RFFL [The Human Chemical-Genetic Interaction Map Project]

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======= RFFL =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: RFFL
  * **<color #00a2e8>Official Name</color>**: ring finger and FYVE like domain containing E3 ubiquitin protein ligase
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=117584|117584]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q8WZ73|Q8WZ73]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=RFFL&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20RFFL|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/609735|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Mediates 'Lys-48'-linked polyubiquitination of PRR5L and its subsequent proteasomal degradation thereby indirectly regulating cell migration through the mTORC2 complex. Ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate cell death downstream of death domain receptors in the extrinsic pathway of apoptosis. Negatively regulates the tumor necrosis factor-mediated signaling pathway through targeting of RIPK1 to ubiquitin-mediated proteasomal degradation. Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation. Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN. May also play a role in endocytic recycling. {ECO:0000269|PubMed:15069192, ECO:0000269|PubMed:17121812, ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:18450452, ECO:0000269|PubMed:22609986}.

<button type='default' 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'>
No Pfam Domain information is available for this gene.
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|tumor necrosis factor receptor superfamily complex|
|negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis|
|regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis|
|negative regulation of tumor necrosis factor-mediated signaling pathway|
|negative regulation of execution phase of apoptosis|
|regulation of fibroblast migration|
|negative regulation of signal transduction by p53 class mediator|
|negative regulation of extrinsic apoptotic signaling pathway via death domain receptors|
|regulation of execution phase of apoptosis|
|protein K48-linked ubiquitination|
|regulation of extrinsic apoptotic signaling pathway via death domain receptors|
|regulation of tumor necrosis factor-mediated signaling pathway|
|negative regulation of cytokine-mediated signaling pathway|
|negative regulation of response to cytokine stimulus|
|p53 binding|
|negative regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|recycling endosome membrane|
|negative regulation of cysteine-type endopeptidase activity|
|negative regulation of extrinsic apoptotic signaling pathway|
|protease binding|
|regulation of TOR signaling|
|regulation of extrinsic apoptotic signaling pathway|
|regulation of cytokine-mediated signaling pathway|
|regulation of response to cytokine stimulus|
|regulation of signal transduction by p53 class mediator|
|endosome membrane|
|regulation of cysteine-type endopeptidase activity involved in apoptotic process|
|ubiquitin protein ligase activity|
|negative regulation of apoptotic signaling pathway|
|regulation of cysteine-type endopeptidase activity|
|negative regulation of endopeptidase activity|
|lysosome|
|negative regulation of peptidase activity|
|ubiquitin protein ligase binding|
|protein polyubiquitination|
|proteasome-mediated ubiquitin-dependent protein catabolic process|
|proteasomal protein catabolic process|
|negative regulation of proteolysis|
|regulation of apoptotic signaling pathway|
|regulation of endopeptidase activity|
|regulation of peptidase activity|
|negative regulation of hydrolase activity|
|protein kinase binding|
|negative regulation of intracellular signal transduction|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|modification-dependent macromolecule catabolic process|
|proteolysis involved in cellular protein catabolic process|
|Golgi membrane|
|cellular protein catabolic process|
|protein catabolic process|
|protein ubiquitination|
|regulation of proteolysis|
|protein modification by small protein conjugation|
|negative regulation of catalytic activity|
|regulation of cell migration|
|negative regulation of apoptotic process|
|cellular macromolecule catabolic process|
|negative regulation of programmed cell death|
|regulation of cell motility|
|apoptotic process|
|regulation of locomotion|
|protein modification by small protein conjugation or removal|
|regulation of cellular component movement|
|negative regulation of cell death|
|negative regulation of cellular protein metabolic process|
|macromolecule catabolic process|
|programmed cell death|
|organonitrogen compound catabolic process|
|cell death|
|negative regulation of protein metabolic process|
|negative regulation of molecular function|
|negative regulation of signal transduction|
|proteolysis|
|regulation of hydrolase activity|
|negative regulation of cell communication|
|negative regulation of signaling|
|regulation of apoptotic process|
|regulation of programmed cell death|
|negative regulation of response to stimulus|
|regulation of cell death|
|organic substance catabolic process|
|cellular catabolic process|
|regulation of intracellular signal transduction|
|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:exp478|Doxorubicin 0.02μM R08 exp478]]|-1.82|
|[[:results:exp232|Epothilone-D 0.004 to 0.006μM on day4 R05 exp232]]|1.74|
|[[:results:exp27|Pimelic-diphenylamide-106 0.5μM R00 exp27]]|2.19|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:t:tceb3cl2|TCEB3CL2]]|0.472|
|[[:human genes:t:tceb3c|TCEB3C]]|0.469|
|[[:human genes:p:pcf11|PCF11]]|0.461|
|[[:human genes:a:akirin2|AKIRIN2]]|0.461|
|[[:human genes:c:c14orf93|C14orf93]]|0.448|
|[[:human genes:t:tceb3cl|TCEB3CL]]|0.447|
|[[:human genes:r:rbbp5|RBBP5]]|0.437|
|[[:human genes:n:nop16|NOP16]]|0.432|
|[[:human genes:c:cnot1|CNOT1]]|0.431|
|[[:human genes:n:npipb5|NPIPB5]]|0.426|
|[[:human genes:a:aamp|AAMP]]|0.422|
|[[:human genes:s:slc6a17|SLC6A17]]|0.42|
|[[:human genes:s:sf3a3|SF3A3]]|0.417|
|[[:human genes:n:nol10|NOL10]]|0.416|
|[[:human genes:a:ankle1|ANKLE1]]|0.415|
|[[:human genes:r:rpl30|RPL30]]|0.414|
|[[:human genes:r:rps28|RPS28]]|0.413|
|[[:human genes:r:rps12|RPS12]]|0.412|
|[[:human genes:i:ik|IK]]|0.411|
|[[:human genes:l:lrr1|LRR1]]|0.411|
|[[:human genes:s:snip1|SNIP1]]|0.41|
|[[:human genes:k:kctd17|KCTD17]]|0.41|
|[[:human genes:w:wdr87|WDR87]]|0.41|
|[[:human genes:z:znf830|ZNF830]]|0.409|
|[[:human genes:m:myo1h|MYO1H]]|0.409|
|[[:human genes:p:parp3|PARP3]]|0.409|
|[[:human genes:c:chd4|CHD4]]|0.408|
|[[:human genes:o:orc1|ORC1]]|0.407|
|[[:human genes:t:tinf2|TINF2]]|0.406|
|[[:human genes:s:supt6h|SUPT6H]]|0.404|
|[[:human genes:t:tbc1d3h|TBC1D3H]]|0.404|
|[[:human genes:n:nup160|NUP160]]|0.404|
|[[:human genes:e:eif4a3|EIF4A3]]|0.402|
|[[:human genes:c:cope|COPE]]|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: 3/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|1/28|
|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>**: 1874
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 4.62 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='RFFL Expression in NALM6 Cells: 4.62'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>