TISIDB

Summary
Symbol	ANGPTL3
Name	angiopoietin-like 3
Aliases	angiopoietin 5; ANGPT5; ANG-5; ANL3; FHBL2; Angiopoietin-like protein 3; Angiopoietin-5; Angiopoietin-relate ......
Chromosomal Location	1p31.3
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	Secreted Cell projection, lamellipodium Note=Colocalized with HSPG2 and activated ITGB3 on podocytes.
Domain	PF00147 Fibrinogen beta and gamma chains
Function	Acts in part as a hepatokine that is involved in regulation of lipid and glucose metabolism (PubMed:11788823, PubMed:12909640, PubMed:23661675, PubMed:25495645). Proposed to play a role in the trafficking of energy substrates to either storage or oxidative tissues in response to food intake (By similarity). Has a stimulatory effect on plasma triglycerides (TG), which is achieved by suppressing plasma TG clearance via inhibition of LPL activity. The inhibition of LPL activity appears to be an indirect mechanism involving recruitment of proprotein convertases PCSK6 and FURIN to LPL leading to cleavage and dissociation of LPL from the cell surface; the function does not require ANGPTL3 proteolytic cleavage but seems to be mediated by the N-terminal domain, and is not inhibited by GPIHBP1 (PubMed:12097324, PubMed:19318355, PubMed:20581395). Can inhibit endothelial lipase, causing increased plasma levels of high density lipoprotein (HDL) cholesterol and phospholipids (PubMed:17110602, PubMed:19028676). Can bind to adipocytes to activate lipolysis, releasing free fatty acids and glycerol (PubMed:12565906). Suppresses LPL specifically in oxidative tissues which is required to route very low density lipoprotein (VLDL)-TG to white adipose tissue (WAT) for storage in response to food; the function may involve cooperation with circulating, liver-derived ANGPTL8 and ANGPTL4 expression in WAT (By similarity). Contributes to lower plasma levels of low density lipoprotein (LDL)-cholesterol by a mechanism that is independent of the canonical pathway implicating APOE and LDLR. May stimulate hypothalamic LPL activity (By similarity). ; FUNCTION: ANGPTL3(17-221): In vitro inhibits LPL activity; not effective on GPIHBP1-stabilized LPL. ; FUNCTION: Involved in angiogenesis. Binds to endothelial cells via integrin alpha-V/beta-3 (ITGAV:ITGB3), activates FAK, MAPK and Akt signaling pathways and induces cell adhesion and cell migration (PubMed:11877390). Secreted from podocytes, may modulate properties of glomerular endothelial cells involving integrin alpha-V/beta-3 and Akt signaling (PubMed:18535744). May increase the motility of podocytes. May induce actin filament rearrangements in podocytes implicating integrin alpha-V/beta-3 and Rac1 activation. Binds to hematopoietic stem cells (HSC) and is involved in the regulation of HSC activity probably implicating down-regulation of IKZF1/IKAROS (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0006066 alcohol metabolic process GO:0006071 glycerol metabolic process GO:0006631 fatty acid metabolic process GO:0006644 phospholipid metabolic process GO:0007160 cell-matrix adhesion GO:0007229 integrin-mediated signaling pathway GO:0008202 steroid metabolic process GO:0008203 cholesterol metabolic process GO:0009395 phospholipid catabolic process GO:0009894 regulation of catabolic process GO:0009896 positive regulation of catabolic process GO:0010517 regulation of phospholipase activity GO:0010519 negative regulation of phospholipase activity GO:0010876 lipid localization GO:0016042 lipid catabolic process GO:0016125 sterol metabolic process GO:0019216 regulation of lipid metabolic process GO:0019400 alditol metabolic process GO:0019751 polyol metabolic process GO:0019915 lipid storage GO:0030335 positive regulation of cell migration GO:0031589 cell-substrate adhesion GO:0040017 positive regulation of locomotion GO:0042632 cholesterol homeostasis GO:0044242 cellular lipid catabolic process GO:0044262 cellular carbohydrate metabolic process GO:0044723 single-organism carbohydrate metabolic process GO:0045765 regulation of angiogenesis GO:0045766 positive regulation of angiogenesis GO:0045834 positive regulation of lipid metabolic process GO:0046434 organophosphate catabolic process GO:0048514 blood vessel morphogenesis GO:0048844 artery morphogenesis GO:0050994 regulation of lipid catabolic process GO:0050996 positive regulation of lipid catabolic process GO:0051004 regulation of lipoprotein lipase activity GO:0051005 negative regulation of lipoprotein lipase activity GO:0051235 maintenance of location GO:0051272 positive regulation of cellular component movement GO:0051346 negative regulation of hydrolase activity GO:0055088 lipid homeostasis GO:0055090 acylglycerol homeostasis GO:0055091 phospholipid homeostasis GO:0055092 sterol homeostasis GO:0060191 regulation of lipase activity GO:0060192 negative regulation of lipase activity GO:0060840 artery development GO:0070328 triglyceride homeostasis GO:1901342 regulation of vasculature development GO:1901615 organic hydroxy compound metabolic process GO:1902652 secondary alcohol metabolic process GO:1904018 positive regulation of vasculature development GO:2000147 positive regulation of cell motility
Molecular Function	GO:0004857 enzyme inhibitor activity GO:0004859 phospholipase inhibitor activity GO:0005178 integrin binding GO:0005539 glycosaminoglycan binding GO:0008083 growth factor activity GO:0008201 heparin binding GO:0050839 cell adhesion molecule binding GO:0055102 lipase inhibitor activity GO:1901681 sulfur compound binding
Cellular Component	GO:0005769 early endosome GO:0030027 lamellipodium GO:0031252 cell leading edge

