ID PRGR_HUMAN Reviewed; 933 AA. AC P06401; A7LQ08; A7X8B0; B4E3T0; Q8TDS3; Q9UPF7; DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot. DT 21-MAR-2006, sequence version 4. DT 27-MAR-2024, entry version 263. DE RecName: Full=Progesterone receptor; DE Short=PR; DE AltName: Full=Nuclear receptor subfamily 3 group C member 3; GN Name=PGR; Synonyms=NR3C3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE PROMOTER USAGE, AND VARIANT RP THR-344. RX PubMed=2328727; DOI=10.1002/j.1460-2075.1990.tb08280.x; RA Kastner P., Krust A., Turcotte B., Stropp U., Tora L., Gronemeyer H., RA Chambon P.; RT "Two distinct estrogen-regulated promoters generate transcripts encoding RT the two functionally different human progesterone receptor forms A and B."; RL EMBO J. 9:1603-1614(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-660. RX PubMed=3551956; DOI=10.1016/0006-291x(87)91416-1; RA Misrahi M., Atger M., D'Auriol L., Loosfelt H., Meriel C., Fridlansky F., RA Guiochon-Mantel A., Galibert F., Milgrom E.; RT "Complete amino acid sequence of the human progesterone receptor deduced RT from cloned cDNA."; RL Biochem. Biophys. Res. Commun. 143:740-748(1987). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-660. RA Kieback D.G., Agoulnik I.U., Tong X.-W.; RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). RC TISSUE=Mammary tumor; RA Hisatomi H., Wakita K., Kohno N., Nagao K., Hirata H., Hikiji K.; RT "Progesterone Receptor, alternative splicing variant, mRNA."; RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=18375150; DOI=10.1016/j.ympev.2007.12.026; RA Chen C., Opazo J.C., Erez O., Uddin M., Santolaya-Forgas J., Goodman M., RA Grossman L.I., Romero R., Wildman D.E.; RT "The human progesterone receptor shows evidence of adaptive evolution RT associated with its ability to act as a transcription factor."; RL Mol. Phylogenet. Evol. 47:637-649(2008). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), ALTERNATIVE PROMOTER USAGE, AND RP VARIANT LEU-660. RC TISSUE=Adipose tissue, and Aorta; RX PubMed=12644308; DOI=10.1016/s0303-7207(02)00380-5; RA Saner K.J., Welter B.H., Zhang F., Hansen E., Dupont B., Wei Y., RA Price T.M.; RT "Cloning and expression of a novel, truncated, progesterone receptor."; RL Mol. Cell. Endocrinol. 200:155-163(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Uterus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-50; VAL-120; LEU-186; RP ARG-301; THR-344; SER-444; LEU-529; PRO-536; VAL-651 AND LEU-865. RG NIEHS SNPs program; RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP PROTEIN SEQUENCE OF 11-22 AND 673-679, PHOSPHORYLATION AT SER-20; SER-102; RP SER-130; SER-162; SER-190; SER-213; SER-345 AND SER-676, AND IDENTIFICATION RP BY MASS SPECTROMETRY. RX PubMed=11110801; DOI=10.1074/jbc.m009805200; RA Knotts T.A., Orkiszewski R.S., Cook R.G., Edwards D.P., Weigel N.L.; RT "Identification of a phosphorylation site in the hinge region of the human RT progesterone receptor and additional amino-terminal phosphorylation RT sites."; RL J. Biol. Chem. 276:8475-8483(2001). RN [12] RP PROTEIN SEQUENCE OF 204-217, FUNCTION (ISOFORM 4), AND SUBCELLULAR LOCATION RP (ISOFORM 4). RC TISSUE=Heart; RX PubMed=23518922; DOI=10.1210/me.2012-1292; RA Dai Q., Shah A.A., Garde R.V., Yonish B.A., Zhang L., Medvitz N.A., RA Miller S.E., Hansen E.L., Dunn C.N., Price T.M.; RT "A truncated progesterone receptor (PR-M) localizes to the mitochondrion RT and controls cellular respiration."; RL Mol. Endocrinol. 27:741-753(2013). RN [13] RP FUNCTION. RX PubMed=1587864; DOI=10.1016/s0021-9258(19)50100-4; RA Meyer M.E., Quirin-Stricker C., Lerouge T., Bocquel M.T., Gronemeyer H.; RT "A limiting factor mediates the differential activation of promoters by the RT human progesterone receptor isoforms."; RL J. Biol. Chem. 267:10882-10887(1992). RN [14] RP INTERACTION WITH GTF2B. RX PubMed=1517211; DOI=10.1016/s0021-9258(19)37087-5; RA Ing N.H., Beekman J.M., Tsai S.Y., Tsai M.J., O'Malley B.W.; RT "Members of the steroid hormone receptor superfamily interact with TFIIB RT (S300-II)."; RL J. Biol. Chem. 267:17617-17623(1992). RN [15] RP FUNCTION (ISOFORM A). RX PubMed=8264658; DOI=10.1210/mend.7.10.8264658; RA Vegeto E., Shahbaz M.M., Wen D.X., Goldman M.E., O'Malley B.W., RA McDonnell D.P.; RT "Human progesterone receptor A form is a cell- and promoter-specific RT repressor of human progesterone receptor B function."; RL Mol. Endocrinol. 7:1244-1255(1993). RN [16] RP FUNCTION (ISOFORM A). RX PubMed=8180103; DOI=10.1016/0960-0760(94)90190-2; RA McDonnell D.P., Shahbaz M.M., Vegeto E., Goldman M.E.; RT "The human progesterone receptor A-form functions as a transcriptional RT modulator of mineralocorticoid receptor transcriptional activity."; RL J. Steroid Biochem. Mol. Biol. 48:425-432(1994). RN [17] RP FUNCTION. RX PubMed=7969170; DOI=10.1128/mcb.14.12.8356-8364.1994; RA Wen D.X., Xu Y.F., Mais D.E., Goldman M.E., McDonnell D.P.; RT "The A and B isoforms of the human progesterone receptor operate through RT distinct signaling pathways within target cells."; RL Mol. Cell. Biol. 14:8356-8364(1994). RN [18] RP PHOSPHORYLATION AT SER-81 AND SER-162. RX PubMed=7476977; DOI=10.1210/mend.9.8.7476977; RA Zhang Y., Beck C.A., Poletti A., Edwards D.P., Weigel N.L.; RT "Identification of a group of Ser-Pro motif hormone-inducible RT phosphorylation sites in the human progesterone receptor."; RL Mol. Endocrinol. 