Cullin structure of the cul1-rbx1-skp1-f boxskp2 scf ubiquitin ligase complex Identifiers Symbol Cullin Pfam PF00888 InterPro IPR001373 PROSITE PDOC00967 SCOP 1ldj Available protein structures: Pfam structures PDB RCSB PDB; PDBe PDBsum structure summary Cullin protein neddylation domain structure of the cul1-rbx1-skp1-f boxskp2 scf ubiquitin ligase complex Identifiers Symbol Cullin_Nedd8 Pfam PF10557 InterPro IPR019559 Available protein structures: Pfam structures PDB RCSB PDB; PDBe PDBsum structure summary
Cullins are a family of hydrophobic proteins providing a scaffold 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 a myriad of cellular processes.
Human genome contains seven cullin genes:
- CUL1, part of SCF complex
- CUL2, part of ECS complex (Elongin C - CUL2 - SOCS-box)
- CUL3, part of CUL3-BTB complex
- a more distant member called ANAPC2, part of Anaphase-promoting complex
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. 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.
With the exception of APC2, 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.
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Cell cycle proteins Cyclin CDK CDK inhibitor P53 p63 p73 family Phases and
checkpointsOther cellular phases
B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°) Enzymes: CO CS and CN ligases (EC 6.1-6.3) 6.1: Carbon-OxygenAminoacyl tRNA synthetase (Tyrosine, Tryptophan, Threonine, Leucine, Isoleucine, Lysine, Alanine, Valine, Methionine, Serine, Aspartate, D-alanine-poly(phosphoribitol) ligase, Glycine, Proline, Cysteine, Glutamate, Glutamine, Arginine, Phenylalanine, Histidine, Asparagine, Aspartate, Glutamate, Lysine) 6.2: Carbon-Sulfur 6.3: Carbon-NitrogenGlutamine synthetase - Ubiquitin ligase (Cullin, Von Hippel-Lindau tumor suppressor, UBE3A, Mdm2, Anaphase-promoting complex, UBR1) - Glutathione synthetase - CTP synthase - Adenylosuccinate synthase - Argininosuccinate synthetase - Holocarboxylase synthetase - GMP synthase - Asparagine synthetase - Carbamoyl phosphate synthetase (I, II) - Gamma-glutamylcysteine synthetase B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 126.96.36.199, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6 Chaperones/
Protein targeting UbiquitinBIRC6 • UFC1 Other see also posttranslational modification disorders
B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)
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