Tchem BACE1 Beta-secretase 1

Protein Classes

PANTHER Classes

Protein / Hydrolase / Protease / Aspartic Protease / Beta-secretase 1

DTO Classes

Protein / Enzyme / Protease / Aspartic Protease / Beta-secretase 1

Protein Summary

Description

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. Cleaves APP with much more catalytic efficiency than for the wild-type. 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]

Uniprot Accession IDs

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

Gene Name

• BACE1

Ensembl ID

• ENST00000313005
• ENSP00000318585
• ENSG00000186318
• ENST00000392937
• ENSP00000475405
• ENST00000428381
• ENSP00000402228
• ENST00000445823
• ENSP00000403685
• ENST00000510630
• ENSP00000422461
• ENST00000513780
• ENSP00000424536

Symbol

• BACE
• KIAA1149
• ASP2
• BACE
• HSPC104

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
cellular component	0.97
drug	0.93
virus perturbation	0.88
microRNA	0.83
transcription factor perturbation	0.8

Related Tools

Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2554.55   (req: < 5)

Gene RIFs: 310   (req: <= 3)

Antibodies: 845   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2554.55   (req: >= 5)

Gene RIFs: 310   (req: > 3)

Antibodies: 845   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 20

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 4952

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Active Ligands (4952)

Explore Active Ligands

1 – 10 of 4952

CHEMBL297453

BACE1Tchem Enzyme

IC50 : 6.12

CHEMBL1241578

BACE1Tchem Enzyme

IC50 : 6.76

CHEMBL1233882

BACE1Tchem Enzyme

IC50 : 6.66

CHEMBL3354688

BACE1Tchem Enzyme

IC50 : 8.7

CHEMBL1097342

BACE1Tchem Enzyme

Ki : 9.1

CHEMBL509210

BACE1Tchem Enzyme

Ki : 8.52

CHEMBL403727

BACE1Tchem Enzyme

IC50 : 8.52

CHEMBL270359

BACE1Tchem Enzyme

IC50 : 8.3

CHEMBL507651

BACE1Tchem Enzyme

IC50 : 8.3

CHEMBL2181010

BACE1Tchem Enzyme

IC50 : 7

GWAS Traits (3)

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1 – 3 of 3

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean platelet volume	EFO_0004584	2	1	2		80.6
apolipoprotein A 1 measurement	EFO_0004614	1	1	1		60.6
high density lipoprotein cholesterol measurement	EFO_0004612	1	1	1		54.2

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
mean platelet volume	EFO_0004584	2		80.6
apolipoprotein A 1 measurement	EFO_0004614	1		60.6
high density lipoprotein cholesterol measurement	EFO_0004612	1		54.2

Reset Zoom  Beta Count   Odds Ratio

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	beta-secretase 1	VGNC:10433	451573
Macaque	beta-secretase 1		697694
Mouse	beta-site APP cleaving enzyme 1	MGI:1346542	23821
Rat	beta-secretase 1	RGD:2191	29392
Dog	beta-secretase 1	VGNC:38358	489390

Species	Name	OMA	EggNOG	Inparanoid
Chimp	beta-secretase 1
Macaque	beta-secretase 1
Mouse	beta-site APP cleaving enzyme 1
Rat	beta-secretase 1
Dog	beta-secretase 1

Protein Structure (373 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P56817-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 373

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (32)

Reactome (2)

KEGG (1)

PathwayCommons (2)

WikiPathways (27)

Amyloid fiber formation (R-HSA-977225)

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Find Similar Targets

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Amyloid fiber formation	79 targets	R-HSA-977225
Reactome	Metabolism of proteins	2050 targets	R-HSA-392499

Name	Explore in Pharos	Explore in Source
Amyloid fiber formation	79 targets	R-HSA-977225
Metabolism of proteins	2050 targets	R-HSA-392499

Gene Ontology Terms (43)

Functions (6)

Components (23)

Processes (14)

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10

1 – 6 of 6

GO Term	Evidence	Assigned by
aspartic-type endopeptidase activity	Inferred from Direct Assay (IDA)	UniProtKB
endopeptidase activity	Inferred from Direct Assay (IDA)	UniProtKB
peptidase activity	Inferred from Direct Assay (IDA)	CACAO
amyloid-beta binding	Inferred from Physical Interaction (IPI)	Alzheimers_University_of_Toronto
enzyme binding	Inferred from Physical Interaction (IPI)	UniProtKB
beta-aspartyl-peptidase activity	Traceable Author Statement (TAS)	Reactome

Protein-Protein Interactions (194)

Explore Interacting Targets

1 – 10 of 194

• See Interactions on String-DB

SCGB1D4

Tdark

Novelty: 0.15597658

p_int: 0.996425702

p_ni: 0.001137923

p_wrong: 0.002436375

Score: 0.369

Data Source: BioPlex,STRINGDB

SCGB2A1

Tbio

Novelty: 0.01902973

p_int: 0.770605629

p_ni: 0.000096222

p_wrong: 0.229298149

Data Source: BioPlex

APP

Tchem

Novelty: 0.00008964

Score: 0.997

Data Source: Reactome,STRINGDB

GGA1

Tbio

Novelty: 0.00866392

Score: 0.985

Data Source: Reactome,STRINGDB

GGA3

Tbio

Novelty: 0.01898553

Score: 0.983

Data Source: Reactome,STRINGDB

FURIN

Tchem

Family: Enzyme

Novelty: 0.00055079

Score: 0.972

Data Source: STRINGDB

PSEN1

Tchem

Family: Enzyme

Novelty: 0.00024189

Score: 0.958

Data Source: STRINGDB

GGA2

Tbio

Novelty: 0.01750948

Score: 0.958

Data Source: Reactome,STRINGDB

LRP1

Tbio

Novelty: 0.00200788

Score: 0.928

Data Source: STRINGDB

NCSTN

Tbio

Novelty: 0.00453935

Score: 0.926

Data Source: STRINGDB

Publication Statistics

PubMed Score  2554.55

PubMed score by year

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PubTator Score  1207.61

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

Show Full Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Acetylation
Alternative splicing
Aspartyl protease
Cell membrane
Complete proteome
Cytoplasmic vesicle
Direct protein sequencing
Disulfide bond
Endoplasmic reticulum

GWAS Trait Find Similar Targets

apolipoprotein A 1 measurement
high density lipoprotein cholesterol measurement
mean platelet volume

MGI Phenotype Find Similar Targets

behavior/neurological phenotype
cellular phenotype
growth/size/body region phenotype
integument phenotype
mortality/aging
muscle phenotype
nervous system phenotype