6n5m

Structural highlights

Function

[UBC_MOUSE] 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] [TNIP1_MOUSE] Inhibits NF-kappa-B activation and TNF-induced NF-kappa-B-dependent gene expression by regulating A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG. Involved in regulation of EGF-induced ERK1/ERK2 signaling pathway; blocks MAPK3/MAPK1 nuclear translocation and MAPK1-dependent transcription. Increases cell surface CD4(T4) antigen expression. Involved in the anti-inflammatory response of macrophages and positively regulates TLR-induced activation of CEBPB. Involved in the prevention of autoimmunity; this function implicates binding to polyubiquitin. Involved in leukocyte integrin activation during inflammation; this function is mediated by association with SELPLG and dependent on phosphorylation by SRC-family kinases.^{[2] [3] [4]}

References

1. ↑ 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
2. ↑ Heyninck K, Kreike MM, Beyaert R. Structure-function analysis of the A20-binding inhibitor of NF-kappa B activation, ABIN-1. FEBS Lett. 2003 Feb 11;536(1-3):135-40. doi: 10.1016/s0014-5793(03)00041-3. PMID:12586352 doi:http://dx.doi.org/10.1016/s0014-5793(03)00041-3
3. ↑ Nanda SK, Venigalla RK, Ordureau A, Patterson-Kane JC, Powell DW, Toth R, Arthur JS, Cohen P. Polyubiquitin binding to ABIN1 is required to prevent autoimmunity. J Exp Med. 2011 Jun 6;208(6):1215-28. doi: 10.1084/jem.20102177. Epub 2011 May, 23. PMID:21606507 doi:10.1084/jem.20102177
4. ↑ Zhou J, Wu R, High AA, Slaughter CA, Finkelstein D, Rehg JE, Redecke V, Hacker H. A20-binding inhibitor of NF-kappaB (ABIN1) controls Toll-like receptor-mediated CCAAT/enhancer-binding protein beta activation and protects from inflammatory disease. Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):E998-1006. doi:, 10.1073/pnas.1106232108. Epub 2011 Oct 19. PMID:22011580 doi:http://dx.doi.org/10.1073/pnas.1106232108
5. ↑ Herhaus L, van den Bedem H, Tang S, Maslennikov I, Wakatsuki S, Dikic I, Rahighi S. Molecular Recognition of M1-Linked Ubiquitin Chains by Native and Phosphorylated UBAN Domains. J Mol Biol. 2019 Jun 24. pii: S0022-2836(19)30376-6. doi:, 10.1016/j.jmb.2019.06.012. PMID:31247202 doi:http://dx.doi.org/10.1016/j.jmb.2019.06.012