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Molecule Details

General Information of the Molecule
Name
E3 ubiquitin ligase MUL1 (MUL1)
Synonyms
Mitochondrial ubiquitin ligase activator of NFKB 1; E3 SUMO-protein ligase MUL1; E3 ubiquitin-protein ligase MUL1; Growth inhibition and death E3 ligase; Mitochondrial-anchored protein ligase; Protein Hades; Putative NF-kappa-B-activating protein 266; RING finger protein 218; RING-type E3 ubiquitin transferase NFKB 1
Gene Name
MUL1
Gene ID
79594
Sequence
MESGGRPSLCQFILLGTTSVVTAALYSVYRQKARVSQELKGAKKVHLGEDLKSILSEAPG
KCVPYAVIEGAVRSVKETLNSQFVENCKGVIQRLTLQEHKMVWNRTTHLWNDCSKIIHQR
TNTVPFDLVPHEDGVDVAVRVLKPLDSVDLGLETVYEKFHPSIQSFTDVIGHYISGERPK
GIQETEEMLKVGATLTGVGELVLDNNSVRLQPPKQGMQYYLSSQDFDSLLQRQESSVRLW
KVLALVFGFATCATLFFILRKQYLQRQERLRLKQMQEEFQEHEAQLLSRAKPEDRESLKS
ACVVCLSSFKSCVFLECGHVCSCTECYRALPEPKKCPICRQAITRVIPLYNS
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Function
Exhibits weak E3 ubiquitin-protein ligase activity. 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. 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. Mediates polyubiquitination of cytoplasmic TP53 at 'Lys-24' which targets TP53 for proteasomal degradation, thus reducing TP53 levels in the cytoplasm and mitochondrion. Proposed to preferentially act as a SUMO E3 ligase at physiological concentrations. Plays a role in the control of mitochondrial morphology by promoting mitochondrial fragmentation, and influences mitochondrial localization. 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. May also be involved in the sumoylation of the membrane fission protein DNM1L. Inhibits cell growth. When overexpressed, activates JNK through MAP3K7/TAK1 and induces caspase-dependent apoptosis. Involved in the modulation of innate immune defense against viruses by inhibiting DDX58-dependent antiviral response. Can mediate DDX58 sumoylation and disrupt its polyubiquitination.
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Uniprot ID
MUL1_HUMAN
EC Number
EC: 2.3.2.27
Pfam
PF12483
KEGG ID
hsa79594
A List of Drug Combination(s) Able to Regulate This Molecule
          Expression Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Expression of This Molecule [1]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + Rapamycin   Drug Info 
                    Structure +
References
Reference 1 Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT signaling. Cancer Lett. 2011 Feb 28;301(2):168-76.
Cite NPCDR
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Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China