P43354 (NR4A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nuclear receptor subfamily 4 group A member 2

Alternative name(s):
Immediate-early response protein NOT
Orphan nuclear receptor NURR1
Transcriptionally-inducible nuclear receptor

Gene names

Name:	NR4A2
Synonyms:	NOT, NURR1, TINUR

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	598 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development. It is crucial for expression of a set of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons By similarity. Ref.8
Subunit structure	Interacts with SFPQ, NCOR2, SIN3A and HADC1. The interaction with NCOR2 increases in the absence of PITX3 By similarity.
Subcellular location	Nucleus Ref.8.
Tissue specificity	Expressed in a number of cell lines of T-cell, B-cell and fibroblast origin. Strong expression in brain tissue.
Developmental stage	Rapidly and only very transiently expressed after cell activation, during the G0-G1 transition of the cell cycle.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR4 subfamily. Contains 1 nuclear receptor DNA-binding domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Receptor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adult locomotory behavior Inferred from electronic annotation. Source: Compara cellular response to extracellular stimulus Inferred from direct assay Ref.1. Source: MGI cellular response to stress Inferred from electronic annotation. Source: Compara central nervous system projection neuron axonogenesis Inferred from electronic annotation. Source: Compara death Inferred from electronic annotation. Source: Compara dopamine biosynthetic process Inferred from electronic annotation. Source: Compara dopaminergic neuron differentiation Inferred from sequence or structural similarity. Source: UniProtKB habenula development Inferred from electronic annotation. Source: Compara negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara neuron maturation Inferred from electronic annotation. Source: Compara neuron migration Inferred from electronic annotation. Source: Compara positive regulation of catalytic activity Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara post-embryonic development Inferred from electronic annotation. Source: Compara regulation of dopamine metabolic process Inferred from electronic annotation. Source: Compara regulation of respiratory gaseous exchange Inferred from electronic annotation. Source: Compara response to amphetamine Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to inorganic substance Inferred from electronic annotation. Source: Compara response to insecticide Inferred from electronic annotation. Source: Compara transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Traceable author statement Ref.1. Source: ProtInc sequence-specific DNA binding Inferred from electronic annotation. Source: Compara steroid hormone receptor activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TCEAL5	Q5H9L2	2	EBI-2681738,EBI-2681773

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 598

598

Nuclear receptor subfamily 4 group A member 2

PRO_0000053718

Regions

DNA binding

260 – 335

76

Nuclear receptor

Zinc finger

263 – 283

21

NR C4-type

Zinc finger

299 – 323

25

NR C4-type

Region

409 – 459

51

Ligand-binding Potential

Compositional bias

80 – 138

59

Gln-rich

Compositional bias

127 – 233

107

Pro-rich

Compositional bias

346 – 391

46

Pro-rich

Experimental info

Sequence conflict

465

1

C → W in AAB33999. Ref.7

Sequence conflict

468

1

V → W in AAB33999. Ref.7

Secondary structure

1

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598

Helix Strand Turn

Details...

