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TargetGamma-secretase subunit APH-1A/Gamma-secretase subunit PEN-2/Nicastrin [34-709]/Presenilin-1
LigandBDBM28925
Substrate/CompetitorBeta amyloid A4 protein
Meas. Tech.Cell-Based Assay for Amyloid-beta Accumulation
EC50 25±n/a nM
Comments10 fold selectivity vs Notch inhibition.
Citation Mayer, SCKreft, AFHarrison, BAbou-Gharbia, MAntane, MAschmies, SAtchison, KChlenov, MCole, DCComery, TDiamantidis, GEllingboe, JFan, KGalante, RGonzales, CHo, DMHoke, MEHu, YHuryn, DJain, UJin, MKremer, KKubrak, DLin, MLu, PMagolda, RMartone, RMoore, WOganesian, APangalos, MNPorte, AReinhart, PResnick, LRiddell, DRSonnenberg-Reines, JStock, JRSun, SCWagner, EWang, TWoller, KXu, ZZaleska, MMZeldis, JZhang, MZhou, HJacobsen, JS Discovery of begacestat, a Notch-1-sparing gamma-secretase inhibitor for the treatment of Alzheimer's disease. J Med Chem51:7348-51 (2008) [PubMed]  Article
More Info.:Get all data from this article,   Solution Info,  Assay Method
 
Gamma-secretase subunit APH-1A/Gamma-secretase subunit PEN-2/Nicastrin [34-709]/Presenilin-1
Name:Gamma-secretase subunit APH-1A/Gamma-secretase subunit PEN-2/Nicastrin [34-709]/Presenilin-1
Synonyms:Gamma-Secretase
Type:Multi-subunit protease complex
Mol. Mass.:n/a
Description:A complex composed of a presenilin homodimer, nicastrin, APH1 and PEN2. It is the minimal complex sufficient for secretase activity.
Components:This complex has 4 components.
Component 1
Name:Gamma-secretase subunit APH-1A
Synonyms:APH-1a | APH1A | APH1A_HUMAN | Aph-1alpha | Gamma-Secretase Subunit APH-1A | PSF | Presenilin-stabilization factor
Type:Enzyme subunit; multi-pass membrane protein
Mol. Mass.:28998.73
Organism:Homo sapiens (Human)
Description:n/a
Residue:265
Sequence:
MGAAVFFGCTFVAFGPAFALFLITVAGDPLRVIILVAGAFFWLVSLLLASVVWFILVHVT
DRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYV
SGLSFGIISGVFSVINILADALGPGVVGIHGDSPYYFLTSAFLTAAIILLHTFWGVVFFD
ACERRRYWALGLVVGSHLLTSGLTFLNPWYEASLLPIYAVTVSMGLWAFITAGGSLRSIQ
RSLLCRRQEDSRVMVYSALRIPPED
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Component 2
Name:Gamma-secretase subunit PEN-2
Synonyms:Gamma-Secretase Subunit PEN-2 | Gamma-secretase | PEN2 | PEN2_HUMAN | PSENEN | Presenilin enhancer protein 2
Type:Enzyme subunit; multi-pass membrane protein
Mol. Mass.:12031.98
Organism:Homo sapiens (Human)
Description:n/a
Residue:101
Sequence:
MNLERVSNEEKLNLCRKYYLGGFAFLPFLWLVNIFWFFREAFLVPAYTEQSQIKGYVWRS
AVGFLFWVIVLTSWITIFQIYRPRWGALGDYLSFTIPLGTP
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Component 3
Name:Nicastrin [34-709]
Synonyms:Gamma-Secretase Subunit Nicastrin | KIAA0253 | NCSTN | NICA_HUMAN
Type:Single-pass type I membrane protein
Mol. Mass.:75243.23
Organism:Homo sapiens (Human)
Description:Q92542[34-709]
Residue:676
Sequence:
NSVERKIYIPLNKTAPCVRLLNATHQIGCQSSISGDTGVIHVVEKEEDLQWVLTDGPNPP
YMVLLESKHFTRDLMEKLKGRTSRIAGLAVSLTKPSPASGFSPSVQCPNDGFGVYSNSYG
PEFAHCREIQWNSLGNGLAYEDFSFPIFLLEDENETKVIKQCYQDHNLSQNGSAPTFPLC
AMQLFSHMHAVISTATCMRRSSIQSTFSINPEIVCDPLSDYNVWSMLKPINTTGTLKPDD
RVVVAATRLDSRSFFWNVAPGAESAVASFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGE
TFDYIGSSRMVYDMEKGKFPVQLENVDSFVELGQVALRTSLELWMHTDPVSQKNESVRNQ
