CUL3 [The Human Chemical-Genetic Interaction Map Project]

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======= CUL3 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: CUL3
  * **<color #00a2e8>Official Name</color>**: cullin 3
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=8452|8452]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q13618|Q13618]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=CUL3&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CUL3|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/603136|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a member of the cullin protein family. The encoded protein plays a critical role in the polyubiquitination and subsequent degradation of specific protein substrates as the core component and scaffold protein of an E3 ubiquitin ligase complex. Complexes including the encoded protein may also play a role in late endosome maturation. Mutations in this gene are a cause of type 2E pseudohypoaldosteronism. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Core component of multiple cullin-RING-based BCR (BTB- CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. BCR complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin- protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1. The functional specificity of the BCR complex depends on the BTB domain-containing protein as the substrate recognition component. BCR(KLHL42) is involved in ubiquitination of KATNA1. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, BRMS1, H2AFY and DAXX, GLI2 and GLI3. Can also form a cullin-RING-based BCR (BTB-CUL3- RBX1) E3 ubiquitin-protein ligase complex containing homodimeric SPOPL or the heterodimer formed by SPOP and SPOPL; these complexes have lower ubiquitin ligase activity. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B) (PubMed:22358839, PubMed:27716508). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; by mediating ubiquitination of WNK4 (PubMed:23387299, PubMed:23453970, PubMed:23576762). The BCR(KLHL20) E3 ubiquitin ligase complex is involved in interferon response and anterograde Golgi to endosome transport: it mediates both ubiquitination leading to degradation and 'Lys-33'-linked ubiquitination (PubMed:20389280, PubMed:21840486, PubMed:21670212, PubMed:24768539). The BCR(KLHL21) E3 ubiquitin ligase complex regulates localization of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase and mediates the ubiquitination of AURKB (PubMed:19995937). The BCR(KLHL22) ubiquitin ligase complex mediates monoubiquitination of PLK1, leading to PLK1 dissociation from phosphoreceptor proteins and subsequent removal from kinetochores, allowing silencing of the spindle assembly checkpoint (SAC) and chromosome segregation (PubMed:23455478). The BCR(KLHL25) ubiquitin ligase complex is involved in translational homeostasis by mediating ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) (PubMed:22578813). The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832). Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. In concert with ATF2 and RBX1, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. The BCR(KCTD17) E3 ubiquitin ligase complex mediates ubiquitination and degradation of TCHP, a down-regulator of cilium assembly, thereby inducing ciliogenesis (PubMed:25270598). The BCR(KLHL24) E3 ubiquitin ligase complex mediates ubiquitination of KRT14, controls KRT14 levels during keratinocytes differentiation, and is essential for skin integrity (PubMed:27798626). {ECO:0000269|PubMed:10500095, ECO:0000269|PubMed:11311237, ECO:0000269|PubMed:15897469, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16524876, ECO:0000269|PubMed:17543862, ECO:0000269|PubMed:18397884, ECO:0000269|PubMed:19261606, ECO:0000269|PubMed:19995937, ECO:0000269|PubMed:20389280, ECO:0000269|PubMed:21670212, ECO:0000269|PubMed:21840486, ECO:0000269|PubMed:22085717, ECO:0000269|PubMed:22358839, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:22632832, ECO:0000269|PubMed:23387299, ECO:0000269|PubMed:23453970, ECO:0000269|PubMed:23455478, ECO:0000269|PubMed:23576762, ECO:0000269|PubMed:24768539, ECO:0000269|PubMed:25270598, ECO:0000269|PubMed:26399832, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:27716508, ECO:0000269|PubMed:27798626}.

