H
IPR036317

Cullin homology domain superfamily

InterPro entry
Short nameCullin_homology_sf
Overlapping entries
 
Cullin, N-terminal (IPR001373)
Cullin (IPR045093)

Description

Cullins are a family of hydrophobic proteins that act as scaffolds for ubiquitin ligases (E3). Cullins are found throughout eukaryotes. Humans express several cullins (Cul1, 2, 3, 4A, 4B, 5, 7 and 9), each forming part of a multi-subunit ubiquitin complex
[2, 1]
. Cullin-RING ubiquitin ligases (CRLs), such as Cul1 (SCF)
[3]
, play an essential role in targeting proteins for ubiquitin-mediated destruction; as such, they are diverse in terms of composition and function, regulating many different processes from glucose sensing and DNA replication to limb patterning and circadian rhythms. The catalytic core of CRLs consists of a RING protein and a cullin family member. For Cul1, the C-terminal cullin-homology domain binds the RING protein. The RING protein appears to function as a docking site for ubiquitin-conjugating enzymes (E2s). Other proteins contain a cullin-homology domain, such as the APC2 subunit of the anaphase-promoting complex/cyclosome and the p53 cytoplasmic anchor PARC; both APC2 and PARC have ubiquitin ligase activity. The N-terminal region of cullins is more variable, and is used to interact with specific adaptor proteins
[5, 6, 4]
.

This entry represents the cullin-homology domain superfamily. This domain is composed of three subdomains: a 4-helical bundle domain, an α+β domain, and a winged helix-like domain.

References

1.CUL9 mediates the functions of the 3M complex and ubiquitylates survivin to maintain genome integrity. Li Z, Pei XH, Yan J, Yan F, Cappell KM, Whitehurst AW, Xiong Y. Mol. Cell 54, 805-19, (2014). View articlePMID: 24793696

2.The COP9 signalosome: A versatile regulatory hub of Cullin-RING ligases. Schulze-Niemand E, Naumann M. Trends Biochem Sci 48, 82-95, (2023). PMID: 36041947

3.cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family. Kipreos ET, Lander LE, Wing JP, He WW, Hedgecock EM. Cell 85, 829-39, (1996). View articlePMID: 8681378

4.Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases. Goldenberg SJ, Cascio TC, Shumway SD, Garbutt KC, Liu J, Xiong Y, Zheng N. Cell 119, 517-28, (2004). View articlePMID: 15537541

5.Function and regulation of cullin-RING ubiquitin ligases. Petroski MD, Deshaies RJ. Nat. Rev. Mol. Cell Biol. 6, 9-20, (2005). View articlePMID: 15688063

6.Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Zheng N, Schulman BA, Song L, Miller JJ, Jeffrey PD, Wang P, Chu C, Koepp DM, Elledge SJ, Pagano M, Conaway RC, Conaway JW, Harper JW, Pavletich NP. Nature 416, 703-9, (2002). View articlePMID: 11961546

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