ID NR4A2_HUMAN Reviewed; 598 AA. AC P43354; Q16311; Q53RZ2; Q6NXU0; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 27-MAR-2024, entry version 229. DE RecName: Full=Nuclear receptor subfamily 4 group A member 2; DE AltName: Full=Immediate-early response protein NOT; DE AltName: Full=Orphan nuclear receptor NURR1; DE AltName: Full=Transcriptionally-inducible nuclear receptor; GN Name=NR4A2; Synonyms=NOT, NURR1, TINUR; 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=Blood; RX PubMed=7877627; DOI=10.1210/mend.8.11.7877627; RA Mages H.W., Rilke O., Bravo R., Senger G., Kroczek R.A.; RT "NOT, a human immediate-early response gene closely related to the RT steroid/thyroid hormone receptor NAK1/TR3."; RL Mol. Endocrinol. 8:1583-1591(1994). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Fibroblast; RX PubMed=10216262; DOI=10.1016/s0378-1119(99)00065-7; RA Ichinose H., Ohye T., Suzuki T., Sumi-Ichinose C., Nomura T., Hagino Y., RA Nagatsu T.; RT "Molecular cloning of the human Nurr1 gene: characterization of the human RT gene and cDNAs."; RL Gene 230:233-239(1999). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10216261; DOI=10.1016/s0378-1119(99)00064-5; RA Torii T., Kawarai T., Nakamura S., Kawakami H.; RT "Organization of the human orphan nuclear receptor Nurr1 gene."; RL Gene 230:225-232(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [6] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Skin, and Testis; 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 [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 59-598 (ISOFORM 1). RX PubMed=7706727; RA Okabe T., Takayanagi R., Imasaki K., Haji M., Nawata H., Watanabe T.; RT "cDNA cloning of a NGFI-B/nur77-related transcription factor from an RT apoptotic human T cell line."; RL J. Immunol. 154:3871-3879(1995). RN [9] RP FUNCTION. RX PubMed=15716272; DOI=10.1074/jbc.m413175200; RA Flaig R., Greschik H., Peluso-Iltis C., Moras D.; RT "Structural basis for the cell-specific activities of the NGFI-B and the RT Nurr1 ligand-binding domain."; RL J. Biol. Chem. 280:19250-19258(2005). RN [10] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=17184956; DOI=10.1016/j.ijdevneu.2006.11.003; RA Messmer K., Remington M.P., Skidmore F., Fishman P.S.; RT "Induction of tyrosine hydroxylase expression by the transcription factor RT Pitx3."; RL Int. J. Dev. Neurosci. 25:29-37(2007). RN [11] RP IDENTIFICATION BY 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 [12] RP SUBCELLULAR LOCATION, NUCLEAR LOCALIZATION SIGNALS, AND NUCLEAR EXPORT RP SEQUENCES. RX PubMed=23283970; DOI=10.1074/jbc.m112.439190; RA Garcia-Yague A.J., Rada P., Rojo A.I., Lastres-Becker I., Cuadrado A.; RT "Nuclear import and export signals control the subcellular localization of RT Nurr1 protein in response to oxidative stress."; RL J. Biol. Chem. 288:5506-5517(2013). