NR4A3_HUMAN
ID NR4A3_HUMAN Reviewed; 626 AA.
AC Q92570; A2A3I7; Q12935; Q14979; Q16420; Q4VXA8; Q4VXA9; Q9UEK2; Q9UEK3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 3.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Nuclear receptor subfamily 4 group A member 3;
DE AltName: Full=Mitogen-induced nuclear orphan receptor;
DE AltName: Full=Neuron-derived orphan receptor 1;
DE AltName: Full=Nuclear hormone receptor NOR-1;
GN Name=NR4A3; Synonyms=CHN, CSMF, MINOR, NOR1, TEC;
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 ALPHA).
RC TISSUE=Fetal brain;
RX PubMed=8809112; DOI=10.1016/0167-4781(96)00101-7;
RA Ohkura N., Ito M., Tsukada T., Sasaki K., Yamaguchi K., Miki K.;
RT "Structure, mapping and expression of a human NOR-1 gene, the third member
RT of the Nur77/NGFI-B family.";
RL Biochim. Biophys. Acta 1308:205-214(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
RC TISSUE=Peripheral blood;
RX PubMed=8614405; DOI=10.1210/mend.9.12.8614405;
RA Hedvat C.V., Irving S.G.;
RT "The isolation and characterization of MINOR, a novel mitogen-inducible
RT nuclear orphan receptor.";
RL Mol. Endocrinol. 9:1692-1700(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
RC TISSUE=Fetal brain;
RX PubMed=8570200;
RA Clark J., Benjamin H., Gill S., Sidhar S., Goodwin G., Crew J.,
RA Gusterson B.A., Shipley J., Cooper C.S.;
RT "Fusion of the EWS gene to CHN, a member of the steroid/thyroid receptor
RT gene superfamily, in a human myxoid chondrosarcoma.";
RL Oncogene 12:229-235(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA), AND CHROMOSOMAL TRANSLOCATION
RP WITH EWS.
RC TISSUE=Fetal heart;
RX PubMed=8634690; DOI=10.1093/hmg/4.12.2219;
RA Labelle Y., Zucman J., Stenman G., Kindblom L.-G., Knight J.,
RA Turc-Carel C., Dockhorn-Dworniczak B., Mandahl N., Desmaze C., Peter M.,
RA Aurias A., Delattre O., Thomas G.;
RT "Oncogenic conversion of a novel orphan nuclear receptor by chromosome
RT translocation.";
RL Hum. Mol. Genet. 4:2219-2226(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING
RP (ISOFORM 3).
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 (JAN-2009) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-69 AND 301-443 (ISOFORM BETA), AND
RP ALTERNATIVE SPLICING.
RC TISSUE=Skeletal muscle;
RX PubMed=9573341; DOI=10.1016/s0378-1119(98)00095-x;
RA Ohkura N., Ito M., Tsukada T., Sasaki K., Yamaguchi K., Miki K.;
RT "Alternative splicing generates isoforms of human neuron-derived orphan
RT receptor-1 (NOR-1) mRNA.";
RL Gene 211:79-85(1998).
RN [8]
RP INTERACTION WITH SIX3.
RX PubMed=12543801;
RA Laflamme C., Filion C., Bridge J.A., Ladanyi M., Goldring M.B., Labelle Y.;
RT "The homeotic protein Six3 is a coactivator of the nuclear receptor NOR-1
RT and a corepressor of the fusion protein EWS/NOR-1 in human extraskeletal
RT myxoid chondrosarcomas.";
RL Cancer Res. 63:449-454(2003).
RN [9]
RP FUNCTION, AND INDUCTION.
RX PubMed=20558821; DOI=10.1161/circresaha.110.222083;
RA Zhao Y., Howatt D.A., Gizard F., Nomiyama T., Findeisen H.M., Heywood E.B.,
RA Jones K.L., Conneely O.M., Daugherty A., Bruemmer D.;
RT "Deficiency of the NR4A orphan nuclear receptor NOR1 decreases monocyte
RT adhesion and atherosclerosis.";
RL Circ. Res. 107:501-511(2010).
RN [10]
RP FUNCTION.
RX PubMed=24022864; DOI=10.1152/ajpendo.00169.2013;
RA Liu Q., Zhu X., Xu L., Fu Y., Garvey W.T.;
RT "6-Mercaptopurine augments glucose transport activity in skeletal muscle
RT cells in part via a mechanism dependent upon orphan nuclear receptor
RT NR4A3.";
RL Am. J. Physiol. 305:E1081-E1092(2013).
