NR4A1_HUMAN
ID NR4A1_HUMAN Reviewed; 598 AA.
AC P22736; B4DML7; Q15627; Q53Y00; Q6IBU8;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 227.
DE RecName: Full=Nuclear receptor subfamily 4 group A member 1;
DE AltName: Full=Early response protein NAK1;
DE AltName: Full=Nuclear hormone receptor NUR/77;
DE Short=Nur77;
DE AltName: Full=Orphan nuclear receptor HMR;
DE AltName: Full=Orphan nuclear receptor TR3;
DE AltName: Full=ST-59;
DE AltName: Full=Testicular receptor 3;
GN Name=NR4A1; Synonyms=GFRP1, HMR, NAK1;
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] (ISOFORM 1).
RC TISSUE=Fetal skeletal muscle;
RX PubMed=2283997; DOI=10.1210/mend-4-10-1438;
RA Nakai A., Kartha S., Sakurai A., Toback F.G., Degroot L.J.;
RT "A human early response gene homologous to murine nur77 and rat NGFI-B, and
RT related to the nuclear receptor superfamily.";
RL Mol. Endocrinol. 4:1438-1443(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2626032; DOI=10.1016/0022-4731(89)90114-3;
RA Chang C., Kokontis J., Liao S., Chang Y.;
RT "Isolation and characterization of human TR3 receptor: a member of steroid
RT receptor superfamily.";
RL J. Steroid Biochem. 34:391-395(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Skeletal muscle;
RA Ohkura N., Ito M., Tsukada T., Sasaki K., Yamaguchi K., Miki K.;
RT "Identification of an isoform of human TR3 (NGFI-B, Nur77).";
RL Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Kobayashi T., Kodani Y., Sawasaki T., Endo Y.;
RT "Comprehensive DNA-binding analysis of human hormone nuclear receptors by
RT fluorescence correlation spectroscopy based on cell-free system.";
RL Submitted (DEC-2008) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RA Kaighin V.A., Martin A.L., Aronstam R.S.;
RT "Isolation of cDNA coding for multiple human nuclear receptor clones.";
RL Submitted (DEC-2010) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Brain, and Trachea;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 35-398 (ISOFORM 1).
RC TISSUE=Colon adenocarcinoma;
RX PubMed=1651101;
RA Bondy G.P.;
RT "Phorbol ester, forskolin, and serum induction of a human colon nuclear
RT hormone receptor gene related to the NUR 77/NGFI-B genes.";
RL Cell Growth Differ. 2:203-208(1991).
RN [13]
RP INTERACTION WITH RXRA, AND SUBCELLULAR LOCATION.
RX PubMed=15509776; DOI=10.1128/mcb.24.22.9705-9725.2004;
RA Cao X., Liu W., Lin F., Li H., Kolluri S.K., Lin B., Han Y.H., Dawson M.I.,
RA Zhang X.K.;
RT "Retinoid X receptor regulates Nur77/TR3-dependent apoptosis [corrected] by
RT modulating its nuclear export and mitochondrial targeting.";
RL Mol. Cell. Biol. 24:9705-9725(2004).
RN [14]
RP FUNCTION.
RX PubMed=15466594; DOI=10.1093/nar/gkh856;
RA Harant H., Lindley I.J.;
RT "Negative cross-talk between the human orphan nuclear receptor Nur77/NAK-
RT 1/TR3 and nuclear factor-kappaB.";
RL Nucleic Acids Res. 32:5280-5290(2004).
RN [15]
RP INTERACTION WITH GADD45GIP1.
RX PubMed=15459248; DOI=10.1210/me.2004-0107;
RA Park K.C., Song K.-H., Chung H.K., Kim H., Kim D.W., Song J.H., Hwang E.S.,
RA Jung H.S., Park S.-H., Bae I., Lee I.K., Choi H.-S., Shong M.;
RT "CR6-interacting factor 1 interacts with orphan nuclear receptor Nur77 and
RT inhibits its transactivation.";
RL Mol. Endocrinol. 19:12-24(2005).
