P62509 (ERR3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Estrogen-related receptor gamma

Alternative name(s):
Estrogen receptor-related protein 3
Nuclear receptor subfamily 3 group B member 3

Gene names

Name:	Esrrg
Synonyms:	Err3, Kiaa0832, Nr3b3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	458 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements. Ref.1
Subunit structure	Homodimer. Interacts with NRIP1, NCOA1 and NCOR2 By similarity. Binds TLE1, PNRC1 and PNRC2 By similarity. Binds GRIP1. Ref.1 Ref.5
Subcellular location	Nucleus Probable.
Tissue specificity	Highly expressed in the heart, brain and kidney and low expression in the liver. Ref.1
Post-translational modification	Sumoylation on Lys-40 is enhanced by phosphorylation at Ser-45 and represses transcriptional activity By similarity. Phosphorylation on Ser-45 enhances sumoylation on Lys-40 thus repressing transcriptional activity By similarity.
Miscellaneous	No physiological activating ligand is known for this orphan receptor, but 4-hydroxytamoxifen and diethylstilbestrol act as inverse agonists and deactivate ESRRG By similarity.
Sequence similarities	Belongs to the nuclear hormone receptor family. NR3 subfamily. Contains 1 nuclear receptor DNA-binding domain.
Sequence caution	The sequence BAC41450.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Activator Receptor
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	multicellular organismal development Non-traceable author statement Ref.1. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from direct assay Ref.1PubMed 12715898. Source: UniProtKB
Cellular_component	nucleus Non-traceable author statement PubMed 10072763. Source: UniProtKB
Molecular_function	DNA binding Non-traceable author statement Ref.1. Source: UniProtKB calmodulin binding Non-traceable author statement PubMed 12715898. Source: UniProtKB ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity Non-traceable author statement PubMed 10072763. Source: UniProtKB retinoic acid receptor activity Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro steroid binding Inferred from electronic annotation. Source: InterPro 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
CREBZF	Q9NS37	3	EBI-5274019,EBI-632965	From a different organism.
Crebzf	Q91ZR3	3	EBI-5274019,EBI-5274001

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P62509-1)

Also known as: Long;

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.

Isoform 2 (identifier: P62509-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 458

458

Estrogen-related receptor gamma

PRO_0000053666

Regions

DNA binding

125 – 200

76

Nuclear receptor

Zinc finger

128 – 148

21

NR C4-type

Zinc finger

164 – 188

25

NR C4-type

Amino acid modifications

Modified residue

45

1

Phosphoserine Probable

Cross-link

40

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Natural variations

Alternative sequence

1 – 23

23

Missing in isoform 2.

VSP_010766

Experimental info

Mutagenesis

449

1

L → A: Loss of transcriptional activation; when associated with A-450. Ref.1

Mutagenesis

450

1

F → A: Loss of transcriptional activation; when associated with A-449. Ref.1

Mutagenesis

453

1

M → A: Loss of transcriptional activation; when associated with A-454. Ref.1

Mutagenesis

454

1

L → A: Loss of transcriptional activation; when associated with A-453. Ref.1

Sequence conflict

153

1

K → N in BAC41450. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

458

Helix Strand Turn

Details...

