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: 42.6102
Threshold Setting Gi: 74543387
Created: 26-Apr-2007
Updated: 17-Jan-2013
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:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                     ##  #                                                              
3B4R_A        41 AVLFILLFVSVVLHELGHSYVAKKYGv-----------------kIEKILLLPi-----GGVAMMDKipk---------e 89
gi 150383801  19 LAAIIIVVFSVCAHEFMHAWIALLQGdgtaaerghltmsplkqmgPWSLFMLAfi---gIAWGQVPVdpsrm----rhry 91
gi 120401689  47 VFVIFGWLVTLCLHEFGHAYSAYRFGdrdvavrgyltlnplkyshPLLSLGLPvlfialGGIGLPGGavyvqta-hmtdr 125
gi 81340857   47 VMVIAGWLVSLCLHEFGHAFTAWRFGdhdvavrgyltldprryshPMLSLGLPmlfialGGIGLPGAavyvhtw-fmtta 125
gi 134102898  40 LIVLGGWATSLCLHEFGHALTAYRGGdlsvrskgylsldprhytdPVLSIVLPllfvaiGGIPLPGGavwinhhalrtrr 119
gi 159039083  53 LFVVSGWLVSLCLHEYAHALVAFRAGdrsvahqgyltlnplkyshPLLSIAFPvlvvllGGIGLPGGavwvdrhaipgrl 132
gi 81550422   45 LFVTAAWVVSLCLHEYAHARTALHSGdisvgakgyltlnpvkythALLSIVLPvlfvimGGIGLPGGavfiergrirgrw 124
gi 81534329   76 AFVAAAWVLSVGIHEFGHAFTAYKAGdttivekgyltldplkysdLFTTIIIPlvalalGGIGFPGGavylredlmrsrg 155
gi 74542305   47 IIPYIVALLAIIPHEIGHRQAARRYGcfsrftlsfsgfwttlilnIIGSFVGIlvf-fsGYTSISCGlln--------rd 117
gi 74544327   41 AVSFLVAVTAFLMHELAHRYVARSYGgiayfkmwplglllalitsLLGFIFAApgavniGGIYRRDQ------------- 107
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                              #       #                 
3B4R_A        90 gELRIGIAGPLVSFIIGIVLLIVSqffdin----ingyplLYTLSLLNLMLGGFNLIPAFPMDGGRILRAilskky---- 161
gi 150383801  92 sHALVAFAGPATNLLLGVAFSLLCflafrnevgteftwdmLYFGATINMVLFLLNLLPVPGFDGWAILVTffpkimr-id 170
gi 120401689 126 qKTLVSLAGPGVNLIFAVLLLALTrllydpa--hsvfwagVAFLGFLQVTALLLNMLPIPGLDGYGALEPhlspdtqral 203
gi 81340857  126 rRTLVSLAGPTVNLALAMLLLAATrllfdpi--havlwagVAFLAFLQLTALVLNLLPIPGLDGYAALEPhlrpetqral 203
gi 134102898 120 vESMVSLAGPLTNLVLGIALTAVVvsvpmp----eglgsgLSYLAYLQVIAFVLNILPIPGLDGYGAIEPwlsgparefg 195
gi 159039083 133 rHTLVSLAGPATNVVFTLVLVVAVrlaatggg-pvefwaaVALLAFLQLTASLLNLLPVPGLDGGNMIQPwltppyrray 211
gi 81550422  125 rHSLISAAGPLTNVLFAVVCTAPFwldaldgv-prdfrlaLAFLALLQVTAAILNFLPVPGLDGYGVIEPwlsynvrrqv 203
gi 81534329  156 wRSLASLAGPLGTLVVLVVIAVSLplaaas----pplfnaLSLLAMLQASALVLNLLPVPGLDGYGVIRPflpegvqarm 231
gi 74542305  118 vEGKTALAGPLTNIIVGFVGLIGAslvpfs-----lvglfFFELARFNFWVAFFNLLPFWVLDGLKIFRWn--------- 183
gi 74544327  108 -IGKTSLAGPAMNIFLGILFYAISlftlip-----vaiaiFRYVAEMNFWFGFFNLLPIPPLDGYKVFSWd--------- 172
                        170       180
                 ....*....|....*....|.
Feature 1                             
3B4R_A       162 gylksTKIAANIGKSLALIML 182
gi 150383801 171 seivkGSFFVIIILVFMGIGK 191
gi 120401689 204 npakqWGFFILLILLIAPPLN 224
gi 81340857  204 apakqFALVFLLVLFLAPTLN 224
gi 134102898 196 ekarpWAPLVLFALILATPLG 216
gi 159039083 212 dlfapYGFLLLFALLWNPRIN 232
gi 81550422  204 eplapFGLLIVFALLWIPALN 224
gi 81534329  232 mkverVGFLILFALIFWAPGV 252
gi 74542305  184 ----mIVWAVLIIIAFALTFL 200
gi 74544327  173 ----lYVYIVSVVIALVFVVL 189

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