NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|492186389|ref|WP_005773030|]
View 

site-2 protease family protein [Coxiella burnetii]

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

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

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) ...
 10-193 2.13e-61

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: 190.07  E-value: 2.13e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389  10 IAVVVLPLLFAITLHEAAHGWVANKLGDKTALMMGRVTLNPLKHIDPFGTVILPILililskFTFAFGWAKPVPVTWQNL 89
Cdd:cd06158    1 ILIVIIAVLLAITLHEFAHAYVAYRLGDPTARRAGRLTLNPLAHIDPIGTIILPLL------LPFLFGWAKPVPVNPRNF 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389  90 RKLRRDMALVAVAGPLSNLFMALLWAAIAKLSVTFGVnavnpvvkTVTLFFYHAGLFGILINLVLMLLNLIPVPPLDGSR 169
Cdd:cd06158   75 KNPRRGMLLVSLAGPLSNLLLALLFALLLRLLPAFGG--------VVASFLFLMLAYGVLINLVLAVFNLLPIPPLDGSK 146

                        170       180
                 ....*....|....*....|....
gi 492186389 170 IVSAILPPKAAYAYSKIEPYGIWI 193
Cdd:cd06158  147 ILAALLPRRLAEAYARLEPYGFLI 170
 
Name Accession Description Interval E-value
S2P-M50_like_1 cd06158
Uncharacterized homologs of Site-2 protease (S2P), zinc metalloproteases (MEROPS family M50) ...
 10-193 2.13e-61

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: 190.07  E-value: 2.13e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389  10 IAVVVLPLLFAITLHEAAHGWVANKLGDKTALMMGRVTLNPLKHIDPFGTVILPILililskFTFAFGWAKPVPVTWQNL 89
Cdd:cd06158    1 ILIVIIAVLLAITLHEFAHAYVAYRLGDPTARRAGRLTLNPLAHIDPIGTIILPLL------LPFLFGWAKPVPVNPRNF 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389  90 RKLRRDMALVAVAGPLSNLFMALLWAAIAKLSVTFGVnavnpvvkTVTLFFYHAGLFGILINLVLMLLNLIPVPPLDGSR 169
Cdd:cd06158   75 KNPRRGMLLVSLAGPLSNLLLALLFALLLRLLPAFGG--------VVASFLFLMLAYGVLINLVLAVFNLLPIPPLDGSK 146

                        170       180
                 ....*....|....*....|....
gi 492186389 170 IVSAILPPKAAYAYSKIEPYGIWI 193
Cdd:cd06158  147 ILAALLPRRLAEAYARLEPYGFLI 170
SpoIVFB COG1994
Zn-dependent protease (includes sporulation protein SpoIVFB) [Posttranslational modification, ...
 1-193 7.96e-37

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


Pssm-ID: 441597  Cd Length: 175  Bit Score: 127.25  E-value: 7.96e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389   1 MSFNNIVHI-IAVVVLPLLFAITLHEAAHGWVANKLGDKTAlmmgRVTLNPLKhidpfgtvilpilililskftfaFGWA 79
Cdd:COG1994    1 MGIPVRLHPsILIFALALFLSVLLHELAHALVARRLGDPTA----KITLNPLK-----------------------GGWA 53

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389  80 KpvpvtWQNLRKLRRDMALVAVAGPLSNLFMALLWAAIAKLSVTFGVNavnpvvktvtlFFYHAGLFGILINLVLMLLNL 159
Cdd:COG1994   54 K-----INRNFRNPRDEALVALAGPLANLLLALLFALLLRLLPALGLG-----------PLALLLGYLALINLVLAVFNL 117

                        170       180       190
                 ....*....|....*....|....*....|....
gi 492186389 160 IPVPPLDGSRIVSAILPPKAAYAYSKIEPYGIWI 193
Cdd:COG1994  118 LPIPPLDGGRILRALLPRRTARRATRLEPYGFLI 151
Peptidase_M50 pfam02163
Peptidase family M50;
146-175 2.38e-03

Peptidase family M50;


Pssm-ID: 426630 [Multi-domain]  Cd Length: 291  Bit Score: 38.24  E-value: 2.38e-03
                          10        20        30
                  ....*....|....*....|....*....|
gi 492186389  146 FGILINLVLMLLNLIPVPPLDGSRIVSAIL 175
Cdd:pfam02163 235 FLALINLNLGIFNLLPVPPLDGGHILRALL 264
 
Name Accession Description Interval E-value
S2P-M50_like_1 cd06158
Uncharacterized homologs of Site-2 protease (S2P), zinc metalloproteases (MEROPS family M50) ...
 10-193 2.13e-61