<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'>
|Cullin|
|Cullin Nedd8|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|trophectodermal cellular morphogenesis|
|POZ domain binding|
|fibroblast apoptotic process|
|nuclear protein quality control by the ubiquitin-proteasome system|
|polar microtubule|
|liver morphogenesis|
|embryonic cleavage|
|positive regulation of mitotic sister chromatid separation|
|positive regulation of mitotic metaphase/anaphase transition|
|positive regulation of metaphase/anaphase transition of cell cycle|
|positive regulation of chromosome separation|
|cullin-RING ubiquitin ligase complex|
|trophectodermal cell differentiation|
|stress fiber assembly|
|contractile actin filament bundle assembly|
|positive regulation of mitotic sister chromatid segregation|
|negative regulation of Rho protein signal transduction|
|cellular response to misfolded protein|
|response to misfolded protein|
|Notch binding|
|positive regulation of chromosome segregation|
|protein quality control for misfolded or incompletely synthesized proteins|
|cyclin binding|
|stem cell division|
|Cul3-RING ubiquitin ligase complex|
|blastocyst formation|
|positive regulation of cytokinesis|
|sperm flagellum|
|mitotic metaphase plate congression|
|protein destabilization|
|regulation of mitotic metaphase/anaphase transition|
|negative regulation of Ras protein signal transduction|
|positive regulation of mitotic nuclear division|
|regulation of metaphase/anaphase transition of cell cycle|
|metaphase plate congression|
|regulation of mitotic sister chromatid separation|
|negative regulation of small GTPase mediated signal transduction|
|protein monoubiquitination|
|regulation of chromosome separation|
|vesicle targeting, rough ER to cis-Golgi|
|actin filament bundle assembly|
|COPII vesicle coating|
|SCF ubiquitin ligase complex|
|actin filament bundle organization|
|positive regulation of nuclear division|
|vesicle coating|
|regulation of mitotic sister chromatid segregation|
|COPII-coated vesicle budding|
|vesicle targeting, to, from or within Golgi|
|establishment of chromosome localization|
|chromosome localization|
|Golgi vesicle budding|
|positive regulation of mitotic cell cycle phase transition|
|regulation of sister chromatid segregation|
|anaphase-promoting complex-dependent catabolic process|
|positive regulation of cell division|
|regulation of cytokinesis|
|vesicle targeting|
|positive regulation of cell cycle phase transition|
|integrin-mediated signaling pathway|
|SCF-dependent proteasomal ubiquitin-dependent protein catabolic process|
|vesicle budding from membrane|
|blastocyst development|
|gland morphogenesis|
|regulation of chromosome segregation|
|mitotic sister chromatid segregation|
|actomyosin structure organization|
|positive regulation of protein ubiquitination|
|G1/S transition of mitotic cell cycle|
|cell cycle G1/S phase transition|
|liver development|
|hepaticobiliary system development|
|positive regulation of protein modification by small protein conjugation or removal|
|sister chromatid segregation|
|regulation of Rho protein signal transduction|
|mitotic nuclear division|
|cellular response to topologically incorrect protein|
|intrinsic apoptotic signaling pathway|
|positive regulation of mitotic cell cycle|
|gastrulation|
|regulation of mitotic nuclear division|
|regulation of cell division|
|negative regulation of canonical Wnt signaling pathway|
|positive regulation of chromosome organization|
|establishment of vesicle localization|
|vesicle localization|
|response to topologically incorrect protein|
|regulation of nuclear division|
|regulation of protein ubiquitination|
|negative regulation of Wnt signaling pathway|
|endoplasmic reticulum to Golgi vesicle-mediated transport|
|nuclear chromosome segregation|
|regulation of protein modification by small protein conjugation or removal|
|actin filament organization|
|regulation of Ras protein signal transduction|
|ubiquitin-protein transferase activity|
|mitotic cell cycle phase transition|
|chromosome segregation|
|cell cycle phase transition|
|regulation of canonical Wnt signaling pathway|
|apoptotic signaling pathway|
|nuclear division|
|positive regulation of cell cycle process|
|regulation of protein stability|
|ubiquitin protein ligase binding|
|protein polyubiquitination|
|vesicle organization|
|organelle fission|
|proteasome-mediated ubiquitin-dependent protein catabolic process|
|regulation of small GTPase mediated signal transduction|
|proteasomal protein catabolic process|
|regulation of chromosome organization|
|cell-cell signaling by wnt|
|Wnt signaling pathway|
|regulation of Wnt signaling pathway|
|post-translational protein modification|
|establishment of organelle localization|
|MAPK cascade|
|Golgi vesicle transport|
|positive regulation of cell cycle|
|in utero embryonic development|
|signal transduction by protein phosphorylation|
