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Protein

Nuclear receptor subfamily 4 group A member 1

Gene

NR4A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2. Participates in energy homeostasis by sequestrating the kinase STK11 in the nucleus, thereby attenuating cytoplasmic AMPK activation.By similarity2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi264 – 339Nuclear receptorPROSITE-ProRule annotationAdd BLAST76
Zinc fingeri267 – 287NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri303 – 327NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

GO - Biological processi

  • cell migration involved in sprouting angiogenesis Source: BHF-UCL
  • cellular response to corticotropin-releasing hormone stimulus Source: UniProtKB
  • cellular response to fibroblast growth factor stimulus Source: BHF-UCL
  • cellular response to vascular endothelial growth factor stimulus Source: BHF-UCL
  • endothelial cell chemotaxis Source: BHF-UCL
  • fat cell differentiation Source: UniProtKB
  • negative regulation of cell cycle Source: UniProtKB
  • positive regulation of endothelial cell proliferation Source: BHF-UCL
  • positive regulation of transcription by RNA polymerase II Source: MGI
  • regulation of type B pancreatic cell proliferation Source: UniProtKB
  • signal transduction Source: ProtInc
  • transcription initiation from RNA polymerase II promoter Source: Reactome

Keywordsi

Molecular functionDNA-binding, Receptor
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-198693 AKT phosphorylates targets in the nucleus
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer
SignaLinkiP22736
SIGNORiP22736

Protein family/group databases

MoonDBiP22736 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear receptor subfamily 4 group A member 1
Alternative name(s):
Early response protein NAK1
Nuclear hormone receptor NUR/77
Short name:
Nur77
Orphan nuclear receptor HMR
Orphan nuclear receptor TR3
ST-59
Testicular receptor 3
Gene namesi
Name:NR4A1
Synonyms:GFRP1, HMR, NAK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000123358.19
HGNCiHGNC:7980 NR4A1
MIMi139139 gene
neXtProtiNX_P22736

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi595T → E: Strongly weakens interaction with STK11. 1 Publication1

Organism-specific databases

DisGeNETi3164
OpenTargetsiENSG00000123358
PharmGKBiPA31761

Chemistry databases

ChEMBLiCHEMBL1293229

Polymorphism and mutation databases

BioMutaiNR4A1
DMDMi127819

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000537151 – 598Nuclear receptor subfamily 4 group A member 1Add BLAST598

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei341Phosphoserine; by PKABy similarity1
Modified residuei351PhosphoserineCombined sources1 Publication1

Post-translational modificationi

Phosphorylated at Ser-351 by RPS6KA1 and RPS6KA3 in response to mitogenic or stress stimuli.1 Publication
Acetylated by p300/CBP, acetylation increases stability. Deacetylated by HDAC1.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP22736
PaxDbiP22736
PeptideAtlasiP22736
PRIDEiP22736
ProteomicsDBi54032
54033 [P22736-2]

PTM databases

iPTMnetiP22736
PhosphoSitePlusiP22736

Expressioni

Tissue specificityi

Fetal muscle and adult liver, brain and thyroid.

Inductioni

By growth-stimulating agents.

Gene expression databases

BgeeiENSG00000123358
CleanExiHS_NR4A1
ExpressionAtlasiP22736 baseline and differential
GenevisibleiP22736 HS

Organism-specific databases

HPAiHPA059742
HPA070142

Interactioni

Subunit structurei

Binds DNA as a monomer (By similarity). Interacts with GADD45GIP1. Interacts with STK11.By similarity2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109407, 100 interactors
DIPiDIP-40392N
IntActiP22736, 104 interactors
MINTiP22736
STRINGi9606.ENSP00000353427

Chemistry databases

BindingDBiP22736

Structurei

Secondary structure

1598
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi364 – 373Combined sources10
Helixi379 – 381Combined sources3
Beta strandi395 – 397Combined sources3
Helixi400 – 422Combined sources23
Helixi427 – 429Combined sources3
Helixi432 – 454Combined sources23
Helixi457 – 459Combined sources3
Beta strandi461 – 463Combined sources3
Beta strandi467 – 471Combined sources5
Helixi472 – 479Combined sources8
Helixi482 – 495Combined sources14
Helixi500 – 511Combined sources12
Helixi521 – 541Combined sources21
Turni544 – 546Combined sources3
Helixi550 – 556Combined sources7
Helixi558 – 579Combined sources22
Helixi586 – 594Combined sources9

3D structure databases

ProteinModelPortaliP22736
SMRiP22736
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP22736

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini360 – 595NR LBDPROSITE-ProRule annotationAdd BLAST236

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi82 – 92Poly-SerAdd BLAST11
Compositional biasi583 – 586Poly-Pro4

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri267 – 287NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri303 – 327NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4217 Eukaryota
ENOG410YWNC LUCA
GeneTreeiENSGT00760000118887
HOGENOMiHOG000230925
HOVERGENiHBG052663
InParanoidiP22736
KOiK04465
PhylomeDBiP22736
TreeFamiTF315430

