TISIDB

Summary
Symbol	PGR
Name	progesterone receptor
Aliases	NR3C3; nuclear receptor subfamily 3 group C member 3
Chromosomal Location	11q22-q23
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	Nucleus. Cytoplasm. Note=Nucleoplasmic shuttling is both hormone- and cell cycle-dependent. On hormone stimulation, retained in the cytoplasm in the G(1) and G(2)/M phases.; SUBCELLULAR LOCATION: Isoform A: Nucleus. Cytoplasm. Note=Mainly nuclear.; SUBCELLULAR LOCATION: Isoform 4: Mitochondrion outer membrane
Domain	PF00104 Ligand-binding domain of nuclear hormone receptor PF02161 Progesterone receptor PF00105 Zinc finger
Function	The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor. ; FUNCTION: Isoform A: Ligand-dependent transdominant repressor of steroid hormone receptor transcriptional activity including repression of its isoform B, MR and ER. Transrepressional activity may involve recruitment of corepressor NCOR2. ; FUNCTION: Isoform B: Transcriptional activator of several progesteron-dependent promoters in a variety of cell types. Involved in activation of SRC-dependent MAPK signaling on hormone stimulation. ; FUNCTION: Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.

> Gene Ontology [ TOP ]
Biological Process	GO:0006352 DNA-templated transcription, initiation GO:0006367 transcription initiation from RNA polymerase II promoter GO:0009755 hormone-mediated signaling pathway GO:0043401 steroid hormone mediated signaling pathway GO:0048545 response to steroid hormone GO:0071383 cellular response to steroid hormone stimulus GO:0071396 cellular response to lipid GO:0071407 cellular response to organic cyclic compound
Molecular Function	GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0000987 core promoter proximal region sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001159 core promoter proximal region DNA binding GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding GO:0003707 steroid hormone receptor activity GO:0005496 steroid binding GO:0051117 ATPase binding
Cellular Component	GO:0005741 mitochondrial outer membrane GO:0019867 outer membrane GO:0031968 organelle outer membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04114 Oocyte meiosis hsa04914 Progesterone-mediated oocyte maturation
Reactome	R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-383280: Nuclear Receptor transcription pathway R-HSA-1251985: Nuclear signaling by ERBB4 R-HSA-162582: Signal Transduction R-HSA-1236394: Signaling by ERBB4

Summary
Symbol	PGR
Name	progesterone receptor
Aliases	NR3C3; nuclear receptor subfamily 3 group C member 3
Chromosomal Location	11q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PGR 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

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Literatures describing the relation between PGR and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
21483002	Breast Carcinoma (ERBB-(+))	Inhibit immunity (infiltration)	The total number of CD8(+) cells was positively correlated with tumor grade (r(s) = 0.20; P < .001) and inversely correlated with patient's age at diagnosis, estrogen receptor-alpha (ER-α), and progesterone receptor (PgR) expression (Mann-Whitney U test, P < .001).

Summary
Symbol	PGR
Name	progesterone receptor
Aliases	NR3C3; nuclear receptor subfamily 3 group C member 3
Chromosomal Location	11q22-q23
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 PGR 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	PGR
Name	progesterone receptor
Aliases	NR3C3; nuclear receptor subfamily 3 group C member 3
Chromosomal Location	11q22-q23
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 PGR 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	0.273	0.645
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.499	0.745
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.023	0.989
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.042	0.948
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.715	0.475
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.718	0.496
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.066	0.897
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	0.053	0.94
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.394	0.0438

