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SummaryStructural detailsExperimental detailsFunctional detailsSequence NeighborHistoryDownloads

8KCS

Cryo-EM structure of human gamma-secretase in complex with BMS906024

Functional Information from GO Data
ChainGOidnamespacecontents
A0016020cellular_componentmembrane
A0016485biological_processprotein processing
B0000122biological_processnegative regulation of transcription by RNA polymerase II
B0000139cellular_componentGolgi membrane
B0000776cellular_componentkinetochore
B0001921biological_processpositive regulation of receptor recycling
B0002265biological_processastrocyte activation involved in immune response
B0003407biological_processneural retina development
B0004175molecular_functionendopeptidase activity
B0004190molecular_functionaspartic-type endopeptidase activity
B0005262molecular_functioncalcium channel activity
B0005515molecular_functionprotein binding
B0005634cellular_componentnucleus
B0005640cellular_componentnuclear outer membrane
B0005737cellular_componentcytoplasm
B0005739cellular_componentmitochondrion
B0005743cellular_componentmitochondrial inner membrane
B0005765cellular_componentlysosomal membrane
B0005769cellular_componentearly endosome
B0005783cellular_componentendoplasmic reticulum
B0005789cellular_componentendoplasmic reticulum membrane
B0005790cellular_componentsmooth endoplasmic reticulum
B0005791cellular_componentrough endoplasmic reticulum
B0005794cellular_componentGolgi apparatus
B0005813cellular_componentcentrosome
B0005886cellular_componentplasma membrane
B0005938cellular_componentcell cortex
B0006508biological_processproteolysis
B0006509biological_processmembrane protein ectodomain proteolysis
B0006915biological_processapoptotic process
B0006974biological_processDNA damage response
B0007155biological_processcell adhesion
B0007219biological_processNotch signaling pathway
B0007220biological_processNotch receptor processing
B0007611biological_processlearning or memory
B0007613biological_processmemory
B0008013molecular_functionbeta-catenin binding
B0008021cellular_componentsynaptic vesicle
B0008233molecular_functionpeptidase activity
B0009986cellular_componentcell surface
B0010468biological_processregulation of gene expression
B0010628biological_processpositive regulation of gene expression
B0010629biological_processnegative regulation of gene expression
B0010975biological_processregulation of neuron projection development
B0016020cellular_componentmembrane
B0016235cellular_componentaggresome
B0016485biological_processprotein processing
B0016787molecular_functionhydrolase activity
B0021549biological_processcerebellum development
B0030165molecular_functionPDZ domain binding
B0030424cellular_componentaxon
B0030425cellular_componentdendrite
B0030426cellular_componentgrowth cone
B0031410cellular_componentcytoplasmic vesicle
B0031594cellular_componentneuromuscular junction
B0031901cellular_componentearly endosome membrane
B0031965cellular_componentnuclear membrane
B0032436biological_processpositive regulation of proteasomal ubiquitin-dependent protein catabolic process
B0032469biological_processendoplasmic reticulum calcium ion homeostasis
B0032760biological_processpositive regulation of tumor necrosis factor production
B0032991cellular_componentprotein-containing complex
B0034205biological_processamyloid-beta formation
B0035253cellular_componentciliary rootlet
B0035556biological_processintracellular signal transduction
B0035577cellular_componentazurophil granule membrane
B0042383cellular_componentsarcolemma
B0042500molecular_functionaspartic endopeptidase activity, intramembrane cleaving
B0042734cellular_componentpresynaptic membrane
B0042982biological_processamyloid precursor protein metabolic process
B0042987biological_processamyloid precursor protein catabolic process
B0043005cellular_componentneuron projection
B0043025cellular_componentneuronal cell body
B0043066biological_processnegative regulation of apoptotic process
B0043198cellular_componentdendritic shaft
B0043524biological_processnegative regulation of neuron apoptotic process
B0043589biological_processskin morphogenesis
B0044233cellular_componentmitochondria-associated endoplasmic reticulum membrane contact site
B0045121cellular_componentmembrane raft
B0045202cellular_componentsynapse
B0045296molecular_functioncadherin binding
B0045821biological_processpositive regulation of glycolytic process
B0045893biological_processpositive regulation of DNA-templated transcription
B0048143biological_processastrocyte activation
B0050808biological_processsynapse organization
B0051117molecular_functionATPase binding
B0055074biological_processcalcium ion homeostasis
B0060090molecular_functionmolecular adaptor activity
B0060828biological_processregulation of canonical Wnt signaling pathway
B0060999biological_processpositive regulation of dendritic spine development
B0070588biological_processcalcium ion transmembrane transport
B0070765cellular_componentgamma-secretase complex
B0070851molecular_functiongrowth factor receptor binding
B0097060cellular_componentsynaptic membrane