RN [11]
RP INTERACTION WITH PRKDC; XRCC6 AND XRCC5, AND PHOSPHORYLATION.
RX PubMed=25852083; DOI=10.1093/cvr/cvv126;
RA Medunjanin S., Daniel J.M., Weinert S., Dutzmann J., Burgbacher F.,
RA Brecht S., Bruemmer D., Kaehne T., Naumann M., Sedding D.G.,
RA Zuschratter W., Braun-Dullaeus R.C.;
RT "DNA-dependent protein kinase (DNA-PK) permits vascular smooth muscle cell
RT proliferation through phosphorylation of the orphan nuclear receptor
RT NOR1.";
RL Cardiovasc. Res. 106:488-497(2015).
CC -!- FUNCTION: Transcriptional activator that binds to regulatory elements
CC in promoter regions in a cell- and response element (target)-specific
CC manner. Induces gene expression by binding as monomers to the NR4A1
CC response element (NBRE) 5'-AAAAGGTCA-3' site and as homodimers to the
CC Nur response element (NurRE) site in the promoter of their regulated
CC target genes (By similarity). Plays a role in the regulation of
CC proliferation, survival and differentiation of many different cell
CC types and also in metabolism and inflammation. Mediates proliferation
CC of vascular smooth muscle, myeloid progenitor cell and type B
CC pancreatic cells; promotes mitogen-induced vascular smooth muscle cell
CC proliferation through transactivation of SKP2 promoter by binding a
CC NBRE site (By similarity). Upon PDGF stimulation, stimulates vascular
CC smooth muscle cell proliferation by regulating CCND1 and CCND2
CC expression. In islets, induces type B pancreatic cell proliferation
CC through up-regulation of genes that activate cell cycle, as well as
CC genes that cause degradation of the CDKN1A (By similarity). Negatively
CC regulates myeloid progenitor cell proliferation by repressing RUNX1 in
CC a NBRE site-independent manner. During inner ear, plays a role as a key
CC mediator of the proliferative growth phase of semicircular canal
CC development (By similarity). Mediates also survival of neuron and
CC smooth muscle cells; mediates CREB-induced neuronal survival, and
CC during hippocampus development, plays a critical role in pyramidal cell
CC survival and axonal guidance. Is required for S phase entry of the cell
CC cycle and survival of smooth muscle cells by inducing CCND1, resulting
CC in RB1 phosphorylation. Binds to NBRE motif in CCND1 promoter,
CC resulting in the activation of the promoter and CCND1 transcription (By
CC similarity). Also plays a role in inflammation; upon TNF stimulation,
CC mediates monocyte adhesion by inducing the expression of VCAM1 and
CC ICAM1 by binding to the NBRE consensus site (By similarity)
CC (PubMed:20558821). In mast cells activated by Fc-epsilon receptor
CC cross-linking, promotes the synthesis and release of cytokines but
CC impairs events leading to degranulation (By similarity). Also plays a
CC role in metabolism; by modulating feeding behavior; and by playing a
CC role in energy balance by inhibiting the glucocorticoid-induced
CC orexigenic neuropeptides AGRP expression, at least in part by forming a
CC complex with activated NR3C1 on the AGRP- glucocorticoid response
CC element (GRE), and thus weakening the DNA binding activity of NR3C1.
CC Upon catecholamines stimulation, regulates gene expression that
CC controls oxidative metabolism in skeletal muscle (By similarity). Plays
CC a role in glucose transport by regulating translocation of the SLC2A4
CC glucose transporter to the cell surface (PubMed:24022864). Finally,
CC during gastrulation plays a crucial role in the formation of anterior
CC mesoderm by controlling cell migration. Inhibits adipogenesis (By
CC similarity). Also participates in cardiac hypertrophy by activating
CC PARP1 (By similarity). {ECO:0000250|UniProtKB:P51179,
CC ECO:0000250|UniProtKB:Q9QZB6, ECO:0000269|PubMed:20558821,
CC ECO:0000269|PubMed:24022864}.
