TISIDB

Summary
Symbol	OTULIN
Name	OTU deubiquitinase with linear linkage specificity
Aliases	FLJ34884; gumby; FAM105B; family with sequence similarity 105, member B; GUM; OTU domain-containing deubiqui ......
Chromosomal Location	5p15.2
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
Domain	PF16218 Peptidase family C101
Function	Deubiquitinase that specifically removes linear ('Met-1'-linked) polyubiquitin chains to substrates and acts as a regulator of angiogenesis and innate immune response (PubMed:23708998, PubMed:23746843, PubMed:23806334, PubMed:23827681, PubMed:27523608, PubMed:27559085, PubMed:24726323, PubMed:24726327). Associates with the LUBAC complex via direct interaction with RNF31 and counteracts its action by cleaving linear polyubiquitin chains to substrates (PubMed:23708998, PubMed:23746843, PubMed:23806334, PubMed:23827681, PubMed:24726323, PubMed:24726327). Required during angiogenesis, craniofacial and neuronal development by regulating the canonical Wnt signaling together with the LUBAC complex (PubMed:23708998). Acts as a negative regulator of NF-kappa-B by counteracting activity of the LUBAC complex (PubMed:23746843, PubMed:23806334). Required for homeostasis of the LUBAC complex by restricting autoubiquination of the LUBAC complex subunit RNF31 (PubMed:24726323). Some results have suggested that OTULIN function is restricted to homeostasis of the LUBAC complex, because it is not stably associated with TNF or NOD2 receptor signaling complexes (RSCs) (PubMed:26670046). However, further report have shown that it plays active roles in receptor signaling (PubMed:26997266, PubMed:27523608). Acts as a key negative regulator of inflammation by restricting spontaneous inflammation and maintaining immune homeostasis (PubMed:27523608). In myeloid cell, required to prevent unwarranted secretion of cytokines leading to inflammation and autoimmunity by restricting linear polyubiquitin formation (PubMed:27523608). Plays a key role in innate immune response by restricting linear polyubiquitin formation on RIPK2 in response to NOD2 stimulation, probably to limit NOD2-dependent proinflammatory signaling (PubMed:23806334).

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0001959 regulation of cytokine-mediated signaling pathway GO:0002040 sprouting angiogenesis GO:0002218 activation of innate immune response GO:0002221 pattern recognition receptor signaling pathway GO:0002753 cytoplasmic pattern recognition receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway GO:0016055 Wnt signaling pathway GO:0016579 protein deubiquitination GO:0030522 intracellular receptor signaling pathway GO:0031348 negative regulation of defense response GO:0031349 positive regulation of defense response GO:0032088 negative regulation of NF-kappaB transcription factor activity GO:0032102 negative regulation of response to external stimulus GO:0033209 tumor necrosis factor-mediated signaling pathway GO:0034612 response to tumor necrosis factor GO:0035872 nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0048514 blood vessel morphogenesis GO:0050727 regulation of inflammatory response GO:0050728 negative regulation of inflammatory response GO:0051090 regulation of sequence-specific DNA binding transcription factor activity GO:0060070 canonical Wnt signaling pathway GO:0060759 regulation of response to cytokine stimulus GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway GO:0070431 nucleotide-binding oligomerization domain containing 2 signaling pathway GO:0070646 protein modification by small protein removal GO:0071356 cellular response to tumor necrosis factor GO:0198738 cell-cell signaling by wnt GO:1990108 protein linear deubiquitination
Molecular Function	GO:0004843 thiol-dependent ubiquitin-specific protease activity GO:0008234 cysteine-type peptidase activity GO:0019783 ubiquitin-like protein-specific protease activity GO:0036459 thiol-dependent ubiquitinyl hydrolase activity GO:0101005 ubiquitinyl hydrolase activity
Cellular Component	GO:0000151 ubiquitin ligase complex GO:0071797 LUBAC complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-73887: Death Receptor Signalling R-HSA-392499: Metabolism of proteins R-HSA-597592: Post-translational protein modification R-HSA-8852135: Protein ubiquitination R-HSA-5357905: Regulation of TNFR1 signaling R-HSA-162582: Signal Transduction R-HSA-8866652: Synthesis of active ubiquitin R-HSA-75893: TNF signaling

Summary
Symbol	OTULIN
Name	OTU deubiquitinase with linear linkage specificity
Aliases	FLJ34884; gumby; FAM105B; family with sequence similarity 105, member B; GUM; OTU domain-containing deubiqui ......
Chromosomal Location	5p15.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between OTULIN 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	OTULIN
Name	OTU deubiquitinase with linear linkage specificity
Aliases	FLJ34884; gumby; FAM105B; family with sequence similarity 105, member B; GUM; OTU domain-containing deubiqui ......
Chromosomal Location	5p15.2
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 OTULIN 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: -3.73; FDR: 0.00124	Resistant to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	logFC: -2.39; FDR: 0.04110	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: 4.25; FDR: 0.013	Resistant to T cell-mediated killing
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	OTULIN
Name	OTU deubiquitinase with linear linkage specificity
Aliases	FLJ34884; gumby; FAM105B; family with sequence similarity 105, member B; GUM; OTU domain-containing deubiqui ......
Chromosomal Location	5p15.2
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 OTULIN 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	-0.078	0.669
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.007	0.995
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.133	0.862
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	1
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	1
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	1
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.031	0.926
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.168	0.912
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.173	0.915
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.48	0.612
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	-0.296	0.83
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.05	0.476

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of OTULIN 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	5.9	-5.9	0.447
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	9.1	-9.1	0.458
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	0	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	7.7	-7.7	0.371
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	OTULIN
Name	OTU deubiquitinase with linear linkage specificity
Aliases	FLJ34884; gumby; FAM105B; family with sequence similarity 105, member B; GUM; OTU domain-containing deubiqui ......
Chromosomal Location	5p15.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of OTULIN. 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	OTULIN
Name	OTU deubiquitinase with linear linkage specificity
Aliases	FLJ34884; gumby; FAM105B; family with sequence similarity 105, member B; GUM; OTU domain-containing deubiqui ......
Chromosomal Location	5p15.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of OTULIN. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by OTULIN. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	OTULIN
Name	OTU deubiquitinase with linear linkage specificity
Aliases	FLJ34884; gumby; FAM105B; family with sequence similarity 105, member B; GUM; OTU domain-containing deubiqui ......
Chromosomal Location	5p15.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of OTULIN. 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	OTULIN
Name	OTU deubiquitinase with linear linkage specificity
Aliases	FLJ34884; gumby; FAM105B; family with sequence similarity 105, member B; GUM; OTU domain-containing deubiqui ......
Chromosomal Location	5p15.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of OTULIN expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	OTULIN
Name	OTU deubiquitinase with linear linkage specificity
Aliases	FLJ34884; gumby; FAM105B; family with sequence similarity 105, member B; GUM; OTU domain-containing deubiqui ......
Chromosomal Location	5p15.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between OTULIN and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	OTULIN
Name	OTU deubiquitinase with linear linkage specificity
Aliases	FLJ34884; gumby; FAM105B; family with sequence similarity 105, member B; GUM; OTU domain-containing deubiqui ......
Chromosomal Location	5p15.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting OTULIN collected from DrugBank database.

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

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