Beta-secretase 1

NameBeta-secretase 1
Synonyms3.4.23.46 Asp 2 ASP2 Aspartyl protease 2 BACE Beta-site amyloid precursor protein cleaving enzyme 1 Beta-site APP cleaving enzyme 1 KIAA1149 Memapsin-2 Membrane-associated aspartic protease 2
Gene NameBACE1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0037109|Beta-secretase 1
MAQALPWLLLWMGAGVLPAHGTQHGIRLPLRSGLGGAPLGLRLPRETDEEPEEPGRRGSF
VEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFLHRYYQRQLSST
YRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRANIAAITESDKFFINGSNWEGIL
GLAYAEIARPDDSLEPFFDSLVKQTHVPNLFSLQLCGAGFPLNQSEVLASVGGSMIIGGI
DHSLYTGSLWYTPIRREWYYEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKK
VFEAAVKSIKAASSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRIT
ILPQQYLRPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSAC
HVHDEFRTAAVEGPFVTLDMEDCGYNIPQTDESTLMTIAYVMAAICALFMLPLCLMVCQW
CCLRCLRQQHDDFADDISLLK
Number of residues501
Molecular Weight55710.28
Theoretical pI5.19
GO Classification
Functions
    peptidase activity
beta-aspartyl-peptidase activity
aspartic-type endopeptidase activity
enzyme binding
beta-amyloid binding
Processes
    cellular protein metabolic process
proteolysis
beta-amyloid metabolic process
membrane protein ectodomain proteolysis
protein catabolic process
Components
    integral component of plasma membrane
trans-Golgi network
endoplasmic reticulum lumen
multivesicular body
Golgi-associated vesicle lumen
endosome
cytoplasmic vesicle membrane
plasma membrane
late endosome
cell surface
axon
Golgi apparatus
integral component of membrane
endosome membrane
General FunctionPeptidase activity
Specific FunctionResponsible 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.
Transmembrane Regions458-478
GenBank Protein ID6118539
UniProtKB IDP56817
UniProtKB Entry NameBACE1_HUMAN
Cellular LocationMembrane
Gene sequence
>lcl|BSEQ0001966|1506 bp
ATGGCCCAAGCCCTGCCCTGGCTCCTGCTGTGGATGGGCGCGGGAGTGCTGCCTGCCCAC
GGCACCCAGCACGGCATCCGGCTGCCCCTGCGCAGCGGCCTGGGGGGCGCCCCCCTGGGG
CTGCGGCTGCCCCGGGAGACCGACGAAGAGCCCGAGGAGCCCGGCCGGAGGGGCAGCTTT
GTGGAGATGGTGGACAACCTGAGGGGCAAGTCGGGGCAGGGCTACTACGTGGAGATGACC
GTGGGCAGCCCCCCGCAGACGCTCAACATCCTGGTGGATACAGGCAGCAGTAACTTTGCA
GTGGGTGCTGCCCCCCACCCCTTCCTGCATCGCTACTACCAGAGGCAGCTGTCCAGCACA
TACCGGGACCTCCGGAAGGGTGTGTATGTGCCCTACACCCAGGGCAAGTGGGAAGGGGAG
CTGGGCACCGACCTGGTAAGCATCCCCCATGGCCCCAACGTCACTGTGCGTGCCAACATT
GCTGCCATCACTGAATCAGACAAGTTCTTCATCAACGGCTCCAACTGGGAAGGCATCCTG
GGGCTGGCCTATGCTGAGATTGCCAGGCCTGACGACTCCCTGGAGCCTTTCTTTGACTCT
CTGGTAAAGCAGACCCACGTTCCCAACCTCTTCTCCCTGCAGCTTTGTGGTGCTGGCTTC
CCCCTCAACCAGTCTGAAGTGCTGGCCTCTGTCGGAGGGAGCATGATCATTGGAGGTATC
GACCACTCGCTGTACACAGGCAGTCTCTGGTATACACCCATCCGGCGGGAGTGGTATTAT
GAGGTGATCATTGTGCGGGTGGAGATCAATGGACAGGATCTGAAAATGGACTGCAAGGAG
TACAACTATGACAAGAGCATTGTGGACAGTGGCACCACCAACCTTCGTTTGCCCAAGAAA
