TISIDB

Summary
Symbol	DTX3L
Name	deltex 3 like, E3 ubiquitin ligase
Aliases	BBAP; rhysin 2; deltex 3-like (Drosophila); B-lymphoma- and BAL-associated protein; deltex 3-like; rhysin-2; ......
Chromosomal Location	3q21.1
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 Nucleus Early endosome membrane Peripheral membrane protein Cytoplasmic side Lysosome membrane Peripheral membrane protein Cytoplasmic side Note=Translocates to the nucleus in response to IFNG or IFNB1 stimulation (PubMed:26479788). Localizes at sites of DNA damage in a PARP1-dependent manner (PubMed:23230272). Localization to early endosomes is increased upon CXCL12 stimulation where it co-localizes with ITCH, CXCL4, HGS and STAM (PubMed:24790097). A minor proportion localizes to lysosomes (PubMed:24790097).
Domain	-
Function	E3 ubiquitin-protein ligase which, in association with ADP-ribosyltransferase PARP9, plays a role in DNA damage repair and in interferon-mediated antiviral responses (PubMed:12670957, PubMed:19818714, PubMed:26479788, PubMed:23230272). Monoubiquitinates several histones, including histone H2A, H2B, H3 and H4 (PubMed:28525742). In response to DNA damage, mediates monoubiquitination of 'Lys-91' of histone H4 (H4K91ub1) (PubMed:19818714). The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 'Lys-20' methylation (H4K20me) (PubMed:19818714). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272). By monoubiquitinating histone H2B HIST1H2BH/H2BJ and thereby promoting chromatin remodeling, positively regulates STAT1-dependent interferon-stimulated gene transcription and thus STAT1-mediated control of viral replication (PubMed:26479788). Independently of its catalytic activity, promotes the sorting of chemokine receptor CXCR4 from early endosome to lysosome following CXCL12 stimulation by reducing E3 ligase ITCH activity and thus ITCH-mediated ubiquitination of endosomal sorting complex required for transport ESCRT-0 components HGS and STAM (PubMed:24790097). In addition, required for the recruitment of HGS and STAM to early endosomes (PubMed:24790097). In association with PARP9, plays a role in antiviral responses by mediating 'Lys-48'-linked ubiquitination of encephalomyocarditis virus (EMCV) and human rhinovirus (HRV) C3 proteases and thus promoting their proteosomal-mediated degradation (PubMed:26479788).

> Gene Ontology [ TOP ]
Biological Process	GO:0000209 protein polyubiquitination GO:0006302 double-strand break repair GO:0006513 protein monoubiquitination GO:0010390 histone monoubiquitination GO:0016570 histone modification GO:0016574 histone ubiquitination
Molecular Function	GO:0004842 ubiquitin-protein transferase activity GO:0016874 ligase activity GO:0019787 ubiquitin-like protein transferase activity GO:0042393 histone binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04330 Notch 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-168256: Immune System

Summary
Symbol	DTX3L
Name	deltex 3 like, E3 ubiquitin ligase
Aliases	BBAP; rhysin 2; deltex 3-like (Drosophila); B-lymphoma- and BAL-associated protein; deltex 3-like; rhysin-2; ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between DTX3L 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	DTX3L
Name	deltex 3 like, E3 ubiquitin ligase
Aliases	BBAP; rhysin 2; deltex 3-like (Drosophila); B-lymphoma- and BAL-associated protein; deltex 3-like; rhysin-2; ......
Chromosomal Location	3q21.1
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 DTX3L 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	logFC: -2.69; FDR: 0.02860	Resistant to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
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	DTX3L
Name	deltex 3 like, E3 ubiquitin ligase
Aliases	BBAP; rhysin 2; deltex 3-like (Drosophila); B-lymphoma- and BAL-associated protein; deltex 3-like; rhysin-2; ......
Chromosomal Location	3q21.1
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

[ TOP ]

Points in the above scatter plot represent the expression difference of DTX3L 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	0.127	0.617
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.311	0.868
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.004	0.998
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.506	0.165
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.37	0.86
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.681	0.803
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.423	0.414
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.621	0.733
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.199	0.922
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.7	0.627
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	0.915	0.676
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.216	0.00964

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of DTX3L 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	0	2.7	-2.7	1
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	0	3.4	-3.4	1
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	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
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	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	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	DTX3L
Name	deltex 3 like, E3 ubiquitin ligase
Aliases	BBAP; rhysin 2; deltex 3-like (Drosophila); B-lymphoma- and BAL-associated protein; deltex 3-like; rhysin-2; ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of DTX3L. 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	DTX3L
Name	deltex 3 like, E3 ubiquitin ligase
Aliases	BBAP; rhysin 2; deltex 3-like (Drosophila); B-lymphoma- and BAL-associated protein; deltex 3-like; rhysin-2; ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of DTX3L. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by DTX3L. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	DTX3L
Name	deltex 3 like, E3 ubiquitin ligase
Aliases	BBAP; rhysin 2; deltex 3-like (Drosophila); B-lymphoma- and BAL-associated protein; deltex 3-like; rhysin-2; ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of DTX3L. 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	DTX3L
Name	deltex 3 like, E3 ubiquitin ligase
Aliases	BBAP; rhysin 2; deltex 3-like (Drosophila); B-lymphoma- and BAL-associated protein; deltex 3-like; rhysin-2; ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of DTX3L expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	DTX3L
Name	deltex 3 like, E3 ubiquitin ligase
Aliases	BBAP; rhysin 2; deltex 3-like (Drosophila); B-lymphoma- and BAL-associated protein; deltex 3-like; rhysin-2; ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between DTX3L and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	DTX3L
Name	deltex 3 like, E3 ubiquitin ligase
Aliases	BBAP; rhysin 2; deltex 3-like (Drosophila); B-lymphoma- and BAL-associated protein; deltex 3-like; rhysin-2; ......
Chromosomal Location	3q21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting DTX3L collected from DrugBank database.

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

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