TISIDB

Summary
Symbol	ANG
Name	angiogenin, ribonuclease, RNase A family, 5
Aliases	RNASE5; RAA1; ALS9; HEL168; RNase 5; epididymis luminal protein 168; ribonuclease 5; ribonuclease A A1; Angi ......
Chromosomal Location	14q11.1-q11.2
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	Cytoplasmic vesicle, secretory vesicle lumen Secreted Nucleus Nucleus, nucleolus Note=Rapidly endocytosed by target cells and translocated to the nucleus where it accumulates in the nucleolus and binds to DNA (PubMed:12051708).
Domain	PF00074 Pancreatic ribonuclease
Function	Binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus. Stimulates ribosomal RNA synthesis including that containing the initiation site sequences of 45S rRNA. Cleaves tRNA within anticodon loops to produce tRNA-derived stress-induced fragments (tiRNAs) which inhibit protein synthesis and triggers the assembly of stress granules (SGs). Angiogenin induces vascularization of normal and malignant tissues. Angiogenic activity is regulated by interaction with RNH1 in vivo.

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0001541 ovarian follicle development GO:0001556 oocyte maturation GO:0001666 response to hypoxia GO:0001878 response to yeast GO:0001890 placenta development GO:0001935 endothelial cell proliferation GO:0001936 regulation of endothelial cell proliferation GO:0001938 positive regulation of endothelial cell proliferation GO:0006417 regulation of translation GO:0006638 neutral lipid metabolic process GO:0006639 acylglycerol metabolic process GO:0006651 diacylglycerol biosynthetic process GO:0006959 humoral immune response GO:0007015 actin filament organization GO:0007202 activation of phospholipase C activity GO:0007281 germ cell development GO:0007292 female gamete generation GO:0007548 sex differentiation GO:0008154 actin polymerization or depolymerization GO:0008406 gonad development GO:0008585 female gonad development GO:0009303 rRNA transcription GO:0009306 protein secretion GO:0009620 response to fungus GO:0009994 oocyte differentiation GO:0010517 regulation of phospholipase activity GO:0010518 positive regulation of phospholipase activity GO:0010608 posttranscriptional regulation of gene expression GO:0010863 positive regulation of phospholipase C activity GO:0017148 negative regulation of translation GO:0019730 antimicrobial humoral response GO:0019731 antibacterial humoral response GO:0019732 antifungal humoral response GO:0021700 developmental maturation GO:0022412 cellular process involved in reproduction in multicellular organism GO:0022602 ovulation cycle process GO:0030041 actin filament polymerization GO:0032147 activation of protein kinase activity GO:0032148 activation of protein kinase B activity GO:0032429 regulation of phospholipase A2 activity GO:0032430 positive regulation of phospholipase A2 activity GO:0032431 activation of phospholipase A2 activity GO:0033002 muscle cell proliferation GO:0033674 positive regulation of kinase activity GO:0034248 regulation of cellular amide metabolic process GO:0034249 negative regulation of cellular amide metabolic process GO:0034330 cell junction organization GO:0034332 adherens junction organization GO:0036293 response to decreased oxygen levels GO:0042698 ovulation cycle GO:0042742 defense response to bacterium GO:0045017 glycerolipid biosynthetic process GO:0045137 development of primary sexual characteristics GO:0045216 cell-cell junction organization GO:0045860 positive regulation of protein kinase activity GO:0046339 diacylglycerol metabolic process GO:0046460 neutral lipid biosynthetic process GO:0046463 acylglycerol biosynthetic process GO:0046486 glycerolipid metabolic process GO:0046545 development of primary female sexual characteristics GO:0046660 female sex differentiation GO:0048469 cell maturation GO:0048477 oogenesis GO:0048511 rhythmic process GO:0048514 blood vessel morphogenesis GO:0048599 oocyte development GO:0048608 reproductive structure development GO:0048659 smooth muscle cell proliferation GO:0048660 regulation of smooth muscle cell proliferation GO:0048662 negative regulation of smooth muscle cell proliferation GO:0050673 epithelial cell proliferation GO:0050678 regulation of epithelial cell proliferation GO:0050679 positive regulation of epithelial cell proliferation GO:0050708 regulation of protein secretion GO:0050714 positive regulation of protein secretion GO:0050830 defense response to Gram-positive bacterium GO:0050832 defense response to fungus GO:0051047 positive regulation of secretion GO:0051222 positive regulation of protein transport GO:0051258 protein polymerization GO:0060191 regulation of lipase activity GO:0060193 positive regulation of lipase activity GO:0061458 reproductive system development GO:0070482 response to oxygen levels GO:0090305 nucleic acid phosphodiester bond hydrolysis GO:0090501 RNA phosphodiester bond hydrolysis GO:0098542 defense response to other organism GO:0098781 ncRNA transcription GO:1900274 regulation of phospholipase C activity GO:1903532 positive regulation of secretion by cell GO:1904951 positive regulation of establishment of protein localization
Molecular Function	GO:0003779 actin binding GO:0004518 nuclease activity GO:0004519 endonuclease activity GO:0004540 ribonuclease activity GO:0005507 copper ion binding GO:0005539 glycosaminoglycan binding GO:0008201 heparin binding GO:0019843 rRNA binding GO:0033218 amide binding GO:0042277 peptide binding GO:1901681 sulfur compound binding
Cellular Component	GO:0005578 proteinaceous extracellular matrix GO:0005604 basement membrane GO:0005605 basal lamina GO:0030426 growth cone GO:0030427 site of polarized growth GO:0032311 angiogenin-PRI complex GO:0043025 neuronal cell body GO:0044297 cell body GO:0044420 extracellular matrix component

