Reaction Details |
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Target | Gamma-secretase subunit APH-1A/Gamma-secretase subunit PEN-2/Nicastrin [34-709]/Presenilin-1 |
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Ligand | BDBM28976 |
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Substrate/Competitor | Beta amyloid A4 protein |
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Meas. Tech. | Cell-Based Assay for Amyloid-beta Accumulation |
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EC50 | 0.51±0.02 nM |
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Citation | Churcher, I; Beher, D; Best, JD; Castro, JL; Clarke, EE; Gentry, A; Harrison, T; Hitzel, L; Kay, E; Kerrad, S; Lewis, HD; Morentin-Gutierrez, P; Mortishire-Smith, R; Oakley, PJ; Reilly, M; Shaw, DE; Shearman, MS; Teall, MR; Williams, S; Wrigley, JD 4-substituted cyclohexyl sulfones as potent, orally active gamma-secretase inhibitors. Bioorg Med Chem Lett16:280-4 (2006) [PubMed] Article |
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More Info.: | Get all data from this article, Solution Info, Assay Method |
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Gamma-secretase subunit APH-1A/Gamma-secretase subunit PEN-2/Nicastrin [34-709]/Presenilin-1 |
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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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BDBM28976 |
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Beta amyloid A4 protein |
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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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