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 328-598. RX PubMed=12774125; DOI=10.1038/nature01645; RA Wang Z., Benoit G., Liu J., Prasad S., Aarnisalo P., Liu X., Xu H., RA Walker N.P., Perlmann T.; RT "Structure and function of Nurr1 identifies a class of ligand-independent RT nuclear receptors."; RL Nature 423:555-560(2003). RN [14] RP INVOLVEMENT IN IDLDP. RX PubMed=31428396; DOI=10.1002/ccr3.2260; RA Ramos L.L.P., Monteiro F.P., Sampaio L.P.B., Costa L.A., Ribeiro M.D.O., RA Freitas E.L., Kitajima J.P., Kok F.; RT "Heterozygous loss of function of NR4A2 is associated with intellectual RT deficiency, rolandic epilepsy, and language impairment."; RL Clin. Case Rep. 7:1582-1584(2019). RN [15] RP INVOLVEMENT IN IDLDP, AND VARIANTS IDLDP TYR-280; SER-286; TYR-305; RP PHE-323; GLY-392 AND 526-GLU--PHE-598 DEL. RX PubMed=32366965; DOI=10.1038/s41436-020-0815-4; RA Singh S., Gupta A., Zech M., Sigafoos A.N., Clark K.J., Dincer Y., RA Wagner M., Humberson J.B., Green S., van Gassen K., Brandt T., Schnur R.E., RA Millan F., Si Y., Mall V., Winkelmann J., Gavrilova R.H., Klee E.W., RA Engleman K., Safina N.P., Slaugh R., Bryant E.M., Tan W.H., Granadillo J., RA Misra S.N., Schaefer G.B., Towner S., Brilstra E.H., Koeleman B.P.C.; RT "De novo variants of NR4A2 are associated with neurodevelopmental disorder RT and epilepsy."; RL Genet. Med. 22:1413-1417(2020). RN [16] RP INVOLVEMENT IN IDLDP. RX PubMed=31922365; DOI=10.1002/mds.27982; RA Wirth T., Mariani L.L., Bergant G., Baulac M., Habert M.O., Drouot N., RA Ollivier E., Hodzic A., Rudolf G., Nitschke P., Rudolf G., Chelly J., RA Tranchant C., Anheim M., Roze E.; RT "Loss-of-Function Mutations in NR4A2 Cause Dopa-Responsive Dystonia RT Parkinsonism."; RL Mov. Disord. 35:880-885(2020). RN [17] RP INVOLVEMENT IN IDLDP, AND VARIANT IDLDP GLN-319. RX PubMed=33585677; DOI=10.1212/nxg.0000000000000543; RA Jesus S., Hinarejos I., Carrillo F., Martinez-Rubio D., Macias-Garcia D., RA Sanchez-Monteagudo A., Adarmes A., Lupo V., Perez-Duenas B., Mir P., RA Espinos C.; RT "NR4A2 Mutations Can Cause Intellectual Disability and Language Impairment RT With Persistent Dystonia-Parkinsonism."; RL Neurol. Genet. 7:e543-e543(2021). CC -!- FUNCTION: Transcriptional regulator which is important for the CC differentiation and maintenance of meso-diencephalic dopaminergic CC (mdDA) neurons during development (PubMed:17184956, PubMed:15716272). CC It is crucial for expression of a set of genes such as SLC6A3, SLC18A2, CC TH and DRD2 which are essential for development of mdDA neurons (By CC similarity). {ECO:0000250|UniProtKB:Q06219, CC ECO:0000269|PubMed:15716272, ECO:0000269|PubMed:17184956}. CC -!- SUBUNIT: Interacts with SFPQ, NCOR2, SIN3A and HADC1. The interaction CC with NCOR2 increases in the absence of PITX3. Interacts with PER2 (By CC similarity). {ECO:0000250}. CC -!- INTERACTION: CC P43354; P05067: APP; NbExp=3; IntAct=EBI-2681738, EBI-77613; CC P43354; P55273: CDKN2D; NbExp=4; IntAct=EBI-2681738, EBI-745859; CC P43354; Q5T2S8: ODAD2; NbExp=3; IntAct=EBI-2681738, EBI-12200605; CC P43354; Q5H9L2: TCEAL5; NbExp=2; IntAct=EBI-2681738, EBI-2681773; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23283970}. Nucleus CC {ECO:0000269|PubMed:17184956, ECO:0000269|PubMed:23283970}. Note=Mostly CC nuclear; oxidative stress promotes cytoplasmic localization. CC {ECO:0000269|PubMed:23283970}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P43354-1; Sequence=Displayed; CC Name=2; CC IsoId=P43354-2; Sequence=VSP_056057; CC -!