Ubiquitin ligase

Ubiquitin—protein ligase
E3 ubiquitin ligase Cbl (blue) in complex with E2 (cyan) and substrate peptide (green). PDB entry 4a4c[1]
Identifiers
EC no.2.3.2.27
CAS no.74812-49-0
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
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PMCarticles
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NCBIproteins
Ubiquitin ligase
Identifiers
SymbolUbiquitin ligase
OPM superfamily471
OPM protein4v6p
Membranome240

A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 to the protein substrate. In simple and more general terms, the ligase enables movement of ubiquitin from a ubiquitin carrier to another protein (the substrate) by some mechanism. The ubiquitin, once it reaches its destination, ends up being attached by an isopeptide bond to a lysine residue, which is part of the target protein.[2] E3 ligases interact with both the target protein and the E2 enzyme, and so impart substrate specificity to the E2. Commonly, E3s polyubiquitinate their substrate with Lys48-linked chains of ubiquitin, targeting the substrate for destruction by the proteasome. However, many other types of linkages are possible and alter a protein's activity, interactions, or localization. Ubiquitination by E3 ligases regulates diverse areas such as cell trafficking, DNA repair, and signaling and is of profound importance in cell biology. E3 ligases are also key players in cell cycle control, mediating the degradation of cyclins, as well as cyclin dependent kinase inhibitor proteins.[3] The human genome encodes over 600 putative E3 ligases, allowing for tremendous diversity in substrates.[4]

  1. ^ Dou H, Buetow L, Hock A, Sibbet GJ, Vousden KH, Huang DT (January 2012). "Structural basis for autoinhibition and phosphorylation-dependent activation of c-Cbl". Nature Structural & Molecular Biology. 19 (2): 184–92. doi:10.1038/nsmb.2231. PMC 3880865. PMID 22266821.
  2. ^ Hershko A, Ciechanover A (1998). "The ubiquitin system". Annual Review of Biochemistry. 67: 425–79. doi:10.1146/annurev.biochem.67.1.425. PMID 9759494.
  3. ^ Teixeira LK, Reed SI (2013). "Ubiquitin ligases and cell cycle control". Annual Review of Biochemistry. 82: 387–414. doi:10.1146/annurev-biochem-060410-105307. PMID 23495935.
  4. ^ Li W, Bengtson MH, Ulbrich A, Matsuda A, Reddy VA, Orth A, Chanda SK, Batalov S, Joazeiro CA (January 2008). "Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signaling". PLOS ONE. 3 (1): e1487. Bibcode:2008PLoSO...3.1487L. doi:10.1371/journal.pone.0001487. PMC 2198940. PMID 18213395.