Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PGR (P06401) - Overview - Molecular Target Synopsis

Protein


PGR, Progesterone receptor
UniProt P06401

Also Known as PRGR_HUMAN, PGR, NR3C3

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., 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., 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., Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone. Interacts with SMARD1 and UNC45A. Interacts with CUEDC2; the interaction promotes ubiquitination, decreases sumoylation, and represses transcriptional activity. Interacts with PIAS3; the interaction promotes sumoylation of PR in a hormone-dependent manner, inhibits DNA-binding, and alters nuclear export. Interacts with SP1; the interaction requires ligand-induced phosphorylation on Ser-345 by ERK1/2 MAPK. Interacts with PRMT2. Isoform A interacts with NCOR2. Isoform B (but not isoform A) interacts with NCOA2 and NCOA1. Isoform B (but not isoform A) interacts with KLF9. Interacts with GTF2B (PubMed:1517211).

5CC0
ANCSR2 - TSLP NGRE COMPLEX
RCSB/PDB
Inspect Structure
See all 3D Structures for PGR

Isoforms / Transcripts (Protein Coding)


Drugs


PGR is targeted by Approved Drugs Megestrol Acetate, Hydroxyprogesterone Caproate, Norethindrone Acetate, Medroxyprogesterone Acetate, Norethisterone, Norelgestromin, Drospirenone, Ulipristal Acetate, Desogestrel, Ethynodiol Diacetate, Ulipristal, Dydrogesterone, Etonogestrel, Norgestimate, Progesterone, Levonorgestrel, Norgestrel, Norethynodrel, Danazol, Mifepristone, Onapristone. (see details)
Megestrol Acetate
Hydroxyprogesterone Caproate
Norethindrone Acetate
Medroxyprogesterone Acetate
Norethisterone
Norelgestromin
Drospirenone
Ulipristal Acetate
Desogestrel
Ethynodiol Diacetate
Ulipristal
Dydrogesterone
Etonogestrel
Norgestimate
Progesterone
Levonorgestrel
Norgestrel
Norethynodrel
Danazol
Mifepristone
Onapristone

Sub-cellular localization


UniProt: PGR is active in the following subcellular-locations: cytoplasm, mitochondrion outer membrane, nucleus.
GO terms: PGR is active in the following subcellular-locations: cytosol, mitochondrial outer membrane, nucleoplasm.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PGR has gain in 11 cell-lines, loss in 6 cell-lines and no signal in 987 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: T47D, TK_10, KM12

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: T-47D, UACC-812, CAMA-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, NHLF, HSMM

(see details)

3D Structures


For PGR there are:
20 structures (37 chains) solved
18 are solved in complex with at least one small molecule ligand
6 are solved with an approved drug

PGR is solved in complex with the approved drug(s):

NOG/LEVONORGESTREL (3D90_A, 3D90_B),
STR/PROGESTERONE (1A28_A, 1A28_B),
MOF/MOMETASONE FUROATE (1SR7_A, 1SR7_B),
NDR/NORETHISTERONE (1SQN_A, 1SQN_B, 2W8Y_B),
2S0/ULIPRISTAL ACETATE (4OAR_A),
486/MIFEPRISTONE (2W8Y_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PGR has been screened with 2585 compounds (5317 bioactivities), 1335 compounds have bioactivities that show binding affinity of <= 500nM (2193 bioactivities). (see details)