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Details on Person UniProt:P22736 NR4A1

Class:Id	ReferenceGeneProduct:60434
_chainChangeLog	chain:1-598 added on Fri February 6 2015
_displayName	UniProt:P22736 NR4A1
_timestamp	2024-11-03 20:11:04
chain	chain:1-598
checksum	41DAAEA7C25FDA22
comment	FUNCTION Orphan nuclear receptor. Binds the NGFI-B response element (NBRE) 5'-AAAGGTCA-3' (PubMed:18690216, PubMed:8121493, PubMed:9315652). Binds 9-cis-retinoic acid outside of its ligand-binding (NR LBD) domain (PubMed:18690216). Participates in energy homeostasis by sequestrating the kinase STK11 in the nucleus, thereby attenuating cytoplasmic AMPK activation (PubMed:22983157). Regulates the inflammatory response in macrophages by regulating metabolic adaptations during inflammation, including repressing the transcription of genes involved in the citric acid cycle (TCA) (By similarity). Inhibits NF-kappa-B signaling by binding to low-affinity NF-kappa-B binding sites, such as at the IL2 promoter (PubMed:15466594). May act concomitantly with NR4A2 in regulating the expression of delayed-early genes during liver regeneration (By similarity). Plays a role in the vascular response to injury (By similarity).FUNCTION In the cytosol, upon its detection of both bacterial lipopolysaccharide (LPS) and NBRE-containing mitochondrial DNA released by GSDMD pores during pyroptosis, it promotes non-canonical NLRP3 inflammasome activation by stimulating association of NLRP3 and NEK7.COFACTOR Binds 2 zinc ions.ACTIVITY REGULATION Its transcription factor activity is activated by binding cytosporone B (Csn-B) via its ligand-binding (NR LBD) domain and stimulates recruitment of coactivators NCOA1 and NCOA2, but not NCOA3, to promoters (PubMed:18690216). Csn-B-binding is also accompanied by its translocation to the mitochondrion (PubMed:18690216). Its transcription factor activity is activated by corticotropin-releasing hormone (CRH) and forskolin (PubMed:9315652). Not activated by binding cytosporone C (Csn-C) (PubMed:18690216).SUBUNIT Binds the NGFI-B response element (NBRE) as a monomer (PubMed:18690216). Binds the Nur response element (NurRE), consisting of two inverse NBRE-related octanucleotide repeats separated by 6 base-pairs, as a dimer (PubMed:18690216, PubMed:9315652). Interacts (via N-terminus) with NLRP3 (via LRR repeat domain); the interaction is direct, requires binding of NR4A1/Nur77 to NBRE-containing dsDNA and lipopolysaccharide, and leads to non-canonical NLRP3 inflammasome activation (By similarity). Interacts with GADD45GIP1 (PubMed:15459248). Interacts with STK11 (PubMed:22983157). Interacts with IFI27 (PubMed:22427340). Heterodimer (via DNA-binding domain) with RXRA (via C-terminus); DNA-binding of the heterodimer is enhanced by 9-cis retinoic acid (PubMed:15509776, PubMed:17761950). Competes for the RXRA interaction with EP300 and thereby attenuates EP300 mediated acetylation of RXRA (PubMed:17761950). Interacts with NCOA1 (PubMed:18690216). Interacts with NCOA2 (PubMed:18690216). Interacts with NCOA3 (PubMed:18690216).INTERACTION Nuclear export to the cytosol is XPO1-mediated and positively regulated by IFI27 (PubMed:22427340). Translocation to the mitochondrion upon interaction with RXRA and upon the presence of 9-cis retinoic acid (PubMed:17761950).ALTERNATIVE PRODUCTS Fetal muscle and adult liver, brain and thyroid.INDUCTION Induced by cytosporone B (Csn-B); directly stimulates its own expression (PubMed:18690216). Induced by corticotropin-releasing hormone (CRH) (PubMed:9315652). Induced by growth-stimulating agents (PubMed:1651101).DOMAIN The NR LBD domain binds the lipid A moiety of lipopolysaccharide (LPS) in the cytosol.PTM Phosphorylated at Ser-351 by RPS6KA1 and RPS6KA3 in response to mitogenic or stress stimuli.PTM Acetylated by p300/CBP, acetylation increases stability. Deacetylated by HDAC1.SIMILARITY Belongs to the nuclear hormone receptor family. NR4 subfamily.
description	recommendedName: Nuclear receptor subfamily 4immunitygroup A member 1 alternativeName: Early response protein NAK1 alternativeName: Nuclear hormone receptor NUR/77 shortName: Nur77 alternativeName: Orphan nuclear receptor HMR alternativeName: Orphan nuclear receptor TR3 alternativeName: ST-59 alternativeName: Testicular receptor 3
geneName	NR4A1 GFRP1 HMR NAK1
identifier	P22736
isSequenceChanged	FALSE
keyword	3D-structure Acetylation Alternative splicing Cytoplasm DNA-binding Inflammatory response Metal-binding Mitochondrion Nucleus Phosphoprotein Proteomics identification Receptor Reference proteome Transcription Transcription regulation Zinc Zinc-finger
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
name	NR4A1
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8999644] ENSEMBL:ENSG00000123358 NR4A1 [Homo sapiens]
secondaryIdentifier	NR4A1_HUMAN B4DML7 Q15627 Q53Y00 Q6IBU8
sequenceLength	598
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:8972046] UniProt:P22736-1 NR4A1 [Homo sapiens] [ReferenceIsoform:8972047] UniProt:P22736-2 NR4A1 [Homo sapiens] [ReferenceIsoform:8972048] UniProt:P22736-3 NR4A1 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:199831] NR4A1 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:199846] p-S351-NR4A1 [nucleoplasm] [Homo sapiens]
(referenceSequence)	[ModifiedResidue:199851] O-phospho-L-serine at 351
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No pathways have been reviewed or authored by UniProt:P22736 NR4A1 (60434)