Angiogenin (ribonuclease 5) (ANG)

Angiogenin is a 14 kDa, 123–amino acid, secreted basic protein encoded by ANG and classified as RNase 5 within the RNase A superfamily; structurally, it has an RNase A fold with a catalytic triad (His13–Lys40–His114), a nuclear localization sequence (Ile29–Leu35), and a cell-binding loop (residues ~60–68 plus Asn109). Its catalytic efficiency toward conventional RNA substrates is 10^4–10^6-fold lower than RNase A due to occlusion of the pyrimidine-binding B1 site by Gln117, yet this RNase activity is essential for angiogenic function. ANG binds actin on endothelial cells, is internalized and translocates to the nucleus where it enhances rRNA transcription; it also cleaves tRNA to generate tiRNAs that repress translation and promote stress granules during stress. ANG drives endothelial migration, invasion, proliferation, and tube formation, contributing to vascularization in normal physiology and tumors; its activity is regulated in vivo by ribonuclease inhibitor RNH1. Given its roles in cancer angiogenesis and links to neurodegenerative disease via functional variants, ANG is actively pursued as a therapeutic target and biomarker.

Other names

Angiogenin (ANG)Ribonuclease 5 (RNase 5)Human angiogenin (hANG)

Anti-angiogenic strategies (investigational): inhibition of ANG catalytic site (His13-Lys40-His114 triad) to block RNase function required for angiogenesis. Blockade of cell-binding loop (residues ~60–68 and Asn109) to prevent receptor engagement/endocytosis. Interference with nuclear localization sequence (Ile29–Leu35) to prevent rRNA transcription upregulation. Enhancement of endogenous inhibitor RNH1 binding to neutralize ANG activity in vivo.