6kg6

Structural highlights

Function

UBE2N_HUMAN The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes (By similarity).^{[1] [2] [3] [4] [5]}

See Also

• 3D structures of ubiquitin conjugating enzyme

References

1. ↑ Hofmann RM, Pickart CM. Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell. 1999 Mar 5;96(5):645-53. PMID:10089880
2. ↑ Bothos J, Summers MK, Venere M, Scolnick DM, Halazonetis TD. The Chfr mitotic checkpoint protein functions with Ubc13-Mms2 to form Lys63-linked polyubiquitin chains. Oncogene. 2003 Oct 16;22(46):7101-7. PMID:14562038 doi:10.1038/sj.onc.1206831
3. ↑ Tcherpakov M, Delaunay A, Toth J, Kadoya T, Petroski MD, Ronai ZA. Regulation of endoplasmic reticulum-associated degradation by RNF5-dependent ubiquitination of JNK-associated membrane protein (JAMP). J Biol Chem. 2009 May 1;284(18):12099-109. doi: 10.1074/jbc.M808222200. Epub 2009, Mar 6. PMID:19269966 doi:10.1074/jbc.M808222200
4. ↑ David Y, Ziv T, Admon A, Navon A. The E2 ubiquitin conjugating enzymes direct polyubiquitination to preferred lysines. J Biol Chem. 2010 Jan 8. PMID:20061386 doi:M109.089003
5. ↑ Pertel T, Hausmann S, Morger D, Zuger S, Guerra J, Lascano J, Reinhard C, Santoni FA, Uchil PD, Chatel L, Bisiaux A, Albert ML, Strambio-De-Castillia C, Mothes W, Pizzato M, Grutter MG, Luban J. TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature. 2011 Apr 21;472(7343):361-5. doi: 10.1038/nature09976. PMID:21512573 doi:10.1038/nature09976
6. ↑ Mu Y, Wang Y, Huang Y, Li D, Han Y, Chang M, Fu J, Xie Y, Ren J, Wang H, Zhang Y, Luo ZQ, Feng Y. Structural insights into the mechanism and inhibition of transglutaminase-induced ubiquitination by the Legionella effector MavC. Nat Commun. 2020 Apr 14;11(1):1774. doi: 10.1038/s41467-020-15645-7. PMID:32286321 doi:http://dx.doi.org/10.1038/s41467-020-15645-7