TISIDB

Summary
Symbol	UBR4
Name	ubiquitin protein ligase E3 component n-recognin 4
Aliases	KIAA1307; KIAA0462; RBAF600; ZUBR1; zinc finger, UBR1 type 1; N-recognin-4; retinoblastoma-associated factor ......
Chromosomal Location	1p36.13
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	Membrane Multi-pass membrane protein Cytoplasm. Cytoplasm, cytoskeleton. Nucleus. Note=Concentrates at the leading edge of membrane structures involved in actin motility.
Domain	PF13764 E3 ubiquitin-protein ligase UBR4 PF02207 Putative zinc finger in N-recognin (UBR box)
Function	E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. Together with clathrin, forms meshwork structures involved in membrane morphogenesis and cytoskeletal organization. Regulates integrin-mediated signaling. May play a role in activation of FAK in response to cell-matrix interactions. Mediates ubiquitination of ACLY, leading to its subsequent degradation.

> Gene Ontology [ TOP ]
Biological Process	GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process
Molecular Function	GO:0004842 ubiquitin-protein transferase activity GO:0005516 calmodulin binding GO:0016874 ligase activity GO:0019787 ubiquitin-like protein transferase activity
Cellular Component	GO:0005813 centrosome

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-983168: Antigen processing R-HSA-983169: Class I MHC mediated antigen processing & presentation R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-6798695: Neutrophil degranulation

Summary
Symbol	UBR4
Name	ubiquitin protein ligase E3 component n-recognin 4
Aliases	KIAA1307; KIAA0462; RBAF600; ZUBR1; zinc finger, UBR1 type 1; N-recognin-4; retinoblastoma-associated factor ......
Chromosomal Location	1p36.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between UBR4 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	UBR4
Name	ubiquitin protein ligase E3 component n-recognin 4
Aliases	KIAA1307; KIAA0462; RBAF600; ZUBR1; zinc finger, UBR1 type 1; N-recognin-4; retinoblastoma-associated factor ......
Chromosomal Location	1p36.13
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 UBR4 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	logFC: -2.35; FDR: 0.01650	Resistant to T cell-mediated killing
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
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	UBR4
Name	ubiquitin protein ligase E3 component n-recognin 4
Aliases	KIAA1307; KIAA0462; RBAF600; ZUBR1; zinc finger, UBR1 type 1; N-recognin-4; retinoblastoma-associated factor ......
Chromosomal Location	1p36.13
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 UBR4 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	-0.191	0.303
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.167	0.921
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.451	0.709
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.303	0.434
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.099	0.977
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.814	0.854
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.347	0.421
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.362	0.854
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.329	0.882
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.704	0.756
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	0.259	0.94
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.027	0.454

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of UBR4 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	14.8	9.6	5.2	0.482
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	14.8	11.9	2.9	0.735
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	19	11.8	7.2	0.672
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	30.8	18.2	12.6	0.649
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	33.3	6.2	27.1	0.116
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	11.1	8.9	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	50	0	50	0.109
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	3.7	-1.1	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	7.7	-3.2	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	18.2	0	18.2	0.199
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	33.3	0	33.3	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	UBR4
Name	ubiquitin protein ligase E3 component n-recognin 4
Aliases	KIAA1307; KIAA0462; RBAF600; ZUBR1; zinc finger, UBR1 type 1; N-recognin-4; retinoblastoma-associated factor ......
Chromosomal Location	1p36.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of UBR4. 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	UBR4
Name	ubiquitin protein ligase E3 component n-recognin 4
Aliases	KIAA1307; KIAA0462; RBAF600; ZUBR1; zinc finger, UBR1 type 1; N-recognin-4; retinoblastoma-associated factor ......
Chromosomal Location	1p36.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of UBR4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by UBR4. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	UBR4
Name	ubiquitin protein ligase E3 component n-recognin 4
Aliases	KIAA1307; KIAA0462; RBAF600; ZUBR1; zinc finger, UBR1 type 1; N-recognin-4; retinoblastoma-associated factor ......
Chromosomal Location	1p36.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of UBR4. 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	UBR4
Name	ubiquitin protein ligase E3 component n-recognin 4
Aliases	KIAA1307; KIAA0462; RBAF600; ZUBR1; zinc finger, UBR1 type 1; N-recognin-4; retinoblastoma-associated factor ......
Chromosomal Location	1p36.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of UBR4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	UBR4
Name	ubiquitin protein ligase E3 component n-recognin 4
Aliases	KIAA1307; KIAA0462; RBAF600; ZUBR1; zinc finger, UBR1 type 1; N-recognin-4; retinoblastoma-associated factor ......
Chromosomal Location	1p36.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between UBR4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	UBR4
Name	ubiquitin protein ligase E3 component n-recognin 4
Aliases	KIAA1307; KIAA0462; RBAF600; ZUBR1; zinc finger, UBR1 type 1; N-recognin-4; retinoblastoma-associated factor ......
Chromosomal Location	1p36.13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting UBR4 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting UBR4.

ID	Name	Drug Type	Targets	#Targets
DB04959	HspE7	Biotech	KRT7, UBR4	2
DB05483	PCL-016	Small Molecule	UBR4, ZFY	2

Browse UBR4