TISIDB

Summary
Symbol	GCG
Name	glucagon
Aliases	GLP2; GRPP; glicentin-related polypeptide; glucagon-like peptide 1; glucagon-like peptide 2; preproglucagon
Chromosomal Location	2q36-q37
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.
Domain	PF00123 Peptide hormone
Function	Glucagon plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes.; FUNCTION: GLP-1 is a potent stimulator of glucose-dependent insulin release. Play important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Have growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation. Inhibits beta cell apoptosis.; FUNCTION: GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability.; FUNCTION: Oxyntomodulin significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness.; FUNCTION: Glicentin may modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life.

> Gene Ontology [ TOP ]
Biological Process	GO:0001678 cellular glucose homeostasis GO:0002790 peptide secretion GO:0002791 regulation of peptide secretion GO:0002793 positive regulation of peptide secretion GO:0005996 monosaccharide metabolic process GO:0006006 glucose metabolic process GO:0006094 gluconeogenesis GO:0006109 regulation of carbohydrate metabolic process GO:0006111 regulation of gluconeogenesis GO:0006140 regulation of nucleotide metabolic process GO:0006164 purine nucleotide biosynthetic process GO:0006171 cAMP biosynthetic process GO:0006479 protein methylation GO:0006816 calcium ion transport GO:0007187 G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger GO:0007188 adenylate cyclase-modulating G-protein coupled receptor signaling pathway GO:0007631 feeding behavior GO:0008213 protein alkylation GO:0009150 purine ribonucleotide metabolic process GO:0009152 purine ribonucleotide biosynthetic process GO:0009165 nucleotide biosynthetic process GO:0009187 cyclic nucleotide metabolic process GO:0009190 cyclic nucleotide biosynthetic process GO:0009260 ribonucleotide biosynthetic process GO:0009306 protein secretion GO:0009743 response to carbohydrate GO:0009746 response to hexose GO:0009749 response to glucose GO:0009914 hormone transport GO:0009991 response to extracellular stimulus GO:0010675 regulation of cellular carbohydrate metabolic process GO:0010676 positive regulation of cellular carbohydrate metabolic process GO:0010737 protein kinase A signaling GO:0010799 regulation of peptidyl-threonine phosphorylation GO:0010800 positive regulation of peptidyl-threonine phosphorylation GO:0010817 regulation of hormone levels GO:0010906 regulation of glucose metabolic process GO:0010907 positive regulation of glucose metabolic process GO:0010959 regulation of metal ion transport GO:0015833 peptide transport GO:0016051 carbohydrate biosynthetic process GO:0016570 histone modification GO:0016571 histone methylation GO:0018022 peptidyl-lysine methylation GO:0018105 peptidyl-serine phosphorylation GO:0018107 peptidyl-threonine phosphorylation GO:0018205 peptidyl-lysine modification GO:0018209 peptidyl-serine modification GO:0018210 peptidyl-threonine modification GO:0019318 hexose metabolic process GO:0019319 hexose biosynthetic process GO:0023061 signal release GO:0030072 peptide hormone secretion GO:0030073 insulin secretion GO:0030799 regulation of cyclic nucleotide metabolic process GO:0030801 positive regulation of cyclic nucleotide metabolic process GO:0030802 regulation of cyclic nucleotide biosynthetic process GO:0030804 positive regulation of cyclic nucleotide biosynthetic process GO:0030808 regulation of nucleotide biosynthetic process GO:0030810 positive regulation of nucleotide biosynthetic process GO:0030814 regulation of cAMP metabolic process GO:0030816 positive regulation of cAMP metabolic process GO:0030817 regulation of cAMP biosynthetic process GO:0030819 positive regulation of cAMP biosynthetic process GO:0031056 regulation of histone modification GO:0031058 positive regulation of histone modification GO:0031060 regulation of histone methylation GO:0031062 positive regulation of histone methylation GO:0031667 response to nutrient levels GO:0032024 positive regulation of insulin secretion GO:0032092 positive regulation of protein binding GO:0032259 methylation GO:0032844 regulation of homeostatic process GO:0032846 positive regulation of homeostatic process GO:0033135 regulation of peptidyl-serine phosphorylation GO:0033138 positive regulation of peptidyl-serine phosphorylation GO:0033500 carbohydrate homeostasis GO:0033674 positive regulation of kinase activity GO:0033762 response to glucagon