UniProt:P06401-2 PGR

chain
  • chain:1-933
checksum 80452E54FF3A0454
comment
  • 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 a transcriptional activator or repressor.FUNCTION 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 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 Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.SUBUNIT 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).INTERACTION 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 Mainly nuclear.SUBCELLULAR LOCATION In reproductive tissues the expression of isoform A and isoform B varies as a consequence of developmental and hormonal status. Isoform A and isoform B are expressed in comparable levels in uterine glandular epithelium during the proliferative phase of the menstrual cycle. Expression of isoform B but not of isoform A persists in the glands during mid-secretory phase. In the stroma, isoform A is the predominant form throughout the cycle. Heterogeneous isoform expression between the glands of the endometrium basalis and functionalis is implying region-specific responses to hormonal stimuli.DOMAIN Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.PTM Phosphorylated on multiple serine sites. Several of these sites are hormone-dependent. Phosphorylation on Ser-294 occurs preferentially on isoform B, is highly hormone-dependent and modulates ubiquitination and sumoylation on Lys-388. Phosphorylation on Ser-102 and Ser-345 also requires induction by hormone. Basal phosphorylation on Ser-81, Ser-162, Ser-190 and Ser-400 is increased in response to progesterone and can be phosphorylated in vitro by the CDK2-A1 complex. Increased levels of phosphorylation on Ser-400 also in the presence of EGF, heregulin, IGF, PMA and FBS. Phosphorylation at this site by CDK2 is ligand-independent, and increases nuclear translocation and transcriptional activity. Phosphorylation at Ser-162 and Ser-294, but not at Ser-190, is impaired during the G(2)/M phase of the cell cycle. Phosphorylation on Ser-345 by ERK1/2 MAPK is required for interaction with SP1.PTM Sumoylation is hormone-dependent and represses transcriptional activity. Sumoylation on all three sites is enhanced by PIAS3. Desumoylated by SENP1. Sumoylation on Lys-388, the main site of sumoylation, is repressed by ubiquitination on the same site, and modulated by phosphorylation at Ser-294.PTM Ubiquitination is hormone-dependent and represses sumoylation on the same site. Promoted by MAPK-mediated phosphorylation on Ser-294.PTM Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation.MISCELLANEOUS Produced by alternative promoter usage.MISCELLANEOUS Produced by alternative promoter usage.MISCELLANEOUS Produced by alternative splicing of isoform B.MISCELLANEOUS Produced by alternative promoter usage.MISCELLANEOUS Produced by alternative splicing of isoform B.SIMILARITY Belongs to the nuclear hormone receptor family. NR3 subfamily.ONLINE INFORMATION Progesterone receptor entry
crossReference
databaseName UniProt
dbId 152438
description
  • recommendedName: Progesterone receptor shortName: PR alternativeName: Nuclear receptor subfamily 3 group C member 3
displayName UniProt:P06401-2 PGR
geneName
  • PGR
  • NR3C3
identifier P06401
isSequenceChanged false
isoformParent
keyword
  • 3D-structure
  • Alternative promoter usage
  • Alternative splicing
  • Cytoplasm
  • Direct protein sequencing
  • DNA-binding
  • Isopeptide bond
  • Lipid-binding
  • Lipoprotein
  • Membrane
  • Metal-binding
  • Mitochondrion
  • Mitochondrion outer membrane
  • Nucleus
  • Palmitate
  • Phosphoprotein
  • Receptor
  • Reference proteome
  • Steroid-binding
  • Transcription
  • Transcription regulation
  • Ubl conjugation
  • Zinc
  • Zinc-finger
modified [InstanceEdit:12187927] Wright, Adam, 2024-03-12
name
  • PGR
otherIdentifier
  • 11726167_a_at
  • 11726168_at
  • 11750900_a_at
  • 11750901_x_at
  • 160021_r_at
  • 16743577
  • 208305_PM_at
  • 208305_at
  • 228554_PM_at
  • 228554_at
  • 3388369
  • 3388370
  • 3388371
  • 3388372
  • 3388373
  • 3388374
  • 3388375
  • 3388376
  • 3388377
  • 3388378
  • 3388379
  • 3388380
  • 3388382
  • 3388383
  • 3388387
  • 3388393
  • 3388407
  • 3388408
  • 3388410
  • 3388411
  • 3388412
  • 3388413
  • 3388414
  • 3388415
  • 426_at
  • 44598_at
  • 5241
  • 7951165
  • 81847_at
  • 83526_at
  • A_23_P138938
  • A_32_P49199
  • GE59760
  • GE630055
  • GE900767
  • GO:0000785
  • GO:0000978
  • GO:0000981
  • GO:0001223
  • GO:0001228
  • GO:0001542
  • GO:0002070
  • GO:0002071
  • GO:0003676
  • GO:0003677
  • GO:0003700
  • GO:0003707
  • GO:0004879
  • GO:0004930
  • GO:0005102
  • GO:0005496
  • GO:0005515
  • GO:0005634
  • GO:0005654
  • GO:0005694
  • GO:0005737
  • GO:0005739
  • GO:0005741
  • GO:0005829
  • GO:0005886
  • GO:0006351
  • GO:0006355
  • GO:0006357
  • GO:0007165
  • GO:0007186
  • GO:0007267
  • GO:0008270
  • GO:0008289
  • GO:0010628
  • GO:0010629
  • GO:0016020
  • GO:0019899
  • GO:0022414
  • GO:0023052
  • GO:0030154
  • GO:0030518
  • GO:0030879
  • GO:0034056
  • GO:0038001
  • GO:0042802
  • GO:0043226
  • GO:0043401
  • GO:0043565
  • GO:0045944
  • GO:0046872
  • GO:0048286
  • GO:0048856
  • GO:0050678
  • GO:0050847
  • GO:0051117
  • GO:0060089
  • GO:0060748
  • GO:0140110
  • HMNXSV003001822
  • HMNXSV003041440
  • Hs.32405.0.S1_3p_at
  • ILMN_1811014
  • PH_hs_0000369
  • PH_hs_0002738
  • TC11002220.hg
  • TC11003308.hg
  • TC11003309.hg
  • X51730_at
  • g4505766_3p_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceIsoform
secondaryIdentifier
  • PRGR_HUMAN
  • A7LQ08
  • A7X8B0
  • B4E3T0
  • Q8TDS3
  • Q9UPF7
sequenceLength 933
species [Species:48887] Homo sapiens
url https://purl.uniprot.org/uniprot/P06401-2
variantIdentifier P06401-2
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