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
IPR003071 Nuc_orp_HMR_rcpt
IPR003070 Nuc_orph_rcpt
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR01285 HMRNUCRECPTR
PR01284 NUCLEARECPTR
PR00398 STRDHORMONER
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 1 hit
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P22736-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPCIQAQYGT PAPSPGPRDH LASDPLTPEF IKPTMDLASP EAAPAAPTAL
60 70 80 90 100
PSFSTFMDGY TGEFDTFLYQ LPGTVQPCSS ASSSASSTSS SSATSPASAS
110 120 130 140 150
FKFEDFQVYG CYPGPLSGPV DEALSSSGSD YYGSPCSAPS PSTPSFQPPQ
160 170 180 190 200
LSPWDGSFGH FSPSQTYEGL RAWTEQLPKA SGPPQPPAFF SFSPPTGPSP
210 220 230 240 250
SLAQSPLKLF PSQATHQLGE GESYSMPTAF PGLAPTSPHL EGSGILDTPV
260 270 280 290 300
TSTKARSGAP GGSEGRCAVC GDNASCQHYG VRTCEGCKGF FKRTVQKNAK
310 320 330 340 350
YICLANKDCP VDKRRRNRCQ FCRFQKCLAV GMVKEVVRTD SLKGRRGRLP
360 370 380 390 400
SKPKQPPDAS PANLLTSLVR AHLDSGPSTA KLDYSKFQEL VLPHFGKEDA
410 420 430 440 450
GDVQQFYDLL SGSLEVIRKW AEKIPGFAEL SPADQDLLLE SAFLELFILR
460 470 480 490 500
LAYRSKPGEG KLIFCSGLVL HRLQCARGFG DWIDSILAFS RSLHSLLVDV
510 520 530 540 550
PAFACLSALV LITDRHGLQE PRRVEELQNR IASCLKEHVA AVAGEPQPAS
560 570 580 590
CLSRLLGKLP ELRTLCTQGL QRIFYLKLED LVPPPPIIDK IFMDTLPF
Length:598
Mass (Da):64,463
Last modified:August 1, 1991 - v1
Checksum:i41DAAEA7C25FDA22
GO
Isoform 2 (identifier: P22736-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MWLAKACWSIQSEM

Note: No experimental confirmation available.
Show »
Length:611
Mass (Da):65,998
Checksum:i21F3BC282AE6BE8D
GO
Isoform 3 (identifier: P22736-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     293-325: RTVQKNAKYICLANKDCPVDKRRRNRCQFCRFQ → VPRSPRWGLLLEMERGWPHPIGTCGLPLGSPPS
     326-598: Missing.

Show »
Length:325
Mass (Da):33,754
Checksum:iBCF2490A32A09175
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti253T → I (PubMed:1651101).Curated1
Sequence conflicti262G → P in AAA36763 (PubMed:2626032).Curated1
Sequence conflicti360S → F in CAG32985 (Ref. 8) Curated1
Sequence conflicti370R → L in AAA36763 (PubMed:2626032).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06153426L → V. Corresponds to variant dbSNP:rs1882118Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0430861M → MWLAKACWSIQSEM in isoform 2. 1 Publication1
Alternative sequenceiVSP_047769293 – 325RTVQK…FCRFQ → VPRSPRWGLLLEMERGWPHP IGTCGLPLGSPPS in isoform 3. 2 PublicationsAdd BLAST33
Alternative sequenceiVSP_047770326 – 598Missing in isoform 3. 2 PublicationsAdd BLAST273

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D49728 mRNA Translation: BAA08565.1
L13740 mRNA Translation: AAA36763.1
D85245 mRNA Translation: BAA12746.1
AK297526 mRNA Translation: BAG59929.1
HQ692855 mRNA Translation: ADZ17366.1
AB307717 mRNA Translation: BAH02308.1
BT007144 mRNA Translation: AAP35808.1
AK314437 mRNA Translation: BAG37048.1
CR456704 mRNA Translation: CAG32985.1
AC025259 Genomic DNA No translation available.
CH471111 Genomic DNA Translation: EAW58222.1
CH471111 Genomic DNA Translation: EAW58224.1
CH471111 Genomic DNA Translation: EAW58225.1
BC016147 mRNA Translation: AAH16147.1
CCDSiCCDS55828.1 [P22736-2]
CCDS8818.1 [P22736-1]
PIRiA37251
RefSeqiNP_001189162.1, NM_001202233.1 [P22736-2]
NP_002126.2, NM_002135.4 [P22736-1]
NP_775180.1, NM_173157.2 [P22736-1]
XP_005268881.1, XM_005268824.3 [P22736-1]
XP_006719426.1, XM_006719363.1 [P22736-1]
XP_006719427.1, XM_006719364.3 [P22736-1]
UniGeneiHs.524430
Hs.670088

Genome annotation databases

EnsembliENST00000243050; ENSP00000243050; ENSG00000123358 [P22736-1]
ENST00000360284; ENSP00000353427; ENSG00000123358 [P22736-2]
ENST00000394824; ENSP00000378301; ENSG00000123358 [P22736-1]
ENST00000394825; ENSP00000378302; ENSG00000123358 [P22736-1]
ENST00000548232; ENSP00000449587; ENSG00000123358 [P22736-3]
ENST00000550082; ENSP00000449539; ENSG00000123358 [P22736-2]
GeneIDi3164
KEGGihsa:3164
UCSCiuc001rzs.4 human [P22736-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNR4A1_HUMAN
AccessioniPrimary (citable) accession number: P22736
Secondary accession number(s): B4DML7
, Q15627, Q53Y00, Q6IBU8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: August 1, 1991
Last modified: July 18, 2018
This is version 201 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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