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Conserved domains on  [gi|497588214|ref|WP_009902398|]
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site-2 protease family protein [Clostridioides difficile]

Protein Classification

site-2 protease family protein( domain architecture ID 10150298)

Site-2 protease (S2P) homolog is a zinc metalloprotease which cleaves transmembrane domains of substrate proteins, regulating intramembrane proteolysis (RIP) of diverse signal transduction mechanisms, including processes as sporulation, cell division, stress response, and cell differentiation

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
S2P-M50_like_1 cd06158
Uncharacterized homologs of Site-2 protease (S2P), zinc metalloproteases (MEROPS family M50) ...
 9-180 9.80e-59

Uncharacterized homologs of Site-2 protease (S2P), zinc metalloproteases (MEROPS family M50) which cleave transmembrane domains of substrate proteins, regulating intramembrane proteolysis (RIP) of diverse signal transduction mechanisms. Members of the S2P/M50 family of RIP proteases use proteolytic activity within the membrane to transfer information across membranes to integrate gene expression with physiologic stresses occurring in another cellular compartment. In eukaryotic cells they regulate such processes as sterol and lipid metabolism, and endoplasmic reticulum stress responses. In prokaryotes they regulate such processes as sporulation, cell division, stress response, and cell differentiation. This group includes bacterial, eukaryotic, and Archaeal S2P/M50s homologs with a minimal core protein and no PDZ domains.


:

Pssm-ID: 100079  Cd Length: 181  Bit Score: 181.98  E-value: 9.80e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497588214   9 IVASLVGIAMAISIHEFGHAYSAHLLGDDTAKAYGRMTLNPVRHVDPIGLLAMFIL---KIGWAKPVPVNPNNFKNYKIG 85
Cdd:cd06158    1 ILIVIIAVLLAITLHEFAHAYVAYRLGDPTARRAGRLTLNPLAHIDPIGTIILPLLlpfLFGWAKPVPVNPRNFKNPRRG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497588214  86 NLIVSLAGVFCNVLTAILCVIINKYVHMYA------INTIAEYVFLYSIGFAAFNLLPIPPLDGWGVISTFVPYKWNEYL 159
Cdd:cd06158   81 MLLVSLAGPLSNLLLALLFALLLRLLPAFGgvvasfLFLMLAYGVLINLVLAVFNLLPIPPLDGSKILAALLPRRLAEAY 160

                        170       180
                 ....*....|....*....|.
gi 497588214 160 YKFESMSYIILLIALFTGMYR 180
Cdd:cd06158  161 ARLEPYGFLILLALLFTGILG 181
 
Name Accession Description Interval E-value
S2P-M50_like_1 cd06158
Uncharacterized homologs of Site-2 protease (S2P), zinc metalloproteases (MEROPS family M50) ...
 9-180 9.80e-59

Uncharacterized homologs of Site-2 protease (S2P), zinc metalloproteases (MEROPS family M50) which cleave transmembrane domains of substrate proteins, regulating intramembrane proteolysis (RIP) of diverse signal transduction mechanisms. Members of the S2P/M50 family of RIP proteases use proteolytic activity within the membrane to transfer information across membranes to integrate gene expression with physiologic stresses occurring in another cellular compartment. In eukaryotic cells they regulate such processes as sterol and lipid metabolism, and endoplasmic reticulum stress responses. In prokaryotes they regulate such processes as sporulation, cell division, stress response, and cell differentiation. This group includes bacterial, eukaryotic, and Archaeal S2P/M50s homologs with a minimal core protein and no PDZ domains.


Pssm-ID: 100079  Cd Length: 181  Bit Score: 181.98  E-value: 9.80e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497588214   9 IVASLVGIAMAISIHEFGHAYSAHLLGDDTAKAYGRMTLNPVRHVDPIGLLAMFIL---KIGWAKPVPVNPNNFKNYKIG 85
Cdd:cd06158    1 ILIVIIAVLLAITLHEFAHAYVAYRLGDPTARRAGRLTLNPLAHIDPIGTIILPLLlpfLFGWAKPVPVNPRNFKNPRRG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497588214  86 NLIVSLAGVFCNVLTAILCVIINKYVHMYA------INTIAEYVFLYSIGFAAFNLLPIPPLDGWGVISTFVPYKWNEYL 159
Cdd:cd06158   81 MLLVSLAGPLSNLLLALLFALLLRLLPAFGgvvasfLFLMLAYGVLINLVLAVFNLLPIPPLDGSKILAALLPRRLAEAY 160

