P10588 (NR2F6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nuclear receptor subfamily 2 group F member 6

Alternative name(s):
V-erbA-related protein 2
Short name=EAR-2

Gene names

Name:	NR2F6
Synonyms:	EAR2, ERBAL2

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	404 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcription factor predominantly involved in transcriptional repression. Binds to promoter/enhancer response elements that contain the imperfect 5'-AGGTCA-3' direct or inverted repeats with various spacings which are also recognized by other nuclear hormone receptors. Involved in modulation of hormonal responses. Represses transcriptional activity of the lutropin-choriogonadotropic hormone receptor/LHCGR gene, the renin/REN gene and the oxytocin-neurophysin/OXT gene. Represses the triiodothyronine-dependent and -independent transcriptional activity of the thyroid hormone receptor gene in a cell type-specific manner. The corepressing function towards thyroid hormone receptor beta/THRB involves at least in part the inhibition of THRB binding to triiodothyronine response elements (TREs) by NR2F6. Inhibits NFATC transcription factor DNA binding and subsequently its transcriptional activity. Acts as transcriptional repressor of IL-17 expression in Th-17 differentiated CD4+ T cells and may be involved in induction and/or maintenance of peripheral immunological tolerance and autoimmunity. Involved in development of forebrain circadian clock; is required early in the development of the locus coeruleus (LC). Ref.5 Ref.6 Ref.7 Ref.8
Subunit structure	Binds DNA as dimer; homodimer and heterodimer with NR2F2 and probably NR2F1 By similarity. Interacts with THRB. Ref.6 Ref.7
Subcellular location	Nucleus Ref.5 Ref.8.
Tissue specificity	Expressed in heart, placenta, liver, skeletal muscle, kidney and pancreas. Ref.6
Induction	Inhibited by gonadotropin in granulosa cells. Ref.7
Sequence similarities	Belongs to the nuclear hormone receptor family. NR2 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 Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	detection of temperature stimulus involved in sensory perception of pain Inferred from electronic annotation. Source: Compara entrainment of circadian clock by photoperiod Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.5. Source: UniProtKB neuron development Inferred from electronic annotation. Source: Compara transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome
Cellular_component	nucleoplasm Traceable author statement. Source: Reactome
Molecular_function	sequence-specific DNA binding Inferred from direct assay Ref.5. Source: UniProtKB steroid hormone receptor activity Traceable author statement Ref.1. Source: ProtInc thyroid hormone receptor activity Traceable author statement Ref.1. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CBX1	P83916	2	EBI-2681496,EBI-78129
NAP1L1	P55209	2	EBI-2681496,EBI-356392

