Insulin-like growth factor binding protein;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 229093139   37 CPEHCDPTRCAPPPTDCEGGRVRDACGCCEVCGALEGAACGLQEGPCGEGLQC 89
Cdd:pfam00219   1 CPPPCDPERCPPPPPGCPAGVVLDGCGCCKVCARQEGEPCGVYTPPCGKGLRC 53

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139  172 IADVVEKIAPAVVHIELYRK------------------------LPFSKREVPVAS-GSGFIVSEDGLIVTNAHVVTNKN 226
Cdd:TIGR02037   3 FAPLVEKVAPAVVNISVEGTvkrrnrppalppffrqffgddmpdFPRQQREQKVRGlGSGVIISADGYVLTNNHVVDGAD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139  227 RVKVELKNGATYEAKIKDVDEKADIALIKIDHQGKLPVLLLGRSSELRPGEFVVAIGSPFSLQNTVTTGIVSTTQRGGKE 306
Cdd:TIGR02037  83 EITVTLSDGREFKAKLVGKDPRTDIAVLKIDAKKNLPVIKLGDSDKLRVGDWVLAIGNPFGLGQTVTSGIVSALGRSGLG 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139  307 LGLRNsdmDYIQTDAIINYGNSGGPLVNLDGEVIGINTLKVT-----AGISFAIPSDKIKKFLTeshdrQAKGKAVTKKK 381
Cdd:TIGR02037 163 IGDYE---NFIQTDAAINPGNSGGPLVNLRGEVIGINTAILSpsggnVGIGFAIPSNMAKNVVD-----QLIEGGKVKRG 234

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139  382 YIGIRMMSLTSSKAKELKDRHRdfpdvlSGAYIIEVIPDTPAEAGGLKENDVIISINGQSVVTANDVSDVI---KKENTL 458
Cdd:TIGR02037 235 WLGVTIQEVTSDLAKSLGLEKQ------RGALVAQVLPGSPAEKAGLKAGDVITSVNGKPISSFADLRRAIgtlKPGKKV 308

                         330
                  ....*....|....*.
gi 229093139  459 NMVVRRGNEDIVITVI 474
Cdd:TIGR02037 309 TLGILRKGKEKTITVT 324

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139 380 KKYIGIRMMSLTSSKAKELKDRHRDFPDVLSGAYIIEVIPDTPAEAGGLKENDVIISINGQSVVTANDVSDVIKKENTLN 459
Cdd:cd06785    1 KRYIGIRMLTLTPSLLEELKQRNPDFPDVSSGVYVHKVIPGSPAQRAGLKDGDVIISINGKPVKSSSDVYEAVKSGSSLL 80

                         90
                 ....*....|....*...
gi 229093139 460 MVVRRGNEDIVITVIPEE 477
Cdd:cd06785   81 VVVRRGNEDLLLTVTPEE 98

Insulin-like growth factor binding protein;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 229093139   37 CPEHCDPTRCAPPPTDCEGGRVRDACGCCEVCGALEGAACGLQEGPCGEGLQC 89
Cdd:pfam00219   1 CPPPCDPERCPPPPPGCPAGVVLDGCGCCKVCARQEGEPCGVYTPPCGKGLRC 53

MarP family serine protease; The founding member of this family of membrane-spanning serine proteases, which is restricted to Actinobacteria, is the acid resistance periplasmic serine protease MarP of Mycobacterium tuberculosis. Recent work shows that MarP is required to cleave and activate the peptidoglycan hydrolase RipA, and loss of RipA activity creates a defect in progeny separation during cell division. Therefore, the requirement for MarP in order to survive acidic conditions may be a consequence of peptidoglycan hydrolysis requirements, explaining why MarP family members are distributed more broadly in the Actinobacteria than the subset of species capable of surviving intracellularly as pathogens.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139 173 ADVVEKIAPAVVHIelyrklpfskreVPVA-------SGSGFIVSeDGLIVTNAHVVTNKNRVKVELKNGATYEAKIKDV 245
Cdd:NF033740 187 SPAVRRARPSVVKV------------RGTApscgralEGSGFVVA-PDRVMTNAHVVAGTDEVTVETVGGGTLDARVVYY 253

