13sc

Structural highlights

Function

MYLIP_HUMAN E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Activity depends on E2 enzymes of the UBE2D family. Proteasomal degradation of MRLC leads to inhibit neurite outgrowth in presence of NGF by counteracting the stabilization of MRLC by saposin-like protein (CNPY2/MSAP) and reducing CNPY2-stimulated neurite outgrowth. Acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating ubiquitination and subsequent degradation of LDLR.^{[1] [2] [3] [4] [5] [6]}

References

1. ↑ Olsson PA, Korhonen L, Mercer EA, Lindholm D. MIR is a novel ERM-like protein that interacts with myosin regulatory light chain and inhibits neurite outgrowth. J Biol Chem. 1999 Dec 17;274(51):36288-92. PMID:10593918
2. ↑ Bornhauser BC, Johansson C, Lindholm D. Functional activities and cellular localization of the ezrin, radixin, moesin (ERM) and RING zinc finger domains in MIR. FEBS Lett. 2003 Oct 9;553(1-2):195-9. PMID:14550572
3. ↑ Bornhauser BC, Olsson PA, Lindholm D. MSAP is a novel MIR-interacting protein that enhances neurite outgrowth and increases myosin regulatory light chain. J Biol Chem. 2003 Sep 12;278(37):35412-20. Epub 2003 Jun 24. PMID:12826659 doi:10.1074/jbc.M306271200
4. ↑ Zelcer N, Hong C, Boyadjian R, Tontonoz P. LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. Science. 2009 Jul 3;325(5936):100-4. doi: 10.1126/science.1168974. Epub 2009 Jun , 11. PMID:19520913 doi:10.1126/science.1168974
5. ↑ Hong C, Duit S, Jalonen P, Out R, Scheer L, Sorrentino V, Boyadjian R, Rodenburg KW, Foley E, Korhonen L, Lindholm D, Nimpf J, van Berkel TJ, Tontonoz P, Zelcer N. The E3 ubiquitin ligase IDOL induces the degradation of the low density lipoprotein receptor family members VLDLR and ApoER2. J Biol Chem. 2010 Jun 25;285(26):19720-6. doi: 10.1074/jbc.M110.123729. Epub 2010, Apr 28. PMID:20427281 doi:10.1074/jbc.M110.123729
6. ↑ Calkin AC, Goult BT, Zhang L, Fairall L, Hong C, Schwabe JW, Tontonoz P. FERM-dependent E3 ligase recognition is a conserved mechanism for targeted degradation of lipoprotein receptors. Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):20107-12. doi:, 10.1073/pnas.1111589108. Epub 2011 Nov 22. PMID:22109552 doi:10.1073/pnas.1111589108