Aspartyl/asparaginyl beta-hydroxylase (HAAH) is an enzyme that in humans is encoded by the ASPH gene. ASPH, a ~86KD type II transmembrane protein, is a member of the α-ketoglutarate-dependent dioxygenase family. It catalyzes the β-hydroxylation of aspartyl and asparaginyl residues in epidermal growth factor (EGF)-like repeats of various proteins such as Notch.
|Basic Information of ASPH|
|Protein Name||Aspartyl/asparaginyl beta-hydroxylase|
|Aliases||Aspartate beta-hydroxylase, ASP beta-hydroxylase, Peptide-aspartate beta-dioxygenase, BAH|
|Organism||Homo sapiens (Human)|
ASPH is a highly conserved enzyme, which catalyzes the hydroxylation of aspartyl and asparaginyl residues in epidermal growth factor-like domains of proteins including Notch and homologs. It was originally described as overexpressed in HCC and cholangiocellular carcinoma. Currently, ASPH has been found upregulated in more than 20 tumor types, such as HCC, CCC, pancreatic, colon, breast and non-small cell lung cancer. Overexpression of ASPH was found in HCC with a malignant phenotype characterized by increased cell motility, invasion, and metastasis. ASPH has been reported to mediate cell migration via hydroxylation-dependent activation of Notch signaling networks.
Fig.1 Schematic representation of proposed role of ASPH in key signaling pathways responsible for infiltrative spread of GBM. (Sturla, 2016)
GBM treatment strategies could be made more effective by including small molecule inhibitors of ASPH.
ASPH enzymatic activity is a novel therapeutic target for hepatocellular carcinoma.
ASPH protein and related peptides were highly immunogenic in patients with HCC and produce the type of cellular immune responses required for generation of anti-tumor activity.
Critical involvement of ASPH in PC growth and progression, provide new insight into the molecular mechanisms leading to tumor development and growth and have important therapeutic implications.
ASPH-knockout mice had a foreshortened snout, which corresponds to the facial abnormalities in individuals with Traboulsi syndrome.
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