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139 246 DEKADIALIKIDHqGKLPVLLLGrSSELRPGEFVVAIGSPFSLQNTVTTGIV--STTQRGGKELGLRNSDMDYIQTDAII 323
Cdd:NF033740 254 DPDRDIAVLAVPG-LGLPPLPFA-DEPAETGDDAIVLGYPEGGPFTATPARVreRIALSGPDIYGSGTVTREVYTLRGTV 331

                        170
                 ....*....|....*....
gi 229093139 324 NYGNSGGPLVNLDGEVIGI 342
Cdd:NF033740 332 RPGNSGGPLLDPDGRVLGV 350

Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and follistatin-like domains.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 229093139   115 SEPVCGSDAKTYTNLCQLRAASRRSeklrQPPVIVLQRGAC 155
Cdd:smart00280  10 YDPVCGSDGVTYSNECHLCKAACES----GKSIEVKHDGPC 46

Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 229093139  110 CVC--ASSEPVCGSDAKTYTNLCQLRAASRRSEKLRQPPViVLQRGAC 155
Cdd:pfam07648   4 CQCpkTEYEPVCGSDGVTYPSPCALCAAGCKLGKEVKEEK-VKYDGSC 50

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139  172 IADVVEKIAPAVVHIELYRK------------------------LPFSKREVPVAS-GSGFIVSEDGLIVTNAHVVTNKN 226
Cdd:TIGR02037   3 FAPLVEKVAPAVVNISVEGTvkrrnrppalppffrqffgddmpdFPRQQREQKVRGlGSGVIISADGYVLTNNHVVDGAD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139  227 RVKVELKNGATYEAKIKDVDEKADIALIKIDHQGKLPVLLLGRSSELRPGEFVVAIGSPFSLQNTVTTGIVSTTQRGGKE 306
Cdd:TIGR02037  83 EITVTLSDGREFKAKLVGKDPRTDIAVLKIDAKKNLPVIKLGDSDKLRVGDWVLAIGNPFGLGQTVTSGIVSALGRSGLG 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139  307 LGLRNsdmDYIQTDAIINYGNSGGPLVNLDGEVIGINTLKVT-----AGISFAIPSDKIKKFLTeshdrQAKGKAVTKKK 381
Cdd:TIGR02037 163 IGDYE---NFIQTDAAINPGNSGGPLVNLRGEVIGINTAILSpsggnVGIGFAIPSNMAKNVVD-----QLIEGGKVKRG 234

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139  382 YIGIRMMSLTSSKAKELKDRHRdfpdvlSGAYIIEVIPDTPAEAGGLKENDVIISINGQSVVTANDVSDVI---KKENTL 458
Cdd:TIGR02037 235 WLGVTIQEVTSDLAKSLGLEKQ------RGALVAQVLPGSPAEKAGLKAGDVITSVNGKPISSFADLRRAIgtlKPGKKV 308

                         330
                  ....*....|....*.
gi 229093139  459 NMVVRRGNEDIVITVI 474
Cdd:TIGR02037 309 TLGILRKGKEKTITVT 324

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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139 380 KKYIGIRMMSLTSSKAKELKDRHRDFPDVLSGAYIIEVIPDTPAEAGGLKENDVIISINGQSVVTANDVSDVIKKENTLN 459
Cdd:cd06785    1 KRYIGIRMLTLTPSLLEELKQRNPDFPDVSSGVYVHKVIPGSPAQRAGLKDGDVIISINGKPVKSSSDVYEAVKSGSSLL 80

                         90
                 ....*....|....*...
gi 229093139 460 MVVRRGNEDIVITVIPEE 477
Cdd:cd06785   81 VVVRRGNEDLLLTVTPEE 98

serine endoprotease DegS;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139 176 VEKIAPAVVHIELYRKLPFSKREVPVAS-GSGFIVSEDGLIVTNAHVVTNKNRVKVELKNGATYEAKIKDVDEKADIALI 254
Cdd:PRK10898  51 VRRAAPAVVNVYNRSLNSTSHNQLEIRTlGSGVIMDQRGYILTNKHVINDADQIIVALQDGRVFEALLVGSDSLTDLAVL 130

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139 255 KIDHQGkLPVLLLGRSSELRPGEFVVAIGSPFSLQNTVTTGIVSTTQRggkeLGLRNSD-MDYIQTDAIINYGNSGGPLV 333
Cdd:PRK10898 131 KINATN-LPVIPINPKRVPHIGDVVLAIGNPYNLGQTITQGIISATGR----IGLSPTGrQNFLQTDASINHGNSGGALV 205

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139 334 NLDGEVIGINTL--------KVTAGISFAIPSD---KIKKFLTEShdrqakGKAVtkKKYIGIRmmsltsskAKELKDRH 402
Cdd:PRK10898 206 NSLGELMGINTLsfdksndgETPEGIGFAIPTQlatKIMDKLIRD------GRVI--RGYIGIG--------GREIAPLH 269

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139 403 --RDFPDVLSGAYIIEVIPDTPAEAGGLKENDVIISINGQSVVTANDVSDV---IKKENTLNMVVRRGNEDIVITVIPEE 477
Cdd:PRK10898 270 aqGGGIDQLQGIVVNEVSPDGPAAKAGIQVNDLIISVNNKPAISALETMDQvaeIRPGSVIPVVVMRDDKQLTLQVTIQE 349

                 ...
gi 229093139 478 IDP 480
Cdd:PRK10898 350 YPA 352

Insulin-like growth factor binding protein;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 229093139   37 CPEHCDPTRCAPPPTDCEGGRVRDACGCCEVCGALEGAACGLQEGPCGEGLQC 89
Cdd:pfam00219   1 CPPPCDPERCPPPPPGCPAGVVLDGCGCCKVCARQEGEPCGVYTPPCGKGLRC 53

permuted PDZ domain of Deg/high-temperature requirement factor A (HtrA) family of housekeeping serine proteases and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Deg/HtrA-type serine proteases that participate in folding and degradation of aberrant proteins, and in processing and maturation of native proteins. Typically, these proteases have an N-terminal serine protease domain and at least one C-terminal PDZ domain that recognizes substrates, and in some cases activates the protease function. An exception is yeast Nma11p which has two protease domains and four PDZ domains; its N-terminal half is comprised of a protease domain, followed by two PDZ domains, and its C-terminal half has a similar domain arrangement. HtrA-type proteases include the human HtrA1-4 and MBTPS2, tricorn protease, DegS, DegP and C-terminal processing peptidase, cyanobacterial serine proteases Hhoa, HhoB, and HtrA, and yeast Nma11p. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-termini of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains and 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 Deg/HtrA family PDZ domain is a circularly permuted PDZ domain which places beta-strand A at 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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139 382 YIGIRMMSLTSSKAKELkdrhrdFPDVLSGAYIIEVIPDTPAEAGGLKENDVIISINGQSVVTANDVSDVIKKE---NTL 458
Cdd:cd06779    3 YLGIEMENISPLLAKEL------GLPVNRGVLVAEVIPGSPAAKAGLKEGDVILSVNGKPVTSFNDLRAALDTKkpgDSL 76

                         90
                 ....*....|....*
gi 229093139 459 NMVVRRGNEDIVITV 473
Cdd:cd06779   77 NLTILRDGKTLTVTV 91

circularly permuted PDZ domain of Synechocystis sp. PCC 6803 putative serine proteases HhoA, HhoB, and HtrA and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of the cyanobacterial Synechocystis sp. PCC 6803 putative serine proteases HhoA, HhoB and HtrA, and related domains. These three proteases are functionally overlapping, and are involved in a number of key physiological responses, ranging from protection against light and heat stresses to phototaxis. HhoA assembles into trimers, mediated by its protease domain and further into a hexamer by a novel interaction between the PDZ domains of opposing trimers. 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 and 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 HhoA-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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139 382 YIGIRMMSLTSSKAKELKdRHRDFPDVL---SGAYIIEVIPDTPAEAGGLKENDVIISINGQSVVTANDVSDVIKKE--- 455
Cdd:cd10838    3 YLGIQMTTLTPELAQQNN-RNPNSPVRIpevDGVLIMQVLPNSPAARAGLRRGDVIQAVDGQPVTTADDVQRIVEQAgvg 81

                         90       100
                 ....*....|....*....|..
gi 229093139 456 NTLNMVVRRGNEDIVITVIPEE 477
Cdd:cd10838   82 EELELTVLRGDRRQTLAVKPGD 103

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 229093139 408 VLSGAYIIEVIPDTPAEAGGLKENDVIISINGQSVVTANDVSDVIKK--ENTLNMVVRRGNEDIVITVIPEEIDP 480
Cdd:COG0750  126 VLTPPVVGEVVPGSPAAKAGLQPGDRIVAINGQPVTSWDDLVDIIRAspGKPLTLTVERDGEELTLTVTPRLVEE 200

circularly permuted PDZ domains of Escherichia coli Regulator of sigma-E protease (RseP) and related domains; Permuted PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of ResP (also known as Site-2 protease RseP, and YaeL), and related domains. RseP is involved in the regulation of an extracytoplasmic stress response through the cleavage of membrane-spanning anti-stress-response transcription factor (anti-sigmE) protein RseA; it cleaves the peptide bond between the critical alanine and cysteine in the transmembrane region of RseA, releasing the cytoplasmic domain of RseA with its associated sigmaE. RseP contains two tandem-arranged periplasmic PDZ domains (PDZ-N/PDZ1 and PDZ-C/PDZ2) which act to negatively regulate protease action on intact RseA; they serve as a size-exclusion filter which prevents the access of an intact RseA into the active site of RseP. PDZ domains usually bind in 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 and 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 beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F. This RseP family PDZ domain is a circularly permuted PDZ domain which places both beta-strands A and B at the C-terminus. Another permutation exists in the PDZ superfamily which places beta-strand A at the C-terminus.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 229093139 416 EVIPDTPAEAGGLKENDVIISINGQSVVTANDVSDVIK--KENTLNMVVRRGNEDIVITVIPEEID 479
Cdd:cd23081    5 EVVANSPAAEAGLKPGDRILKIDGQKVRTWEDIVRIVRenPGKPLTLKIERDGKILTVTVTPELVE 70

circularly permuted first PDZ domain (PDZ1) of Escherichia coli periplasmic serine endoprotease DegP and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 1 of Escherichia coli DegP (also known as heat shock protein DegP and Protease Do) and related domains. DegP belongs to the HtrA family of housekeeping proteases. It acts as a protease, degrading transiently denatured and unfolded or misfolded proteins which accumulate in the periplasm following heat shock or other stress conditions, and as a molecular chaperone at low temperatures. DegP has two PDZ domains in addition to the protease domain; its PDZ1 domain is responsible for identifying the distinct substrate sequences that affect degradation (degron) of the substrate sequence, and its PDZ2 domain is responsible for combining with other DegP monomers to form a stable oligomer structure. 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 and 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 DegP family PDZ domain 1 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        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139 382 YIGIRMMSLTSSKAKELKdrhrdfPDVLSGAYIIEVIPDTPAEAGGLKENDVIISINGQSVVTANDVSDVI---KKENTL 458
Cdd:cd10839    3 WLGVQIQELTPDLAESFG------LKEPKGALVAQVLPDSPAAKAGLKAGDVILSLNGKPITSSADLRNRVattKPGTKV 76

