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Protein

Beta-secretase 1

Gene

Bace1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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

Keywordsi

Molecular functionAspartyl protease, Hydrolase, Protease

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi2191 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

Chemistry databases

ChEMBLiCHEMBL3259473

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
PropeptideiPRO_000002594322 – 45Sequence analysisAdd BLAST24
ChainiPRO_000002594446 – 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 cysteineBy similarity1
Lipidationi478S-palmitoyl cysteineBy similarity1
Lipidationi482S-palmitoyl cysteineBy similarity1
Lipidationi485S-palmitoyl cysteineBy similarity1
Modified residuei498PhosphoserineBy similarity1

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.By similarity

Keywords - PTMi

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

Proteomic databases

PaxDbiP56819
PRIDEiP56819

Expressioni

Gene expression databases

BgeeiENSRNOG00000016847
GenevisibleiP56819 RN

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

BioGridi248044, 1 interactor
CORUMiP56819
STRINGi10116.ENSRNOP00000022796

Chemistry databases

BindingDBiP56819

Structurei

3D structure databases

ProteinModelPortaliP56819
SMRiP56819
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
InParanoidiP56819
KOiK04521
OMAiPDMEDCG
OrthoDBiEOG091G0CNK
PhylomeDBiP56819

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

Sequencei

Sequence statusi: Complete.

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

P56819-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPALRWLLL WVGSGMLPAQ GTHLGIRLPL RSGLAGPPLG LRLPRETDEE
60 70 80 90 100
PEEPGRRGSF VEMVDNLRGK SGQGYYVEMT VGSPPQTLNI LVDTGSSNFA
110 120 130 140 150
VGAAPHPFLH RYYQRQLSST YRDLRKSVYV 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):55,807
Last modified:May 30, 2000 - v1
Checksum:i24B445BC8BE87DE3
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF190727 mRNA Translation: AAF04144.1
RefSeqiNP_062077.1, NM_019204.2
UniGeneiRn.207201

Genome annotation databases

EnsembliENSRNOT00000022796; ENSRNOP00000022796; ENSRNOG00000016847
GeneIDi29392
KEGGirno:29392
UCSCiRGD:2191 rat

Similar proteinsi

Entry informationi

Entry nameiBACE1_RAT
AccessioniPrimary (citable) accession number: P56819
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 30, 2000
Last modified: March 28, 2018
This is version 138 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health