Beta-secretase 1

BACE1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1FKN, 1M4H, 1PY1, 1SGZ, 1TQF, 1UJJ, 1UJK, 1W50, 1W51, 1XN2, 1XN3, 1XS7, 1YM2, 1YM4, 2B8L, 2B8V, 2F3E, 2F3F, 2FDP, 2G94, 2HIZ, 2HM1, 2IQG, 2IRZ, 2IS0, 2NTR, 2OAH, 2OF0, 2OHK, 2OHL, 2OHM, 2OHN, 2OHP, 2OHQ, 2OHR, 2OHS, 2OHT, 2OHU, 2P4J, 2P83, 2P8H, 2PH6, 2PH8, 2Q11, 2Q15, 2QK5, 2QMD, 2QMF, 2QMG, 2QP8, 2QU2, 2QU3, 2QZK, 2QZL, 2VA5, 2VA6, 2VA7, 2VIE, 2VIJ, 2VIY, 2VIZ, 2VJ6, 2VJ7, 2VJ9, 2VKM, 2VNM, 2VNN, 2WEZ, 2WF0, 2WF1, 2WF2, 2WF3, 2WF4, 2WJO, 2XFI, 2XFJ, 2XFK, 2ZDZ, 2ZE1, 2ZHR, 2ZHS, 2ZHT, 2ZHU, 2ZHV, 2ZJH, 2ZJI, 2ZJJ, 2ZJK, 2ZJL, 2ZJM, 2ZJN, 3BRA, 3BUF, 3BUG, 3BUH, 3CIB, 3CIC, 3CID, 3CKP, 3CKR, 3DM6, 3DUY, 3DV1, 3DV5, 3EXO, 3FKT, 3H0B, 3HVG, 3HW1, 3I25, 3IGB, 3IN3, 3IN4, 3IND, 3INE, 3INF, 3INH, 3IVH, 3IVI, 3IXJ, 3IXK, 3KYR, 3L38, 3L3A, 3LHG, 3LNK, 3MSJ, 3MSK, 3MSL, 3N4L, 3NSH, 3OOZ, 3QI1, 3R1G, 3RSV, 3RTM, 3RVI, 3S2O, 3S7L, 3S7M, 3TPJ, 3TPL, 3TPP, 3TPR, 3UDH, 3UDJ, 3UDK, 3UDM, 3UDN, 3UDP, 3UDQ, 3UDR, 3UDY, 3UFL, 3UQP, 3UQR, 3UQU, 3UQW, 3UQX, 3VEU, 3VF3, 3VG1, 3VV6, 3VV7, 3ZMG, 3ZOV, 4ACU, 4ACX, 4AZY, 4B00, 4B05, 4B0Q, 4B1C, 4B1D, 4B1E, 4B70, 4B72, 4B77, 4B78, 4BEK, 4BFD, 4D83, 4D85, 4D88, 4D89, 4D8C, 4DH6, 4DI2, 4DJU, 4DJV, 4DJW, 4DJX, 4DJY, 4DPF, 4DPI, 4DUS, 4DV9, 4DVF, 4EWO, 4EXG, 4FCO, 4FGX, 4FM7, 4FM8, 4FRI, 4FRJ, 4FRK, 4FRS, 4FS4, 4FSE, 4FSL, 4GMI, 4H1E, 4H3F, 4H3G, 4H3I, 4H3J, 4HA5, 4HZT, 4I0E, 4I0F, 4I0G, 4I0H, 4I0J, 4I0Z, 4I10, 4I11, 4I12, 4I1C, 4J0T, 4J0V, 4J0Y, 4J0Z, 4J17, 4J1C, 4J1E, 4J1F, 4J1H, 4J1I, 4J1K, 4JOO, 4JP9, 4JPC, 4JPE, 4K8S, 4K9H, 4KE0, 4KE1, 3K5C, 3K5D, 3K5F, 3K5G, 3KMX, 3KMY, 3KN0, 3L58, 3L59, 3L5B, 3L5C, 3L5D, 3L5E, 3L5F, 3LPI, 3LPJ, 3LPK, 3OHF, 3OHH, 3PI5, 3QBH, 3R2F, 3RSX, 3RTH, 3RTN, 3RU1, 3SKF, 3SKG, 3U6A, 4GID, 4LXA, 4LXK, 4LXM, 3WB4, 3WB5, 4I0D, 4I0I, 4IVS, 4IVT, 4J0P, 4L7G, 4L7H, 4L7J, 4LC7, 4N00, 4PZW, 4PZX, 4R5N, 4R8Y, 4R91, 4R92, 4R93, 4R95, 4RCD, 4RCE, 4RCF, 4RRN, 4RRO, 4RRS, 4WY1, 4WY6, 4X2L, 4X7I, 4XKX, 4XXS, 4YBI, 4TRW, 4TRZ, 4ZSM, 4ZSP, 4ZSQ, 4ZSR, 4TRY, 4ZPF, 4ZPG, 5CLM, 5F01, 5EZZ, 5DQC, 5F00, 5EZX, 5HE7, 5HD0, 5HDX, 5HDV, 5HE5, 5HE4, 5HDU, 5HDZ, 5I3X, 5I3W, 5I3V, 5IE1, 5I3Y, 5ENK
Identifiers
Aliases	BACE1, ASP2, BACE, HSPC104, beta-secretase 1
External IDs	OMIM: 604252; MGI: 1346542; HomoloGene: 8014; GeneCards: BACE1; OMA:BACE1 - orthologs
EC number	3.4.23.46
