NR4A1_MOUSE
ID NR4A1_MOUSE Reviewed; 601 AA.
AC P12813;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Nuclear receptor subfamily 4 group A member 1;
DE AltName: Full=Nuclear hormone receptor NUR/77;
DE AltName: Full=Nuclear protein N10;
DE AltName: Full=Orphan nuclear receptor HMR;
GN Name=Nr4a1; Synonyms=Gfrp, Hmr, N10, Nur77;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3186734; DOI=10.1073/pnas.85.22.8444;
RA Hazel T.G., Nathans D., Lau L.F.;
RT "A gene inducible by serum growth factors encodes a member of the steroid
RT and thyroid hormone receptor superfamily.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:8444-8448(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SUBCELLULAR LOCATION.
RC TISSUE=Kidney, and Liver;
RX PubMed=2555161; DOI=10.1002/j.1460-2075.1989.tb08494.x;
RA Ryseck R.P., Macdonald-Bravo H., Mattei M.-G., Ruppert S., Bravo R.;
RT "Structure, mapping and expression of a growth factor inducible gene
RT encoding a putative nuclear hormonal binding receptor.";
RL EMBO J. 8:3327-3335(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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).
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 May inhibit NF-kappa-B transactivation of IL2. Participates in energy
CC homeostasis by sequestrating the kinase STK11 in the nucleus, thereby
CC attenuating cytoplasmic AMPK activation (By similarity). Plays a role
CC in the vascular response to injury (PubMed:22427340). {ECO:0000250,
CC ECO:0000269|PubMed:22427340}.
CC -!- SUBUNIT: Binds DNA as a monomer (By similarity). Interacts with
CC GADD45GIP1. Interacts with STK11 (By similarity). Interacts with IFI27
CC (By similarity). Heterodimer (via DNA-binding domain) with RXRA (via C-
CC terminus); DNA-binding of the heterodimer is enhanced by 9-cis retinoic
CC acid (By similarity). Competes for the RXRA interaction with EP300 and
CC thereby attenuates EP300 mediated acetylation of RXRA (By similarity).
CC {ECO:0000250|UniProtKB:P22736, ECO:0000250|UniProtKB:P22829}.
CC -!- INTERACTION:
CC P12813; Q8VHR5: Gatad2b; NbExp=2; IntAct=EBI-10896863, EBI-3043880;
CC P12813; Q9R190: Mta2; NbExp=2; IntAct=EBI-10896863, EBI-904134;
CC P12813; Q7TPV4: Mybbp1a; NbExp=3; IntAct=EBI-10896863, EBI-1373622;
CC P12813; Q9DBD5: Pelp1; NbExp=3; IntAct=EBI-10896863, EBI-6909114;
CC P12813; Q04207: Rela; NbExp=2; IntAct=EBI-10896863, EBI-644400;
CC P12813; Q62318: Trim28; NbExp=3; IntAct=EBI-10896863, EBI-346909;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:2555161}. Cytoplasm
CC {ECO:0000250|UniProtKB:P22736}. Mitochondrion
CC {ECO:0000250|UniProtKB:P22736}. Note=Nuclear export to the cytoplasm is
CC XPO1-mediated and positively regulated by IFI27. Translocation to the
CC mitochondrion upon interaction with RXRA and upon the presence of 9-cis
CC retinoic acid (By similarity). {ECO:0000250|UniProtKB:P22736}.
CC -!- TISSUE SPECIFICITY: Highest levels occur in the testis followed by
CC brain and muscle tissue.
CC -!- DEVELOPMENTAL STAGE: Highest levels are found in the adult with barely
CC detectable levels in pre- and early postnatal tissue.
CC -!- INDUCTION: By serum growth factors and during liver regeneration.
CC -!- PTM: Phosphorylated at Ser-354 by RPS6KA1 and RPS6KA3 in response to
CC mitogenic or stress stimuli. {ECO:0000250}.
CC -!- PTM: Acetylated by p300/CBP, acetylation increases stability.
CC Deacetylated by HDAC1 (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Homozygous knockout mice display restenosis, the
CC narrowing of blood vessels upon vascular injury.
CC {ECO:0000269|PubMed:22427340}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR4
CC subfamily. {ECO:0000305}.
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DR EMBL; J04113; AAA39843.1; -; mRNA.
DR EMBL; X16995; CAA34862.1; -; Genomic_DNA.
DR EMBL; X60132; CAA42718.1; -; mRNA.
DR EMBL; BC004770; AAH04770.1; -; mRNA.
DR CCDS; CCDS27848.1; -.
DR PIR; S06953; QRMSN1.
DR RefSeq; NP_034574.1; NM_010444.2.
DR RefSeq; XP_006520518.1; XM_006520455.1.
DR RefSeq; XP_006520519.1; XM_006520456.1.
DR RefSeq; XP_006520521.1; XM_006520458.1.
DR RefSeq; XP_006520522.1; XM_006520459.3.
DR RefSeq; XP_017171925.1; XM_017316436.1.
DR AlphaFoldDB; P12813; -.
DR SMR; P12813; -.
DR BioGRID; 200346; 8.
DR CORUM; P12813; -.
DR DIP; DIP-61643N; -.
DR ELM; P12813; -.
DR IntAct; P12813; 16.
