Beta-secretase 1

Function

Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase. Cleaves CHL1 (By similarity).

Classification

Family (Pfam)

PF00026 Asp

InterPro

Aspartic_peptidase_A1, Aspartic_peptidase_AS, BACE, BACE1, Memapsin-like, PEPTIDASE_A1, Peptidase_aspartic_dom_sf

Functional cluster

S-Adenosylmethionine Synthases & related

Experimental structures · PDB · 431

• 1FKN X-ray 1.90A
• 1M4H X-ray 2.10A
• 1PY1 X-ray 2.60A
• 1SGZ X-ray 2.00A
• 1TQF X-ray 1.80A
• 1UJJ X-ray 2.60A
• 1UJK X-ray 1.90A
• 1W50 X-ray 1.75A
• 1W51 X-ray 2.55A
• 1XN2 X-ray 1.90A
• 1XN3 X-ray 2.00A
• 1XS7 X-ray 2.80A
• … and 419 more

A predicted model is available from AlphaFold.

Gene Ontology · 45

• GO:0030424 axon
• GO:0009986 cell surface
• GO:0030425 dendrite
• GO:0005769 early endosome
• GO:0005788 endoplasmic reticulum lumen
• GO:0005768 endosome
• GO:0010008 endosome membrane
• GO:0005794 Golgi apparatus
• GO:0070931 Golgi-associated vesicle lumen
• GO:0098686 hippocampal mossy fiber to CA3 synapse
• GO:0005770 late endosome
• GO:0005764 lysosome
• GO:0016020 membrane
• GO:0045121 membrane raft
• GO:0005771 multivesicular body
• GO:0043025 neuronal cell body
• GO:0005886 plasma membrane
• GO:0055037 recycling endosome
• GO:0008021 synaptic vesicle
• GO:0005802 trans-Golgi network
• GO:0001540 amyloid-beta binding
• GO:0004190 aspartic-type endopeptidase activity
• GO:0008798 beta-aspartyl-peptidase activity
• GO:0004175 endopeptidase activity
• GO:0019899 enzyme binding
• GO:0008233 peptidase activity
• GO:0120283 protein serine/threonine kinase binding
• GO:1990000 amyloid fibril formation
• GO:0042987 amyloid precursor protein catabolic process
• GO:0034205 amyloid-beta formation
• GO:0050435 amyloid-beta metabolic process
• GO:1904646 cellular response to amyloid-beta
• GO:0071280 cellular response to copper ion
• GO:0071287 cellular response to manganese ion
• GO:0050966 detection of mechanical stimulus involved in sensory perception of pain
• GO:0006509 membrane protein ectodomain proteolysis
• GO:0043525 positive regulation of neuron apoptotic process
• GO:0060134 prepulse inhibition
• GO:0099171 presynaptic modulation of chemical synaptic transmission
• GO:0016485 protein processing
• GO:0006508 proteolysis
• GO:1990418 response to insulin-like growth factor stimulus
• GO:0010288 response to lead ion
• GO:0140448 signaling receptor ligand precursor processing
• GO:0036269 swimming behavior

Drugs targeting this protein · 4

• VERUBECESTAT inhibitor
• ATABECESTAT inhibitor
• LANABECESTAT inhibitor
• ELENBECESTAT inhibitor

Related proteins · sequence + function similarity

• Beta-secretase 1 1.00
• Beta-secretase 1 1.00
• Beta-secretase 1 1.00
• Beta-secretase 1 0.98
• Beta-secretase 2 0.74
• Beta-secretase 2 0.74
• Beta-secretase 2 0.73
• Beta-secretase 0.72
• Aspartic proteinase PCS1 0.55
• Aspartic protease 2 0.53
• UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 2 0.51
• Dermatan-sulfate epimerase 0.51

Co-cited proteins · studied together in the literature

• Beta-secretase 2 4 shared papers
• Beta-secretase 1 1 shared papers
• Beta-secretase 1 4 shared papers
• Septin-8 1 shared papers
• ADP-ribosylation factor-binding protein GGA3 3 shared papers
• Ubiquitin carboxyl-terminal hydrolase 8 1 shared papers
• Sorting nexin-6 1 shared papers
• Napsin-A 1 shared papers
• ADP-ribosylation factor-binding protein GGA1 3 shared papers
• Reticulon-3 3 shared papers
• Proprotein convertase subtilisin/kexin type 9 1 shared papers
• Amyloid-beta precursor protein 3 shared papers

Literature · 37 cited papers

• The Endosome-associated Deubiquitinating Enzyme USP8 Regulates BACE1 Enzyme Ubiquitination and Degradation. J. Biol. Chem. · 2016
• BIN1 regulates BACE1 intracellular trafficking and amyloid-beta production. Hum. Mol. Genet. · 2016
• SEPT8 modulates beta-amyloidogenic processing of APP by affecting the sorting and accumulation of BACE1. J. Cell Sci. · 2016
• Transcriptional regulation of BACE1 by NFAT3 leads to enhanced amyloidogenic processing. Neurochem. Res. · 2015
• BACE1 protein endocytosis and trafficking are differentially regulated by ubiquitination at lysine 501 and the Di-leucine motif in the carboxyl terminus. J. Biol. Chem. · 2012
• AT-1 is the ER membrane acetyl-CoA transporter and is essential for cell viability. J. Cell Sci. · 2010
• Ubiquitin regulates GGA3-mediated degradation of BACE1. J. Biol. Chem. · 2010
• Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing. FASEB J. · 2010
• Two endoplasmic reticulum (ER)/ER Golgi intermediate compartment-based lysine acetyltransferases post-translationally regulate BACE1 levels. J. Biol. Chem. · 2009
• PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1. EMBO Rep. · 2008
• A reversible form of lysine acetylation in the ER and Golgi lumen controls the molecular stabilization of BACE1. Biochem. J. · 2007
• Mapping of interaction domains mediating binding between BACE1 and RTN/Nogo proteins. J. Mol. Biol. · 2006
• … and 25 more in the literature graph