Human Gene BACE1 (ENST00000513780.5) Description and Page Index
  Description: Homo sapiens beta-secretase 1 (BACE1), transcript variant b, mRNA. (from RefSeq NM_138972)
RefSeq Summary (NM_138972): 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].
Gencode Transcript: ENST00000513780.5
Gencode Gene: ENSG00000186318.16
Transcript (Including UTRs)
   Position: hg38 chr11:117,289,535-117,315,798 Size: 26,264 Total Exon Count: 9 Strand: -
Coding Region
   Position: hg38 chr11:117,289,566-117,315,795 Size: 26,230 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr11:117,289,535-117,315,798)mRNA (may differ from genome)Protein (476 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGIneXtProtOMIMPubMed
ReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: BACE1_HUMAN
DESCRIPTION: RecName: Full=Beta-secretase 1; EC=3.4.23.46; AltName: Full=Aspartyl protease 2; Short=ASP2; Short=Asp 2; AltName: Full=Beta-site amyloid precursor protein cleaving enzyme 1; Short=Beta-site APP cleaving enzyme 1; AltName: Full=Memapsin-2; AltName: Full=Membrane-associated aspartic protease 2; Flags: Precursor;
FUNCTION: Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase.
CATALYTIC ACTIVITY: Broad endopeptidase specificity. Cleaves Glu- Val-Asn-Leu-|-Asp-Ala-Glu-Phe in the Swedish variant of Alzheimer amyloid precursor protein.
ENZYME REGULATION: Inhibited by RTN3 and RTN4.
SUBUNIT: Monomer. Interacts with GGA1, GGA2 and GGA3. Interacts with RTN3 and RTN4. Interacts with SNX6. Interacts with PCSK9.
SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. Golgi apparatus, trans-Golgi network. Endoplasmic reticulum. Endosome. Cell surface. Cytoplasmic vesicle membrane. Note=Predominantly localized to the later Golgi/trans-Golgi network (TGN) and minimally detectable in the early Golgi compartments. A small portion is also found in the endoplasmic reticulum, endosomes and on the cell surface.
TISSUE SPECIFICITY: Expressed at high levels in the brain and pancreas. In the brain, expression is highest in the substantia nigra, locus coruleus and medulla oblongata.
DOMAIN: The transmembrane domain is necessary for its activity. It determines its late Golgi localization and access to its substrate, APP.
PTM: Glycosylated.
SIMILARITY: Belongs to the peptidase A1 family.
SEQUENCE CAUTION: Sequence=BAA86463.2; Type=Frameshift; Positions=34;
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/bace1/";

-  MalaCards Disease Associations
  MalaCards Gene Search: BACE1
Diseases sorted by gene-association score: nervous system disease (27), alzheimer disease (23), central nervous system disease (16), disease of mental health (16), autonomic nervous system neoplasm (14), peripheral nervous system neoplasm (14), chromosomal disease (14), hypotrichosis 1 (13), deafness, autosomal recessive 74 (11), toxic encephalopathy (11), acquired metabolic disease (10), inclusion body myositis (10), amyloidosis (9), myositis (9), cerebral amyloid angiopathy (8), nervous system cancer (7), cystoisosporiasis (6), balanoposthitis (6), tracheitis (6), glucose metabolism disease (5), dementia (5), hair disease (5), peroneal nerve paralysis (5), down syndrome (5), hermansky-pudlak syndrome 5 (5), retinitis pigmentosa 33 (4), dementia, frontotemporal (4), skull base meningioma (4), basal ganglia disease (4), achromatopsia 3 (3), neuroblastoma (2), schizophrenia (1), achromatopsia (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 31.70 RPKM in Brain - Spinal cord (cervical c-1)
Total median expression: 384.03 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
3' UTR -3.6031-0.116 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR009119 - Pept_A1_BACE
IPR009120 - Pept_A1_BACE1
IPR001461 - Peptidase_A1
IPR021109 - Peptidase_aspartic
IPR001969 - Peptidase_aspartic_AS
IPR009007 - Peptidase_aspartic_catalytic

