Reactome | UniProt:P22736 NR4A1

Schema > ReferenceGeneProduct > Entries

UniProt:P22736 NR4A1 Show undefined attributes

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.
crossReference	[DatabaseIdentifier:11497747] ENSEMBL:ENSG00000123358 [DatabaseIdentifier:12816246] ZINC target:P22736 [DatabaseIdentifier:12812861] ZINC - Substances:NR4A1_HUMAN [DatabaseIdentifier:12808505] ZINC - Predictions - Purchasable:NR4A1_HUMAN [DatabaseIdentifier:12804315] ZINC - Biogenic:NR4A1_HUMAN [DatabaseIdentifier:12423754] RefSeq:XP_054227880.1 [DatabaseIdentifier:12423755] RefSeq:NP_002126.2 [DatabaseIdentifier:12423757] RefSeq:XP_005268881.1 [DatabaseIdentifier:12423758] RefSeq:NP_001189162.1 [DatabaseIdentifier:12423759] RefSeq:NP_775180.1 [DatabaseIdentifier:12423756] RefSeq:XP_047284712.1 [DatabaseIdentifier:12288837] Pharos - Targets:P22736 [DatabaseIdentifier:12250149] PRO:P22736 [DatabaseIdentifier:12205661] PDB:4JGV [DatabaseIdentifier:12205659] PDB:8WUY [DatabaseIdentifier:12205656] PDB:8Z5A [DatabaseIdentifier:12205647] PDB:4RE8 [DatabaseIdentifier:12205655] PDB:4RZG [DatabaseIdentifier:12205657] PDB:3V3Q [DatabaseIdentifier:12205648] PDB:6KZ5 [DatabaseIdentifier:12205662] PDB:6LC1 [DatabaseIdentifier:12205660] PDB:4WHG [DatabaseIdentifier:12205652] PDB:4RZE [DatabaseIdentifier:12205650] PDB:8Y7L [DatabaseIdentifier:12205658] PDB:4WHF [DatabaseIdentifier:12205664] PDB:4KZJ [DatabaseIdentifier:12205645] PDB:4REE [DatabaseIdentifier:12205653] PDB:4KZM [DatabaseIdentifier:12205651] PDB:3V3E [DatabaseIdentifier:12205654] PDB:4RZF [DatabaseIdentifier:12205663] PDB:4KZI [DatabaseIdentifier:12205649] PDB:2QW4 [DatabaseIdentifier:12205646] PDB:4REF [DatabaseIdentifier:12128616] OpenTargets:ENSG00000123358 [DatabaseIdentifier:11606779] ENSEMBL:ENSP00000243050 [DatabaseIdentifier:11606778] ENSEMBL:ENSP00000353427 [DatabaseIdentifier:11606775] ENSEMBL:ENSP00000449539 [DatabaseIdentifier:11606776] ENSEMBL:ENSP00000378302 [DatabaseIdentifier:11606777] ENSEMBL:ENSP00000378301 [DatabaseIdentifier:11729474] ENSEMBL:ENST00000243050 [DatabaseIdentifier:11729477] ENSEMBL:ENST00000550082 [DatabaseIdentifier:11729476] ENSEMBL:ENST00000394824 [DatabaseIdentifier:11729475] ENSEMBL:ENST00000360284 [DatabaseIdentifier:11729478] ENSEMBL:ENST00000394825 [DatabaseIdentifier:11779043] Guide to Pharmacology - Targets:629 [DatabaseIdentifier:11790994] GeneCards:NR4A1 [DatabaseIdentifier:11806925] GlyGen:P22736 [DatabaseIdentifier:11843998] HPA:ENSG00000123358-NR4A1
databaseName	UniProt
dbId	60434
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
displayName	UniProt:P22736 NR4A1
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:9926675] Weiser, Joel, 2024-11-03
moleculeType	Protein
name	NR4A1
physicalEntity	[EntityWithAccessionedSequence:R-HSA-199831] NR4A1 [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-199846] p-S351-NR4A1 [nucleoplasm] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:12077158] NCBI Gene:3164 NR4A1 [ReferenceDNASequence:12754805] UCSC:P22736 NR4A1 [ReferenceDNASequence:12113366] OMIM:139139 NR4A1 [ReferenceDNASequence:ensembl:ENSG00000123358] ENSEMBL:ENSG00000123358 NR4A1 [ReferenceDNASequence:11363276] BioGPS Gene:3164 NR4A1 [ReferenceDNASequence:11401938] COSMIC - genes:NR4A1 NR4A1 [ReferenceDNASequence:11418571] CTD Gene:3164 NR4A1 [ReferenceDNASequence:11439353] dbSNP Gene:3164 NR4A1 [ReferenceDNASequence:11822659] HGNC:7980 NR4A1 [ReferenceDNASequence:11902055] KEGG:hsa:3164 NR4A1 [ReferenceDNASequence:11993065] Monarch:3164 NR4A1
referenceTranscript	[ReferenceRNASequence:12605349] RefSeq:NM_002135.4 NR4A1 [ReferenceRNASequence:12605347] RefSeq:NM_001202233.2 NR4A1 [ReferenceRNASequence:12605350] RefSeq:XM_047428756.1 NR4A1 [ReferenceRNASequence:12605345] RefSeq:XM_054371905.1 NR4A1 [ReferenceRNASequence:12605348] RefSeq:XM_005268824.4 NR4A1 [ReferenceRNASequence:12605346] RefSeq:NM_173157.3 NR4A1
schemaClass	ReferenceGeneProduct
secondaryIdentifier	NR4A1_HUMAN B4DML7 Q15627 Q53Y00 Q6IBU8
sequenceLength	598
species	[Species:48887] Homo sapiens
stId	uniprot:P22736
url	http://purl.uniprot.org/uniprot/P22736

