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Details on Person UniProt:P56817 BACE1

Class:Id	ReferenceGeneProduct:50659
_chainChangeLog	signal peptide:1-21 added on Sat February 7 2015;propeptide:22-45 added on Sat February 7 2015;chain:46-501 added on Sat February 7 2015
_displayName	UniProt:P56817 BACE1
_timestamp	2025-05-21 21:10:31
chain	signal peptide:1-21 propeptide:22-45 chain:46-501
checksum	377CE4C824ACEF05
comment	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 (PubMed:10656250, PubMed:10677483, PubMed:20354142). Cleaves CHL1 (By similarity).CATALYTIC ACTIVITY Broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-\|-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein.ACTIVITY REGULATION Inhibited by RTN3 and RTN4.BIOPHYSICOCHEMICAL PROPERTIES kcat is 0.67 sec(-1) and 2.45 sec(-1) for APP cleaved by PSEN1 and APP Swedish variant, respectively (PubMed:10677483).SUBUNIT Monomer. Interacts (via DXXLL motif) with GGA1, GGA2 and GGA3 (via their VHS domain); the interaction highly increases when BACE1 is phosphorylated at Ser-498 (PubMed:14567678, PubMed:15886016). Interacts with RTN1; RTN2; RTN3 and RTN4; the interaction leads to inhibition of amyloid precursor protein processing (PubMed:15286784, PubMed:16965550, PubMed:16979658). Interacts with SNX6 (PubMed:20354142). Interacts with PCSK9 (PubMed:18660751). Interacts with NAT8 and NAT8B (PubMed:19011241). Interacts with BIN1 (PubMed:27179792). Interacts (via extracellular domain) with ADAM10 (via extracellular domain) (By similarity). Interacts with SORL1; this interaction may affect binding with APP and hence reduce APP cleavage (PubMed:16407538). Interacts with NRDC AND NRG1 (By similarity).INTERACTION Predominantly localized to the later Golgi/trans-Golgi network (TGN) and minimally detectable in the early Golgi compartments. A small portion is also found in the endoplasmic reticulum, endosomes and on the cell surface (PubMed:11466313, PubMed:17425515). Colocalization with APP in early endosomes is due to addition of bisecting N-acetylglucosamine which blocks targeting to late endosomes and lysosomes (By similarity). Retrogradly transported from endosomal compartments to the trans-Golgi network in a phosphorylation- and GGA1- dependent manner (PubMed:15886016).ALTERNATIVE PRODUCTS Expressed at high levels in the brain and pancreas. In the brain, expression is highest in the substantia nigra, locus coruleus and medulla oblongata.INDUCTION Up-regulated by the Ca(2+)-regulated transcription factor NFATC4.DOMAIN DXXLL motif is required for a proper endocytosis and retrograde transport to the trans-Golgi network, as well as for regulation of lysosomal degradation.DOMAIN The transmembrane domain is necessary for its activity. It determines its late Golgi localization and access to its substrate, APP.PTM N-Glycosylated (PubMed:11083922, PubMed:17425515). Addition of a bisecting N-acetylglucosamine by MGAT3 blocks lysosomal targeting, further degradation and is required for maintaining stability under stress conditions (By similarity).PTM Acetylated in the endoplasmic reticulum at Lys-126, Lys-275, Lys-279, Lys-285, Lys-299, Lys-300 and Lys-307. Acetylation by NAT8 and NAT8B is transient and deacetylation probably occurs in the Golgi. Acetylation regulates the maturation, the transport to the plasma membrane, the stability and the expression of the protein.PTM Palmitoylation mediates lipid raft localization.PTM Ubiquitinated at Lys-501, ubiquitination leads to lysosomal degradation (PubMed:16033761, PubMed:20484053, PubMed:23109336, PubMed:27302062). Monoubiquitinated and 'Lys-63'-linked polyubitinated (PubMed:20484053). Deubiquitnated by USP8; inhibits lysosomal degradation (PubMed:27302062).PTM Phosphorylation at Ser-498 is required for interaction with GGA1 and retrograded transport from endosomal compartments to the trans-Golgi network. Non-phosphorylated BACE1 enters a direct recycling route to the cell surface.SIMILARITY Belongs to the peptidase A1 family.
description	recommendedName: fullName evidence="38"Beta-secretase 1 ecNumber evidence="8"3.4.23.46 alternativeName: fullName evidence="32"Aspartyl protease 2 shortName evidence="32"ASP2 shortName evidence="32"Asp 2 alternativeName: Beta-site amyloid precursor protein cleaving enzyme 1 shortName: Beta-site APP cleaving enzyme 1 alternativeName: fullName evidence="33 35"Memapsin-2 alternativeName: Membrane-associated aspartic protease 2
geneName	BACE1 BACE KIAA1149
identifier	P56817
isSequenceChanged	FALSE
keyword	3D-structure Acetylation Alternative splicing Aspartyl protease Cell membrane Cell projection Cytoplasmic vesicle Direct protein sequencing Disulfide bond Endoplasmic reticulum Endosome Glycoprotein Golgi apparatus Hydrolase Isopeptide bond Lipoprotein Lysosome Membrane Palmitate Phosphoprotein Protease Proteomics identification Reference proteome Signal Transmembrane Transmembrane helix Ubl conjugation Zymogen
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21
name	BACE1
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8994679] ENSEMBL:ENSG00000186318 BACE1 [Homo sapiens]
secondaryIdentifier	BACE1_HUMAN A0M8W7 B0YIU9 E9PE65 H7BXJ9 Q9BYB9 Q9BYC0 Q9BYC1 Q9UJT5 Q9ULS1
sequenceLength	501
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:144463] UniProt:P56817-2 BACE1 [Homo sapiens] [ReferenceIsoform:144464] UniProt:P56817-3 BACE1 [Homo sapiens] [ReferenceIsoform:144465] UniProt:P56817-4 BACE1 [Homo sapiens] [ReferenceIsoform:404479] UniProt:P56817-1 BACE1 [Homo sapiens] [ReferenceIsoform:8974612] UniProt:P56817-5 BACE1 [Homo sapiens] [ReferenceIsoform:8974613] UniProt:P56817-6 BACE1 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:5692933] BACE1(46-501) [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:5692942] BACE1 [endosome membrane] [Homo sapiens] [EntityWithAccessionedSequence:5693006] 7K-BACE1 [endoplasmic reticulum lumen] [Homo sapiens] [EntityWithAccessionedSequence:5693069] BACE1(22-45) [Golgi-associated vesicle lumen] [Homo sapiens] [EntityWithAccessionedSequence:5693095] 7K-BACE1 [Golgi-associated vesicle lumen] [Homo sapiens] [EntityWithAccessionedSequence:5693105] BACE1(46-501) [Golgi-associated vesicle lumen] [Homo sapiens] [EntityWithAccessionedSequence:5693106] 7K-BACE1(46-501) [Golgi-associated vesicle lumen] [Homo sapiens] [EntityWithAccessionedSequence:6783326] BACE1 [endoplasmic reticulum lumen] [Homo sapiens]
(referenceSequence)	[ModifiedResidue:5692987] N6-acetyl-L-lysine at 275 [ModifiedResidue:5692990] N6-acetyl-L-lysine at 285 [ModifiedResidue:5692995] N6-acetyl-L-lysine at 126 [ModifiedResidue:5692997] N6-acetyl-L-lysine at 279 [ModifiedResidue:5692998] N6-acetyl-L-lysine at 299 [ModifiedResidue:5693002] N6-acetyl-L-lysine at 307 [ModifiedResidue:5693007] N6-acetyl-L-lysine at 300
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