GO:0034284 response to monosaccharide GO:0034968 histone lysine methylation GO:0035773 insulin secretion involved in cellular response to glucose stimulus GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus GO:0035947 regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoter GO:0035948 positive regulation of gluconeogenesis by positive regulation of transcription from RNA polymerase II promoter GO:0042593 glucose homeostasis GO:0042594 response to starvation GO:0042886 amide transport GO:0043255 regulation of carbohydrate biosynthetic process GO:0043270 positive regulation of ion transport GO:0043393 regulation of protein binding GO:0043410 positive regulation of MAPK cascade GO:0043414 macromolecule methylation GO:0043434 response to peptide hormone GO:0044262 cellular carbohydrate metabolic process GO:0044283 small molecule biosynthetic process GO:0044723 single-organism carbohydrate metabolic process GO:0045722 positive regulation of gluconeogenesis GO:0045860 positive regulation of protein kinase activity GO:0045913 positive regulation of carbohydrate metabolic process GO:0045981 positive regulation of nucleotide metabolic process GO:0046058 cAMP metabolic process GO:0046364 monosaccharide biosynthetic process GO:0046390 ribose phosphate biosynthetic process GO:0046879 hormone secretion GO:0046883 regulation of hormone secretion GO:0046887 positive regulation of hormone secretion GO:0050708 regulation of protein secretion GO:0050714 positive regulation of protein secretion GO:0050796 regulation of insulin secretion GO:0051047 positive regulation of secretion GO:0051098 regulation of binding GO:0051099 positive regulation of binding GO:0051222 positive regulation of protein transport GO:0051568 histone H3-K4 methylation GO:0051569 regulation of histone H3-K4 methylation GO:0051571 positive regulation of histone H3-K4 methylation GO:0051924 regulation of calcium ion transport GO:0051928 positive regulation of calcium ion transport GO:0052652 cyclic purine nucleotide metabolic process GO:0061178 regulation of insulin secretion involved in cellular response to glucose stimulus GO:0070371 ERK1 and ERK2 cascade GO:0070372 regulation of ERK1 and ERK2 cascade GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:0070509 calcium ion import GO:0070838 divalent metal ion transport GO:0071322 cellular response to carbohydrate stimulus GO:0071326 cellular response to monosaccharide stimulus GO:0071331 cellular response to hexose stimulus GO:0071333 cellular response to glucose stimulus GO:0071375 cellular response to peptide hormone stimulus GO:0071377 cellular response to glucagon stimulus GO:0071417 cellular response to organonitrogen compound GO:0072511 divalent inorganic cation transport GO:0072522 purine-containing compound biosynthetic process GO:0090087 regulation of peptide transport GO:0090276 regulation of peptide hormone secretion GO:0090277 positive regulation of peptide hormone secretion GO:0090279 regulation of calcium ion import GO:0090280 positive regulation of calcium ion import GO:0097193 intrinsic apoptotic signaling pathway GO:0097194 execution phase of apoptosis GO:1900117 regulation of execution phase of apoptosis GO:1900118 negative regulation of execution phase of apoptosis GO:1900371 regulation of purine nucleotide biosynthetic process GO:1900373 positive regulation of purine nucleotide biosynthetic process GO:1900542 regulation of purine nucleotide metabolic process GO:1900544 positive regulation of purine nucleotide metabolic process GO:1901293 nucleoside phosphate biosynthetic process GO:1901652 response to peptide GO:1901653 cellular response to peptide GO:1902275 regulation of chromatin organization GO:1902532 negative regulation of intracellular signal transduction GO:1903532 positive regulation of secretion by cell GO:1904951 positive regulation of establishment of protein localization GO:1905269 positive regulation of chromatin organization GO:2001233 regulation of apoptotic signaling pathway GO:2001234 negative regulation of apoptotic signaling pathway GO:2001242 regulation of intrinsic apoptotic signaling pathway GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
Molecular Function	GO:0001664 G-protein coupled receptor binding GO:0005179 hormone activity GO:0031769 glucagon receptor binding
Cellular Component	GO:0005788 endoplasmic reticulum lumen GO:0030141 secretory granule GO:0031983 vesicle lumen GO:0034774 secretory granule lumen GO:0060205 cytoplasmic membrane-bounded vesicle lumen GO:0099503 secretory vesicle

