PDZ domain of Rap guanine nucleotide exchange factor 2 and Rap guanine nucleotide exchange factor 6, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Rap guanine nucleotide exchange factor 2 (RapGEF2, also named RA-GEF-1, PDZ-GEF1, CNrasGEF and nRapGEP) and Rap guanine nucleotide exchange factor 6 (RapGEF6, also named RA-GEF-2 and PDZ-GEF2). RapGEF2 and RapGEF6 constitute a subfamily of guanine nucleotide exchange factors (GEFs) for RAP small GTPases that is characterized by the possession of the PDZ and Ras/Rap-associating domains. They activate Rap small GTPases, by catalyzing the release of GDP from the inactive GDP-bound forms, thereby accelerating GTP loading to yield the active GTP-bound forms. The PDZ domain of RapGEF6 (also known as PDZ-GEF2) binds junctional adhesion molecule A (JAM-A). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RapGEF2 and RapGEF6 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354  529 RQVVLQKASRESPLHFCLTGGSEKGFGVFVEEVESGSKAADAGLKRGDQVMEVNGQNFENITLAKALEILRNNTHLALTV 608
Cdd:cd06755     1 RTVTLTRPSRESPLHFSLLGGSEKGFGIFVSKVEKGSKAAEAGLKRGDQILEVNGQNFENITLKKALEILRNNTHLSITV 80

                  ...
gi 568972354  609 KTN 611
Cdd:cd06755    81 KTN 83

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354    412 KGHIVIKATPERLIMHLIEEHSIVDPTYIEDFLLTYRTFLETPLDVGIKLLEWFKID------------NLRDKVTRIVL 479
Cdd:smart00229    1 DGGLIKGGTLEALIEHLTEAFDKADPSFVETFLLTYRSFITTQELLQLLLYRYNAIPpeswveekvnprRVKNRVLNILR 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*..
gi 568972354    480 LWVNNHFNDFEGDPAMTQFLEEFERNLEDTKMNG-HLRLLNIACAAK 525
Cdd:smart00229   81 TWVENYWEDFEDDPKLISFLLEFLELVDDEKYPGlVTSLLNLLRRLS 127

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
                  ....*....|....*....|....*....|....*....|....*.
gi 568972354   37 ILSNLREHQLRLMSTRARYERYSGNQMLFCSETIARCWYILLSGSV 82
Cdd:cd00038     1 LFSGLDDEELEELADALEERRFPAGEVIIRQGDPADSLYIVLSGSV 46

Guanine nucleotide exchange factor for Ras-like small GTPases;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354    857 LQLSTIEVATQLSMRDFDLFRNIEPTEYIDDLFKLDSKTGNTH--LKQFEDIVNQETFWVASEILSESNQLKRMKIIKHF 934
Cdd:smart00147    2 LLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPSPlnLEAFIRRFNEVSNWVATEILKQTTPKDRAELLSKF 81

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354    935 IKIALHCRECKNFNSMFAIISGLNLAPVARLRGTWEKLPSKYEKHLQDLQDLFDPSRNMAKYRNILSSQSmQPPIIPLFP 1014
Cdd:smart00147   82 IQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELLSPERNYKNYREALSSCN-LPPCIPFLG 160

                           170       180       190       200       210       220       230
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568972354   1015 VVKKDMTFLHEGNDSKV-DGLVNFEKLRMIAKEIRHIIRMTSANMDPAMMFRQRKKRWRSLGSLSQGSTNSNMLDVQ 1090
Cdd:smart00147  161 VLLKDLTFIDEGNPDFLeNGLVNFEKRRQIAEILREIRQLQSQPYNLRPNRSDIQSLLQQLLDHLDEEEELYQLSLK 237

