Cullin-3 gene is mapped on chromosome 2q36.2 containing 18 exons which has spliced transcript variants encoding multiple isoforms that plays an important role in polyubiquitination and subsequent degradation of particular protein substrates as a core element and gallows protein of an E3ubiquitin ligase complex. It functions in late endosomes maturation and form cullin ring based containing homodimeric SPOPL that has lesser ubiquitin ligase activity. It also involved ininterferon response and anterograde Golgi to endosomes transfer thus, arbitrates ubiquitination to degradation and Lys-33 linked ubiquitination.
Cullin-3 overexpression resulted in cell-autonomous stabilization that highlights the tissue specific regulation during development. It also characterized to regulate the development of several structures like it inhibitssensory organ during adult development and modulates Notch pathway activity. Moreover, cullin-3 confirmed and extends functions in Hedgehog signaling thereby encroaches on the action of various signaling pathways and development events through obliteration or modification of specific proteins.
Cullin-3 gene mutations implicated in type 2E pseudohypoaldosteronism, an autosomal dominant disorder typified by severe hypertension,hyperkalemia, hyperchloremia, correction of physiologic abnormalities by thiazide diuretics and hyperchloremic metabolicacidosis.
Gene name: CUL3
Protein name: Cullin 3