Browse STUB1

Summary
SymbolSTUB1
NameSTIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase
Aliases UBOX1; CHIP; SDCCAG7; HSPABP2; NY-CO-7; STIP1 homology and U-box containing protein 1; SCAR16; CLL-associate ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm Nucleus Note=Translocates to the nucleus in response to inflammatory signals in regulatory T-cells (Treg).
Domain PF04564 U-box domain
Function

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). Likely mediates polyubiquitination and downregulates plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity. Negatively regulates TGF-beta signaling by modulating the basal level of SMAD3 via ubiquitin-mediated degradation (PubMed:24613385).

> Gene Ontology
 
Biological Process GO:0000209 protein polyubiquitination
GO:0006515 misfolded or incompletely synthesized protein catabolic process
GO:0006986 response to unfolded protein
GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0007179 transforming growth factor beta receptor signaling pathway
GO:0008202 steroid metabolic process
GO:0008211 glucocorticoid metabolic process
GO:0009894 regulation of catabolic process
GO:0009896 positive regulation of catabolic process
GO:0010498 proteasomal protein catabolic process
GO:0010817 regulation of hormone levels
GO:0017015 regulation of transforming growth factor beta receptor signaling pathway
GO:0019216 regulation of lipid metabolic process
GO:0019218 regulation of steroid metabolic process
GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway
GO:0030579 ubiquitin-dependent SMAD protein catabolic process
GO:0030968 endoplasmic reticulum unfolded protein response
GO:0031329 regulation of cellular catabolic process
GO:0031331 positive regulation of cellular catabolic process
GO:0031334 positive regulation of protein complex assembly
GO:0031396 regulation of protein ubiquitination
GO:0031398 positive regulation of protein ubiquitination
GO:0031647 regulation of protein stability
GO:0031943 regulation of glucocorticoid metabolic process
GO:0032091 negative regulation of protein binding
GO:0032350 regulation of hormone metabolic process
GO:0032434 regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0034620 cellular response to unfolded protein
GO:0034976 response to endoplasmic reticulum stress
GO:0035966 response to topologically incorrect protein
GO:0035967 cellular response to topologically incorrect protein
GO:0036503 ERAD pathway
GO:0038127 ERBB signaling pathway
GO:0038128 ERBB2 signaling pathway
GO:0042176 regulation of protein catabolic process
GO:0042445 hormone metabolic process
GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0043254 regulation of protein complex assembly
GO:0043393 regulation of protein binding
GO:0044089 positive regulation of cellular component biogenesis
GO:0045732 positive regulation of protein catabolic process
GO:0045862 positive regulation of proteolysis
GO:0051098 regulation of binding
GO:0051100 negative regulation of binding
GO:0051131 chaperone-mediated protein complex assembly
GO:0051438 regulation of ubiquitin-protein transferase activity
GO:0051443 positive regulation of ubiquitin-protein transferase activity
GO:0051604 protein maturation
GO:0051788 response to misfolded protein
GO:0051865 protein autoubiquitination
GO:0061136 regulation of proteasomal protein catabolic process
GO:0070534 protein K63-linked ubiquitination
GO:0071218 cellular response to misfolded protein
GO:0071559 response to transforming growth factor beta
GO:0071560 cellular response to transforming growth factor beta stimulus
GO:0090034 regulation of chaperone-mediated protein complex assembly
GO:0090035 positive regulation of chaperone-mediated protein complex assembly
GO:0090092 regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0090101 negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0090287 regulation of cellular response to growth factor stimulus
GO:0090288 negative regulation of cellular response to growth factor stimulus
GO:1901800 positive regulation of proteasomal protein catabolic process
GO:1903050 regulation of proteolysis involved in cellular protein catabolic process
GO:1903052 positive regulation of proteolysis involved in cellular protein catabolic process
GO:1903320 regulation of protein modification by small protein conjugation or removal
GO:1903322 positive regulation of protein modification by small protein conjugation or removal
GO:1903362 regulation of cellular protein catabolic process
GO:1903364 positive regulation of cellular protein catabolic process
GO:1903844 regulation of cellular response to transforming growth factor beta stimulus
GO:1903845 negative regulation of cellular response to transforming growth factor beta stimulus
Molecular Function GO:0001664 G-protein coupled receptor binding
GO:0004842 ubiquitin-protein transferase activity
GO:0016874 ligase activity
GO:0019787 ubiquitin-like protein transferase activity
GO:0030544 Hsp70 protein binding
GO:0030674 protein binding, bridging
GO:0030911 TPR domain binding
GO:0031072 heat shock protein binding
GO:0031625 ubiquitin protein ligase binding
GO:0034450 ubiquitin-ubiquitin ligase activity
GO:0044389 ubiquitin-like protein ligase binding
GO:0046332 SMAD binding
GO:0051787 misfolded protein binding
GO:0051879 Hsp90 protein binding
GO:0060090 binding, bridging
GO:0061630 ubiquitin protein ligase activity
GO:0061659 ubiquitin-like protein ligase activity
GO:1904264 ubiquitin protein ligase activity involved in ERAD pathway
Cellular Component GO:0000151 ubiquitin ligase complex
GO:0016234 inclusion body
GO:0030016 myofibril
GO:0030017 sarcomere
GO:0030018 Z disc
GO:0031371 ubiquitin conjugating enzyme complex
GO:0031674 I band
GO:0042405 nuclear inclusion body
GO:0043292 contractile fiber
GO:0044449 contractile fiber part
GO:0045111 intermediate filament cytoskeleton
> KEGG and Reactome Pathway
 
