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: 2-Oct-2020
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:
Feature 1                                                                                        
Q9V622         6 FFIVLASLYGVLYFFdrffks--cmhypYDAFLKNTGLSINFmSLHWHTSAFNRTLLrWGSAGNSCTRRVMITSFNVGVL 83  fruit fly
NP_001020632   6 VVVCVMGGWCTVYLAdtllrssssvknrYESWLSSNGFTLSPfHIKWHTGIFNRLFArCAHFNPHFLYIWFSAGMVFGVL 85  zebrafish
XP_425566     64 AQGFRVFGVGFFLIPcelngsssslkasYEDWLVNYGLSVSPfHMRWQTALFNRQFYnWGRWKPRFLYLWFSMGMVFGIA 143 chicken
AAI35272       6 LVVVVLGGWCAIYLAdtfltssqslknsYEEWLTARGLSISPfHIRWQTTLFNRLFYkWGRWKPNFLYIWFTLGVAFGII 85  western clawed ...
XP_001633156   6 SIYLVIFFWTLVFIVnavlknyrkysrrYKEFLEDHGITMSLcQIRWYTTQLNRWFIwFGRLHPYLLHLWFSLGVFVGVG 85  starlet sea ane...
XP_001663668   6 LLGVVVAIYGVLLFFdnffks--cmhypYEAFLKGTGLSVKFlRLQWHTTALNRSIVkWSTAYPKLLELNFSLGVYLSIL 83  yellow fever mo...
O43462         6 LVVVVVGGWTVVYLTdlvlkssvyfkhsYEDWLENNGLSISPfHIRWQTAVFNRAFYsWGRRKARMLYQWFNFGMVFGVI 85  human
Feature 1                                                                                        
Q9V622        84 VTFslLPIGLILLIAtifssgeqdsss---------------------svsspvgvpvqLEILLPGVNLPLeEIGYYITT 142 fruit fly
NP_001020632  86 AMF--GSVVLLSKTLlqtlhqmmad-------------------------tpdgsheqvLQVVVPGVNLPVsQLAYFFIA 138 zebrafish
XP_425566    144 AMF--GSVILLGKTLmqtltqmlte-------------------------aptapndrmLQVVVPGVNLPVsQLTYFFSA 196 chicken
AAI35272      86 AMF--GSIFLLGKTLvqtlnqmmae-------------------------spasqndrmLQVVVPGVNLPIsQLSYFFSA 138 western clawed ...
XP_001633156  86 LMA--LSVMVLSLTLyqaftk--------------------------------eapeqvLTPVMPGVNLPWsQLMYYLIT 131 starlet sea ane...
XP_001663668  84 LMP--LASLLIVVSAfhtkssgkpssds------------------aagasgavaetvsLDLLIPGVNLPLnEIGFYIAA 143 yellow fever mo...
O43462        86 AMF--SSFFLLGKTLmqtlaqmmadspssyssssssssssssssssssssssslhneqvLQVVVPGINLPVnQLTYFFTA 163 human
Feature 1               ##  #                                                                    
Q9V622       143 LVLCLVVHEMGHALAAVMEDVPVtGFGIKFIFCLPLAYTELSHDHLNSLRWFRKLRVLCAGIWHNFVFAGVCYLLIstvg 222 fruit fly
NP_001020632 139 ILVSGVIHEFGHGVAALREQVRLnGFGMFMFVIYPGAFVDLFTTHLNLISPVQQLRIFCAGVWHNFMLCVVALSFLfllp 218 zebrafish
XP_425566    197 ILISGVIHEVGHGVAAIREQVRFnGFGIFIFIVYPGAFVDLFTTHLQLISPVQQLRIFCAGVWHNFVLGVVSFMVLfllp 276 chicken
AAI35272     139 ILISGVLHEVGHGVAAVRESVRFnGFGMFIFIVYPGAFVDLFTTHLQLVSPVQQLRIFCAGVWHNFVLGILGILILvplp 218 western clawed ...
XP_001633156 132 LAVSGVFHEMGHAVAAVREQVRVnGFGMFFMAIYPGAYVDLYTDHLTMISPIRQLRIYCAGVWHNVILVLLGLLLLwslp 211 starlet sea ane...
XP_001663668 144 LAINSVVHELGHGLAAVLEDVPIkGFGFHVMLIIPMAYTQLDSDQLNALKTWKRLKVLCAGIWHNLLLGAFAYLLFvttp 223 yellow fever mo...
