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Protein

Beta-secretase 1

Gene

Bace1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity

Catalytic activityi

Broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-|-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein.

Activity regulationi

Inhibited by RTN3 and RTN4.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei93PROSITE-ProRule annotation1
Active sitei289PROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionAspartyl protease, Hydrolase, Protease

Enzyme and pathway databases

BRENDAi3.4.23.46 3474

Protein family/group databases

MEROPSiA01.004

Names & Taxonomyi

Protein namesi
Recommended name:
Beta-secretase 1 (EC:3.4.23.46)
Alternative name(s):
Aspartyl protease 2
Short name:
ASP2
Short name:
Asp 2
Beta-site amyloid precursor protein cleaving enzyme 1
Short name:
Beta-site APP cleaving enzyme 1
Memapsin-2
Membrane-associated aspartic protease 2
Gene namesi
Name:Bace1
Synonyms:Bace
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1346542 Bace1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 457ExtracellularSequence analysisAdd BLAST436
Transmembranei458 – 478HelicalSequence analysisAdd BLAST21
Topological domaini479 – 501CytoplasmicSequence analysisAdd BLAST23

Keywords - Cellular componenti

Cytoplasmic vesicle, Endoplasmic reticulum, Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice show a higher mortality rate early in life.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi474C → A: Completely abolishes S-palmitoylation; when associated with A-478; A-482 and A-485. Doesn't affect trans-Golgi network and endosome localization; when associated with A-478; A-482 and A-485. Reduces membrane raft association; when associated with A-478; A-482 and A-485. Doesn't affect APP processing; when associated with A-478; A-482 and A-485. 1 Publication1
Mutagenesisi478C → A: Significantly reduces S-palmitoylation; when associated with A-482 and A-485. Completely abolishes S-palmitoylation; when associated with A-474; A-482 and A-485. Doesn't affect trans-Golgi network and endosome localization; when associated with A-474; A-482 and A-485. Reduces membrane raft association; when associated with A-474; A-482 and A-485. Doesn't affect APP processing; when associated with A-474; A-482 and A-485. 1 Publication1
Mutagenesisi482C → A: Significantly reduces S-palmitoylation; when associated with A-478 and A-485. Completely abolishes S-palmitoylation; when associated with A-474; A-478 and A-485. Doesn't affect trans-Golgi network and endosome localization; when associated with A-474; A-478 and A-485. Reduces membrane raft association; when associated with A-474; A-478 and A-485. Doesn't affect APP processing; when associated with A-474; A-478 and A-485. 1 Publication1
Mutagenesisi485C → A: Significantly reduces S-palmitoylation; when associated with A-478 and A-482. Completely abolishes S-palmitoylation; when associated with A-474; A-478 and A-482. Doesn't affect trans-Golgi network and endosome localization; when associated with A-474; A-478 and A-482. Reduces membrane raft association; when associated with A-474; A-478 and A-482. Doesn't affect APP processing; when associated with A-474; A-478 and A-482. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL4593

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
PropeptideiPRO_000002594122 – 45Sequence analysisAdd BLAST24
ChainiPRO_000002594246 – 501Beta-secretase 1Add BLAST456

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei126N6-acetyllysineBy similarity1
Glycosylationi153N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi172N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi216 ↔ 420By similarity
Glycosylationi223N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei275N6-acetyllysineBy similarity1
Disulfide bondi278 ↔ 443By similarity
Modified residuei279N6-acetyllysineBy similarity1
Modified residuei285N6-acetyllysineBy similarity1
Modified residuei299N6-acetyllysineBy similarity1
Modified residuei300N6-acetyllysineBy similarity1
Modified residuei307N6-acetyllysineBy similarity1
Disulfide bondi330 ↔ 380By similarity
Glycosylationi354N-linked (GlcNAc...) asparagineSequence analysis1
Lipidationi474S-palmitoyl cysteine1 Publication1
Lipidationi478S-palmitoyl cysteine1 Publication1
Lipidationi482S-palmitoyl cysteine1 Publication1
Lipidationi485S-palmitoyl cysteine1 Publication1
Modified residuei498PhosphoserineCombined sources1

Post-translational modificationi

N-Glycosylated.By similarity
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 (By similarity).By similarity
Palmitoylation mediates lipid raft localization.1 Publication

Keywords - PTMi

Acetylation, Disulfide bond, Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein, Zymogen

Proteomic databases

MaxQBiP56818
PaxDbiP56818
PeptideAtlasiP56818
PRIDEiP56818

PTM databases

iPTMnetiP56818
PhosphoSitePlusiP56818
SwissPalmiP56818

Expressioni

Tissue specificityi

Brain.

