======= MUL1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: MUL1
  * **<color #00a2e8>Official Name</color>**: mitochondrial E3 ubiquitin protein ligase 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=79594|79594]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q969V5|Q969V5]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=MUL1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20MUL1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/612037|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  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 mitchondrial fragmentation, and influences mitochondrial localization (PubMed:19407830, PubMed:18207745, PubMed:18213395). Likely to promote mitchondrial 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). {ECO:0000269|PubMed:18207745, ECO:0000269|PubMed:18213395, ECO:0000269|PubMed:18591963, ECO:0000269|PubMed:19407830, ECO:0000269|PubMed:22410793, ECO:0000269|PubMed:23399697, ECO:0000269|PubMed:24898855}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|GIDE|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|negative regulation of defense response to virus by host|
|negative regulation of chemokine (C-C motif) ligand 5 production|
|negative regulation of mitochondrial fusion|
|regulation of chemokine (C-C motif) ligand 5 production|
|regulation of mitochondrial fusion|
|positive regulation of protein sumoylation|
|positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization|
|regulation of autophagy of mitochondrion in response to mitochondrial depolarization|
|negative regulation of type I interferon-mediated signaling pathway|
|positive regulation of mitochondrial fission|
|SUMO transferase activity|
|cellular response to exogenous dsRNA|
|mitochondrial fission|
|response to mitochondrial depolarisation|
|positive regulation of autophagy of mitochondrion|
|negative regulation of chemokine production|
|integral component of mitochondrial outer membrane|
|regulation of protein sumoylation|
|cellular response to dsRNA|
|regulation of mitochondrial fission|
|positive regulation of dendrite extension|
|negative regulation of defense response to virus|
|regulation of dendrite extension|
|regulation of type I interferon-mediated signaling pathway|
|regulation of defense response to virus by host|
|activation of JUN kinase activity|
|regulation of autophagy of mitochondrion|
|regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway|
|response to exogenous dsRNA|
|negative regulation of protein kinase B signaling|
|mitochondrion localization|
|protein destabilization|
|response to dsRNA|
|negative regulation of mitochondrion organization|
|negative regulation of innate immune response|
|negative regulation of cytokine-mediated signaling pathway|
|negative regulation of response to cytokine stimulus|
|protein sumoylation|
|regulation of mitochondrial membrane potential|
|regulation of mitochondrial membrane permeability|
|positive regulation of JUN kinase activity|
|regulation of defense response to virus|
|regulation of chemokine production|
|regulation of membrane permeability|
|JNK cascade|
|activation of cysteine-type endopeptidase activity involved in apoptotic process|
|regulation of JUN kinase activity|
|negative regulation of response to biotic stimulus|
|stress-activated MAPK cascade|
|peroxisome|
|positive regulation of mitochondrion organization|
|negative regulation of immune effector process|
|positive regulation of autophagy|
|mitochondrial membrane organization|
|positive regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|positive regulation of protein modification by small protein conjugation or removal|
|positive regulation of JNK cascade|
|stress-activated protein kinase signaling cascade|
|negative regulation of immune response|
|positive regulation of cysteine-type endopeptidase activity|
|activation of MAPK activity|
|positive regulation of cell growth|
|regulation of cytokine-mediated signaling pathway|
|positive regulation of stress-activated MAPK cascade|
|positive regulation of stress-activated protein kinase signaling cascade|
|positive regulation of developmental growth|
|positive regulation of endopeptidase activity|
|regulation of response to cytokine stimulus|
|protein stabilization|
|regulation of mitochondrion organization|
|negative regulation of cell growth|
|positive regulation of I-kappaB kinase/NF-kappaB signaling|
|regulation of JNK cascade|
|positive regulation of peptidase activity|
|negative regulation of defense response|
|regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|negative regulation of multi-organism process|
|mitochondrial transport|
|regulation of protein kinase B signaling|
|regulation of protein modification by small protein conjugation or removal|
|regulation of stress-activated MAPK cascade|
|regulation of I-kappaB kinase/NF-kappaB signaling|
|regulation of stress-activated protein kinase signaling cascade|
|regulation of cysteine-type endopeptidase activity|
|negative regulation of growth|
|ubiquitin-protein transferase activity|
|positive regulation of growth|
|positive regulation of MAP kinase activity|
|negative regulation of cytokine production|
|positive regulation of neuron projection development|
|regulation of protein stability|
|ubiquitin protein ligase binding|
|axon|
|organelle fission|
|peptidyl-lysine modification|
|activation of protein kinase activity|
|regulation of developmental growth|
|regulation of autophagy|
|positive regulation of protein serine/threonine kinase activity|