GTGTTTGAAGCTGCAGTCAAATCCATCAAGGCAGCCTCCTCCACGGAGAAGTTCCCTGAT
GGTTTCTGGCTAGGAGAGCAGCTGGTGTGCTGGCAAGCAGGCACCACCCCTTGGAACATT
TTCCCAGTCATCTCACTCTACCTAATGGGTGAGGTTACCAACCAGTCCTTCCGCATCACC
ATCCTTCCGCAGCAATACCTGCGGCCAGTGGAAGATGTGGCCACGTCCCAAGACGACTGT
TACAAGTTTGCCATCTCACAGTCATCCACGGGCACTGTTATGGGAGCTGTTATCATGGAG
GGCTTCTACGTTGTCTTTGATCGGGCCCGAAAACGAATTGGCTTTGCTGTCAGCGCTTGC
CATGTGCACGATGAGTTCAGGACGGCAGCGGTGGAAGGCCCTTTTGTCACCTTGGACATG
GAAGACTGTGGCTACAACATTCCACAGACAGATGAGTCAACCCTCATGACCATAGCCTAT
GTCATGGCTGCCATCTGCGCCCTCTTCATGCTGCCACTCTGCCTCATGGTGTGTCAGTGG
CGCTGCCTCCGCTGCCTGCGCCAGCAGCATGATGACTTTGCTGATGACATCTCCCTGCTG
AAGTGA
GenBank Gene IDAF190725
GeneCard IDNone
GenAtlas IDBACE1
HGNC IDHGNC:933
Chromosome LocationNone
Locus11q23.2-q23.3
References
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  12. He X, Zhu G, Koelsch G, Rodgers KK, Zhang XC, Tang J: Biochemical and structural characterization of the interaction of memapsin 2 (beta-secretase) cytosolic domain with the VHS domain of GGA proteins. Biochemistry. 2003 Oct 28;42(42):12174-80.[14567678 ]
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  14. Murayama KS, Kametani F, Saito S, Kume H, Akiyama H, Araki W: Reticulons RTN3 and RTN4-B/C interact with BACE1 and inhibit its ability to produce amyloid beta-protein. Eur J Neurosci. 2006 Sep;24(5):1237-44. Epub 2006 Sep 8.[16965550 ]
  15. He W, Hu X, Shi Q, Zhou X, Lu Y, Fisher C, Yan R: Mapping of interaction domains mediating binding between BACE1 and RTN/Nogo proteins. J Mol Biol. 2006 Oct 27;363(3):625-34. Epub 2006 Aug 11.[16979658 ]
  16. Costantini C, Ko MH, Jonas MC, Puglielli L: A reversible form of lysine acetylation in the ER and Golgi lumen controls the molecular stabilization of BACE1. Biochem J. 2007 Nov 1;407(3):383-95.[17425515 ]
  17. Jonas MC, Costantini C, Puglielli L: PCSK9 is required for the disposal of non-acetylated intermediates of the nascent membrane protein BACE1. EMBO Rep. 2008 Sep;9(9):916-22. doi: 10.1038/embor.2008.132. Epub 2008 Jul 25.[18660751 ]
  18. Ko MH, Puglielli L: Two endoplasmic reticulum (ER)/ER Golgi intermediate compartment-based lysine acetyltransferases post-translationally regulate BACE1 levels. J Biol Chem. 2009 Jan 23;284(4):2482-92. doi: 10.1074/jbc.M804901200. Epub 2008 Nov 14.[19011241 ]
  19. Okada H, Zhang W, Peterhoff C, Hwang JC, Nixon RA, Ryu SH, Kim TW: Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing. FASEB J. 2010 Aug;24(8):2783-94. doi: 10.1096/fj.09-146357. Epub 2010 Mar 30.[20354142 ]
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  21. Hong L, Turner RT 3rd, Koelsch G, Shin D, Ghosh AK, Tang J: Crystal structure of memapsin 2 (beta-secretase) in complex with an inhibitor OM00-3. Biochemistry. 2002 Sep 10;41(36):10963-7.[12206667 ]
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