PRGR_HUMAN
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 03-AUG-2022, entry version 254.
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 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 ---------------------------------------------------------------------------
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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; 73.
DR DIP; DIP-5967N; -.
DR ELM; P06401; -.
DR IntAct; P06401; 89.
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; P06401; -.
DR PeptideAtlas; P06401; -.
DR PRIDE; P06401; -.
DR ProteomicsDB; 51901; -. [P06401-1]
DR ProteomicsDB; 51902; -. [P06401-2]
DR ProteomicsDB; 5919; -.
DR ProteomicsDB; 74334; -.
DR Antibodypedia; 1685; 3059 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 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; YPKSSDE; -.
DR OrthoDB; 615449at2759; -.
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; 8 hits in 1095 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 136 other tissues.
DR ExpressionAtlas; P06401; baseline and differential.
DR Genevisible; P06401; HS.
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: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: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: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; IEA:Ensembl.
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 DisProt; DP01542; -.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 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 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; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
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 A-
FT 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