9:1029-1040(1995). RN [19] RP PHOSPHORYLATION AT SER-81; SER-102; SER-162; SER-294 AND SER-345. RX PubMed=8702648; DOI=10.1074/jbc.271.32.19546; RA Beck C.A., Zhang Y., Altmann M., Weigel N.L., Edwards D.P.; RT "Stoichiometry and site-specific phosphorylation of human progesterone RT receptor in native target cells and in the baculovirus expression system."; RL J. Biol. Chem. 271:19546-19555(1996). RN [20] RP FUNCTION. RX PubMed=9407067; DOI=10.1074/jbc.272.52.32889; RA Giangrande P.H., Pollio G., McDonnell D.P.; RT "Mapping and characterization of the functional domains responsible for the RT differential activity of the A and B isoforms of the human progesterone RT receptor."; RL J. Biol. Chem. 272:32889-32900(1997). RN [21] RP PHOSPHORYLATION AT SER-162; SER-190 AND SER-400. RX PubMed=9171245; DOI=10.1210/mend.11.6.0006; RA Zhang Y., Beck C.A., Poletti A., Clement J.P. IV, Prendergast P., RA Yip T.-T., Hutchens T.W., Edwards D.P., Weigel N.L.; RT "Phosphorylation of human progesterone receptor by cyclin-dependent kinase RT 2 on three sites that are authentic basal phosphorylation sites in vivo."; RL Mol. Endocrinol. 11:823-832(1997). RN [22] RP TISSUE SPECIFICITY. RX PubMed=11041221; DOI=10.1093/humrep/15.suppl_3.48; RA Mote P.A., Balleine R.L., McGowan E.M., Clarke C.L.; RT "Heterogeneity of progesterone receptors A and B expression in human RT endometrial glands and stroma."; RL Hum. Reprod. 15:48-56(2000). RN [23] RP FUNCTION, AND INTERACTION WITH NCOR2; NCOA2 AND NCOA1. RX PubMed=10757795; DOI=10.1128/mcb.20.9.3102-3115.2000; RA Giangrande P.H., Kimbrel E.A., Edwards D.P., McDonnell D.P.; RT "The opposing transcriptional activities of the two isoforms of the human RT progesterone receptor are due to differential cofactor binding."; RL Mol. Cell. Biol. 20:3102-3115(2000). RN [24] RP PHOSPHORYLATION AT SER-190 AND SER-294. RX PubMed=10628747; DOI=10.1210/mend.14.1.0413; RA Clemm D.L., Sherman L., Boonyaratanakornkit V., Schrader W.T., Weigel N.L., RA Edwards D.P.; RT "Differential hormone-dependent phosphorylation of progesterone receptor A RT and B forms revealed by a phosphoserine site-specific monoclonal RT antibody."; RL Mol. Endocrinol. 14:52-65(2000). RN [25] RP PHOSPHORYLATION AT SER-294, UBIQUITINATION, AND MUTAGENESIS OF SER-294; RP SER-344 AND SER-345. RX PubMed=10655479; DOI=10.1073/pnas.97.3.1032; RA Lange C.A., Shen T., Horwitz K.B.; RT "Phosphorylation of human progesterone receptors at serine-294 by mitogen- RT activated protein kinase signals their degradation by the 26S proteasome."; RL Proc. Natl. Acad. Sci. U.S.A. 97:1032-1037(2000). RN [26] RP FUNCTION, AND MUTAGENESIS OF LEU-55; LEU-58; LEU-59; LEU-115; LEU-118; RP LEU-119 AND TRP-140. RX PubMed=11546784; DOI=10.1074/jbc.m106843200; RA Tung L., Shen T., Abel M.G., Powell R.L., Takimoto G.S., Sartorius C.A., RA Horwitz K.B.; RT "Mapping the unique activation function 3 in the progesterone B-receptor RT upstream segment. Two LXXLL motifs and a tryptophan residue are required RT for activity."; RL J. Biol. Chem. 276:39843-39851(2001). RN [27] RP INTERACTION WITH PRMT2. RX PubMed=12039952; DOI=10.1074/jbc.m201053200; RA Qi C., Chang J., Zhu Y., Yeldandi A.V., Rao S.M., Zhu Y.-J.; RT "Identification of protein arginine methyltransferase 2 as a coactivator RT for estrogen receptor alpha."; RL J. Biol. Chem. 277:28624-28630(2002). RN [28] RP INTERACTION WITH SMARD1. RX PubMed=12917342; DOI=10.1128/mcb.23.17.6210-6220.2003; RA Hsiao P.W., Fryer C.J., Trotter K.W., Wang W., Archer T.K.; RT "BAF60a mediates critical interactions between nuclear receptors and the RT BRG1 chromatin-remodeling complex for transactivation."; RL Mol. Cell. Biol. 23:6210-6220(2003). RN [29] RP PHOSPHORYLATION AT SER-400, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS RP OF SER-400. RX PubMed=15572662; DOI=10.1128/mcb.24.24.10542-10557.2004; RA Pierson-Mullany L.K., Lange C.A.; RT "Phosphorylation of progesterone receptor serine 400 mediates ligand- RT independent transcriptional activity in response to activation of cyclin- RT dependent protein kinase 2."; RL Mol. Cell. Biol. 24:10542-10557(2004). RN [30] RP PHOSPHORYLATION AT SER-162; SER-190 AND SER-294, SUBCELLULAR LOCATION, AND RP FUNCTION. RX PubMed=15798179; DOI=10.1128/mcb.25.8.2885-2898.2005; RA Narayanan R., Edwards D.P., Weigel N.L.; RT "Human progesterone receptor displays cell cycle-dependent changes in RT transcriptional activity."; RL Mol. Cell. Biol. 25:2885-2898(2005). RN [31] RP INTERACTION WITH UNC45A. RX PubMed=16478993; DOI=10.1128/mcb.26.5.1722-1730.2006; RA Chadli A., Graham J.D., Abel M.G., Jackson T.A., Gordon D.F., Wood W.M., RA Felts S.J., Horwitz K.B., Toft D.; RT "GCUNC-45 is a novel regulator for the progesterone receptor/hsp90 RT chaperoning pathway."; RL Mol. Cell. Biol. 26:1722-1730(2006). RN [32] RP SUMOYLATION AT LYS-7; LYS-388 AND LYS-531, INTERACTION WITH PIAS3, RP FUNCTION, AND MUTAGENESIS OF LYS-7; LYS-388 AND LYS-531. RX PubMed=17020914; DOI=10.1093/nar/gkl691; RA Man J.