGEHHEKAVELLKA 73

PDZ domain 1 of syntenin-1, syntenin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of syntenin-1, syntenin-2, and related domains. Syntenins are implicated in various cellular processes such as trafficking, signaling, and cancer metastasis. They bind to signaling and adhesion molecules, such as syndecans, neurexins, ephrin B, and phospholipid PIP2. Through its tandem PDZ domains (PDZ1 and PDZ2), syntenin links syndecans to other cell surface receptors and kinases, such as E-cadherin and ephrin-B, establishing signaling crosstalk. During syndecan binding, syntenin PDZ2 serves as a high-affinity domain, and PDZ1, also necessary for binding, acts as a complementary, low-affinity domain; this is also the case for syntenin binding to proto-oncogene c-Src. The syntenin PDZ domain-PIP2 interaction controls Arf6-mediated syndecan recycling through endosomal compartments; both PDZ1 and PDZ2 interact with PIP2. Different binding partners and downstream regulators of syntenin1 PDZ domains, such as to proto-oncogene c-Src, mitogen-activated protein kinase (MAPK), and focal adhesion kinase (FAK), have been identified that promote the progression and invasion of a variety of cancers, such as melanoma, glioblastoma multiforme and breast cancer. 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 syntenin-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
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1720405454  391 GIFVDSVDSCSKATEAGLKRGDQILEVNGQNFENIQLSKAMEILRNNTHLSITV 444
Cdd:cd06721     23 GVFVQLVQANSPAALAGLRFGDQILQINGENVAGWSSDKAHKVLKKASPERITL 76