O08580 (ERR1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Steroid hormone receptor ERR1

Alternative name(s):
Estrogen receptor-like 1
Estrogen-related receptor alpha
Short name=ERR-alpha
Nuclear receptor subfamily 3 group B member 1

Gene names

Name:	Esrra
Synonyms:	Err1, Estrra, Nr3b1

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

General annotation (Comments)

Function	Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and may act as an important regulator of MCAD promoter. Binds to the C1 region of the lactoferrin gene promoter. Requires dimerization and the coactivator, PGC-1A, for full activity. The ERRalpha/PGC1alpha complex is a regulator of energy metabolism By similarity.
Subunit structure	Binds DNA as a monomer or a homodimer. Interacts (via the AF2 domain) with coactivator PPARGC1A (via the L3 motif); the interaction greatly enhances transriptional activity of genes involved in energy metabolism. Interacts with PIAS4; the interaction enhances sumoylation By similarity.
Subcellular location	Nucleus By similarity.
Tissue specificity	Most highly expressed in kidney, heart, and brown adipocytes. Also found in utERus, cervix and vagina.
Developmental stage	Expressed in an organ specific mannER through mid-to late embryonic development with persistent high-level expression in brown adipose tissue and intestinal mucosa.
Induction	Activated by diethylstilbestrol (DES) and estradiol in the uterus.
Post-translational modification	Phosphorylation on Ser-19 enhances sumoylation on Lys-14 increasing repression of transcriptional activity By similarity. Ref.7 Sumoylated with SUMO2. Main site is Lys-14 which is enhanced by phosphorylation on Ser-19, cofactor activation, and by interaction with PIAS4. Sumoylation enhances repression of transcriptional activiy, but has no effect on subcellular location nor on DNA binding By similarity. Ref.7
Disruption phenotype	No visible phenotype; mice are viable, fertile and display no gross anatomical alterations, with the exception of reduced body weight and peripheral fat deposits. Mice are resistant to a high-fat diet-induced obesity. Ref.5
Sequence similarities	Belongs to the nuclear hormone receptor family. NR3 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
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cartilage development Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 21106753. Source: BHF-UCL regulation of cell proliferation Inferred from electronic annotation. Source: Compara regulation of osteoblast differentiation Inferred from electronic annotation. Source: Compara regulation of osteoclast differentiation Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from direct assay PubMed 18234909. Source: MGI
Molecular_function	DNA binding Inferred from direct assay PubMed 18234909. Source: MGI sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 18234909. Source: MGI 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...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 422	422	Steroid hormone receptor ERR1		PRO_0000053661
Regions
	DNA binding	76 – 151	76	Nuclear receptor
	Zinc finger	79 – 99	21	NR C4-type
	Zinc finger	115 – 134	20	NR C4-type
	Region	1 – 76	76	Repressor domain
	Region	205 – 401	197	Ligand binding domain By similarity
	Region	402 – 422	21	AF-2 domain By similarity
Sites
	Site	124	1	Required for DNA-dependent dimerization By similarity
Amino acid modifications
	Modified residue	19	1	Phosphoserine Ref.6 Ref.7
	Modified residue	22	1	Phosphoserine By similarity
	Cross-link	14		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
	Cross-link	402		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Experimental info
	Sequence conflict	275	1	R → G in AAB51250. Ref.1
	Sequence conflict	308	1	Missing in AAB51250. Ref.1
