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Protein

Beta-secretase 1

Gene

Bace1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei93 – 931PROSITE-ProRule annotation
Active sitei289 – 2891PROSITE-ProRule annotation

GO - Molecular functioni

  • aspartic-type endopeptidase activity Source: UniProtKB
  • beta-amyloid binding Source: GO_Central
  • peptidase activity Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Aspartyl 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi2191. Bace1.

Subcellular locationi

  • Membrane; Single-pass type I membrane protein
  • Golgi apparatustrans-Golgi network By similarity
  • Endoplasmic reticulum By similarity
  • Endosome By similarity
  • Cell surface By similarity
  • Cytoplasmic vesicle membrane By similarity
  • Membrane raft By similarity

  • Note: 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 (By similarity).By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 457436ExtracellularSequence analysisAdd
BLAST
Transmembranei458 – 47821HelicalSequence analysisAdd
BLAST
Topological domaini479 – 50123CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL3259473.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence analysisAdd
BLAST
Propeptidei22 – 4524Sequence analysisPRO_0000025943Add
BLAST
Chaini46 – 501456Beta-secretase 1PRO_0000025944Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei126 – 1261N6-acetyllysineBy similarity
Glycosylationi153 – 1531N-linked (GlcNAc...)Sequence analysis
Glycosylationi172 – 1721N-linked (GlcNAc...)Sequence analysis
Disulfide bondi216 ↔ 420By similarity
Glycosylationi223 – 2231N-linked (GlcNAc...)Sequence analysis
Modified residuei275 – 2751N6-acetyllysineBy similarity
Disulfide bondi278 ↔ 443By similarity
Modified residuei279 – 2791N6-acetyllysineBy similarity
Modified residuei285 – 2851N6-acetyllysineBy similarity
Modified residuei299 – 2991N6-acetyllysineBy similarity
Modified residuei300 – 3001N6-acetyllysineBy similarity
Modified residuei307 – 3071N6-acetyllysineBy similarity
Disulfide bondi330 ↔ 380By similarity
Glycosylationi354 – 3541N-linked (GlcNAc...)Sequence analysis
Lipidationi474 – 4741S-palmitoyl cysteineBy similarity
Lipidationi478 – 4781S-palmitoyl cysteineBy similarity
Lipidationi482 – 4821S-palmitoyl cysteineBy similarity
Lipidationi485 – 4851S-palmitoyl cysteineBy similarity
Modified residuei498 – 4981PhosphoserineBy similarity

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

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

Protein-protein interaction databases

BioGridi248044. 1 interaction.
STRINGi10116.ENSRNOP00000022796.

Chemistry

BindingDBiP56819.

Structurei

3D structure databases

ProteinModelPortaliP56819.
SMRiP56819. Positions 55-447.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini75 – 416342Peptidase A1PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni479 – 50123Interaction with RTN3By similarityAdd
BLAST

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.
InParanoidiP56819.
KOiK04521.
OMAiYLMSENH.
OrthoDBiEOG7DNNVW.
PhylomeDBiP56819.

Family and domain databases

Gene3Di2.40.70.10. 2 hits.
InterProiIPR001461. Aspartic_peptidase_A1.
IPR001969. Aspartic_peptidase_AS.
IPR009119. BACE.
IPR009120. BACE1.
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.

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.

Cross-referencesi

Sequence databases

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

3D structure databases

ProteinModelPortaliP56819.
SMRiP56819. Positions 55-447.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248044. 1 interaction.
STRINGi10116.ENSRNOP00000022796.

Chemistry

BindingDBiP56819.
ChEMBLiCHEMBL3259473.

Protein family/group databases

MEROPSiA01.004.

Proteomic databases

PaxDbiP56819.
PRIDEiP56819.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi23621.
RGDi2191. Bace1.

Phylogenomic databases

eggNOGiKOG1339. Eukaryota.
ENOG410XNV7. LUCA.
GeneTreeiENSGT00760000118929.
HOGENOMiHOG000036572.
HOVERGENiHBG059578.
InParanoidiP56819.
KOiK04521.
OMAiYLMSENH.
OrthoDBiEOG7DNNVW.
PhylomeDBiP56819.

Miscellaneous databases

PROiP56819.

Gene expression databases

GenevisibleiP56819. RN.

Family and domain databases

Gene3Di2.40.70.10. 2 hits.
InterProiIPR001461. Aspartic_peptidase_A1.
IPR001969. Aspartic_peptidase_AS.
IPR009119. BACE.
IPR009120. BACE1.
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...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiBACE1_RAT
AccessioniPrimary (citable) accession number: P56819
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 30, 2000
Last modified: July 6, 2016
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. 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.