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    BACE2 beta-secretase 2 [ Homo sapiens (human) ]

    Gene ID: 25825, updated on 2-Nov-2024

    Summary

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    Official Symbol
    BACE2provided by HGNC
    Official Full Name
    beta-secretase 2provided by HGNC
    Primary source
    HGNC:HGNC:934
    See related
    Ensembl:ENSG00000182240 MIM:605668; AllianceGenome:HGNC:934
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ASP1; BAE2; DRAP; AEPLC; ALP56; ASP21; CDA13; CEAP1
    Summary
    This gene encodes an integral membrane glycoprotein that functions as an aspartic protease. The encoded protein cleaves amyloid precursor protein into amyloid beta peptide, which is a critical step in the etiology of Alzheimer's disease and Down syndrome. The protein precursor is further processed into an active mature peptide. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]
    Expression
    Ubiquitous expression in stomach (RPKM 12.5), gall bladder (RPKM 11.8) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See BACE2 in Genome Data Viewer
    Location:
    21q22.2-q22.3
    Exon count:
    11
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 21 NC_000021.9 (41168160..41282530)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 21 NC_060945.1 (39556492..39670904)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 21 NC_000021.8 (42540087..42654457)

    Chromosome 21 - NC_000021.9Genomic Context describing neighboring genes Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr21:42519321-42519905 Neighboring gene long intergenic non-protein coding RNA 323 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13329 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr21:42551642-42552451 Neighboring gene microRNA 3197 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42572358-42572858 Neighboring gene placenta enriched 4 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42572859-42573359 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42594561-42595060 Neighboring gene ReSE screen-validated silencer GRCh37_chr21:42612073-42612217 Neighboring gene NANOG hESC enhancer GRCh37_chr21:42616252-42616757 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr21:42646500-42647699 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42651763-42652318 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42652319-42652873 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42661864-42662364 Neighboring gene FAM3 metabolism regulating signaling molecule B Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18470 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr21:42731293-42732096 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18471 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18472 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 13330 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18473 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42739613-42740114 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 18474 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42740714-42741402 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42741403-42742089 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 21:42745414 Neighboring gene melanoma risk locus-associated MPRA allelic enhancers 21:42746568 and 21:42746578 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42750497-42750998 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr21:42750999-42751498 Neighboring gene MX dynamin like GTPase 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. BACE2, as a novel APP theta-secretase, is not responsible for the pathogenesis of Alzheimer's disease in Down syndrome. Sun X, et al. FASEB J, 2006 Jul. PMID 16816112
    2. BACE-2 is overexpressed in Down's syndrome. Barbiero L, et al. Exp Neurol, 2003 Aug. PMID 12895444
    3. Insights from modeling the tertiary structure of human BACE2. Chou KC. J Proteome Res, 2004 Sep-Oct. PMID 15473697
    4. A novel aspartic protease gene, ALP56, is up-regulated in human breast cancer independently from the cathepsin D gene. Kondoh K, et al. Breast Cancer Res Treat, 2003 Mar. PMID 12611455
    5. Identification of BACE2 as an avid ß-amyloid-degrading protease. Abdul-Hay SO, et al. Mol Neurodegener, 2012 Sep 17. PMID 22986058, Free PMC Article

    See all (82) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The Alzheimer's disease-linked protease BACE2 cleaves VEGFR3 and modulates its signaling.
      Title: The Alzheimer's disease-linked protease BACE2 cleaves VEGFR3 and modulates its signaling.
    2. BACE2 deficiency impairs expression and function of endothelial nitric oxide synthase in brain endothelial cells.
      Title: BACE2 deficiency impairs expression and function of endothelial nitric oxide synthase in brain endothelial cells.
    3. m(6)A RNA hypermethylation-induced BACE2 boosts intracellular calcium release and accelerates tumorigenesis of ocular melanoma.
      Title: m(6)A RNA hypermethylation-induced BACE2 boosts intracellular calcium release and accelerates tumorigenesis of ocular melanoma.
    4. Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain.
      Title: Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene dose-sensitive AD suppressor in human brain.
    5. Cell surface GRP78 regulates BACE2 via lysosome-dependent manner to maintain mesenchymal phenotype of glioma stem cells.
      Title: Cell surface GRP78 regulates BACE2 via lysosome-dependent manner to maintain mesenchymal phenotype of glioma stem cells.
    6. RCAN1 Inhibits BACE2 Turnover by Attenuating Proteasome-Mediated BACE2 Degradation.
      Title: RCAN1 Inhibits BACE2 Turnover by Attenuating Proteasome-Mediated BACE2 Degradation.
    7. TGFbeta1-induced beta-site APP-cleaving enzyme 2 upregulation promotes tumorigenesis through the NF-kappaB signalling pathway in human gliomas.
      Title: TGFβ1-induced beta-site APP-cleaving enzyme 2 upregulation promotes tumorigenesis through the NF-κB signalling pathway in human gliomas.
    8. BACE2 degradation is mediated by both the proteasome and lysosome pathways.
      Title: BACE2 degradation is mediated by both the proteasome and lysosome pathways.
    9. Common BACE2 Polymorphisms are Associated with Altered Risk for Alzheimer's Disease and CSF Amyloid Biomarkers in APOE epsilon4 Non-Carriers.
      Title: Common BACE2 Polymorphisms are Associated with Altered Risk for Alzheimer's Disease and CSF Amyloid Biomarkers in APOE ε4 Non-Carriers.
    10. the behavior of the flap tips during simulations is different between BACE1 and BACE2. The BACE1 active site cavity is more spacious as compared to that of BACE2. The analysis of 10S loop and 113S loop showed a similar trend to that of flaps, with the BACE1 loops being more flexible and less stable than those of BACE2
      Title: A comparative molecular dynamics study on BACE1 and BACE2 flap flexibility.
    Submit: New GeneRIF Correction See all GeneRIFs (42)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.
    EBI GWAS Catalog
    Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of beta-site APP-cleaving enzyme 2 (BACE2) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat recruits APP into lipid rafts to facilitate the processing of APP by beta-secretase, which leads to increased levels of ABeta42 in HIV-1 infected U-87 MG cells PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ13585