                        170       180
                 ....*....|....*....|.
gi 497588214 160 YKFESMSYIILLIALFTGMYR 180
Cdd:cd06158  161 ARLEPYGFLILLALLFTGILG 181
SpoIVFB COG1994
Zn-dependent protease (includes sporulation protein SpoIVFB) [Posttranslational modification, ...
 9-191 1.47e-31

Zn-dependent protease (includes sporulation protein SpoIVFB) [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 441597  Cd Length: 175  Bit Score: 112.61  E-value: 1.47e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497588214   9 IVASLVGIAMAISIHEFGHAYSAHLLGDDTAkaygRMTLNPvrhvdpigllamfiLKIGWAKpvpVNpNNFKNYKiGNLI 88
Cdd:COG1994   11 ILIFALALFLSVLLHELAHALVARRLGDPTA----KITLNP--------------LKGGWAK---IN-RNFRNPR-DEAL 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497588214  89 VSLAGVFCNVLTAILCVIINKYVHM---YAINTIAEYVFLYSIGFAAFNLLPIPPLDGWGVISTFVPYKWNEYLYKFESM 165
Cdd:COG1994   68 VALAGPLANLLLALLFALLLRLLPAlglGPLALLLGYLALINLVLAVFNLLPIPPLDGGRILRALLPRRTARRATRLEPY 147

                        170       180
                 ....*....|....*....|....*...
gi 497588214 166 SYIILLIALFTGMY--RIILTPIYAVLL 191
Cdd:COG1994  148 GFLILLLLIFLGLLlgNIWLSPLLNLLI 175
 
Name Accession Description Interval E-value
S2P-M50_like_1 cd06158
Uncharacterized homologs of Site-2 protease (S2P), zinc metalloproteases (MEROPS family M50) ...
 9-180 9.80e-59

Uncharacterized homologs of Site-2 protease (S2P), zinc metalloproteases (MEROPS family M50) which cleave transmembrane domains of substrate proteins, regulating intramembrane proteolysis (RIP) of diverse signal transduction mechanisms. Members of the S2P/M50 family of RIP proteases use proteolytic activity within the membrane to transfer information across membranes to integrate gene expression with physiologic stresses occurring in another cellular compartment. In eukaryotic cells they regulate such processes as sterol and lipid metabolism, and endoplasmic reticulum stress responses. In prokaryotes they regulate such processes as sporulation, cell division, stress response, and cell differentiation. This group includes bacterial, eukaryotic, and Archaeal S2P/M50s homologs with a minimal core protein and no PDZ domains.


Pssm-ID: 100079  Cd Length: 181  Bit Score: 181.98  E-value: 9.80e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497588214   9 IVASLVGIAMAISIHEFGHAYSAHLLGDDTAKAYGRMTLNPVRHVDPIGLLAMFIL---KIGWAKPVPVNPNNFKNYKIG 85
Cdd:cd06158    1 ILIVIIAVLLAITLHEFAHAYVAYRLGDPTARRAGRLTLNPLAHIDPIGTIILPLLlpfLFGWAKPVPVNPRNFKNPRRG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497588214  86 NLIVSLAGVFCNVLTAILCVIINKYVHMYA------INTIAEYVFLYSIGFAAFNLLPIPPLDGWGVISTFVPYKWNEYL 159
Cdd:cd06158   81 MLLVSLAGPLSNLLLALLFALLLRLLPAFGgvvasfLFLMLAYGVLINLVLAVFNLLPIPPLDGSKILAALLPRRLAEAY 160

                        170       180
                 ....*....|....*....|.
gi 497588214 160 YKFESMSYIILLIALFTGMYR 180
Cdd:cd06158  161 ARLEPYGFLILLALLFTGILG 181
S2P-M50 cd05709
Site-2 protease (S2P) class of zinc metalloproteases (MEROPS family M50) cleaves transmembrane ...
 10-179 2.18e-34

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.