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: 190.07  E-value: 2.13e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389  10 IAVVVLPLLFAITLHEAAHGWVANKLGDKTALMMGRVTLNPLKHIDPFGTVILPILililskFTFAFGWAKPVPVTWQNL 89
Cdd:cd06158    1 ILIVIIAVLLAITLHEFAHAYVAYRLGDPTARRAGRLTLNPLAHIDPIGTIILPLL------LPFLFGWAKPVPVNPRNF 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389  90 RKLRRDMALVAVAGPLSNLFMALLWAAIAKLSVTFGVnavnpvvkTVTLFFYHAGLFGILINLVLMLLNLIPVPPLDGSR 169
Cdd:cd06158   75 KNPRRGMLLVSLAGPLSNLLLALLFALLLRLLPAFGG--------VVASFLFLMLAYGVLINLVLAVFNLLPIPPLDGSK 146

                        170       180
                 ....*....|....*....|....
gi 492186389 170 IVSAILPPKAAYAYSKIEPYGIWI 193
Cdd:cd06158  147 ILAALLPRRLAEAYARLEPYGFLI 170
S2P-M50 cd05709
Site-2 protease (S2P) class of zinc metalloproteases (MEROPS family M50) cleaves transmembrane ...
 11-193 6.00e-38

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: 130.44  E-value: 6.00e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389  11 AVVVLPLLFAITLHEAAHGWVANKLGDKTALMMGRVTLNPLKHIDPFGTVilpilililskFTFAFGWAKPVPVTWQNLR 90
Cdd:cd05709    1 LAFILALLISVTVHELGHALVARRLGVKVARFSGGFTLNPLKHGDPYGII-----------LIPLGGYAKPVGENPRAFK 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389  91 KLRRDMALVAVAGPLSNLFMALLWAAIAKLsvtFGVNAVNPVVKTVTLFFYHAGLFGILINLVLMLLNLIPVPPLDGSRI 170
Cdd:cd05709   70 KPRWQRLLVALAGPLANLLLALLLLLLLLL---LGGLPPAPVGQAASSGLANLLAFLALINLNLAVFNLLPIPPLDGGRI 146

                        170       180
                 ....*....|....*....|...
gi 492186389 171 VSAILPPKAAYAYSKIEPYGIWI 193
Cdd:cd05709  147 LRALLEAIRGRVEERLEAYGFAI 169
SpoIVFB COG1994
Zn-dependent protease (includes sporulation protein SpoIVFB) [Posttranslational modification, ...
 1-193 7.96e-37

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


Pssm-ID: 441597  Cd Length: 175  Bit Score: 127.25  E-value: 7.96e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389   1 MSFNNIVHI-IAVVVLPLLFAITLHEAAHGWVANKLGDKTAlmmgRVTLNPLKhidpfgtvilpilililskftfaFGWA 79
Cdd:COG1994    1 MGIPVRLHPsILIFALALFLSVLLHELAHALVARRLGDPTA----KITLNPLK-----------------------GGWA 53

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389  80 KpvpvtWQNLRKLRRDMALVAVAGPLSNLFMALLWAAIAKLSVTFGVNavnpvvktvtlFFYHAGLFGILINLVLMLLNL 159
Cdd:COG1994   54 K-----INRNFRNPRDEALVALAGPLANLLLALLFALLLRLLPALGLG-----------PLALLLGYLALINLVLAVFNL 117

                        170       180       190
                 ....*....|....*....|....*....|....
gi 492186389 160 IPVPPLDGSRIVSAILPPKAAYAYSKIEPYGIWI 193
Cdd:COG1994  118 LPIPPLDGGRILRALLPRRTARRATRLEPYGFLI 151
S2P-M50_SpoIVFB_CBS cd06164
SpoIVFB Site-2 protease (S2P), a zinc metalloprotease (MEROPS family M50B), regulates ...
 17-175 2.62e-06

SpoIVFB Site-2 protease (S2P), a zinc metalloprotease (MEROPS family M50B), regulates intramembrane proteolysis (RIP), and is involved in the pro-sigmaK pathway of bacterial spore formation. In this subgroup, SpoIVFB (sporulation protein, stage IV cell wall formation, F locus, promoter-distal B) contains two tandem repeats of the cystathionine beta-synthase (CBS pair) domain. SpoIVFB is one of 4 proteins involved in endospore formation; the others are SpoIVFA (sporulation protein, stage IV cell wall formation, F locus, promoter-proximal A), BofA (bypass-of-forespore A), and SpoIVB (sporulation protein, stage IV cell wall formation, B locus). SpoIVFB is negatively regulated by SpoIVFA and BofA and activated by SpoIVB. It is thought that SpoIVFB, SpoIVFA, and BofA are located in the mother-cell membrane that surrounds the forespore and that SpoIVB is secreted from the forespore into the space between the two where it activates SpoIVFB. It has been proposed that the CBS domain may play a regulatory role, although its exact function is unknown.


