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    BACE1 beta-site APP-cleaving enzyme 1 [ Homo sapiens (human) ]

    Gene ID: 23621, updated on 16-Jun-2013
    Official Symbol
    BACE1provided by HGNC
    Official Full Name
    beta-site APP-cleaving enzyme 1provided by HGNC
    Primary source
    HGNC:933
    See related
    Ensembl:ENSG00000186318; HPRD:07255; MIM:604252; Vega:OTTHUMG00000160636
    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
    Cerebral deposition of amyloid beta peptide is an early and critical feature of Alzheimer's disease. Amyloid beta peptide is generated by proteolytic cleavage of amyloid precursor protein (APP) by two proteases, one of which is the protein encoded by this gene. The encoded protein, a member of the peptidase A1 protein family, is a type I integral membrane glycoprotein and aspartic protease that is found mainly in the Golgi. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2011]
    Location :
    11q23.2-q23.3
    Sequence :
    Chromosome: 11; NC_000011.9 (117156402..117186972, complement)
    See BACE1 in Epigenomics, MapViewer

    Chromosome 11 - NC_000011.9Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC100652768 Neighboring gene transgelin Neighboring gene proprotein convertase subtilisin/kexin type 7 Neighboring gene ring finger protein 214 Neighboring gene BACE1 antisense RNA Neighboring gene proline rich 13 pseudogene Neighboring gene centrosomal protein 164kDa Neighboring gene Down syndrome cell adhesion molecule like 1

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details

    Related articles in PubMed

    1. Inhibitory evaluation of sulfonamide chalcones on β-secretase and acylcholinesterase. Kang JE, et al. Molecules, 2012 Dec 21. PMID 23344193.
    2. [Influence of inhibited α7 nicotinic acetylcholine receptor gene expression on the production of β-amyloid peptide in SH-SY5Y cells]. Ouyang K, et al. Zhonghua Bing Li Xue Za Zhi, 2012 Dec. PMID 23324234.
    3. Inhibition of GSK3β-mediated BACE1 expression reduces Alzheimer-associated phenotypes. Ly PT, et al. J Clin Invest, 2013 Jan 2. PMID 23202730.
    4. Transcriptional and post-transcriptional regulation of β-secretase. Tamagno E, et al. IUBMB Life, 2012 Dec. PMID 23180460.
    5. BACE1 protein endocytosis and trafficking are differentially regulated by ubiquitination at lysine 501 and the Di-leucine motif in the carboxyl terminus. Kang EL, et al. J Biol Chem, 2012 Dec 14. PMID 23109336.

    See all (247) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Inhibiting Chrna7 expression markedly stimulated the production of Abeta through the mechanism of increased expression of BACE1 and inhibited expression of BACE2 in SH-SY5Y cells.
      Title: [Influence of inhibited α7 nicotinic acetylcholine receptor gene expression on the production of β-amyloid peptide in SH-SY5Y cells].
    2. BACE1 is increased by SUMO1, interacting via a dileucine motif in BACE1.
      Title: SUMO1 modulates Aβ generation via BACE1 accumulation.
    3. BACE1 initiates the pathological cascade by cleaving amyloid beta precursor protein at the N-terminal end. (Review)
      Title: Transcriptional and post-transcriptional regulation of β-secretase.
    4. Differential gene expression of BACE1 and PSEN1 in the knockdown cells, which is possibly a consequence of MAT2A deregulation and may indicate a self regulatory mechanism.
      Title: The amyloid precursor protein (APP) family members are key players in S-adenosylmethionine formation by MAT2A and modify BACE1 and PSEN1 gene expression-relevance for Alzheimer's disease.
    5. Low protein levels of Uch-L1 are associated with high protein levels of BACE1 in sporadic AD brains.
      Title: Aβ1-42-mediated down-regulation of Uch-L1 is dependent on NF-κB activation and impaired BACE1 lysosomal degradation.
    6. SNX12 interacts with BACE1 and downregulation of sorting nexin 12 accelerates BACE1 endocytosis and decreases steady-state level of cell surface BACE1.
      Title: Sorting nexin 12 interacts with BACE1 and regulates BACE1-mediated APP processing.
    7. These data provide evidence for regulation of BACE1 expression and AD pathogenesis by GSK3beta and that inhibition of GSK3 signaling can reduce Abeta neuropathology and alleviate memory deficits in AD model mice
      Title: Inhibition of GSK3β-mediated BACE1 expression reduces Alzheimer-associated phenotypes.
    8. Lysophosphatidic acid,the most bioactive component of oxLDL induces increased production of Abeta and BACE1 expression.
      Title: Lysophosphatidic acid induces increased BACE1 expression and Aβ formation.
    9. a possible association of a common synonymous BACE1 polymorphism (rs638405) with sporadic Creutzfeldt-Jakob disease
      Title: A common BACE1 polymorphism is a risk factor for sporadic Creutzfeldt-Jakob disease.
    10. analysis of biological aspects of BACE1, and the effects of several natural products that modulate BACE1-processing of APP [review]
      Title: Natural compounds that modulate BACE1-processing of amyloid-beta precursor protein in Alzheimer's disease.
    Submit: New GeneRIF Correction See all (205)

