Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

BACE1 (P56817) - Overview - Molecular Target Synopsis


BACE1, Beta-secretase 1
Enzyme Classification
UniProt P56817

Also Known as BACE1_HUMAN, BACE1, BACE, KIAA1149

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. Monomer. Interacts (via DXXLL motif) with GGA1, GGA2 and GGA3 (via their VHS domain); the interaction highly increases when BACE1 is phosphorylated at Ser-498 (PubMed:14567678, PubMed:15886016). Interacts with RTN3 and RTN4 (PubMed:15286784, PubMed:16965550, PubMed:16979658). Interacts with SNX6 (PubMed:20354142). Interacts with PCSK9 (PubMed:18660751). Interacts with NAT8 and NAT8B (PubMed:19011241). Interacts with BIN1 (PubMed:27179792).

Inspect Structure
See all 3D Structures for BACE1

Isoforms / Transcripts (Protein Coding)

Sub-cellular localization

UniProt: BACE1 is active in the following subcellular-locations: cell membrane, cell surface, cytoplasmic vesicle membrane, early endosome, endoplasmic reticulum, endosome, golgi apparatus, late endosome, lysosome, membrane raft, recycling endosome, trans-golgi network.
GO terms: BACE1 is active in the following subcellular-locations: axon, cell surface, cytoplasmic vesicle membrane, dendrite, early endosome, endoplasmic reticulum lumen, endosome, endosome membrane, Golgi apparatus, Golgi-associated vesicle lumen, hippocampal mossy fiber to CA3 synapse, integral component of membrane, integral component of plasma membrane, late endosome, lysosome, membrane, membrane raft, multivesicular body, neuronal cell body, plasma membrane, recycling endosome, synaptic vesicle, trans-Golgi network.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project BACE1 has gain in 1 cell-lines, loss in 5 cell-lines and no signal in 999 cell-lines. (see details)

Gene Expression

In NCI60, the highest expressing cell lines are: MDA_MB_231, SNB_75, SF_295

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: DMS 454, DMS 53, NCI-H727

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, NHLF, HSMM

(see details)

3D Structures

For BACE1 there are:
378 structures (589 chains) solved
349 are solved in complex with at least one small molecule ligand
13 are solved with an approved drug

BACE1 is solved in complex with the approved drug(s):

TAR/TARTARIC ACID (2QMD_A, 2QMD_B, 2QMF_A, 2QMF_B, 2QMG_A, 2QMG_B, 2QP8_A, 2QP8_B, 3CIB_A, 3CIB_B, 3CIC_A, 3CIC_B, 3CID_A, 3CID_B, 3L59_A, 3L59_B, 3L5B_A, 3L5B_B, 3L5C_A, 3L5C_B, 3L5D_A, 3L5D_B, 3L5E_A, 3L5E_B, 3L5F_A, 3L5F_B).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

BACE1 has been screened with 8932 compounds (14215 bioactivities), 4749 compounds have bioactivities that show binding affinity of <= 500nM (7140 bioactivities). (see details)