KEGG hsa04120 Ubiquitin mediated proteolysis
hsa04141 Protein processing in endoplasmic reticulum
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-983168: Antigen processing
R-HSA-983169: Class I MHC mediated antigen processing & presentation
R-HSA-8863795: Downregulation of ERBB2 signaling
R-HSA-2173788: Downregulation of TGF-beta receptor signaling
R-HSA-168256: Immune System
R-HSA-162582: Signal Transduction
R-HSA-1227986: Signaling by ERBB2
R-HSA-170834: Signaling by TGF-beta Receptor Complex
R-HSA-2173789: TGF-beta receptor signaling activates SMADs
Summary
SymbolSTUB1
NameSTIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase
Aliases UBOX1; CHIP; SDCCAG7; HSPABP2; NY-CO-7; STIP1 homology and U-box containing protein 1; SCAR16; CLL-associate ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between STUB1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between STUB1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28723893Bladder carcinoma, head and neck squamous cell carcinoma, lung carcinoma, melanomaInhibit immunity (T cell function); decrease the efficacy of immunotherapyThese genes were Ptpn2, a phosphatase involved in multiple signalling processes; H2-T23, a non-classical MHC-I gene; Ripk1, a kinase that regulates cell death and inflammation; and Stub1, an E3 ubiquitin ligase involved in the regulation of the unfolded protein response. In vivo competition assays showed that tumour cells deleted of each of the four genes were strongly selected against in wild-type animals treated with immunotherapy, but grew at equivalent rates to control tumour cells in vitro and in Tcra?/? mice (Fig. 2b, c; P < 0.01, Student’s t-test). This suggests that loss of function of these genes renders tumour cells more sensitive to immunotherapy, but does not alter their cell growth or survival in the absence of T cells.
Summary
SymbolSTUB1
NameSTIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase
Aliases UBOX1; CHIP; SDCCAG7; HSPABP2; NY-CO-7; STIP1 homology and U-box containing protein 1; SCAR16; CLL-associate ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of STUB1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell logFC: -2.39; FDR: 0.04170 Resistant to T cell-mediated killing
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell logFC: -2.79; FDR: 0.00495 Resistant to T cell-mediated killing
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 STARS Score: 6.31; FDR: 0.000 Resistant to T cell-mediated killing
28723893CRISPR-Cas9 melanomaB16GVAX STARS Score: 5.85; FDR: 0.002 Resistant to T cell-mediated killing
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolSTUB1
NameSTIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase
Aliases UBOX1; CHIP; SDCCAG7; HSPABP2; NY-CO-7; STIP1 homology and U-box containing protein 1; SCAR16; CLL-associate ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of STUB1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.080.806
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.2870.919
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.0750.97
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.1970.609
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.1490.94
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.2570.917
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.0240.939
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.2820.779
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.3090.793
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.1110.955
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 28-0.1330.965
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0540.382
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of STUB1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolSTUB1
NameSTIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase
Aliases UBOX1; CHIP; SDCCAG7; HSPABP2; NY-CO-7; STIP1 homology and U-box containing protein 1; SCAR16; CLL-associate ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of STUB1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolSTUB1
NameSTIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase
Aliases UBOX1; CHIP; SDCCAG7; HSPABP2; NY-CO-7; STIP1 homology and U-box containing protein 1; SCAR16; CLL-associate ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of STUB1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by STUB1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolSTUB1
NameSTIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase
Aliases UBOX1; CHIP; SDCCAG7; HSPABP2; NY-CO-7; STIP1 homology and U-box containing protein 1; SCAR16; CLL-associate ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of STUB1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolSTUB1
NameSTIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase
Aliases UBOX1; CHIP; SDCCAG7; HSPABP2; NY-CO-7; STIP1 homology and U-box containing protein 1; SCAR16; CLL-associate ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of STUB1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolSTUB1
NameSTIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase
Aliases UBOX1; CHIP; SDCCAG7; HSPABP2; NY-CO-7; STIP1 homology and U-box containing protein 1; SCAR16; CLL-associate ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between STUB1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolSTUB1
NameSTIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase
Aliases UBOX1; CHIP; SDCCAG7; HSPABP2; NY-CO-7; STIP1 homology and U-box containing protein 1; SCAR16; CLL-associate ......
Chromosomal Location16p13.3
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting STUB1 collected from DrugBank database.
> Drugs from DrugBank database
 

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