RN [16]
RP PHOSPHORYLATION AT SER-351.
RX PubMed=17360704; DOI=10.1074/jbc.m700906200;
RA Roux P.P., Shahbazian D., Vu H., Holz M.K., Cohen M.S., Taunton J.,
RA Sonenberg N., Blenis J.;
RT "RAS/ERK signaling promotes site-specific ribosomal protein S6
RT phosphorylation via RSK and stimulates cap-dependent translation.";
RL J. Biol. Chem. 282:14056-14064(2007).
RN [17]
RP INTERACTION WITH RXRA, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 1-MET--LYS-50 AND 299-ALA--PRO-361.
RX PubMed=17761950; DOI=10.1210/me.2007-0107;
RA Zhao W.X., Tian M., Zhao B.X., Li G.D., Liu B., Zhan Y.Y., Chen H.Z.,
RA Wu Q.;
RT "Orphan receptor TR3 attenuates the p300-induced acetylation of retinoid X
RT receptor-alpha.";
RL Mol. Endocrinol. 21:2877-2889(2007).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-351, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [20]
RP ACETYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=20438716; DOI=10.1016/j.bcp.2010.04.026;
RA Kang S.A., Na H., Kang H.J., Kim S.H., Lee M.H., Lee M.O.;
RT "Regulation of Nur77 protein turnover through acetylation and deacetylation
RT induced by p300 and HDAC1.";
RL Biochem. Pharmacol. 80:867-873(2010).
RN [21]
RP INTERACTION WITH IFI27, AND SUBCELLULAR LOCATION.
RX PubMed=22427340; DOI=10.1161/circresaha.111.258814;
RA Papac-Milicevic N., Breuss J.M., Zaujec J., Ryban L., Plyushch T.,
RA Wagner G.A., Fenzl S., Dremsek P., Cabaravdic M., Steiner M., Glass C.K.,
RA Binder C.J., Uhrin P., Binder B.R.;
RT "The interferon stimulated gene 12 inactivates vasculoprotective functions
RT of NR4A nuclear receptors.";
RL Circ. Res. 110:E50-E63(2012).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS) OF 351-598 ALONE AND IN COMPLEX WITH
RP ANTAGONIST, FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH STK11, AND
RP MUTAGENESIS OF THR-595.
RX PubMed=22983157; DOI=10.1038/nchembio.1069;
RA Zhan Y.Y., Chen Y., Zhang Q., Zhuang J.J., Tian M., Chen H.Z., Zhang L.R.,
RA Zhang H.K., He J.P., Wang W.J., Wu R., Wang Y., Shi C., Yang K., Li A.Z.,
RA Xin Y.Z., Li T.Y., Yang J.Y., Zheng Z.H., Yu C.D., Lin S.C., Chang C.,
RA Huang P.Q., Lin T., Wu Q.;
RT "The orphan nuclear receptor Nur77 regulates LKB1 localization and
RT activates AMPK.";
RL Nat. Chem. Biol. 8:897-904(2012).
CC -!- FUNCTION: Orphan nuclear receptor. May act concomitantly with NURR1 in
CC regulating the expression of delayed-early genes during liver
CC regeneration. Binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3'
CC (By similarity). May inhibit NF-kappa-B transactivation of IL2.
CC Participates in energy homeostasis by sequestrating the kinase STK11 in
CC the nucleus, thereby attenuating cytoplasmic AMPK activation. Plays a
CC role in the vascular response to injury (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P12813, ECO:0000269|PubMed:15466594,
CC ECO:0000269|PubMed:22983157}.
CC -!- SUBUNIT: Binds DNA as a monomer (By similarity). Interacts with
CC GADD45GIP1 (PubMed:15459248). Interacts with STK11 (PubMed:22983157).