	Sequence conflict	408 – 412	5	PMHKL → HAQV in AAB51250. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O08580 [UniParc]. Last modified July 27, 2011. Version 4. Checksum: 2F54EEA1BD3B511D	FASTA	422	45,464
	10 20 30 40 50 60 MSSQVVGIEP LYIKAEPASP DSPKGSSETE TEPPVTLASG PAPARCLPGH KEEEDGEGAG 70 80 90 100 110 120 SGEQGSGKLV LSSLPKRLCL VCGDVASGYH YGVASCEACK AFFKRTIQGS IEYSCPASNE 130 140 150 160 170 180 CEITKRRRKA CQACRFTKCL RVGMLKEGVR LDRVRGGRQK YKRRPEVDPL PFPGPFPAGP 190 200 210 220 230 240 LAVAGGPRKT APVNALVSHL LVVEPEKLYA MPDPASPDGH LPAVATLCDL FDREIVVTIS 250 260 270 280 290 300 WAKSIPGFSS LSLSDQMSVL QSVWMEVLVL GVAQRSLPLQ DELAFAEDLV LDEEGARAAG 310 320 330 340 350 360 LGDLGAALLQ LVRRLQALRL EREEYVLLKA LALANSDSVH IEDAEAVEQL REALHEALLE 370 380 390 400 410 420 YEAGRAGPGG GAERRRAGRL LLTLPLLRQT AGKVLAHFYG VKLEGKVPMH KLFLEMLEAM MD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The orphan nuclear receptor estrogen-related receptor alpha is a transcriptional regulator of the human medium-chain acyl coenzyme A dehydrogenase gene." Sladek R., Bader J.-A., Giguere V. Mol. Cell. Biol. 17:5400-5409(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c.
[2]	"The mouse estrogen receptor-related orphan receptor alpha 1: molecular cloning and estrogen responsiveness." Shigeta H., Zuo W., Yang N., DiAugustine R., Teng C.T. J. Mol. Endocrinol. 19:299-309(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain and Kidney.
[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]. Strain: NOD. Tissue: Spleen.
[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: Brain.
[5]	"Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor alpha." Luo J., Sladek R., Carrier J., Bader J.A., Richard D., Giguere V. Mol. Cell. Biol. 23:7947-7956(2003) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[6]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, MASS SPECTROMETRY. Tissue: Liver.
[7]	"Phosphorylation-dependent sumoylation regulates estrogen-related receptor-alpha and -gamma transcriptional activity through a synergy control motif." Tremblay A.M., Wilson B.J., Yang X.-J., Giguere V. Mol. Endocrinol. 22:570-584(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION, PHOSPHORYLATION AT SER-19.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U85259 mRNA. Translation: AAB51250.1. AK156371 mRNA. Translation: BAE33690.1. BC138586 mRNA. Translation: AAI38587.1. BC171958 mRNA. Translation: AAI71958.1.
IPI	IPI00762735.
RefSeq	NP_031979.2. NM_007953.2.
UniGene	Mm.386776.
3D structure databases
ProteinModelPortal	O08580.
SMR	O08580. Positions 73-421.
ModBase	Search...
Protein-protein interaction databases
IntAct	O08580. 2 interactions.
PTM databases
PhosphoSite	O08580.
Proteomic databases
PaxDb	O08580.
PRIDE	O08580.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000025906; ENSMUSP00000025906; ENSMUSG00000024955.
GeneID	26379.
KEGG	mmu:26379.
Organism-specific databases
CTD	2101.
MGI	MGI:1346831. Esrra.
Phylogenomic databases
eggNOG	NOG282629.
GeneTree	ENSGT00700000104391.
HOGENOM	HOG000233467.
HOVERGEN	HBG108344.
InParanoid	B2RRU9.
KO	K08552.
OMA	PLPFPGS.
OrthoDB	EOG48KRBN.
Gene expression databases
ArrayExpress	O08580.
Bgee	O08580.
CleanEx	MM_ESRRA.
Genevestigator	O08580.
GermOnline	ENSMUSG00000024955. 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. 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	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	CHEMBL1914280.
NextBio	304289.
SOURCE	Search...

Entry information

Entry name

ERR1_MOUSE

Accession

Primary (citable) accession number: O08580
Secondary accession number(s): B2RRU9, Q3U110

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	July 27, 2011
Last modified:	April 3, 2013
This is version 117 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program