TISIDB

Summary
Symbol	ARIH1
Name	ariadne RBR E3 ubiquitin protein ligase 1
Aliases	HARI; HHARI; UBCH7BP; ARI; ariadne, Drosophila, homolog of; ariadne (Drosophila) homolog, ubiquitin-conjugat ......
Chromosomal Location	15q24
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 Nucleus, Cajal body Note=Mainly cytoplasmic (PubMed:11278816). Present in Lewy body (PubMed:21590270).
Domain	PF01485 IBR domain
Function	E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3 (PubMed:15236971, PubMed:21532592, PubMed:24076655, PubMed:27565346, PubMed:23707686). Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-RING ubiquitin ligase (CRL) complexes and initiating ubiquitination of CRL substrates: associates with CRL complexes and specifically mediates addition of the first ubiquitin on CRLs targets (PubMed:27565346). The initial ubiquitin is then elongated by CDC34/UBE2R1 and UBE2R2 (PubMed:27565346). E3 ubiquitin-protein ligase activity is activated upon binding to neddylated cullin-RING ubiquitin ligase complexes (PubMed:24076655, PubMed:27565346). Plays a role in protein translation in response to DNA damage by mediating ubiquitination of EIF4E2, the consequences of EIF4E2 ubiquitination are however unclear (PubMed:25624349). According to a report, EIF4E2 ubiquitination leads to promote EIF4E2 cap-binding and protein translation arrest (PubMed:25624349). According to another report EIF4E2 ubiquitination leads to its subsequent degradation (PubMed:14623119). Acts as the ligase involved in ISGylation of EIF4E2 (PubMed:17289916).

> Gene Ontology [ TOP ]
Biological Process	GO:0000209 protein polyubiquitination GO:0009894 regulation of catabolic process GO:0009896 positive regulation of catabolic process GO:0010498 proteasomal protein catabolic process GO:0031329 regulation of cellular catabolic process GO:0031331 positive regulation of cellular catabolic process GO:0032434 regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0042176 regulation of protein catabolic process GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0045732 positive regulation of protein catabolic process GO:0045862 positive regulation of proteolysis GO:0061136 regulation of proteasomal protein catabolic process 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:1903362 regulation of cellular protein catabolic process GO:1903364 positive regulation of cellular protein catabolic process
Molecular Function	GO:0004842 ubiquitin-protein transferase activity GO:0016874 ligase activity GO:0019787 ubiquitin-like protein transferase activity GO:0031624 ubiquitin conjugating enzyme binding GO:0031625 ubiquitin protein ligase binding GO:0044389 ubiquitin-like protein ligase binding GO:0044390 ubiquitin-like protein conjugating enzyme binding GO:0061630 ubiquitin protein ligase activity GO:0061659 ubiquitin-like protein ligase activity
Cellular Component	GO:0000151 ubiquitin ligase complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-1169410: Antiviral mechanism by IFN-stimulated genes R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-1169408: ISG15 antiviral mechanism R-HSA-168256: Immune System R-HSA-913531: Interferon Signaling

Summary
Symbol	ARIH1
Name	ariadne RBR E3 ubiquitin protein ligase 1
Aliases	HARI; HHARI; UBCH7BP; ARI; ariadne, Drosophila, homolog of; ariadne (Drosophila) homolog, ubiquitin-conjugat ......
Chromosomal Location	15q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ARIH1 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	ARIH1
Name	ariadne RBR E3 ubiquitin protein ligase 1
Aliases	HARI; HHARI; UBCH7BP; ARI; ariadne, Drosophila, homolog of; ariadne (Drosophila) homolog, ubiquitin-conjugat ......
Chromosomal Location	15q24
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 ARIH1 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: 0.72	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	ARIH1
Name	ariadne RBR E3 ubiquitin protein ligase 1
Aliases	HARI; HHARI; UBCH7BP; ARI; ariadne, Drosophila, homolog of; ariadne (Drosophila) homolog, ubiquitin-conjugat ......
Chromosomal Location	15q24
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 ARIH1 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	0.249	0.3
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.575	0.753
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.01	0.994
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.556	0.0529
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.665	0.752
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.422	0.87
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.089	0.826
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.025	0.989
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.201	0.919
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.327	0.776
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	0.651	0.704
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.002	0.971

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ARIH1 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	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	33.3	-33.3	0.231
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	11.1	0	11.1	0.36
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	25	0	25	0.364
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	ARIH1
Name	ariadne RBR E3 ubiquitin protein ligase 1
Aliases	HARI; HHARI; UBCH7BP; ARI; ariadne, Drosophila, homolog of; ariadne (Drosophila) homolog, ubiquitin-conjugat ......
Chromosomal Location	15q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ARIH1. 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	ARIH1
Name	ariadne RBR E3 ubiquitin protein ligase 1
Aliases	HARI; HHARI; UBCH7BP; ARI; ariadne, Drosophila, homolog of; ariadne (Drosophila) homolog, ubiquitin-conjugat ......
Chromosomal Location	15q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ARIH1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ARIH1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ARIH1
Name	ariadne RBR E3 ubiquitin protein ligase 1
Aliases	HARI; HHARI; UBCH7BP; ARI; ariadne, Drosophila, homolog of; ariadne (Drosophila) homolog, ubiquitin-conjugat ......
Chromosomal Location	15q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ARIH1. 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	ARIH1
Name	ariadne RBR E3 ubiquitin protein ligase 1
Aliases	HARI; HHARI; UBCH7BP; ARI; ariadne, Drosophila, homolog of; ariadne (Drosophila) homolog, ubiquitin-conjugat ......
Chromosomal Location	15q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ARIH1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ARIH1
Name	ariadne RBR E3 ubiquitin protein ligase 1
Aliases	HARI; HHARI; UBCH7BP; ARI; ariadne, Drosophila, homolog of; ariadne (Drosophila) homolog, ubiquitin-conjugat ......
Chromosomal Location	15q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ARIH1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ARIH1
Name	ariadne RBR E3 ubiquitin protein ligase 1
Aliases	HARI; HHARI; UBCH7BP; ARI; ariadne, Drosophila, homolog of; ariadne (Drosophila) homolog, ubiquitin-conjugat ......
Chromosomal Location	15q24
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ARIH1 collected from DrugBank database.

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

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