-H., Li H.-Y., Zhang P.-J., Zhou T., He K., Pan X., Liang B., RA Li A.-L., Zhao J., Gong W.-L., Jin B.-F., Xia Q., Yu M., Shen B.-F., RA Zhang X.-M.; RT "PIAS3 induction of PRB sumoylation represses PRB transactivation by RT destabilizing its retention in the nucleus."; RL Nucleic Acids Res. 34:5552-5566(2006). RN [33] RP INTERACTION WITH CUEDC2, SUMOYLATION AT LYS-388, UBIQUITINATION AT LYS-388, RP FUNCTION, AND MUTAGENESIS OF LYS-388. RX PubMed=17347654; DOI=10.1038/sj.emboj.7601602; RA Zhang P.-J., Zhao J., Li H.-Y., Man J.-H., He K., Zhou T., Pan X., RA Li A.-L., Gong W.-L., Jin B.-F., Xia Q., Yu M., Shen B.-F., Zhang X.-M.; RT "CUE domain containing 2 regulates degradation of progesterone receptor by RT ubiquitin-proteasome."; RL EMBO J. 26:1831-1842(2007). RN [34] RP PHOSPHORYLATION AT SER-294, SUMOYLATION AT LYS-388, FUNCTION, AND RP MUTAGENESIS OF SER-294 AND LYS-388. RX PubMed=17717077; DOI=10.1210/me.2007-0248; RA Daniel A.R., Faivre E.J., Lange C.A.; RT "Phosphorylation-dependent antagonism of sumoylation derepresses RT progesterone receptor action in breast cancer cells."; RL Mol. Endocrinol. 21:2890-2906(2007). RN [35] RP PHOSPHORYLATION AT SER-294, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS RP OF SER-294. RX PubMed=17173941; DOI=10.1016/j.steroids.2006.11.009; RA Daniel A.R., Qiu M., Faivre E.J., Ostrander J.H., Skildum A., Lange C.A.; RT "Linkage of progestin and epidermal growth factor signaling: RT phosphorylation of progesterone receptors mediates transcriptional RT hypersensitivity and increased ligand-independent breast cancer cell RT growth."; RL Steroids 72:188-201(2007). RN [36] RP PHOSPHORYLATION AT SER-294; SER-345 AND SER-400, INTERACTION WITH SP1, RP FUNCTION, AND MUTAGENESIS OF SER-344; SER-345 AND SER-400. RX PubMed=18202149; DOI=10.1210/me.2007-0437; RA Faivre E.J., Daniel A.R., Hillard C.J., Lange C.A.; RT "Progesterone receptor rapid signaling mediates serine 345 phosphorylation RT and tethering to specificity protein 1 transcription factors."; RL Mol. Endocrinol. 22:823-837(2008). RN [37] RP PALMITOYLATION. RX PubMed=22031296; DOI=10.1091/mbc.e11-07-0638; RA Pedram A., Razandi M., Deschenes R.J., Levin E.R.; RT "DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors."; RL Mol. Biol. Cell 23:188-199(2012). RN [38] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-162, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [39] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 682-933. RX PubMed=9620806; DOI=10.1038/30775; RA Williams S.P., Sigler P.B.; RT "Atomic structure of progesterone complexed with its receptor."; RL Nature 393:392-396(1998). RN [40] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 676-933. RX PubMed=15937332; DOI=10.1074/jbc.m504144200; RA Zhang Z., Olland A.M., Zhu Y., Cohen J., Berrodin T., Chippari S., RA Appavu C., Li S., Wilhem J., Chopra R., Fensome A., Zhang P., Wrobel J., RA Unwalla R.J., Lyttle C.R., Winneker R.C.; RT "Molecular and pharmacological properties of a potent and selective novel RT nonsteroidal progesterone receptor agonist tanaproget."; RL J. Biol. Chem. 280:28468-28475(2005). CC -!- FUNCTION: The steroid hormones and their receptors are involved in the CC regulation of eukaryotic gene expression and affect cellular CC proliferation and differentiation in target tissues. Depending on the CC isoform, progesterone receptor functions as a transcriptional activator CC or repressor. {ECO:0000269|PubMed:10757795, ECO:0000269|PubMed:1587864, CC ECO:0000269|PubMed:9407067, ECO:0000305}. CC -!- FUNCTION: [Isoform A]: Ligand-dependent transdominant repressor of CC steroid hormone receptor transcriptional activity including repression CC of its isoform B, MR and ER. Transrepressional activity may involve CC recruitment of corepressor NCOR2. {ECO:0000269|PubMed:7969170, CC ECO:0000269|PubMed:8180103, ECO:0000269|PubMed:8264658, ECO:0000305, CC ECO:0000305|PubMed:10757795}. CC -!- FUNCTION: [Isoform B]: Transcriptional activator of several CC progesteron-dependent promoters in a variety of cell types. Involved in CC activation of SRC-dependent MAPK signaling on hormone stimulation. CC {ECO:0000269|PubMed:7969170}. CC -!- FUNCTION: [Isoform 4]: Increases mitochondrial membrane potential and CC cellular respiration upon stimulation by progesterone. CC -!- SUBUNIT: Interacts with SMARD1 and UNC45A. Interacts with CUEDC2; the CC interaction promotes ubiquitination, decreases sumoylation, and CC represses transcriptional activity. Interacts with PIAS3; the CC interaction promotes sumoylation of PR in a hormone-dependent manner, CC inhibits DNA-binding, and alters nuclear export. Interacts with SP1; CC the interaction requires ligand-induced phosphorylation on Ser-345 by CC ERK1/2 MAPK. Interacts with PRMT2. Isoform A interacts with NCOR2. CC Isoform B (but not isoform A) interacts with NCOA2 and NCOA1. Isoform B CC (but not isoform A) interacts with KLF9. Interacts with GTF2B CC (PubMed:1517211). {ECO:0000250|UniProtKB:Q00175, CC ECO:0000269|PubMed:10757795, ECO:0000269|PubMed:12039952, CC ECO:0000269|PubMed:12917342, ECO:0000269|PubMed:1517211, CC ECO:0000269|PubMed:16478993, ECO:0000269|PubMed:17020914, CC ECO:0000269|PubMed:17347654, ECO:0000269|PubMed:18202149}. CC -!