Helix

364 – 374

11

Helix

400 – 412

13

Helix

413 – 422

10

Helix

427 – 429

3

Helix

432 – 454

23

Beta strand

461 – 463

3

Beta strand

467 – 471

5

Helix

472 – 476

5

Helix

482 – 494

13

Helix

500 – 511

12

Helix

521 – 541

21

Helix

551 – 556

6

Helix

557 – 579

23

Helix

586 – 595

10

Sequences

	Sequence		Length	Mass (Da)
	P43354 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 28D8199AACE3E211	FASTA	598	66,591
	10 20 30 40 50 60 MPCVQAQYGS SPQGASPASQ SYSYHSSGEY SSDFLTPEFV KFSMDLTNTE ITATTSLPSF 70 80 90 100 110 120 STFMDNYSTG YDVKPPCLYQ MPLSGQQSSI KVEDIQMHNY QQHSHLPPQS EEMMPHSGSV 130 140 150 160 170 180 YYKPSSPPTP TTPGFQVQHS PMWDDPGSLH NFHQNYVATT HMIEQRKTPV SRLSLFSFKQ 190 200 210 220 230 240 SPPGTPVSSC QMRFDGPLHV PMNPEPAGSH HVVDGQTFAV PNPIRKPASM GFPGLQIGHA 250 260 270 280 290 300 SQLLDTQVPS PPSRGSPSNE GLCAVCGDNA ACQHYGVRTC EGCKGFFKRT VQKNAKYVCL 310 320 330 340 350 360 ANKNCPVDKR RRNRCQYCRF QKCLAVGMVK EVVRTDSLKG RRGRLPSKPK SPQEPSPPSP 370 380 390 400 410 420 PVSLISALVR AHVDSNPAMT SLDYSRFQAN PDYQMSGDDT QHIQQFYDLL TGSMEIIRGW 430 440 450 460 470 480 AEKIPGFADL PKADQDLLFE SAFLELFVLR LAYRSNPVEG KLIFCNGVVL HRLQCVRGFG 490 500 510 520 530 540 EWIDSIVEFS SNLQNMNIDI SAFSCIAALA MVTERHGLKE PKRVEELQNK IVNCLKDHVT 550 560 570 580 590 FNNGGLNRPN YLSKLLGKLP ELRTLCTQGL QRIFYLKLED LVPPPAIIDK LFLDTLPF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"NOT, a human immediate-early response gene closely related to the steroid/thyroid hormone receptor NAK1/TR3." Mages H.W., Rilke O., Bravo R., Senger G., Kroczek R.A. Mol. Endocrinol. 8:1583-1591(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Blood.
[2]	"Molecular cloning of the human Nurr1 gene: characterization of the human gene and cDNAs." Ichinose H., Ohye T., Suzuki T., Sumi-Ichinose C., Nomura T., Hagino Y., Nagatsu T. Gene 230:233-239(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Fibroblast.
[3]	"Organization of the human orphan nuclear receptor Nurr1 gene." Torii T., Kawarai T., Nakamura S., Kawakami H. Gene 230:225-232(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Skin.
[7]	"cDNA cloning of a NGFI-B/nur77-related transcription factor from an apoptotic human T cell line." Okabe T., Takayanagi R., Imasaki K., Haji M., Nawata H., Watanabe T. J. Immunol. 154:3871-3879(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 59-598.
[8]	"Induction of tyrosine hydroxylase expression by the transcription factor Pitx3." Messmer K., Remington M.P., Skidmore F., Fishman P.S. Int. J. Dev. Neurosci. 25:29-37(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X75918 mRNA. Translation: CAA53518.1.
AB017586 Genomic DNA. Translation: BAA75666.1.
AB019433 Genomic DNA. Translation: BAA77328.1.
AC074099 Genomic DNA. Translation: AAY24203.1.
CH471058 Genomic DNA. Translation: EAX11454.1.
CH471058 Genomic DNA. Translation: EAX11455.1.
BC009288 mRNA. Translation: AAH09288.1.
S77154 mRNA. Translation: AAB33999.1.

IPI

IPI01013823.

PIR

A57040.

RefSeq

NP_006177.1. NM_006186.3.

UniGene

Hs.563344.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1OVL	X-ray	2.20	A/B/C/D/E/F	328-598	[»]

ProteinModelPortal

P43354.

ModBase

Search...

Protein-protein interaction databases

IntAct

P43354. 14 interactions.

STRING

9606.ENSP00000344479.

PTM databases

PhosphoSite

P43354.

Polymorphism databases

DMDM

1171750.

Proteomic databases

PaxDb

P43354.

PRIDE

P43354.

Protocols and materials databases

DNASU

4929.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000339562; ENSP00000344479; ENSG00000153234.
ENST00000409572; ENSP00000386747; ENSG00000153234.

GeneID

4929.

KEGG

hsa:4929.

UCSC

uc002tyx.4. human.

Organism-specific databases

CTD

4929.

GeneCards

GC02M157180.

HGNC

HGNC:7981. NR4A2.

HPA

CAB010481.
HPA000543.

MIM

601828. gene.

neXtProt

NX_P43354.

Orphanet

2828. Young adult-onset Parkinsonism.

PharmGKB

PA31762.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG245120.

HOVERGEN

HBG052663.

InParanoid

P43354.

KO

K08558.

OrthoDB

EOG40CHGK.

PhylomeDB

P43354.

Enzyme and pathway databases

Reactome

REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

P43354.

Bgee

P43354.

CleanEx

HS_NR4A2.

Genevestigator

P43354.

GermOnline

ENSG00000153234. Homo sapiens.

Family and domain databases

Gene3D

1.10.565.10. 1 hit.
3.30.50.10. 1 hit.

InterPro

IPR003070. Nuc_orph_rcpt.
IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR003073. NURR_rcpt.
IPR001723. Str_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]

Pfam

PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]

PRINTS

PR01284. NUCLEARECPTR.
PR01287. NURRNUCRCPTR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.

SMART

SM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]

SUPFAM

SSF48508. Str_ncl_receptor. 1 hit.

PROSITE

PS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChEMBL

CHEMBL5002.

ChiTaRS

NR4A2. human.

EvolutionaryTrace

P43354.

GenomeRNAi

4929.

NextBio

18989.

SOURCE

Search...

Entry information

Entry name

NR4A2_HUMAN

Accession

Primary (citable) accession number: P43354
Secondary accession number(s): Q16311, Q53RZ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 144 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.