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. APH-1 proteins have a similar but different set of motifs as compared to other families. Their four motifs are: QExxR, Fxxxx, Hxxxs and Hxxxs respectively. Given the inferred homology between APH-1 and other membrane proteases such as type II CAAX proteases and PrsW proteases, it is speculated that APH-1 may possess protease activity.
Statistics
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PSSM-Id: 461830
Aligned: 48 rows
Threshold Bit Score: 201.626
Created: 22-Mar-2022
Updated: 17-Oct-2022
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 
XP_015623034   3 VAAGLGYALVALGPAFSLFAGVVARKPFLVLTLLTSTLFWLISLIILSGIWRVFLPIRSGaw-----wpYAILILTSVAF 77 
XP_009416016   3 VAAGFGYVLISLGPALSLFVSVIAKKPFLILTLLASMLFWLISLIVLSGAWRGFLPLKSAsw-----wpYVILIVTSVGF 77 
EDQ64714       3 LVAGFGYFLIALGPALTIFGSSVAPKPFLILTVLASALVWLASLNIAAIVWRAFLPGPSw--------vFLLILTTSVAL 74 
XP_002976250   3 VASGVGYTLIALGPGFSLFFLSIVSKPLLILTLLASTLVWLASLVALAIVWRGFLPLGSSdw------iCLPLLASSVAL 76 
XP_004998769   3 QATLWGSLFIIFSMPLAIFWFVVRRSPKLVIVLVASAFMWLLAALLTGIIWIIIPPLQDD---------YWFVILISVPI 73 
XP_003291659   3 QVLFYGCLFITFSPILAFFFLVIAKNSQLVILTIGGSFFWLVSILLSAIWWYIIPPMREQ---------WWFTIPFAVVF 73 
XP_018645655   3 CLGGVGCTLIGVGPCLILFLCTVANCPIKVILLTASGFFWLVSLLITSVMWFIVTPLRAY---------LAFGILIGVLI 73 
Q55FS3         3 QVLFYGCLFITFSPILAFFFMVIAKNSQLVILTIGGSFFWLVSILIAAIWWYIIPPMREH---------WWFIISFSVLF 73  Dictyostelium d...
5A63_C        83 QEVFRFAYYKLlkkADEGLASLSEDGRSPISIRQM--------------------------------------------- 117
XP_006347279  78 QEGLRILFWKVykkLEDILDAFAD----RVSKPRLfmtd----------------------------------------- 112
XP_015623034  78 QEGIRLVFWRLykkMEEMLDSFAD----RISKPRLcltd----------------------------------------- 112
XP_009416016  78 QEATRLIFWKLykkLEVILDAFAE----EKFRSRLswtd----------------------------------------- 112
EDQ64714      75 QEAFRLLYWHLylkIEKYLNVLAT----KLSKPQCnyld----------------------------------------- 109
XP_002976250  77 QEFLRVHFWRTfkkVESSLNGVAV----RISKPPLrpse----------------------------------------- 111
XP_004998769  74 QEAFRYFFWKMlhkAEKGLSTLTPDGDVVITREKL--------------------------------------------- 108
XP_003291659  74 QEAIRYLFYRL---YSWGFNDRPSLNQIKETQHQMsldqmkkrkqvktsyqnenynndndnnnnnnndddtfsidn---- 146
XP_018645655  74 QEILRFLFFLLifkAESGLQLIVSSSTTPVSRPQLvdginndniidnhshgreaernevsnltrnrkisss--------- 144
Q55FS3        74 QEIFRYIFFRL---YSYGFNDRPSLNQIKETQHQMaldsmrkrkqaqqqkqqpptneiesinneiidttnnntnnnnnnn 150 Dictyostelium d...