PDZ domain of Rap guanine nucleotide exchange factor 2 and Rap guanine nucleotide exchange factor 6, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Rap guanine nucleotide exchange factor 2 (RapGEF2, also named RA-GEF-1, PDZ-GEF1, CNrasGEF and nRapGEP) and Rap guanine nucleotide exchange factor 6 (RapGEF6, also named RA-GEF-2 and PDZ-GEF2). RapGEF2 and RapGEF6 constitute a subfamily of guanine nucleotide exchange factors (GEFs) for RAP small GTPases that is characterized by the possession of the PDZ and Ras/Rap-associating domains. They activate Rap small GTPases, by catalyzing the release of GDP from the inactive GDP-bound forms, thereby accelerating GTP loading to yield the active GTP-bound forms. The PDZ domain of RapGEF6 (also known as PDZ-GEF2) binds junctional adhesion molecule A (JAM-A). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RapGEF2 and RapGEF6 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354  529 RQVVLQKASRESPLHFCLTGGSEKGFGVFVEEVESGSKAADAGLKRGDQVMEVNGQNFENITLAKALEILRNNTHLALTV 608
Cdd:cd06755     1 RTVTLTRPSRESPLHFSLLGGSEKGFGIFVSKVEKGSKAAEAGLKRGDQILEVNGQNFENITLKKALEILRNNTHLSITV 80

                  ...
gi 568972354  609 KTN 611
Cdd:cd06755    81 KTN 83

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354    412 KGHIVIKATPERLIMHLIEEHSIVDPTYIEDFLLTYRTFLETPLDVGIKLLEWFKID------------NLRDKVTRIVL 479
Cdd:smart00229    1 DGGLIKGGTLEALIEHLTEAFDKADPSFVETFLLTYRSFITTQELLQLLLYRYNAIPpeswveekvnprRVKNRVLNILR 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*..
gi 568972354    480 LWVNNHFNDFEGDPAMTQFLEEFERNLEDTKMNG-HLRLLNIACAAK 525
Cdd:smart00229   81 TWVENYWEDFEDDPKLISFLLEFLELVDDEKYPGlVTSLLNLLRRLS 127

RasGEF N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this motif/domain N-terminal to the RasGef (Cdc25-like) domain.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354   415 IVIKATPERLIMHLIEEHSIVDPTYIEDFLLTYRTFLeTPLDVGIKLLEWFKI-----------------DNLRDKVTRI 477
Cdd:pfam00618    1 QVKAGTLEKLVEYLTSTRIMLDDSFLSTFLLTYRSFT-TPAELLELLIERYNIpppldlssdsywiskktLPIRIRVLSV 79

                           90       100
                   ....*....|....*....|....*
gi 568972354   478 VLLWVNNHFNDFEGDPAMTQFLEEF 502
Cdd:pfam00618   80 LRHWVENYFSDFNDDPVLLSRLEKF 104

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 568972354  280 AFANMTMSVRRELCSVMVFEVVeQAGAVILEDGQELDSWYVILNGTVEISH--PDGK---IENLFMGNSFGIVPTLDKQH 354
Cdd:cd00038     1 LFSGLDDEELEELADALEERRF-PAGEVIIRQGDPADSLYIVLSGSVEVYKldEDGReqiVGFLGPGDLFGELALLGNGP 79

                          90       100
                  ....*....|....*....|....*.
gi 568972354  355 MHGAVRTKvDDCQFVCIAQQDYWRIL 380
Cdd:cd00038    80 RSATVRAL-TDSELLVLPRSDFRRLL 104

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354   749 PDQVIRVF----KADQQSCYIIISKDTTAKEVVCQAVQEFGLTGASDTYSLCEVSvtpEGVIKQRRLPDQFSKLADRIQL 824
Cdd:pfam00788    1 DDGVLKVYtedgKPGTTYKTILVSSSTTAEEVIEALLEKFGLEDDPRDYVLVEVL---ERGGGERRLPDDECPLQIQLQW 77

                           90
                   ....*....|....*
gi 568972354   825 -----NGRYYLKNNM 834
Cdd:pfam00788   78 prdasDSRFLLRKRD 92

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354   530 QVVLQKASREsPLHFCLTGGSEKGF-GVFVEEVESGSKAADAGLKRGDQVMEVNGQNFENITLAKALEILRN-NTHLALT 607
Cdd:pfam00595    1 QVTLEKDGRG-GLGFSLKGGSDQGDpGIFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKGsGGKVTLT 79