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-199831] NR4A1 [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-199846] p-S351-NR4A1 [nucleoplasm]
(referenceSequence)	[ModifiedResidue:199851] O-phospho-L-serine at 351
(interactor)	[UndirectedInteraction:11143179] UniProt:P40763 <-> UniProt:P22736 (IntAct) [UndirectedInteraction:11143675] UniProt:Q99873 <-> UniProt:P22736 (IntAct) [UndirectedInteraction:11200319] UniProt:P04637 <-> UniProt:P22736 (IntAct) [UndirectedInteraction:11222017] UniProt:P50552 <-> UniProt:P22736 (IntAct) [UndirectedInteraction:11248385] UniProt:P22736 <-> UniProt:P10415 (IntAct) [UndirectedInteraction:11248387] UniProt:P22736 <-> UniProt:P55273 (IntAct) [UndirectedInteraction:11248391] UniProt:P22736 <-> IntAct:EBI-20568042 (IntAct) [UndirectedInteraction:11248395] UniProt:P22736 <-> UniProt:P40305-2 (IntAct) [UndirectedInteraction:11248397] UniProt:P22736 <-> UniProt:P32189 (IntAct) [UndirectedInteraction:11248399] UniProt:P22736 <-> IntAct:EBI-10173330 (IntAct) [UndirectedInteraction:11248401] UniProt:P22736 <-> UniProt:Q96JS3 (IntAct) [UndirectedInteraction:11248403] UniProt:P22736 <-> UniProt:P60370 (IntAct) [UndirectedInteraction:11248405] UniProt:P22736 <-> UniProt:Q17RB8 (IntAct) [UndirectedInteraction:11248407] UniProt:P22736 <-> UniProt:P03120 (IntAct) [UndirectedInteraction:11248409] UniProt:P22736 <-> UniProt:Q13162 (IntAct) [UndirectedInteraction:11248411] UniProt:P22736 <-> UniProt:Q504T8 (IntAct) [UndirectedInteraction:11248413] UniProt:P22736 <-> UniProt:Q709F0 (IntAct) [UndirectedInteraction:11248417] UniProt:P22736 <-> UniProt:Q9P2G1 (IntAct) [UndirectedInteraction:11248419] UniProt:P22736 <-> UniProt:P04350 (IntAct) [UndirectedInteraction:11248421] UniProt:P22736 <-> UniProt:O60888 (IntAct) [UndirectedInteraction:11248423] UniProt:P22736 <-> UniProt:Q9Y4D7 (IntAct)

Cite Us!