Pfam Domains:
PF00026 - Eukaryotic aspartyl protease

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1FKN
- X-ray MuPIT

1M4H
- X-ray MuPIT

1PY1
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
1SGZ - X-ray MuPIT 1TQF - X-ray MuPIT 1UJJ - X-ray MuPIT
1UJK - X-ray MuPIT 1W50 - X-ray MuPIT 1W51 - X-ray MuPIT
1XN2 - X-ray MuPIT 1XN3 - X-ray MuPIT 1XS7 - X-ray MuPIT
1YM2 - X-ray MuPIT 1YM4 - X-ray MuPIT 2B8L - X-ray MuPIT
2B8V - X-ray MuPIT 2F3E - X-ray MuPIT 2F3F - X-ray MuPIT
2FDP - X-ray MuPIT 2G94 - X-ray MuPIT 2HIZ - X-ray MuPIT
2HM1 - X-ray MuPIT 2IQG - X-ray MuPIT 2IRZ - X-ray MuPIT
2IS0 - X-ray MuPIT 2NTR - X-ray MuPIT 2OAH - X-ray MuPIT
2OF0 - X-ray MuPIT 2OHK - X-ray MuPIT 2OHL - X-ray MuPIT
2OHM - X-ray MuPIT 2OHN - X-ray MuPIT 2OHP - X-ray MuPIT
2OHQ - X-ray MuPIT 2OHR - X-ray MuPIT 2OHS - X-ray MuPIT
2OHT - X-ray MuPIT 2OHU - X-ray MuPIT 2P4J - X-ray MuPIT
2P83 - X-ray MuPIT 2P8H - X-ray MuPIT 2PH6 - X-ray MuPIT
2PH8 - X-ray MuPIT 2Q11 - X-ray MuPIT 2Q15 - X-ray MuPIT
2QK5 - X-ray MuPIT 2QMD - X-ray MuPIT 2QMF - X-ray MuPIT
2QMG - X-ray MuPIT 2QP8 - X-ray MuPIT 2QU2 - X-ray MuPIT
2QU3 - X-ray MuPIT 2QZK - X-ray MuPIT 2QZL - X-ray MuPIT
2VA5 - X-ray MuPIT 2VA6 - X-ray MuPIT 2VA7 - X-ray MuPIT
2VIE - X-ray MuPIT 2VIJ - X-ray MuPIT 2VIY - X-ray MuPIT
2VIZ - X-ray MuPIT 2VJ6 - X-ray MuPIT 2VJ7 - X-ray MuPIT
2VJ9 - X-ray MuPIT 2VKM - X-ray MuPIT 2VNM - X-ray MuPIT
2VNN - X-ray MuPIT 2WEZ - X-ray MuPIT 2WF0 - X-ray MuPIT
2WF1 - X-ray MuPIT 2WF2 - X-ray MuPIT 2WF3 - X-ray MuPIT
2WF4 - X-ray MuPIT 2WJO - X-ray MuPIT 2XFI - X-ray MuPIT
2XFJ - X-ray MuPIT 2XFK - X-ray MuPIT 2ZDZ - X-ray MuPIT
2ZE1 - X-ray MuPIT 2ZHR - X-ray MuPIT 2ZHS - X-ray MuPIT
2ZHT - X-ray MuPIT 2ZHU - X-ray MuPIT 2ZHV - X-ray MuPIT
2ZJH - X-ray MuPIT 2ZJI - X-ray MuPIT 2ZJJ - X-ray MuPIT
2ZJK - X-ray MuPIT 2ZJL - X-ray MuPIT 2ZJM - X-ray MuPIT
2ZJN - X-ray MuPIT 3BRA - X-ray MuPIT 3BUF - X-ray MuPIT
3BUG - X-ray MuPIT 3BUH - X-ray MuPIT 3CIB - X-ray MuPIT
3CIC - X-ray MuPIT 3CID - X-ray MuPIT 3CKP - X-ray MuPIT
3CKR - X-ray MuPIT 3DM6 - X-ray MuPIT 3DUY - X-ray MuPIT
3DV1 - X-ray MuPIT 3DV5 - X-ray MuPIT 3EXO - X-ray MuPIT
3FKT - X-ray MuPIT 3H0B - X-ray MuPIT 3HVG - X-ray MuPIT
3HW1 - X-ray MuPIT 3I25 - X-ray MuPIT 3IGB - X-ray MuPIT