- INTERACTION: CC P06401; Q9H467: CUEDC2; NbExp=9; IntAct=EBI-78539, EBI-1248228; CC P06401; P03372: ESR1; NbExp=20; IntAct=EBI-78539, EBI-78473; CC P06401; P06401: PGR; NbExp=2; IntAct=EBI-78539, EBI-78539; CC P06401; P40763: STAT3; NbExp=3; IntAct=EBI-78539, EBI-518675; CC P06401-1; P03372: ESR1; NbExp=4; IntAct=EBI-12590474, EBI-78473; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Nucleoplasmic shuttling CC is both hormone- and cell cycle-dependent. On hormone stimulation, CC retained in the cytoplasm in the G(1) and G(2)/M phases. CC -!- SUBCELLULAR LOCATION: [Isoform A]: Nucleus. Cytoplasm. Note=Mainly CC nuclear. CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Mitochondrion outer membrane CC {ECO:0000269|PubMed:23518922}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=5; CC Name=B; Synonyms=PRB, PR-B; CC IsoId=P06401-1; Sequence=Displayed; CC Name=A; Synonyms=PRA, PR-A; CC IsoId=P06401-2; Sequence=VSP_003706; CC Name=3; CC IsoId=P06401-3; Sequence=VSP_046942; CC Name=4; Synonyms=PR-M; CC IsoId=P06401-4; Sequence=VSP_047454, VSP_047455; CC Name=5; Synonyms=delta4; CC IsoId=P06401-5; Sequence=VSP_053543; CC -!- TISSUE SPECIFICITY: In reproductive tissues the expression of isoform A CC and isoform B varies as a consequence of developmental and hormonal CC status. Isoform A and isoform B are expressed in comparable levels in CC uterine glandular epithelium during the proliferative phase of the CC menstrual cycle. Expression of isoform B but not of isoform A persists CC in the glands during mid-secretory phase. In the stroma, isoform A is CC the predominant form throughout the cycle. Heterogeneous isoform CC expression between the glands of the endometrium basalis and CC functionalis is implying region-specific responses to hormonal stimuli. CC {ECO:0000269|PubMed:11041221}. CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a CC DNA-binding domain and a C-terminal ligand-binding domain. CC -!- PTM: Phosphorylated on multiple serine sites. Several of these sites CC are hormone-dependent. Phosphorylation on Ser-294 occurs preferentially CC on isoform B, is highly hormone-dependent and modulates ubiquitination CC and sumoylation on Lys-388. Phosphorylation on Ser-102 and Ser-345 also CC requires induction by hormone. Basal phosphorylation on Ser-81, Ser- CC 162, Ser-190 and Ser-400 is increased in response to progesterone and CC can be phosphorylated in vitro by the CDK2-A1 complex. Increased levels CC of phosphorylation on Ser-400 also in the presence of EGF, heregulin, CC IGF, PMA and FBS. Phosphorylation at this site by CDK2 is ligand- CC independent, and increases nuclear translocation and transcriptional CC activity. Phosphorylation at Ser-162 and Ser-294, but not at Ser-190, CC is impaired during the G(2)/M phase of the cell cycle. Phosphorylation CC on Ser-345 by ERK1/2 MAPK is required for interaction with SP1. CC {ECO:0000269|PubMed:10628747, ECO:0000269|PubMed:10655479, CC ECO:0000269|PubMed:11110801, ECO:0000269|PubMed:15572662, CC ECO:0000269|PubMed:15798179, ECO:0000269|PubMed:17020914, CC ECO:0000269|PubMed:17173941, ECO:0000269|PubMed:17347654, CC ECO:0000269|PubMed:17717077, ECO:0000269|PubMed:18202149, CC ECO:0000269|PubMed:7476977, ECO:0000269|PubMed:8702648, CC ECO:0000269|PubMed:9171245}. CC -!- PTM: Sumoylation is hormone-dependent and represses transcriptional CC activity. Sumoylation on all three sites is enhanced by PIAS3. CC Desumoylated by SENP1. Sumoylation on Lys-388, the main site of CC sumoylation, is repressed by ubiquitination on the same site, and CC modulated by phosphorylation at Ser-294. {ECO:0000269|PubMed:10628747, CC ECO:0000269|PubMed:10655479, ECO:0000269|PubMed:15798179, CC ECO:0000269|PubMed:17020914, ECO:0000269|PubMed:17173941, CC ECO:0000269|PubMed:17347654, ECO:0000269|PubMed:17717077, CC ECO:0000269|PubMed:18202149, ECO:0000269|PubMed:8702648}. CC -!- PTM: Ubiquitination is hormone-dependent and represses sumoylation on CC the same site. Promoted by MAPK-mediated phosphorylation on Ser-294. CC {ECO:0000269|PubMed:10628747, ECO:0000269|PubMed:10655479, CC ECO:0000269|PubMed:15798179, ECO:0000269|PubMed:17173941, CC ECO:0000269|PubMed:17717077, ECO:0000269|PubMed:18202149, CC ECO:0000269|PubMed:8702648}. CC -!- PTM: Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required CC for plasma membrane targeting and for rapid intracellular signaling via CC ERK and AKT kinases and cAMP generation. {ECO:0000269|PubMed:22031296}. CC -!- MISCELLANEOUS: [Isoform B]: Produced by alternative promoter usage. CC -!- MISCELLANEOUS: [Isoform A]: Produced by alternative promoter usage. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative splicing of isoform CC B. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative promoter usage. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 5]: Produced by alternative splicing of isoform CC B. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3 CC subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/pgr/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Progesterone receptor entry; CC URL="https://en.wikipedia.org/wiki/Progesterone_receptor"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X51730; CAA36018.1; -; mRNA. DR EMBL; M15716; AAA60081.1; -; mRNA. DR EMBL; AF016381; AAD01587.1; -; mRNA. DR EMBL; AB084248; BAB91074.1; -; mRNA. DR EMBL; DQ234979; ABB72139.1; -; Genomic_DNA. DR EMBL; AY212933; AAO61671.1; -; mRNA. DR EMBL; AK304853; BAG65592.1; -; mRNA. DR EMBL; AY525610; AAS00096.1; -; Genomic_DNA. DR EMBL; AP001533; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471065; EAW66999.1; -; Genomic_DNA. DR EMBL; CH471065; EAW67000.1; -; Genomic_DNA. DR CCDS; CCDS59229.1; -. [P06401-3] DR CCDS; CCDS8310.1; -. [P06401-1] DR PIR; S09971; QRHUP. DR RefSeq; NP_000917.3; NM_000926.4. [P06401-1] DR RefSeq; NP_001189403.1; NM_001202474.3. [P06401-2] DR RefSeq; NP_001258090.1; NM_001271161.2. DR RefSeq; NP_001258091.1; NM_001271162.1. [P06401-3] DR PDB; 1A28; X-ray; 1.80 A; A/B=678-933. DR PDB; 1E3K; X-ray; 2.80 A; A/B=676-933. DR PDB; 1SQN; X-ray; 1.45 A; A/B=673-933. DR PDB; 1SR7; X-ray; 1.46 A; A/B=676-933. DR PDB; 1ZUC; X-ray; 2.00 A; A/B=676-933. DR PDB; 2C7A; X-ray; 2.50 A; A/B=563-640. DR PDB; 2OVH; X-ray; 2.00 A; A=678-933. DR PDB; 2OVM; X-ray; 2.60 A; A=678-933. DR PDB; 2W8Y; X-ray; 1.80 A; A/B=678-933. DR PDB; 3D90; X-ray; 2.26 A; A/B=676-933. DR PDB; 3G8O; X-ray; 1.90 A; A/B=673-933. DR PDB; 3HQ5; X-ray; 2.10 A; A/B=678-933. DR PDB; 3KBA; X-ray; 2.00 A; A/B=681-933. DR PDB; 3ZR7; X-ray; 1.65 A; A/B=678-933. DR PDB; 3ZRA; X-ray; 1.90 A; A/B=678-933. DR PDB; 3ZRB; X-ray; 1.80 A; A/B=678-933. DR PDB; 4A2J; X-ray; 2.00 A; A/B=678-933. DR PDB; 4APU; X-ray; 1.90 A; A/B=678-933. DR PDB; 4OAR; X-ray; 2.41 A; A=678-933. DR PDB; 5CC0; X-ray; 2.40 A; A/B=561-641. DR PDBsum; 1A28; -. DR PDBsum; 1E3K; -. DR PDBsum; 1SQN; -. DR PDBsum; 1SR7; -. DR PDBsum; 1ZUC; -. DR PDBsum; 2C7A; -. DR PDBsum; 2OVH; -. DR PDBsum; 2OVM; -. DR PDBsum; 2W8Y; -. DR PDBsum; 3D90; -. DR PDBsum; 3G8O; -. DR PDBsum; 3HQ5; -. DR PDBsum; 3KBA; -. DR PDBsum; 3ZR7; -. DR PDBsum; 3ZRA; -. DR PDBsum; 3ZRB; -. DR PDBsum; 4A2J; -. DR PDBsum; 4APU; -. DR PDBsum; 4OAR; -. DR PDBsum; 5CC0; -. DR AlphaFoldDB; P06401; -. DR SMR; P06401; -. DR BioGRID; 111260; 75. DR DIP; DIP-5967N; -. DR ELM; P06401; -. DR IntAct; P06401; 88. DR MINT; P06401; -. DR STRING; 9606.ENSP00000325120; -. DR BindingDB; P06401; -. DR ChEMBL; CHEMBL208; -. DR DrugBank; DB01431; Allylestrenol. DR DrugBank; DB06680; Asoprisnil. DR DrugBank; DB01406; Danazol. DR DrugBank; DB12941; Darolutamide. DR DrugBank; DB13857; Demegestone. DR DrugBank; DB00304; Desogestrel. DR DrugBank; DB09123; Dienogest. DR DrugBank; DB01395; Drospirenone. DR DrugBank; DB00378; Dydrogesterone. DR DrugBank; DB11219; Enzacamene. DR DrugBank; DB00823; Ethynodiol diacetate. DR DrugBank; DB00294; Etonogestrel. DR DrugBank; DB13867; Fluticasone. DR DrugBank; DB08906; Fluticasone furoate. DR DrugBank; DB00588; Fluticasone propionate. DR DrugBank; DB06730; Gestodene. DR DrugBank; DB11619; Gestrinone. DR DrugBank; DB11064; Homosalate. DR DrugBank; DB06789; Hydroxyprogesterone caproate. DR DrugBank; DB00367; Levonorgestrel. DR DrugBank; DB00431; Lindane. DR DrugBank; DB09124; Medrogestone. DR DrugBank; DB00603; Medroxyprogesterone acetate. DR DrugBank; DB00351; Megestrol acetate. DR DrugBank; DB02998; Metribolone. DR DrugBank; DB00834; Mifepristone. DR DrugBank; DB00648; Mitotane. DR DrugBank; DB00764; Mometasone. DR DrugBank; DB14512; Mometasone furoate. DR DrugBank; DB06713; Norelgestromin. DR DrugBank; DB00717; Norethisterone. DR DrugBank; DB00957; Norgestimate. DR DrugBank; DB09389; Norgestrel. DR DrugBank; DB01428; Oxybenzone. DR DrugBank; DB02746; Phthalic Acid. DR DrugBank; DB00396; Progesterone. DR DrugBank; DB14583; Segesterone acetate. DR DrugBank; DB00421; Spironolactone. DR DrugBank; DB04787; Tanaproget. DR DrugBank; DB05253; Telapristone acetate. DR DrugBank; DB08867; Ulipristal. DR DrugCentral; P06401; -. DR GuidetoPHARMACOLOGY; 627; -. DR SwissLipids; SLP:000001574; -. DR TCDB; 9.B.208.1.5; the vitamin d3 receptor (vdr) family. DR GlyGen; P06401; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P06401; -. DR PhosphoSitePlus; P06401; -. DR SwissPalm; P06401; -. DR BioMuta; PGR; -. DR DMDM; 90110048; -. DR jPOST; P06401; -. DR MassIVE; P06401; -. DR MaxQB; P06401; -. DR PaxDb; 9606-ENSP00000325120; -. DR PeptideAtlas; P06401; -. DR ProteomicsDB; 51901; -. [P06401-1] DR ProteomicsDB; 51902; -. [P06401-2] DR ProteomicsDB; 5919; -. DR ProteomicsDB; 74334; -. DR Antibodypedia; 1685; 3409 antibodies from 56 providers. DR CPTC; P06401; 2 antibodies. DR DNASU; 5241; -. DR Ensembl; ENST00000263463.9; ENSP00000263463.5; ENSG00000082175.16. [P06401-5] DR Ensembl; ENST00000325455.10; ENSP00000325120.5; ENSG00000082175.16. [P06401-1] DR Ensembl; ENST00000534013.5; ENSP00000436561.1; ENSG00000082175.16. [P06401-3] DR GeneID; 5241; -. DR KEGG; hsa:5241; -. DR MANE-Select; ENST00000325455.10; ENSP00000325120.5; NM_000926.4; NP_000917.3. DR