Gene location (Human)
Chr.	Chromosome 11 (human)
End	117,316,259 bp
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)
End	45,775,697 bp
RNA expression pattern
	Top expressed in
	inferior ganglion of vagus nerve; ; body of pancreas; ; C1 segment; ; corpus callosum; ; stromal cell of endometrium; ; subthalamic nucleus; ; medulla oblongata; ; ventral tegmental area; ; inferior olivary nucleus; ; superior vestibular nucleus;
	Top expressed in
	external carotid artery; ; internal carotid artery; ; Rostral migratory stream; ; medullary collecting duct; ; epithelium of lens; ; facial motor nucleus; ; vas deferens; ; ciliary body; ; anterior horn of spinal cord; ; renal corpuscle;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	endopeptidase activity; amyloid-beta binding; beta-aspartyl-peptidase activity; protein binding; enzyme binding; hydrolase activity; peptidase activity; aspartic-type endopeptidase activity;
Cellular component	multivesicular body; late endosome; endoplasmic reticulum lumen; membrane; plasma membrane; cell surface; axon; endoplasmic reticulum; Golgi-associated vesicle lumen; endosome membrane; cytoplasmic vesicle membrane; cytoplasmic vesicle; integral component of plasma membrane; membrane raft; Golgi apparatus; integral component of membrane; endosome; trans-Golgi network; lysosome; early endosome; synaptic vesicle; dendrite; soma; recycling endosome; hippocampal mossy fiber to CA3 synapse; presynapse;
Biological process	protein catabolic process; proteolysis; amyloid-beta metabolic process; membrane protein ectodomain proteolysis; modulation of chemical synaptic transmission; response to radiation; response to lead ion; positive regulation of neuron apoptotic process; detection of mechanical stimulus involved in sensory perception of pain; prepulse inhibition; cellular response to copper ion; cellular response to manganese ion; cellular response to amyloid-beta; regulation of synaptic vesicle exocytosis;
	Sources:Amigo / QuickGO
Orthologs
	23621
	23821
	ENSG00000186318
	ENSMUSG00000032086
	P56817
	P56818
NM_138973; NM_001207048; NM_001207049; NM_012104; NM_138971;
	NM_138972
	NM_001145947; NM_011792
NP_001193977; NP_001193978; NP_036236; NP_620427; NP_620428;
	NP_620429; NP_036236.1
	NP_001139419; NP_035922
	Wikidata
View/Edit Human	View/Edit Mouse

