| Structural highlights
6h77 is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ATP, EDO, MG, PEG, ZN |
| Gene: | UBA5, UBE1DC1 (HUMAN), UFM1, C13orf20, BM-002 (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[UBA5_HUMAN] E1-like enzyme which activates UFM1 and SUMO2.[1] [2] [3] [UFM1_HUMAN] Ubiquitin-like modifier protein which binds to a number of target proteins, such as DDRGK1.[4] [5]
Publication Abstract from PubMed
Modification of proteins by the ubiquitin-like protein, UFM1, requires activation of UFM1 by the E1-activating enzyme, UBA5. In humans, UBA5 possesses two isoforms, each comprising an adenylation domain, but only one containing an N-terminal extension. Currently, the role of the N-terminal extension in UFM1 activation is not clear. Here we provide structural and biochemical data on UBA5 N-terminal extension to understand its contribution to UFM1 activation. The crystal structures of the UBA5 long isoform bound to ATP with and without UFM1 show that the N-terminus not only is directly involved in ATP binding but also affects how the adenylation domain interacts with ATP. Surprisingly, in the presence of the N-terminus, UBA5 no longer retains the 1:2 ratio of ATP to UBA5, but rather this becomes a 1:1 ratio. Accordingly, the N-terminus significantly increases the affinity of ATP to UBA5. Finally, the N-terminus, although not directly involved in the E2 binding, stimulates transfer of UFM1 from UBA5 to the E2, UFC1.
An N-Terminal Extension to UBA5 Adenylation Domain Boosts UFM1 Activation: Isoform-Specific Differences in Ubiquitin-like Protein Activation.,Soudah N, Padala P, Hassouna F, Kumar M, Mashahreh B, Lebedev AA, Isupov MN, Cohen-Kfir E, Wiener R J Mol Biol. 2019 Feb 1;431(3):463-478. doi: 10.1016/j.jmb.2018.10.007. Epub 2018 , Nov 6. PMID:30412706[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Komatsu M, Chiba T, Tatsumi K, Iemura S, Tanida I, Okazaki N, Ueno T, Kominami E, Natsume T, Tanaka K. A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier. EMBO J. 2004 May 5;23(9):1977-86. Epub 2004 Apr 8. PMID:15071506 doi:https://dx.doi.org/10.1038/sj.emboj.7600205
- ↑ Zheng M, Gu X, Zheng D, Yang Z, Li F, Zhao J, Xie Y, Ji C, Mao Y. UBE1DC1, an ubiquitin-activating enzyme, activates two different ubiquitin-like proteins. J Cell Biochem. 2008 Aug 15;104(6):2324-34. doi: 10.1002/jcb.21791. PMID:18442052 doi:https://dx.doi.org/10.1002/jcb.21791
- ↑ Bacik JP, Walker JR, Ali M, Schimmer AD, Dhe-Paganon S. Crystal structure of the human ubiquitin-activating enzyme 5 (UBA5) bound to ATP: mechanistic insights into a minimalistic E1 enzyme. J Biol Chem. 2010 Jun 25;285(26):20273-80. Epub 2010 Apr 5. PMID:20368332 doi:10.1074/jbc.M110.102921
- ↑ Komatsu M, Chiba T, Tatsumi K, Iemura S, Tanida I, Okazaki N, Ueno T, Kominami E, Natsume T, Tanaka K. A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier. EMBO J. 2004 May 5;23(9):1977-86. Epub 2004 Apr 8. PMID:15071506 doi:https://dx.doi.org/10.1038/sj.emboj.7600205
- ↑ Tatsumi K, Sou YS, Tada N, Nakamura E, Iemura S, Natsume T, Kang SH, Chung CH, Kasahara M, Kominami E, Yamamoto M, Tanaka K, Komatsu M. A novel type of E3 ligase for the Ufm1 conjugation system. J Biol Chem. 2010 Feb 19;285(8):5417-27. doi: 10.1074/jbc.M109.036814. Epub 2009 , Dec 14. PMID:20018847 doi:https://dx.doi.org/10.1074/jbc.M109.036814
- ↑ Soudah N, Padala P, Hassouna F, Kumar M, Mashahreh B, Lebedev AA, Isupov MN, Cohen-Kfir E, Wiener R. An N-Terminal Extension to UBA5 Adenylation Domain Boosts UFM1 Activation: Isoform-Specific Differences in Ubiquitin-like Protein Activation. J Mol Biol. 2019 Feb 1;431(3):463-478. doi: 10.1016/j.jmb.2018.10.007. Epub 2018 , Nov 6. PMID:30412706 doi:https://dx.doi.org/10.1016/j.jmb.2018.10.007
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