NR4A1_RAT
ID NR4A1_RAT Reviewed; 597 AA.
AC P22829; Q4V8M4;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Nuclear receptor subfamily 4 group A member 1;
DE AltName: Full=NUR77;
DE AltName: Full=Nerve growth factor-induced protein I-B;
DE Short=NGFI-B;
DE AltName: Full=Orphan nuclear receptor HMR;
GN Name=Nr4a1; Synonyms=Hmr, Ngfib;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3272167; DOI=10.1016/0896-6273(88)90138-9;
RA Milbrandt J.;
RT "Nerve growth factor induces a gene homologous to the glucocorticoid
RT receptor gene.";
RL Neuron 1:183-188(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [3]
RP CHARACTERIZATION.
RX PubMed=8395013; DOI=10.1128/mcb.13.9.5794-5804.1993;
RA Wilson T.E., Fahrner T.J., Milbrandt J.;
RT "The orphan receptors NGFI-B and steroidogenic factor 1 establish monomer
RT binding as a third paradigm of nuclear receptor-DNA interaction.";
RL Mol. Cell. Biol. 13:5794-5804(1993).
RN [4]
RP DNA-BINDING REGION.
RX PubMed=1314418; DOI=10.1126/science.1314418;
RA Wilson T.E., Paulsen R.E., Padgett K.A., Milbrandt J.;
RT "Participation of non-zinc finger residues in DNA binding by two nuclear
RT orphan receptors.";
RL Science 256:107-110(1992).
RN [5]
RP PHOSPHORYLATION AT SER-340 AND SER-350, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS.
RX PubMed=8227042; DOI=10.1016/s0021-9258(19)74536-0;
RA Hirata Y., Kiuchi K., Chen H.-C., Milbrandt J., Guroff G.;
RT "The phosphorylation and DNA binding of the DNA-binding domain of the
RT orphan nuclear receptor NGFI-B.";
RL J. Biol. Chem. 268:24808-24812(1993).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 264-351 IN COMPLEX WITH NBRE, AND
RP METAL-BINDING.
RX PubMed=10331876; DOI=10.1038/8276;
RA Meinke G., Sigler P.B.;
RT "DNA-binding mechanism of the monomeric orphan nuclear receptor NGFI-B.";
RL Nat. Struct. Biol. 6:471-477(1999).
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 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P12813}.
CC -!- SUBUNIT: Binds DNA as a monomer (PubMed:10331876). 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:0000269|PubMed:10331876}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305|PubMed:8227042}. 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: Expressed in lung, brain and superior cervical
CC ganglia. High levels are seen in the adrenal tissue.
CC -!- INDUCTION: By nerve growth factor and during liver regeneration.
CC -!- PTM: Phosphorylated at Ser-350 by RPS6KA1 and RPS6KA3 in response to
CC mitogenic or stress stimuli (By similarity). Phosphorylation of Ser-350
CC results in decrease in NBRE binding while phosphorylation of Ser-340
CC has little effect on it. {ECO:0000250, ECO:0000269|PubMed:8227042}.
CC -!- PTM: Acetylated by p300/CBP, acetylation increases stability.
CC Deacetylated by HDAC1 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR4
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA56770.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH97313.2; Type=Erroneous initiation; Evidence={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; U17254; AAA56770.1; ALT_INIT; mRNA.
DR EMBL; BC097313; AAH97313.2; ALT_INIT; mRNA.
DR PIR; JQ0623; JQ0623.
DR RefSeq; NP_077364.2; NM_024388.2.
DR RefSeq; XP_006242418.1; XM_006242356.2.
DR RefSeq; XP_006242420.1; XM_006242358.2.
DR RefSeq; XP_017450619.1; XM_017595130.1.
DR PDB; 1CIT; X-ray; 2.70 A; A=264-352.
DR PDB; 1YJE; X-ray; 2.40 A; A=354-597.
DR PDBsum; 1CIT; -.
DR PDBsum; 1YJE; -.
DR AlphaFoldDB; P22829; -.
DR SMR; P22829; -.
DR IntAct; P22829; 2.
DR MINT; P22829; -.
DR STRING; 10116.ENSRNOP00000010171; -.
DR iPTMnet; P22829; -.
DR PhosphoSitePlus; P22829; -.
DR PaxDb; P22829; -.
DR PRIDE; P22829; -.
DR Ensembl; ENSRNOT00000010171; ENSRNOP00000010171; ENSRNOG00000007607.
DR GeneID; 79240; -.
DR KEGG; rno:79240; -.
DR CTD; 3164; -.
DR RGD; 620029; Nr4a1.
DR eggNOG; KOG4217; Eukaryota.
DR GeneTree; ENSGT00950000183038; -.
DR HOGENOM; CLU_007368_14_2_1; -.
DR InParanoid; P22829; -.
DR OMA; HASCQHY; -.
DR OrthoDB; 454476at2759; -.
DR PhylomeDB; P22829; -.
DR TreeFam; TF315430; -.
DR Reactome; R-RNO-198693; AKT phosphorylates targets in the nucleus.
DR Reactome; R-RNO-383280; Nuclear Receptor transcription pathway.
DR EvolutionaryTrace; P22829; -.
DR PRO; PR:P22829; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000007607; Expressed in skeletal muscle tissue and 19 other tissues.
DR ExpressionAtlas; P22829; baseline and differential.
DR Genevisible; P22829; RN.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0031965; C:nuclear membrane; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0005667; C:transcription regulator complex; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
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; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0035259; F:nuclear glucocorticoid receptor binding; IPI:UniProtKB.
