5A63


Conserved Protein Domain Family
Aph-1

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pfam06105: Aph-1 
Aph-1 protein
This family consists of several eukaryotic Aph-1 proteins.Gamma-secretase catalyzes the intramembrane proteolysis of Notch, beta-amyloid precursor protein, and other substrates as part of a new signaling paradigm and as a key step in the pathogenesis of Alzheimer's disease. It is thought that the presenilin heterodimer comprises the catalytic site and that a highly glycosylated form of nicastrin associates with it. Aph-1 and Pen-2, two membrane proteins genetically linked to gamma-secretase, associate directly with presenilin and nicastrin in the active protease complex. Co-expression of all four proteins leads to marked increases in presenilin heterodimers, full glycosylation of nicastrin, and enhanced gamma-secretase activity.
Statistics
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PSSM-Id: 399242
Aligned: 50 rows
Threshold Bit Score: 203.166
Threshold Setting Gi: 302788963
Created: 21-May-2020
Updated: 7-Aug-2020
Structure
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Program:
Drawing:
Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
5A63_C         3 AAVFFGCTFVAFGPAFALFLITVAGDPLRVIILVAGAFFWLVSLLLASVVWFILVHVTDRsdarlqyglLIFGAAVSVLL 82 
XP_006347279   3 VAAGIGYALLALGPSLSLFIALISKKPFLILTLLSSTLVWLMSLIVMSALWRAFLPLKTTaw-----wpYAILILTSVGF 77  potato
XP_015623034   3 VAAGLGYALVALGPAFSLFAGVVARKPFLVLTLLTSTLFWLISLIILSGIWRVFLPIRSGaw-----wpYAILILTSVAF 77  Japanese rice
XP_009416016   3 VAAGFGYVLISLGPALSLFVSVIAKKPFLILTLLASMLFWLISLIVLSGAWRGFLPLKSAsw-----wpYVILIVTSVGF 77  wild Malaysian ...
EDQ64714       3 LVAGFGYFLIALGPALTIFGSSVAPKPFLILTVLASALVWLASLNIAAIVWRAFLPGPSw--------vFLLILTTSVAL 74  Physcomitrella ...
XP_002976250   3 VASGVGYTLIALGPGFSLFFLSIVSKPLLILTLLASTLVWLASLVALAIVWRGFLPLGSSdw------iCLPLLASSVAL 76  Selaginella moe...
XP_004998769   3 QATLWGSLFIIFSMPLAIFWFVVRRSPKLVIVLVASAFMWLLAALLTGIIWIIIPPLQDD---------YWFVILISVPI 73  Salpingoeca ros...
XP_003291659   3 QVLFYGCLFITFSPILAFFFLVIAKNSQLVILTIGGSFFWLVSILLSAIWWYIIPPMREQ---------WWFTIPFAVVF 73  Dictyostelium p...
XP_018645655   3 CLGGVGCTLIGVGPCLILFLCTVANCPIKVILLTASGFFWLVSLLITSVMWFIVTPLRAY---------LAFGILIGVLI 73  Schistosoma man...
Q55FS3         3 QVLFYGCLFITFSPILAFFFMVIAKNSQLVILTIGGSFFWLVSILIAAIWWYIIPPMREH---------WWFIISFSVLF 73  Dictyostelium d...
5A63_C        83 QEVFRFAYYKLlkkADEGLASLSEdgrsPISIRQM--------------------------------------------- 117
XP_006347279  78 QEGLRILFWKVykkLEDILDAFAD----RVSKPRLfmtd----------------------------------------- 112 potato
XP_015623034  78 QEGIRLVFWRLykkMEEMLDSFAD----RISKPRLcltd----------------------------------------- 112 Japanese rice
XP_009416016  78 QEATRLIFWKLykkLEVILDAFAE----EKFRSRLswtd----------------------------------------- 112 wild Malaysian ...
EDQ64714      75 QEAFRLLYWHLylkIEKYLNVLAT----KLSKPQCnyld----------------------------------------- 109 Physcomitrella ...
XP_002976250  77 QEFLRVHFWRTfkkVESSLNGVAV----RISKPPLrpse----------------------------------------- 111 Selaginella moe...
XP_004998769  74 QEAFRYFFWKMlhkAEKGLSTLTPdgdvVITREKL--------------------------------------------- 108 Salpingoeca ros...
XP_003291659  74 QEAIRYLFYRL---YSWGFNDRPSlnqiKETQHQMsldqmkkrkqvktsyqnenynndndnnnnnnndddtfsidn---- 146 Dictyostelium p...
XP_018645655  74 QEILRFLFFLLifkAESGLQLIVSssttPVSRPQLvdginndniidnhshgreaernevsnltrnrkisss--------- 144 Schistosoma man...
Q55FS3        74 QEIFRYIFFRL---YSYGFNDRPSlnqiKETQHQMaldsmrkrkqaqqqkqqpptneiesinneiidttnnntnnnnnnn 150 Dictyostelium d...
