7qs2

Structural highlights

Function

TRI15_HUMAN E3 ubiquitin ligase that plays a role in several processes including innate antiviral immnity, cell migration and chemotaxis (PubMed:34142270, PubMed:23077300). Acts as a 'Lys-63'-specific ubiquitin ligase for MAPK1/ERK2 and MAPK3/ERK1, promoting their activation by facilitating their interaction with MAP2K1 and MAP2K2 (PubMed:34497368). Plays also a role in cell migration and chemotaxis by acting as a stable focal adhesion component upon recruitment by multi-adapter protein paxillin/PXN (PubMed:25015296). Functions in the RIGI-mediated interferon induction pathway upstream or at the level of MAVS (PubMed:23077300). Inhibits NF-kappa-B activation by turnover of 'Lys-63'-linked ubiquitination of MAP3K7/TAK1. Mechanistically, prevents TRIM8 cytoplasmic translocation and thus inhibits TRIM8-mediated 'Lys-63'-linked polyubiquitination of MAP3K7/TAK1 in the cytoplasm (PubMed:34871740). Plays also an important regulatory effect on the activation of hepatic stellate cells (HSCs).^{[1] [2] [3] [4] [5]}

References

1. ↑ Uchil PD, Hinz A, Siegel S, Coenen-Stass A, Pertel T, Luban J, Mothes W. TRIM protein-mediated regulation of inflammatory and innate immune signaling and its association with antiretroviral activity. J Virol. 2013 Jan;87(1):257-72. PMID:23077300 doi:10.1128/JVI.01804-12
2. ↑ Uchil PD, Pawliczek T, Reynolds TD, Ding S, Hinz A, Munro JB, Huang F, Floyd RW, Yang H, Hamilton WL, Bewersdorf J, Xiong Y, Calderwood DA, Mothes W. TRIM15 is a focal adhesion protein that regulates focal adhesion disassembly. J Cell Sci. 2014 Sep 15;127(Pt 18):3928-42. PMID:25015296 doi:10.1242/jcs.143537
3. ↑ Zhang J, Chen Y, Tian Y, Chen S, Liu H. Knockdown of TRIM15 inhibits the activation of hepatic stellate cells. J Mol Histol. 2021 Aug;52(4):839-848. PMID:34142270 doi:10.1007/s10735-021-09997-7
4. ↑ Zhu G, Herlyn M, Yang X. TRIM15 and CYLD regulate ERK activation via lysine-63-linked polyubiquitination. Nat Cell Biol. 2021 Sep;23(9):978-991. PMID:34497368 doi:10.1038/s41556-021-00732-8
5. ↑ Roy M, Singh K, Shinde A, Singh J, Mane M, Bedekar S, Tailor Y, Gohel D, Vasiyani H, Currim F, Singh R. TNF-α-induced E3 ligase, TRIM15 inhibits TNF-α-regulated NF-κB pathway by promoting turnover of K63 linked ubiquitination of TAK1. Cell Signal. 2022 Mar;91:110210. PMID:34871740 doi:10.1016/j.cellsig.2021.110210