CC -!- SUBUNIT: Interacts with SIX3 (via homeobox); differentially regulates
CC the transcriptional activities of NR4A3 (PubMed:12543801). Interacts
CC with the constituents of DNA-PK heterotrimer PRKDC, XRCC6 and XRCC5;
CC phosphorylates and prevents NR4A3 ubiquitinylation and degradation
CC (PubMed:25852083). Interacts with NCOA2; potentiates the activity of
CC the NR4A3. Interacts with NCOA1, NCOA3, MED1 and KAT2B. Interacts with
CC EP300 and NCOA2; mediates the recruitment of MED1 in the coactivator
CC complex (By similarity). Interacts with NR3C1 (via nuclear receptor
CC DNA-binding domain); the interactions represses transcription activity
CC of NR4A3 on the POMC promoter Nur response element (NurRE). Interacts
CC with TRIM28; the interactions potentiates NR4A3 activity on NurRE
CC promoter. Binds DNA as a monomer and homodimer. Interacts with PARP1;
CC activates PARP1 by improving acetylation of PARP1 and suppressing the
CC interaction between PARP1 and SIRT1 (By similarity).
CC {ECO:0000250|UniProtKB:P51179, ECO:0000250|UniProtKB:Q9QZB6,
CC ECO:0000269|PubMed:12543801, ECO:0000269|PubMed:25852083}.
CC -!- INTERACTION:
CC Q92570; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-13644623, EBI-10173507;
CC Q92570; P05187: ALPP; NbExp=3; IntAct=EBI-13644623, EBI-1211484;
CC Q92570; P55273: CDKN2D; NbExp=3; IntAct=EBI-13644623, EBI-745859;
CC Q92570; Q9H2X0: CHRD; NbExp=3; IntAct=EBI-13644623, EBI-947551;
CC Q92570; Q08AG9: CYP21A2; NbExp=3; IntAct=EBI-13644623, EBI-14156412;
CC Q92570; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-13644623, EBI-3867333;
CC Q92570; Q12805: EFEMP1; NbExp=3; IntAct=EBI-13644623, EBI-536772;
CC Q92570; Q9H2F3: HSD3B7; NbExp=3; IntAct=EBI-13644623, EBI-3918847;
CC Q92570; Q5T749: KPRP; NbExp=3; IntAct=EBI-13644623, EBI-10981970;
CC Q92570; P60370: KRTAP10-5; NbExp=5; IntAct=EBI-13644623, EBI-10172150;
CC Q92570; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-13644623, EBI-10171774;
CC Q92570; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-13644623, EBI-11953334;
CC Q92570; P60329: KRTAP12-4; NbExp=3; IntAct=EBI-13644623, EBI-10176396;
CC Q92570; Q9BYQ6: KRTAP4-11; NbExp=3; IntAct=EBI-13644623, EBI-10302392;
CC Q92570; Q9BYR5: KRTAP4-2; NbExp=3; IntAct=EBI-13644623, EBI-10172511;
CC Q92570; Q9BYR3: KRTAP4-4; NbExp=3; IntAct=EBI-13644623, EBI-11958132;
CC Q92570; Q6L8G4: KRTAP5-11; NbExp=3; IntAct=EBI-13644623, EBI-11993296;
CC Q92570; Q6L8H2: KRTAP5-3; NbExp=3; IntAct=EBI-13644623, EBI-11974251;
CC Q92570; Q6L8G9: KRTAP5-6; NbExp=3; IntAct=EBI-13644623, EBI-10250562;
CC Q92570; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-13644623, EBI-3958099;
CC Q92570; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-13644623, EBI-1044640;
CC Q92570; Q9BYQ3: KRTAP9-3; NbExp=3; IntAct=EBI-13644623, EBI-1043191;
CC Q92570; Q9BYQ0: KRTAP9-8; NbExp=3; IntAct=EBI-13644623, EBI-11958364;
CC Q92570; O14633: LCE2B; NbExp=3; IntAct=EBI-13644623, EBI-11478468;
CC Q92570; Q5TA82: LCE2D; NbExp=3; IntAct=EBI-13644623, EBI-10246750;
CC Q92570; Q8N5G2: MACO1; NbExp=3; IntAct=EBI-13644623, EBI-2683507;
CC Q92570; Q92692-2: NECTIN2; NbExp=3; IntAct=EBI-13644623, EBI-6979889;
CC Q92570; Q92824-2: PCSK5; NbExp=3; IntAct=EBI-13644623, EBI-11956269;
CC Q92570; Q13526: PIN1; NbExp=3; IntAct=EBI-13644623, EBI-714158;
CC Q92570; Q6P9E2: RECK; NbExp=3; IntAct=EBI-13644623, EBI-10253121;
CC Q92570; O95343: SIX3; NbExp=3; IntAct=EBI-13644623, EBI-13644574;
CC Q92570; Q9H4F8-2: SMOC1; NbExp=3; IntAct=EBI-13644623, EBI-12162539;
CC Q92570; O14817: TSPAN4; NbExp=3; IntAct=EBI-13644623, EBI-8652667;
CC Q92570; Q05086-3: UBE3A; NbExp=3; IntAct=EBI-13644623, EBI-11026619;
CC Q92570; Q6EMK4: VASN; NbExp=3; IntAct=EBI-13644623, EBI-10249550;
CC Q92570; B2RUY7: VWC2L; NbExp=3; IntAct=EBI-13644623, EBI-11747707;
CC Q92570; Q9Y3S2: ZNF330; NbExp=3; IntAct=EBI-13644623, EBI-373456;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Alpha;
CC IsoId=Q92570-1; Sequence=Displayed;
CC Name=Beta;
CC IsoId=Q92570-2; Sequence=VSP_003712, VSP_003713;
CC Name=3;
CC IsoId=Q92570-3; Sequence=VSP_037877;
CC -!- TISSUE SPECIFICITY: Isoform alpha is highly expressed in skeletal
CC muscle. Isoform beta is highly expressed in skeletal muscle and low
CC expressed in fetal brain and placenta.