5A63_C       118 -----------------------------------------------AYVSGLSFGIISGVFSVINILADALGPGVVGIH 150
XP_006347279 113 -------------------------------------------kmqiALAGGLGHGVAHAVFFCLGLLTPAFGPATYYVE 149 potato
XP_015623034 113 -------------------------------------------kmliSLAGGLGHGVAHAVFFCLSLLTPAFGRATFYVE 149 Japanese rice
XP_009416016 113 -------------------------------------------kmqiALAGGLGHGVAHAVFFCVSLLTPSFGPATFFVD 149 wild Malaysian ...
EDQ64714     110 -------------------------------------------rleiALASGVGHGLAHAVFFGLSIIAPAFGPATYYTS 146 Physcomitrella ...
XP_002976250 112 -------------------------------------------kieiAIALGFGHGLAHSIMFCLSLLTPAFGPGTFYLR 148 Selaginella moe...
XP_004998769 109 -----------------------------------------------WFVSGLGFGVMSAVMMMSNMLDIMTGPGMVPAR 141 Salpingoeca ros...
XP_003291659 147 -------kndsdendndkseskesdkaevvinnrletlsarpnhtlsATAIGVGNGTAYGFIMFGSILWESTGPGTMFSP 219 Dictyostelium p...
XP_018645655 145 -----------niiitndydhnilndnnsgdinnnnnhaiqldhltvAYVSGLGYGLMSCIIQSLRILIDSYGPGITIYS 213 Schistosoma man...
Q55FS3       151 nnindddnkeiteeekekrkiekqkqreieinarletlsarpnhtlsSAAIGVGSGVAYGFIMFGSILWESTGPGTLFSP 230 Dictyostelium d...
5A63_C       151 G-DSPYYFLTSAFLTAAIILLHTFWGVVFFDACERRR-----Y-----WALGLVVGSHLLTSGLTFL-NP-----WYEAS 213
XP_006347279 150 KcSKIPFFLVSAIIALAFATIHTFSMVIAFSGYEEGN-----K-----VDQCFAPVVHLIAGMLTLT-NLafggcMIGIP 218 potato
XP_015623034 150 KcSRMPFFLVSAIISLGFLVIHTFSMIIAFNGYDERK-----R-----SDQVFVPVVHLIASVMTLI-NLapggcVIGTP 218 Japanese rice
XP_009416016 150 RcSHMPFFLVSAIISLGFMIIHTFSMVIAFNAYAEGR-----K-----LDQIIIPIIHILAAVMTLI-NLapggcAIGVP 218 wild Malaysian ...
EDQ64714     147 ScKQMPLFLVSALSSLAFFLLHTFSMVIAFNAYTYDN-----I-----SQKLFVPIMHLGAALLTLV-NLlpngcTAGVP 215 Physcomitrella ...
XP_002976250 149 ScPQMPFFLVISLISLGFLLIHTFSMVIFFKGYEDHN-----S-----GLRFFVPAMHAVASSLTLV-NLvqngcVIGTP 217 Selaginella moe...
XP_004998769 142 GcPDFNLFTISALVSAAIVMCHAFWGVIAGKAWEQRTisksmFipsrdWKLFFVLAMHYFVAFLTIDaDKt----TCVGF 217 Salpingoeca ros...
XP_003291659 220 AcPTVNLFMLSSIITLCMTILHVVYNVLAFQGYRSRK-----Y-----HLVVYVVIVHFLTSFLTLL-NQps--kSCIGS 286 Dictyostelium p...
XP_018645655 214 TwNSRTFFLFSSCQCMCISMLQVFWSLILFSAFVQRA-----Y-----GQIILVYFMHFGLAGMSLI-NTys--sPCSEI 280 Schistosoma man...
Q55FS3       231 AcPSVNLFMLSSIITLFMTLLHVVYNVLAFQGYRSKK-----Y-----HLVAFVIITHFVTTYLTLL-NLptkttSCVGS 299 Dictyostelium d...
5A63_C       214 LLPIYAVTVS--MGLWAF 229
XP_006347279 219 LLYCVAIVTLvhCGKMAW 236 potato
XP_015623034 219 LLCVMGAVTLqyCWQMVW 236 Japanese rice
XP_009416016 219 LLYIIGGVVLrhCWQMVW 236 wild Malaysian banana
EDQ64714     216 LVFLCTALTMayGGKIVW 233 Physcomitrella patens
XP_002976250 218 LVMLCAALTLfvCGKSLW 235 Selaginella moellendorffii
XP_004998769 218 LLPIYGATLL--CACTAW 233 Salpingoeca rosetta
XP_003291659 287 VLPISLITIF--SVCFCL 302 Dictyostelium purpureum
XP_018645655 281 VCAIYMICLIgmiifayc 298 Schistosoma mansoni
Q55FS3       300 ILPIGIITVF--SVGFCI 315 Dictyostelium discoideum
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