BACE1 beta-secretase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: BACE1provided by HGNC
Official Full Name: beta-secretase 1provided by HGNC
Primary source: HGNC:HGNC:933
See related: Ensembl:ENSG00000186318 MIM:604252; AllianceGenome:HGNC:933
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: ASP2; BACE; HSPC104
Summary: This gene encodes a member of the peptidase A1 family of aspartic proteases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protease. This transmembrane protease catalyzes the first step in the formation of amyloid beta peptide from amyloid precursor protein. Amyloid beta peptides are the main constituent of amyloid beta plaques, which accumulate in the brains of human Alzheimer's disease patients. [provided by RefSeq, Nov 2015]
Expression: Ubiquitous expression in pancreas (RPKM 33.5), brain (RPKM 30.2) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q23.3

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (117285698..117316256, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (117302503..117333060, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (117156414..117186972, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The beta-Secretase BACE1 Drives Fibroblast Activation in Systemic Sclerosis through the APP/beta-Catenin/Notch Signaling Axis.
Title: The β-Secretase BACE1 Drives Fibroblast Activation in Systemic Sclerosis through the APP/β-Catenin/Notch Signaling Axis.
Serum Beta-Secretase 1 Activity Is a Potential Marker for the Differential Diagnosis between Alzheimer's Disease and Frontotemporal Dementia: A Pilot Study.
Title: Serum Beta-Secretase 1 Activity Is a Potential Marker for the Differential Diagnosis between Alzheimer's Disease and Frontotemporal Dementia: A Pilot Study.
Associations of CSF BACE1 with amyloid pathology, neurodegeneration, and cognition in Alzheimer's disease.
Title: Associations of CSF BACE1 with amyloid pathology, neurodegeneration, and cognition in Alzheimer's disease.
Cerebrovascular Endothelial Dysfunction: Role of BACE1.
Title: Cerebrovascular Endothelial Dysfunction: Role of BACE1.
Determining Structural Changes for Ligand Recognition between Human and Rat Phosphorylated BACE1 in Silico and Its Phosphorylation by GSK3beta at Thr252 by in Vitro Studies.
Title: Determining Structural Changes for Ligand Recognition between Human and Rat Phosphorylated BACE1 in Silico and Its Phosphorylation by GSK3β at Thr252 by in Vitro Studies.
m6A modified BACE1-AS contributes to liver metastasis and stemness-like properties in colorectal cancer through TUFT1 dependent activation of Wnt signaling.
Title: m6A modified BACE1-AS contributes to liver metastasis and stemness-like properties in colorectal cancer through TUFT1 dependent activation of Wnt signaling.
Characterizing the transmembrane domains of ADAM10 and BACE1 and the impact of membrane composition.
Title: Characterizing the transmembrane domains of ADAM10 and BACE1 and the impact of membrane composition.
APP-BACE1 Interaction and Intracellular Localization Regulate Abeta Production in iPSC-Derived Cortical Neurons.
Title: APP-BACE1 Interaction and Intracellular Localization Regulate Aβ Production in iPSC-Derived Cortical Neurons.
BACE1 SUMOylation deregulates phosphorylation and ubiquitination in Alzheimer's disease pathology.
Title: BACE1 SUMOylation deregulates phosphorylation and ubiquitination in Alzheimer's disease pathology.
Inhibition of BACE1 attenuates microglia-induced neuroinflammation after intracerebral hemorrhage by suppressing STAT3 activation.
Title: Inhibition of BACE1 attenuates microglia-induced neuroinflammation after intracerebral hemorrhage by suppressing STAT3 activation.

Submit: New GeneRIF Correction See all GeneRIFs (381)

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
Genetic determinants of cardiovascular events among women with migraine: a genome-wide association study. 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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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

