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5A63

Cryo-EM structure of the human gamma-secretase complex at 3.4 angstrom resolution.

Replaces:  4UPC
Functional Information from GO Data
ChainGOidnamespacecontents
A0016020cellular_componentmembrane
A0016485biological_processprotein processing
B0000045biological_processautophagosome assembly
B0000122biological_processnegative regulation of transcription by RNA polymerase II
B0000139cellular_componentGolgi membrane
B0000776cellular_componentkinetochore
B0001568biological_processblood vessel development
B0001708biological_processcell fate specification
B0001756biological_processsomitogenesis
B0001764biological_processneuron migration
B0001921biological_processpositive regulation of receptor recycling
B0001947biological_processheart looping
B0002038biological_processpositive regulation of L-glutamate import across plasma membrane
B0002244biological_processhematopoietic progenitor cell differentiation
B0002265biological_processastrocyte activation involved in immune response
B0002286biological_processT cell activation involved in immune response
B0002573biological_processmyeloid leukocyte differentiation
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
B0005654cellular_componentnucleoplasm
B0005737cellular_componentcytoplasm
B0005739cellular_componentmitochondrion
B0005743cellular_componentmitochondrial inner membrane
B0005765cellular_componentlysosomal membrane
B0005768cellular_componentendosome
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
B0006486biological_processprotein glycosylation
B0006508biological_processproteolysis
B0006509biological_processmembrane protein ectodomain proteolysis
B0006839biological_processmitochondrial transport
B0006874biological_processintracellular calcium ion homeostasis
B0006914biological_processautophagy
B0006915biological_processapoptotic process
B0006974biological_processDNA damage response
B0006979biological_processresponse to oxidative stress
B0007155biological_processcell adhesion
B0007175biological_processnegative regulation of epidermal growth factor-activated receptor activity
B0007219biological_processNotch signaling pathway
B0007220biological_processNotch receptor processing
B0007420biological_processbrain development
B0007507biological_processheart development
B0007611biological_processlearning or memory
B0007613biological_processmemory
B0008013molecular_functionbeta-catenin binding
B0008021cellular_componentsynaptic vesicle
B0008233molecular_functionpeptidase activity
B0009791biological_processpost-embryonic development
B0009986cellular_componentcell surface
B0010467biological_processgene expression
B0010468biological_processregulation of gene expression
B0010628biological_processpositive regulation of gene expression
B0010629biological_processnegative regulation of gene expression
B0010975biological_processregulation of neuron projection development
B0015031biological_processprotein transport
B0015871biological_processcholine transport
B0016020cellular_componentmembrane
B0016080biological_processsynaptic vesicle targeting
B0016235cellular_componentaggresome
B0016485biological_processprotein processing
B0021549biological_processcerebellum development
B0021795biological_processcerebral cortex cell migration
B0021870biological_processCajal-Retzius cell differentiation
B0021904biological_processdorsal/ventral neural tube patterning
B0021987biological_processcerebral cortex development
B0022008biological_processneurogenesis
B0030054cellular_componentcell junction
B0030165molecular_functionPDZ domain binding
B0030182biological_processneuron differentiation
B0030326biological_processembryonic limb morphogenesis
B0030424cellular_componentaxon
B0030425cellular_componentdendrite
B0030426cellular_componentgrowth cone
B0030900biological_processforebrain development
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
B0035282biological_processsegmentation
B0035556biological_processintracellular signal transduction
B0035577cellular_componentazurophil granule membrane
B0040011biological_processlocomotion
B0042307biological_processpositive regulation of protein import into nucleus
B0042325biological_processregulation of phosphorylation
B0042383cellular_componentsarcolemma
B0042500molecular_functionaspartic endopeptidase activity, intramembrane cleaving
B0042734cellular_componentpresynaptic membrane
B0042982biological_processamyloid precursor protein metabolic process
B0042987biological_processamyloid precursor protein catabolic process
B0042995cellular_componentcell projection
B0043005cellular_componentneuron projection
B0043011biological_processmyeloid dendritic cell differentiation
B0043025cellular_componentneuronal cell body
B0043065biological_processpositive regulation of apoptotic process
B0043066biological_processnegative regulation of apoptotic process
B0043198cellular_componentdendritic shaft
B0043524biological_processnegative regulation of neuron apoptotic process
B0043589biological_processskin morphogenesis
B0045121cellular_componentmembrane raft
B0045202cellular_componentsynapse
B0045296molecular_functioncadherin binding
B0045821biological_processpositive regulation of glycolytic process
B0045893biological_processpositive regulation of DNA-templated transcription
B0048143biological_processastrocyte activation
B0048167biological_processregulation of synaptic plasticity
B0048538biological_processthymus development
B0048666biological_processneuron development
B0048705biological_processskeletal system morphogenesis
B0048854biological_processbrain morphogenesis
B0050435biological_processamyloid-beta metabolic process
B0050673biological_processepithelial cell proliferation
B0050771biological_processnegative regulation of axonogenesis
B0050808biological_processsynapse organization
B0050820biological_processpositive regulation of coagulation
B0050852biological_processT cell receptor signaling pathway
B0051117molecular_functionATPase binding
B0051208biological_processsequestering of calcium ion
B0051402biological_processneuron apoptotic process
B0051444biological_processnegative regulation of ubiquitin-protein transferase activity
B0051563biological_processsmooth endoplasmic reticulum calcium ion homeostasis
B0051604biological_processprotein maturation
B0051966biological_processregulation of synaptic transmission, glutamatergic
B0055074biological_processcalcium ion homeostasis
B0060075biological_processregulation of resting membrane potential
B0060828biological_processregulation of canonical Wnt signaling pathway
B0060999biological_processpositive regulation of dendritic spine development
B0070050biological_processneuron cellular homeostasis
B0070588biological_processcalcium ion transmembrane transport
B0070765cellular_componentgamma-secretase complex
B0070851molecular_functiongrowth factor receptor binding
B0097060cellular_componentsynaptic membrane
B0097190biological_processapoptotic signaling pathway
B0098609biological_processcell-cell adhesion
B0098693biological_processregulation of synaptic vesicle cycle
B0098712biological_processL-glutamate import across plasma membrane
B0098794cellular_componentpostsynapse
B0098978cellular_componentglutamatergic synapse
B0099175biological_processregulation of postsynapse organization
B0140249biological_processprotein catabolic process at postsynapse
B1904646biological_processcellular response to amyloid-beta
B1904797biological_processnegative regulation of core promoter binding
B1905598biological_processnegative regulation of low-density lipoprotein receptor activity
B1905908biological_processpositive regulation of amyloid fibril formation
B1990535biological_processneuron projection maintenance
B2000059biological_processnegative regulation of ubiquitin-dependent protein catabolic process
B2001234biological_processnegative regulation of apoptotic signaling pathway
C0000139cellular_componentGolgi membrane
C0001656biological_processmetanephros development
C0005515molecular_functionprotein binding
C0005769cellular_componentearly endosome
C0005783cellular_componentendoplasmic reticulum
C0005789cellular_componentendoplasmic reticulum membrane
C0005794cellular_componentGolgi apparatus
C0005886cellular_componentplasma membrane
C0006509biological_processmembrane protein ectodomain proteolysis
C0007219biological_processNotch signaling pathway
C0007220biological_processNotch receptor processing
C0008021cellular_componentsynaptic vesicle
C0010008cellular_componentendosome membrane
C0010950biological_processpositive regulation of endopeptidase activity
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 Residues36
DetailsTOPO_DOM: Cytoplasmic => ECO:0000269|PubMed:26280335
ChainResidueDetails
DMET1-LYS17
DPHE37-VAL57
CASP140-LEU158
CPRO208-SER213
BLYS429-LEU432