CC Interacts with IFI27 (PubMed:22427340). Heterodimer (via DNA-binding
CC domain) with RXRA (via C-terminus); DNA-binding of the heterodimer is
CC enhanced by 9-cis retinoic acid (PubMed:17761950, PubMed:15509776).
CC Competes for the RXRA interaction with EP300 and thereby attenuates
CC EP300 mediated acetylation of RXRA (PubMed:17761950).
CC {ECO:0000250|UniProtKB:P22829, ECO:0000269|PubMed:15459248,
CC ECO:0000269|PubMed:15509776, ECO:0000269|PubMed:17761950,
CC ECO:0000269|PubMed:22427340, ECO:0000269|PubMed:22983157}.
CC -!- INTERACTION:
CC P22736; Q9P2G1: ANKIB1; NbExp=2; IntAct=EBI-721550, EBI-2687890;
CC P22736; P10415: BCL2; NbExp=7; IntAct=EBI-721550, EBI-77694;
CC P22736; P55273: CDKN2D; NbExp=4; IntAct=EBI-721550, EBI-745859;
CC P22736; O60888: CUTA; NbExp=2; IntAct=EBI-721550, EBI-1051556;
CC P22736; P32189: GK; NbExp=3; IntAct=EBI-721550, EBI-3926629;
CC P22736; P40305-2: IFI27; NbExp=8; IntAct=EBI-721550, EBI-27124263;
CC P22736; P60370: KRTAP10-5; NbExp=3; IntAct=EBI-721550, EBI-10172150;
CC P22736; Q17RB8: LONRF1; NbExp=3; IntAct=EBI-721550, EBI-2341787;
CC P22736; P43243: MATR3; NbExp=2; IntAct=EBI-721550, EBI-352602;
CC P22736; Q96JS3: PGBD1; NbExp=3; IntAct=EBI-721550, EBI-10290053;
CC P22736; Q9Y4D7: PLXND1; NbExp=2; IntAct=EBI-721550, EBI-310731;
CC P22736; Q99873: PRMT1; NbExp=6; IntAct=EBI-721550, EBI-78738;
CC P22736; P40763: STAT3; NbExp=3; IntAct=EBI-721550, EBI-518675;
CC P22736; P04637: TP53; NbExp=6; IntAct=EBI-721550, EBI-366083;
CC P22736; P04350: TUBB4A; NbExp=2; IntAct=EBI-721550, EBI-355007;
CC P22736; P50552: VASP; NbExp=2; IntAct=EBI-721550, EBI-748201;
CC P22736; O14980: XPO1; NbExp=2; IntAct=EBI-721550, EBI-355867;
CC P22736; P03120: E2; Xeno; NbExp=3; IntAct=EBI-721550, EBI-1779322;
CC P22736; PRO_0000037545 [Q9WMX2]; Xeno; NbExp=2; IntAct=EBI-721550, EBI-9028517;
CC P22736-1; O60238: BNIP3L; NbExp=4; IntAct=EBI-16085263, EBI-849893;
CC P22736-1; Q16539-1: MAPK14; NbExp=5; IntAct=EBI-16085263, EBI-15834191;
CC P22736-1; Q04206: RELA; NbExp=3; IntAct=EBI-16085263, EBI-73886;
CC P22736-1; P12235: SLC25A4; NbExp=2; IntAct=EBI-16085263, EBI-359074;
CC P22736-2; Q96JS3: PGBD1; NbExp=3; IntAct=EBI-12697871, EBI-10290053;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15509776,
CC ECO:0000269|PubMed:17761950, ECO:0000269|PubMed:20438716,
CC ECO:0000269|PubMed:22427340, ECO:0000269|PubMed:22983157}. Cytoplasm
CC {ECO:0000269|PubMed:15509776, ECO:0000269|PubMed:20438716,
CC ECO:0000269|PubMed:22427340}. Mitochondrion
CC {ECO:0000269|PubMed:17761950}. Note=Nuclear export to the cytoplasm is
CC XPO1-mediated and positively regulated by IFI27 (PubMed:22427340).