|gland development|
|regulation of mitotic cell cycle phase transition|
|cell surface receptor signaling pathway involved in cell-cell signaling|
|regulation of cell cycle phase transition|
|supramolecular fiber organization|
|protein heterodimerization activity|
|cell division|
|actin cytoskeleton organization|
|negative regulation of intracellular signal transduction|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|modification-dependent macromolecule catabolic process|
|cell morphogenesis involved in differentiation|
|embryonic morphogenesis|
|actin filament-based process|
|organelle localization|
|proteolysis involved in cellular protein catabolic process|
|mitotic cell cycle process|
|Golgi membrane|
|cellular protein catabolic process|
|positive regulation of organelle organization|
|regulation of mitotic cell cycle|
|chordate embryonic development|
|embryo development ending in birth or egg hatching|
|protein catabolic process|
|mitotic cell cycle|
|protein ubiquitination|
|cell morphogenesis|
|regulation of cell cycle process|
|protein modification by small protein conjugation|
|cellular component morphogenesis|
|membrane organization|
|negative regulation of transcription by RNA polymerase II|
|protein homodimerization activity|
|anatomical structure formation involved in morphogenesis|
|cellular macromolecule catabolic process|
|positive regulation of cell population proliferation|
|apoptotic process|
|animal organ morphogenesis|
|cell migration|
|protein phosphorylation|
|embryo development|
|protein modification by small protein conjugation or removal|
|cell cycle process|
|macromolecule catabolic process|
|programmed cell death|
|organonitrogen compound catabolic process|
|chromosome organization|
|cell motility|
|localization of cell|
|cell death|
|cytoskeleton organization|
|cell-cell signaling|
|cell projection organization|
|regulation of cell cycle|
|negative regulation of transcription, DNA-templated|
|positive regulation of cellular component organization|
|positive regulation of protein modification process|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|negative regulation of signal transduction|
|proteolysis|
|phosphorylation|
|regulation of organelle organization|
|locomotion|
|negative regulation of RNA metabolic process|
|cell cycle|
|negative regulation of cell communication|
|negative regulation of signaling|
|negative regulation of cellular macromolecule biosynthetic process|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|negative regulation of cellular biosynthetic process|
|intracellular transport|
|negative regulation of biosynthetic process|
|movement of cell or subcellular component|
|protein-containing complex assembly|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|cell development|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|organic substance catabolic process|
|cellular catabolic process|
|regulation of intracellular signal transduction|
|establishment of localization in cell|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|vesicle-mediated 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:exp429|Rapamycin 0.001μM R08 exp429]]|-2.82|
|[[:results:exp452|Azithromycin 100μM R08 exp452]]|-2.1|
|[[:results:exp483|FTY720 3μM R08 exp483]]|-1.98|
|[[:results:exp391|Pomalidomide 20μM R07 exp391]]|-1.84|
|[[:results:exp32|Rifampicin 10μM R00 exp32]]|-1.83|
|[[:results:exp177|Apcin 25μM plus proTAME 2μM R04 exp177]]|-1.79|
|[[:results:exp263|Aphidicolin 0.04μM R06 exp263]]|-1.78|
|[[:results:exp534|Trientine 500μM R08 exp534]]|-1.75|
|[[:results:exp416|Tubacin 1.6μM R07 exp416]]|-1.72|
|[[:results:exp13|Chloramphenicol 20μM R00 exp13]]|-1.71|
|[[:results:exp3|Actinomycin-D 0.001μM R00 exp3]]|1.73|
|[[:results:exp431|Rotenone 0.07μM R08 exp431]]|1.73|
|[[:results:exp85|UM0129480 7μM R02 exp85]]|1.77|
|[[:results:exp217|Mdivi-1 15μM R05 exp217]]|1.86|
|[[:results:exp96|BI-2536 0.02μM R03 exp96]]|1.99|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:u:ube2m|UBE2M]]|0.452|
|[[:human genes:u:ubqln1|UBQLN1]]|0.426|
|[[:human genes:f:fbxo11|FBXO11]]|0.424|
|[[:human genes:s:spop|SPOP]]|0.407|
|[[:human genes:r:rptor|RPTOR]]|0.404|
|[[:human genes:f:faf2|FAF2]]|0.403|
|[[:human genes:d:dohh|DOHH]]|0.4|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 18/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|1/28|
|blood|0/28|
|bone|1/26|
|breast|3/33|
|central nervous system|2/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|1/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|1/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|1/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|1/22|
|urinary tract|1/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 2530
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.62 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='CUL3 Expression in NALM6 Cells: 6.62'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>