    Review eQTL and phenotype association data in this region using PheGenI

    Products Interactant Other Gene Complex Source Pubs Description
    NP_036236.1 AAH00006.1 ATP1B1    BIND  PubMed BACE1 interacts with ATP1B1 (Na/K-ATPase, beta-subunit). This interaction was modelled on a demonstrated interaction between mouse BACE1 and human Na/K-ATPase, beta-subunit. 
    NP_036236.1 AAH14961.1 CMPK1    BIND  PubMed BACE1 interacts with UMP-CMPK. This interaction was modelled on a demonstrated interaction between mouse BACE1 and human UMP-CMPK. 
    NP_036236.1 NP_112188.1 ITM2C    BIND  PubMed BACE1 interacts with ITM2C (BRI3). 
    NP_036236.1 NP_003676.1 KHSRP    BIND  PubMed BACE1 interacts with KHSRP. This interaction was modelled on a demonstrated interaction between mouse BACE1 and human KHSRP. 
    NP_036236.1 NP_056146.1 NCSTN    BIND  PubMed Nicastrin interacts with BACE1. 
    NP_036236.1 NP_005304.3 PDIA3    BIND  PubMed BACE1 interacts with PDIA3 (ERp60). This interaction was modelled on a demonstrated interaction between mouse BACE1 and human PDIA3. 
    NP_036236.1 NP_002769.1 PSAP    BIND  PubMed BACE1 interacts with PSAP (prosaposin). This interaction was modelled on a demonstrated interaction between mouse BACE1 and human prosaposin. 
    NP_036236.1 NP_005484.2 RANBP9    BIND  PubMed BACE1 interacts with RANBP9 (RANBPM). This interaction was modelled on a demonstrated interaction between mouse BACE1 and human RANBPM. 
    P56817 P05067 APP    HPRD  PubMed  
    P56817 P05026 ATP1B1    HPRD  PubMed  
    P56817 O95415 BRI3    HPRD  PubMed  
    P56817 P30085 CMPK1    HPRD  PubMed  
    P56817 P48730 CSNK1D    HPRD  PubMed  
    P56817 P09958 FURIN    HPRD  PubMed  
    P56817 Q9UJY4 GGA2    HPRD  PubMed  
    P56817 Q9NQX7 ITM2C    HPRD  PubMed  
    P56817 Q92945 KHSRP    HPRD  PubMed  
    P56817 Q07954 LRP1    HPRD  PubMed  
    P56817 P08253 MMP2    HPRD  PubMed  
    P56817 Q92542 NCSTN    HPRD  PubMed  
    P56817 P30101 PDIA3    HPRD  PubMed  
    P56817 O15162 PLSCR1    HPRD  PubMed  
    P56817 P07602 PSAP    HPRD  PubMed  
    P56817 P49768 PSEN1    HPRD  PubMed  
    P56817 Q96S59 RANBP9    HPRD  PubMed  
    P56817 Q14242 SELPLG    HPRD  PubMed  
    BioGRID:117154 BioGRID:117623 FBXO2    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity 
    BioGRID:117154 BioGRID:117540 GGA1    BioGRID  PubMed Affinity Capture-Western; Co-crystal Structure; FRET; Reconstituted Complex 
    BioGRID:117154 BioGRID:116697 GGA2    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:117154 BioGRID:116775 GGA3    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:117154 BioGRID:116961 NCSTN    BioGRID  PubMed Reconstituted Complex 
    BioGRID:117154 BioGRID:129116 PCSK9    BioGRID  PubMed Biochemical Activity; Reconstituted Complex 
    BioGRID:117154 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-Western 
    • Alzheimer's disease, organism-specific biosystem (from KEGG)
      Alzheimer's disease, organism-specific biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
    • Alzheimer's disease, conserved biosystem (from KEGG)
      Alzheimer's disease, conserved biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
    • Alzheimers Disease, organism-specific biosystem (from WikiPathways)
      Alzheimers Disease, organism-specific biosystemThis pathway displays current genes, proteolytic events and other processes associated with the progression of Alzheimer's disease. This pathway was adapted from KEGG on 10/7/2011. Note: mitochondria...

