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Protein

Beta-secretase 1

Gene

BACE1

Organism
Bos taurus (Bovine)
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)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

Protein family/group databases

MEROPSiA01.004.

Names & Taxonomyi

Protein namesi
Recommended name:
Beta-secretase 1 (EC:3.4.23.46)
Alternative name(s):
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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 15

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
PropeptideiPRO_000024580222 – 45By similarityAdd BLAST24
ChainiPRO_000024580346 – 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 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

PaxDbiQ2HJ40.

Expressioni

Gene expression databases

BgeeiENSBTAG00000019365.
ExpressionAtlasiQ2HJ40. baseline and differential.

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

STRINGi9913.ENSBTAP00000039837.

Structurei

3D structure databases

ProteinModelPortaliQ2HJ40.
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.
InParanoidiQ2HJ40.
KOiK04521.
OMAiYLMSENH.
OrthoDBiEOG091G0CNK.
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.

Q2HJ40-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAQALPWLLL WMGSGVLPAH GSQPGIRLPL RSGLGGAPLG LRLPRETDEE
60 70 80 90 100
SEEPGRRGSF VEMVDNLRGK SGQGYYVEMT LGSPPQTLNI 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
LVKQTHVPNL FSLQLCGAGF PLNQSEALAS VGGSMIIGGI DHSLYMGSLW
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 YKFAISQSST GTVMGAVIME
410 420 430 440 450
GFYVVFDRAR KRIGFAVSAC HVHDEFRTAA VEGPFVTPDM EDCGYNIPQT
460 470 480 490 500
DESTLMTIAY VMAAICALFM LPLCLMVCQW RCLRCLRHQH DDFADDISLL

K
Length:501
Mass (Da):55,725
Last modified:March 21, 2006 - v1
Checksum:i8E5EA730FC91C295
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC113325 mRNA. Translation: AAI13326.1.
RefSeqiNP_001039996.1. NM_001046531.1.
UniGeneiBt.28273.

Genome annotation databases

EnsembliENSBTAT00000040056; ENSBTAP00000039837; ENSBTAG00000019365.
GeneIDi614333.
KEGGibta:614333.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC113325 mRNA. Translation: AAI13326.1.
RefSeqiNP_001039996.1. NM_001046531.1.
UniGeneiBt.28273.

3D structure databases

ProteinModelPortaliQ2HJ40.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000039837.

Protein family/group databases

MEROPSiA01.004.

Proteomic databases

PaxDbiQ2HJ40.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000040056; ENSBTAP00000039837; ENSBTAG00000019365.
GeneIDi614333.
KEGGibta:614333.

Organism-specific databases

CTDi23621.

Phylogenomic databases

eggNOGiKOG1339. Eukaryota.
ENOG410XNV7. LUCA.
GeneTreeiENSGT00760000118929.
HOGENOMiHOG000036572.
HOVERGENiHBG059578.
InParanoidiQ2HJ40.
KOiK04521.
OMAiYLMSENH.
OrthoDBiEOG091G0CNK.
TreeFamiTF329595.

Gene expression databases

BgeeiENSBTAG00000019365.
ExpressionAtlasiQ2HJ40. baseline and differential.

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_BOVIN
AccessioniPrimary (citable) accession number: Q2HJ40
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2006
Last sequence update: March 21, 2006
Last modified: November 30, 2016
This is version 85 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.