Gene expression databases

BgeeiENSMUSG00000032086 Expressed in 265 organ(s), highest expression level in external carotid artery
CleanExiMM_BACE1
ExpressionAtlasiP56818 baseline and differential
GenevisibleiP56818 MM

Interactioni

Subunit structurei

Monomer. Interacts with GGA1, GGA2 and GGA3. Interacts with RTN3 and RTN4. Interacts with SNX6 (By similarity). Interacts with PCSK9 (By similarity). Interacts with NAT8 and NAT8B (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204741, 7 interactors
IntActiP56818, 1 interactor
MINTiP56818
STRINGi10090.ENSMUSP00000034591

Chemistry databases

BindingDBiP56818

Structurei

3D structure databases

ProteinModelPortaliP56818
SMRiP56818
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini75 – 416Peptidase A1PROSITE-ProRule annotationAdd BLAST342

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni479 – 501Interaction with RTN3By similarityAdd BLAST23

Domaini

The transmembrane domain is necessary for its activity. It determines its late Golgi localization and access to its substrate, APP (By similarity).By similarity

Sequence similaritiesi

Belongs to the peptidase A1 family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1339 Eukaryota
ENOG410XNV7 LUCA
GeneTreeiENSGT00910000144168
HOGENOMiHOG000036572
HOVERGENiHBG059578
InParanoidiP56818
KOiK04521
OMAiNGQDLNM
OrthoDBiEOG091G0CNK
PhylomeDBiP56818
TreeFamiTF329595

Family and domain databases

CDDicd05473 beta_secretase_like, 1 hit
Gene3Di2.40.70.10, 2 hits
InterProiView protein in InterPro
IPR001461 Aspartic_peptidase_A1
IPR001969 Aspartic_peptidase_AS
IPR009119 BACE
IPR009120 BACE1
IPR033874 Memapsin-like
IPR033121 PEPTIDASE_A1
IPR021109 Peptidase_aspartic_dom_sf
PANTHERiPTHR13683 PTHR13683, 1 hit
PTHR13683:SF245 PTHR13683:SF245, 1 hit
PfamiView protein in Pfam
PF00026 Asp, 1 hit
PRINTSiPR01816 BACE1
PR01815 BACEFAMILY
PR00792 PEPSIN
SUPFAMiSSF50630 SSF50630, 1 hit
PROSITEiView protein in PROSITE
PS00141 ASP_PROTEASE, 1 hit
PS51767 PEPTIDASE_A1, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

P56818-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAPALHWLLL WVGSGMLPAQ GTHLGIRLPL RSGLAGPPLG LRLPRETDEE
60 70 80 90 100
SEEPGRRGSF VEMVDNLRGK SGQGYYVEMT VGSPPQTLNI LVDTGSSNFA
110 120 130 140 150
VGAAPHPFLH RYYQRQLSST YRDLRKGVYV PYTQGKWEGE LGTDLVSIPH
160 170 180 190 200
GPNVTVRANI AAITESDKFF INGSNWEGIL GLAYAEIARP DDSLEPFFDS
210 220 230 240 250
LVKQTHIPNI FSLQLCGAGF PLNQTEALAS VGGSMIIGGI DHSLYTGSLW
260 270 280 290 300
YTPIRREWYY EVIIVRVEIN GQDLKMDCKE YNYDKSIVDS GTTNLRLPKK
310 320 330 340 350
VFEAAVKSIK AASSTEKFPD GFWLGEQLVC WQAGTTPWNI FPVISLYLMG
360 370 380 390 400
EVTNQSFRIT ILPQQYLRPV EDVATSQDDC YKFAVSQSST GTVMGAVIME
410 420 430 440 450
GFYVVFDRAR KRIGFAVSAC HVHDEFRTAA VEGPFVTADM EDCGYNIPQT
460 470 480 490 500
DESTLMTIAY VMAAICALFM LPLCLMVCQW RCLRCLRHQH DDFADDISLL