- TISSUE SPECIFICITY: Expressed in a number of cell lines of T-cell, B- CC cell and fibroblast origin. Strong expression in brain tissue. CC -!- DEVELOPMENTAL STAGE: Rapidly and only very transiently expressed after CC cell activation, during the G0-G1 transition of the cell cycle. CC -!- DOMAIN: the ligand-binding domain (LBD) contains no cavity as a result CC of the tight packing of side chains from several bulky hydrophobic CC residues in the region normally occupied by ligands. NR4A2 lacks a CC 'classical' binding site for coactivators (PubMed:12774125). CC {ECO:0000269|PubMed:12774125}. CC -!- DISEASE: Intellectual developmental disorder with language impairment CC and early-onset DOPA-responsive dystonia-parkinsonism (IDLDP) CC [MIM:619911]: An autosomal dominant disorder characterized by global CC developmental delay affecting motor, cognitive, and speech domains CC apparent in early childhood or infancy. Most patients also show CC movement abnormalities, often hypotonia with later development of dopa- CC responsive dystonia or parkinsonism. About half of patients develop CC various types of seizures. {ECO:0000269|PubMed:31428396, CC ECO:0000269|PubMed:31922365, ECO:0000269|PubMed:32366965, CC ECO:0000269|PubMed:33585677}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR4 CC subfamily. {ECO:0000305}. 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; X75918; CAA53518.1; -; mRNA. DR EMBL; AB017586; BAA75666.1; -; Genomic_DNA. DR EMBL; AB019433; BAA77328.1; -; Genomic_DNA. DR EMBL; AK291456; BAF84145.1; -; mRNA. DR EMBL; AC074099; AAY24203.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11454.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11455.1; -; Genomic_DNA. DR EMBL; BC009288; AAH09288.1; -; mRNA. DR EMBL; BC066890; AAH66890.1; -; mRNA. DR EMBL; S77154; AAB33999.1; -; mRNA. DR CCDS; CCDS2201.1; -. [P43354-1] DR CCDS; CCDS86887.1; -. [P43354-2] DR PIR; A57040; A57040. DR RefSeq; NP_006177.1; NM_006186.3. [P43354-1] DR RefSeq; XP_005246679.1; XM_005246622.3. DR RefSeq; XP_016859708.1; XM_017004219.1. DR PDB; 1OVL; X-ray; 2.20 A; A/B/C/D/E/F=328-598. DR PDB; 5Y41; X-ray; 2.05 A; A/B=328-598. DR PDB; 5YD6; X-ray; 2.34 A; A/B/C/D=328-598. DR PDB; 6DDA; X-ray; 3.20 A; A/B/C=328-598. DR PDB; 6L6L; X-ray; 2.78 A; A/B=262-346. DR PDB; 6L6Q; X-ray; 2.60 A; A/B=262-346. DR PDB; 7WNH; X-ray; 3.10 A; A/B/C/D=258-598. DR PDBsum; 1OVL; -. DR PDBsum; 5Y41; -. DR PDBsum; 5YD6; -. DR PDBsum; 6DDA; -. DR PDBsum; 6L6L; -. DR PDBsum; 6L6Q; -. DR PDBsum; 7WNH; -. DR AlphaFoldDB; P43354; -. DR BMRB; P43354; -. DR SMR; P43354; -. DR BioGRID; 110983; 21. DR IntAct; P43354; 19. DR STRING; 9606.ENSP00000344479; -. DR BindingDB; P43354; -. DR ChEMBL; CHEMBL5002; -. DR GuidetoPHARMACOLOGY; 630; -. DR iPTMnet; P43354; -. DR PhosphoSitePlus; P43354; -. DR