IB1111 (e-PCR)
- UniSTS:37403

BACE_290 (e-PCR)
- UniSTS:277022

G32977 (e-PCR)
- UniSTS:117554

G20524 (e-PCR)
- UniSTS:56386

A005U47 (e-PCR)
- UniSTS:56387

A009Y15 (e-PCR)
- UniSTS:82764

RH12629 (e-PCR)
- UniSTS:9047

D11S2294E (e-PCR)
- UniSTS:24416

RH46256 (e-PCR)
- UniSTS:4714

D11S2254E (e-PCR)
- UniSTS:151410

D11S2277E (e-PCR)
- UniSTS:151414

WI-14206 (e-PCR)
- UniSTS:79766

WI-15498 (e-PCR)
- UniSTS:81310

G20259 (e-PCR)
- UniSTS:25555

A005A12 (e-PCR)
- UniSTS:25556

D11S2298E (e-PCR)
- UniSTS:26102

WI-18163 (e-PCR)
- UniSTS:28924

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables amyloid-beta binding	IPI Inferred from Physical Interaction more info	PubMed
enables aspartic-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables beta-aspartyl-peptidase activity	TAS Traceable Author Statement more info
enables endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine/threonine kinase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in amyloid fibril formation	TAS Traceable Author Statement more info
involved_in amyloid precursor protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in amyloid-beta formation	IDA Inferred from Direct Assay more info	PubMed
involved_in amyloid-beta metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in amyloid-beta metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to amyloid-beta	IEA Inferred from Electronic Annotation more info
involved_in cellular response to copper ion	IEA Inferred from Electronic Annotation more info
involved_in cellular response to manganese ion	IEA Inferred from Electronic Annotation more info
involved_in detection of mechanical stimulus involved in sensory perception of pain	IEA Inferred from Electronic Annotation more info
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	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of neuron apoptotic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in prepulse inhibition	IEA Inferred from Electronic Annotation more info
involved_in presynaptic modulation of chemical synaptic transmission	IEA Inferred from Electronic Annotation more info
involved_in protein processing	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in response to lead ion	IEA Inferred from Electronic Annotation more info
involved_in signaling receptor ligand precursor processing	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi-associated vesicle lumen	TAS Traceable Author Statement more info
located_in axon	IEA Inferred from Electronic Annotation more info
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in cell surface	ISS Inferred from Sequence or Structural Similarity more info
located_in dendrite	IEA Inferred from Electronic Annotation more info
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
is_active_in endosome	IBA Inferred from Biological aspect of Ancestor more info
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endosome membrane	TAS Traceable Author Statement more info
located_in hippocampal mossy fiber to CA3 synapse	IEA Inferred from Electronic Annotation more info
located_in late endosome	IDA Inferred from Direct Assay more info	PubMed
located_in lysosome	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
located_in membrane raft	IEA Inferred from Electronic Annotation more info
located_in multivesicular body	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
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
located_in plasma membrane	TAS Traceable Author Statement more info
located_in recycling endosome	IDA Inferred from Direct Assay more info	PubMed
located_in synaptic vesicle	IEA Inferred from Electronic Annotation more info
is_active_in trans-Golgi network	IBA Inferred from Biological aspect of Ancestor more info
located_in trans-Golgi network	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: beta-secretase 1

Names: APP beta-secretase; asp 2; aspartyl protease 2; beta-site APP cleaving enzyme 1; beta-site APP-cleaving enzyme; beta-site amyloid beta A4 precursor protein-cleaving enzyme; memapsin-2; membrane-associated aspartic protease 2; transmembrane aspartic proteinase Asp2

NP_001193977.1

EC 3.4.23.46

NP_001193978.1

EC 3.4.23.46

NP_001397968.1

EC 3.4.23.46

NP_036236.1

EC 3.4.23.46

NP_620427.1

EC 3.4.23.46

NP_620428.1

EC 3.4.23.46

NP_620429.1

EC 3.4.23.46

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.

Genomic

NG_029372.2 RefSeqGene

Range

5000..35558

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001207048.3 → NP_001193977.1 beta-secretase 1 isoform E

See identical proteins and their annotated locations for NP_001193977.1

Status: REVIEWED

Description

Transcript Variant: This variant (e) lacks two exons from the 5' end and has an alternate 5' exon, compared to variant a. The resulting isoform (E) has a shorter and distinct N-terminus, and lacks a predicted signal peptide compared to isoform A.

Source sequence(s)

AP000892, KC877486

Consensus CDS

CCDS55787.1

UniProtKB/TrEMBL

B7Z3Z4, Q5W9H2

Related

ENSP00000475405.1, ENST00000392937.10

Conserved Domains (1) summary

cd05473
Location:18 → 337

beta_secretase_like; Beta-secretase, aspartic-acid protease important in the pathogenesis of Alzheimer's disease
NM_001207049.3 → NP_001193978.1 beta-secretase 1 isoform F

See identical proteins and their annotated locations for NP_001193978.1

Status: REVIEWED

Description

Transcript Variant: This variant (f) lacks two exons from the 5' end and has an alternate 5' exon and an alternate splice site in the coding region, compared to variant a. The resulting isoform (F) is shorter and lacks a predicted signal peptide compared to isoform A.