                   ..
gi 568972354   608 VK 609
Cdd:pfam00595   80 IL 81

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568972354  555 GVFVEEVESGSKAADAGLKRGDQVMEVNGQNFENI-TLAKA-----------LEILRNNTHLALTVK 609
Cdd:COG0265   202 GVLVARVEPGSPAAKAGLRPGDVILAVDGKPVTSArDLQRLlaslkpgdtvtLTVLRGGKELTVTVT 268

periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various designated DegP, heat shock protein HtrA, and protease DO. The ortholog in Pseudomonas aeruginosa is designated MucD and is found in an operon that controls mucoid phenotype. This family also includes the DegQ (HhoA) paralog in E. coli which can rescue a DegP mutant, but not the smaller DegS paralog, which cannot. Members of this family are located in the periplasm and have separable functions as both protease and chaperone. Members have a trypsin domain and two copies of a PDZ domain. This protein protects bacteria from thermal and other stresses and may be important for the survival of bacterial pathogens.// The chaperone function is dominant at low temperatures, whereas the proteolytic activity is turned on at elevated temperatures. [Protein fate, Protein folding and stabilization, Protein fate, Degradation of proteins, peptides, and glycopeptides]

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568972354   555 GVFVEEVESGSKAADAGLKRGDQVMEVNGQNFENIT-LAKALEILRNNTHLALTVKTN---IFVF 615
Cdd:TIGR02037  363 GVVVTKVVSGSPAARAGLQPGDVILSVNQQPVSSVAeLRKVLARAKKGGRVALLILRGgatIFVT 427

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
                  ....*....|....*....|....*....|....*....|....*.
gi 568972354   37 ILSNLREHQLRLMSTRARYERYSGNQMLFCSETIARCWYILLSGSV 82
Cdd:cd00038     1 LFSGLDDEELEELADALEERRFPAGEVIIRQGDPADSLYIVLSGSV 46

Guanine nucleotide exchange factor for Ras-like small GTPases;

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354    857 LQLSTIEVATQLSMRDFDLFRNIEPTEYIDDLFKLDSKTGNTH--LKQFEDIVNQETFWVASEILSESNQLKRMKIIKHF 934
Cdd:smart00147    2 LLLDPKELAEQLTLLDFELFRKIDPSELLGSVWGKRSKKSPSPlnLEAFIRRFNEVSNWVATEILKQTTPKDRAELLSKF 81

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354    935 IKIALHCRECKNFNSMFAIISGLNLAPVARLRGTWEKLPSKYEKHLQDLQDLFDPSRNMAKYRNILSSQSmQPPIIPLFP 1014
Cdd:smart00147   82 IQVAKHCRELNNFNSLMAIVSALSSSPISRLKKTWEKLPSKYKKLFEELEELLSPERNYKNYREALSSCN-LPPCIPFLG 160

                           170       180       190       200       210       220       230
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568972354   1015 VVKKDMTFLHEGNDSKV-DGLVNFEKLRMIAKEIRHIIRMTSANMDPAMMFRQRKKRWRSLGSLSQGSTNSNMLDVQ 1090
Cdd:smart00147  161 VLLKDLTFIDEGNPDFLeNGLVNFEKRRQIAEILREIRQLQSQPYNLRPNRSDIQSLLQQLLDHLDEEEELYQLSLK 237

