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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
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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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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

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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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.

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