BTRC [The Human Chemical-Genetic Interaction Map Project]

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======= BTRC =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: BTRC
  * **<color #00a2e8>Official Name</color>**: beta-transducin repeat 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=8945|8945]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9Y297|Q9Y297]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=BTRC&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20BTRC|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/603482|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbws class; in addition to an F-box, this protein contains multiple WD-40 repeats. The encoded protein mediates degradation of CD4 via its interaction with HIV-1 Vpu. It has also been shown to ubiquitinate phosphorylated NFKBIA (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), targeting it for degradation and thus activating nuclear factor kappa-B. Alternatively spliced transcript variants have been described. A related pseudogene exists in chromosome 6. [provided by RefSeq, Mar 2012]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Substrate recognition component of a SCF (SKP1-CUL1-F- box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes and binds to phosphorylated target proteins (PubMed:10066435, PubMed:10497169, PubMed:10644755, PubMed:10835356, PubMed:11238952, PubMed:11359933, PubMed:11994270, PubMed:12791267, PubMed:12902344, PubMed:14603323, PubMed:14681206, PubMed:14988407, PubMed:15448698, PubMed:15917222, PubMed:16371461, PubMed:25503564, PubMed:25704143, PubMed:9859996). SCF(BTRC) mediates the ubiquitination of CTNNB1 and participates in Wnt signaling (PubMed:12077367, PubMed:12820959). SCF(BTRC) mediates the ubiquitination of phosphorylated NFKB1, ATF4, CDC25A, DLG1, FBXO5, PER1, SMAD3, SMAD4, SNAI1 and probably NFKB2 (PubMed:10835356, PubMed:11238952, PubMed:14681206, PubMed:14603323). SCF(BTRC) mediates the ubiquitination of NFKBIA, NFKBIB and NFKBIE; the degradation frees the associated NFKB1 to translocate into the nucleus and to activate transcription (PubMed:10066435, PubMed:10497169, PubMed:10644755). Ubiquitination of NFKBIA occurs at 'Lys-21' and 'Lys-22' (PubMed:10066435). SCF(BTRC) mediates the ubiquitination of CEP68; this is required for centriole separation during mitosis (PubMed:25704143, PubMed:25503564). SCF(BTRC) mediates the ubiquitination and subsequent degradation of nuclear NFE2L1 (By similarity). Has an essential role in the control of the clock- dependent transcription via degradation of phosphorylated PER1 and PER2 (PubMed:15917222). May be involved in ubiquitination and subsequent proteasomal degradation through a DBB1-CUL4 E3 ubiquitin-protein ligase. Required for activation of NFKB-mediated transcription by IL1B, MAP3K14, MAP3K1, IKBKB and TNF. Required for proteolytic processing of GLI3 (PubMed:16371461). {ECO:0000250|UniProtKB:Q3ULA2, ECO:0000269|PubMed:10066435, ECO:0000269|PubMed:10497169, ECO:0000269|PubMed:10644755, ECO:0000269|PubMed:10835356, ECO:0000269|PubMed:11238952, ECO:0000269|PubMed:11359933, ECO:0000269|PubMed:11994270, ECO:0000269|PubMed:12077367, ECO:0000269|PubMed:12791267, ECO:0000269|PubMed:12820959, ECO:0000269|PubMed:12902344, ECO:0000269|PubMed:14603323, ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:14988407, ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15917222, ECO:0000269|PubMed:16371461, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:9859996}.

