| Structural highlights
Function
[DTX3L_HUMAN] Ubiquitin ligase that mediates monoubiquitination of 'Lys-91' of histone H4 (H4K91ub1), in response to DNA damage. Protects cells exposed to DNA-damaging agents. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 'Lys-20' methylation (H4K20me). Involved in the recruitment of 53BP1/TP53BP1 to sites of DNA damage by mediating H4K91ub1 formation. In concert with PARP9, plays a role in PARP1-dependent DNA damage repair. PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites.[1] [2] [3]
Publication Abstract from PubMed
Human Deltex 3-like (DTX3L) is a member of the Deltex family of proteins. Initially identified as a B-lymphoma and BAL-associated protein, DTX3L is an E3 ligase that regulates subcellular localization of its partner protein, BAL, by a dynamic nucleocytoplasmic trafficking mechanism. Unlike other members of the Deltex family of proteins, DTX3L lacks the highly basic N-terminal motif and the central proline-rich motif present in other Deltex proteins, and instead contains other unique N-terminal domains. The C-terminal domains are, however, homologous with other members of the Deltex family of proteins; these include a RING domain and a previously unidentified C-terminal domain. In this study, we report the high-resolution crystal structure of this previously uncharacterized C-terminal domain of human DTX3L, which we term the Deltex C-terminal domain.
Fold of the conserved DTC domain in Deltex proteins.,Obiero J, Walker JR, Dhe-Paganon S Proteins. 2012 May;80(5):1495-9. doi: 10.1002/prot.24054. Epub 2012 Mar 13. PMID:22411408[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Takeyama K, Aguiar RC, Gu L, He C, Freeman GJ, Kutok JL, Aster JC, Shipp MA. The BAL-binding protein BBAP and related Deltex family members exhibit ubiquitin-protein isopeptide ligase activity. J Biol Chem. 2003 Jun 13;278(24):21930-7. Epub 2003 Apr 1. PMID:12670957 doi:http://dx.doi.org/10.1074/jbc.M301157200
- ↑ Yan Q, Dutt S, Xu R, Graves K, Juszczynski P, Manis JP, Shipp MA. BBAP monoubiquitylates histone H4 at lysine 91 and selectively modulates the DNA damage response. Mol Cell. 2009 Oct 9;36(1):110-20. doi: 10.1016/j.molcel.2009.08.019. PMID:19818714 doi:http://dx.doi.org/10.1016/j.molcel.2009.08.019
- ↑ Yan Q, Xu R, Zhu L, Cheng X, Wang Z, Manis J, Shipp MA. BAL1 and its partner E3 ligase, BBAP, link Poly(ADP-ribose) activation, ubiquitylation, and double-strand DNA repair independent of ATM, MDC1, and RNF8. Mol Cell Biol. 2013 Feb;33(4):845-57. doi: 10.1128/MCB.00990-12. Epub 2012 Dec, 10. PMID:23230272 doi:http://dx.doi.org/10.1128/MCB.00990-12
- ↑ Obiero J, Walker JR, Dhe-Paganon S. Fold of the conserved DTC domain in Deltex proteins. Proteins. 2012 May;80(5):1495-9. doi: 10.1002/prot.24054. Epub 2012 Mar 13. PMID:22411408 doi:http://dx.doi.org/10.1002/prot.24054
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