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables aspartic-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in amyloid-beta metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in glucose homeostasis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in melanosome organization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in membrane protein ectodomain proteolysis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in membrane protein ectodomain proteolysis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in membrane protein ectodomain proteolysis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of amyloid precursor protein biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in peptide hormone processing NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in protein processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in proteolysis NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in endosome IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in melanosome membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in trans-Golgi network IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    beta-secretase 2
    Names
    56 kDa aspartic-like protease
    Down syndrome region aspartic protease
    SLCO3A1/BACE2 fusion
    aspartyl protease 1
    beta-site APP-cleaving enzyme 2
    beta-site amyloid beta A4 precursor protein-cleaving enzyme 2
    memapsin-1
    membrane-associated aspartic protease 1
    theta-secretase
    transmembrane aspartic proteinase Asp1
    NP_036237.2
    NP_620476.1
    NP_620477.1
    XP_016883803.1
    XP_054180398.1
    XP_054180399.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_012105.5 → NP_036237.2  beta-secretase 2 isoform A preproprotein

      See identical proteins and their annotated locations for NP_036237.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (a) represents the longest transcript and encodes the longest isoform (A).
      Source sequence(s)
      AF178532, AF188276, AF200342, AL773578
      Consensus CDS
      CCDS13668.1
      UniProtKB/Swiss-Prot
      A8K7P1, Q5DIH8, Q8N2D4, Q9H2V8, Q9NZL1, Q9NZL2, Q9UJT6, Q9Y5Z0
      Related
      ENSP00000332979.6, ENST00000330333.11
      Conserved Domains (2) summary
      cd05473
      Location:89 → 450
      beta_secretase_like; Beta-secretase, aspartic-acid protease important in the pathogenesis of Alzheimer's disease
      pfam00026
      Location:92 → 430
      Asp; Eukaryotic aspartyl protease

    2. NM_138991.3 → NP_620476.1  beta-secretase 2 isoform C preproprotein

      See identical proteins and their annotated locations for NP_620476.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (c) lacks an alternate in-frame exon, compared to variant a. The encoded isoform (C) is shorter than isoform A.
      Source sequence(s)
      AF188276, AF200342, AL773578
      Consensus CDS
      CCDS13669.1
      UniProtKB/Swiss-Prot
      Q9Y5Z0
      Related
      ENSP00000327528.4, ENST00000347667.5
      Conserved Domains (2) summary
      pfam00026
      Location:92 → 380
      Asp; Eukaryotic aspartyl protease
      cl11403
      Location:89 → 400
      pepsin_retropepsin_like; Cellular and retroviral pepsin-like aspartate proteases

    3. NM_138992.3 → NP_620477.1  beta-secretase 2 isoform B preproprotein

      See identical proteins and their annotated locations for NP_620477.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (b) lacks an exon in the 3' coding region, which results in a frameshift, compared to variant a. The encoded isoform (B) is shorter and has a distinct C-terminus, compared to isoform A.
      Source sequence(s)
      AF188276, AF188277, AF200342, AL773578
      Consensus CDS
      CCDS13670.1
      UniProtKB/Swiss-Prot
      Q9Y5Z0
      Related
      ENSP00000333854.6, ENST00000328735.10
      Conserved Domains (1) summary
      cl11403
      Location:89 → 393
      pepsin_retropepsin_like; Cellular and retroviral pepsin-like aspartate proteases

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000021.9 Reference GRCh38.p14 Primary Assembly

      Range
      41168160..41282530
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017028314.2 → XP_016883803.1  beta-secretase 2 isoform X1

      UniProtKB/TrEMBL
      B3KNE8

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060945.1 Alternate T2T-CHM13v2.0

      Range
      39556492..39670904
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054324423.1 → XP_054180398.1  beta-secretase 2 isoform X1

    2. XM_054324424.1 → XP_054180399.1  beta-secretase 2 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y5Z0.1 GenPept UniProtKB/Swiss-Prot:Q9Y5Z0

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Molecular Biology Databases
    Research Materials
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