<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'>
|F-box|
|F-box-like|
|Beta-TrCP D|
|WD40|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|protein phosphorylated amino acid binding|
|Pwp2p-containing subcomplex of 90S preribosome|
|mammary gland epithelial cell proliferation|
|ligase activity|
|positive regulation of circadian rhythm|
|branching involved in mammary gland duct morphogenesis|
|negative regulation of smoothened signaling pathway|
|mammary gland duct morphogenesis|
|maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)|
|small-subunit processome|
|mammary gland morphogenesis|
|protein destabilization|
|maturation of SSU-rRNA|
|mammary gland epithelium development|
|SCF ubiquitin ligase complex|
|ribosomal small subunit biogenesis|
|regulation of smoothened signaling pathway|
|NIK/NF-kappaB signaling|
|beta-catenin binding|
|epithelial cell proliferation|
|SCF-dependent proteasomal ubiquitin-dependent protein catabolic process|
|interleukin-1-mediated signaling pathway|
|gland morphogenesis|
|stress-activated MAPK cascade|
|stimulatory C-type lectin receptor signaling pathway|
|regulation of circadian rhythm|
|innate immune response activating cell surface receptor signaling pathway|
|mammary gland development|
|G2/M transition of mitotic cell cycle|
|branching morphogenesis of an epithelial tube|
|cell cycle G2/M phase transition|
|stress-activated protein kinase signaling cascade|
|morphogenesis of a branching epithelium|
|protein dimerization activity|
|negative regulation of DNA-binding transcription factor activity|
|morphogenesis of a branching structure|
|Fc-epsilon receptor signaling pathway|
|cellular response to interleukin-1|
|T cell receptor signaling pathway|
|regulation of proteasomal protein catabolic process|
|response to interleukin-1|
|rRNA processing|
|protein dephosphorylation|
|regulation of proteolysis involved in cellular protein catabolic process|
|ubiquitin protein ligase activity|
|rRNA metabolic process|
|innate immune response-activating signal transduction|
|regulation of I-kappaB kinase/NF-kappaB signaling|
|Fc receptor signaling pathway|
|ubiquitin-protein transferase activity|
|regulation of cellular protein catabolic process|
|activation of innate immune response|
|mitotic cell cycle phase transition|
|rhythmic process|
|cell cycle phase transition|
|regulation of canonical Wnt signaling pathway|
|regulation of protein stability|
|antigen receptor-mediated signaling pathway|
|protein polyubiquitination|
|ribosome biogenesis|
|epithelial tube morphogenesis|
|dephosphorylation|
|proteasome-mediated ubiquitin-dependent protein catabolic process|
|positive regulation of innate immune response|
|proteasomal protein catabolic process|
|Wnt signaling pathway|
|positive regulation of proteolysis|
|cell-cell signaling by wnt|
|regulation of Wnt signaling pathway|
|positive regulation of response to biotic stimulus|
|post-translational protein modification|
|MAPK cascade|
|regulation of protein catabolic process|
|ncRNA processing|
|signal transduction by protein phosphorylation|
|gland development|
|regulation of mitotic cell cycle phase transition|
|regulation of DNA-binding transcription factor activity|
|cell surface receptor signaling pathway involved in cell-cell signaling|
|morphogenesis of an epithelium|
|regulation of cell cycle phase transition|
|immune response-activating cell surface receptor signaling pathway|
|regulation of innate immune response|
|ribonucleoprotein complex biogenesis|
|positive regulation of defense response|
|ncRNA metabolic process|
|immune response-regulating cell surface receptor signaling pathway|
|positive regulation of multi-organism process|
|regulation of response to biotic stimulus|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|cellular response to organic cyclic compound|
|modification-dependent macromolecule catabolic process|
|cell population proliferation|
|immune response-activating signal transduction|
|tissue morphogenesis|
|proteolysis involved in cellular protein catabolic process|
|immune response-regulating signaling pathway|
|mitotic cell cycle process|
|positive regulation of response to external stimulus|
|cellular protein catabolic process|
|activation of immune response|
|regulation of mitotic cell cycle|
|tube morphogenesis|
|cytokine-mediated signaling pathway|
|mitotic cell cycle|
|protein catabolic process|
|protein ubiquitination|
|viral process|
|regulation of proteolysis|
|regulation of cell cycle process|
|regulation of defense response|
|protein modification by small protein conjugation|
|regulation of multi-organism process|
|symbiotic process|
|interspecies interaction between organisms|
|regulation of cellular catabolic process|
|tube development|
|positive regulation of immune response|
|RNA processing|
|cellular macromolecule catabolic process|
|response to organic cyclic compound|
|animal organ morphogenesis|
|protein phosphorylation|
|protein modification by small protein conjugation or removal|
|regulation of catabolic process|
|cell cycle process|
|cellular response to cytokine stimulus|
|macromolecule catabolic process|
|organonitrogen compound catabolic process|
|regulation of response to external stimulus|
|response to cytokine|
|epithelium development|
|cell-cell signaling|
|negative regulation of molecular function|
|positive regulation of immune system process|
|regulation of immune response|
|regulation of cell cycle|
|negative regulation of transcription, DNA-templated|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|negative regulation of signal transduction|
|proteolysis|
|phosphorylation|
|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|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|positive regulation of transcription, DNA-templated|
|negative regulation of biosynthetic process|
|positive regulation of cellular protein metabolic process|
|negative regulation of response to stimulus|
|positive regulation of nucleic acid-templated transcription|
|positive regulation of RNA biosynthetic process|
|regulation of immune system process|
|RNA metabolic process|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|positive regulation of RNA metabolic process|
|tissue development|
|organic substance catabolic process|
|cellular catabolic process|
|regulation of intracellular signal transduction|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of macromolecule biosynthetic process|
|positive regulation of cellular biosynthetic process|
|positive regulation of gene expression|
|gene expression|
|positive regulation of biosynthetic process|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' 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:exp149|SB203580 25μM R03 exp149]]|1.75|
|[[:results:exp235|Geldanamycin 0.01μM R05 exp235]]|1.91|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</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>**: 16173
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 4.24 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='BTRC Expression in NALM6 Cells: 4.24'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>