A7X8C4 (PRGR_MACSY) Reviewed, UniProtKB/Swiss-Prot
Last modified October 16, 2013. Version 31. History...
Names and origin
|Protein names||Recommended name:|
Nuclear receptor subfamily 3 group C member 3
|Organism||Macaca sylvanus (Barbary macaque)|
|Taxonomic identifier||9546 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Cercopithecidae › Cercopithecinae › Macaca|
|Sequence length||935 AA.|
|Protein existence||Inferred from homology|
General annotation (Comments)
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor is involved in activation of c-SRC/MAPK signaling on hormone stimulation By similarity.
Interacts with SMARD1 and UNC45A. Interacts with CUEDC2; the interaction promotes ubiquitination, decreases sumoylation, and repesses 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 By similarity.
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Phosphorylated on multiple serine sites. Several of these sites are hormone-dependent. Phosphorylation on Ser-294 is highly hormone-dependent and modulates ubiquitination and sumoylation on Lys-388. Phosphorylation on 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 G2/M phase of the cell cycle. Phosphorylation on Ser-345 by ERK1/2 MAPK is required for interaction with SP1 By similarity.
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 By similarity.
Ubiquitination is hormone-dependent and represses sumoylation on the same site. Promoted by MAPK-mediated phosphorylation on Ser-294 By similarity.
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 By similarity.
Belongs to the nuclear hormone receptor family.
Contains 1 nuclear receptor DNA-binding domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 935||935||Progesterone receptor||PRO_0000375856|
|DNA binding||569 – 641||73||Nuclear receptor|
|Zinc finger||569 – 589||21||NR C4-type|
|Zinc finger||605 – 629||25||NR C4-type|
|Region||1 – 568||568||Modulating, Pro-Rich|
|Region||683 – 935||253||Steroid-binding|
|Motif||183 – 187||5||Nuclear localization signal Potential|
Amino acid modifications
|Modified residue||20||1||Phosphoserine By similarity|
|Modified residue||81||1||Phosphoserine By similarity|
|Modified residue||130||1||Phosphoserine By similarity|
|Modified residue||162||1||Phosphoserine By similarity|
|Modified residue||190||1||Phosphoserine By similarity|
|Modified residue||213||1||Phosphoserine By similarity|
|Modified residue||294||1||Phosphoserine; by MAPK1 By similarity|
|Modified residue||345||1||Phosphoserine; by MAPK By similarity|
|Modified residue||400||1||Phosphoserine; by CDK2 By similarity|
|Modified residue||678||1||Phosphoserine By similarity|
|Cross-link||7||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity|
|Cross-link||388||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate By similarity|
|Cross-link||388||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate By similarity|
|Cross-link||533||Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity|
|||"The human progesterone receptor shows evidence of adaptive evolution associated with its ability to act as a transcription factor."|
Chen C., Opazo J.C., Erez O., Uddin M., Santolaya-Forgas J., Goodman M., Grossman L.I., Romero R., Wildman D.E.
Mol. Phylogenet. Evol. 47:637-649(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
|DQ234985 Genomic DNA. Translation: ABB72145.1.|
3D structure databases
|SMR||A7X8C4. Positions 565-642, 684-934. |
Protocols and materials databases
Family and domain databases
|Gene3D||1.10.565.10. 1 hit. |
188.8.131.52. 1 hit.
|InterPro||IPR008946. Nucl_hormone_rcpt_ligand-bd. |
|Pfam||PF00104. Hormone_recep. 1 hit. |
PF02161. Prog_receptor. 1 hit.
PF00105. zf-C4. 1 hit.
|PRINTS||PR00544. PROGESTRONER. |
|SMART||SM00430. HOLI. 1 hit. |
SM00399. ZnF_C4. 1 hit.
|SUPFAM||SSF48508. SSF48508. 2 hits. |
|PROSITE||PS00031. NUCLEAR_REC_DBD_1. 1 hit. |
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
|Accession||Primary (citable) accession number: A7X8C4|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families