Beta-secretase 1, also known as beta-site amyloid precursor protein cleaving enzyme 1, beta-site APP cleaving enzyme 1 (BACE1), membrane-associated aspartic protease 2, memapsin-2, aspartyl protease 2, and ASP2, is an enzyme that in humans is encoded by the BACE1 gene.^[5] Expression of BACE1 is observed mainly in neurons and oligodendrocytes.^[6]

BACE1 is an aspartic acid protease important in the formation of myelin sheaths in peripheral nerve cells: in mice the expression of BACE1 is high in the postnatal stages, when myelination occurs.^[7] The transmembrane protein contains two active site aspartate residues in its extracellular protein domain and may function as a dimer, its cytoplasmic tail is required for the correct maturation and an efficient intracellular trafficking, but does not affect the activity. It is produced as a pro-enzyme, the endoproteolitc removal occurs after BACE leaves endoplasmic reticulum, in the Golgi apparatus. In addition the pro-peptide receives additional sugars to increase the molecular mass.^[8] and the tail became a palmitoylated.

The BACE1 expression is influenced by the inflammatory state: during AD the cytokines reduce the PPAR1 an inhibitor of BACE1 mRNA.

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000186318 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000032086 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, et al. (October 1999). "Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE". Science. 286 (5440): 735–741. doi:10.1126/science.286.5440.735. PMID 10531052. S2CID 42481897. Archived from the original on 2019-04-09. Retrieved 2019-07-01.
^ Rajani RM, Ellingford R, Hellmuth M, Harris SS, Taso OS, Graykowski D, et al. (July 2024). "Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer's disease". PLOS Biology. 22 (7): e3002727. doi:10.1371/journal.pbio.3002727. PMC 11265669. PMID 39042667.
^
Willem M, Garratt AN, Novak B, Citron M, Kaufmann S, Rittger A, et al. (October 2006). "Control of peripheral nerve myelination by the beta-secretase BACE1". Science. 314 (5799): 664–666. Bibcode:2006Sci...314..664W. doi:10.1126/science.1132341. PMID 16990514. S2CID 8432207.
- Lay summary in: Phillips ML (September 21, 2006). "Alzheimer's enzyme important for myelin". The Scientist.
^ Capell A, Steiner H, Willem M, Kaiser H, Meyer C, Walter J, et al. (October 2000). "Maturation and pro-peptide cleavage of beta-secretase". The Journal of Biological Chemistry. 275 (40): 30849–30854. doi:10.1074/jbc.M003202200. PMID 10801872.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000186318 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000032086 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid10531052-5] Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, et al. (October 1999). "Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE". Science. 286 (5440): 735–741. doi:10.1126/science.286.5440.735. PMID 10531052. S2CID 42481897. Archived from the original on 2019-04-09. Retrieved 2019-07-01.

[6] Rajani RM, Ellingford R, Hellmuth M, Harris SS, Taso OS, Graykowski D, et al. (July 2024). "Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer's disease". PLOS Biology. 22 (7): e3002727. doi:10.1371/journal.pbio.3002727. PMC 11265669. PMID 39042667.

[pmid16990514-7] Willem M, Garratt AN, Novak B, Citron M, Kaufmann S, Rittger A, et al. (October 2006). "Control of peripheral nerve myelination by the beta-secretase BACE1". Science. 314 (5799): 664–666. Bibcode:2006Sci...314..664W. doi:10.1126/science.1132341. PMID 16990514. S2CID 8432207.
Lay summary in: Phillips ML (September 21, 2006). "Alzheimer's enzyme important for myelin". The Scientist.

[8] Lay summary in: Phillips ML (September 21, 2006). "Alzheimer's enzyme important for myelin". The Scientist.

[8] Capell A, Steiner H, Willem M, Kaiser H, Meyer C, Walter J, et al. (October 2000). "Maturation and pro-peptide cleavage of beta-secretase". The Journal of Biological Chemistry. 275 (40): 30849–30854. doi:10.1074/jbc.M003202200. PMID 10801872.

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