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Aspartate β-hydroxylase
- Molecular classification
- Enzyme, α-ketoglutarate-dependent dioxygenase, Type II transmembrane protein
01
Overview
Aspartate β-hydroxylase (ASPH) is an enzyme that catalyzes the post-translational hydroxylation of specific aspartic acid and asparagine residues within epidermal growth factor-like (EGF-like) domains of various substrate proteins, including Notch receptors and ligands. This modification enhances protein-protein interactions, particularly stabilizing Notch receptor-ligand complexes and facilitating downstream signaling events. ASPH plays roles in various biological processes, and its overexpression is associated with poor prognosis in multiple malignancies, making it a therapeutic target.
- Other names
- Aspartyl/asparaginyl beta-hydroxylaseHAAH
02
Mechanism of action
Small molecule inhibitors block enzymatic activity; Monoclonal antibodies against extracellular epitopes
03
Biological functions
Post-translational modificationHydroxylationRegulation of Notch signalingCalcium homeostasisOxygen sensingCellular growthCell motilityCell adhesionCell migrationCell invasionAngiogenesisImmunosuppression
04
Disease associations
CancerHepatocellular carcinomaPancreatic adenocarcinomaColorectal cancerProstate cancerLung cancerAcute myeloid leukemiaTraboulsi syndrome
05
Safety considerations
Targeting ASPH may have developmental effects due to its role in fetal development.
06
Biomarkers
ASPH overexpression as prognostic marker in multiple cancers
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