======= STUB1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: STUB1
  * **<color #00a2e8>Official Name</color>**: STIP1 homology and U-box containing protein 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=10273|10273]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9UNE7|Q9UNE7]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=STUB1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20STUB1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/607207|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a protein containing tetratricopeptide repeat and a U-box that functions as a ubiquitin ligase/cochaperone. The encoded protein binds to and ubiquitinates shock cognate 71 kDa protein (Hspa8) and DNA polymerase beta (Polb), among other targets. Mutations in this gene cause spinocerebellar ataxia, autosomal recessive 16. Alternative splicing results in multiple transcript variants. There is a pseudogene for this gene on chromosome 2. [provided by RefSeq, Jun 2014]. 
  * **<color #00a2e8>UniProt Summary</color>**:  E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation. Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension. Ubiquitinates NOS1 in concert with Hsp70 and Hsp40. Modulates the activity of several chaperone complexes, including Hsp70, Hsc70 and Hsp90. Mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation. Mediates polyubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF- BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome. Mediates polyubiquitination of CYP3A4. Ubiquitinates EPHA2 and may regulate the receptor stability and activity through proteasomal degradation. Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and promotes ubiquitin- mediated protein degradation (PubMed:27708256). Negatively regulates the suppressive function of regulatory T-cells (Treg) during inflammation by mediating the ubiquitination and degradation of FOXP3 in a HSPA1A/B-dependent manner (PubMed:23973223). Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation (PubMed:24613385). {ECO:0000269|PubMed:10330192, ECO:0000269|PubMed:11146632, ECO:0000269|PubMed:11557750, ECO:0000269|PubMed:15466472, ECO:0000269|PubMed:19103148, ECO:0000269|PubMed:19567782, ECO:0000269|PubMed:19713937, ECO:0000269|PubMed:23973223, ECO:0000269|PubMed:23990462, ECO:0000269|PubMed:24613385}.

<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'>
|TPR 1|
|U-box|
|Apc3|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|regulation of chaperone-mediated protein complex assembly|
|positive regulation of chaperone-mediated protein complex assembly|
|ubiquitin conjugating enzyme complex|
|ubiquitin-dependent SMAD protein catabolic process|
|chaperone-mediated autophagy|
|TPR domain binding|
|regulation of glucocorticoid metabolic process|
|chaperone complex|
|nuclear inclusion body|
|ubiquitin-ubiquitin ligase activity|
|cellular response to misfolded protein|
|misfolded protein binding|
|response to misfolded protein|
|protein quality control for misfolded or incompletely synthesized proteins|
|positive regulation of ubiquitin-protein transferase activity|
|ERBB2 signaling pathway|
|regulation of hormone metabolic process|
|protein K63-linked ubiquitination|
|Hsp90 protein binding|
|Hsp70 protein binding|
|tau protein binding|
|response to ischemia|
|regulation of ubiquitin-protein transferase activity|
|SMAD binding|
|heat shock protein binding|
|protein autoubiquitination|
|G protein-coupled receptor binding|
|cellular response to heat|
|ERBB signaling pathway|
|ubiquitin-dependent ERAD pathway|
|negative regulation of transforming growth factor beta receptor signaling pathway|
|negative regulation of cellular response to transforming growth factor beta stimulus|
|protein binding, bridging|
|positive regulation of proteasomal ubiquitin-dependent protein catabolic process|
|ERAD pathway|
|kinase binding|
|positive regulation of ubiquitin-dependent protein catabolic process|
|chaperone binding|
|negative regulation of protein binding|
|positive regulation of proteasomal protein catabolic process|
|ubiquitin ligase complex|
|endoplasmic reticulum unfolded protein response|
|response to heat|
|regulation of transforming growth factor beta receptor signaling pathway|
|regulation of steroid metabolic process|
|regulation of cellular response to transforming growth factor beta stimulus|
|positive regulation of protein ubiquitination|
|negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|positive regulation of proteolysis involved in cellular protein catabolic process|
|regulation of proteasomal ubiquitin-dependent protein catabolic process|
|cellular response to unfolded protein|
|Z disc|
|positive regulation of protein modification by small protein conjugation or removal|