Pssm-ID: 100078 [Multi-domain]  Cd Length: 180  Bit Score: 120.04  E-value: 2.18e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497588214  10 VASLVGIAMAISIHEFGHAYSAHLLGDDTAKAYGRMTLNPVRHVDPIGLLAMFIlkIGWAKPVPVNPNNFKNYKIGNLIV 89
Cdd:cd05709    1 LAFILALLISVTVHELGHALVARRLGVKVARFSGGFTLNPLKHGDPYGIILIPL--GGYAKPVGENPRAFKKPRWQRLLV 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497588214  90 SLAGVFCNVLTAILCVIINKYVHMYA-----------INTIAEYVFLYSIGFAAFNLLPIPPLDGWGVISTFVPYKWNEY 158
Cdd:cd05709   79 ALAGPLANLLLALLLLLLLLLLGGLPpapvgqaassgLANLLAFLALINLNLAVFNLLPIPPLDGGRILRALLEAIRGRV 158

                        170       180
                 ....*....|....*....|.
gi 497588214 159 LYKFESMSYIILLIALFTGMY 179
Cdd:cd05709  159 EERLEAYGFAILLGLLLLLLL 179
SpoIVFB COG1994
Zn-dependent protease (includes sporulation protein SpoIVFB) [Posttranslational modification, ...
 9-191 1.47e-31

Zn-dependent protease (includes sporulation protein SpoIVFB) [Posttranslational modification, protein turnover, chaperones];


Pssm-ID: 441597  Cd Length: 175  Bit Score: 112.61  E-value: 1.47e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497588214   9 IVASLVGIAMAISIHEFGHAYSAHLLGDDTAkaygRMTLNPvrhvdpigllamfiLKIGWAKpvpVNpNNFKNYKiGNLI 88
Cdd:COG1994   11 ILIFALALFLSVLLHELAHALVARRLGDPTA----KITLNP--------------LKGGWAK---IN-RNFRNPR-DEAL 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 497588214  89 VSLAGVFCNVLTAILCVIINKYVHM---YAINTIAEYVFLYSIGFAAFNLLPIPPLDGWGVISTFVPYKWNEYLYKFESM 165
Cdd:COG1994   68 VALAGPLANLLLALLFALLLRLLPAlglGPLALLLGYLALINLVLAVFNLLPIPPLDGGRILRALLPRRTARRATRLEPY 147

                        170       180
                 ....*....|....*....|....*...
gi 497588214 166 SYIILLIALFTGMY--RIILTPIYAVLL 191
Cdd:COG1994  148 GFLILLLLIFLGLLlgNIWLSPLLNLLI 175
S2P-M50_PDZ_RseP-like cd06163
RseP-like Site-2 proteases (S2P), zinc metalloproteases (MEROPS family M50A), cleave ...
 87-143 4.40e-04

RseP-like Site-2 proteases (S2P), zinc metalloproteases (MEROPS family M50A), cleave transmembrane domains of substrate proteins, regulating intramembrane proteolysis (RIP) of diverse signal transduction mechanisms. In Escherichia coli, the S2P homolog RseP is involved in the sigmaE pathway of extracytoplasmic stress responses. Also included in this group are such homologs as Bacillus subtilis YluC, Mycobacterium tuberculosis Rv2869c S2P, and Bordetella bronchiseptica HurP. Rv2869c S2P appears to have a role in the regulation of prokaryotic lipid biosynthesis and membrane composition and YluC of Bacillus has a role in transducing membrane stress. This group includes bacterial and eukaryotic S2P/M50s homologs with either one or two PDZ domains present. PDZ domains are believed to have a regulatory role. The RseP PDZ domain is required for the inhibitory reaction that prevents cleavage of its substrate, RseA.


Pssm-ID: 100084 [Multi-domain]  Cd Length: 182  Bit Score: 39.32  E-value: 4.40e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 497588214  87 LIVSLAGVFCNVLTAILCVIInkyvhmyaintIAEYVFLYSIGFAAFNLLPIPPLDG 143
Cdd:cd06163   91 ILIVFAGPLANFLLAIVLFAV-----------LLSFLALLSINLGILNLLPIPALDG 136
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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