SwissPalm; P43354; -. DR BioMuta; NR4A2; -. DR DMDM; 1171750; -. DR jPOST; P43354; -. DR MassIVE; P43354; -. DR MaxQB; P43354; -. DR PaxDb; 9606-ENSP00000344479; -. DR PeptideAtlas; P43354; -. DR ProteomicsDB; 55616; -. [P43354-1] DR ProteomicsDB; 66777; -. DR Antibodypedia; 621; 527 antibodies from 40 providers. DR DNASU; 4929; -. DR Ensembl; ENST00000339562.9; ENSP00000344479.4; ENSG00000153234.16. [P43354-1] DR Ensembl; ENST00000409572.5; ENSP00000386747.1; ENSG00000153234.16. [P43354-1] DR Ensembl; ENST00000426264.5; ENSP00000389986.1; ENSG00000153234.16. [P43354-2] DR GeneID; 4929; -. DR KEGG; hsa:4929; -. DR MANE-Select; ENST00000339562.9; ENSP00000344479.4; NM_006186.4; NP_006177.1. DR UCSC; uc002tyx.5; human. [P43354-1] DR AGR; HGNC:7981; -. DR CTD; 4929; -. DR DisGeNET; 4929; -. DR GeneCards; NR4A2; -. DR HGNC; HGNC:7981; NR4A2. DR HPA; ENSG00000153234; Tissue enhanced (adrenal gland, bone marrow, ovary). DR MalaCards; NR4A2; -. DR MIM; 601828; gene. DR MIM; 619911; phenotype. DR neXtProt; NX_P43354; -. DR OpenTargets; ENSG00000153234; -. DR Orphanet; 98808; Autosomal dominant dopa-responsive dystonia. DR PharmGKB; PA31762; -. DR VEuPathDB; HostDB:ENSG00000153234; -. DR eggNOG; KOG4217; Eukaryota. DR GeneTree; ENSGT00950000183038; -. DR HOGENOM; CLU_007368_14_2_1; -. DR InParanoid; P43354; -. DR OMA; GSCQMRF; -. DR OrthoDB; 5395768at2759; -. DR PhylomeDB; P43354; -. DR TreeFam; TF315430; -. DR PathwayCommons; P43354; -. DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway. DR Reactome; R-HSA-4090294; SUMOylation of intracellular receptors. DR SignaLink; P43354; -. DR SIGNOR; P43354; -. DR BioGRID-ORCS; 4929; 20 hits in 1187 CRISPR screens. DR ChiTaRS; NR4A2; human. DR EvolutionaryTrace; P43354; -. DR GeneWiki; Nuclear_receptor_related-1_protein; -. DR GenomeRNAi; 4929; -. DR Pharos; P43354; Tchem. DR PRO; PR:P43354; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P43354; Protein. DR Bgee; ENSG00000153234; Expressed in mucosa of paranasal sinus and 195 other cell types or tissues. DR ExpressionAtlas; P43354; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0016607; C:nuclear speck; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; TAS:ParkinsonsUK-UCL. DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central. DR GO; GO:0008013; F:beta-catenin binding; TAS:ParkinsonsUK-UCL. DR GO; GO:0003677; F:DNA binding; TAS:ParkinsonsUK-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:0035259; F:nuclear glucocorticoid receptor binding; IBA:GO_Central. DR GO; GO:0004879; F:nuclear receptor activity; TAS:ParkinsonsUK-UCL. DR GO; GO:0046965; F:nuclear retinoid X receptor binding; TAS:ParkinsonsUK-UCL. 