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Protein

Beta-secretase 1

Gene

BACE1

Organism
Cavia porcellus (Guinea pig)
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 sitei90PROSITE-ProRule annotation1
Active sitei261PROSITE-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):
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaHystricomorphaCaviidaeCavia
Proteomesi
  • UP000005447 Componenti: Unassembled WGS sequence

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 – 429ExtracellularSequence analysisAdd BLAST408
Transmembranei430 – 450HelicalSequence analysisAdd BLAST21
Topological domaini451 – 473CytoplasmicSequence analysisAdd BLAST23

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...) asparagineSequence analysis1
Glycosylationi169N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi188 ↔ 392By similarity
Glycosylationi195N-linked (GlcNAc...) asparagineSequence 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...) asparagineSequence 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

Expressioni

Gene expression databases

BgeeiENSCPOG00000012754

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

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1339 Eukaryota
ENOG410XNV7 LUCA
HOGENOMiHOG000036572
HOVERGENiHBG059578
InParanoidiQ1KLR6
OMAiPDMEDCG
OrthoDBiEOG091G0CNK
TreeFamiTF329595

Family and domain databases

CDDicd05473 beta_secretase_like, 1 hit
Gene3Di2.40.70.102 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, 2 hits
PTHR13683:SF245 PTHR13683:SF245, 2 hits
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.

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

GeneIDi100135485

Similar proteinsi

Entry informationi

Entry nameiBACE1_CAVPO
AccessioniPrimary (citable) accession number: Q1KLR6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 11, 2006
Last sequence update: May 30, 2006
Last modified: April 25, 2018
This is version 84 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