O43462       164 VLISGVVHEIGHGIAAIREQVRFnGFGIFLFIIYPGAFVDLFTTHLQLISPVQQLRIFCAGIWHNFVLALLGILALvllp 243 human
Feature 1                                                                                        
Q9V622       223 itmsplyaynqhvvvteltrksplrgerglqvdnqitqvngcpvnseeswvtclqnslklkpgycvsadfvqlndessai 302 fruit fly
NP_001020632 219 iflfpfyytgagalvtevaegspssgprglflgdlitqledctvrgvqdwhscvqhlshnpqtgycvhtaklhlsytqgr 298 zebrafish
XP_425566    277 aflfpfyytgvgafvtevtedspangprglfvgdivtslqdcpiygvedwnsclgdlsqksqigycinaatlqqlsfpar 356 chicken
AAI35272     219 allfpfyytgvgalvtevvedspasgprglfvqdlithvqdcqvtgvddwhtclteisqmpqigycintatlqqlqfpsr 298 western clawed ...
XP_001633156 212 yllvplymadqgavvtkvsrnspvfgsinrgdtiysvygcpvnnkndwiqcvsrtlnspqhgycsnmftvtrqnssqgsf 291 starlet sea ane...
XP_001663668 224 vmlsaiyrvnesvmvtsiknnspllgargleegdiitsinscevrnevswydclleslhsqpsycispdfvhlndesvpi 303 yellow fever mo...
O43462       244 villpfyytgvgvlitevaedspaigprglfvgdlvthlqdcpvtnvqdwnecldtiayepqigycisastlqqlsfpvr 323 human
Feature 1                                                                                        
Q9V622       303 shhsidgqlqccdelnpnvscfevvedangdvpvelpqhvclnvrrtleevsehcssgvcnegfclrplirnitaimtfk 382 fruit fly
NP_001020632 299 afkrldgtmeccgnnsl-------tdlcfsysnnvesklfaclpvrktieasrtchtntdcqtdftpslclipslenqtr 371 zebrafish
XP_425566    357 vyrrldgtveccsnnsl-------tdicfsyntnldshryaclparkvieaskvcrtnadcqkdfvpsfcvtpslenqtr 429 chicken
AAI35272     299 vyrrldgsieccnnnsl-------sdicfsynsnsnqqqfaclparksiynsqecrsnidcqktdaasvcavpsienqtr 371 western clawed ...
XP_001633156 292 tdgvyeccgnlttss-----------rlcfryesiksekgyaclaarsimqasqfcslpehchgpgnkacvhpsldnssr 360 starlet sea ane...
XP_001663668 304 shkndglieccsvenka------sncfeymvdvneedvalpqhmclnirkviensfgychqkpicseghcfkpminnftt 377 yellow fever mo...
O43462       324 aykrldgsteccnnhsl-------tdvcfsyrnnfnkrlhtclparkaveatqvcrtnkdckksssssfciipslethtr 396 human
Feature 1                                                                      #       #         
Q9V622       383 rqnfrgeklppviyvghpwdvtrtvevsafvprysllkaawpdaWLLLLKYNVVFSIGLALINAIPCFGFDGAHITSTVI 462 fruit fly
NP_001020632 372 lirvkhppqtdmlfvgysshlqysvsltnfvprlgflhpdlpvmLETFCKYLVSLSGALAVVNAVPCFALDGQWMLTAFL 451 zebrafish
XP_425566    430 lirvkhpphmdmlfvghpmhlqytvslssfvprhnflsidlpvvIETFCKYLISLSGALAVINAVPCFALDGQWILNSFL 509 chicken
AAI35272     372 lirvkhspqldmlfigypvhlqyavslssfvprynflsislpvvIETFCKYLISLSGALAVINAVPCFALDGQWILNSFI 451 western clawed ...
XP_001633156 361 lirvrrlggpdvlyvgdpillqytvavvnysprspilpmelptiIETFLIYLISLSGALALLNIVPCYSLDGQWALFALV 440 starlet sea ane...
XP_001663668 378 ilqirrdhkpdviyighpadltrtvrisqfvpktsifrpgfaddIQLLLKYVTVFALGLSVINVIPCFGFDGQHIVSTLL 457 yellow fever mo...
O43462       397 likvkhppqidmlyvghplhlhytvsitsfiprfnflsidlpvvVETFVKYLISLSGALAIVNAVPCFALDGQWILNSFL 476 human
Feature 1                                         
Q9V622       463 Hsflvgrvd-qhakrdiISLIITSVGSLLFALA 494 fruit fly
NP_001020632 452 Eatlssviq-ernnrelIGFFFLLGGSALLAAN 483 zebrafish
XP_425566    510 Eatlssliv-ekqnrelVGFLILLAGSTLLAAN 541 chicken
AAI35272     452 Eatlssvia-ekqnrelLAFFILLAGSALLTAN 483 western clawed frog
XP_001633156 441 Dhtlgniip-nedqrstLCTVILTMGTLLLAAN 472 starlet sea anemone
XP_001663668 458 TnglvvsrvpqkskrdvIALCINIVGTLFVFIL 490 yellow fever mosquito
O43462       477 Datltsvig-dndvkdlIGFFILLGGSVLLAAN 508 human

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