    Markers

    Genotypes

    Homology

    Clone Names

    • FLJ90568, KIAA1149

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    aspartic-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    beta-aspartyl-peptidase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enzyme binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    beta-amyloid metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    membrane protein ectodomain proteolysis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    proteolysis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cell surface IEA
    Inferred from Electronic Annotation
    more info
    		  
    cytoplasmic vesicle membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
    		  
    endosome IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    integral to membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    integral to plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    trans-Golgi network IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Preferred Names
    beta-secretase 1
    Names
    beta-secretase 1
    asp 2
    memapsin-2
    APP beta-secretase
    aspartyl protease 2
    beta-site APP cleaving enzyme 1
    beta-secretase 1 precursor variant 1
    transmembrane aspartic proteinase Asp2
    membrane-associated aspartic protease 2
    beta-site amyloid beta A4 precursor protein-cleaving enzyme
    NP_001193977.1
    NP_001193978.1
    NP_036236.1
    NP_620427.1
    NP_620428.1
    NP_620429.1

    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

    1. NG_029372.1 RefSeqGene

      Range
      5001..35571
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

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

      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, compared to isoform A.
      Source sequence(s)
      AB177847, AK296535, BM996673, DC343475
      Consensus CDS
      CCDS55787.1
      UniProtKB/TrEMBL
      B7Z3Z4
      UniProtKB/TrEMBL
      Q5W9H2
      Conserved Domains (1) summary
      cd05473
      Location:18 – 337
      Blast Score: 1646
      beta_secretase_like; Beta-secretase, aspartic-acid protease important in the pathogenesis of Alzheimer's disease.

    2. NM_001207049.1 → NP_001193978.1  beta-secretase 1 isoform F

      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) has a shorter and distinct N-terminus and lacks an internal segment, compared to isoform A.
      Source sequence(s)
      AB032975, AK296015, BM996673, DC343475
      Consensus CDS
      CCDS55786.1
      UniProtKB/TrEMBL
      B7Z3K2
      UniProtKB/Swiss-Prot
      P56817
      Conserved Domains (1) summary
      cl11403
      Location:18 – 312
      Blast Score: 1477
      pepsin_retropepsin_like; Cellular and retroviral pepsin-like aspartate proteases.

