7un3

Structural highlights

Function

RL40_HUMAN Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.^{[1] [2]} Ribosomal protein L40 is a component of the 60S subunit of the ribosome.^{[3] [4]} UBE2O_HUMAN E2/E3 hybrid ubiquitin-protein ligase that displays both E2 and E3 ligase activities and mediates monoubiquitination of target proteins (PubMed:23455153, PubMed:24703950). Negatively regulates TRAF6-mediated NF-kappa-B activation independently of its E2 activity (PubMed:23381138). Acts as a positive regulator of BMP7 signaling by mediating monoubiquitination of SMAD6, thereby regulating adipogenesis (PubMed:23455153). Mediates monoubiquitination at different sites of the nuclear localization signal (NLS) of BAP1, leading to cytoplasmic retention of BAP1. Also able to monoubiquitinate the NLS of other chromatin-associated proteins, such as INO80 and CXXC1, affecting their subcellular location (PubMed:24703950). Acts as a regulator of retrograde transport by assisting the TRIM27:MAGEL2 E3 ubiquitin ligase complex to mediate 'Lys-63'-linked ubiquitination of WASHC1, leading to promote endosomal F-actin assembly (PubMed:23452853).^{[5] [6] [7] [8]} RL8_HUMAN

References

1. ↑ Huang F, Kirkpatrick D, Jiang X, Gygi S, Sorkin A. Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell. 2006 Mar 17;21(6):737-48. PMID:16543144 doi:S1097-2765(06)00120-1
2. ↑ Komander D. The emerging complexity of protein ubiquitination. Biochem Soc Trans. 2009 Oct;37(Pt 5):937-53. doi: 10.1042/BST0370937. PMID:19754430 doi:10.1042/BST0370937
3. ↑ Huang F, Kirkpatrick D, Jiang X, Gygi S, Sorkin A. Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell. 2006 Mar 17;21(6):737-48. PMID:16543144 doi:S1097-2765(06)00120-1
4. ↑ Komander D. The emerging complexity of protein ubiquitination. Biochem Soc Trans. 2009 Oct;37(Pt 5):937-53. doi: 10.1042/BST0370937. PMID:19754430 doi:10.1042/BST0370937
5. ↑ Zhang X, Zhang J, Zhang L, van Dam H, ten Dijke P. UBE2O negatively regulates TRAF6-mediated NF-kappaB activation by inhibiting TRAF6 polyubiquitination. Cell Res. 2013 Mar;23(3):366-77. doi: 10.1038/cr.2013.21. Epub 2013 Feb 5. PMID:23381138 doi:http://dx.doi.org/10.1038/cr.2013.21
6. ↑ Hao YH, Doyle JM, Ramanathan S, Gomez TS, Jia D, Xu M, Chen ZJ, Billadeau DD, Rosen MK, Potts PR. Regulation of WASH-dependent actin polymerization and protein trafficking by ubiquitination. Cell. 2013 Feb 28;152(5):1051-64. doi: 10.1016/j.cell.2013.01.051. PMID:23452853 doi:http://dx.doi.org/10.1016/j.cell.2013.01.051
7. ↑ Zhang X, Zhang J, Bauer A, Zhang L, Selinger DW, Lu CX, Ten Dijke P. Fine-tuning BMP7 signalling in adipogenesis by UBE2O/E2-230K-mediated monoubiquitination of SMAD6. EMBO J. 2013 Apr 3;32(7):996-1007. doi: 10.1038/emboj.2013.38. Epub 2013 Mar 1. PMID:23455153 doi:http://dx.doi.org/10.1038/emboj.2013.38
8. ↑ Mashtalir N, Daou S, Barbour H, Sen NN, Gagnon J, Hammond-Martel I, Dar HH, Therrien M, Affar el B. Autodeubiquitination protects the tumor suppressor BAP1 from cytoplasmic sequestration mediated by the atypical ubiquitin ligase UBE2O. Mol Cell. 2014 May 8;54(3):392-406. doi: 10.1016/j.molcel.2014.03.002. Epub 2014 , Apr 3. PMID:24703950 doi:http://dx.doi.org/10.1016/j.molcel.2014.03.002