Conserved Protein Domain Family
S2P-M50_PDZ_SREBP

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cd06162: S2P-M50_PDZ_SREBP 
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.
Statistics
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PSSM-Id: 100083
View PSSM: cd06162
Aligned: 7 rows
Threshold Bit Score: 270.052
Threshold Setting Gi: 74867376
Created: 25-Jan-2008
Updated: 17-Jan-2013
Structure
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Aligned Rows:
 
active siteputative
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                                                                                        
gi 74867376    6 FFIVLASLYGVLYFFdrffks--cmhypYDAFLKNTGLSINFmSLHWHTSAFNRTLLrWGSAGNSCTRRVMITSFNVGVL 83
gi 70887549    6 VVVCVMGGWCTVYLAdtllrssssvknrYESWLSSNGFTLSPfHIKWHTGIFNRLFArCAHFNPHFLYIWFSAGMVFGVL 85
gi 118084081  64 AQGFRVFGVGFFLIPcelngsssslkasYEDWLVNYGLSVSPfHMRWQTALFNRQFYnWGRWKPRFLYLWFSMGMVFGIA 143
gi 134025958   6 LVVVVLGGWCAIYLAdtfltssqslknsYEEWLTARGLSISPfHIRWQTTLFNRLFYkWGRWKPNFLYIWFTLGVAFGII 85
gi 156384073   6 SIYLVIFFWTLVFIVnavlknyrkysrrYKEFLEDHGITMSLcQIRWYTTQLNRWFIwFGRLHPYLLHLWFSLGVFVGVG 85
gi 157136134   6 LLGVVVAIYGVLLFFdnffks--cmhypYEAFLKGTGLSVKFlRLQWHTTALNRSIVkWSTAYPKLLELNFSLGVYLSIL 83
gi 6016601     6 LVVVVVGGWTVVYLTdlvlkssvyfkhsYEDWLENNGLSISPfHIRWQTAVFNRAFYsWGRRKARMLYQWFNFGMVFGVI 85
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 74867376   84 VTFslLPIGLILLIAtifssgeqdsss---------------------svsspvgvpvqLEILLPGVNLPLeEIGYYITT 142
gi 70887549   86 AMF--GSVVLLSKTLlqtlhqmmad-------------------------tpdgsheqvLQVVVPGVNLPVsQLAYFFIA 138
gi 118084081 144 AMF--GSVILLGKTLmqtltqmlte-------------------------aptapndrmLQVVVPGVNLPVsQLTYFFSA 196
gi 134025958  86 AMF--GSIFLLGKTLvqtlnqmmae-------------------------spasqndrmLQVVVPGVNLPIsQLSYFFSA 138
gi 156384073  86 LMA--LSVMVLSLTLyqaftk--------------------------------eapeqvLTPVMPGVNLPWsQLMYYLIT 131
gi 157136134  84 LMP--LASLLIVVSAfhtkssgkpssds------------------aagasgavaetvsLDLLIPGVNLPLnEIGFYIAA 143
gi 6016601    86 AMF--SSFFLLGKTLmqtlaqmmadspssyssssssssssssssssssssssslhneqvLQVVVPGINLPVnQLTYFFTA 163
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1               ##  #                                                                    
gi 74867376  143 LVLCLVVHEMGHALAAVMEDVPVtGFGIKFIFCLPLAYTELSHDHLNSLRWFRKLRVLCAGIWHNFVFAGVCYLLIstvg 222
gi 70887549  139 ILVSGVIHEFGHGVAALREQVRLnGFGMFMFVIYPGAFVDLFTTHLNLISPVQQLRIFCAGVWHNFMLCVVALSFLfllp 218
gi 118084081 197 ILISGVIHEVGHGVAAIREQVRFnGFGIFIFIVYPGAFVDLFTTHLQLISPVQQLRIFCAGVWHNFVLGVVSFMVLfllp 276
gi 134025958 139 ILISGVLHEVGHGVAAVRESVRFnGFGMFIFIVYPGAFVDLFTTHLQLVSPVQQLRIFCAGVWHNFVLGILGILILvplp 218
gi 156384073 132 LAVSGVFHEMGHAVAAVREQVRVnGFGMFFMAIYPGAYVDLYTDHLTMISPIRQLRIYCAGVWHNVILVLLGLLLLwslp 211
gi 157136134 144 LAINSVVHELGHGLAAVLEDVPIkGFGFHVMLIIPMAYTQLDSDQLNALKTWKRLKVLCAGIWHNLLLGAFAYLLFvttp 223
gi 6016601   164 VLISGVVHEIGHGIAAIREQVRFnGFGIFLFIIYPGAFVDLFTTHLQLISPVQQLRIFCAGIWHNFVLALLGILALvllp 243