CC Translocation to the mitochondrion upon interaction with RXRA and upon
CC the presence of 9-cis retinoic acid (PubMed:17761950).
CC {ECO:0000269|PubMed:17761950, ECO:0000269|PubMed:22427340}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P22736-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P22736-2; Sequence=VSP_043086;
CC Name=3;
CC IsoId=P22736-3; Sequence=VSP_047769, VSP_047770;
CC -!- TISSUE SPECIFICITY: Fetal muscle and adult liver, brain and thyroid.
CC -!- INDUCTION: By growth-stimulating agents.
CC -!- PTM: Phosphorylated at Ser-351 by RPS6KA1 and RPS6KA3 in response to
CC mitogenic or stress stimuli. {ECO:0000269|PubMed:17360704}.
CC -!- PTM: Acetylated by p300/CBP, acetylation increases stability.
CC Deacetylated by HDAC1. {ECO:0000269|PubMed:20438716}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR4
CC subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NR4A1ID41573ch12q13.html";
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; D49728; BAA08565.1; -; mRNA.
DR EMBL; L13740; AAA36763.1; -; mRNA.
DR EMBL; D85245; BAA12746.1; -; mRNA.
DR EMBL; AK297526; BAG59929.1; -; mRNA.
DR EMBL; HQ692855; ADZ17366.1; -; mRNA.
DR EMBL; AB307717; BAH02308.1; -; mRNA.
DR EMBL; BT007144; AAP35808.1; -; mRNA.
DR EMBL; AK314437; BAG37048.1; -; mRNA.
DR EMBL; CR456704; CAG32985.1; -; mRNA.
DR EMBL; AC025259; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471111; EAW58222.1; -; Genomic_DNA.
DR EMBL; CH471111; EAW58224.1; -; Genomic_DNA.
DR EMBL; CH471111; EAW58225.1; -; Genomic_DNA.
DR EMBL; BC016147; AAH16147.1; -; mRNA.
DR CCDS; CCDS55828.1; -. [P22736-2]
DR CCDS; CCDS8818.1; -. [P22736-1]
DR PIR; A37251; A37251.
DR RefSeq; NP_001189162.1; NM_001202233.1. [P22736-2]
DR RefSeq; NP_002126.2; NM_002135.4. [P22736-1]
DR RefSeq; NP_775180.1; NM_173157.2. [P22736-1]
DR RefSeq; XP_005268881.1; XM_005268824.3. [P22736-1]
DR RefSeq; XP_006719426.1; XM_006719363.1. [P22736-1]
DR RefSeq; XP_006719427.1; XM_006719364.3. [P22736-1]
DR PDB; 2QW4; X-ray; 2.80 A; A/B/C/D=347-598.
DR PDB; 3V3E; X-ray; 2.06 A; A/B=351-598.
DR PDB; 3V3Q; X-ray; 2.22 A; A/B=351-598.
DR PDB; 4JGV; X-ray; 3.01 A; A/B=351-598.
DR PDB; 4KZI; X-ray; 2.41 A; A/B=351-598.
DR PDB; 4KZJ; X-ray; 2.12 A; A/B=351-598.
DR PDB; 4KZM; X-ray; 2.30 A; A/B=351-598.
DR PDB; 4RE8; X-ray; 2.16 A; A/B=351-598.
DR PDB; 4REE; X-ray; 2.37 A; A/B=351-598.
DR PDB; 4REF; X-ray; 2.10 A; A/B=351-598.
DR PDB; 4RZE; X-ray; 2.49 A; A/B=351-598.
DR PDB; 4RZF; X-ray; 1.99 A; A/B=351-598.
DR PDB; 4RZG; X-ray; 2.70 A; A/B=351-598.
DR PDB; 4WHF; X-ray; 2.27 A; A/B=351-598.
DR PDB; 4WHG; X-ray; 2.18 A; A/B=351-598.
DR PDB; 6KZ5; X-ray; 4.45 A; A/B=351-598.