|regulation of MAP kinase activity|
|positive regulation of proteolysis|
|negative regulation of response to external stimulus|
|positive regulation of cellular catabolic process|
|positive regulation of neuron differentiation|
|neuronal cell body|
|MAPK cascade|
|negative regulation of organelle organization|
|positive regulation of cell projection organization|
|signal transduction by protein phosphorylation|
|regulation of apoptotic signaling pathway|
|regulation of cell growth|
|regulation of endopeptidase activity|
|regulation of membrane potential|
|positive regulation of catabolic process|
|negative regulation of immune system process|
|mitochondrion organization|
|regulation of peptidase activity|
|regulation of innate immune response|
|regulation of immune effector process|
|positive regulation of neurogenesis|
|regulation of cell morphogenesis|
|regulation of neuron projection development|
|negative regulation of intracellular signal transduction|
|regulation of protein serine/threonine kinase activity|
|regulation of response to biotic stimulus|
|positive regulation of protein kinase activity|
|positive regulation of nervous system development|
|positive regulation of cell development|
|cellular response to organic cyclic compound|
|positive regulation of MAPK cascade|
|positive regulation of kinase activity|
|organelle localization|
|positive regulation of organelle organization|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|regulation of neuron differentiation|
|positive regulation of transferase activity|
|cellular response to nitrogen compound|
|regulation of growth|
|protein ubiquitination|
|regulation of cytokine production|
|regulation of plasma membrane bounded cell projection organization|
|positive regulation of cell death|
|negative regulation of cellular component organization|
|regulation of cell projection organization|
|regulation of proteolysis|
|regulation of cellular response to stress|
|regulation of MAPK cascade|
|regulation of defense response|
|positive regulation of hydrolase activity|
|protein modification by small protein conjugation|
|regulation of multi-organism process|
|regulation of protein kinase activity|
|regulation of neurogenesis|
|regulation of cellular catabolic process|
|membrane organization|
|regulation of kinase activity|
|peptidyl-amino acid modification|
|response to organic cyclic compound|
|apoptotic process|
|regulation of nervous system development|
|regulation of cell development|
|negative regulation of developmental process|
|positive regulation of cell differentiation|
|protein phosphorylation|
|regulation of transferase activity|
|protein modification by small protein conjugation or removal|
|regulation of catabolic process|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|programmed cell death|
|positive regulation of phosphorylation|
|regulation of anatomical structure morphogenesis|
|identical protein binding|
|response to nitrogen compound|
|cell death|
|regulation of response to external stimulus|
|positive regulation of phosphate metabolic process|
|positive regulation of phosphorus metabolic process|
|regulation of immune response|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|positive regulation of protein modification process|
|mitochondrion|
|negative regulation of signal transduction|
|regulation of hydrolase activity|
|phosphorylation|
|regulation of organelle organization|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of developmental process|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|regulation of response to stress|
|generation of neurons|
|regulation of apoptotic process|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|negative regulation of response to stimulus|
|neurogenesis|
|positive regulation of signal transduction|
|regulation of immune system process|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|positive regulation of multicellular organismal process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|regulation of transport|
|membrane|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp67|BVD-523 15μM R02 exp67]]|-2.62|
|[[:results:exp459|Bleomycin 5μM R08 exp459]]|-2.52|
|[[:results:exp19|Etoposide 1μM R00 exp19]]|-2.43|
|[[:results:exp7|Bortezomib 0.05μM R00 exp7]]|-2.32|
|[[:results:exp85|UM0129480 7μM R02 exp85]]|-2.08|
|[[:results:exp28|Pimelic-diphenylamide-106 5μM R00 exp28]]|-2.06|
|[[:results:exp355|Dinaciclib 0.007μM R07 exp355]]|-2.05|
|[[:results:exp72|LB-100 4.1μM R02 exp72]]|-2.01|
|[[:results:exp443|SNS-032 15μM R08 exp443]]|-1.99|
|[[:results:exp20|Etoposide 10μM R00 exp20]]|-1.88|
|[[:results:exp134|MS023 2μM R03 exp134]]|-1.78|
|[[:results:exp518|RK-33 8μM R08 exp518]]|-1.75|
|[[:results:exp34|Rotenone 20μM R00 exp34]]|-1.73|
|[[:results:exp356|Docosahexaenoic-acid 50μM R07 exp356]]|1.86|
|[[:results:exp471|Cholesterol 0.003 to 0.006 to 0.1μM on day2 then day6 R08 exp471]]|2.05|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:p:polr2j3|POLR2J3]]|0.477|
|[[:human genes:r:ruvbl2|RUVBL2]]|0.447|
|[[:human genes:m:mtch2|MTCH2]]|0.444|
|[[:human genes:s:smg7|SMG7]]|0.433|
|[[:human genes:z:zfand5|ZFAND5]]|0.415|
|[[:human genes:m:mbtd1|MBTD1]]|0.401|
|[[:human genes:r:rrp7a|RRP7A]]|0.401|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 7930
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.08 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='MUL1 Expression in NALM6 Cells: 5.08'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>