| Structural highlights
6m2d is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Gene: | MUL1, C1orf166, GIDE, MAPL, MULAN, RNF218 (HUMAN) |
| Activity: | RING-type E3 ubiquitin transferase, with EC number 2.3.2.27 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[MUL1_HUMAN] Exhibits weak E3 ubiquitin-protein ligase activity (PubMed:18591963, PubMed:19407830, PubMed:22410793). E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates (PubMed:18591963, PubMed:19407830, PubMed:22410793). Can ubiquitinate AKT1 preferentially at 'Lys-284' involving 'Lys-48'-linked polyubiquitination and seems to be involved in regulation of Akt signaling by targeting phosphorylated Akt to proteosomal degradation (PubMed:22410793). Proposed to preferentially act as a SUMO E3 ligase at physiological concentrations (PubMed:19407830). Plays a role in the control of mitochondrial morphology by promoting mitochondrial fragmentation, and influences mitochondrial localization (PubMed:19407830, PubMed:18207745, PubMed:18213395). Likely to promote mitochondrial fission through negatively regulating the mitochondrial fusion proteins MFN1 and MFN2, acting in a pathway that is parallel to the PRKN/PINK1 regulatory pathway (PubMed:24898855). May also be involved in the sumoylation of the membrane fission protein DNM1L (PubMed:18207745, PubMed:19407830). Inhibits cell growth (PubMed:18591963, PubMed:22410793). When overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis (PubMed:23399697). Involved in the modulation of innate immune defense against viruses by inhibiting DDX58-dependent antiviral response (PubMed:23399697). Can mediate DDX58 sumoylation and disrupt its polyubiquitination (PubMed:23399697).[1] [2] [3] [4] [5] [6] [7]
References
- ↑ Neuspiel M, Schauss AC, Braschi E, Zunino R, Rippstein P, Rachubinski RA, Andrade-Navarro MA, McBride HM. Cargo-selected transport from the mitochondria to peroxisomes is mediated by vesicular carriers. Curr Biol. 2008 Jan 22;18(2):102-8. PMID:18207745 doi:http://dx.doi.org/S0960-9822(07)02435-9
- ↑ Li W, Bengtson MH, Ulbrich A, Matsuda A, Reddy VA, Orth A, Chanda SK, Batalov S, Joazeiro CA. Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signaling. PLoS One. 2008 Jan 23;3(1):e1487. doi: 10.1371/journal.pone.0001487. PMID:18213395 doi:http://dx.doi.org/10.1371/journal.pone.0001487
- ↑ Zhang B, Huang J, Li HL, Liu T, Wang YY, Waterman P, Mao AP, Xu LG, Zhai Z, Liu D, Marrack P, Shu HB. GIDE is a mitochondrial E3 ubiquitin ligase that induces apoptosis and slows growth. Cell Res. 2008 Sep;18(9):900-10. PMID:18591963 doi:http://dx.doi.org/cr200875
- ↑ Braschi E, Zunino R, McBride HM. MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial fission. EMBO Rep. 2009 Jul;10(7):748-54. Epub 2009 May 1. PMID:19407830 doi:http://dx.doi.org/embor200986
- ↑ Bae S, Kim SY, Jung JH, Yoon Y, Cha HJ, Lee H, Kim K, Kim J, An IS, Kim J, Um HD, Park IC, Lee SJ, Nam SY, Jin YW, Lee JH, An S. Akt is negatively regulated by the MULAN E3 ligase. Cell Res. 2012 May;22(5):873-85. doi: 10.1038/cr.2012.38. Epub 2012 Mar 13. PMID:22410793 doi:http://dx.doi.org/10.1038/cr.2012.38
- ↑ Jenkins K, Khoo JJ, Sadler A, Piganis R, Wang D, Borg NA, Hjerrild K, Gould J, Thomas BJ, Nagley P, Hertzog PJ, Mansell A. Mitochondrially localised MUL1 is a novel modulator of antiviral signaling. Immunol Cell Biol. 2013 Apr;91(4):321-30. doi: 10.1038/icb.2013.7. Epub 2013 Feb , 12. PMID:23399697 doi:http://dx.doi.org/10.1038/icb.2013.7
- ↑ Yun J, Puri R, Yang H, Lizzio MA, Wu C, Sheng ZH, Guo M. MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin and compensates for loss of PINK1/parkin. Elife. 2014 Jun 4;3:e01958. doi: 10.7554/eLife.01958. PMID:24898855 doi:http://dx.doi.org/10.7554/eLife.01958
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