Source sequence(s)

AP000892, KC877486

Consensus CDS

CCDS55786.1

UniProtKB/TrEMBL

B7Z3K2, Q5W9H2

Related

ENSP00000422461.1, ENST00000510630.5

Conserved Domains (1) summary

cl11403
Location:18 → 312

pepsin_retropepsin_like; Cellular and retroviral pepsin-like aspartate proteases
NM_001411039.1 → NP_001397968.1 beta-secretase 1 isoform G

Status: REVIEWED

Source sequence(s)

AP000892, KC877486

Consensus CDS

CCDS91601.1

UniProtKB/TrEMBL

A0A7P0TAB4

Related

ENSP00000506107.1, ENST00000680971.1
NM_012104.6 → NP_036236.1 beta-secretase 1 isoform A preproprotein

See identical proteins and their annotated locations for NP_036236.1

Status: REVIEWED

Description

Transcript Variant: This variant (a) is the longest transcript and it encodes the longest isoform (A).

Source sequence(s)

AP000892, KC877486

Consensus CDS

CCDS8383.1

UniProtKB/Swiss-Prot

A0M8W7, B0YIU9, E9PE65, H7BXJ9, P56817, Q9BYB9, Q9BYC0, Q9BYC1, Q9UJT5, Q9ULS1

UniProtKB/TrEMBL

Q8IYC8

Related

ENSP00000318585.6, ENST00000313005.11

Conserved Domains (1) summary

cd05473
Location:72 → 437

beta_secretase_like; Beta-secretase, aspartic-acid protease important in the pathogenesis of Alzheimer's disease
NM_138971.4 → NP_620427.1 beta-secretase 1 isoform C precursor

See identical proteins and their annotated locations for NP_620427.1

Status: REVIEWED

Description

Transcript Variant: This variant (c) has an alternate splice site in the coding region, compared to variant a. The resulting isoform (C) lacks an internal segment, compared to isoform A. This isoform (C) may not undergo proteolytic processing similar to isoform A.

Source sequence(s)

AP000892, KC877486

Consensus CDS

CCDS44740.1

UniProtKB/TrEMBL

Q8IYC8

Related

ENSP00000403685.2, ENST00000445823.6

Conserved Domains (1) summary

cd05473
Location:72 → 393

beta_secretase_like; Beta-secretase, aspartic-acid protease important in the pathogenesis of Alzheimer's disease
NM_138972.4 → NP_620428.1 beta-secretase 1 isoform B precursor

See identical proteins and their annotated locations for NP_620428.1

Status: REVIEWED

Description

Transcript Variant: This variant (b) has an alternate splice site in the coding region, compared to variant a. The resulting isoform (B) lacks an internal segment, compared to isoform A. This isoform (B) may not undergo proteolytic processing similar to isoform A.

Source sequence(s)

AP000892, KC877486

Consensus CDS

CCDS44739.1

UniProtKB/TrEMBL

Q8IYC8

Related

ENSP00000424536.1, ENST00000513780.5

Conserved Domains (1) summary

cd05473
Location:72 → 412

beta_secretase_like; Beta-secretase, aspartic-acid protease important in the pathogenesis of Alzheimer's disease
NM_138973.4 → NP_620429.1 beta-secretase 1 isoform D precursor

See identical proteins and their annotated locations for NP_620429.1

Status: REVIEWED

Description

Transcript Variant: This variant (d) has an alternate splice junction in the coding region, compared to variant a. The resulting isoform (D) lacks an internal segment, compared to isoform A. This isoform (D) may undergo proteolytic processing similar to isoform A.

Source sequence(s)

AP000892, KC877486

Consensus CDS

CCDS44741.1

UniProtKB/TrEMBL

Q8IYC8

Related

ENSP00000402228.2, ENST00000428381.6

Conserved Domains (1) summary

cl11403
Location:72 → 368

pepsin_retropepsin_like; Cellular and retroviral pepsin-like aspartate proteases