TISIDB

Summary
Symbol	GUCY2C
Name	guanylate cyclase 2C
Aliases	STA receptor; heat stable enterotoxin receptor; GUC2C; guanylate cyclase 2C (heat stable enterotoxin recepto ......
Chromosomal Location	12p12
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	Cell membrane Single-pass type I membrane protein Endoplasmic reticulum membrane Single-pass type I membrane protein Note=The 145 kDa plasma membrane form of GC-C contains sialic acid and galactose residues, while a differencially glycosylated 130 Kda form is a high mannose form that is resident in the endoplasmic reticulum and may serve as the precursor for the cell surface form.
Domain	PF00211 Adenylate and Guanylate cyclase catalytic domain PF07714 Protein tyrosine kinase
Function	Receptor for the E.coli heat-stable enterotoxin (E.coli enterotoxin markedly stimulates the accumulation of cGMP in mammalian cells expressing GC-C). Also activated by the endogenous peptides guanylin and uroguanylin.

> Gene Ontology [ TOP ]
Biological Process	GO:0006164 purine nucleotide biosynthetic process GO:0006182 cGMP biosynthetic process GO:0007168 receptor guanylyl cyclase signaling pathway 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:0009636 response to toxic substance GO:0046068 cGMP metabolic process GO:0046390 ribose phosphate biosynthetic process GO:0052652 cyclic purine nucleotide metabolic process GO:0072522 purine-containing compound biosynthetic process GO:1901293 nucleoside phosphate biosynthetic process
Molecular Function	GO:0004383 guanylate cyclase activity GO:0005525 GTP binding GO:0009975 cyclase activity GO:0015643 toxic substance binding GO:0016829 lyase activity GO:0016849 phosphorus-oxygen lyase activity GO:0019001 guanyl nucleotide binding GO:0032561 guanyl ribonucleotide binding
Cellular Component	GO:0008074 guanylate cyclase complex, soluble GO:0044445 cytosolic part

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00230 Purine metabolism
Reactome	R-HSA-1643685: Disease R-HSA-5663205: Infectious disease R-HSA-8942233: Intestinal infectious diseases R-HSA-1430728: Metabolism R-HSA-8935690: Miscellaneous digestion events R-HSA-5339562: Uptake and actions of bacterial toxins

Summary
Symbol	GUCY2C
Name	guanylate cyclase 2C
Aliases	STA receptor; heat stable enterotoxin receptor; GUC2C; guanylate cyclase 2C (heat stable enterotoxin recepto ......
Chromosomal Location	12p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between GUCY2C 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	GUCY2C
Name	guanylate cyclase 2C
Aliases	STA receptor; heat stable enterotoxin receptor; GUC2C; guanylate cyclase 2C (heat stable enterotoxin recepto ......
Chromosomal Location	12p12
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 GUCY2C 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	Total # shRNA with >= 4-fold: 1	Resistant to T-cell proliferation
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	GUCY2C
Name	guanylate cyclase 2C
Aliases	STA receptor; heat stable enterotoxin receptor; GUC2C; guanylate cyclase 2C (heat stable enterotoxin recepto ......
Chromosomal Location	12p12
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 GUCY2C 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	-0.659	0.379
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.123	0.551
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.082	0.969
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.362	0.487
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.181	0.816
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.513	0.534
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.024	0.951
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	-0.024	0.968
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.044	0.854

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of GUCY2C 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	11	-3.6	0.725
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	13.6	-6.2	0.495
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	5.9	3.6	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	16.7	-4.2	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	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	13.2	11.1	2.1	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	18.2	15.4	2.8	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	7.1	-0.9	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	18.2	0	18.2	0.199
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	16.7	0	16.7	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	20	0	20	0.294

Summary
Symbol	GUCY2C
Name	guanylate cyclase 2C
Aliases	STA receptor; heat stable enterotoxin receptor; GUC2C; guanylate cyclase 2C (heat stable enterotoxin recepto ......
Chromosomal Location	12p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of GUCY2C. 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	GUCY2C
Name	guanylate cyclase 2C
Aliases	STA receptor; heat stable enterotoxin receptor; GUC2C; guanylate cyclase 2C (heat stable enterotoxin recepto ......
Chromosomal Location	12p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of GUCY2C. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by GUCY2C. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	GUCY2C
Name	guanylate cyclase 2C
Aliases	STA receptor; heat stable enterotoxin receptor; GUC2C; guanylate cyclase 2C (heat stable enterotoxin recepto ......
Chromosomal Location	12p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of GUCY2C. 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	GUCY2C
Name	guanylate cyclase 2C
Aliases	STA receptor; heat stable enterotoxin receptor; GUC2C; guanylate cyclase 2C (heat stable enterotoxin recepto ......
Chromosomal Location	12p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of GUCY2C expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	GUCY2C
Name	guanylate cyclase 2C
Aliases	STA receptor; heat stable enterotoxin receptor; GUC2C; guanylate cyclase 2C (heat stable enterotoxin recepto ......
Chromosomal Location	12p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between GUCY2C and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	GUCY2C
Name	guanylate cyclase 2C
Aliases	STA receptor; heat stable enterotoxin receptor; GUC2C; guanylate cyclase 2C (heat stable enterotoxin recepto ......
Chromosomal Location	12p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting GUCY2C collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting GUCY2C.

ID	Name	Drug Type	Targets	#Targets
DB08890	Linaclotide	Small Molecule	GUCY2C	1

Browse GUCY2C