K
Length:501
Mass (Da):55,748
Last modified:August 14, 2001 - v2
Checksum:iC085A013145E474E
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q8C4F4Q8C4F4_MOUSE
Beta-secretase 1
Bace1 mCG_130204
467Annotation score:
F6TV37F6TV37_MOUSE
Beta-secretase 1
Bace1
360Annotation score:
F6UH57F6UH57_MOUSE
Beta-secretase 1
Bace1
65Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF190726 mRNA Translation: AAF04143.2
AF200346 mRNA Translation: AAF17082.1
AK014464 mRNA Translation: BAB29370.1
AK033112 mRNA Translation: BAC28156.1
AK041285 mRNA Translation: BAC30889.1
BC048189 mRNA Translation: AAH48189.1
CCDSiCCDS23135.1
RefSeqiNP_001139419.1, NM_001145947.2
NP_035922.4, NM_011792.6
UniGeneiMm.24044

Genome annotation databases

EnsembliENSMUST00000034591; ENSMUSP00000034591; ENSMUSG00000032086
GeneIDi23821
KEGGimmu:23821
UCSCiuc009pgh.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF190726 mRNA Translation: AAF04143.2
AF200346 mRNA Translation: AAF17082.1
AK014464 mRNA Translation: BAB29370.1
AK033112 mRNA Translation: BAC28156.1
AK041285 mRNA Translation: BAC30889.1
BC048189 mRNA Translation: AAH48189.1
CCDSiCCDS23135.1
RefSeqiNP_001139419.1, NM_001145947.2
NP_035922.4, NM_011792.6
UniGeneiMm.24044

3D structure databases

ProteinModelPortaliP56818
SMRiP56818
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204741, 7 interactors
IntActiP56818, 1 interactor
MINTiP56818
STRINGi10090.ENSMUSP00000034591

Chemistry databases

BindingDBiP56818
ChEMBLiCHEMBL4593

Protein family/group databases

MEROPSiA01.004

PTM databases

iPTMnetiP56818
PhosphoSitePlusiP56818
SwissPalmiP56818

Proteomic databases

MaxQBiP56818
PaxDbiP56818
PeptideAtlasiP56818
PRIDEiP56818

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034591; ENSMUSP00000034591; ENSMUSG00000032086
GeneIDi23821
KEGGimmu:23821
UCSCiuc009pgh.2 mouse

Organism-specific databases

CTDi23621
MGIiMGI:1346542 Bace1

Phylogenomic databases

eggNOGiKOG1339 Eukaryota
ENOG410XNV7 LUCA
GeneTreeiENSGT00910000144168
HOGENOMiHOG000036572
HOVERGENiHBG059578
InParanoidiP56818
KOiK04521
OMAiNGQDLNM
OrthoDBiEOG091G0CNK
PhylomeDBiP56818
TreeFamiTF329595

Enzyme and pathway databases

BRENDAi3.4.23.46 3474

Miscellaneous databases

ChiTaRSiBace1 mouse
PROiPR:P56818
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032086 Expressed in 265 organ(s), highest expression level in external carotid artery
CleanExiMM_BACE1
ExpressionAtlasiP56818 baseline and differential
GenevisibleiP56818 MM

Family and domain databases

CDDicd05473 beta_secretase_like, 1 hit
Gene3Di2.40.70.10, 2 hits
InterProiView protein in InterPro
IPR001461 Aspartic_peptidase_A1
IPR001969 Aspartic_peptidase_AS
IPR009119 BACE
IPR009120 BACE1
IPR033874 Memapsin-like
IPR033121 PEPTIDASE_A1
IPR021109 Peptidase_aspartic_dom_sf
PANTHERiPTHR13683 PTHR13683, 1 hit
PTHR13683:SF245 PTHR13683:SF245, 1 hit
PfamiView protein in Pfam
PF00026 Asp, 1 hit
PRINTSiPR01816 BACE1
PR01815 BACEFAMILY
PR00792 PEPSIN
SUPFAMiSSF50630 SSF50630, 1 hit
PROSITEiView protein in PROSITE
PS00141 ASP_PROTEASE, 1 hit
PS51767 PEPTIDASE_A1, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiBACE1_MOUSE
AccessioniPrimary (citable) accession number: P56818
Secondary accession number(s): Q544D0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: August 14, 2001
Last modified: November 7, 2018
This is version 168 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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