Helix

236 – 243

8

Helix

261 – 283

23

Turn

287 – 291

5

Helix

294 – 316

23

Turn

317 – 319

3

Beta strand

320 – 322

3

Beta strand

324 – 327

4

Beta strand

330 – 332

3

Helix

334 – 338

5

Turn

339 – 341

3

Helix

343 – 359

17

Helix

363 – 375

13

Helix

385 – 406

22

Helix

413 – 418

6

Helix

421 – 440

20

Helix

448 – 455

8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) [UniParc]. Last modified July 19, 2004. Version 1. Checksum: 63D36CFD37573152	FASTA	458	51,306
	10 20 30 40 50 60 MDSVELCLPE SFSLHYEEEL LCRMSNKDRH IDSSCSSFIK TEPSSPASLT DSVNHHSPGG 70 80 90 100 110 120 SSDASGSYSS TMNGHQNGLD SPPLYPSAPI LGGSGPVRKL YDDCSSTIVE DPQTKCEYML 130 140 150 160 170 180 NSMPKRLCLV CGDIASGYHY GVASCEACKA FFKRTIQGNI EYSCPATNEC EITKRRRKSC 190 200 210 220 230 240 QACRFMKCLK VGMLKEGVRL DRVRGGRQKY KRRIDAENSP YLNPQLVQPA KKPYNKIVSH 250 260 270 280 290 300 LLVAEPEKIY AMPDPTVPDS DIKALTTLCD LADRELVVII GWAKHIPGFS TLSLADQMSL 310 320 330 340 350 360 LQSAWMEILI LGVVYRSLSF EDELVYADDY IMDEDQSKLA GLLDLNNAIL QLVKKYKSMK 370 380 390 400 410 420 LEKEEFVTLK AIALANSDSM HIEDVEAVQK LQDVLHEALQ DYEAGQHMED PRRAGKMLMT 430 440 450 LPLLRQTSTK AVQHFYNIKL EGKVPMHKLF LEMLEAKV
	Isoform 2 (Short) [UniParc]. Checksum: 63F81CDBE3A9C2D5	FASTA	435	48,581
	10 20 30 40 50 60 MSNKDRHIDS SCSSFIKTEP SSPASLTDSV NHHSPGGSSD ASGSYSSTMN GHQNGLDSPP 70 80 90 100 110 120 LYPSAPILGG SGPVRKLYDD CSSTIVEDPQ TKCEYMLNSM PKRLCLVCGD IASGYHYGVA 130 140 150 160 170 180 SCEACKAFFK RTIQGNIEYS CPATNECEIT KRRRKSCQAC RFMKCLKVGM LKEGVRLDRV 190 200 210 220 230 240 RGGRQKYKRR IDAENSPYLN PQLVQPAKKP YNKIVSHLLV AEPEKIYAMP DPTVPDSDIK 250 260 270 280 290 300 ALTTLCDLAD RELVVIIGWA KHIPGFSTLS LADQMSLLQS AWMEILILGV VYRSLSFEDE 310 320 330 340 350 360 LVYADDYIMD EDQSKLAGLL DLNNAILQLV KKYKSMKLEK EEFVTLKAIA LANSDSMHIE 370 380 390 400 410 420 DVEAVQKLQD VLHEALQDYE AGQHMEDPRR AGKMLMTLPL LRQTSTKAVQ HFYNIKLEGK 430 VPMHKLFLEM LEAKV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Hormone-independent transcriptional activation and coactivator binding by novel orphan nuclear receptor ERR3." Hong H., Yang L., Stallcup M.R. J. Biol. Chem. 274:22618-22626(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH GRIP1, MUTAGENESIS OF LEU-449; PHE-450; MET-453 AND LEU-454, FUNCTION, TISSUE SPECIFICITY.
[2]	"Prediction of the coding sequences of mouse homologues of KIAA gene: I. The complete nucleotide sequences of 100 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Hara Y., Nagase T., Ohara O., Koga H. DNA Res. 9:179-188(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: C57BL/6J. Tissue: Kidney.
[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] (ISOFORM 1). Strain: C57BL/6. Tissue: Brain.
[5]	"Structural basis for the deactivation of the estrogen-related receptor gamma by diethylstilbestrol or 4-hydroxytamoxifen and determinants of selectivity." Greschik H., Flaig R., Renaud J.-P., Moras D. J. Biol. Chem. 279:33639-33646(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 229-458 IN COMPLEXES WITH INVERSE AGONISTS, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF117254 mRNA. Translation: AAD48369.1.
AB093266 mRNA. Translation: BAC41450.1. Different initiation.
AK052731 mRNA. Translation: BAC35120.1.
BC082324 mRNA. Translation: AAH82324.1.

IPI

IPI00453754.
IPI00468998.

RefSeq

NP_001230721.1. NM_001243792.1.
NP_036065.1. NM_011935.3.

UniGene

Mm.388156.
Mm.421613.
Mm.89989.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1S9P	X-ray	2.13	A/B/C/D	232-458	[»]
1S9Q	X-ray	2.20	A/B	229-456	[»]

ProteinModelPortal

P62509.

ModBase

Search...

Protein-protein interaction databases

IntAct

P62509. 2 interactions.

PTM databases

PhosphoSite

P62509.

Proteomic databases

PRIDE

P62509.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000027906; ENSMUSP00000027906; ENSMUSG00000026610.
ENSMUST00000110938; ENSMUSP00000106563; ENSMUSG00000026610.
ENSMUST00000110939; ENSMUSP00000106564; ENSMUSG00000026610.

GeneID

26381.

KEGG

mmu:26381.

UCSC

uc007eaa.1. mouse.
uc007eab.1. mouse.

Organism-specific databases

CTD

2104.

MGI

MGI:1347056. Esrrg.

Rouge

Search...

Phylogenomic databases

eggNOG

NOG282629.

GeneTree

ENSGT00700000104391.

HOGENOM

HOG000233467.

HOVERGEN

HBG108344.

InParanoid

P62509.

KO

K08554.

OMA

RMSSKDR.

OrthoDB

EOG479F71.

Gene expression databases

ArrayExpress

P62509.

Bgee

P62509.

CleanEx

MM_ESRRG.

Genevestigator

P62509.

GermOnline

ENSMUSG00000026610. Mus musculus.

Family and domain databases

Gene3D

1.10.565.10. 1 hit.
3.30.50.10. 1 hit.

InterPro

IPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR027289. Oest-rel_rcp.
IPR024178. Oest_rcpt/oest-rel_rcp.
IPR003078. Retinoic_acid_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]

PIRSF

PIRSF002527. ER-like_NR. 1 hit.
PIRSF500939. ERR1-2-3. 1 hit.

PRINTS

PR01292. RETNOICACIDR.
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

BindingDB

P62509.

NextBio

304297.

SOURCE

Search...

Entry information

Entry name

ERR3_MOUSE

Accession

Primary (citable) accession number: P62509
Secondary accession number(s): O75454 , O96021, Q8CHC9, Q9R1F3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2004
Last sequence update:	July 19, 2004
Last modified:	May 1, 2013
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program