======= CUL4A =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: CUL4A
  * **<color #00a2e8>Official Name</color>**: cullin 4A
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=8451|8451]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q13619|Q13619]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=CUL4A&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20CUL4A|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/603137|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination of target proteins. 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 E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. DCX(DET1-COP1) directs ubiquitination of JUN. DCX(DDB2) directs ubiquitination of XPC. DCX(DDB2) ubiquitinates histones H3-H4 and is required for efficient histone deposition during replication-coupled (H3.1) and replication-independent (H3.3) nucleosome assembly, probably by facilitating the transfer of H3 from ASF1A/ASF1B to other chaperones involved in histone deposition. DCX(DTL) plays a role in PCNA-dependent polyubiquitination of CDT1 and MDM2-dependent ubiquitination of TP53 in response to radiation-induced DNA damage and during DNA replication. In association with DDB1 and SKP2 probably is involved in ubiquitination of CDKN1B/p27kip. Is involved in ubiquitination of HOXA9. DCX(DTL) directs autoubiquitination of DTL. {ECO:0000269|PubMed:14578910, ECO:0000269|PubMed:14609952, ECO:0000269|PubMed:15448697, ECO:0000269|PubMed:15548678, ECO:0000269|PubMed:16537899, ECO:0000269|PubMed:16678110, ECO:0000269|PubMed:23478445, ECO:0000269|PubMed:24209620}.

<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'>
|regulation of nucleotide-excision repair|
|negative regulation of granulocyte differentiation|
|Cul4A-RING E3 ubiquitin ligase complex|
|cullin-RING ubiquitin ligase complex|
|regulation of granulocyte differentiation|
|regulation of DNA damage checkpoint|
|nucleotide-excision repair, preincision complex stabilization|
|nucleotide-excision repair, DNA incision, 3-to lesion|
|nucleotide-excision repair, DNA duplex unwinding|
|nucleotide-excision repair, DNA damage recognition|
|global genome nucleotide-excision repair|
|Cul4-RING E3 ubiquitin ligase complex|
|nucleotide-excision repair, preincision complex assembly|
|regulation of cell cycle checkpoint|
|positive regulation of G1/S transition of mitotic cell cycle|
|nucleotide-excision repair, DNA incision, 5-to lesion|
|DNA damage response, detection of DNA damage|
|nucleotide-excision repair, DNA incision|
|negative regulation of myeloid leukocyte differentiation|
|positive regulation of cell cycle G1/S phase transition|
|SCF ubiquitin ligase complex|
|somatic stem cell population maintenance|
|transcription-coupled nucleotide-excision repair|
|negative regulation of myeloid cell differentiation|
|positive regulation of mitotic cell cycle phase transition|
|positive regulation of cell cycle phase transition|
|SCF-dependent proteasomal ubiquitin-dependent protein catabolic process|
|negative regulation of leukocyte differentiation|
|nucleotide-excision repair|
|DNA duplex unwinding|
|regulation of myeloid leukocyte differentiation|
|G1/S transition of mitotic cell cycle|
|DNA geometric change|
|cell cycle G1/S phase transition|
|regulation of DNA repair|
|stem cell population maintenance|
|maintenance of cell number|
|negative regulation of hemopoiesis|
|intrinsic apoptotic signaling pathway|
|regulation of G1/S transition of mitotic cell cycle|
|positive regulation of mitotic cell cycle|
|regulation of cell cycle G1/S phase transition|
|protein-DNA complex assembly|
|regulation of response to DNA damage stimulus|
|regulation of myeloid cell differentiation|
|protein-DNA complex subunit organization|
|positive regulation of protein complex assembly|
|mitotic cell cycle phase transition|
|regulation of leukocyte differentiation|
|rhythmic process|
|cell cycle phase transition|
|apoptotic signaling pathway|
|positive regulation of cell cycle process|
|ubiquitin protein ligase binding|
|DNA conformation change|
|nucleic acid phosphodiester bond hydrolysis|
|ribosome biogenesis|
|proteasome-mediated ubiquitin-dependent protein catabolic process|
|proteasomal protein catabolic process|
|regulation of DNA metabolic process|
|post-translational protein modification|
|positive regulation of cell cycle|
|in utero embryonic development|
|regulation of mitotic cell cycle phase transition|
|negative regulation of immune system process|
|regulation of cell cycle phase transition|
|regulation of hemopoiesis|
|regulation of protein complex assembly|
|ribonucleoprotein complex biogenesis|
|DNA repair|
|positive regulation of cellular component biogenesis|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|modification-dependent macromolecule catabolic process|
|hemopoiesis|
|proteolysis involved in cellular protein catabolic process|
|mitotic cell cycle process|
|hematopoietic or lymphoid organ development|
|cellular protein catabolic process|
|regulation of mitotic cell cycle|
|chordate embryonic development|
|immune system development|
|embryo development ending in birth or egg hatching|
|protein catabolic process|
|mitotic cell cycle|
|protein ubiquitination|
|detection of stimulus|
|viral process|
|negative regulation of cell differentiation|
|regulation of cellular response to stress|
|DNA metabolic process|
|regulation of cell cycle process|
|protein modification by small protein conjugation|
|cellular response to DNA damage stimulus|
|symbiotic process|
|interspecies interaction between organisms|
|cellular protein-containing complex assembly|
|cellular macromolecule catabolic process|
|positive regulation of cell population proliferation|
|apoptotic process|
|negative regulation of developmental process|
|regulation of cellular component biogenesis|
|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 death|
|regulation of cell cycle|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|proteolysis|
|cell cycle|
|regulation of response to stress|
|protein-containing complex assembly|
|regulation of cell population proliferation|
|regulation of immune system process|
|intracellular signal transduction|
|cellular response to stress|
|organic substance catabolic process|
|cellular catabolic process|
|regulation of cell differentiation|
|protein-containing complex subunit organization|
</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:exp21|MLN-4924 0.2μM R00 exp21]]|-2.97|
|[[:results:exp413|THZ531 0.11 to 0.175μM on day4 R07 exp413]]|-2.31|
|[[:results:exp438|NN-Diethyl-meta-toluamide 500μM R08 exp438]]|-2.21|
|[[:results:exp430|Rifampicin 30μM R08 exp430]]|-1.7|
|[[:results:exp33|Rotenone 2μM R00 exp33]]|1.83|
|[[:results:exp198|Etoposide 0.1μM R05 exp198]]|1.92|
|[[:results:exp36|TRAIL 50ng/ml R00 exp36]]|2.15|
|[[:results:exp35|TRAIL 5ng/ml R00 exp35]]|2.16|
|[[:results:exp360|Genistein 15μM R07 exp360]]|2.32|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:u:ube2g1|UBE2G1]]|0.542|
|[[:human genes:u:ube3a|UBE3A]]|0.47|
|[[:human genes:r:rbm17|RBM17]]|0.443|
|[[:human genes:s:slc38a2|SLC38A2]]|0.423|
|[[:human genes:t:thoc6|THOC6]]|0.422|
|[[:human genes:f:fbxo11|FBXO11]]|0.415|
|[[:human genes:h:hars|HARS]]|0.413|
</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>**: 7043
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.1 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='CUL4A Expression in NALM6 Cells: 7.1'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>