B0098609biological_processcell-cell adhesion
B0098693biological_processregulation of synaptic vesicle cycle
B0098794cellular_componentpostsynapse
B0098978cellular_componentglutamatergic synapse
B0099175biological_processregulation of postsynapse organization
B0140249biological_processprotein catabolic process at postsynapse
B1904646biological_processcellular response to amyloid-beta
B1905908biological_processpositive regulation of amyloid fibril formation
B1990535biological_processneuron projection maintenance
B2000059biological_processnegative regulation of ubiquitin-dependent protein catabolic process
C0000139cellular_componentGolgi membrane
C0005515molecular_functionprotein binding
C0005769cellular_componentearly endosome
C0005783cellular_componentendoplasmic reticulum
C0005789cellular_componentendoplasmic reticulum membrane
C0005794cellular_componentGolgi apparatus
C0005886cellular_componentplasma membrane
C0006508biological_processproteolysis
C0006509biological_processmembrane protein ectodomain proteolysis
C0007219biological_processNotch signaling pathway
C0007220biological_processNotch receptor processing
C0008021cellular_componentsynaptic vesicle
C0010008cellular_componentendosome membrane
C0016020cellular_componentmembrane
C0016485biological_processprotein processing
C0019899molecular_functionenzyme binding
C0030674molecular_functionprotein-macromolecule adaptor activity
C0031293biological_processmembrane protein intracellular domain proteolysis
C0032580cellular_componentGolgi cisterna membrane
C0034205biological_processamyloid-beta formation
C0042734cellular_componentpresynaptic membrane
C0042982biological_processamyloid precursor protein metabolic process
C0042987biological_processamyloid precursor protein catabolic process
C0043085biological_processpositive regulation of catalytic activity
C0061133molecular_functionendopeptidase activator activity
C0070765cellular_componentgamma-secretase complex
C0097060cellular_componentsynaptic membrane
D0000139cellular_componentGolgi membrane
D0005515molecular_functionprotein binding
D0005783cellular_componentendoplasmic reticulum
D0005789cellular_componentendoplasmic reticulum membrane
D0005794cellular_componentGolgi apparatus
D0005886cellular_componentplasma membrane
D0006509biological_processmembrane protein ectodomain proteolysis
D0007219biological_processNotch signaling pathway
D0007220biological_processNotch receptor processing
D0010008cellular_componentendosome membrane
D0010950biological_processpositive regulation of endopeptidase activity
D0016020cellular_componentmembrane
D0016485biological_processprotein processing
D0019899molecular_functionenzyme binding
D0031293biological_processmembrane protein intracellular domain proteolysis
D0032580cellular_componentGolgi cisterna membrane
D0034205biological_processamyloid-beta formation
D0042734cellular_componentpresynaptic membrane
D0042982biological_processamyloid precursor protein metabolic process
D0042987biological_processamyloid precursor protein catabolic process
D0061133molecular_functionendopeptidase activator activity
D0070765cellular_componentgamma-secretase complex
Functional Information from PROSITE/UniProt
site_idPS00678
Number of Residues15
DetailsWD_REPEATS_1 Trp-Asp (WD) repeats signature. VAATrlDsRSFFWNV
ChainResidueDetails
AVAL277-VAL291
Functional Information from SwissProt/UniProt
site_idSWS_FT_FI1
Number of Residues635
DetailsTopological domain: {"description":"Extracellular","evidences":[{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000305"},{"source":"PubMed","id":"26776682","evidenceCode":"ECO:0000305"}]}
ChainResidueDetails
site_idSWS_FT_FI2
Number of Residues20
DetailsTransmembrane: {"description":"Helical","evidences":[{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000305"},{"source":"PubMed","id":"26776682","evidenceCode":"ECO:0000305"}]}
ChainResidueDetails
site_idSWS_FT_FI3
Number of Residues2
DetailsGlycosylation: {"description":"N-linked (GlcNAc...) asparagine","evidences":[{"source":"PubMed","id":"19159218","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"30598546","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"30630874","evidenceCode":"ECO:0000269"},{"source":"PDB","id":"5A63","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"6IDF","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"6IYC","evidenceCode":"ECO:0007744"}]}
ChainResidueDetails
site_idSWS_FT_FI4
Number of Residues8
DetailsGlycosylation: {"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000255"},{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"30598546","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"30630874","evidenceCode":"ECO:0000269"},{"source":"PDB","id":"5A63","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"6IDF","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"6IYC","evidenceCode":"ECO:0007744"}]}
ChainResidueDetails
site_idSWS_FT_FI5
Number of Residues3
DetailsGlycosylation: {"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000255"}]}
ChainResidueDetails
site_idSWS_FT_FI6
Number of Residues1