    3. NM_012104.4 → NP_036236.1  beta-secretase 1 isoform A preproprotein

      Status: REVIEWED

      Description
      Transcript Variant: This variant (a) is the longest transcript and it encodes the longest isoform (A).
      Source sequence(s)
      AB032975, BC065492, BM996673
      Consensus CDS
      CCDS8383.1
      UniProtKB/Swiss-Prot
      P56817
      Related
      ENSP00000318585, OTTHUMP00000218630, ENST00000313005, OTTHUMT00000361505
      Conserved Domains (2) summary
      cd05473
      Location:72 – 437
      Blast Score: 1903
      beta_secretase_like; Beta-secretase, aspartic-acid protease important in the pathogenesis of Alzheimer's disease.
      pfam00026
      Location:75 – 416
      Blast Score: 386
      Asp; Eukaryotic aspartyl protease

    4. NM_138971.3 → NP_620427.1  beta-secretase 1 isoform C preproprotein

      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.
      Source sequence(s)
      AB032975, BC065492, BM996673
      Consensus CDS
      CCDS44740.1
      UniProtKB/Swiss-Prot
      P56817
      Conserved Domains (2) summary
      cd05473
      Location:72 – 393
      Blast Score: 1609
      beta_secretase_like; Beta-secretase, aspartic-acid protease important in the pathogenesis of Alzheimer's disease.
      pfam00026
      Location:75 – 372
      Blast Score: 303
      Asp; Eukaryotic aspartyl protease

    5. NM_138972.3 → NP_620428.1  beta-secretase 1 isoform B preproprotein

      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.
      Source sequence(s)
      AB032975, BC065492, BM996673
      Consensus CDS
      CCDS44739.1
      UniProtKB/Swiss-Prot
      P56817
      Conserved Domains (2) summary
      cd05473
      Location:72 – 412
      Blast Score: 1734
      beta_secretase_like; Beta-secretase, aspartic-acid protease important in the pathogenesis of Alzheimer's disease.
      pfam00026
      Location:75 – 391
      Blast Score: 344
      Asp; Eukaryotic aspartyl protease

    6. NM_138973.3 → NP_620429.1  beta-secretase 1 isoform D preproprotein

      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.
      Source sequence(s)
      AB032975, BC065492, BM996673
      Consensus CDS
      CCDS44741.1
      UniProtKB/Swiss-Prot
      P56817
      Conserved Domains (2) summary
      pfam00026
      Location:75 – 347
      Blast Score: 278
      Asp; Eukaryotic aspartyl protease
      cl11403
      Location:72 – 368
      Blast Score: 1409
      pepsin_retropepsin_like; Cellular and retroviral pepsin-like aspartate proteases.

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

    Reference GRCh37.p10 Primary Assembly

    Genomic

    1. NC_000011.9 Reference GRCh37.p10 Primary Assembly

      Range
      117156402..117186972, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000143.1 Alternate HuRef

      Range
      113090543..113121018, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.0

    Genomic

    1. NC_018922.1 Alternate CHM1_1.0

      Range
      117019975..117050546, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    genomic ABBA01039728.1 None
    genomic ABBA01039729.1 (8454..16984) None
    genomic AMYH01004062.1 (52535..83106) None
    genomic AP000892.4 (84180..114738) None
    genomic AY162468.1 AAO23912.1
    genomic CH471065.1 EAW67308.1
      EAW67309.1
      EAW67310.1
      EAW67311.1
      EAW67312.1
      EAW67313.1
      EAW67314.1
      EAW67315.1
      EAW67316.1
      EAW67317.1
    genomic CS027018.1 CAI61888.1
    genomic DQ007053.1 AAY16982.1
    genomic EF444940.1 ACA05927.1
    mRNA AB032975.2 BAA86463.2
    mRNA AB050436.1 BAB40931.1
    mRNA AB050437.1 BAB40932.1
    mRNA AB050438.1 BAB40933.1
    mRNA AB089958.1 BAC81826.1
    mRNA AB177847.1 BAD66825.1
    mRNA AF161367.1 AAF28927.1
    mRNA AF190725.1 AAF04142.1
    mRNA AF200193.1 AAF13715.1
    mRNA AF200343.1 AAF17079.1
    mRNA AF201468.1 AAF18982.1
    mRNA AF204943.1 AAF26367.1
    mRNA AF324837.1 AAM54050.1
    mRNA AF338816.1 AAK38374.1
    mRNA AF338817.1 AAK38375.1
    mRNA AF527782.1 AAM92013.1
    mRNA AK075049.1 BAG52056.1
    mRNA AK296015.1 BAH12238.1
    mRNA AK296535.1 BAH12380.1
    mRNA AL833810.1 CAD38674.1
    mRNA BC036084.1 AAH36084.1
    mRNA BC065492.1 AAH65492.1
    mRNA BM996673.1 None
    mRNA BQ005204.1 None
    mRNA DC343475.1 None
    other-genetic DQ891509.2 ABM82435.1
    other-genetic DQ894700.2 ABM85626.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P56817.2 GenPept UniProtKB/Swiss-Prot:P56817