DR PDB; 6LC1; X-ray; 3.12 A; A/D/G/J=265-351.
DR PDBsum; 2QW4; -.
DR PDBsum; 3V3E; -.
DR PDBsum; 3V3Q; -.
DR PDBsum; 4JGV; -.
DR PDBsum; 4KZI; -.
DR PDBsum; 4KZJ; -.
DR PDBsum; 4KZM; -.
DR PDBsum; 4RE8; -.
DR PDBsum; 4REE; -.
DR PDBsum; 4REF; -.
DR PDBsum; 4RZE; -.
DR PDBsum; 4RZF; -.
DR PDBsum; 4RZG; -.
DR PDBsum; 4WHF; -.
DR PDBsum; 4WHG; -.
DR PDBsum; 6KZ5; -.
DR PDBsum; 6LC1; -.
DR AlphaFoldDB; P22736; -.
DR SMR; P22736; -.
DR BioGRID; 109407; 206.
DR DIP; DIP-40392N; -.
DR IntAct; P22736; 113.
DR MINT; P22736; -.
DR STRING; 9606.ENSP00000440864; -.
DR BindingDB; P22736; -.
DR ChEMBL; CHEMBL1293229; -.
DR MoonDB; P22736; Predicted.
DR GlyGen; P22736; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P22736; -.
DR PhosphoSitePlus; P22736; -.
DR BioMuta; NR4A1; -.
DR DMDM; 127819; -.
DR EPD; P22736; -.
DR jPOST; P22736; -.
DR MassIVE; P22736; -.
DR MaxQB; P22736; -.
DR PaxDb; P22736; -.
DR PeptideAtlas; P22736; -.
DR PRIDE; P22736; -.
DR ProteomicsDB; 54032; -. [P22736-1]
DR ProteomicsDB; 54033; -. [P22736-2]
DR ProteomicsDB; 60662; -.
DR Antibodypedia; 14466; 718 antibodies from 45 providers.
DR DNASU; 3164; -.
DR Ensembl; ENST00000243050.5; ENSP00000243050.1; ENSG00000123358.20. [P22736-1]
DR Ensembl; ENST00000360284.7; ENSP00000353427.3; ENSG00000123358.20. [P22736-2]
DR Ensembl; ENST00000394824.2; ENSP00000378301.2; ENSG00000123358.20. [P22736-1]
DR Ensembl; ENST00000394825.6; ENSP00000378302.1; ENSG00000123358.20. [P22736-1]
DR Ensembl; ENST00000548232.1; ENSP00000449587.1; ENSG00000123358.20. [P22736-3]
DR Ensembl; ENST00000550082.5; ENSP00000449539.1; ENSG00000123358.20. [P22736-2]
DR GeneID; 3164; -.
DR KEGG; hsa:3164; -.
DR MANE-Select; ENST00000394825.6; ENSP00000378302.1; NM_173157.3; NP_775180.1.
DR UCSC; uc001rzs.4; human. [P22736-1]
DR CTD; 3164; -.
DR DisGeNET; 3164; -.
DR GeneCards; NR4A1; -.
DR HGNC; HGNC:7980; NR4A1.
DR HPA; ENSG00000123358; Low tissue specificity.
DR MIM; 139139; gene.
DR neXtProt; NX_P22736; -.
DR OpenTargets; ENSG00000123358; -.
DR PharmGKB; PA31761; -.
DR VEuPathDB; HostDB:ENSG00000123358; -.
DR eggNOG; KOG4217; Eukaryota.
DR GeneTree; ENSGT00950000183038; -.
DR HOGENOM; CLU_007368_14_2_1; -.
DR InParanoid; P22736; -.
DR OMA; HASCQHY; -.
DR OrthoDB; 454476at2759; -.
DR PhylomeDB; P22736; -.
DR TreeFam; TF315430; -.
DR PathwayCommons; P22736; -.
DR Reactome; R-HSA-198693; AKT phosphorylates targets in the nucleus.
DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer.
DR SignaLink; P22736; -.
DR SIGNOR; P22736; -.
DR BioGRID-ORCS; 3164; 14 hits in 1098 CRISPR screens.
DR ChiTaRS; NR4A1; human.
DR EvolutionaryTrace; P22736; -.
DR GeneWiki; Nerve_Growth_factor_IB; -.
DR GenomeRNAi; 3164; -.
DR Pharos; P22736; Tchem.
DR PRO; PR:P22736; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P22736; protein.
DR Bgee; ENSG00000123358; Expressed in mucosa of stomach and 205 other tissues.
DR ExpressionAtlas; P22736; baseline and differential.
DR Genevisible; P22736; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS:BHF-UCL.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; ISS:BHF-UCL.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0035259; F:nuclear glucocorticoid receptor binding; IBA:GO_Central.
DR GO; GO:0004879; F:nuclear receptor activity; TAS:ProtInc.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006915; P:apoptotic process; IEA:Ensembl.
DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; IDA:BHF-UCL.
DR GO; GO:0071376; P:cellular response to corticotropin-releasing hormone stimulus; ISS:UniProtKB.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IMP:BHF-UCL.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IMP:BHF-UCL.
DR GO; GO:0035767; P:endothelial cell chemotaxis; IMP:BHF-UCL.
DR GO; GO:0045444; P:fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Ensembl.
DR GO; GO:0014860; P:neurotransmitter secretion involved in regulation of skeletal muscle contraction; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0061469; P:regulation of type B pancreatic cell proliferation; ISS:UniProtKB.
DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl.
DR GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR003071; Nuc_orp_HMR_rcpt.
DR InterPro; IPR003070; Nuc_orph_rcpt.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR01285; HMRNUCRECPTR.
DR PRINTS; PR01284; NUCLEARECPTR.
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; Acetylation; Alternative splicing; Cytoplasm; DNA-binding;
KW Metal-binding; Mitochondrion; Nucleus; Phosphoprotein; Receptor;
KW Reference proteome; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..598
FT /note="Nuclear receptor subfamily 4 group A member 1"
FT /id="PRO_0000053715"
FT DOMAIN 360..595
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 264..339
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 267..287
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 303..327
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 131..158
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 171..466
FT /note="Required for nuclear import"
FT /evidence="ECO:0000269|PubMed:15509776"
FT REGION 177..206
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 221..265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 299..361
FT /note="Required for the interaction with RXRA"
FT /evidence="ECO:0000269|PubMed:17761950"
FT REGION 341..361
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 180..194
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 341
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P22829"
FT MOD_RES 351
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17360704,
FT ECO:0007744|PubMed:18669648"
FT VAR_SEQ 1
FT /note="M -> MWLAKACWSIQSEM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043086"
FT VAR_SEQ 293..325
FT /note="RTVQKNAKYICLANKDCPVDKRRRNRCQFCRFQ -> VPRSPRWGLLLEMER
FT GWPHPIGTCGLPLGSPPS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3"
FT /id="VSP_047769"
FT VAR_SEQ 326..598
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039, ECO:0000303|Ref.3"
FT /id="VSP_047770"
FT VARIANT 26
FT /note="L -> V (in dbSNP:rs1882118)"
FT /id="VAR_061534"
FT MUTAGEN 1..50
FT /note="Missing: No impact on the interaction with RXRA."
FT /evidence="ECO:0000269|PubMed:17761950"
FT MUTAGEN 299..361
FT /note="Missing: Loss of interaction with RXRA."
FT /evidence="ECO:0000269|PubMed:17761950"
FT MUTAGEN 595
FT /note="T->E: Strongly weakens interaction with STK11."
