Cullin

{{Short description|Hydrophobic scaffold protein}} {{distinguish|text=Cuillin, a mountain range in Scotland, or with Culin}} {{Infobox protein family | Symbol = Cullin | Name = Cullin | image = PDB 1ldk EBI.jpg | width = | caption = structure of the cul1-rbx1-skp1-f boxskp2 scf ubiquitin ligase complex | Pfam = PF00888 | Pfam_clan = | InterPro = IPR001373 | SMART = | PROSITE = PDOC00967 | MEROPS = | SCOP = 1ldj | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }} {{Infobox protein family | Symbol = Cullin_Nedd8 | Name = Cullin protein neddylation domain | image = PDB 1ldk EBI.jpg | width = | caption = structure of the cul1-rbx1-skp1-f boxskp2 scf ubiquitin ligase complex | Pfam = PF10557 | Pfam_clan = | InterPro = IPR019559 | SMART = | PROSITE = | MEROPS = | SCOP = | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }} '''Cullins''' are a family of hydrophobic scaffold proteins which provide support for ubiquitin ligases (E3). All eukaryotes appear to have cullins. They combine with RING proteins to form ''Cullin-RING ubiquitin ligases'' (CRLs) that are highly diverse and play a role in myriad cellular processes, most notably protein degradation by ubiquitination.<ref>{{Cite journal|doi=10.1186/1747-1028-3-7|title=Cullin-RING ubiquitin ligases: Global regulation and activation cycles|year=2008|last1=Bosu|first1=Dimple R.|last2=Kipreos|first2=Edward T.|journal=Cell Division|volume=3|page=7|pmid=18282298|pmc=2266742 |doi-access=free }}</ref><ref>{{Cite book|title=Molecular biology of the cell|last=Bruce|first=Alberts|isbn=9780815344322|edition= Sixth |location=New York, NY|oclc=887605755|date = 2014-11-18}}</ref>

The human genome contains eight cullin genes * CUL1, part of SCF complex * CUL2, part of ECS complex (Elongin C - CUL2 - SOCS-box) * CUL3, part of CUL3-BTB complex * CUL4A * CUL4B * CUL5 * CUL7 * CUL9, also known as PARC

There is also a more distant member called ANAPC2 (or APC2), part of the Anaphase-promoting complex.

CUL1, 2, 3, 4A, 4B, 5 and 7 each form part of a multi-subunit ubiquitin complex.

==Cullin-RING ubiquitin ligases== Cullin-RING ubiquitin ligases (CRLs), such as Cul1 (SCF) 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.<ref name="pmid8681378">{{cite journal | vauthors = Kipreos ET, Lander LE, Wing JP, He WW, Hedgecock EM | title = cul-1 is required for cell cycle exit in C. elegans and identifies a novel gene family | journal = Cell | volume = 85 | issue = 6 | pages = 829–39 |date=June 1996 | pmid = 8681378 | doi = 10.1016/S0092-8674(00)81267-2| s2cid = 15805562 | doi-access = free }}</ref> 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 CUL9, also known as p53 cytoplasmic anchor PARC, and the ANAPC2 subunit of the anaphase-promoting complex/cyclosome; both CUL9 and ANAPC2 have ubiquitin ligase activity. The N-terminal region of cullins is more variable, and is used to interact with specific adaptor proteins.<ref name="pmid15688063">{{cite journal | vauthors = Petroski MD, Deshaies RJ | title = Function and regulation of cullin-RING ubiquitin ligases | journal = Nat. Rev. Mol. Cell Biol. | volume = 6 | issue = 1 | pages = 9–20 |date=January 2005 | pmid = 15688063 | doi = 10.1038/nrm1547 | s2cid = 24159190 | url = https://authors.library.caltech.edu/55905/2/nrm1547-S1.pdf}}</ref><ref name="pmid11961546">{{cite journal | vauthors = 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 | title = Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex | journal = Nature | volume = 416 | issue = 6882 | pages = 703–9 |date=April 2002 | pmid = 11961546 | doi = 10.1038/416703a | bibcode = 2002Natur.416..703Z | s2cid = 4423882 }}</ref><ref name="pmid15537541">{{cite journal | vauthors = Goldenberg SJ, Cascio TC, Shumway SD, Garbutt KC, Liu J, Xiong Y, Zheng N | title = Structure of the Cand1-Cul1-Roc1 complex reveals regulatory mechanisms for the assembly of the multisubunit cullin-dependent ubiquitin ligases | journal = Cell | volume = 119 | issue = 4 | pages = 517–28 |date=November 2004 | pmid = 15537541 | doi = 10.1016/j.cell.2004.10.019 | s2cid = 1606360 | doi-access = free }}</ref>

==Modification by NEDD8== With the exception of ANAPC2, each member of the cullin family is modified by Nedd8 and several cullins function in Ubiquitin-dependent proteolysis, a process in which the 26S proteasome recognises and subsequently degrades a target protein tagged with K48-linked poly-ubiquitin chains. Nedd8/Rub1 is a small ubiquitin-like protein, which was originally found to be conjugated to Cdc53, a cullin component of the SCF (Skp1-Cdc53/CUL1-F-box protein) E3 Ub ligase complex in ''Saccharomyces cerevisiae'' (Baker's yeast), and Nedd8 modification has now emerged as a regulatory pathway of fundamental importance for cell cycle control and for embryogenesis in metazoans. The only identified Nedd8 substrates are cullins. Neddylation results in covalent conjugation of a Nedd8 moiety onto a conserved cullin lysine residue.<ref name="pmid15021886">{{cite journal | vauthors = Pan ZQ, Kentsis A, Dias DC, Yamoah K, Wu K | title = Nedd8 on cullin: building an expressway to protein destruction | journal = Oncogene | volume = 23 | issue = 11 | pages = 1985–97 |date=March 2004 | pmid = 15021886 | doi = 10.1038/sj.onc.1207414 | doi-access = free }}</ref>

==References== {{reflist}}

== External links == * [https://web.archive.org/web/20100616004255/http://pfam.sanger.ac.uk/family?id=Cullin Cullin family] - Sanger Institute website. * {{MeshName|Cullin+Proteins}}

Category:Protein families