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:0008344; P:adult locomotory behavior; IEA:Ensembl. DR GO; GO:0060070; P:canonical Wnt signaling pathway; TAS:ParkinsonsUK-UCL. DR GO; GO:0071376; P:cellular response to corticotropin-releasing hormone stimulus; ISS:UniProtKB. DR GO; GO:0031668; P:cellular response to extracellular stimulus; IDA:MGI. DR GO; GO:0034599; P:cellular response to oxidative stress; IEA:Ensembl. DR GO; GO:0021953; P:central nervous system neuron differentiation; IBA:GO_Central. DR GO; GO:0021952; P:central nervous system projection neuron axonogenesis; IEA:Ensembl. DR GO; GO:0006351; P:DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0042416; P:dopamine biosynthetic process; IEA:Ensembl. DR GO; GO:0071542; P:dopaminergic neuron differentiation; ISS:UniProtKB. DR GO; GO:0045444; P:fat cell differentiation; ISS:UniProtKB. DR GO; GO:0051866; P:general adaptation syndrome; IEA:Ensembl. DR GO; GO:0021986; P:habenula development; IEA:Ensembl. DR GO; GO:1904948; P:midbrain dopaminergic neuron differentiation; TAS:ParkinsonsUK-UCL. DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IMP:ParkinsonsUK-UCL. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:ParkinsonsUK-UCL. DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl. DR GO; GO:0042551; P:neuron maturation; IEA:Ensembl. DR GO; GO:0001764; P:neuron migration; TAS:ParkinsonsUK-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl. DR GO; GO:0042053; P:regulation of dopamine metabolic process; IEA:Ensembl. DR GO; GO:0043576; P:regulation of respiratory gaseous exchange; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; NAS:ProtInc. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. DR CDD; cd06969; NR_DBD_NGFI-B; 1. DR CDD; cd07071; NR_LBD_Nurr1; 1. 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; IPR003070; NR4A1-3. DR InterPro; IPR003073; NR4A2. 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 PANTHER; PTHR24085; NUCLEAR HORMONE RECEPTOR; 1. DR PANTHER; PTHR24085:SF0; NUCLEAR RECEPTOR SUBFAMILY 4 GROUP A MEMBER 2; 1. DR Pfam; PF00104; Hormone_recep; 1. DR Pfam; PF00105; zf-C4; 1. DR PRINTS; PR01284; NUCLEARECPTR. DR PRINTS; PR01287; NURRNUCRCPTR. 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; P43354; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; Disease variant; KW DNA-binding; Dystonia; Intellectual disability; Metal-binding; Nucleus; KW Parkinsonism; Receptor; Reference proteome; Transcription; KW Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1..598 FT /note="Nuclear receptor subfamily 4 group A member 2" FT /id="PRO_0000053718" FT DOMAIN 360..595 FT /note="NR LBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189" FT DNA_BIND 260..335 FT /note="Nuclear receptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 263..283 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 299..323 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT REGION 1..22 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 337..361 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 287..314 FT /note="Bipartite nuclear localization signal (NLS1)" FT MOTIF 338..350 FT /note="Nuclear localization signal (NLS1)" FT /evidence="ECO:0000269|PubMed:23283970" FT MOTIF 443..452 FT /note="nuclear export sequence (NES1)" FT MOTIF 568..577 FT /note="nuclear export sequence (NES2)" FT VAR_SEQ 1..63 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_056057" FT