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-174800: Chylomicron-mediated lipid transport R-HSA-73923: Lipid digestion, mobilization, and transport R-HSA-174824: Lipoprotein metabolism R-HSA-1430728: Metabolism R-HSA-556833: Metabolism of lipids and lipoproteins

Summary
Symbol	ANGPTL3
Name	angiopoietin-like 3
Aliases	angiopoietin 5; ANGPT5; ANG-5; ANL3; FHBL2; Angiopoietin-like protein 3; Angiopoietin-5; Angiopoietin-relate ......
Chromosomal Location	1p31.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ANGPTL3 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	ANGPTL3
Name	angiopoietin-like 3
Aliases	angiopoietin 5; ANGPT5; ANG-5; ANL3; FHBL2; Angiopoietin-like protein 3; Angiopoietin-5; Angiopoietin-relate ......
Chromosomal Location	1p31.3
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 ANGPTL3 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	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	ANGPTL3
Name	angiopoietin-like 3
Aliases	angiopoietin 5; ANGPT5; ANG-5; ANL3; FHBL2; Angiopoietin-like protein 3; Angiopoietin-5; Angiopoietin-relate ......
Chromosomal Location	1p31.3
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 ANGPTL3 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	0.653	0.256
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.002	0.998
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	1.141	0.173
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.354	0.435
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.202	0.892
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-1.062	0.53
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.096	0.927
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.495	0.79
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.815	0.62
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.565	0.695
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	1.848	0.311
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.818	0.0256

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ANGPTL3 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	0	3.7	0.27
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	0	3.7	0.314
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	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	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	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	ANGPTL3
Name	angiopoietin-like 3
Aliases	angiopoietin 5; ANGPT5; ANG-5; ANL3; FHBL2; Angiopoietin-like protein 3; Angiopoietin-5; Angiopoietin-relate ......
Chromosomal Location	1p31.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ANGPTL3. 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	ANGPTL3
Name	angiopoietin-like 3
Aliases	angiopoietin 5; ANGPT5; ANG-5; ANL3; FHBL2; Angiopoietin-like protein 3; Angiopoietin-5; Angiopoietin-relate ......
Chromosomal Location	1p31.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ANGPTL3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ANGPTL3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ANGPTL3
Name	angiopoietin-like 3
Aliases	angiopoietin 5; ANGPT5; ANG-5; ANL3; FHBL2; Angiopoietin-like protein 3; Angiopoietin-5; Angiopoietin-relate ......
Chromosomal Location	1p31.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ANGPTL3. 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	ANGPTL3
Name	angiopoietin-like 3
Aliases	angiopoietin 5; ANGPT5; ANG-5; ANL3; FHBL2; Angiopoietin-like protein 3; Angiopoietin-5; Angiopoietin-relate ......
Chromosomal Location	1p31.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ANGPTL3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ANGPTL3
Name	angiopoietin-like 3
Aliases	angiopoietin 5; ANGPT5; ANG-5; ANL3; FHBL2; Angiopoietin-like protein 3; Angiopoietin-5; Angiopoietin-relate ......
Chromosomal Location	1p31.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ANGPTL3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ANGPTL3
Name	angiopoietin-like 3
Aliases	angiopoietin 5; ANGPT5; ANG-5; ANL3; FHBL2; Angiopoietin-like protein 3; Angiopoietin-5; Angiopoietin-relate ......
Chromosomal Location	1p31.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ANGPTL3 collected from DrugBank database.

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

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