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Protein

Beta-secretase 1

Gene

BACE1

Organism
Cavia porcellus (Guinea pig)
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 sitei90PROSITE-ProRule annotation1
Active sitei261PROSITE-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
OrganismiCavia porcellus (Guinea pig)
Taxonomic identifieri10141 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaHystricognathiCaviidaeCavia
Proteomesi
  • UP000005447 Componenti: Unassembled WGS sequence

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 – 429ExtracellularSequence analysisAdd BLAST408
Transmembranei430 – 450HelicalSequence analysisAdd BLAST21
Topological domaini451 – 473CytoplasmicSequence 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_000024580422 – 45By similarityAdd BLAST24
ChainiPRO_000024580546 – 473Beta-secretase 1Add BLAST428

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei123N6-acetyllysineBy similarity1
Glycosylationi150N-linked (GlcNAc...)Sequence analysis1
Glycosylationi169N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi188 ↔ 392By similarity
Glycosylationi195N-linked (GlcNAc...)Sequence analysis1
Modified residuei247N6-acetyllysineBy similarity1
Disulfide bondi250 ↔ 415By similarity
Modified residuei251N6-acetyllysineBy similarity1
Modified residuei257N6-acetyllysineBy similarity1
Modified residuei271N6-acetyllysineBy similarity1
Modified residuei272N6-acetyllysineBy similarity1
Modified residuei279N6-acetyllysineBy similarity1
Disulfide bondi302 ↔ 352By similarity
Glycosylationi326N-linked (GlcNAc...)Sequence analysis1
Lipidationi446S-palmitoyl cysteineBy similarity1
Lipidationi450S-palmitoyl cysteineBy similarity1
Lipidationi454S-palmitoyl cysteineBy similarity1
Lipidationi457S-palmitoyl cysteineBy similarity1
Modified residuei470PhosphoserineBy similarity1

Post-translational modificationi

N-Glycosylated.By similarity
Acetylated in the endoplasmic reticulum at Lys-123, Lys-247, Lys-251, Lys-257, Lys-271, Lys-272, and Lys-279. 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

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

STRINGi10141.ENSCPOP00000011476.

Structurei

3D structure databases

ProteinModelPortaliQ1KLR6.
SMRiQ1KLR6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini72 – 388Peptidase A1PROSITE-ProRule annotationAdd BLAST317

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni451 – 473Interaction 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.
InParanoidiQ1KLR6.
OMAiVEGPFIT.
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.

Q1KLR6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPALPWLLL WVGSGVLPVH GTQDGIRLPL RSGLAGAPLG LRLPRETDEE
60 70 80 90 100
PGRRGSFVEM VDNLRGKSGQ GYYVEMTVGS PPQTLNILVD TGSSNFAVGA
110 120 130 140 150
APHPFLHRYY QRQRSSTYRD LRKGVYVPYT QGKWEGELGT DLVSIPHGPN
160 170 180 190 200
VTVRANIAAI TESDKFFING SNWEGILGLA YAEIARLCGA GFPLNQSEAV
210 220 230 240 250
ASVGGSMIIG GIDHSLYTGN LWYTPIRREW YYEVIIVRVE INGQDLKMDC
260 270 280 290 300
KEYNYDKSIV DSGTTNLRLP KKVFEAAVKS IKAASSTEKF PDGFWLGEQL
310 320 330 340 350
VCWQAGTTPW NIFPVISLYL MGEVTNQSFR ITILPQQYLR PVEDVATSQD
360 370 380 390 400
DCYKFAISQS STGTVMGAVI MEGFYVVFDR ARKRIGFAVS ACHVHDEFRT
410 420 430 440 450
ATVEGPFVTP DMEDCGYNIP QTDESTLMTI AYVMAAICAL FMLPLCLMVC
460 470
QWRCLRCLRH QHDDFADDIS LLK
Length:473
Mass (Da):52,576
Last modified:May 30, 2006 - v1
Checksum:iF9583693A13F86E9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ471956 mRNA. Translation: ABF13340.1.
RefSeqiNP_001166390.1. NM_001172919.1.

Genome annotation databases

EnsembliENSCPOT00000012877; ENSCPOP00000011476; ENSCPOG00000012754.
GeneIDi100135485.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ471956 mRNA. Translation: ABF13340.1.
RefSeqiNP_001166390.1. NM_001172919.1.

3D structure databases

ProteinModelPortaliQ1KLR6.
SMRiQ1KLR6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10141.ENSCPOP00000011476.

Protein family/group databases

MEROPSiA01.004.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSCPOT00000012877; ENSCPOP00000011476; ENSCPOG00000012754.
GeneIDi100135485.

Organism-specific databases

CTDi23621.

Phylogenomic databases

eggNOGiKOG1339. Eukaryota.
ENOG410XNV7. LUCA.
GeneTreeiENSGT00760000118929.
HOGENOMiHOG000036572.
HOVERGENiHBG059578.
InParanoidiQ1KLR6.
OMAiVEGPFIT.
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]
ProtoNetiSearch...

Entry informationi

Entry nameiBACE1_CAVPO
AccessioniPrimary (citable) accession number: Q1KLR6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2006
Last sequence update: May 30, 2006
Last modified: November 30, 2016
This is version 74 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.