4pw6

Structural highlights

Disease

UHRF2_HUMAN Associated with various cancers. DNA copy number loss is found in multiple kinds of malignancies originating from the brain, breast, stomach, kidney, hematopoietic tissue and lung.

Function

UHRF2_HUMAN E3 ubiquitin-protein ligase that is an intermolecular hub protein in the cell cycle network. Through cooperative DNA and histone binding, may contribute to a tighter epigenetic control of gene expression in differentiated cells. Ubiquitinates cyclins, CCND1 and CCNE1, in an apparently phosphorylation-independent manner and induces G1 arrest. Also ubiquitinates PCNP leading to its degradation by the proteasome. E3 SUMO-, but not ubiquitin-, protein ligase for ZNF131.^{[1] [2] [3] [4] [5] [6]}

See Also

• Ubiquitin protein ligase 3D structures

References

1. ↑ Mori T, Li Y, Hata H, Ono K, Kochi H. NIRF, a novel RING finger protein, is involved in cell-cycle regulation. Biochem Biophys Res Commun. 2002 Aug 23;296(3):530-6. PMID:12176013
2. ↑ Li Y, Mori T, Hata H, Homma Y, Kochi H. NIRF induces G1 arrest and associates with Cdk2. Biochem Biophys Res Commun. 2004 Jun 25;319(2):464-8. PMID:15178429 doi:http://dx.doi.org/10.1016/j.bbrc.2004.04.190
3. ↑ Mori T, Li Y, Hata H, Kochi H. NIRF is a ubiquitin ligase that is capable of ubiquitinating PCNP, a PEST-containing nuclear protein. FEBS Lett. 2004 Jan 16;557(1-3):209-14. PMID:14741369
4. ↑ Unoki M, Nishidate T, Nakamura Y. ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain. Oncogene. 2004 Oct 7;23(46):7601-10. PMID:15361834 doi:10.1038/sj.onc.1208053
5. ↑ Mori T, Ikeda DD, Fukushima T, Takenoshita S, Kochi H. NIRF constitutes a nodal point in the cell cycle network and is a candidate tumor suppressor. Cell Cycle. 2011 Oct 1;10(19):3284-99. doi: 10.4161/cc.10.19.17176. Epub 2011 Oct, 1. PMID:21952639 doi:http://dx.doi.org/10.4161/cc.10.19.17176
6. ↑ Oh Y, Chung KC. UHRF2, a ubiquitin E3 ligase, acts as a small ubiquitin-like modifier E3 ligase for zinc finger protein 131. J Biol Chem. 2013 Mar 29;288(13):9102-11. doi: 10.1074/jbc.M112.438234. Epub 2013, Feb 12. PMID:23404503 doi:http://dx.doi.org/10.1074/jbc.M112.438234
7. ↑ Zhou T, Xiong J, Wang M, Yang N, Wong J, Zhu B, Xu RM. Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2. Mol Cell. 2014 May 7. pii: S1097-2765(14)00313-X. doi:, 10.1016/j.molcel.2014.04.003. PMID:24813944 doi:http://dx.doi.org/10.1016/j.molcel.2014.04.003