PDZ domain of Rap guanine nucleotide exchange factor 2 and Rap guanine nucleotide exchange factor 6, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Rap guanine nucleotide exchange factor 2 (RapGEF2, also named RA-GEF-1, PDZ-GEF1, CNrasGEF and nRapGEP) and Rap guanine nucleotide exchange factor 6 (RapGEF6, also named RA-GEF-2 and PDZ-GEF2). RapGEF2 and RapGEF6 constitute a subfamily of guanine nucleotide exchange factors (GEFs) for RAP small GTPases that is characterized by the possession of the PDZ and Ras/Rap-associating domains. They activate Rap small GTPases, by catalyzing the release of GDP from the inactive GDP-bound forms, thereby accelerating GTP loading to yield the active GTP-bound forms. The PDZ domain of RapGEF6 (also known as PDZ-GEF2) binds junctional adhesion molecule A (JAM-A). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This RapGEF2 and RapGEF6 family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354  529 RQVVLQKASRESPLHFCLTGGSEKGFGVFVEEVESGSKAADAGLKRGDQVMEVNGQNFENITLAKALEILRNNTHLALTV 608
Cdd:cd06755     1 RTVTLTRPSRESPLHFSLLGGSEKGFGIFVSKVEKGSKAAEAGLKRGDQILEVNGQNFENITLKKALEILRNNTHLSITV 80

                  ...
gi 568972354  609 KTN 611
Cdd:cd06755    81 KTN 83

Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif; A subset of guanine nucleotide exchange factor for Ras-like small GTPases appear to possess this domain N-terminal to the RasGef (Cdc25-like) domain. The recent crystal structureof Sos shows that this domain is alpha-helical and plays a "purely structural role" (Nature 394, 337-343).

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354    412 KGHIVIKATPERLIMHLIEEHSIVDPTYIEDFLLTYRTFLETPLDVGIKLLEWFKID------------NLRDKVTRIVL 479
Cdd:smart00229    1 DGGLIKGGTLEALIEHLTEAFDKADPSFVETFLLTYRSFITTQELLQLLLYRYNAIPpeswveekvnprRVKNRVLNILR 80

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|....*..
gi 568972354    480 LWVNNHFNDFEGDPAMTQFLEEFERNLEDTKMNG-HLRLLNIACAAK 525
Cdd:smart00229   81 TWVENYWEDFEDDPKLISFLLEFLELVDDEKYPGlVTSLLNLLRRLS 127

PDZ domain 2 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the second PDZ domain of the canonical isoform of PDZD7- isoform 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 PDZD7-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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354  529 RQVVLQKASRESPLHFCLTGGSEKGFGVFVEEVESGSKAADAGLKRGDQVMEVNGQNFENITLAKALEILRNNTHLALTV 608
Cdd:cd10834     2 RIVHLYTTSDDYCLGFNIRGGSEYGLGIYVSKVDPGGLAEQNGIKVGDQILAVNGVSFEDITHSKAVEVLKSQTHLMLTI 81

                  .
gi 568972354  609 K 609
Cdd:cd10834    82 K 82

PDZ domain 1 of the canonical isoform 1 of PDZ domain containing 7 (PDZD7), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of the long isoform 1 of PDZD7, and related domains. PDZD7 is critical for the organization of Usher syndrome type 2 (USH2) complex. Usher syndrome is the leading cause of hereditary sensory deaf-blindness in humans; USH2 is the most common sub-type. Formation of the USH2 complex is based upon heterodimerization between PDZD7 and whirlin (another PDZ domain-containing protein) and a subsequent dynamic interplay between USH2 proteins via their multiple PDZ domains. The PDZD7 PDZ2 domain binds GPR98 (also known as VLGR1) and usherin (USH2A). PDZD7 and whirlin form heterodimers through their multiple PDZ domains; whirlin and PDZD7 interact with usherin and GPR98 to form an interdependent ankle link complex. PDZD7 also interacts with myosin VIIa. PDZD7 also forms homodimers through its PDZ2 domain. Various isoforms of PDZD7 produced by alternative splicing have been identified; this subgroup includes the first PDZ domain of the canonical isoform of PDZD7- isoform 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 PDZD7-like family PDZ1 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568972354  537 SRESPLHFCLTGGSEKGFGVFVEEVESGSKAADAGLKRGDQVMEVNGQNFENITLAKALEILRNNTHLALTVK 609
Cdd:cd10833     9 SPDGSLGFSVRGGSEHGLGIFVSKVEEGSAAERAGLCVGDKITEVNGVSLENITMSSAVKVLTGSNRLRMVVR 81