CC -!- INDUCTION: Induced by inflammatory stimuli in endothelial cells through
CC an NF-kappa-B-dependent transactivation of the NR4A3 Promoter.
CC {ECO:0000269|PubMed:20558821}.
CC -!- DOMAIN: The AF-1 domain mediates transcription activation. The N-
CC terminal region (1-292) directly interacts with the C-terminal LBD
CC (380-627): the interaction is potentiated by AF-1-mediated recruitment
CC of NCOA2. {ECO:0000250|UniProtKB:Q9QZB6}.
CC -!- PTM: Phosphorylated by PRKDC. {ECO:0000269|PubMed:25852083}.
CC -!- DISEASE: Ewing sarcoma (ES) [MIM:612219]: A highly malignant,
CC metastatic, primitive small round cell tumor of bone and soft tissue
CC that affects children and adolescents. It belongs to the Ewing sarcoma
CC family of tumors, a group of morphologically heterogeneous neoplasms
CC that share the same cytogenetic features. They are considered neural
CC tumors derived from cells of the neural crest. Ewing sarcoma represents
CC the less differentiated form of the tumors. Note=The gene represented
CC in this entry is involved in disease pathogenesis. A chromosomal
CC aberration involving NR4A3 is found in patients with Erwing sarcoma.
CC Translocation t(9;22)(q22-31;q11-12) with EWSR1.
CC -!- DISEASE: Note=A chromosomal aberration involving NR4A3 is a cause of a
CC form of extraskeletal myxoid chondrosarcomas (EMC). Translocation
CC t(9;17)(q22;q11) with TAF2N.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR4
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB02581.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAB36006.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/TECID75.html";
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DR EMBL; D78579; BAA11419.1; -; mRNA.
DR EMBL; U12767; AAB02581.1; ALT_FRAME; mRNA.
DR EMBL; S81243; AAB36006.1; ALT_INIT; mRNA.
DR EMBL; X89894; CAA61984.1; -; mRNA.
DR EMBL; AL359710; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL358937; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471105; EAW58915.1; -; Genomic_DNA.
DR EMBL; D85241; BAA28608.1; -; mRNA.
DR EMBL; D85242; BAA31221.1; -; mRNA.
DR CCDS; CCDS6742.1; -. [Q92570-3]
DR CCDS; CCDS6743.1; -. [Q92570-1]
DR CCDS; CCDS6744.1; -. [Q92570-2]
DR PIR; S71930; S71930.
DR RefSeq; NP_008912.2; NM_006981.3. [Q92570-1]
DR RefSeq; NP_775291.1; NM_173199.2. [Q92570-2]
DR RefSeq; NP_775292.1; NM_173200.2. [Q92570-3]
DR RefSeq; XP_016870651.1; XM_017015162.1. [Q92570-1]
DR AlphaFoldDB; Q92570; -.
DR SMR; Q92570; -.
DR BioGRID; 113713; 46.
DR IntAct; Q92570; 38.
DR MINT; Q92570; -.
DR STRING; 9606.ENSP00000482027; -.
DR BindingDB; Q92570; -.
DR ChEMBL; CHEMBL1961792; -.
DR DrugBank; DB01254; Dasatinib.
DR iPTMnet; Q92570; -.
