STUB1

Gene Information

Official Symbol: STUB1
Official Name: STIP1 homology and U-box containing protein 1
Aliases and Previous Symbols: N/A
Entrez ID: 10273
UniProt: Q9UNE7
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: 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].
UniProt Summary: 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}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
Bortezomib 0.05μM R00 exp7	-2.69
TRAIL 5ng/ml R00 exp35	-2.68
Phorbol-12-myristate-13-acetate 0.57μM R08 exp514	-2.5
Nocodazole 0.2μM R00 exp24	-2.05
Aminopterin 0.005μM R07 exp335	-1.99
Bisphenol A 100μM R06 exp269	-1.86
TRAIL 50ng/ml R00 exp36	-1.79
SB202190 10μM R03 exp148	1.82
PT-1 25μM R07 exp392	1.87
Prochlorperazine 5.2μM R02 exp77	1.99
Trimetrexate 0.03μM R08 exp535	3.94

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

Essentiality in NALM6

Essentiality Rank: 1993
Expression level (log2 read counts): 5.43

Expression Distribution

TPR 1
U-box
Apc3

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