Pssm-ID: 100085  Cd Length: 227  Bit Score: 46.76  E-value: 2.62e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389  17 LLFA-ITLHEAAHGWVANKLGDKTAlmmgRVTLNPlkhidpFGTVILPilililskftfafgwaKPVPVTWqnlrklrRD 95
Cdd:cd06164   51 LLFAsVLLHELGHSLVARRYGIPVR----SITLFL------FGGVARL----------------EREPETP-------GQ 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389  96 MALVAVAGPLSNLFMALLWAAIAKLSVTFGVNAVNPVVKTVTLffyhaglfgilINLVLMLLNLIPVPPLDGSRIVSAIL 175
Cdd:cd06164   98 EFVIAIAGPLVSLVLALLFLLLSLALPGSGAGPLGVLLGYLAL-----------INLLLAVFNLLPAFPLDGGRVLRALL 166
S2P-M50_SpoIVFB cd06161
SpoIVFB Site-2 protease (S2P), a zinc metalloprotease (MEROPS family M50B), regulates ...
 94-175 4.80e-06

SpoIVFB Site-2 protease (S2P), a zinc metalloprotease (MEROPS family M50B), regulates intramembrane proteolysis (RIP), and is involved in the pro-sigmaK pathway of bacterial spore formation. SpoIVFB (sporulation protein, stage IV cell wall formation, F locus, promoter-distal B) is one of 4 proteins involved in endospore formation; the others are SpoIVFA (sporulation protein, stage IV cell wall formation, F locus, promoter-proximal A), BofA (bypass-of-forespore A), and SpoIVB (sporulation protein, stage IV cell wall formation, B locus). SpoIVFB is negatively regulated by SpoIVFA and BofA and activated by SpoIVB. It is thought that SpoIVFB, SpoIVFA, and BofA are located in the mother-cell membrane that surrounds the forespore and that SpoIVB is secreted from the forespore into the space between the two where it activates SpoIVFB.


Pssm-ID: 100082 [Multi-domain]  Cd Length: 208  Bit Score: 45.61  E-value: 4.80e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389  94 RDMALVAVAGPLSNLFMALLWAAIAKLSVTFGVnavnpvvktvtlfFYHAGLFGILINLVLMLLNLIPVPPLDGSRIVSA 173
Cdd:cd06161   81 KEEFVIALAGPLVSLLLAGLFYLLYLLLPGGGP-------------LSSLLEFLAQVNLILGLFNLLPALPLDGGRVLRA 147


                 ..
gi 492186389 174 IL 175
Cdd:cd06161  148 LL 149
S2P-M50_like_2 cd06160
Uncharacterized homologs of Site-2 protease (S2P), zinc metalloproteases (MEROPS family M50) ...
 15-184 2.91e-05

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 additional putative N- and C-terminal transmembrane spanning regions, relative to the core protein, and no PDZ domains.


Pssm-ID: 100081  Cd Length: 183  Bit Score: 43.37  E-value: 2.91e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389  15 LPLLFAITLHEAAHGWVANKLGDKTALMMgrvtLNPLKHIDPFGTVIlpilililskftfafGWAKPVPVtwqnlrklRR 94
Cdd:cd06160   38 LALLAILGIHEMGHYLAARRHGVKASLPY----FIPFPFIGTFGAFI---------------RMRSPIPN--------RK 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 492186389  95 DMALVAVAGPLSNLFMALLWAAIaklSVTFgvnavnpvvktvtlffyhAGLFGILINLvlmlLNLIPVPPLDGSRIVSAI 174
Cdd:cd06160   91 ALFDIALAGPLAGLLLALPVLII---GLAV------------------AGWVGLLVTA----LNLLPVGQLDGGHIVRAL 145

                        170
                 ....*....|
gi 492186389 175 LPPKAAYAYS 184
Cdd:cd06160  146 FGRRVAALIG 155
S2P-M50_PDZ_RseP-like cd06163
RseP-like Site-2 proteases (S2P), zinc metalloproteases (MEROPS family M50A), cleave ...
 97-171 4.66e-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: 39.70  E-value: 4.66e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 492186389  97 ALVAVAGPLSNLFMALlwaaiaklsvtfgvnavnpVVKTVTLFFyhaglfGILINLVLMLLNLIPVPPLDGSRIV 171
Cdd:cd06163   91 ILIVFAGPLANFLLAI-------------------VLFAVLLSF------LALLSINLGILNLLPIPALDGGHLL 140
Peptidase_M50 pfam02163
Peptidase family M50;
146-175 2.38e-03

Peptidase family M50;


Pssm-ID: 426630 [Multi-domain]  Cd Length: 291  Bit Score: 38.24  E-value: 2.38e-03
                          10        20        30
                  ....*....|....*....|....*....|
gi 492186389  146 FGILINLVLMLLNLIPVPPLDGSRIVSAIL 175
Cdd:pfam02163 235 FLALINLNLGIFNLLPVPPLDGGHILRALL 264
RseP COG0750
Membrane-associated protease RseP, regulator of RpoE activity [Posttranslational modification, ...
 146-171 3.54e-03

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


Pssm-ID: 440513 [Multi-domain]  Cd Length: 349  Bit Score: 37.76  E-value: 3.54e-03
                         10        20
                 ....*....|....*....|....*.
gi 492186389 146 FGILINLVLMLLNLIPVPPLDGSRIV 171
Cdd:COG0750  280 FLALLSINLGVLNLLPIPALDGGHLL 305
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH