ID H0WUA0_OTOGA Unreviewed; 501 AA.
AC H0WUA0;
DT 22-FEB-2012, integrated into UniProtKB/TrEMBL.
DT 22-FEB-2012, sequence version 1.
DT 27-MAR-2024, entry version 75.
DE RecName: Full=Beta-secretase 1 {ECO:0000256|ARBA:ARBA00017314};
DE EC=3.4.23.46 {ECO:0000256|ARBA:ARBA00013261};
DE AltName: Full=Beta-site amyloid precursor protein cleaving enzyme 1 {ECO:0000256|ARBA:ARBA00031276};
DE AltName: Full=Memapsin-2 {ECO:0000256|ARBA:ARBA00032591};
DE AltName: Full=Membrane-associated aspartic protease 2 {ECO:0000256|ARBA:ARBA00032613};
GN Name=BACE1 {ECO:0000313|Ensembl:ENSOGAP00000005784.2};
OS Otolemur garnettii (Small-eared galago) (Garnett's greater bushbaby).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Strepsirrhini; Lorisiformes;
OC Galagidae; Otolemur.
OX NCBI_TaxID=30611 {ECO:0000313|Ensembl:ENSOGAP00000005784.2, ECO:0000313|Proteomes:UP000005225};
RN [1] {ECO:0000313|Proteomes:UP000005225}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG The Broad Institute Genome Sequencing Platform;
RA Di Palma F., Johnson J., Lander E.S., Lindblad-Toh K., Jaffe D.B.,
RA Gnerre S., MacCallum I., Przybylski D., Ribeiro F.J., Burton J.N.,
RA Walker B.J., Sharpe T., Hall G.;
RT "Version 3 of the genome sequence of Otolemur garnettii (Bushbaby).";
RL Submitted (MAR-2011) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSOGAP00000005784.2}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Broad endopeptidase specificity. Cleaves Glu-Val-Asn-Leu-|-
CC Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid
CC precursor protein.; EC=3.4.23.46;
CC Evidence={ECO:0000256|ARBA:ARBA00000187};
CC -!- SUBCELLULAR LOCATION: Cell projection, axon
CC {ECO:0000256|ARBA:ARBA00004489}. Cell projection, dendrite
CC {ECO:0000256|ARBA:ARBA00004279}. Cell surface
CC {ECO:0000256|ARBA:ARBA00004241}. Early endosome
CC {ECO:0000256|ARBA:ARBA00004412}. Endosome
CC {ECO:0000256|ARBA:ARBA00004177}. Golgi apparatus, trans-Golgi network
CC {ECO:0000256|ARBA:ARBA00004601}. Late endosome
CC {ECO:0000256|ARBA:ARBA00004603}. Membrane raft
CC {ECO:0000256|ARBA:ARBA00004285}. Membrane
CC {ECO:0000256|ARBA:ARBA00004479}; Single-pass type I membrane protein
CC {ECO:0000256|ARBA:ARBA00004479}. Recycling endosome
CC {ECO:0000256|ARBA:ARBA00004172}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family.
CC {ECO:0000256|ARBA:ARBA00007447, ECO:0000256|RuleBase:RU000454}.
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DR EMBL; AAQR03130901; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAQR03130902; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_003796914.1; XM_003796866.2.
DR AlphaFoldDB; H0WUA0; -.
DR STRING; 30611.ENSOGAP00000005784; -.
DR MEROPS; A01.004; -.
DR Ensembl; ENSOGAT00000006471.2; ENSOGAP00000005784.2; ENSOGAG00000006467.2.
DR GeneID; 100943044; -.
DR KEGG; oga:100943044; -.
DR CTD; 23621; -.
DR eggNOG; KOG1339; Eukaryota.
DR GeneTree; ENSGT00940000157786; -.
DR HOGENOM; CLU_039009_0_0_1; -.
DR InParanoid; H0WUA0; -.
DR OMA; MLMTIAY; -.
DR OrthoDB; 603414at2759; -.
DR TreeFam; TF329595; -.
DR Proteomes; UP000005225; Unassembled WGS sequence.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IEA:Ensembl.
DR GO; GO:0005764; C:lysosome; IEA:Ensembl.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005771; C:multivesicular body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-KW.
DR GO; GO:0098793; C:presynapse; IEA:Ensembl.
DR GO; GO:0055037; C:recycling endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005802; C:trans-Golgi network; IEA:Ensembl.