    Gene LinkOut

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

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content

      Table of contents

      Related information

      • Order cDNA clone
        Order cDNA clone
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        3D structure of a gene
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        BioAssay, by Protein Target
      • BioProjects
        BioProjects related to a gene
      • BioSystems
        BioSystems
      • CCDS
        Links from Gene to CCDS are established if a gene encodes a protein sequence that is a member of a Consensus CDS (CCDS).
      • Conserved Domains
        Conserved Domain Database Links between Entrez Gene and Conserved Domain Database (CDD) are calculated from the domains annotated by the CDD group on Reference Sequence proteins.
      • dbVar
        Link from Gene to dbVar
      • EST
        Link to related EST entry
      • Full text in PMC
        PMC links
      • Full text in PMC_nucleotide
        Full text in PubMedCentral identified from shared sequence links
      • GAP
        GAP Links
      • Genome
        Genome records having the gene annotated on corresponding genomic reference sequence.
      • GEO Profiles
        Related GEO
      • HomoloGene
        Links between HomoloGene and Gene are provided by the HomoloGene group when a gene is included in a HomoloGene record.
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      • Nucleotide
        Link to related Nucleotide entry
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      • Probe
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        Link to related protein entry
      • PubChem Compound
        PubChem Compounds
      • PubChem Substance
        PubChem Substances
      • PubMed
        Links between Gene and PubMed are the result of the following: 1. Manual curation within NCBI. Part of the process of generating a REVIEWED RefSeq is an analysis of the current literature. Papers that are seminal in defining the gene, its sequence, and its function are added to the record at that time. Alert users point out gaps or errors in papers associated with a Gene record. These messages are reviewed and implemented as required. 2. Integration of information from other public databases. Gene integrates gene-citation from resources external to NCBI such as model organism-specific databases, Gene Ontology (GO), groups curating interactions, and sequence databases. The assumption in using these source is that they report citations specific to a gene in a known species. Gene does not process citations from OMIM automatically, because many of citations in OMIM refer to studies of genes in species other than human.
      • PubMed (GeneRIF)
        GeneRIF -- Gene Reference Into Function Staff of the Index Section in the National Library of Medicine review the current literature. When they find articles focused on the structure and function of a gene, they write a brief summary of the impact of the paper and make the connection between the citation (PubMed) and Gene. An interface exists for interested users to submit such data as well. http://www.ncbi.nlm.nih.gov/projects/GeneRIF/GeneRIFhelp.html
      • PubMed (OMIM)
        Links are provided when Gene has a link to a record in OMIM, and OMIM explicitly cites these publications in PubMed.
      • PubMed(nucleotide/PMC)
        Citations in PubMed identified from shared sequence and PMC links.
      • RefSeq Proteins
        Link to Protein RefSeqs
      • RefSeq RNAs
        Link to Nucleotide RefSeq RNAs
      • RefSeqGene
        Link to Nucleotide RefSeqGenes
      • SNP
        Related SNP records
      • SNP: GeneView
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      • SNP: Genotype
        Gene Genotype Report
      • Taxonomy
        Link to related taxonomy entry
      • UniGene
        Links are provided between Gene and UniGene when both databases calculate links to the same mRNA record (gi).
      • UniSTS
        Related UniSTS records

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