3IN3 - X-ray MuPIT 3IN4 - X-ray MuPIT 3IND - X-ray MuPIT
3INE - X-ray MuPIT 3INF - X-ray MuPIT 3INH - X-ray MuPIT
3IVH - X-ray MuPIT 3IVI - X-ray MuPIT 3IXJ - X-ray MuPIT
3IXK - X-ray MuPIT 3K5C - X-ray MuPIT 3K5D - X-ray MuPIT
3K5F - X-ray MuPIT 3K5G - X-ray MuPIT 3KMX - X-ray MuPIT
3KMY - X-ray MuPIT 3KN0 - X-ray MuPIT 3KYR - X-ray MuPIT
3L38 - X-ray MuPIT 3L3A - X-ray MuPIT 3L58 - X-ray MuPIT
3L59 - X-ray MuPIT 3L5B - X-ray MuPIT 3L5C - X-ray MuPIT
3L5D - X-ray MuPIT 3L5E - X-ray MuPIT 3L5F - X-ray MuPIT
3LHG - X-ray MuPIT 3LNK - X-ray MuPIT 3LPI - X-ray MuPIT
3LPJ - X-ray MuPIT 3LPK - X-ray MuPIT 3MSJ - X-ray MuPIT
3MSK - X-ray MuPIT 3MSL - X-ray MuPIT 3N4L - X-ray MuPIT
3NSH - X-ray MuPIT 3OHF - X-ray MuPIT 3OHH - X-ray MuPIT
3OOZ - X-ray MuPIT 3PI5 - X-ray MuPIT 3QBH - X-ray MuPIT
3QI1 - X-ray MuPIT 3R1G - X-ray MuPIT 3R2F - X-ray MuPIT
3RSV - X-ray MuPIT 3RSX - X-ray MuPIT 3RTH - X-ray MuPIT
3RTM - X-ray MuPIT 3RTN - X-ray MuPIT 3RU1 - X-ray MuPIT
3RVI - X-ray MuPIT 3S2O - X-ray MuPIT 3S7L - X-ray MuPIT
3S7M - X-ray MuPIT 3SKF - X-ray MuPIT 3SKG - X-ray MuPIT
3TPJ - X-ray MuPIT 3TPL - X-ray MuPIT 3TPP - X-ray MuPIT
3TPR - X-ray MuPIT 3U6A - X-ray MuPIT 3UDH - X-ray MuPIT
3UDJ - X-ray MuPIT 3UDK - X-ray MuPIT 3UDM - X-ray MuPIT
3UDN - X-ray MuPIT 3UDP - X-ray MuPIT 3UDQ - X-ray MuPIT
3UDR - X-ray MuPIT 3UDY - X-ray MuPIT 3UFL - X-ray MuPIT
4ACU - X-ray MuPIT 4ACX - X-ray MuPIT 4B1C - X-ray MuPIT
4B1D - X-ray MuPIT 4B1E - X-ray MuPIT 4DH6 - X-ray MuPIT
4DI2 - X-ray MuPIT 4DJU - X-ray MuPIT 4DJV - X-ray MuPIT
4DJW - X-ray MuPIT 4DJX - X-ray MuPIT 4DJY - X-ray MuPIT
4DPF - X-ray MuPIT 4DPI - X-ray MuPIT 4DUS - X-ray MuPIT
4FM7 - X-ray MuPIT 4FM8 - X-ray MuPIT 4FRI - X-ray MuPIT
4FRJ - X-ray MuPIT 4FRK - X-ray MuPIT 4FRS - X-ray MuPIT
4FS4 - X-ray MuPIT 4FSE - X-ray MuPIT 4FSL - X-ray MuPIT
4GID - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P56817
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001540 beta-amyloid binding
GO:0004175 endopeptidase activity
GO:0004190 aspartic-type endopeptidase activity
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0008798 beta-aspartyl-peptidase activity
GO:0016787 hydrolase activity
GO:0019899 enzyme binding