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 74867376  223 itmsplyaynqhvvvteltrksplrgerglqvdnqitqvngcpvnseeswvtclqnslklkpgycvsadfvqlndessai 302
gi 70887549  219 iflfpfyytgagalvtevaegspssgprglflgdlitqledctvrgvqdwhscvqhlshnpqtgycvhtaklhlsytqgr 298
gi 118084081 277 aflfpfyytgvgafvtevtedspangprglfvgdivtslqdcpiygvedwnsclgdlsqksqigycinaatlqqlsfpar 356
gi 134025958 219 allfpfyytgvgalvtevvedspasgprglfvqdlithvqdcqvtgvddwhtclteisqmpqigycintatlqqlqfpsr 298
gi 156384073 212 yllvplymadqgavvtkvsrnspvfgsinrgdtiysvygcpvnnkndwiqcvsrtlnspqhgycsnmftvtrqnssqgsf 291
gi 157136134 224 vmlsaiyrvnesvmvtsiknnspllgargleegdiitsinscevrnevswydclleslhsqpsycispdfvhlndesvpi 303
gi 6016601   244 villpfyytgvgvlitevaedspaigprglfvgdlvthlqdcpvtnvqdwnecldtiayepqigycisastlqqlsfpvr 323
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                                        
gi 74867376  303 shhsidgqlqccdelnpnvscfevvedangdvpvelpqhvclnvrrtleevsehcssgvcnegfclrplirnitaimtfk 382
gi 70887549  299 afkrldgtmeccgnnsl-------tdlcfsysnnvesklfaclpvrktieasrtchtntdcqtdftpslclipslenqtr 371
gi 118084081 357 vyrrldgtveccsnnsl-------tdicfsyntnldshryaclparkvieaskvcrtnadcqkdfvpsfcvtpslenqtr 429
gi 134025958 299 vyrrldgsieccnnnsl-------sdicfsynsnsnqqqfaclparksiynsqecrsnidcqktdaasvcavpsienqtr 371
gi 156384073 292 tdgvyeccgnlttss-----------rlcfryesiksekgyaclaarsimqasqfcslpehchgpgnkacvhpsldnssr 360
gi 157136134 304 shkndglieccsvenka------sncfeymvdvneedvalpqhmclnirkviensfgychqkpicseghcfkpminnftt 377
gi 6016601   324 aykrldgsteccnnhsl-------tdvcfsyrnnfnkrlhtclparkaveatqvcrtnkdckksssssfciipslethtr 396
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                                                      #       #         
gi 74867376  383 rqnfrgeklppviyvghpwdvtrtvevsafvprysllkaawpdaWLLLLKYNVVFSIGLALINAIPCFGFDGAHITSTVI 462
gi 70887549  372 lirvkhppqtdmlfvgysshlqysvsltnfvprlgflhpdlpvmLETFCKYLVSLSGALAVVNAVPCFALDGQWMLTAFL 451
gi 118084081 430 lirvkhpphmdmlfvghpmhlqytvslssfvprhnflsidlpvvIETFCKYLISLSGALAVINAVPCFALDGQWILNSFL 509
gi 134025958 372 lirvkhspqldmlfigypvhlqyavslssfvprynflsislpvvIETFCKYLISLSGALAVINAVPCFALDGQWILNSFI 451
gi 156384073 361 lirvrrlggpdvlyvgdpillqytvavvnysprspilpmelptiIETFLIYLISLSGALALLNIVPCYSLDGQWALFALV 440
gi 157136134 378 ilqirrdhkpdviyighpadltrtvrisqfvpktsifrpgfaddIQLLLKYVTVFALGLSVINVIPCFGFDGQHIVSTLL 457
gi 6016601   397 likvkhppqidmlyvghplhlhytvsitsfiprfnflsidlpvvVETFVKYLISLSGALAIVNAVPCFALDGQWILNSFL 476
                        490       500       510
                 ....*....|....*....|....*....|...
Feature 1                                         
gi 74867376  463 Hsflvgrvd-qhakrdiISLIITSVGSLLFALA 494
gi 70887549  452 Eatlssviq-ernnrelIGFFFLLGGSALLAAN 483
gi 118084081 510 Eatlssliv-ekqnrelVGFLILLAGSTLLAAN 541
gi 134025958 452 Eatlssvia-ekqnrelLAFFILLAGSALLTAN 483
gi 156384073 441 Dhtlgniip-nedqrstLCTVILTMGTLLLAAN 472
gi 157136134 458 TnglvvsrvpqkskrdvIALCINIVGTLFVFIL 490
gi 6016601   477 Datltsvig-dndvkdlIGFFILLGGSVLLAAN 508

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