DR GO; GO:0004879; F:nuclear receptor activity; IEA:InterPro.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
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; ISO:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006915; P:apoptotic process; ISO:RGD.
DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0071310; P:cellular response to organic substance; ISO:RGD.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; ISO:RGD.
DR GO; GO:0035767; P:endothelial cell chemotaxis; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0014860; P:neurotransmitter secretion involved in regulation of skeletal muscle contraction; IMP:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
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; IMP:UniProtKB.
DR GO; GO:0001975; P:response to amphetamine; IMP:RGD.
DR GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; ISO:RGD.
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; Cytoplasm; DNA-binding; Metal-binding;
KW Mitochondrion; Nucleus; Phosphoprotein; Receptor; Reference proteome;
KW Transcription; Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..597
FT /note="Nuclear receptor subfamily 4 group A member 1"
FT /id="PRO_0000053717"
FT DOMAIN 359..594
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 263..338
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 266..286
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 302..326
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 170..465
FT /note="Required for nuclear import"
FT /evidence="ECO:0000250|UniProtKB:P22736"
FT REGION 298..360
FT /note="Required for the interaction with RXRA"
FT /evidence="ECO:0000250|UniProtKB:P22736"
FT REGION 341..360
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 340
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:8227042"
FT MOD_RES 350
FT /note="Phosphoserine; by PKA, RPS6KA1 and RPS6KA3"
FT /evidence="ECO:0000269|PubMed:8227042"
FT MUTAGEN 340
FT /note="S->A: Loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:8227042"
FT MUTAGEN 345
FT /note="R->K: Decreased NBRE binding."
FT /evidence="ECO:0000269|PubMed:8227042"
FT MUTAGEN 348
FT /note="L->V: Almost complete loss of NBRE binding."
FT /evidence="ECO:0000269|PubMed:8227042"
FT MUTAGEN 350
FT /note="S->A: Loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:8227042"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:1CIT"
FT STRAND 275..277
FT /evidence="ECO:0007829|PDB:1CIT"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:1CIT"
FT HELIX 284..296
FT /evidence="ECO:0007829|PDB:1CIT"
FT STRAND 303..306
FT /evidence="ECO:0007829|PDB:1CIT"
FT TURN 312..317
FT /evidence="ECO:0007829|PDB:1CIT"
FT HELIX 319..328
FT /evidence="ECO:0007829|PDB:1CIT"
FT HELIX 333..335
FT /evidence="ECO:0007829|PDB:1CIT"
FT HELIX 339..341
FT /evidence="ECO:0007829|PDB:1CIT"
FT HELIX 363..374
FT /evidence="ECO:0007829|PDB:1YJE"
FT HELIX 378..380
FT /evidence="ECO:0007829|PDB:1YJE"
FT HELIX 399..421
FT /evidence="ECO:0007829|PDB:1YJE"
FT TURN 424..428
FT /evidence="ECO:0007829|PDB:1YJE"
FT HELIX 431..453
FT /evidence="ECO:0007829|PDB:1YJE"
FT TURN 456..459
FT /evidence="ECO:0007829|PDB:1YJE"
FT STRAND 460..462
FT /evidence="ECO:0007829|PDB:1YJE"
FT STRAND 466..470
FT /evidence="ECO:0007829|PDB:1YJE"
FT HELIX 471..478
FT /evidence="ECO:0007829|PDB:1YJE"
FT HELIX 481..495
FT /evidence="ECO:0007829|PDB:1YJE"
FT HELIX 499..510
FT /evidence="ECO:0007829|PDB:1YJE"
FT HELIX 520..540
FT /evidence="ECO:0007829|PDB:1YJE"
FT HELIX 550..555
FT /evidence="ECO:0007829|PDB:1YJE"
FT HELIX 558..578
FT /evidence="ECO:0007829|PDB:1YJE"
FT HELIX 585..592
FT /evidence="ECO:0007829|PDB:1YJE"
SQ SEQUENCE 597 AA; 64282 MW; 9CFA987112337E53 CRC64;
MPCIQAQYGT PATSPGPRDH LTGDPLALEF SKPTMDLASP ETAPTAPATL PSFSTFMDGG
YTGEFDTFLY QLPGTAQPCS SASSTSSSSS SATSPASASF KFEDFQVYGC YPGTLSGPLD
ETLSSSGSDY YGSPCSAPSP PTPNFQPSQL SPWDGSFGHF SPSQTYEGLR VWTEQLPKAS
GPPPPPTFFS FSPPTGPSPS LAQSSLKLFP APATHQLGEG ESYSVPAAFP GLAPTSPNCD
TSGILDAPVT STKARSGSSG GSEGRCAVCG DNASCQHYGV RTCEGCKGFF KRTVQKSAKY
ICLANKDCPV DKRRRNRCQF CRFQKCLAVG MVKEVVRTDS LKGRRGRLPS KPKQPPDASP
TNLLTSLIRA HLDSGPNTAK LDYSKFQELV LPRFGKEDAG DVQQFYDLLS GSLDVIRKWA
EKIPGFIELS PGDQDLLLES AFLELFILRL AYRSKPGEGK LIFCSGLVLH RLQCARGFGD
WIDNILAFSR SLHSLGVDVP AFACLSALVL ITDRHGLQDP RRVEELQNRI ASCLKEHMAA
VAGDPQPASC LSRLLGKLPE LRTLCTQGLQ RIFCLKLEDL VPPPPIVDKI FMDTLSF
