TISIDB

Summary
Symbol	OTC
Name	ornithine carbamoyltransferase
Aliases	OTCase; ornithine transcarbamylase; Ornithine carbamoyltransferase, mitochondrial
Chromosomal Location	Xp21.1
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	Mitochondrion matrix.
Domain	PF00185 Aspartate/ornithine carbamoyltransferase PF02729 Aspartate/ornithine carbamoyltransferase
Function	-

> Gene Ontology [ TOP ]
Biological Process	GO:0000050 urea cycle GO:0000052 citrulline metabolic process GO:0001101 response to acid chemical GO:0001889 liver development GO:0006520 cellular amino acid metabolic process GO:0006525 arginine metabolic process GO:0006526 arginine biosynthetic process GO:0006591 ornithine metabolic process GO:0006593 ornithine catabolic process GO:0007494 midgut development GO:0007584 response to nutrient GO:0008652 cellular amino acid biosynthetic process GO:0009063 cellular amino acid catabolic process GO:0009064 glutamine family amino acid metabolic process GO:0009084 glutamine family amino acid biosynthetic process GO:0009991 response to extracellular stimulus GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0010043 response to zinc ion GO:0016053 organic acid biosynthetic process GO:0016054 organic acid catabolic process GO:0019240 citrulline biosynthetic process GO:0019627 urea metabolic process GO:0031667 response to nutrient levels GO:0032868 response to insulin GO:0033273 response to vitamin GO:0042450 arginine biosynthetic process via ornithine GO:0042493 response to drug GO:0043434 response to peptide hormone GO:0044282 small molecule catabolic process GO:0044283 small molecule biosynthetic process GO:0046394 carboxylic acid biosynthetic process GO:0046395 carboxylic acid catabolic process GO:0048565 digestive tract development GO:0048732 gland development GO:0051259 protein oligomerization GO:0051260 protein homooligomerization GO:0055081 anion homeostasis GO:0055123 digestive system development GO:0061008 hepaticobiliary system development GO:0070206 protein trimerization GO:0070207 protein homotrimerization GO:0070781 response to biotin GO:0071941 nitrogen cycle metabolic process GO:0097272 ammonia homeostasis GO:1901565 organonitrogen compound catabolic process GO:1901605 alpha-amino acid metabolic process GO:1901607 alpha-amino acid biosynthetic process GO:1901652 response to peptide GO:1990267 response to transition metal nanoparticle
Molecular Function	GO:0004585 ornithine carbamoyltransferase activity GO:0005543 phospholipid binding GO:0016597 amino acid binding GO:0016741 transferase activity, transferring one-carbon groups GO:0016743 carboxyl- or carbamoyltransferase activity GO:0031406 carboxylic acid binding GO:0042301 phosphate ion binding GO:0043168 anion binding
Cellular Component	GO:0005743 mitochondrial inner membrane GO:0005759 mitochondrial matrix

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa01100 Metabolic pathways hsa01230 Biosynthesis of amino acids
Reactome	R-HSA-1430728: Metabolism R-HSA-71291: Metabolism of amino acids and derivatives R-HSA-351202: Metabolism of polyamines R-HSA-70635: Urea cycle

Summary
Symbol	OTC
Name	ornithine carbamoyltransferase
Aliases	OTCase; ornithine transcarbamylase; Ornithine carbamoyltransferase, mitochondrial
Chromosomal Location	Xp21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between OTC 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	OTC
Name	ornithine carbamoyltransferase
Aliases	OTCase; ornithine transcarbamylase; Ornithine carbamoyltransferase, mitochondrial
Chromosomal Location	Xp21.1
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

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Statistical results of OTC 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: 0.66	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	OTC
Name	ornithine carbamoyltransferase
Aliases	OTCase; ornithine transcarbamylase; Ornithine carbamoyltransferase, mitochondrial
Chromosomal Location	Xp21.1
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

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Points in the above scatter plot represent the expression difference of OTC 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	0.494	0.293
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.043	0.957
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.897	0.211
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.518	0.533
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.683	0.165
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.954	0.495
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.448	0.632
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.016	0.564
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.301	0.867
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.299	0.813
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	0.792	0.629
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.709	0.0268

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of OTC in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	4.1	-4.1	0.561
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	OTC
Name	ornithine carbamoyltransferase
Aliases	OTCase; ornithine transcarbamylase; Ornithine carbamoyltransferase, mitochondrial
Chromosomal Location	Xp21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of OTC. 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	OTC
Name	ornithine carbamoyltransferase
Aliases	OTCase; ornithine transcarbamylase; Ornithine carbamoyltransferase, mitochondrial
Chromosomal Location	Xp21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of OTC. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by OTC. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	OTC
Name	ornithine carbamoyltransferase
Aliases	OTCase; ornithine transcarbamylase; Ornithine carbamoyltransferase, mitochondrial
Chromosomal Location	Xp21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of OTC. 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	OTC
Name	ornithine carbamoyltransferase
Aliases	OTCase; ornithine transcarbamylase; Ornithine carbamoyltransferase, mitochondrial
Chromosomal Location	Xp21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of OTC expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	OTC
Name	ornithine carbamoyltransferase
Aliases	OTCase; ornithine transcarbamylase; Ornithine carbamoyltransferase, mitochondrial
Chromosomal Location	Xp21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between OTC and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	OTC
Name	ornithine carbamoyltransferase
Aliases	OTCase; ornithine transcarbamylase; Ornithine carbamoyltransferase, mitochondrial
Chromosomal Location	Xp21.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting OTC collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting OTC.

ID	Name	Drug Type	Targets	#Targets
DB00129	Ornithine	Small Molecule	ARG1, ARG2, GATM, OAT, OAZ1, OAZ2, OAZ3, OTC, SLC25A15, SLC25A2, S ......	14
DB00155	L-Citrulline	Small Molecule	ASS1, DDAH1, DDAH2, NOS1, NOS2, NOS3, OTC, PADI1, PADI2, PADI3, PA ......	12
DB02011	N-(Phosphonoacetyl)-L-Ornithine	Small Molecule	OTC	1
DB04185	Norvaline	Small Molecule	GATM, OTC	2

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