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04911 Insulin secretion hsa04922 Glucagon signaling pathway
Reactome	R-HSA-373080: Class B/2 (Secretin family receptors) R-HSA-416476: G alpha (q) signalling events R-HSA-418555: G alpha (s) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-500792: GPCR ligand binding R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-163359: Glucagon signaling in metabolic regulation R-HSA-381676: Glucagon-like Peptide-1 (GLP1) regulates insulin secretion R-HSA-420092: Glucagon-type ligand receptors R-HSA-400508: Incretin synthesis, secretion, and inactivation R-HSA-163685: Integration of energy metabolism R-HSA-1430728: Metabolism R-HSA-392499: Metabolism of proteins R-HSA-2980736: Peptide hormone metabolism R-HSA-422356: Regulation of insulin secretion R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR R-HSA-422085: Synthesis, secretion, and deacylation of Ghrelin R-HSA-381771: Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04911 Insulin secretion
hsa04922 Glucagon signaling pathway

Reactome

R-HSA-373080: Class B/2 (Secretin family receptors)
R-HSA-416476: G alpha (q) signalling events
R-HSA-418555: G alpha (s) signalling events
R-HSA-388396: GPCR downstream signaling
R-HSA-500792: GPCR ligand binding
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-163359: Glucagon signaling in metabolic regulation
R-HSA-381676: Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-420092: Glucagon-type ligand receptors
R-HSA-400508: Incretin synthesis, secretion, and inactivation
R-HSA-163685: Integration of energy metabolism
R-HSA-1430728: Metabolism
R-HSA-392499: Metabolism of proteins
R-HSA-2980736: Peptide hormone metabolism
R-HSA-422356: Regulation of insulin secretion
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
R-HSA-422085: Synthesis, secretion, and deacylation of Ghrelin
R-HSA-381771: Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)

Summary
Symbol	GCG
Name	glucagon
Aliases	GLP2; GRPP; glicentin-related polypeptide; glucagon-like peptide 1; glucagon-like peptide 2; preproglucagon
Chromosomal Location	2q36-q37
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between GCG 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	GCG
Name	glucagon
Aliases	GLP2; GRPP; glicentin-related polypeptide; glucagon-like peptide 1; glucagon-like peptide 2; preproglucagon
Chromosomal Location	2q36-q37
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 GCG 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	Resistant to T cell-mediated killing
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	GCG
Name	glucagon
Aliases	GLP2; GRPP; glicentin-related polypeptide; glucagon-like peptide 1; glucagon-like peptide 2; preproglucagon
Chromosomal Location	2q36-q37
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 GCG 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	1
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0	1
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0	1
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.708	0.346
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.212	0.317
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.066	0.962
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0	1
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0	1
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0	1
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0	1
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	1
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.005	0.976

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of GCG 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	0	1.4	-1.4	1
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	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	11.8	-7	0.577
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	7.7	18.2	-10.5	0.576
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	GCG
Name	glucagon
Aliases	GLP2; GRPP; glicentin-related polypeptide; glucagon-like peptide 1; glucagon-like peptide 2; preproglucagon
Chromosomal Location	2q36-q37
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of GCG. 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	GCG
Name	glucagon
Aliases	GLP2; GRPP; glicentin-related polypeptide; glucagon-like peptide 1; glucagon-like peptide 2; preproglucagon
Chromosomal Location	2q36-q37
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of GCG. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by GCG. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	GCG
Name	glucagon
Aliases	GLP2; GRPP; glicentin-related polypeptide; glucagon-like peptide 1; glucagon-like peptide 2; preproglucagon
Chromosomal Location	2q36-q37
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of GCG. 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	GCG
Name	glucagon
Aliases	GLP2; GRPP; glicentin-related polypeptide; glucagon-like peptide 1; glucagon-like peptide 2; preproglucagon
Chromosomal Location	2q36-q37
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of GCG expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	GCG
Name	glucagon
Aliases	GLP2; GRPP; glicentin-related polypeptide; glucagon-like peptide 1; glucagon-like peptide 2; preproglucagon
Chromosomal Location	2q36-q37
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between GCG and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	GCG
Name	glucagon
Aliases	GLP2; GRPP; glicentin-related polypeptide; glucagon-like peptide 1; glucagon-like peptide 2; preproglucagon
Chromosomal Location	2q36-q37
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting GCG collected from DrugBank database.

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

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