|positive regulation of cellular protein catabolic process|
|negative regulation of cellular response to growth factor stimulus|
|cellular response to topologically incorrect protein|
|regulation of ubiquitin-dependent protein catabolic process|
|response to unfolded protein|
|negative regulation of binding|
|response to temperature stimulus|
|regulation of proteasomal protein catabolic process|
|response to topologically incorrect protein|
|cellular response to hypoxia|
|cellular response to decreased oxygen levels|
|transmembrane receptor protein serine/threonine kinase signaling pathway|
|regulation of protein ubiquitination|
|cellular response to oxygen levels|
|regulation of proteolysis involved in cellular protein catabolic process|
|positive regulation of protein catabolic process|
|regulation of protein binding|
|ubiquitin protein ligase activity|
|protein maturation|
|regulation of protein modification by small protein conjugation or removal|
|regulation of transmembrane receptor protein serine/threonine kinase signaling pathway|
|ubiquitin-protein transferase activity|
|positive regulation of protein complex assembly|
|regulation of cellular protein catabolic process|
|response to endoplasmic reticulum stress|
|process utilizing autophagic mechanism|
|autophagy|
|regulation of cellular response to growth factor stimulus|
|regulation of protein stability|
|ubiquitin protein ligase binding|
|protein polyubiquitination|
|proteasome-mediated ubiquitin-dependent protein catabolic process|
|response to hypoxia|
|enzyme binding|
|proteasomal protein catabolic process|
|response to decreased oxygen levels|
|positive regulation of proteolysis|
|positive regulation of cellular catabolic process|
|regulation of binding|
|response to oxygen levels|
|regulation of protein catabolic process|
|regulation of lipid metabolic process|
|positive regulation of catabolic process|
|regulation of protein complex assembly|
|DNA repair|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|positive regulation of cellular component biogenesis|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|regulation of hormone levels|
|modification-dependent macromolecule catabolic process|
|proteolysis involved in cellular protein catabolic process|
|cellular protein catabolic process|
|positive regulation of transferase activity|
|protein catabolic process|
|protein ubiquitination|
|enzyme linked receptor protein signaling pathway|
|regulation of proteolysis|
|DNA metabolic process|
|protein modification by small protein conjugation|
|cellular response to DNA damage stimulus|
|regulation of cellular catabolic process|
|protein homodimerization activity|
|cellular macromolecule catabolic process|
|regulation of cellular component biogenesis|
|regulation of transferase activity|
|protein modification by small protein conjugation or removal|
|regulation of catabolic process|
|response to organonitrogen compound|
|endoplasmic reticulum|
|macromolecule catabolic process|
|organonitrogen compound catabolic process|
|response to nitrogen compound|
|negative regulation of molecular function|
|response to abiotic stimulus|
|positive regulation of cellular component organization|
|positive regulation of protein modification process|
|negative regulation of signal transduction|
|proteolysis|
|negative regulation of cell communication|
|negative regulation of signaling|
|positive regulation of catalytic activity|
|positive regulation of cellular protein metabolic process|
|negative regulation of response to stimulus|
|cellular response to stress|
|positive regulation of protein metabolic process|
|organic substance catabolic process|
|positive regulation of molecular function|
|cellular catabolic process|
|regulation of protein modification process|
|gene expression|
</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:exp7|Bortezomib 0.05μM R00 exp7]]|-2.69|
|[[:results:exp35|TRAIL 5ng/ml R00 exp35]]|-2.68|
|[[:results:exp514|Phorbol-12-myristate-13-acetate 0.57μM R08 exp514]]|-2.5|
|[[:results:exp24|Nocodazole 0.2μM R00 exp24]]|-2.05|
|[[:results:exp335|Aminopterin 0.005μM R07 exp335]]|-1.99|
|[[:results:exp269|Bisphenol A 100μM R06 exp269]]|-1.86|
|[[:results:exp36|TRAIL 50ng/ml R00 exp36]]|-1.79|
|[[:results:exp148|SB202190 10μM R03 exp148]]|1.82|
|[[:results:exp392|PT-1 25μM R07 exp392]]|1.87|
|[[:results:exp77|Prochlorperazine 5.2μM R02 exp77]]|1.99|
|[[:results:exp535|Trimetrexate 0.03μM R08 exp535]]|3.94|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:t:tmem185b|TMEM185B]]|0.484|
</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>**: 1993
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.43 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='STUB1 Expression in NALM6 Cells: 5.43'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>