5A63_C       118 -----------------------------------------------AYVSGLSFGIISGVFSVINILADALGPGVVGIH 150
XP_006347279 113 -------------------------------------------kmqiALAGGLGHGVAHAVFFCLGLLTPAFGPATYYVE 149
XP_015623034 113 -------------------------------------------kmliSLAGGLGHGVAHAVFFCLSLLTPAFGRATFYVE 149
XP_009416016 113 -------------------------------------------kmqiALAGGLGHGVAHAVFFCVSLLTPSFGPATFFVD 149
EDQ64714     110 -------------------------------------------rleiALASGVGHGLAHAVFFGLSIIAPAFGPATYYTS 146
XP_002976250 112 -------------------------------------------kieiAIALGFGHGLAHSIMFCLSLLTPAFGPGTFYLR 148
XP_004998769 109 -----------------------------------------------WFVSGLGFGVMSAVMMMSNMLDIMTGPGMVPAR 141
XP_003291659 147 -------kndsdendndkseskesdkaevvinnrletlsarpnhtlsATAIGVGNGTAYGFIMFGSILWESTGPGTMFSP 219
XP_018645655 145 -----------niiitndydhnilndnnsgdinnnnnhaiqldhltvAYVSGLGYGLMSCIIQSLRILIDSYGPGITIYS 213
Q55FS3       151 nnindddnkeiteeekekrkiekqkqreieinarletlsarpnhtlsSAAIGVGSGVAYGFIMFGSILWESTGPGTLFSP 230 Dictyostelium d...
5A63_C       151 G-DSPYYFLTSAFLTAAIILLHTFWGVVFFDACERRR-----Y-----WALGLVVGSHLLTSGLTFL-NP-----WYEAS 213
XP_006347279 150 KcSKIPFFLVSAIIALAFATIHTFSMVIAFSGYEEGN-----K-----VDQCFAPVVHLIAGMLTLT-NLafggcMIGIP 218
XP_015623034 150 KcSRMPFFLVSAIISLGFLVIHTFSMIIAFNGYDERK-----R-----SDQVFVPVVHLIASVMTLI-NLapggcVIGTP 218
XP_009416016 150 RcSHMPFFLVSAIISLGFMIIHTFSMVIAFNAYAEGR-----K-----LDQIIIPIIHILAAVMTLI-NLapggcAIGVP 218
EDQ64714     147 ScKQMPLFLVSALSSLAFFLLHTFSMVIAFNAYTYDN-----I-----SQKLFVPIMHLGAALLTLV-NLlpngcTAGVP 215
XP_002976250 149 ScPQMPFFLVISLISLGFLLIHTFSMVIFFKGYEDHN-----S-----GLRFFVPAMHAVASSLTLV-NLvqngcVIGTP 217
XP_004998769 142 GcPDFNLFTISALVSAAIVMCHAFWGVIAGKAWEQRTisksmFipsrdWKLFFVLAMHYFVAFLTIDaDKt----TCVGF 217
XP_003291659 220 AcPTVNLFMLSSIITLCMTILHVVYNVLAFQGYRSRK-----Y-----HLVVYVVIVHFLTSFLTLL-NQps--kSCIGS 286
XP_018645655 214 TwNSRTFFLFSSCQCMCISMLQVFWSLILFSAFVQRA-----Y-----GQIILVYFMHFGLAGMSLI-NTys--sPCSEI 280
Q55FS3       231 AcPSVNLFMLSSIITLFMTLLHVVYNVLAFQGYRSKK-----Y-----HLVAFVIITHFVTTYLTLL-NLptkttSCVGS 299 Dictyostelium d...
5A63_C       214 LLPIYAVTVS--MGLWAFITAG 233
XP_006347279 219 LLYCVAIVTLvhCGKMAWrrli 240
XP_015623034 219 LLCVMGAVTLqyCWQMVWrrls 240
XP_009416016 219 LLYIIGGVVLrhCWQMVWrklt 240
EDQ64714     216 LVFLCTALTMayGGKIVWhnlg 237
XP_002976250 218 LVMLCAALTLfvCGKSLWqkgd 239
XP_004998769 218 LLPIYGATLL--CACTAWFVIR 237
XP_003291659 287 VLPISLITIF--SVCFCLYSLl 306
XP_018645655 281 VCAIYMICLIgmiifaycrfhs 302
Q55FS3       300 ILPIGIITVF--SVGFCIFSLL 319 Dictyostelium discoideum
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