VARIANT 280 FT /note="C -> Y (in IDLDP)" FT /evidence="ECO:0000269|PubMed:32366965" FT /id="VAR_087381" FT VARIANT 286 FT /note="F -> S (in IDLDP; uncertain significance)" FT /evidence="ECO:0000269|PubMed:32366965" FT /id="VAR_087382" FT VARIANT 305 FT /note="C -> Y (in IDLDP)" FT /evidence="ECO:0000269|PubMed:32366965" FT /id="VAR_087383" FT VARIANT 319 FT /note="R -> Q (in IDLDP)" FT /evidence="ECO:0000269|PubMed:33585677" FT /id="VAR_087384" FT VARIANT 323 FT /note="C -> F (in IDLDP; uncertain significance)" FT /evidence="ECO:0000269|PubMed:32366965" FT /id="VAR_087385" FT VARIANT 392 FT /note="D -> G (in IDLDP; uncertain significance)" FT /evidence="ECO:0000269|PubMed:32366965" FT /id="VAR_087386" FT VARIANT 526..598 FT /note="Missing (in IDLDP)" FT /evidence="ECO:0000269|PubMed:32366965" FT /id="VAR_087387" FT CONFLICT 465 FT /note="C -> W (in Ref. 8; AAB33999)" FT /evidence="ECO:0000305" FT CONFLICT 468 FT /note="V -> W (in Ref. 8; AAB33999)" FT /evidence="ECO:0000305" FT TURN 264..266 FT /evidence="ECO:0007829|PDB:6L6Q" FT STRAND 271..274 FT /evidence="ECO:0007829|PDB:6L6Q" FT HELIX 281..292 FT /evidence="ECO:0007829|PDB:6L6Q" FT STRAND 300..303 FT /evidence="ECO:0007829|PDB:6L6Q" FT TURN 310..313 FT /evidence="ECO:0007829|PDB:6L6Q" FT HELIX 316..326 FT /evidence="ECO:0007829|PDB:6L6Q" FT HELIX 330..332 FT /evidence="ECO:0007829|PDB:6L6Q" FT HELIX 338..341 FT /evidence="ECO:0007829|PDB:1OVL" FT HELIX 364..373 FT /evidence="ECO:0007829|PDB:5Y41" FT HELIX 379..381 FT /evidence="ECO:0007829|PDB:5Y41" FT HELIX 392..394 FT /evidence="ECO:0007829|PDB:1OVL" FT HELIX 400..422 FT /evidence="ECO:0007829|PDB:5Y41" FT TURN 425..429 FT /evidence="ECO:0007829|PDB:5Y41" FT HELIX 432..454 FT /evidence="ECO:0007829|PDB:5Y41" FT HELIX 457..459 FT /evidence="ECO:0007829|PDB:5Y41" FT STRAND 461..463 FT /evidence="ECO:0007829|PDB:5Y41" FT STRAND 467..471 FT /evidence="ECO:0007829|PDB:5Y41" FT HELIX 472..479 FT /evidence="ECO:0007829|PDB:5Y41" FT HELIX 482..494 FT /evidence="ECO:0007829|PDB:5Y41" FT HELIX 500..511 FT /evidence="ECO:0007829|PDB:5Y41" FT HELIX 521..542 FT /evidence="ECO:0007829|PDB:5Y41" FT TURN 543..545 FT /evidence="ECO:0007829|PDB:5Y41" FT HELIX 549..556 FT /evidence="ECO:0007829|PDB:5Y41" FT HELIX 558..579 FT /evidence="ECO:0007829|PDB:5Y41" FT HELIX 586..595 FT /evidence="ECO:0007829|PDB:5Y41" SQ SEQUENCE 598 AA; 66591 MW; 28D8199AACE3E211 CRC64; MPCVQAQYGS SPQGASPASQ SYSYHSSGEY SSDFLTPEFV KFSMDLTNTE ITATTSLPSF STFMDNYSTG YDVKPPCLYQ MPLSGQQSSI KVEDIQMHNY QQHSHLPPQS EEMMPHSGSV YYKPSSPPTP TTPGFQVQHS PMWDDPGSLH NFHQNYVATT HMIEQRKTPV SRLSLFSFKQ SPPGTPVSSC QMRFDGPLHV PMNPEPAGSH HVVDGQTFAV PNPIRKPASM GFPGLQIGHA SQLLDTQVPS PPSRGSPSNE GLCAVCGDNA ACQHYGVRTC EGCKGFFKRT VQKNAKYVCL ANKNCPVDKR RRNRCQYCRF QKCLAVGMVK EVVRTDSLKG RRGRLPSKPK SPQEPSPPSP PVSLISALVR AHVDSNPAMT SLDYSRFQAN PDYQMSGDDT QHIQQFYDLL TGSMEIIRGW AEKIPGFADL PKADQDLLFE SAFLELFVLR LAYRSNPVEG KLIFCNGVVL HRLQCVRGFG EWIDSIVEFS SNLQNMNIDI SAFSCIAALA MVTERHGLKE PKRVEELQNK IVNCLKDHVT FNNGGLNRPN YLSKLLGKLP ELRTLCTQGL QRIFYLKLED LVPPPAIIDK LFLDTLPF //