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8.A.32.1.1
β-amyloid cleaving enzyme I of the pepsin/retropepsin-like aspartyl protease superfamily.  BACE1 amplified reconstituted M-currents, altered their voltage dependence, accelerated activation, and slowed deactivation by physical association with channel proteins in a beta-subunit-like fashion (Hessler et al. 2015).  BACE1 has a unique sulfur rich motif (M462xxxC466xxxM470xxxC474xxxC478) in its TMS which is characteristic for proteins involved in copper ion storage and transport. This motif promotes BACE1 trimerization and binding of copper ions in vitro. It conducts copper ions through a constricted, partially solvated, axial pore. A central P472 induced kink enables copper ions to alternate between different coordination sites including the prominent C466 and M470 (Bittner et al. 2018).

Accession Number:P56817
Protein Name:Beta-secretase 1 aka BACE1
Length:501
Molecular Weight:55711.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Membrane1 / Single-pass type I membrane protein2
Substrate NONE

Cross database links:

Genevestigator: P56817
RefSeq: NP_036236.1    NP_620427.1    NP_620428.1    NP_620429.1   
Entrez Gene ID: 23621   
Pfam: PF00026   
OMIM: 604252  gene
KEGG: hsa:23621   

Gene Ontology

GO:0009986 C:cell surface
GO:0005783 C:endoplasmic reticulum
GO:0005768 C:endosome
GO:0005887 C:integral to plasma membrane
GO:0005802 C:trans-Golgi network
GO:0004190 F:aspartic-type endopeptidase activity
GO:0008798 F:beta-aspartyl-peptidase activity
GO:0005515 F:protein binding
GO:0050435 P:beta-amyloid metabolic process
GO:0006509 P:membrane protein ectodomain proteolysis

References (22)

[1] “Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE.”  Vassar R.et.al.   10531052
[2] “Purification and cloning of amyloid precursor protein beta-secretase from human brain.”  Sinha S.et.al.   10591214
[3] “Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity.”  Yan R.et.al.   10591213
[4] “Identification of a novel aspartic proteinase (Asp 2) as beta-secretase.”  Hussain I.et.al.   10656250
[5] “Three novel alternatively spliced isoforms of the human beta-site amyloid precursor protein cleaving enzyme (BACE) and their effect on amyloid beta-peptide production.”  Tanahashi H.et.al.   11516562
[6] “Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain.”  Hirosawa M.et.al.   10574461
[7] “Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.”  Nakajima D.et.al.   12168954
[8] “Human chromosome 11 DNA sequence and analysis including novel gene identification.”  Taylor T.D.et.al.   16554811
[9] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[10] “Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein.”  Lin X.et.al.   10677483
[11] “ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase site.”  Hussain I.et.al.   11083922
[12] “The transmembrane domain of the Alzheimer's beta-secretase (BACE1) determines its late Golgi localization and access to beta -amyloid precursor protein (APP) substrate.”  Yan R.et.al.   11466313
[13] “The disulphide bonds in the catalytic domain of BACE are critical but not essential for amyloid precursor protein processing activity.”  Fischer F.et.al.   11953458
[14] “Biochemical and structural characterization of the interaction of memapsin 2 (beta-secretase) cytosolic domain with the VHS domain of GGA proteins.”  He X.et.al.   14567678
[15] “Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation.”  He W.et.al.   15286784
[16] “Reticulons RTN3 and RTN4-B/C interact with BACE1 and inhibit its ability to produce amyloid beta-protein.”  Murayama K.S.et.al.   16965550
[17] “Mapping of interaction domains mediating binding between BACE1 and RTN/Nogo proteins.”  He W.et.al.   16979658
[18] “Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor.”  Hong L.et.al.   11021803
[19] “Crystal structure of memapsin 2 (beta-secretase) in complex with an inhibitor OM00-3.”  Hong L.et.al.   12206667
[20] “Flap position of free memapsin 2 (beta-secretase), a model for flap opening in aspartic protease catalysis.”  Hong L.et.al.   15096037
[21] “Apo and inhibitor complex structures of BACE (beta-secretase).”  Patel S.et.al.   15451669
[22] “Structural locations and functional roles of new subsites S5, S6, and S7 in memapsin 2 (beta-secretase).”  Turner R.T. IIIet.al.   15628850
Structure:
1FKN   1M4H   1PY1   1SGZ   1TQF   1UJJ   1UJK   1W50   1W51   1XN2   [...more]

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

Analyze:

Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MAQALPWLLL WMGAGVLPAH GTQHGIRLPL RSGLGGAPLG LRLPRETDEE PEEPGRRGSF 
61:	VEMVDNLRGK SGQGYYVEMT VGSPPQTLNI LVDTGSSNFA VGAAPHPFLH RYYQRQLSST 
121:	YRDLRKGVYV PYTQGKWEGE LGTDLVSIPH GPNVTVRANI AAITESDKFF INGSNWEGIL 
181:	GLAYAEIARP DDSLEPFFDS LVKQTHVPNL FSLQLCGAGF PLNQSEVLAS VGGSMIIGGI 
241:	DHSLYTGSLW YTPIRREWYY EVIIVRVEIN GQDLKMDCKE YNYDKSIVDS GTTNLRLPKK 
301:	VFEAAVKSIK AASSTEKFPD GFWLGEQLVC WQAGTTPWNI FPVISLYLMG EVTNQSFRIT 
361:	ILPQQYLRPV EDVATSQDDC YKFAISQSST GTVMGAVIME GFYVVFDRAR KRIGFAVSAC 
421:	HVHDEFRTAA VEGPFVTLDM EDCGYNIPQT DESTLMTIAY VMAAICALFM LPLCLMVCQW 
481:	CCLRCLRQQH DDFADDISLL K