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Protein

Beta-secretase 1

Gene

Bace1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

Enzyme 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

Complete GO annotation...

Keywords - Molecular functioni

Aspartyl 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1346542. Bace1.

Subcellular locationi

Topology

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

GO - Cellular componenti

  • axon Source: MGI
  • cell surface Source: UniProtKB-SubCell
  • cytoplasmic vesicle Source: MGI
  • cytoplasmic vesicle membrane Source: UniProtKB-SubCell
  • endoplasmic reticulum Source: UniProtKB-SubCell
  • endosome Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • integral component of plasma membrane Source: MGI
  • late endosome Source: MGI
  • membrane Source: MGI
  • membrane raft Source: UniProtKB-SubCell
  • multivesicular body Source: MGI
  • plasma membrane Source: MGI
  • trans-Golgi network Source: UniProtKB
Complete GO annotation...

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...)Sequence analysis1
Glycosylationi172N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi216 ↔ 420By similarity
Glycosylationi223N-linked (GlcNAc...)Sequence 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...)Sequence 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.
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.
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
Contains 1 peptidase A1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1339. Eukaryota.
ENOG410XNV7. LUCA.
GeneTreeiENSGT00760000118929.
HOGENOMiHOG000036572.
HOVERGENiHBG059578.
InParanoidiP56818.
KOiK04521.
OMAiYLMSENH.
OrthoDBiEOG091G0CNK.
PhylomeDBiP56818.
TreeFamiTF329595.

Family and domain databases

CDDicd05473. beta_secretase_like. 1 hit.
Gene3Di2.40.70.10. 2 hits.
InterProiIPR001461. Aspartic_peptidase_A1.
IPR001969. Aspartic_peptidase_AS.
IPR009119. BACE.
IPR009120. BACE1.
IPR033874. Memapsin-like.
IPR033121. PEPTIDASE_A1.
IPR021109. Peptidase_aspartic_dom.
[Graphical view]
PANTHERiPTHR13683. PTHR13683. 1 hit.
PTHR13683:SF245. PTHR13683:SF245. 1 hit.
PfamiPF00026. Asp. 1 hit.
[Graphical view]
PRINTSiPR01816. BACE1.
PR01815. BACEFAMILY.
PR00792. PEPSIN.
SUPFAMiSSF50630. SSF50630. 1 hit.
PROSITEiPS00141. ASP_PROTEASE. 1 hit.
PS51767. PEPTIDASE_A1. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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

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.

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.
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.
GeneTreeiENSGT00760000118929.
HOGENOMiHOG000036572.
HOVERGENiHBG059578.
InParanoidiP56818.
KOiK04521.
OMAiYLMSENH.
OrthoDBiEOG091G0CNK.
PhylomeDBiP56818.
TreeFamiTF329595.

Enzyme and pathway databases

BRENDAi3.4.23.46. 3474.

Miscellaneous databases

ChiTaRSiBace1. mouse.
PROiP56818.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000032086.
CleanExiMM_BACE1.
ExpressionAtlasiP56818. baseline and differential.
GenevisibleiP56818. MM.

Family and domain databases

CDDicd05473. beta_secretase_like. 1 hit.
Gene3Di2.40.70.10. 2 hits.
InterProiIPR001461. Aspartic_peptidase_A1.
IPR001969. Aspartic_peptidase_AS.
IPR009119. BACE.
IPR009120. BACE1.
IPR033874. Memapsin-like.
IPR033121. PEPTIDASE_A1.
IPR021109. Peptidase_aspartic_dom.
[Graphical view]
PANTHERiPTHR13683. PTHR13683. 1 hit.
PTHR13683:SF245. PTHR13683:SF245. 1 hit.
PfamiPF00026. Asp. 1 hit.
[Graphical view]
PRINTSiPR01816. BACE1.
PR01815. BACEFAMILY.
PR00792. PEPSIN.
SUPFAMiSSF50630. SSF50630. 1 hit.
PROSITEiPS00141. ASP_PROTEASE. 1 hit.
PS51767. PEPTIDASE_A1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBACE1_MOUSE
AccessioniPrimary (citable) accession number: P56818
Secondary accession number(s): Q544D0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: August 14, 2001
Last modified: November 30, 2016
This is version 153 of the entry and version 2 of the sequence. [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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.