DetailsGlycosylation: {"description":"N-linked (GlcNAc...) asparagine","evidences":[{"source":"PubMed","id":"12754519","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"19159218","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"30598546","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"30630874","evidenceCode":"ECO:0000269"},{"source":"PDB","id":"5A63","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"6IDF","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"6IYC","evidenceCode":"ECO:0007744"}]}
ChainResidueDetails
site_idSWS_FT_FI7
Number of Residues1
DetailsGlycosylation: {"description":"N-linked (GlcNAc...) asparagine","evidences":[{"source":"PubMed","id":"30630874","evidenceCode":"ECO:0000269"},{"source":"PDB","id":"6IYC","evidenceCode":"ECO:0007744"}]}
ChainResidueDetails
site_idSWS_FT_FI8
Number of Residues1
DetailsGlycosylation: {"description":"N-linked (GlcNAc...) asparagine","evidences":[{"source":"PubMed","id":"19349973","evidenceCode":"ECO:0000269"}]}
ChainResidueDetails
site_idSWS_FT_FI9
Number of Residues206
DetailsTransmembrane: {"description":"Helical","evidences":[{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"}]}
ChainResidueDetails
site_idSWS_FT_FI10
Number of Residues56
DetailsTopological domain: {"description":"Lumenal","evidences":[{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"}]}
ChainResidueDetails
site_idSWS_FT_FI11
Number of Residues38
DetailsTopological domain: {"description":"Cytoplasmic","evidences":[{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"}]}
ChainResidueDetails
site_idSWS_FT_FI12
Number of Residues8
DetailsRegion: {"description":"Important for cleavage of target proteins","evidences":[{"source":"PubMed","id":"30598546","evidenceCode":"ECO:0000269"}]}
ChainResidueDetails
site_idSWS_FT_FI13
Number of Residues3
DetailsRegion: {"description":"Interaction with MTCH1","evidences":[{"source":"PubMed","id":"10551805","evidenceCode":"ECO:0000269"}]}
ChainResidueDetails
site_idSWS_FT_FI14
Number of Residues2
DetailsMotif: {"description":"PAL","evidences":[{"source":"PubMed","id":"16305624","evidenceCode":"ECO:0000305"}]}
ChainResidueDetails
site_idSWS_FT_FI15
Number of Residues1
DetailsActive site: {"evidences":[{"source":"PubMed","id":"10206644","evidenceCode":"ECO:0000305"},{"source":"PubMed","id":"10899933","evidenceCode":"ECO:0000305"},{"source":"PubMed","id":"15341515","evidenceCode":"ECO:0000305"}]}
ChainResidueDetails
site_idSWS_FT_FI16
Number of Residues1
DetailsActive site: {"evidences":[{"source":"PubMed","id":"10206644","evidenceCode":"ECO:0000305"},{"source":"PubMed","id":"10899933","evidenceCode":"ECO:0000305"},{"source":"PubMed","id":"15341515","evidenceCode":"ECO:0000305"},{"source":"PubMed","id":"30598546","evidenceCode":"ECO:0000305"},{"source":"PubMed","id":"30630874","evidenceCode":"ECO:0000305"}]}
ChainResidueDetails
site_idSWS_FT_FI17
Number of Residues20
DetailsTransmembrane: {"description":"Helical; Name=1","evidences":[{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"}]}
ChainResidueDetails
site_idSWS_FT_FI18
Number of Residues41
DetailsTopological domain: {"description":"Cytoplasmic","evidences":[{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"14593096","evidenceCode":"ECO:0000305"}]}
ChainResidueDetails
site_idSWS_FT_FI19
Number of Residues20
DetailsTransmembrane: {"description":"Helical; Name=2","evidences":[{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"}]}
ChainResidueDetails
site_idSWS_FT_FI20
Number of Residues38
DetailsTopological domain: {"description":"Lumenal","evidences":[{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"14593096","evidenceCode":"ECO:0000305"}]}
ChainResidueDetails
site_idSWS_FT_FI21
Number of Residues20
DetailsTransmembrane: {"description":"Helical; Name=3","evidences":[{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"}]}
ChainResidueDetails
site_idSWS_FT_FI22
Number of Residues20
DetailsTransmembrane: {"description":"Helical; Name=4","evidences":[{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"}]}
ChainResidueDetails
site_idSWS_FT_FI23
Number of Residues20
DetailsTransmembrane: {"description":"Helical; Name=5","evidences":[{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"}]}
ChainResidueDetails
site_idSWS_FT_FI24
Number of Residues20
DetailsTransmembrane: {"description":"Helical; Name=6","evidences":[{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"}]}
ChainResidueDetails
site_idSWS_FT_FI25
Number of Residues20
DetailsTransmembrane: {"description":"Helical; Name=7","evidences":[{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"}]}
ChainResidueDetails
site_idSWS_FT_FI26
Number of Residues18
DetailsIntramembrane: {"description":"Helical","evidences":[{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"}]}
ChainResidueDetails
site_idSWS_FT_FI27
Number of Residues22
DetailsTopological domain: {"description":"Lumenal","evidences":[{"source":"PubMed","id":"26280335","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"12639958","evidenceCode":"ECO:0000305"}]}
ChainResidueDetails

246333

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