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

Summary

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

Location:: 21q22.2-q22.3

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	21	NC_000021.9 (41168160..41282530)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	21	NC_060945.1 (39556492..39670904)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	21	NC_000021.8 (42540087..42654457)

Chromosome 21 - NC_000021.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
RCAN1 Inhibits BACE2 Turnover by Attenuating Proteasome-Mediated BACE2 Degradation.
Title: RCAN1 Inhibits BACE2 Turnover by Attenuating Proteasome-Mediated BACE2 Degradation.
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.
BACE2 degradation is mediated by both the proteasome and lysosome pathways.
Title: BACE2 degradation is mediated by both the proteasome and lysosome pathways.
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.
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.
RNA-seq evidence of biallelic expression of BACE2 and 10 neighboring genes in at least one primary human tissue tested indicates that the expression of BACE2 is uncoupled from the control of the maternally inherited 5mCpG imprints at the WRB differentially methylated region (DMR) in disomic controls or trisomy (Down syndrome) individuals.
Title: Trisomy 21 Alters DNA Methylation in Parent-of-Origin-Dependent and -Independent Manners.

Submit: New GeneRIF Correction See all GeneRIFs (41)

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 EBI GWAS CatalogPubMed
Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

SHGC-87652 (e-PCR)
- UniSTS:13317

G35323 (e-PCR)
- UniSTS:83209

PMC310729P6 (e-PCR)
- UniSTS:272655

D21S355 (e-PCR)
- UniSTS:147739

BACE2_712 (e-PCR)
- UniSTS:277021

STS_CEB270 (e-PCR)
- UniSTS:255263

RH69858 (e-PCR)
- UniSTS:28714

SHGC-52036 (e-PCR)
- UniSTS:35668

SHGC-6869 (e-PCR)
- UniSTS:89178

RH76632 (e-PCR)
- UniSTS:85344

D21S418E (e-PCR)
- UniSTS:148066

STS-AA035768 (e-PCR)
- UniSTS:32142

SHGC-52055 (e-PCR)
- UniSTS:78223

SHGC-87653 (e-PCR)
- UniSTS:29080

D21S398 (e-PCR)
- UniSTS:147867

SHGC-51917 (e-PCR)
- UniSTS:38556

RH45177 (e-PCR)
- UniSTS:68012

SHGC-87655 (e-PCR)
- UniSTS:68269

G20436 (e-PCR)
- UniSTS:3245

A005R16 (e-PCR)
- UniSTS:3246

D21S53 (e-PCR)
- UniSTS:147886

STS-T66917 (e-PCR)
- UniSTS:70839

SHGC-87646 (e-PCR)
- UniSTS:35525

RH79591 (e-PCR)
- UniSTS:89803

SHGC-106623 (e-PCR)
- UniSTS:169949

RH98903 (e-PCR)
- UniSTS:92410

WI-11358 (e-PCR)
- UniSTS:20989

WI-17388 (e-PCR)
- UniSTS:20990

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

EC 3.4.23.45

NP_620476.1

EC 3.4.23.45

NP_620477.1

EC 3.4.23.45

XP_016883803.1

EC 3.4.23.45

XP_054180398.1

EC 3.4.23.45

XP_054180399.1

EC 3.4.23.45

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)

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
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
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