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Glomulin

Definition:

[Isoform 1]: Regulatory component of cullin-RING-based SCF (SKP1-Cullin-F-box protein) E3 ubiquitin-protein ligase complexes. Inhibits E3 ubiquitin ligase activity by binding to RBX1 (via RING domain) and inhibiting its interaction with the E2 ubiquitin-conjugating enzyme CDC34. Inhibits RBX1-mediated neddylation of CUL1. Required for normal stability and normal cellular levels of key components of SCF ubiquitin ligase complexes, including FBXW7, RBX1, CUL1, CUL2, CUL3, CUL4A, and thereby contributes to the regulation of CCNE1 and MYC levels (By similarity). Essential for normal development of the vasculature. Contributes to the regulation of RPS6KB1 phosphorylation.

References:

[1]. S Grisendi, et al. Ligand-regulated binding of FAP68 to the hepatocyte growth factor receptor. J Biol Chem. 2001 Dec 7;276(49):46632-8. [Content Brief]

[2]. Pascal Brouillard, et al. Mutations in a novel factor, glomulin, are responsible for glomuvenous malformations ("glomangiomas"). Am J Hum Genet. 2002 Apr;70(4):866-74. [Content Brief]

[3]. David M Duda, et al. Structure of a glomulin-RBX1-CUL1 complex: inhibition of a RING E3 ligase through masking of its E2-binding surface. Mol Cell. 2012 Aug 10;47(3):371-82. [Content Brief]

[4]. Adriana E Tron, et al. The glomuvenous malformation protein Glomulin binds Rbx1 and regulates cullin RING ligase-mediated turnover of Fbw7. Mol Cell. 2012 Apr 13;46(1):67-78. [Content Brief]

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