VEDLLATLEKSGAGVPAVILRRPNQSQPLPPSSLQRFLRARNISGVVLADHSGAFHNKYY
QSIYDTAENINVSYPEWLSPEEDLNFVTDTAKALADVATVLGRALYELAGGTNFSDTVQA
DPQTVTRLLYGFLIKANNSWFQSILRQDLRSYLGDGPLQHYIAVSSPTNTTYVVQYALAN
LTGTVVNLTREQCQDPSKVPSENKDLYEYSWVQGPLHSNETDRLPRCVRSTARLARALSP
AFELSQWSSTEYSTWTESRWKDIRARIFLIASKELELITLTVGFGILIFSLIVTYCINAK
ADVLFIAPREPGAVSY
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Component 4
Name:Presenilin-1
Synonyms:3.4.23.- | AD3 | Gamma-Secretase Subunit Presenilin-1 | PS-1 | PS1 | PS1-CTF12 | PSEN1 | PSN1_HUMAN | PSNL1 | Presenilin-1 CTF subunit | Presenilin-1 CTF12 | Presenilin-1 NTF subunit | Protein S182
Type:n/a
Mol. Mass.:52657.13
Organism:Homo sapiens (Human)
Description:P49768
Residue:467
Sequence:
MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSR
QVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTE
DTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFI
YLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKY
LPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAE
GDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAA
VQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCL
TLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI
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BDBM28925
Beta amyloid A4 protein
Name:Amyloid-beta precursor protein
Synonyms:A4 | A4_HUMAN | ABPP | AD1 | AICD-50 | AICD-57 | AICD-59 | AID(50) | AID(57) | AID(59) | APP | APPI | Alzheimer disease amyloid protein | Amyloid beta A4 protein | Amyloid beta Protein | Amyloid beta protein (sAPPbeta) | Amyloid beta protein Abeta(1-42) | Amyloid intracellular domain 50 | Amyloid intracellular domain 57 | Amyloid intracellular domain 59 | Amyloid protein (Abeta42b) | Amyloid β-protein (Aβ42) | Beta amyloid A4 protein | Beta-APP40 | Beta-APP42 | Beta-amyloid protein 40 | Beta-amyloid protein 42 | C31 | C83 | C99 | CVAP | Cerebral vascular amyloid peptide | Gamma Secretase | Gamma-CTF(50) | Gamma-CTF(57) | Gamma-CTF(59) | Gamma-secretase | Gamma-secretase C-terminal fragment 50 | Gamma-secretase C-terminal fragment 57 | Gamma-secretase C-terminal fragment 59 | P3(40) | P3(42) | PN-II | PreA4 | Protease nexin-II | S-APP-alpha | S-APP-beta | Soluble APP-alpha | Soluble APP-beta | beta-Amyloid Precursor Protein (APP)
Type:Single-pass type I membrane protein
Mol. Mass.:86890.41
Organism:Homo sapiens (Human)
Description:P05067
Residue:770
Sequence:
MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTK
TCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVG
EFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFR
GVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEE
EADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPC
RAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARD
PVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQA
KNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITAL
QAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYER
MNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTET
KTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTN
IKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITL
VMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN
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