3B4R


Conserved Protein Domain Family
S2P-M50

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cd05709: S2P-M50 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 100078
View PSSM: cd05709
Aligned: 413 rows
Threshold Bit Score: 44.151
Threshold Setting Gi: 75543517
Created: 26-Apr-2007
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
active siteputative
Conserved site includes 5 residues -Click on image for an interactive view with Cn3D
Feature 1:active site [active site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                          ##  #                                                              
3B4R_A             41 AVLFILLFVSVVLHELGHSYVAKKYGv-----------------kIEKILLLPi-----GGVAMMDKipk---------e 89  Methanocal...
ZP_01922515        19 LAAIIIVVFSVCAHEFMHAWIALLQGdgtaaerghltmsplkqmgPWSLFMLAfi---gIAWGQVPVdpsrm----rhry 91  Victivalli...
YP_951518          47 VFVIFGWLVTLCLHEFGHAYSAYRFGdrdvavrgyltlnplkyshPLLSLGLPvlfialGGIGLPGGavyvqta-hmtdr 125 Mycobacter...
O06309             47 VMVIAGWLVSLCLHEFGHAFTAWRFGdhdvavrgyltldprryshPMLSLGLPmlfialGGIGLPGAavyvhtw-fmtta 125 Mycobacter...
YP_001108559       40 LIVLGGWATSLCLHEFGHALTAYRGGdlsvrskgylsldprhytdPVLSIVLPllfvaiGGIPLPGGavwinhhalrtrr 119 Saccharopo...
REF_jgi:Sare_3543  53 LFVVSGWLVSLCLHEYAHALVAFRAGdrsvahqgyltlnplkyshPLLSIAFPvlvvllGGIGLPGGavwvdrhaipgrl 132 Salinispor...
Q9RKR8             45 LFVTAAWVVSLCLHEYAHARTALHSGdisvgakgyltlnpvkythALLSIVLPvlfvimGGIGLPGGavfiergrirgrw 124 Streptomyc...
Q9A325             76 AFVAAAWVLSVGIHEFGHAFTAYKAGdttivekgyltldplkysdLFTTIIIPlvalalGGIGFPGGavylredlmrsrg 155 Caulobacte...
Q97ZW1             47 IIPYIVALLAIIPHEIGHRQAARRYGcfsrftlsfsgfwttlilnIIGSFVGIlvf-fsGYTSISCGlln--------rd 117 Sulfolobus...
Q9HKN5             41 AVSFLVAVTAFLMHELAHRYVARSYGgiayfkmwplglllalitsLLGFIFAApgavniGGIYRRDQ------------- 107 Thermoplas...
Feature 1                                                                   #       #                 
3B4R_A             90 gELRIGIAGPLVSFIIGIVLLIVSqffdin----ingyplLYTLSLLNLMLGGFNLIPAFPMDGGRILRAilskky---- 161 Methanocal...
ZP_01922515        92 sHALVAFAGPATNLLLGVAFSLLCflafrnevgteftwdmLYFGATINMVLFLLNLLPVPGFDGWAILVTffpkimr-id 170 Victivalli...
YP_951518         126 qKTLVSLAGPGVNLIFAVLLLALTrllydpa--hsvfwagVAFLGFLQVTALLLNMLPIPGLDGYGALEPhlspdtqral 203 Mycobacter...
O06309            126 rRTLVSLAGPTVNLALAMLLLAATrllfdpi--havlwagVAFLAFLQLTALVLNLLPIPGLDGYAALEPhlrpetqral 203 Mycobacter...
YP_001108559      120 vESMVSLAGPLTNLVLGIALTAVVvsvpmp----eglgsgLSYLAYLQVIAFVLNILPIPGLDGYGAIEPwlsgparefg 195 Saccharopo...
REF_jgi:Sare_3543 133 rHTLVSLAGPATNVVFTLVLVVAVrlaatggg-pvefwaaVALLAFLQLTASLLNLLPVPGLDGGNMIQPwltppyrray 211 Salinispor...
Q9RKR8            125 rHSLISAAGPLTNVLFAVVCTAPFwldaldgv-prdfrlaLAFLALLQVTAAILNFLPVPGLDGYGVIEPwlsynvrrqv 203 Streptomyc...
Q9A325            156 wRSLASLAGPLGTLVVLVVIAVSLplaaas----pplfnaLSLLAMLQASALVLNLLPVPGLDGYGVIRPflpegvqarm 231 Caulobacte...
Q97ZW1            118 vEGKTALAGPLTNIIVGFVGLIGAslvpfs-----lvglfFFELARFNFWVAFFNLLPFWVLDGLKIFRWn--------- 183 Sulfolobus...
Q9HKN5            108 -IGKTSLAGPAMNIFLGILFYAISlftlip-----vaiaiFRYVAEMNFWFGFFNLLPIPPLDGYKVFSWd--------- 172 Thermoplas...
Feature 1                                  
3B4R_A            162 gylksTKIAANIGKSLALIML 182 Methanocaldococcus jannaschii
ZP_01922515       171 seivkGSFFVIIILVFMGIGK 191 Victivallis vadensis ATCC BAA-548
YP_951518         204 npakqWGFFILLILLIAPPLN 224 Mycobacterium vanbaalenii PYR-1
O06309            204 apakqFALVFLLVLFLAPTLN 224 Mycobacterium tuberculosis
YP_001108559      196 ekarpWAPLVLFALILATPLG 216 Saccharopolyspora erythraea NRRL 2338
REF_jgi:Sare_3543 212 dlfapYGFLLLFALLWNPRIN 232 Salinispora arenicola CNS-205
Q9RKR8            204 eplapFGLLIVFALLWIPALN 224 Streptomyces coelicolor
Q9A325            232 mkverVGFLILFALIFWAPGV 252 Caulobacter vibrioides
Q97ZW1            184 ----mIVWAVLIIIAFALTFL 200 Sulfolobus solfataricus
Q9HKN5            173 ----lYVYIVSVVIALVFVVL 189 Thermoplasma acidophilum

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