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 1682507369  71 IFCAGVWHNFVLCVAALAFLFLLPFLLLPAYSTGGGALVTEVVQGSAADGPRGLSVGDIVTGLEDCPVGGVEDWSRCLSR 150
Cdd:cd06775     1 IYCAGVWHNFVLVLVALLVLFLLPFLLSPFYYTGSGVVVTEVVENSPVSGPRGLFVGDVITSINDCPVTSVEDWMKCLEE 80

                          90       100
                  ....*....|....*....|....*..
gi 1682507369 151 LARAPQTGYCVPGASLQPSWAHGRAFK 177
Cdd:cd06775    81 VSKSPQSGYCVSADFLQQLDTSSRVYK 107

Site-2 protease (S2P) class of zinc metalloproteases (MEROPS family M50) cleaves transmembrane domains of substrate proteins, regulating intramembrane proteolysis (RIP) of diverse signal transduction mechanisms. Members of this family use proteolytic activity within the membrane to transfer information across membranes to integrate gene expression with physiologic stresses occurring in another cellular compartment. The domain core structure appears to contain at least three transmembrane helices with a catalytic zinc atom coordinated by three conserved residues contained within the consensus sequence HExxH, together with a conserved aspartate residue. The S2P/M50 family of RIP proteases is widely distributed; in eukaryotic cells, they regulate such processes as sterol and lipid metabolism, and endoplasmic reticulum (ER) stress responses. In sterol-depleted mammalian cells, a two-step proteolytic process releases the N-terminal domains of sterol regulatory element-binding proteins (SREBPs) from membranes of the ER. These domains translocate into the nucleus, where they activate genes of cholesterol and fatty acid biosynthesis. It is the second proteolytic step that is carried out by the SREBP Site-2 protease (S2P) which is present in this CD superfamily. Prokaryotic S2P/M50 homologs have been shown to regulate stress responses, sporulation, cell division, and cell differentiation. In Escherichia coli, the S2P homolog RseP is involved in the sigmaE pathway of extracytoplasmic stress responses, and in Bacillus subtilis, the S2P homolog SpoIVFB is involved in the pro-sigmaK pathway of spore formation. Some of the subfamilies within this hierarchy contain one or two PDZ domain insertions, with putative regulatory roles, such as the inhibition of substrate cleavage as seen by the RseP PDZ domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1682507369 287 FAFLHLDLPVFLETFCKYVVSLSGALAVVNSVPCFALDGQWMLNALLEATLVTVVTDRQKRELIGFF 353
Cdd:cd06162   199 FVLGLVGYLLLIETFLKYLISLSGALAVINAVPCFALDGQWILSTFLEATLVSVIVQKDKRDLIGFF 265

circularly permuted PDZ domain of membrane-bound transcription factor site-2 protease (MBTPS2, also known as S2P) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MBTPS2, also known as sterol regulatory element-binding protein (SREBP) Site-2 protease (S2P), and related domains. MBTPS2 is a zinc metalloprotease (MEROPS family M50A). In the Golgi, it catalyzes the second step in the proteolytic activation of sterol regulatory element-binding proteins (SREBPs), releasing the transcriptionally active N-terminal domain of SREBP, which then enters the nucleus and activates genes encoding the low density lipoprotein (LDL) receptor and enzymes for cholesterol and fatty acid biosynthesis. MBTPS2 also mediates the second step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF6. ATF6 is a membrane-bound transcription factor that activates genes in the endoplasmic reticulum (ER) stress response. 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. One permutation places beta-strand A on the C-terminus, another permutation places both beta-strands A and B on the C-terminus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1682507369  71 IFCAGVWHNFVLCVAALAFLFLLPFLLLPAYSTGGGALVTEVVQGSAADGPRGLSVGDIVTGLEDCPVGGVEDWSRCLSR 150
Cdd:cd06775     1 IYCAGVWHNFVLVLVALLVLFLLPFLLSPFYYTGSGVVVTEVVENSPVSGPRGLFVGDVITSINDCPVTSVEDWMKCLEE 80

                          90       100
                  ....*....|....*....|....*..
gi 1682507369 151 LARAPQTGYCVPGASLQPSWAHGRAFK 177
Cdd:cd06775    81 VSKSPQSGYCVSADFLQQLDTSSRVYK 107