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 404	404	Nuclear receptor subfamily 2 group F member 6		PRO_0000053613
Regions
	DNA binding	53 – 128	76	Nuclear receptor Ref.6
	Zinc finger	56 – 76	21	NR C4-type
	Zinc finger	92 – 116	25	NR C4-type
	Region	171 – 404	234	Ligand-binding By similarity
	Region	327 – 404	78	Important for dimerization By similarity
Amino acid modifications
	Modified residue	40	1	Phosphoserine Ref.9
	Modified residue	83	1	Phosphoserine Ref.8
Experimental info
	Mutagenesis	74 – 78	5	EGCKS → GSCKV: Loss of DNA (TRE) binding. Reduces the corepressor activity towards THRB. Ref.6
	Sequence conflict	83	1	S → T in CAA31282. Ref.1
	Sequence conflict	220 – 221	2	AP → G in CAA31282. Ref.1
	Sequence conflict	237	1	L → M in CAA31282. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P10588 [UniParc]. Last modified September 19, 2002. Version 2. Checksum: D1FFE523E782E969	FASTA	404	42,979
	10 20 30 40 50 60 MAMVTGGWGG PGGDTNGVDK AGGYPRAAED DSASPPGAAS DAEPGDEERP GLQVDCVVCG 70 80 90 100 110 120 DKSSGKHYGV FTCEGCKSFF KRSIRRNLSY TCRSNRDCQI DQHHRNQCQY CRLKKCFRVG 130 140 150 160 170 180 MRKEAVQRGR IPHSLPGAVA ASSGSPPGSA LAAVASGGDL FPGQPVSELI AQLLRAEPYP 190 200 210 220 230 240 AAAGRFGAGG GAAGAVLGID NVCELAARLL FSTVEWARHA PFFPELPVAD QVALLRLSWS 250 260 270 280 290 300 ELFVLNAAQA ALPLHTAPLL AAAGLHAAPM AAERAVAFMD QVRAFQEQVD KLGRLQVDSA 310 320 330 340 350 360 EYGCLKAIAL FTPDACGLSD PAHVESLQEK AQVALTEYVR AQYPSQPQRF GRLLLRLPAL 370 380 390 400 RAVPASLISQ LFFMRLVGKT PIETLIRDML LSGSTFNWPY GSGQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of two novel members of erbA superfamily by molecular cloning: the gene products of the two are highly related to each other." Miyajima N., Kadowaki Y., Fukushige S., Shimizu S., Semba K., Yamanashi Y., Matsubara K., Toyoshima K., Yamamoto T. Nucleic Acids Res. 16:11057-11074(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Fetal lung.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: Kidney, Pancreas and Uterus.
[5]	"Nuclear orphan receptors regulate transcription of the gene for the human luteinizing hormone receptor." Zhang Y., Dufau M.L. J. Biol. Chem. 275:2763-2770(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]	"The orphan nuclear receptor Ear-2 is a negative coregulator for thyroid hormone nuclear receptor function." Zhu X.G., Park K.S., Kaneshige M., Bhat M.K., Zhu Q., Mariash C.N., McPhie P., Cheng S.Y. Mol. Cell. Biol. 20:2604-2618(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY, DNA-BINDING, INTERACTION WITH THRB, MUTAGENESIS OF 74-GLU--SER-78.
[7]	"EAR2 and EAR3/COUP-TFI regulate transcription of the rat LH receptor." Zhang Y., Dufau M.L. Mol. Endocrinol. 15:1891-1905(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, INDUCTION BY GONADOTROPIN.
[8]	"The nuclear orphan receptor NR2F6 suppresses lymphocyte activation and T helper 17-dependent autoimmunity." Hermann-Kleiter N., Gruber T., Lutz-Nicoladoni C., Thuille N., Fresser F., Labi V., Schiefermeier N., Warnecke M., Huber L., Villunger A., Eichele G., Kaminski S., Baier G. Immunity 29:205-216(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-83.
[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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X12794 Genomic DNA. Translation: CAA31282.1. AK314961 mRNA. Translation: BAG37465.1. CH471106 Genomic DNA. Translation: EAW84580.1. BC002669 mRNA. Translation: AAH02669.3. BC063018 mRNA. Translation: AAH63018.2. BC084544 mRNA. Translation: AAH84544.2.
IPI	IPI00021429.
PIR	S02709.
RefSeq	NP_005225.2. NM_005234.3.
UniGene	Hs.466148.
3D structure databases
ProteinModelPortal	P10588.
ModBase	Search...
Protein-protein interaction databases
IntAct	P10588. 14 interactions.
STRING	9606.ENSP00000291442.
PTM databases
PhosphoSite	P10588.
Polymorphism databases
DMDM	23503053.
Proteomic databases
PaxDb	P10588.
PRIDE	P10588.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000291442; ENSP00000291442; ENSG00000160113.
GeneID	2063.
KEGG	hsa:2063.
UCSC	uc002nfq.3. human.
Organism-specific databases
CTD	2063.
GeneCards	GC19M017342.
HGNC	HGNC:7977. NR2F6.
MIM	132880. gene.
neXtProt	NX_P10588.
PharmGKB	PA31760.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG277317.
HOGENOM	HOG000260820.
HOVERGEN	HBG005606.
InParanoid	P10588.
KO	K08549.
OMA	DPNGGTN.
OrthoDB	EOG4FN4HT.
PhylomeDB	P10588.
Enzyme and pathway databases
Reactome	REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	P10588.
Bgee	P10588.
CleanEx	HS_NR2F6.
Genevestigator	P10588.
GermOnline	ENSG00000160113. Homo sapiens.
Family and domain databases
Gene3D	1.10.565.10. 1 hit. 3.30.50.10. 1 hit.
InterPro	IPR003068. COUP_TF. IPR008946. Nucl_hormone_rcpt_ligand-bd. IPR000536. Nucl_hrmn_rcpt_lig-bd_core. 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	PR01282. COUPTNFACTOR. 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	CHEMBL1961791.
GenomeRNAi	2063.
NextBio	8381.
SOURCE	Search...

Entry information

Entry name

NR2F6_HUMAN

Accession

Primary (citable) accession number: P10588
Secondary accession number(s): B2RC68 , Q5XGA0, Q6P586, Q9BUE8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	September 19, 2002
Last modified:	May 1, 2013
This is version 146 of the entry and version 2 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.