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354  531 VVLQKASREsPLHFCLTGGSEKGFGVFVEEVESGSKAADAG-LKRGDQVMEVNGQNFENITLAKALEILRNNT-HLALTV 608
Cdd:cd00136     2 VTLEKDPGG-GLGFSIRGGKDGGGGIFVSRVEPGGPAARDGrLRVGDRILEVNGVSLEGLTHEEAVELLKSAGgEVTLTV 80

                  .
gi 568972354  609 K 609
Cdd:cd00136    81 R 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 568972354  529 RQVVLQKASREsPLHFCLTGGSEKGFGVFVEEVESGSKAADAGLKRGDQVMEVNGQNFENITLAKALEILRNNTHLALTV 608
Cdd:cd06752     1 RTVVLKRPPGE-QLGFNIRGGKASGLGIFISKVIPDSDAHRLGLKEGDQILSVNGVDFEDIEHSEAVKVLKTAREIQMRV 79

                  .
gi 568972354  609 K 609
Cdd:cd06752    80 R 80

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 568972354  280 AFANMTMSVRRELCSVMVFEVVeQAGAVILEDGQELDSWYVILNGTVEISH--PDGK---IENLFMGNSFGIVPTLDKQH 354
Cdd:cd00038     1 LFSGLDDEELEELADALEERRF-PAGEVIIRQGDPADSLYIVLSGSVEVYKldEDGReqiVGFLGPGDLFGELALLGNGP 79

                          90       100
                  ....*....|....*....|....*.
gi 568972354  355 MHGAVRTKvDDCQFVCIAQQDYWRIL 380
Cdd:cd00038    80 RSATVRAL-TDSELLVLPRSDFRRLL 104

Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354   749 PDQVIRVF----KADQQSCYIIISKDTTAKEVVCQAVQEFGLTGASDTYSLCEVSvtpEGVIKQRRLPDQFSKLADRIQL 824
Cdd:pfam00788    1 DDGVLKVYtedgKPGTTYKTILVSSSTTAEEVIEALLEKFGLEDDPRDYVLVEVL---ERGGGERRLPDDECPLQIQLQW 77

                           90
                   ....*....|....*
gi 568972354   825 -----NGRYYLKNNM 834
Cdd:pfam00788   78 prdasDSRFLLRKRD 92

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354   530 QVVLQKASREsPLHFCLTGGSEKGF-GVFVEEVESGSKAADAGLKRGDQVMEVNGQNFENITLAKALEILRN-NTHLALT 607
Cdd:pfam00595    1 QVTLEKDGRG-GLGFSLKGGSDQGDpGIFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKGsGGKVTLT 79

                   ..
gi 568972354   608 VK 609
Cdd:pfam00595   80 IL 81

PDZ domain 2 of tyrosine kinase PTPN13, FERM and PDZ domain-containing protein 2 (FRMPD2), and similar domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of human PTPN13, and related domains. PTPN13, also known as Fas-associated protein-tyrosine phosphatase 1 (FAP-1), protein-tyrosine phosphatase 1E (PTP-E1), and protein-tyrosine phosphatase (PTPL1), negatively regulates FAS-mediated apoptosis and NGFR-mediated pro-apoptotic signaling, and may also regulate phosphoinositide 3-kinase (PI3K) signaling. It contains 5 PDZ domains; interaction partners of its second PDZ domain (PDZ2) include the Fas receptor (TNFRSF6) and thyroid receptor-interacting protein 6 (TRIP6). The second PDZ (PDZ2) domain, but not PDZ1 or PDZ3, of FRMPD2 binds to GluN2A and GluN2B, two subunits of N-methyl-d-aspartic acid (NMDA) receptors. Other binding partners of the FRMPDZ2 PDZ2 domain include NOD2, and catenin family members, delta catenin (CTNND2), armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) and p0071 (also known as plakophilin 4; PKP4). 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 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354  530 QVVLQKasRESPLHFCLTGGSEKGF---GVFVEEVESGSKAA-DAGLKRGDQVMEVNGQNFENITLAKALEILRNNTHLA 605
Cdd:cd06792     4 EVELSK--KDGSLGISVTGGINTSVrhgGIYVKSLVPGGAAEqDGRIQKGDRLLEVNGVSLEGVTHKQAVECLKNAGQVV 81