Sterol regulatory element-binding protein (SREBP) Site-2 protease (S2P), a zinc metalloprotease (MEROPS family M50A), regulates intramembrane proteolysis (RIP) of SREBP and is part of a signal transduction mechanism involved in sterol and lipid metabolism. In sterol-depleted mammalian cells, a two-step proteolytic process releases the N-terminal domains of SREBPs from membranes of the endoplasmic reticulum (ER). These domains translocate into the nucleus, where they activate genes of cholesterol and fatty acid biosynthesis. The first cleavage occurs at Site-1 within the ER lumen to generate an intermediate that is subsequently released from the membrane by cleavage at Site-2, which lies within the first transmembrane domain. It is the second proteolytic step that is carried out by the SREBP Site-2 protease (S2P) which is present in this CD family. This group appears to be limited to eumetazoan proteins and contains one PDZ domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1682507369 287 FAFLHLDLPVFLETFCKYVVSLSGALAVVNSVPCFALDGQWMLNALLEATLVTVVTDRQKRELIGFF 353
Cdd:cd06162   199 FVLGLVGYLLLIETFLKYLISLSGALAVINAVPCFALDGQWILSTFLEATLVSVIVQKDKRDLIGFF 265

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1682507369 102 STGGGALVTEVVQGSAADGpRGLSVGDIVTGLEDCPVGGVEDWSRCLSRLA 152
Cdd:COG0265   198 PEPEGVLVARVEPGSPAAK-AGLRPGDVILAVDGKPVTSARDLQRLLASLK 247

circularly permuted PDZ domain of membrane-bound transcription factor site-2 protease (MBTPS2, also known as S2P) and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of MBTPS2, also known as sterol regulatory element-binding protein (SREBP) Site-2 protease (S2P), and related domains. MBTPS2 is a zinc metalloprotease (MEROPS family M50A). In the Golgi, it catalyzes the second step in the proteolytic activation of sterol regulatory element-binding proteins (SREBPs), releasing the transcriptionally active N-terminal domain of SREBP, which then enters the nucleus and activates genes encoding the low density lipoprotein (LDL) receptor and enzymes for cholesterol and fatty acid biosynthesis. MBTPS2 also mediates the second step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF6. ATF6 is a membrane-bound transcription factor that activates genes in the endoplasmic reticulum (ER) stress response. 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. One permutation places beta-strand A on the C-terminus, another permutation places both beta-strands A and B on the C-terminus.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1682507369  71 IFCAGVWHNFVLCVAALAFLFLLPFLLLPAYSTGGGALVTEVVQGSAADGPRGLSVGDIVTGLEDCPVGGVEDWSRCLSR 150
Cdd:cd06775     1 IYCAGVWHNFVLVLVALLVLFLLPFLLSPFYYTGSGVVVTEVVENSPVSGPRGLFVGDVITSINDCPVTSVEDWMKCLEE 80

                          90       100
                  ....*....|....*....|....*..
gi 1682507369 151 LARAPQTGYCVPGASLQPSWAHGRAFK 177
Cdd:cd06775    81 VSKSPQSGYCVSADFLQQLDTSSRVYK 107

Sterol regulatory element-binding protein (SREBP) Site-2 protease (S2P), a zinc metalloprotease (MEROPS family M50A), regulates intramembrane proteolysis (RIP) of SREBP and is part of a signal transduction mechanism involved in sterol and lipid metabolism. In sterol-depleted mammalian cells, a two-step proteolytic process releases the N-terminal domains of SREBPs from membranes of the endoplasmic reticulum (ER). These domains translocate into the nucleus, where they activate genes of cholesterol and fatty acid biosynthesis. The first cleavage occurs at Site-1 within the ER lumen to generate an intermediate that is subsequently released from the membrane by cleavage at Site-2, which lies within the first transmembrane domain. It is the second proteolytic step that is carried out by the SREBP Site-2 protease (S2P) which is present in this CD family. This group appears to be limited to eumetazoan proteins and contains one PDZ domain.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1682507369 287 FAFLHLDLPVFLETFCKYVVSLSGALAVVNSVPCFALDGQWMLNALLEATLVTVVTDRQKRELIGFF 353
Cdd:cd06162   199 FVLGLVGYLLLIETFLKYLISLSGALAVINAVPCFALDGQWILSTFLEATLVSVIVQKDKRDLIGFF 265

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
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1682507369 101 YSTGGGALVTEVVQGSAADGPrGLSVGDIVTGLEDCPVGGVEDWSRCLSRLA 152
Cdd:cd06779    21 LPVNRGVLVAEVIPGSPAAKA-GLKEGDVILSVNGKPVTSFNDLRAALDTKK 71

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1682507369 102 STGGGALVTEVVQGSAADGpRGLSVGDIVTGLEDCPVGGVEDWSRCLSRLA 152
Cdd:COG0265   198 PEPEGVLVARVEPGSPAAK-AGLRPGDVILAVDGKPVTSARDLQRLLASLK 247