DR GO; GO:0001540; F:amyloid-beta binding; IEA:Ensembl.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
DR GO; GO:0034205; P:amyloid-beta formation; IEA:Ensembl.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; IEA:Ensembl.
DR GO; GO:0140448; P:signaling receptor ligand precursor processing; IEA:Ensembl.
DR CDD; cd05473; beta_secretase_like; 1.
DR Gene3D; 2.40.70.10; Acid Proteases; 2.
DR InterPro; IPR001461; Aspartic_peptidase_A1.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
DR InterPro; IPR009119; BACE.
DR InterPro; IPR009120; BACE1.
DR InterPro; IPR033874; Memapsin-like.
DR InterPro; IPR033121; PEPTIDASE_A1.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR PANTHER; PTHR47965; ASPARTYL PROTEASE-RELATED; 1.
DR PANTHER; PTHR47965:SF69; BETA-SECRETASE 1; 1.
DR Pfam; PF00026; Asp; 1.
DR PRINTS; PR01816; BACE1.
DR PRINTS; PR01815; BACEFAMILY.
DR PRINTS; PR00792; PEPSIN.
DR SUPFAM; SSF50630; Acid proteases; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 1.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
PE 3: Inferred from homology;
KW Acetylation {ECO:0000256|ARBA:ARBA00022990};
KW Aspartyl protease {ECO:0000256|RuleBase:RU000454};
KW Cell membrane {ECO:0000256|ARBA:ARBA00022475};
KW Cell projection {ECO:0000256|ARBA:ARBA00023273};
KW Cytoplasmic vesicle {ECO:0000256|ARBA:ARBA00023329};
KW Endoplasmic reticulum {ECO:0000256|ARBA:ARBA00022824};
KW Glycoprotein {ECO:0000256|ARBA:ARBA00023180};
KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|RuleBase:RU000454};
KW Isopeptide bond {ECO:0000256|ARBA:ARBA00022499};
KW Lipoprotein {ECO:0000256|ARBA:ARBA00023139};
KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|SAM:Phobius};
KW Palmitate {ECO:0000256|ARBA:ARBA00023139};
KW Protease {ECO:0000256|ARBA:ARBA00022670, ECO:0000256|RuleBase:RU000454};
KW Reference proteome {ECO:0000313|Proteomes:UP000005225};
KW Signal {ECO:0000256|SAM:SignalP};
KW Transmembrane {ECO:0000256|ARBA:ARBA00022692, ECO:0000256|SAM:Phobius};
KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989,
KW ECO:0000256|SAM:Phobius}; Ubl conjugation {ECO:0000256|ARBA:ARBA00022843};
KW Zymogen {ECO:0000256|ARBA:ARBA00023145}.
FT SIGNAL 1..21
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 22..501
FT /note="Beta-secretase 1"
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5003544350"
FT TRANSMEM 458..478
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT DOMAIN 75..416
FT /note="Peptidase A1"
FT /evidence="ECO:0000259|PROSITE:PS51767"
FT ACT_SITE 93
FT /evidence="ECO:0000256|PIRSR:PIRSR601461-1"
FT ACT_SITE 289
FT /evidence="ECO:0000256|PIRSR:PIRSR601461-1"
SQ SEQUENCE 501 AA; 55803 MW; 9A9D823C4FE1626E CRC64;
MAQALPWLLL WMGSGVLPAH GTQHGIRLPL RSGLGGAPLG LRLPRETDEE PEEPGRRGSF
VEMVDNLRGK SGQGYYVEMT VGSPPQTLNI LVDTGSSNFA VGAAPHPFLH RYYQRQLSST
YRDLRKGVYV PYTQGKWEGE LGTDLVSIPH GPNVTVRANI AAITESDKFF INGSNWEGIL
GLAYAEIARP DDSLEPFFDS LVKQTHVPNL FSLQLCGTGF PLNQSEVLAS VGGSMIIGGI
DHSLYTGSLW YTPIRREWYY EVIIVRVEIN GQDLKMDCKE YNYDKSIVDS GTTNLRLPKK
VFEAAVKSIK AASSTEKFPD GFWLGEQLVC WQAGTTPWNI FPVISLYLMG EVTNQSFRIT
ILPQQYLRPV EDVATSQDDC YKFAISQSST GTVMGAVIME GFYVVFDRAR KRIGFAVSAC
HVHDEFRTAA VEGPFVTPDM EDCGYNIPQT DESTLMTIAY VMAAICALFM LPLCLMVCQW
RCLRCLRHQH DDFADDISLL K
//