                         90
                 ....*....|....*
gi 229093139 459 NMVVRRGNEDIVITV 473
Cdd:cd10839   77 ELKILRDGKEKTLTV 91

circularly permuted second PDZ domain (PDZ2) of Escherichia coli periplasmic serine endoprotease DegP and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of Escherichia coli DegP (also known as heat shock protein DegP and Protease Do), and related domains. DegP belongs to the HtrA family of housekeeping proteases. It acts as a protease, degrading transiently denatured and unfolded or misfolded proteins which accumulate in the periplasm following heat shock or other stress conditions, and as a molecular chaperone at low temperatures. DegP has two PDZ domains in addition to the protease domain; its PDZ1 domain is responsible for the identifying the distinct substrate sequences that affect degradation (degron) of the substrate sequence, and its PDZ2 domain is responsible for the combining with other DegP monomers to form a stable oligomer structure. 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 and 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 DegP family PDZ domain 2 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 229093139 410 SGAYIIEVIPDTPAEAGGLKENDVIISINGQSVVTANDVSDVIK-KENTLNMVVRRGNEDIVITV 473
Cdd:cd23084   18 KGVVVTEVDPGSPAAQSGLKKGDVIIGVNRQPVKSIAELRKVLKsKPSAVLLQIKRGDSSRYLAL 82

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 229093139  411 GAYIIEVIPDTPAEAGGLKENDVIISINGQSVVTANDVSDVIKKENTLNMV 461
Cdd:pfam00595  26 GIFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKGSGGKV 76

Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and follistatin-like domains.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 229093139   115 SEPVCGSDAKTYTNLCQLRAASRRSeklrQPPVIVLQRGAC 155
Cdd:smart00280  10 YDPVCGSDGVTYSNECHLCKAACES----GKSIEVKHDGPC 46

V8-like Glu-specific endopeptidase [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139 182 AVVHIELYRklpfskrevPVASGSGFIVSEDgLIVTNAHVVTNKNR------VKVEL-KNGATY-----------EAKIK 243
Cdd:COG3591    1 AVGRLETDG---------GGGVCTGTLIGPN-LVLTAGHCVYDGAGggwatnIVFVPgYNGGPYgtatatrfrvpPGWVA 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 229093139 244 DVDEKADIALIKIDH--QGKLPVLLLGRSSELRPGEFVVAIGSPFSLQNTVTTgivsttQRGGKelgLRNSDMDYIQTDA 321
Cdd:COG3591   71 SGDAGYDYALLRLDEplGDTTGWLGLAFNDAPLAGEPVTIIGYPGDRPKDLSL------DCSGR---VTGVQGNRLSYDC 141

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 229093139 322 IINYGNSGGPLVNLD---GEVIGINTLKVTAGISFAIP 356
Cdd:COG3591  142 DTTGGSSGSPVLDDSdggGRVVGVHSAGGADRANTGVR 179

Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the cognate enzyme as substrate. The reactive site peptide bond is a combining loop which has an identical conformation in all Kazal inhibitors and in all enzyme/inhibitor complexes. These Kazal domains (small hydrophobic core of alpha/beta structure with 3 to 4 disulfide bonds) often occur in tandem arrays. Similar domains are also present in follistatin (FS) and follistatin-like family members, which play an important role in tissue specific regulation. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a Kazal-like domain and has five disulfide bonds. Although the Kazal-like FS substructure is similar to Kazal proteinase inhibitors, no FS domain has yet been shown to be a proteinase inhibitor. Follistatin-like family members include SPARC, also known as, BM-40 or osteonectin, the Gallus gallus Flik protein, as well as, agrin which has a long array of FS domains. The kazal-type inhibitor domain has also been detected in an extracellular loop region of solute carrier 21 (SLC21) family members (organic anion transporters) , which may regulate the specificity of anion uptake. The distant homolog, Ascidian trypsin inhibitor, is included in this CD.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 229093139 114 SSEPVCGSDAKTYTNLCQLRAASRRSeklrQPPVIVLQRGAC 155
Cdd:cd00104    4 EYDPVCGSDGKTYSNECHLGCAACRS----GRSITVAHNGPC 41