UCSC; uc001pgh.3; human. [P06401-1] DR AGR; HGNC:8910; -. DR CTD; 5241; -. DR DisGeNET; 5241; -. DR GeneCards; PGR; -. DR HGNC; HGNC:8910; PGR. DR HPA; ENSG00000082175; Group enriched (cervix, endometrium, fallopian tube, smooth muscle). DR MalaCards; PGR; -. DR MIM; 607311; gene. DR neXtProt; NX_P06401; -. DR OpenTargets; ENSG00000082175; -. DR PharmGKB; PA266; -. DR VEuPathDB; HostDB:ENSG00000082175; -. DR eggNOG; KOG3575; Eukaryota. DR GeneTree; ENSGT00940000159713; -. DR HOGENOM; CLU_014081_0_0_1; -. DR InParanoid; P06401; -. DR OMA; PDLILNX; -. DR OrthoDB; 5347911at2759; -. DR PhylomeDB; P06401; -. DR TreeFam; TF106510; -. DR PathwayCommons; P06401; -. DR Reactome; R-HSA-1251985; Nuclear signaling by ERBB4. DR Reactome; R-HSA-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand. DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway. DR Reactome; R-HSA-4090294; SUMOylation of intracellular receptors. DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression. DR SignaLink; P06401; -. DR SIGNOR; P06401; -. DR BioGRID-ORCS; 5241; 9 hits in 1179 CRISPR screens. DR ChiTaRS; PGR; human. DR EvolutionaryTrace; P06401; -. DR GeneWiki; Progesterone_receptor; -. DR GenomeRNAi; 5241; -. DR Pharos; P06401; Tclin. DR PRO; PR:P06401; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P06401; Protein. DR Bgee; ENSG00000082175; Expressed in endometrium and 138 other cell types or tissues. DR ExpressionAtlas; P06401; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; IMP:UniProt. DR GO; GO:0051117; F:ATPase binding; IDA:MGI. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0034056; F:estrogen response element binding; IBA:GO_Central. DR GO; GO:0004930; F:G protein-coupled receptor activity; IC:UniProt. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central. DR GO; GO:0003707; F:nuclear steroid receptor activity; TAS:ProtInc. DR GO; GO:0003676; F:nucleic acid binding; EXP:DisProt. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB. DR GO; GO:0005496; F:steroid binding; IEA:UniProtKB-KW. DR GO; GO:0001223; F:transcription coactivator binding; IPI:ARUK-UCL. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0002071; P:glandular epithelial cell maturation; IEA:Ensembl. DR GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; IBA:GO_Central. DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl. DR GO; GO:0010629; P:negative regulation of gene expression; IEP:UniProtKB. DR GO; GO:0001542; P:ovulation from ovarian follicle; IEA:Ensembl. DR GO; GO:0038001; P:paracrine signaling; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; NAS:ARUK-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB. DR GO; GO:0050847; P:progesterone receptor signaling pathway; IC:UniProt. DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0060748; P:tertiary branching involved in mammary gland duct morphogenesis; IEA:Ensembl. DR CDD; cd07172; NR_DBD_GR_PR; 1. DR CDD; cd07074; NR_LBD_PR; 1. DR DisProt; DP01542; -. DR Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1. DR Gene3D; 1.10.565.10; Retinoid X Receptor; 1. DR InterPro; IPR035500; NHR-like_dom_sf. DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd. DR InterPro; IPR001723; Nuclear_hrmn_rcpt. DR InterPro; IPR000128; Progest_rcpt. DR InterPro; IPR001628; Znf_hrmn_rcpt. DR InterPro; IPR013088; Znf_NHR/GATA. DR PANTHER; PTHR48092; KNIRPS-RELATED PROTEIN-RELATED; 1. DR PANTHER; PTHR48092:SF6; PROGESTERONE RECEPTOR; 1. DR Pfam; PF00104; Hormone_recep; 1. DR Pfam; PF02161; Prog_receptor; 1. DR Pfam; PF00105; zf-C4; 1. DR PRINTS; PR00544; PROGESTRONER. DR PRINTS; PR00398; STRDHORMONER. DR PRINTS; PR00047; STROIDFINGER. DR SMART; SM00430; HOLI; 1. DR SMART; SM00399; ZnF_C4; 1. DR SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1. DR SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1. DR PROSITE; PS51843; NR_LBD; 1. DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1. DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1. DR Genevisible; P06401; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative promoter usage; Alternative splicing; Cytoplasm; KW Direct protein sequencing; DNA-binding; Isopeptide bond; Lipid-binding; KW Lipoprotein; Membrane; Metal-binding; Mitochondrion; KW Mitochondrion outer membrane; Nucleus; Palmitate; Phosphoprotein; Receptor; KW Reference proteome; Steroid-binding; Transcription; KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..933 FT /note="Progesterone receptor" FT /id="PRO_0000053693" FT DOMAIN 679..913 FT /note="NR LBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189" FT DNA_BIND 567..639 FT /note="Nuclear receptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 567..587 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 603..627 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT REGION 1..566 FT /note="Modulating, Pro-Rich" FT REGION 1..164 FT /note="AF3; mediates transcriptional activation (in isoform FT B)" FT /evidence="ECO:0000269|PubMed:11546784" FT REGION 1..157 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 165..305 FT /note="Mediates transcriptional transrepression (in isoform FT A)" FT /evidence="ECO:0000269|PubMed:9407067" FT REGION 195..241 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 331..351 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 415..452 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 456..546 FT /note="AF1; mediates transcriptional activation" FT /evidence="ECO:0000269|PubMed:1587864" FT REGION 687..933 FT /note="AF2; mediates transcriptional activation" FT /evidence="ECO:0000269|PubMed:1587864" FT MOTIF 55..59 FT /note="LXXL motif 1" FT /evidence="ECO:0000305|PubMed:11546784" FT MOTIF 115..119 FT /note="LXXL motif 2" FT /evidence="ECO:0000305|PubMed:11546784" FT MOTIF 183..187 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 68..84 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 120..135 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 415..431 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 20 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11110801" FT MOD_RES 81 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:7476977, FT ECO:0000269|PubMed:8702648" FT MOD_RES 102 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11110801, FT ECO:0000269|PubMed:8702648" FT MOD_RES 130 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11110801" FT MOD_RES 162 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11110801, FT ECO:0000269|PubMed:15798179, ECO:0000269|PubMed:7476977, FT ECO:0000269|PubMed:8702648, ECO:0000269|PubMed:9171245, FT ECO:0007744|PubMed:23186163" FT MOD_RES 190 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:10628747, FT ECO:0000269|PubMed:11110801, ECO:0000269|PubMed:15798179, FT ECO:0000269|PubMed:9171245" FT MOD_RES 213 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11110801" FT MOD_RES 294 FT /note="Phosphoserine; by MAPK1" FT /evidence="ECO:0000269|PubMed:10628747, FT ECO:0000269|PubMed:10655479, ECO:0000269|PubMed:15798179, FT ECO:0000269|PubMed:17173941, ECO:0000269|PubMed:17717077, FT ECO:0000269|PubMed:18202149, ECO:0000269|PubMed:8702648" FT MOD_RES 345 FT /note="Phosphoserine; by MAPK" FT /evidence="ECO:0000269|PubMed:11110801, FT ECO:0000269|PubMed:18202149, ECO:0000269|PubMed:8702648" FT MOD_RES 400 FT /note="Phosphoserine; by CDK2" FT /evidence="ECO:0000269|PubMed:15572662, FT ECO:0000269|PubMed:18202149, ECO:0000269|PubMed:9171245" FT MOD_RES 676 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:11110801" FT CROSSLNK 7 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:17020914" FT CROSSLNK 388 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT CROSSLNK 388 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin); alternate" FT /evidence="ECO:0000269|PubMed:17347654" FT CROSSLNK 531 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:17020914" FT VAR_SEQ 1..594 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046942" FT VAR_SEQ 1..164 FT /note="Missing (in isoform A)" FT /evidence="ECO:0000305" FT /id="VSP_003706" FT VAR_SEQ 1..16 FT /note="MTELKAKGPRAPHVAG -> MEFIYIYMNFFFFFSV (in isoform 4)" FT /evidence="ECO:0000303|PubMed:12644308" FT /id="VSP_047454" FT VAR_SEQ 17..635 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:12644308" FT /id="VSP_047455" FT VAR_SEQ 636..737 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_053543" FT VARIANT 50 FT /note="A -> T (in dbSNP:rs11571143)" FT /evidence="ECO:0000269|Ref.8" FT /id="VAR_019221" FT VARIANT 120 FT /note="A -> V (in dbSNP:rs11571144)" FT /evidence="ECO:0000269|Ref.8" FT /id="VAR_019222" FT VARIANT 186 FT /note="P -> L (in dbSNP:rs11571145)" FT /evidence="ECO:0000269|Ref.8" FT /id="VAR_019223" FT VARIANT 301 FT /note="M -> R (in dbSNP:rs11571146)" FT /evidence="ECO:0000269|Ref.8" FT /id="VAR_019224" FT VARIANT 344 FT /note="S -> T (in dbSNP:rs3740753)" FT /evidence="ECO:0000269|PubMed:2328727, ECO:0000269|Ref.8" FT /id="VAR_016117" FT VARIANT 347 FT /note="C -> S (in dbSNP:rs11571147)" FT /id="VAR_025555" FT VARIANT 444 FT /note="A -> S (in dbSNP:rs11571150)" FT /evidence="ECO:0000269|Ref.8" FT /id="VAR_019225" FT VARIANT 529 FT /note="V -> L (in dbSNP:rs11571151)" FT /evidence="ECO:0000269|Ref.8" FT /id="VAR_019226" FT VARIANT 536 FT /note="Q -> P (in dbSNP:rs11571152)" FT /evidence="ECO:0000269|Ref.8" FT /id="VAR_019227" FT VARIANT 625 FT /note="R -> I (in dbSNP:rs2020874)" FT /id="VAR_014627" FT VARIANT 651 FT /note="L -> V (in dbSNP:rs11571222)" FT /evidence="ECO:0000269|Ref.8" FT /id="VAR_019228" FT VARIANT 660 FT /note="V -> L (in dbSNP:rs1042838)" FT /evidence="ECO:0000269|PubMed:12644308, FT ECO:0000269|PubMed:3551956, ECO:0000269|Ref.3" FT /id="VAR_016118" FT VARIANT 865 FT /note="S -> L (in dbSNP:rs2020880)" FT /evidence="ECO:0000269|Ref.8" FT /id="VAR_014628" FT MUTAGEN 7 FT /note="K->R: Some loss of sumoylation; when associated with FT R-531. Complete loss of sumoylation; when associated with FT R-388 and R-531." FT /evidence="ECO:0000269|PubMed:17020914" FT MUTAGEN 55 FT /note="L->A: Reduces transcriptional activation; when FT associated with A-58 and A-59." FT /evidence="ECO:0000269|PubMed:11546784" FT MUTAGEN 58 FT /note="L->A: Reduces transcriptional activation; when FT associated with A-55 and A-59." FT /evidence="ECO:0000269|PubMed:11546784" FT