Ubiquitin-like modifier-activating enzyme 7 (UBA7)

Ubiquitin-like modifier-activating enzyme 7 (UBA7, also known as UBE1L) is an E1 family enzyme responsible for the activation of ISG15, a ubiquitin-like protein involved primarily in immune and antiviral responses[1][2][3]. UBA7 catalyzes the first step in the ISGylation pathway by transferring ISG15 to its cognate E2 enzyme, UBE2L6, which ultimately leads to ISG15 conjugation of various target proteins, modulating key regulatory pathways, particularly following type I interferon stimulation. UBA7 is considered a candidate tumor suppressor in certain cancers such as non-small cell lung cancer, where its expression is frequently lost and may modulate proliferation-related signaling by downregulating cyclin D1 and EGFR. Structural studies reveal an unusual specificity for ISG15 and UBE2L6, and a distinct mechanism from canonical ubiquitin E1 enzymes[1][2][3]. No clinically approved drugs directly target UBA7, but its role in disease and immunity underscores its emerging significance as a biomedical research target.

Other names

UBA7UBE1Lubiquitin-activating enzyme E1-like proteinubiquitin-activating enzyme 7UBE2UBA1BD8UBE7ubiquitin-activating enzyme E1 homologubiquitin-activating enzyme E1-related proteinubiquitin-activating enzyme-2ubiquitin-like modifier-activating enzyme 7

Covalent activation and transfer of ISG15 to substrate proteins via an E1–E2 enzyme cascade Promotes ISG15–protein conjugation, impacting immune signal transduction and tumorigenesis