TISIDB

Summary
Symbol	RNF146
Name	ring finger protein 146
Aliases	DKFZp434O1427; dactylidin; dJ351K20.1; iduna; E3 ubiquitin-protein ligase RNF146
Chromosomal Location	6q22.1-q22.33
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 [ TOP ]
Subcellular Location	Cytoplasm, cytosol. Nucleus. Note=Translocates to the nucleus after DNA damage, such as laser-induced DNA breaks, and concentrates at DNA breaks. This translocation requires PARP1 activation and PAR-binding.
Domain	PF02825 WWE domain
Function	E3 ubiquitin-protein ligase that specifically binds poly-ADP-ribosylated (PARsylated) proteins and mediates their ubiquitination and subsequent degradation. May regulate many important biological processes, such as cell survival and DNA damage response. Acts as an activator of the Wnt signaling pathway by mediating the ubiquitination of PARsylated AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex. Acts in cooperation with tankyrase proteins (TNKS and TNKS2), which mediate PARsylation of target proteins AXIN1, AXIN2, BLZF1, CASC3, TNKS and TNKS2. Recognizes and binds tankyrase-dependent PARsylated proteins via its WWE domain and mediates their ubiquitination, leading to their degradation. Different ubiquitin linkage types have been observed: TNKS2 undergoes ubiquitination at 'Lys-48' and 'Lys-63', while AXIN1 is only ubiquitinated at 'Lys-48'. May regulate TNKS and TNKS2 subcellular location, preventing aggregation at a centrosomal location. Neuroprotective protein. Protects the brain against N-methyl-D-aspartate (NMDA) receptor-mediated glutamate excitotoxicity and ischemia, by interfering with PAR-induced cell death, called parthanatos. Prevents nuclear translocation of AIFM1 in a PAR-binding dependent manner. Does not affect PARP1 activation (By similarity). Protects against cell death induced by DNA damaging agents, such as N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and rescues cells from G1 arrest. Promotes cell survival after gamma-irradiation. Facilitates DNA repair.

> Gene Ontology [ TOP ]
Biological Process	GO:0000209 protein polyubiquitination GO:0016055 Wnt signaling pathway GO:0030111 regulation of Wnt signaling pathway GO:0030177 positive regulation of Wnt signaling pathway GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:0051865 protein autoubiquitination GO:0060070 canonical Wnt signaling pathway GO:0060828 regulation of canonical Wnt signaling pathway GO:0070936 protein K48-linked ubiquitination GO:0090263 positive regulation of canonical Wnt signaling pathway GO:0198738 cell-cell signaling by wnt
Molecular Function	GO:0004842 ubiquitin-protein transferase activity GO:0016874 ligase activity GO:0019787 ubiquitin-like protein transferase activity GO:0061630 ubiquitin protein ligase activity GO:0061659 ubiquitin-like protein ligase activity GO:0072572 poly-ADP-D-ribose binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-4641257: Degradation of AXIN R-HSA-5688426: Deubiquitination R-HSA-392499: Metabolism of proteins R-HSA-597592: Post-translational protein modification R-HSA-162582: Signal Transduction R-HSA-195721: Signaling by Wnt R-HSA-201681: TCF dependent signaling in response to WNT R-HSA-5689880: Ub-specific processing proteases

Summary
Symbol	RNF146
Name	ring finger protein 146
Aliases	DKFZp434O1427; dactylidin; dJ351K20.1; iduna; E3 ubiquitin-protein ligase RNF146
Chromosomal Location	6q22.1-q22.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between RNF146 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 [ TOP ]
There is no record.

Summary
Symbol	RNF146
Name	ring finger protein 146
Aliases	DKFZp434O1427; dactylidin; dJ351K20.1; iduna; E3 ubiquitin-protein ligase RNF146
Chromosomal Location	6q22.1-q22.33
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

[ TOP ]

Statistical results of RNF146 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	Second most enriched score: 0.6	Sensitive to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	RNF146
Name	ring finger protein 146
Aliases	DKFZp434O1427; dactylidin; dJ351K20.1; iduna; E3 ubiquitin-protein ligase RNF146
Chromosomal Location	6q22.1-q22.33
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

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Points in the above scatter plot represent the expression difference of RNF146 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.006	0.979
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.083	0.963
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.067	0.958
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.034	0.947
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.371	0.831
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.543	0.799
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.088	0.794
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.105	0.944
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.055	0.973
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.367	0.774
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.148	0.542
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.075	0.194

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of RNF146 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	0	3.7	0.27
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	0	3.7	0.314
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	12.5	-12.5	0.52
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	22.2	-22.2	0.505
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	RNF146
Name	ring finger protein 146
Aliases	DKFZp434O1427; dactylidin; dJ351K20.1; iduna; E3 ubiquitin-protein ligase RNF146
Chromosomal Location	6q22.1-q22.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of RNF146. 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 [ TOP ]

Summary
Symbol	RNF146
Name	ring finger protein 146
Aliases	DKFZp434O1427; dactylidin; dJ351K20.1; iduna; E3 ubiquitin-protein ligase RNF146
Chromosomal Location	6q22.1-q22.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of RNF146. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by RNF146. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	RNF146
Name	ring finger protein 146
Aliases	DKFZp434O1427; dactylidin; dJ351K20.1; iduna; E3 ubiquitin-protein ligase RNF146
Chromosomal Location	6q22.1-q22.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of RNF146. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	RNF146
Name	ring finger protein 146
Aliases	DKFZp434O1427; dactylidin; dJ351K20.1; iduna; E3 ubiquitin-protein ligase RNF146
Chromosomal Location	6q22.1-q22.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of RNF146 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	RNF146
Name	ring finger protein 146
Aliases	DKFZp434O1427; dactylidin; dJ351K20.1; iduna; E3 ubiquitin-protein ligase RNF146
Chromosomal Location	6q22.1-q22.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between RNF146 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	RNF146
Name	ring finger protein 146
Aliases	DKFZp434O1427; dactylidin; dJ351K20.1; iduna; E3 ubiquitin-protein ligase RNF146
Chromosomal Location	6q22.1-q22.33
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting RNF146 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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