TISIDB

Summary
Symbol	RBCK1
Name	RanBP-type and C3HC4-type zinc finger containing 1
Aliases	RBCK2; RNF54; ZRANB4; UBCE7IP3; HOIL1; heme-oxidized IRP2 ubiquitin ligase 1; C20orf18; chromosome 20 open r ......
Chromosomal Location	20p13
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	-
Domain	PF01485 IBR domain PF13445 RING-type zinc-finger
Function	E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, such as UBE2L3/UBCM4, and then transfers it to substrates. Functions as an E3 ligase for oxidized IREB2 and both heme and oxygen are necessary for IREB2 ubiquitination. Promotes ubiquitination of TAB2 and IRF3 and their degradation by the proteasome. Component of the LUBAC complex which conjugates linear ('Met-1'-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation. LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways. Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation. LUBAC is proposed to be recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex. Together with FAM105B/otulin, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis. Binds polyubiquitin of different linkage types.

> Gene Ontology [ TOP ]
Biological Process	GO:0000209 protein polyubiquitination GO:0001959 regulation of cytokine-mediated signaling pathway GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0006606 protein import into nucleus GO:0006913 nucleocytoplasmic transport GO:0007249 I-kappaB kinase/NF-kappaB signaling GO:0010498 proteasomal protein catabolic process GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway GO:0010939 regulation of necrotic cell death GO:0017038 protein import GO:0031503 protein complex localization GO:0032088 negative regulation of NF-kappaB transcription factor activity GO:0032386 regulation of intracellular transport GO:0032388 positive regulation of intracellular transport GO:0033157 regulation of intracellular protein transport GO:0033209 tumor necrosis factor-mediated signaling pathway GO:0034504 protein localization to nucleus GO:0034612 response to tumor necrosis factor GO:0042306 regulation of protein import into nucleus GO:0042307 positive regulation of protein import into nucleus GO:0042345 regulation of NF-kappaB import into nucleus GO:0042346 positive regulation of NF-kappaB import into nucleus GO:0042348 NF-kappaB import into nucleus GO:0042990 regulation of transcription factor import into nucleus GO:0042991 transcription factor import into nucleus GO:0042993 positive regulation of transcription factor import into nucleus GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity GO:0044744 protein targeting to nucleus GO:0046822 regulation of nucleocytoplasmic transport GO:0046824 positive regulation of nucleocytoplasmic transport GO:0050851 antigen receptor-mediated signaling pathway GO:0050852 T cell receptor signaling pathway GO:0051090 regulation of sequence-specific DNA binding transcription factor activity GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity GO:0051092 positive regulation of NF-kappaB transcription factor activity GO:0051169 nuclear transport GO:0051170 nuclear import GO:0051222 positive regulation of protein transport GO:0060544 regulation of necroptotic process GO:0060546 negative regulation of necroptotic process GO:0060547 negative regulation of necrotic cell death GO:0060759 regulation of response to cytokine stimulus GO:0070265 necrotic cell death GO:0070266 necroptotic process GO:0071356 cellular response to tumor necrosis factor GO:0090316 positive regulation of intracellular protein transport GO:0097039 protein linear polyubiquitination GO:0097191 extrinsic apoptotic signaling pathway GO:0097300 programmed necrotic cell death GO:1900180 regulation of protein localization to nucleus GO:1900182 positive regulation of protein localization to nucleus GO:1902593 single-organism nuclear import GO:1903533 regulation of protein targeting GO:1903829 positive regulation of cellular protein localization GO:1904589 regulation of protein import GO:1904591 positive regulation of protein import GO:1904951 positive regulation of establishment of protein localization GO:2001233 regulation of apoptotic signaling pathway GO:2001235 positive regulation of apoptotic signaling pathway GO:2001236 regulation of extrinsic apoptotic signaling pathway GO:2001238 positive regulation of extrinsic apoptotic signaling pathway
Molecular Function	GO:0004842 ubiquitin-protein transferase activity GO:0016874 ligase activity GO:0019787 ubiquitin-like protein transferase activity GO:0032182 ubiquitin-like protein binding GO:0043130 ubiquitin binding
Cellular Component	GO:0000151 ubiquitin ligase complex GO:0071797 LUBAC complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04621 NOD-like receptor signaling pathway
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-983168: Antigen processing R-HSA-983169: Class I MHC mediated antigen processing & presentation R-HSA-73887: Death Receptor Signalling R-HSA-168256: Immune System R-HSA-5357905: Regulation of TNFR1 signaling R-HSA-162582: Signal Transduction R-HSA-75893: TNF signaling R-HSA-5357956: TNFR1-induced NFkappaB signaling pathway