Biological Process:
GO:0006508 proteolysis
GO:0006509 membrane protein ectodomain proteolysis
GO:0030163 protein catabolic process
GO:0044267 cellular protein metabolic process
GO:0050435 beta-amyloid metabolic process
GO:0050804 modulation of synaptic transmission

Cellular Component:
GO:0005768 endosome
GO:0005769 early endosome
GO:0005770 late endosome
GO:0005771 multivesicular body
GO:0005783 endoplasmic reticulum
GO:0005788 endoplasmic reticulum lumen
GO:0005794 Golgi apparatus
GO:0005802 trans-Golgi network
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009986 cell surface
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0030424 axon
GO:0030659 cytoplasmic vesicle membrane
GO:0031410 cytoplasmic vesicle
GO:0045121 membrane raft
GO:0070931 Golgi-associated vesicle lumen


-  Descriptions from all associated GenBank mRNAs
  LF208465 - JP 2014500723-A/15968: Polycomb-Associated Non-Coding RNAs.
MA444042 - JP 2018138019-A/15968: Polycomb-Associated Non-Coding RNAs.
CQ824591 - Sequence 18 from Patent WO2004047872.
CQ824592 - Sequence 19 from Patent WO2004047872.
CQ824593 - Sequence 20 from Patent WO2004047872.
CQ824594 - Sequence 21 from Patent WO2004047872.
CS236154 - Sequence 18 from Patent WO2005116212.
CS236155 - Sequence 19 from Patent WO2005116212.
CS236156 - Sequence 20 from Patent WO2005116212.
CS236157 - Sequence 21 from Patent WO2005116212.
DL076407 - TREATMENT OF NEURODEGENERATIVE DISEASE THROUGH INTRACRANIAL DELIVERY OF siRNA.
DL076408 - TREATMENT OF NEURODEGENERATIVE DISEASE THROUGH INTRACRANIAL DELIVERY OF siRNA.
DL076409 - TREATMENT OF NEURODEGENERATIVE DISEASE THROUGH INTRACRANIAL DELIVERY OF siRNA.
DL076410 - TREATMENT OF NEURODEGENERATIVE DISEASE THROUGH INTRACRANIAL DELIVERY OF siRNA.
HV187322 - JP 2006515864-A/18: Treatment of Neurodegenerative Disease Through Intracranial Delivery of siRNA.
HV187323 - JP 2006515864-A/19: Treatment of Neurodegenerative Disease Through Intracranial Delivery of siRNA.
HV187324 - JP 2006515864-A/20: Treatment of Neurodegenerative Disease Through Intracranial Delivery of siRNA.
HV187325 - JP 2006515864-A/21: Treatment of Neurodegenerative Disease Through Intracranial Delivery of siRNA.
HV308702 - JP 2010500357-A/18: Compositions, devices and methods for treatment of huntington's disease through intracranial delivery of sirna.
HV308703 - JP 2010500357-A/19: Compositions, devices and methods for treatment of huntington's disease through intracranial delivery of sirna.
HV308704 - JP 2010500357-A/20: Compositions, devices and methods for treatment of huntington's disease through intracranial delivery of sirna.
HV308705 - JP 2010500357-A/21: Compositions, devices and methods for treatment of huntington's disease through intracranial delivery of sirna.
AF201468 - Homo sapiens APP beta-secretase mRNA, complete cds.
JA482030 - Sequence 13 from Patent WO2011072091.
JA482031 - Sequence 14 from Patent WO2011072091.
JA482032 - Sequence 15 from Patent WO2011072091.
JA482033 - Sequence 16 from Patent WO2011072091.
JE980322 - Sequence 13 from Patent EP2862929.
JE980323 - Sequence 14 from Patent EP2862929.
JE980324 - Sequence 15 from Patent EP2862929.
JE980325 - Sequence 16 from Patent EP2862929.
AB032975 - Homo sapiens mRNA for KIAA1149 protein, partial cds.
BC065492 - Homo sapiens beta-site APP-cleaving enzyme 1, mRNA (cDNA clone MGC:71162 IMAGE:6538154), complete cds.
AF200193 - Homo sapiens memapsin 2 mRNA, partial cds.
AF190725 - Homo sapiens beta-site APP cleaving enzyme (BACE) mRNA, complete cds.