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PGR 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	14.3	0	14.3	0.196
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	25	0	25	0.222
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	5.5	-1.8	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	3.7	6.8	-3.1	1
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	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
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	7.9	0	7.9	0.26
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	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	PGR
Name	progesterone receptor
Aliases	NR3C3; nuclear receptor subfamily 3 group C member 3
Chromosomal Location	11q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PGR. 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	PGR
Name	progesterone receptor
Aliases	NR3C3; nuclear receptor subfamily 3 group C member 3
Chromosomal Location	11q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PGR. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PGR. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PGR
Name	progesterone receptor
Aliases	NR3C3; nuclear receptor subfamily 3 group C member 3
Chromosomal Location	11q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PGR. 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	PGR
Name	progesterone receptor
Aliases	NR3C3; nuclear receptor subfamily 3 group C member 3
Chromosomal Location	11q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PGR expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PGR
Name	progesterone receptor
Aliases	NR3C3; nuclear receptor subfamily 3 group C member 3
Chromosomal Location	11q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PGR and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PGR
Name	progesterone receptor
Aliases	NR3C3; nuclear receptor subfamily 3 group C member 3
Chromosomal Location	11q22-q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PGR collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PGR.

ID	Name	Drug Type	Targets	#Targets
DB00294	Etonogestrel	Small Molecule	ESR1, PGR	2
DB00304	Desogestrel	Small Molecule	ESR1, PGR	2
DB00351	Megestrol acetate	Small Molecule	NR3C1, PGR	2
DB00367	Levonorgestrel	Small Molecule	AR, ESR1, PGR, SHBG, SRD5A1	5
DB00378	Dydrogesterone	Small Molecule	PGR	1
DB00396	Progesterone	Small Molecule	AR, CYP17A1, ESR1, NR1I2, NR3C1, NR3C2, OPRK1, ORM1, PGR, SHBG	10
DB00421	Spironolactone	Small Molecule	AR, CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1F, CACNA1G, CACNA1H, ......	27
DB00431	Lindane	Small Molecule	ESR1, GABRB1, GABRB3, GABRR1, GLRA1, GLRA2, GLRA3, GLRB, NR1I2, PG ......	10
DB00588	Fluticasone propionate	Small Molecule	NR3C1, NR3C2, PGR, PLA2G4A	4
DB00603	Medroxyprogesterone acetate	Small Molecule	ESR1, PGR	2
DB00648	Mitotane	Small Molecule	AR, CYP11B1, ESR1, FDX1, PGR	5
DB00717	Norethisterone	Small Molecule	PGR	1
DB00764	Mometasone	Small Molecule	NR3C1, PGR	2
DB00823	Ethynodiol diacetate	Small Molecule	ESR1, PGR	2
DB00834	Mifepristone	Small Molecule	KLK3, NR1I2, NR3C1, PGR	4
DB00957	Norgestimate	Small Molecule	AR, ESR1, PGR	3
DB01395	Drospirenone	Small Molecule	AR, NR3C2, PGR	3
DB01406	Danazol	Small Molecule	AR, CCL2, ESR1, GNRHR, PGR	5
DB01428	Oxybenzone	Small Molecule	AR, ESR1, ESR2, PGR	4
DB01431	Allylestrenol	Small Molecule	ESR1, PGR	2
DB02746	Phthalic Acid	Small Molecule	ESR1, ESR2, PGR, PPARA, PPARD, PPARG, RXRA, RXRB, RXRG	9
DB02998	Methyltrienolone	Small Molecule	AR, NCOA2, NR3C2, PGR	4
DB04787	Tanaproget	Small Molecule	PGR	1
DB05253	Proellex	Small Molecule	PGR	1
DB06680	Asoprisnil	Small Molecule	PGR	1
DB06713	Norelgestromin	Small Molecule	ALB, AR, PGR	3
DB06789	Hydroxyprogesterone caproate	Small Molecule	PGR	1
DB08867	Ulipristal	Small Molecule	AR, NR3C1, PGR	3
DB09123	Dienogest	Small Molecule	AR, PGR	2
DB09124	Medrogestone	Small Molecule	PGR	1
DB09389	Norgestrel	Small Molecule	AR, PGR, SRD5A1	3
DB11064	Homosalate	Small Molecule	AR, ESR1, PGR	3
DB11219	Enzacamene	Small Molecule	AR, ESR1, ESR2, PGR	4
DB11619	Gestrinone	Small Molecule	AR, ESR1, GNRHR, NR3C1, PGR, SHBG	6

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