MUTAGEN 59 FT /note="L->A: Reduces transcriptional activation; when FT associated with A-55 and A-58." FT /evidence="ECO:0000269|PubMed:11546784" FT MUTAGEN 115 FT /note="L->A: Reduces transcriptional activation; when FT associated with A-118 and A-119." FT /evidence="ECO:0000269|PubMed:11546784" FT MUTAGEN 118 FT /note="L->A: Reduces transcriptional activation; when FT associated with A-115 and A-119." FT /evidence="ECO:0000269|PubMed:11546784" FT MUTAGEN 119 FT /note="L->A: Reduces transcriptional activation; when FT associated with A-115 and A-118." FT /evidence="ECO:0000269|PubMed:11546784" FT MUTAGEN 140 FT /note="W->A,F,R: Reduces transcriptional activation." FT /evidence="ECO:0000269|PubMed:11546784" FT MUTAGEN 294 FT /note="S->A: No effect on interaction with CUEDC2. Impaired FT progesterone-induced transcriptional activity. No FT CUEDC2- nor progestin-mediated protein degradation. No FT change in sumoylation; when associated with A-344 and FT A-345." FT /evidence="ECO:0000269|PubMed:10655479, FT ECO:0000269|PubMed:17173941, ECO:0000269|PubMed:17717077" FT MUTAGEN 294 FT /note="S->D: Decreases protein stability and increases FT progesterone-induced transcriptional activity." FT /evidence="ECO:0000269|PubMed:10655479, FT ECO:0000269|PubMed:17173941, ECO:0000269|PubMed:17717077" FT MUTAGEN 344 FT /note="S->A: No interaction with SP1. No change in FT progestin-induced protein degradation; when associated with FT A-345. No change in sumoylation; when associated with A-294 FT and A-345." FT /evidence="ECO:0000269|PubMed:10655479, FT ECO:0000269|PubMed:18202149" FT MUTAGEN 345 FT /note="S->A: No change in progestin-induced protein FT degradation; when associated with A-344. No change in FT sumoylation; when associated with A-294 and A-344." FT /evidence="ECO:0000269|PubMed:10655479, FT ECO:0000269|PubMed:18202149" FT MUTAGEN 388 FT /note="K->R: Great loss of sumoylation; when associated FT with R-7. Completely abolishes sumoylation; when associated FT with R-7 and R-531. Loss of CUEDC2-mediated protein FT degradation. Increased ligand-dependent transcriptional FT activity." FT /evidence="ECO:0000269|PubMed:17020914, FT ECO:0000269|PubMed:17347654, ECO:0000269|PubMed:17717077" FT MUTAGEN 400 FT /note="S->A: Abolishes CDK2-induced activity in the FT absence, but not in the presence, of progestin. Delayed FT nuclear translocation in presence of progestin." FT /evidence="ECO:0000269|PubMed:15572662, FT ECO:0000269|PubMed:18202149" FT MUTAGEN 531 FT /note="K->R: Some loss of sumoylation; when associated with FT R-7. Completely abolishes sumoylation; when associated with FT R-7 and R-388." FT /evidence="ECO:0000269|PubMed:17020914" FT CONFLICT 226 FT /note="G -> S (in Ref. 1; CAA36018)" FT /evidence="ECO:0000305" FT CONFLICT 256 FT /note="V -> S (in Ref. 1; CAA36018)" FT /evidence="ECO:0000305" FT TURN 568..570 FT /evidence="ECO:0007829|PDB:5CC0" FT STRAND 576..578 FT /evidence="ECO:0007829|PDB:5CC0" FT STRAND 581..583 FT /evidence="ECO:0007829|PDB:5CC0" FT HELIX 585..596 FT /evidence="ECO:0007829|PDB:5CC0" FT STRAND 604..607 FT /evidence="ECO:0007829|PDB:5CC0" FT TURN 613..618 FT /evidence="ECO:0007829|PDB:5CC0" FT HELIX 620..629 FT /evidence="ECO:0007829|PDB:5CC0" FT HELIX 686..694 FT /evidence="ECO:0007829|PDB:1SQN" FT HELIX 711..735 FT /evidence="ECO:0007829|PDB:1SQN" FT HELIX 739..741 FT /evidence="ECO:0007829|PDB:1SQN" FT HELIX 744..771 FT /evidence="ECO:0007829|PDB:1SQN" FT STRAND 774..779 FT /evidence="ECO:0007829|PDB:1SQN" FT STRAND 782..784 FT /evidence="ECO:0007829|PDB:1SQN" FT HELIX 786..788 FT /evidence="ECO:0007829|PDB:1SQN" FT HELIX 792..811 FT /evidence="ECO:0007829|PDB:1SQN" FT HELIX 815..826 FT /evidence="ECO:0007829|PDB:1SQN" FT STRAND 828..830 FT /evidence="ECO:0007829|PDB:1SQN" FT HELIX 838..857 FT /evidence="ECO:0007829|PDB:1SQN" FT HELIX 863..896 FT /evidence="ECO:0007829|PDB:1SQN" FT HELIX 898..901 FT /evidence="ECO:0007829|PDB:1SQN" FT HELIX 907..921 FT /evidence="ECO:0007829|PDB:1SQN" FT STRAND 925..927 FT /evidence="ECO:0007829|PDB:1SQN" SQ SEQUENCE 933 AA; 98981 MW; 80452E54FF3A0454 CRC64; MTELKAKGPR APHVAGGPPS PEVGSPLLCR PAAGPFPGSQ TSDTLPEVSA IPISLDGLLF PRPCQGQDPS DEKTQDQQSL SDVEGAYSRA EATRGAGGSS SSPPEKDSGL LDSVLDTLLA PSGPGQSQPS PPACEVTSSW CLFGPELPED PPAAPATQRV LSPLMSRSGC KVGDSSGTAA AHKVLPRGLS PARQLLLPAS ESPHWSGAPV KPSPQAAAVE VEEEDGSESE ESAGPLLKGK PRALGGAAAG GGAAAVPPGA AAGGVALVPK EDSRFSAPRV ALVEQDAPMA PGRSPLATTV MDFIHVPILP LNHALLAART RQLLEDESYD GGAGAASAFA PPRSSPCASS TPVAVGDFPD CAYPPDAEPK DDAYPLYSDF QPPALKIKEE EEGAEASARS PRSYLVAGAN PAAFPDFPLG PPPPLPPRAT PSRPGEAAVT AAPASASVSS ASSSGSTLEC ILYKAEGAPP QQGPFAPPPC KAPGASGCLL PRDGLPSTSA SAAAAGAAPA LYPALGLNGL PQLGYQAAVL KEGLPQVYPP YLNYLRPDSE ASQSPQYSFE SLPQKICLIC GDEASGCHYG VLTCGSCKVF FKRAMEGQHN YLCAGRNDCI VDKIRRKNCP ACRLRKCCQA GMVLGGRKFK KFNKVRVVRA LDAVALPQPV GVPNESQALS QRFTFSPGQD IQLIPPLINL LMSIEPDVIY AGHDNTKPDT SSSLLTSLNQ LGERQLLSVV KWSKSLPGFR NLHIDDQITL IQYSWMSLMV FGLGWRSYKH VSGQMLYFAP DLILNEQRMK ESSFYSLCLT MWQIPQEFVK LQVSQEEFLC MKVLLLLNTI PLEGLRSQTQ FEEMRSSYIR ELIKAIGLRQ KGVVSSSQRF YQLTKLLDNL HDLVKQLHLY CLNTFIQSRA LSVEFPEMMS EVIAAQLPKI LAGMVKPLLF HKK //