8oif

Structural highlights

Function

UBA7_HUMAN E1-activating enzyme that catalyzes the covalent conjugation of the ubiquitin-like protein product of ISG15 to additional interferon stimulated proteins (ISGs) as well as other cellular proteins such as P53 in a process termed protein ISGylation (PubMed:27545325). Plays an essential role in antiviral immunity together with ISG15 by restricting the replication of many viruses including rabies virus, influenza virus, sindbis virus, rotavirus or human cytomegalovirus (PubMed:16254333, PubMed:19073728, PubMed:29056542, PubMed:29743376, PubMed:37722521). For example, ISG15 modification of influenza A protein NS1 disrupts the association of the NS1 with importin-alpha leading to NS1 nuclear import inhibition (PubMed:20133869). ISGylation of human cytomegalovirs protein UL26 regulates its stability and inhibits its activities to suppress NF-kappa-B signaling (PubMed:27564865).^{[1] [2] [3] [4] [5] [6] [7] [8]}

See Also

• 3D structures of Ubiquitin activating enzyme

References

1. ↑ Lenschow DJ, Giannakopoulos NV, Gunn LJ, Johnston C, O'Guin AK, Schmidt RE, Levine B, Virgin HW 4th. Identification of interferon-stimulated gene 15 as an antiviral molecule during Sindbis virus infection in vivo. J Virol. 2005 Nov;79(22):13974-83. PMID:16254333 doi:79/22/13974
2. ↑ Giannakopoulos NV, Arutyunova E, Lai C, Lenschow DJ, Haas AL, Virgin HW. ISG15 Arg151 and the ISG15-conjugating enzyme UbE1L are important for innate immune control of Sindbis virus. J Virol. 2009 Feb;83(4):1602-10. PMID:19073728 doi:10.1128/JVI.01590-08
3. ↑ Zhao C, Hsiang TY, Kuo RL, Krug RM. ISG15 conjugation system targets the viral NS1 protein in influenza A virus-infected cells. Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2253-8. PMID:20133869 doi:10.1073/pnas.0909144107
4. ↑ Park JH, Yang SW, Park JM, Ka SH, Kim JH, Kong YY, Jeon YJ, Seol JH, Chung CH. Positive feedback regulation of p53 transactivity by DNA damage-induced ISG15 modification. Nat Commun. 2016 Aug 22;7:12513. PMID:27545325 doi:10.1038/ncomms12513
5. ↑ Kim YJ, Kim ET, Kim YE, Lee MK, Kwon KM, Kim KI, Stamminger T, Ahn JH. Consecutive Inhibition of ISG15 Expression and ISGylation by Cytomegalovirus Regulators. PLoS Pathog. 2016 Aug 26;12(8):e1005850. PMID:27564865 doi:10.1371/journal.ppat.1005850
6. ↑ Zhao P, Jiang T, Zhong Z, Zhao L, Yang S, Xia X. Inhibition of rabies virus replication by interferon-stimulated gene 15 and its activating enzyme UBA7. Infect Genet Evol. 2017 Dec;56:44-53. PMID:29056542 doi:10.1016/j.meegid.2017.10.016
7. ↑ Lee MK, Kim YJ, Kim YE, Han TH, Milbradt J, Marschall M, Ahn JH. Transmembrane Protein pUL50 of Human Cytomegalovirus Inhibits ISGylation by Downregulating UBE1L. J Virol. 2018 Jul 17;92(15):e00462-18. PMID:29743376 doi:10.1128/JVI.00462-18
8. ↑ Sarkar R, Patra U, Mukherjee A, Mitra S, Komoto S, Chawla-Sarkar M. Rotavirus circumvents the antiviral effects of protein ISGylation via proteasomal degradation of Ube1L. Cell Signal. 2023 Dec;112:110891. PMID:37722521 doi:10.1016/j.cellsig.2023.110891