AF200343 - Homo sapiens chromosome 11 aspartyl protease 2 mRNA, complete cds.
AK075049 - Homo sapiens cDNA FLJ90568 fis, clone OVARC1001570, highly similar to Beta-secretase 1 precursor (EC 3.4.23.46).
BC036084 - Homo sapiens beta-site APP-cleaving enzyme 1, mRNA (cDNA clone MGC:33762 IMAGE:5311572), complete cds.
AB050436 - Homo sapiens BACE mRNA for beta-site APP cleaving enzyme I-476, complete cds.
AB050437 - Homo sapiens BACE mRNA for beta-site APP cleaving enzyme I-457, complete cds.
AB050438 - Homo sapiens BACE mRNA for beta-site APP cleaving enzyme I-432, complete cds.
AF204943 - Homo sapiens transmembrane aspartic proteinase Asp 2 (BACE1) mRNA, complete cds.
AF338816 - Homo sapiens beta-site APP cleaving enzyme type B mRNA, complete cds.
AF338817 - Homo sapiens beta-site APP cleaving enzyme type C mRNA, complete cds.
DQ891509 - Synthetic construct clone IMAGE:100004139; FLH177592.01X; RZPDo839B11126D beta-site APP-cleaving enzyme 1 (BACE1) gene, encodes complete protein.
DQ894700 - Synthetic construct Homo sapiens clone IMAGE:100009160; FLH177588.01L; RZPDo839B11125D beta-site APP-cleaving enzyme 1 (BACE1) gene, encodes complete protein.
AB590539 - Synthetic construct DNA, clone: pFN21AE1947, Homo sapiens BACE1 gene for beta-site APP-cleaving enzyme 1, without stop codon, in Flexi system.
AB089958 - Homo sapiens BACE mRNA for beta-site APP cleaving enzyme isoform I-127, complete cds.
CU688052 - Synthetic construct Homo sapiens gateway clone IMAGE:100022491 5' read BACE1 mRNA.
AB177847 - Homo sapiens mRNA for KIAA1149 splice variant 1.
AK296535 - Homo sapiens cDNA FLJ54693 complete cds, highly similar to Beta-secretase 1 precursor (EC 3.4.23.46).
LF208466 - JP 2014500723-A/15969: Polycomb-Associated Non-Coding RNAs.
MA444043 - JP 2018138019-A/15969: Polycomb-Associated Non-Coding RNAs.
AF161367 - Homo sapiens HSPC104 mRNA, partial cds.
AK296015 - Homo sapiens cDNA FLJ54690 complete cds, highly similar to Beta-secretase 1 precursor (EC 3.4.23.46).
JD267783 - Sequence 248807 from Patent EP1572962.
AF527782 - Homo sapiens beta-site APP-cleaving enzyme (BACE) mRNA, partial cds, alternatively spliced.
LF376504 - JP 2014500723-A/184007: Polycomb-Associated Non-Coding RNAs.
MA612081 - JP 2018138019-A/184007: Polycomb-Associated Non-Coding RNAs.
LF376503 - JP 2014500723-A/184006: Polycomb-Associated Non-Coding RNAs.
MA612080 - JP 2018138019-A/184006: Polycomb-Associated Non-Coding RNAs.
LF376500 - JP 2014500723-A/184003: Polycomb-Associated Non-Coding RNAs.
MA612077 - JP 2018138019-A/184003: Polycomb-Associated Non-Coding RNAs.
LF376487 - JP 2014500723-A/183990: Polycomb-Associated Non-Coding RNAs.
MA612064 - JP 2018138019-A/183990: Polycomb-Associated Non-Coding RNAs.
JD320406 - Sequence 301430 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa05010 - Alzheimer's disease

Reactome (by CSHL, EBI, and GO)

Protein P56817 (Reactome details) participates in the following event(s):

R-HSA-5692934 BACE1 binds GGA1,2,3
R-HSA-5692941 BACE1:GGA1,2,3 translocates from plasma membrane to endosome
R-HSA-5693001 NAT8,8B acetylate BACE1
R-HSA-5692495 BACE1 cleaves APP(18-770) to APP(18-671) and APP(672-770)
R-HSA-977225 Amyloid fiber formation
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: A0M8W7, B0YIU9, BACE, BACE1_HUMAN, KIAA1149, NM_138972, P56817, Q9BYB9, Q9BYC0, Q9BYC1, Q9UJT5, Q9ULS1, uc001pqw.1, uc001pqw.2, uc001pqw.3, uc001pqw.4
UCSC ID: uc001pqw.4
RefSeq Accession: NM_138972
Protein: P56817 (aka BACE1_HUMAN or BAE1_HUMAN)
CCDS: CCDS8383.1, CCDS44739.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.