DR STRING; 10090.ENSMUSP00000023779; -.
DR ChEMBL; CHEMBL3308901; -.
DR iPTMnet; P12813; -.
DR PhosphoSitePlus; P12813; -.
DR PaxDb; P12813; -.
DR PRIDE; P12813; -.
DR ProteomicsDB; 295525; -.
DR Antibodypedia; 14466; 718 antibodies from 45 providers.
DR DNASU; 15370; -.
DR Ensembl; ENSMUST00000023779; ENSMUSP00000023779; ENSMUSG00000023034.
DR Ensembl; ENSMUST00000228985; ENSMUSP00000155225; ENSMUSG00000023034.
DR GeneID; 15370; -.
DR KEGG; mmu:15370; -.
DR UCSC; uc007xsv.2; mouse.
DR CTD; 3164; -.
DR MGI; MGI:1352454; Nr4a1.
DR VEuPathDB; HostDB:ENSMUSG00000023034; -.
DR eggNOG; KOG4217; Eukaryota.
DR GeneTree; ENSGT00950000183038; -.
DR HOGENOM; CLU_007368_14_2_1; -.
DR InParanoid; P12813; -.
DR OMA; HASCQHY; -.
DR OrthoDB; 454476at2759; -.
DR PhylomeDB; P12813; -.
DR TreeFam; TF315430; -.
DR Reactome; R-MMU-198693; AKT phosphorylates targets in the nucleus.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR BioGRID-ORCS; 15370; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Gchfr; mouse.
DR PRO; PR:P12813; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; P12813; protein.
DR Bgee; ENSMUSG00000023034; Expressed in granulocyte and 241 other tissues.
DR ExpressionAtlas; P12813; baseline and differential.
DR Genevisible; P12813; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:BHF-UCL.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0035259; F:nuclear glucocorticoid receptor binding; ISO:MGI.
DR GO; GO:0004879; F:nuclear receptor activity; IEA:InterPro.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; ISO:MGI.
DR GO; GO:0071376; P:cellular response to corticotropin-releasing hormone stimulus; IDA:UniProtKB.
DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; ISO:MGI.
DR GO; GO:0071310; P:cellular response to organic substance; IDA:MGI.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; ISO:MGI.
DR GO; GO:0035767; P:endothelial cell chemotaxis; ISO:MGI.
DR GO; GO:0045444; P:fat cell differentiation; IDA:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; IDA:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:MGI.
DR GO; GO:0014860; P:neurotransmitter secretion involved in regulation of skeletal muscle contraction; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:MGI.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; 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; ISO:MGI.
DR GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl.
DR GO; GO:0010035; P:response to inorganic substance; ISO:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IMP:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IGI:MGI.
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 Acetylation; Cytoplasm; DNA-binding; Metal-binding; Mitochondrion; Nucleus;
KW Phosphoprotein; Receptor; Reference proteome; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..601
FT /note="Nuclear receptor subfamily 4 group A member 1"
FT /id="PRO_0000053716"
FT DOMAIN 363..598
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 267..342
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 270..290
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 306..330
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 173..469
FT /note="Required for nuclear import"
FT /evidence="ECO:0000250|UniProtKB:P22736"
FT REGION 180..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 237..268
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 302..364
FT /note="Required for the interaction with RXRA"
FT /evidence="ECO:0000250|UniProtKB:P22736"
FT REGION 345..364
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 182..197
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 239..263
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 344
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P22829"
FT MOD_RES 354
FT /note="Phosphoserine; by PKA, RPS6KA1 and RPS6KA3"
FT /evidence="ECO:0000250|UniProtKB:P22829"
FT CONFLICT 45
FT /note="A -> T (in Ref. 2; CAA42718)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 601 AA; 64738 MW; 8CFF45B58253887B CRC64;
MPCIQAQYGT PATSPGPRDH LTGDPLALEF GKPTMDLASP ETAPAAPATL PSFSTFMDGY
TGEFDTFLYQ LPGTTQPCSS ACSSASSTSS SSSSATSPAS ASFKFEDFQV YGCYPGTLSG
PLDETLSSSG SEYYGSPCSA PSPSTPNFQP SQLSPWDGSF GHFSPSQTYE GLWAWTEQLP
KASSGPPPPP TFFSFSPPTG PSPSLAQSSL KLFPPPATHQ LGEGESYSMP AAFPGLAPTS
PNRDTSGILD APVTSTKSRS GASGGSEGRC AVCGDNASCQ HYGVRTCEGC KGFFKRTVQK
SAKYICLANK DCPVDKRRRN RCQFCRFQKC LAVGMVKEVV RTDSLKGRRG RLPSKPKQPP
DASPTNLLTS LIRAHLDSGP STAKLDYSKF QELVLPRFGK EDAGDVQQFY DLLSGSLDVI
RKWAEKIPGF IELCPGDQDL LLESAFLELF ILRLAYRSKP GEGKLIFCSG LVLHQLQCAR
GFGDWIDNIL AFSRSLHSLG VDVPAFACLS ALVLITDRHG LQDPRRVEEL QNRIASCLKE
HMATVAGDPQ PASCLSRLLG KLPELRTLCT QGLQRIFCLK LEDLVPPPPI VDKIFMDTLS
F