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-418990: Adherens junctions interactions R-HSA-446728: Cell junction organization R-HSA-1500931: Cell-Cell communication R-HSA-421270: Cell-cell junction organization

Summary
Symbol	ANG
Name	angiogenin, ribonuclease, RNase A family, 5
Aliases	RNASE5; RAA1; ALS9; HEL168; RNase 5; epididymis luminal protein 168; ribonuclease 5; ribonuclease A A1; Angi ......
Chromosomal Location	14q11.1-q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ANG 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	ANG
Name	angiogenin, ribonuclease, RNase A family, 5
Aliases	RNASE5; RAA1; ALS9; HEL168; RNase 5; epididymis luminal protein 168; ribonuclease 5; ribonuclease A A1; Angi ......
Chromosomal Location	14q11.1-q11.2
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 ANG 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: 0.62	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	ANG
Name	angiogenin, ribonuclease, RNase A family, 5
Aliases	RNASE5; RAA1; ALS9; HEL168; RNase 5; epididymis luminal protein 168; ribonuclease 5; ribonuclease A A1; Angi ......
Chromosomal Location	14q11.1-q11.2
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 ANG 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	0.413	0.462
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.189	0.914
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.868	0.443
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.27	0.69
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.022	0.985
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.631	0.677
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.386	0.437
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.614	0.447
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.021	0.983
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-1.062	0.477
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	-0.238	0.912
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.223	0.133

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ANG 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	7.4	0	7.4	0.0709
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	7.4	0	7.4	0.096
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	16.7	-16.7	0.429
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	3.7	-1.1	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	7.1	-7.1	0.467
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	ANG
Name	angiogenin, ribonuclease, RNase A family, 5
Aliases	RNASE5; RAA1; ALS9; HEL168; RNase 5; epididymis luminal protein 168; ribonuclease 5; ribonuclease A A1; Angi ......
Chromosomal Location	14q11.1-q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ANG. 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	ANG
Name	angiogenin, ribonuclease, RNase A family, 5
Aliases	RNASE5; RAA1; ALS9; HEL168; RNase 5; epididymis luminal protein 168; ribonuclease 5; ribonuclease A A1; Angi ......
Chromosomal Location	14q11.1-q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ANG. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ANG. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ANG
Name	angiogenin, ribonuclease, RNase A family, 5
Aliases	RNASE5; RAA1; ALS9; HEL168; RNase 5; epididymis luminal protein 168; ribonuclease 5; ribonuclease A A1; Angi ......
Chromosomal Location	14q11.1-q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ANG. 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	ANG
Name	angiogenin, ribonuclease, RNase A family, 5
Aliases	RNASE5; RAA1; ALS9; HEL168; RNase 5; epididymis luminal protein 168; ribonuclease 5; ribonuclease A A1; Angi ......
Chromosomal Location	14q11.1-q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ANG expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ANG
Name	angiogenin, ribonuclease, RNase A family, 5
Aliases	RNASE5; RAA1; ALS9; HEL168; RNase 5; epididymis luminal protein 168; ribonuclease 5; ribonuclease A A1; Angi ......
Chromosomal Location	14q11.1-q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ANG and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ANG
Name	angiogenin, ribonuclease, RNase A family, 5
Aliases	RNASE5; RAA1; ALS9; HEL168; RNase 5; epididymis luminal protein 168; ribonuclease 5; ribonuclease A A1; Angi ......
Chromosomal Location	14q11.1-q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ANG collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting ANG.

ID	Name	Drug Type	Targets	#Targets
DB03088	Pidolic Acid	Small Molecule	ADAM28, AMY1A, AMY2A, AMY2B, ANG, CCL8, HCRT, KRTAP5-2, TFF2, VEGF ......	10
DB04272	Citric Acid	Small Molecule	AKR1B1, ANG, APRT, BHMT, C8G, CPB1, CS, CTDSP1, GNMT, HGS, HS3ST3A ......	23

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