DR PhosphoSitePlus; Q92570; -.
DR BioMuta; NR4A3; -.
DR DMDM; 90110039; -.
DR jPOST; Q92570; -.
DR MassIVE; Q92570; -.
DR MaxQB; Q92570; -.
DR PaxDb; Q92570; -.
DR PeptideAtlas; Q92570; -.
DR PRIDE; Q92570; -.
DR ProteomicsDB; 75330; -. [Q92570-1]
DR ProteomicsDB; 75331; -. [Q92570-2]
DR ProteomicsDB; 75332; -. [Q92570-3]
DR Antibodypedia; 29057; 424 antibodies from 31 providers.
DR DNASU; 8013; -.
DR Ensembl; ENST00000330847.1; ENSP00000333122.1; ENSG00000119508.18. [Q92570-3]
DR Ensembl; ENST00000338488.8; ENSP00000340301.4; ENSG00000119508.18. [Q92570-2]
DR Ensembl; ENST00000395097.7; ENSP00000378531.2; ENSG00000119508.18. [Q92570-1]
DR Ensembl; ENST00000618101.4; ENSP00000482027.1; ENSG00000119508.18. [Q92570-3]
DR GeneID; 8013; -.
DR KEGG; hsa:8013; -.
DR MANE-Select; ENST00000395097.7; ENSP00000378531.2; NM_006981.4; NP_008912.2.
DR UCSC; uc004bae.3; human. [Q92570-1]
DR CTD; 8013; -.
DR DisGeNET; 8013; -.
DR GeneCards; NR4A3; -.
DR HGNC; HGNC:7982; NR4A3.
DR HPA; ENSG00000119508; Tissue enhanced (brain).
DR MalaCards; NR4A3; -.
DR MIM; 600542; gene+phenotype.
DR MIM; 612219; phenotype.
DR neXtProt; NX_Q92570; -.
DR OpenTargets; ENSG00000119508; -.
DR Orphanet; 209916; Extraskeletal myxoid chondrosarcoma.
DR PharmGKB; PA31763; -.
DR VEuPathDB; HostDB:ENSG00000119508; -.
DR eggNOG; KOG4217; Eukaryota.
DR GeneTree; ENSGT00950000183038; -.
DR HOGENOM; CLU_007368_14_2_1; -.
DR InParanoid; Q92570; -.
DR OMA; MEGHSYG; -.
DR OrthoDB; 454476at2759; -.
DR PhylomeDB; Q92570; -.
DR TreeFam; TF315430; -.
DR PathwayCommons; Q92570; -.
DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR SignaLink; Q92570; -.
DR SIGNOR; Q92570; -.
DR BioGRID-ORCS; 8013; 7 hits in 1094 CRISPR screens.
DR ChiTaRS; NR4A3; human.
DR GeneWiki; Neuron-derived_orphan_receptor_1; -.
DR GenomeRNAi; 8013; -.
DR Pharos; Q92570; Tbio.
DR PRO; PR:Q92570; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q92570; protein.
DR Bgee; ENSG00000119508; Expressed in mucosa of paranasal sinus and 179 other tissues.
DR ExpressionAtlas; Q92570; baseline and differential.
DR Genevisible; Q92570; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0035497; F:cAMP response element binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; NAS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA: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:ProtInc.
DR GO; GO:0003707; F:nuclear steroid receptor activity; TAS:ProtInc.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0045333; P:cellular respiration; ISS:UniProtKB.
DR GO; GO:0071870; P:cellular response to catecholamine stimulus; ISS:UniProtKB.
DR GO; GO:0071376; P:cellular response to corticotropin-releasing hormone stimulus; ISS:UniProtKB.
DR GO; GO:0044320; P:cellular response to leptin stimulus; ISS:UniProtKB.
DR GO; GO:0035726; P:common myeloid progenitor cell proliferation; ISS:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0007369; P:gastrulation; ISS:UniProtKB.
DR GO; GO:0043303; P:mast cell degranulation; ISS:UniProtKB.
DR GO; GO:1903208; P:negative regulation of hydrogen peroxide-induced neuron death; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISS:UniProtKB.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0046321; P:positive regulation of fatty acid oxidation; ISS:UniProtKB.
DR GO; GO:2000253; P:positive regulation of feeding behavior; ISS:UniProtKB.
DR GO; GO:0010828; P:positive regulation of glucose transmembrane transport; IDA:UniProtKB.