                  ...
gi 568972354  606 LTV 608
Cdd:cd06792    82 TLV 84

PDZ domain of Drosophila melanogaster PDZ and LIM domain protein Zasp52 (also known as Zasp), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Drosophila melanogaster Zasp52 and related domains. Drosophila melanogaster Zasp52 (also known as Z band alternatively spliced PDZ-motif protein or Zasp) colocalizes with integrins at myotendinous junctions and with alpha-actinin at Z-disks and is required for muscle attachment as well as Z-disk assembly and maintenance. The Zasp52 actin-binding site includes the extended PDZ domain and the ZM region. The Zasp52-PDZ domain is required for myofibril assembly. 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 Zasp52-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 568972354  530 QVVLQKASRESPLHFCLTGGSEKGFGVFVEEVESGSKAADAGLKRGDQVMEVNGQNFENITLAKAL-EILRNNTHLALTV 608
Cdd:cd23068     1 NIRLRRDDSNTPWGFRLQGGADFGQPLSIQKVNPGSPADKAGLRRGDVILRINGTDTSNLTHKQAQdLIKRAGNDLQLTV 80

                  .
gi 568972354  609 K 609
Cdd:cd23068    81 Q 81

Ras-associating (RA) domain, structurally similar to a beta-grasp ubiquitin-like fold; RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in various functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. The 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. RA-containing proteins include RalGDS, AF6, RIN, RASSF1, SNX27, CYR1, STE50, and phospholipase C epsilon.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354  752 VIRVFKAD----QQSCYIIISKDTTAKEVVCQAVQEFGLTGASDTYSLCEVSvtpEGVIKQRRLPDQFSKLADRI----- 822
Cdd:cd17043     1 VLKVYDDDlapgSAYKSILVSSTTTAREVVQLLLEKYGLEEDPEDYSLYEVS---EKQETERVLHDDECPLLIQLewgpq 77

                          90
                  ....*....|
gi 568972354  823 QLNGRYYLKN 832
Cdd:cd17043    78 GTEFRFVLKR 87

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 568972354  529 RQVVLQKasRESPLHFCLTGGsEKGFGVFVEEVESGSKAADAG-LKRGDQVMEVNGQNFENITLAKALEILRN 600
Cdd:cd06795     3 RKIVLHK--GSTGLGFNIVGG-EDGEGIFISFILAGGPADLSGeLRRGDQILSVNGVDLRNATHEQAAAALKN 72

PDZ domain 13 of multi-PDZ-domain protein 1 (MUPP1) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 13 of MUPP1. MUPP1 and PATJ serve as scaffolding proteins linking different proteins and protein complexes involved in the organization of tight junctions and epithelial polarity. MUPP1 contains an L27 (Lin-2 and Lin-7 binding) domain and 13 PDZ domains. PATJ (also known as INAD-like) contains an L27 domain and ten PDZ domains. PATJ lacks 3 PDZ domains seen in MUPP1: PDZ6, PDZ9, and PDZ13. This MuPP1-like PDZ13 domain is therefore absent from PATJ. MUPP1 and PATJ share several binding partners, including junctional adhesion molecules (JAM), zonula occludens (ZO)-3, Pals1 (protein associated with Lin-7), Par (partitioning defective)-6 proteins, and nectins (adherence junction adhesion molecules). PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This MUPP1-like family PDZ13 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568972354  530 QVVLQKASreSPLHFCLTGG---SEKGFGVFVEEV-ESGSKAADAGLKRGDQVMEVNGQNFENITLAKALEILRN-NTHL 604
Cdd:cd06676     1 TITLERGS--DGLGFSIVGGfgsPHGDLPIYVKTVfEKGAAAEDGRLKRGDQILAVNGESLEGVTHEEAVNILKKtKGTV 78