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 229093139 407 DVLSGAYIIEVIPDTPAE-AGGLKENDVIISINGQSV--VTANDVSDVIKK-ENTLNMVVR 463
Cdd:cd00136   21 DGGGGIFVSRVEPGGPAArDGRLRVGDRILEVNGVSLegLTHEEAVELLKSaGGEVTLTVR 81

PDZ domain of tamalin, cytohesin-1-interacting protein (CYTIP), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of tamalin, cytohesin-1-interacting protein, and related domains. Tamalin (trafficking regulator and scaffold protein tamalin, also known as general receptor for phosphoinositides 1-associated scaffold protein, GRASP) functions to link receptors, including group 1 metabotropic glutamate receptors (mGluRs), to neuronal proteins. The tamalin PDZ domain binds the C-terminal domains of group I mGluRs; it also binds potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2), neurotrophin-3 (NT3) TrkCT1-truncated receptor, SAP90/PSD-95-associated protein, and tamalin itself. CYTIP (cytohesin-1-interacting protein, also known as Pleckstrin homology Sec7 and coiled-coil domain-binding protein) sequesters cytohesin-1 in the cytoplasm, limiting its interaction with beta2 integrins; cytohesin-1 binds the CYTIP coiled coil domain. The CYTIP PDZ domain can bind the C-terminal peptide of protocadherin alpha-1 (PCDHA1), indicating a possible interaction between the two. 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 tamalin-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
                 ....*....|....*....|....*....|....*....|....*....|...
gi 229093139 413 YIIEVIPDTPAEAGGLKENDVIISINGQSVVTAN--DVSDVIKKE-NTLNMVV 462
Cdd:cd06713   38 YVCRVHEDSPAYLAGLTAGDVILSVNGVSVEGAShqEIVELIRSSgNTLRLET 90

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
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 229093139 410 SGAYIIEVIPDTPAEAGGLKENDVIISING---QSVVTANDVSdVIKKENTLNMVVR 463
Cdd:cd06752   25 LGIFISKVIPDSDAHRLGLKEGDQILSVNGvdfEDIEHSEAVK-VLKTAREIQMRVR 80

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 229093139 414 IIEVIPDTPAEAGGLKENDVIISINGQSVVTANdVSDVIKkentlnMVVRRGNEDIVITVI 474
Cdd:cd06712   25 VASVDPGSCAAEAGLKEGDYIVSVGGVDCKWSK-HSEVVK------LLKSAGEEGLELQVV 78

PDZ domain of SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2, SHANK3, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of SHANK1, SHANK2, SHANK3, and related domains. SHANK family proteins, SHANK1 (also known as somatostatin receptor-interacting protein, SSTR-interacting protein, SSTRIP), SHANK2 (also known as cortactin-binding protein 1, proline-rich synapse-associated protein 1), and SHANK3 (proline-rich synapse-associated protein 2) are synaptic scaffolding proteins which are highly enriched in the post-synaptic densities of excitatory synapses. They have been implicated in synaptic transmission, synapse formation, synaptic plasticity, and cytoskeletal remodeling, and are regulators of Cav1 calcium current and CREB target expression. Many protein ligands have been identified for the Shank PDZ domain, such as GKAP (also known as SAPAP), betaPIX (a guanine nucleotide exchange factor used by Rho GTPase family members Rac1 and Cdc42), alpha-latrotoxin, neuroligin, group I metabotropic glutamate receptors (mGluRs), and L-type calcium channels. 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 SHANK-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 229093139 413 YIIEVIPDTPAEAGGLKENDVIISINGQSVVTA--NDVSDVIKKE-NTLNMVV 462
Cdd:cd06746   45 YLESVDPGGVADKAGLKKGDFLLEINGEDVVKAshEQVVNLIRQSgNTLVLKV 97