Summary
Symbol	RBCK1
Name	RanBP-type and C3HC4-type zinc finger containing 1
Aliases	RBCK2; RNF54; ZRANB4; UBCE7IP3; HOIL1; heme-oxidized IRP2 ubiquitin ligase 1; C20orf18; chromosome 20 open r ......
Chromosomal Location	20p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between RBCK1 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	RBCK1
Name	RanBP-type and C3HC4-type zinc finger containing 1
Aliases	RBCK2; RNF54; ZRANB4; UBCE7IP3; HOIL1; heme-oxidized IRP2 ubiquitin ligase 1; C20orf18; chromosome 20 open r ......
Chromosomal Location	20p13
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 RBCK1 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: -1.96; 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	STARS Score: 4.32; FDR: 0.012	Resistant to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX	STARS Score: 3.55; FDR: 0.048	Resistant to T cell-mediated killing
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	RBCK1
Name	RanBP-type and C3HC4-type zinc finger containing 1
Aliases	RBCK2; RNF54; ZRANB4; UBCE7IP3; HOIL1; heme-oxidized IRP2 ubiquitin ligase 1; C20orf18; chromosome 20 open r ......
Chromosomal Location	20p13
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 RBCK1 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	-0.16	0.551
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.506	0.827
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.088	0.96
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.487	0.262
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.531	0.814
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.435	0.882
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.042	0.918
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.068	0.966
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.131	0.943
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.016	0.994
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	-0.289	0.926
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.062	0.383

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of RBCK1 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	1.4	2.3	0.469
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	1.7	2	0.532
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	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	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	RBCK1
Name	RanBP-type and C3HC4-type zinc finger containing 1
Aliases	RBCK2; RNF54; ZRANB4; UBCE7IP3; HOIL1; heme-oxidized IRP2 ubiquitin ligase 1; C20orf18; chromosome 20 open r ......
Chromosomal Location	20p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of RBCK1. 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	RBCK1
Name	RanBP-type and C3HC4-type zinc finger containing 1
Aliases	RBCK2; RNF54; ZRANB4; UBCE7IP3; HOIL1; heme-oxidized IRP2 ubiquitin ligase 1; C20orf18; chromosome 20 open r ......
Chromosomal Location	20p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of RBCK1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by RBCK1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	RBCK1
Name	RanBP-type and C3HC4-type zinc finger containing 1
Aliases	RBCK2; RNF54; ZRANB4; UBCE7IP3; HOIL1; heme-oxidized IRP2 ubiquitin ligase 1; C20orf18; chromosome 20 open r ......
Chromosomal Location	20p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of RBCK1. 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	RBCK1
Name	RanBP-type and C3HC4-type zinc finger containing 1
Aliases	RBCK2; RNF54; ZRANB4; UBCE7IP3; HOIL1; heme-oxidized IRP2 ubiquitin ligase 1; C20orf18; chromosome 20 open r ......
Chromosomal Location	20p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of RBCK1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	RBCK1
Name	RanBP-type and C3HC4-type zinc finger containing 1
Aliases	RBCK2; RNF54; ZRANB4; UBCE7IP3; HOIL1; heme-oxidized IRP2 ubiquitin ligase 1; C20orf18; chromosome 20 open r ......
Chromosomal Location	20p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between RBCK1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	RBCK1
Name	RanBP-type and C3HC4-type zinc finger containing 1
Aliases	RBCK2; RNF54; ZRANB4; UBCE7IP3; HOIL1; heme-oxidized IRP2 ubiquitin ligase 1; C20orf18; chromosome 20 open r ......
Chromosomal Location	20p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting RBCK1 collected from DrugBank database.

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

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