Cullin-2

Definition:

Core component of multiple cullin-RING-based ECS (ElonginB/C-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of target proteins. CUL2 may serve as a rigid scaffold in the complex and may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the ECS complex depends on the substrate recognition component. ECS(VHL) mediates the ubiquitination of hypoxia-inducible factor (HIF). A number of ECS complexes (containing either KLHDC2, KLHDC3, KLHDC10, APPBP2, FEM1A, FEM1B or FEM1C as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. ECS complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins. ECS(LRR1) ubiquitinates MCM7 and promotes CMG replisome disassembly by VCP and chromatin extraction during S-phase (By similarity).

References:

[1]. Hsiu-Chuan Lin, et al. C-Terminal End-Directed Protein Elimination by CRL2 Ubiquitin Ligases. Mol Cell. 2018 May 17;70(4):602-613.e3. [Content Brief]

[2]. Kyoeng-Woo Min, et al. TIP120A associates with cullins and modulates ubiquitin ligase activity. J Biol Chem. 2003 May 2;278(18):15905-10. [Content Brief]

[3]. Itay Koren, et al. The Eukaryotic Proteome Is Shaped by E3 Ubiquitin Ligases Targeting C-Terminal Degrons. Cell. 2018 Jun 14;173(7):1622-1635.e14. [Content Brief]

[4]. Daniel C Scott, et al. Two Distinct Types of E3 Ligases Work in Unison to Regulate Substrate Ubiquitylation. Cell. 2016 Aug 25;166(5):1198-1214.e24. [Content Brief]

[5]. Ian R Kelsall, et al. TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes. EMBO J. 2013 Oct 30;32(21):2848-60. [Content Brief]

[6]. Hsiu-Chuan Lin, et al. SELENOPROTEINS. CRL2 aids elimination of truncated selenoproteins produced by failed UGA/Sec decoding. Science. 2015 Jul 3;349(6243):91-5. [Content Brief]

[7]. T Kamura, et al. Activation of HIF1alpha ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex. Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10430-5. [Content Brief]

[8]. T Kamura, et al. Muf1, a novel Elongin BC-interacting leucine-rich repeat protein that can assemble with Cul5 and Rbx1 to reconstitute a ubiquitin ligase. J Biol Chem. 2001 Aug 10;276(32):29748-53. [Content Brief]

[9]. A Pause, et al. The von Hippel-Lindau tumor-suppressor gene product forms a stable complex with human CUL-2, a member of the Cdc53 family of proteins. Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2156-61. [Content Brief]

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