3wwq

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] [FAP20_HUMAN] Component of the Fanconi anemia (FA) complex required to recruit the FA complex to DNA interstrand cross-links (ICLs) and promote ICLs repair. Following DNA damage recognizes and binds 'Lys-63'-linked ubiquitin generated by RNF8 at ICLs and recruits other components of the FA complex. Promotes translesion synthesis via interaction with REV1.^{[2] [3] [4] [5]}

See Also

• 3D structures of ubiquitin

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. ↑ Kim H, Yang K, Dejsuphong D, D'Andrea AD. Regulation of Rev1 by the Fanconi anemia core complex. Nat Struct Mol Biol. 2012 Jan 22;19(2):164-70. doi: 10.1038/nsmb.2222. PMID:22266823 doi:10.1038/nsmb.2222
3. ↑ Ali AM, Pradhan A, Singh TR, Du C, Li J, Wahengbam K, Grassman E, Auerbach AD, Pang Q, Meetei AR. FAAP20: a novel ubiquitin-binding FA nuclear core-complex protein required for functional integrity of the FA-BRCA DNA repair pathway. Blood. 2012 Apr 5;119(14):3285-94. doi: 10.1182/blood-2011-10-385963. Epub 2012, Feb 17. PMID:22343915 doi:http://dx.doi.org/10.1182/blood-2011-10-385963
4. ↑ Leung JW, Wang Y, Fong KW, Huen MS, Li L, Chen J. Fanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repair. Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4491-6. doi:, 10.1073/pnas.1118720109. Epub 2012 Mar 6. PMID:22396592 doi:http://dx.doi.org/10.1073/pnas.1118720109
5. ↑ Yan Z, Guo R, Paramasivam M, Shen W, Ling C, Fox D 3rd, Wang Y, Oostra AB, Kuehl J, Lee DY, Takata M, Hoatlin ME, Schindler D, Joenje H, de Winter JP, Li L, Seidman MM, Wang W. A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubiquitination to the Fanconi anemia DNA repair network. Mol Cell. 2012 Jul 13;47(1):61-75. doi: 10.1016/j.molcel.2012.05.026. Epub 2012, Jun 14. PMID:22705371 doi:10.1016/j.molcel.2012.05.026
6. ↑ Toma A, Takahashi TS, Sato Y, Yamagata A, Goto-Ito S, Nakada S, Fukuto A, Horikoshi Y, Tashiro S, Fukai S. Structural basis for ubiquitin recognition by ubiquitin-binding zinc finger of FAAP20. PLoS One. 2015 Mar 23;10(3):e0120887. doi: 10.1371/journal.pone.0120887., eCollection 2015. PMID:25799058 doi:http://dx.doi.org/10.1371/journal.pone.0120887