site_idSWS_FT_FI2
Number of Residues18
DetailsINTRAMEM: Helical => ECO:0000269|PubMed:26280335
ChainResidueDetails
DTYR18-TRP36
BILE133-LEU153
BILE167-TYR189
BTYR195-LYS216
BLEU221-LEU241
BILE249-VAL272
BLEU381-SER401
BILE408-PHE428
BPRO433-VAL453

site_idSWS_FT_FI3
Number of Residues20
DetailsTRANSMEM: Helical => ECO:0000269|PubMed:26280335
ChainResidueDetails
DTRP58-PHE78
CTYR90-ALA118
CASP180-ARG186
CSER235-ASP265
BGLN454-ILE467

site_idSWS_FT_FI4
Number of Residues22
DetailsTOPO_DOM: Lumenal => ECO:0000269|PubMed:26280335, ECO:0000305|PubMed:12639958
ChainResidueDetails
DGLN79-PRO101
AASN187

site_idSWS_FT_FI5
Number of Residues20
DetailsTRANSMEM: Helical; Name=3 => ECO:0000269|PubMed:26280335
ChainResidueDetails
CTYR69-ALA89
AASN264
AASN435
AASN464
AASN506
AASN530
AASN562
AASN573

site_idSWS_FT_FI6
Number of Residues20
DetailsTRANSMEM: Helical; Name=4 => ECO:0000269|PubMed:26280335
ChainResidueDetails
CTYR119-ALA139
BMET292
AASN417

site_idSWS_FT_FI7
Number of Residues20
DetailsTRANSMEM: Helical; Name=5 => ECO:0000269|PubMed:26280335
ChainResidueDetails
CTHR159-PHE179

site_idSWS_FT_FI8
Number of Residues20
DetailsTRANSMEM: Helical; Name=6 => ECO:0000269|PubMed:26280335
ChainResidueDetails
CTYR187-ASN207

site_idSWS_FT_FI9
Number of Residues20
DetailsTRANSMEM: Helical; Name=7 => ECO:0000269|PubMed:26280335
ChainResidueDetails
CLEU214-GLY234

site_idSWS_FT_FI10
Number of Residues1
DetailsMOD_RES: Phosphoserine => ECO:0000250|UniProtKB:P97887
ChainResidueDetails
BSER51

site_idSWS_FT_FI11
Number of Residues1
DetailsMOD_RES: Phosphoserine; by PKA => ECO:0000269|PubMed:14576165
ChainResidueDetails
BSER310

site_idSWS_FT_FI12
Number of Residues1
DetailsMOD_RES: Phosphoserine; by PKC => ECO:0000269|PubMed:14576165
ChainResidueDetails
BSER346

site_idSWS_FT_FI13
Number of Residues1
DetailsMOD_RES: Phosphoserine => ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163
ChainResidueDetails
BSER367

226707

PDB entries from 2024-10-30

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