DR GO; GO:0038097; P:positive regulation of mast cell activation by Fc-epsilon receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0032765; P:positive regulation of mast cell cytokine production; ISS:UniProtKB.
DR GO; GO:1900625; P:positive regulation of monocyte aggregation; IMP:UniProtKB.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:1904754; P:positive regulation of vascular associated smooth muscle cell migration; IGI:BHF-UCL.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IGI:BHF-UCL.
DR GO; GO:0009444; P:pyruvate oxidation; ISS:UniProtKB.
DR GO; GO:0048660; P:regulation of smooth muscle cell proliferation; IDA:UniProtKB.
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 Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR003072; NOR1_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; PR01286; NORNUCRECPTR.
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 Alternative splicing; Chromosomal rearrangement; DNA-binding;
KW Metal-binding; Nucleus; Proto-oncogene; Receptor; Reference proteome;
KW Transcription; Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..626
FT /note="Nuclear receptor subfamily 4 group A member 3"
FT /id="PRO_0000053722"
FT DOMAIN 394..623
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 289..364
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 292..312
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 328..352
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..291
FT /note="Interaction with NCOA1, NCOA2, NCOA3 and KAT2B"
FT /evidence="ECO:0000250|UniProtKB:Q9QZB6"
FT REGION 1..138
FT /note="Required for DNA-PK heterotrimer"
FT /evidence="ECO:0000269|PubMed:25852083"
FT REGION 1..108
FT /note="Activation function (AF)-1 domain"
FT /evidence="ECO:0000250|UniProtKB:Q9QZB6"
FT REGION 92..152
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 192..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 265..284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 364..394
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 379..626
FT /note="Interaction with KAT2B"
FT /evidence="ECO:0000250|UniProtKB:Q9QZB6"
FT COMPBIAS 94..111
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 112..141
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1
FT /note="M -> MHDSIRFGNVDM (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_037877"
FT VAR_SEQ 419..443
FT /note="YCPTDQAAAGTDAEHVQQFYNLLTA -> VSFMISCFQMNDQGLYLWLLVIR
FT VD (in isoform Beta)"
FT /evidence="ECO:0000303|PubMed:8634690,
FT ECO:0000303|PubMed:9573341"
FT /id="VSP_003712"
FT VAR_SEQ 444..626
FT /note="Missing (in isoform Beta)"
FT /evidence="ECO:0000303|PubMed:8634690,
FT ECO:0000303|PubMed:9573341"
FT /id="VSP_003713"
FT CONFLICT 240
FT /note="S -> G (in Ref. 1 and 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 454
FT /note="K -> R (in Ref. 1; BAA11419)"
FT /evidence="ECO:0000305"
FT CONFLICT 579
FT /note="T -> N (in Ref. 1; BAA11419)"
FT /evidence="ECO:0000305"
FT CONFLICT 585
FT /note="G -> V (in Ref. 1; BAA11419)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 626 AA; 68230 MW; FB4A1AB7667D96F6 CRC64;
MPCVQAQYSP SPPGSSYAAQ TYSSEYTTEI MNPDYTKLTM DLGSTEITAT ATTSLPSIST
FVEGYSSNYE LKPSCVYQMQ RPLIKVEEGR APSYHHHHHH HHHHHHHHQQ QHQQPSIPPA
SSPEDEVLPS TSMYFKQSPP STPTTPAFPP QAGALWDEAL PSAPGCIAPG PLLDPPMKAV
PTVAGARFPL FHFKPSPPHP PAPSPAGGHH LGYDPTAAAA LSLPLGAAAA AGSQAAALES
HPYGLPLAKR AAPLAFPPLG LTPSPTASSL LGESPSLPSP PSRSSSSGEG TCAVCGDNAA
CQHYGVRTCE GCKGFFKRTV QKNAKYVCLA NKNCPVDKRR RNRCQYCRFQ KCLSVGMVKE
VVRTDSLKGR RGRLPSKPKS PLQQEPSQPS PPSPPICMMN ALVRALTDST PRDLDYSRYC
PTDQAAAGTD AEHVQQFYNL LTASIDVSRS WAEKIPGFTD LPKEDQTLLI ESAFLELFVL
RLSIRSNTAE DKFVFCNGLV LHRLQCLRGF GEWLDSIKDF SLNLQSLNLD IQALACLSAL
SMITERHGLK EPKRVEELCN KITSSLKDHQ SKGQALEPTE SKVLGALVEL RKICTLGLQR
IFYLKLEDLV SPPSIIDKLF LDTLPF