FT /evidence="ECO:0000269|PubMed:22983157"
FT CONFLICT 253
FT /note="T -> I (in Ref. 12)"
FT /evidence="ECO:0000305"
FT CONFLICT 262
FT /note="G -> P (in Ref. 2; AAA36763)"
FT /evidence="ECO:0000305"
FT CONFLICT 360
FT /note="S -> F (in Ref. 8; CAG32985)"
FT /evidence="ECO:0000305"
FT CONFLICT 370
FT /note="R -> L (in Ref. 2; AAA36763)"
FT /evidence="ECO:0000305"
FT TURN 268..270
FT /evidence="ECO:0007829|PDB:6LC1"
FT STRAND 276..278
FT /evidence="ECO:0007829|PDB:6LC1"
FT STRAND 281..283
FT /evidence="ECO:0007829|PDB:6LC1"
FT HELIX 286..297
FT /evidence="ECO:0007829|PDB:6LC1"
FT TURN 314..317
FT /evidence="ECO:0007829|PDB:6LC1"
FT HELIX 320..329
FT /evidence="ECO:0007829|PDB:6LC1"
FT HELIX 364..373
FT /evidence="ECO:0007829|PDB:4RZF"
FT HELIX 379..381
FT /evidence="ECO:0007829|PDB:4RZF"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:4REF"
FT HELIX 400..422
FT /evidence="ECO:0007829|PDB:4RZF"
FT HELIX 427..429
FT /evidence="ECO:0007829|PDB:4RZF"
FT HELIX 432..454
FT /evidence="ECO:0007829|PDB:4RZF"
FT HELIX 457..459
FT /evidence="ECO:0007829|PDB:4RZF"
FT STRAND 461..463
FT /evidence="ECO:0007829|PDB:4RZF"
FT STRAND 467..471
FT /evidence="ECO:0007829|PDB:4RZF"
FT HELIX 472..479
FT /evidence="ECO:0007829|PDB:4RZF"
FT HELIX 482..495
FT /evidence="ECO:0007829|PDB:4RZF"
FT HELIX 500..511
FT /evidence="ECO:0007829|PDB:4RZF"
FT HELIX 521..541
FT /evidence="ECO:0007829|PDB:4RZF"
FT TURN 544..546
FT /evidence="ECO:0007829|PDB:3V3Q"
FT HELIX 550..556
FT /evidence="ECO:0007829|PDB:4RZF"
FT HELIX 558..579
FT /evidence="ECO:0007829|PDB:4RZF"
FT HELIX 586..594
FT /evidence="ECO:0007829|PDB:4RZF"
SQ SEQUENCE 598 AA; 64463 MW; 41DAAEA7C25FDA22 CRC64;
MPCIQAQYGT PAPSPGPRDH LASDPLTPEF IKPTMDLASP EAAPAAPTAL PSFSTFMDGY
TGEFDTFLYQ LPGTVQPCSS ASSSASSTSS SSATSPASAS FKFEDFQVYG CYPGPLSGPV
DEALSSSGSD YYGSPCSAPS PSTPSFQPPQ LSPWDGSFGH FSPSQTYEGL RAWTEQLPKA
SGPPQPPAFF SFSPPTGPSP SLAQSPLKLF PSQATHQLGE GESYSMPTAF PGLAPTSPHL
EGSGILDTPV TSTKARSGAP GGSEGRCAVC GDNASCQHYG VRTCEGCKGF FKRTVQKNAK
YICLANKDCP VDKRRRNRCQ FCRFQKCLAV GMVKEVVRTD SLKGRRGRLP SKPKQPPDAS
PANLLTSLVR AHLDSGPSTA KLDYSKFQEL VLPHFGKEDA GDVQQFYDLL SGSLEVIRKW
AEKIPGFAEL SPADQDLLLE SAFLELFILR LAYRSKPGEG KLIFCSGLVL HRLQCARGFG
DWIDSILAFS RSLHSLLVDV PAFACLSALV LITDRHGLQE PRRVEELQNR IASCLKEHVA
AVAGEPQPAS CLSRLLGKLP ELRTLCTQGL QRIFYLKLED LVPPPPIIDK IFMDTLPF
