Steroid hormone receptor ERR1

Details

Name
Steroid hormone receptor ERR1
Synonyms
  • ERR-alpha
  • ERR1
  • ESRL1
  • Estrogen receptor-like 1
  • Estrogen-related receptor alpha
  • NR3B1
  • Nuclear receptor subfamily 3 group B member 1
Gene Name
ESRRA
Organism
Humans
Amino acid sequence
>lcl|BSEQ0007149|Steroid hormone receptor ERR1
MSSQVVGIEPLYIKAEPASPDSPKGSSETETEPPVALAPGPAPTRCLPGHKEEEDGEGAG
PGEQGGGKLVLSSLPKRLCLVCGDVASGYHYGVASCEACKAFFKRTIQGSIEYSCPASNE
CEITKRRRKACQACRFTKCLRVGMLKEGVRLDRVRGGRQKYKRRPEVDPLPFPGPFPAGP
LAVAGGPRKTAAPVNALVSHLLVVEPEKLYAMPDPAGPDGHLPAVATLCDLFDREIVVTI
SWAKSIPGFSSLSLSDQMSVLQSVWMEVLVLGVAQRSLPLQDELAFAEDLVLDEEGARAA
GLGELGAALLQLVRRLQALRLEREEYVLLKALALANSDSVHIEDAEAVEQLREALHEALL
EYEAGRAGPGGGAERRRAGRLLLTLPLLRQTAGKVLAHFYGVKLEGKVPMHKLFLEMLEA
MMD
Number of residues
423
Molecular Weight
45509.11
Theoretical pI
6.33
GO Classification
Functions
DNA binding / protein domain specific binding / RNA polymerase II core promoter proximal region sequence-specific DNA binding / RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding / sequence-specific DNA binding / steroid binding / steroid hormone receptor activity / transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding / transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding / zinc ion binding
Processes
cartilage development / gene expression / intracellular receptor signaling pathway / mitochondrion organization / organelle organization / positive regulation of transcription from RNA polymerase II promoter / regulation of cell proliferation / regulation of osteoblast differentiation / regulation of osteoclast differentiation / regulation of transcription, DNA-templated / transcription initiation from RNA polymerase II promoter
Components
intercellular bridge / microtubule cytoskeleton / nucleolus / nucleoplasm / nucleus
General Function
Zinc ion binding
Specific 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. Induces the expression of PERM1 in the skeletal muscle.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0012595|Steroid hormone receptor ERR1 (ESRRA)
ATGTCCAGCCAGGTGGTGGGCATTGAGCCTCTCTACATCAAGGCAGAGCCGGCCAGCCCT
GACAGTCCAAAGGGTTCCTCGGAGACAGAGACCGAGCCTCCTGTGGCCCTGGCCCCTGGT
CCAGCTCCCACTCGCTGCCTCCCAGGCCACAAGGAAGAGGAGGATGGGGAGGGGGCTGGG
CCTGGCGAGCAGGGCGGTGGGAAGCTGGTGCTCAGCTCCCTGCCCAAGCGCCTCTGCCTG
GTCTGTGGGGACGTGGCCTCCGGCTACCACTATGGTGTGGCATCCTGTGAGGCCTGCAAA
GCCTTCTTCAAGAGGACCATCCAGGGGAGCATCGAGTACAGCTGTCCGGCCTCCAACGAG
TGTGAGATCACCAAGCGGAGACGCAAGGCCTGCCAGGCCTGCCGCTTCACCAAGTGCCTG
CGGGTGGGCATGCTCAAGGAGGGAGTGCGCCTGGACCGCGTCCGGGGTGGGCGGCAGAAG
TACAAGCGGCGGCCGGAGGTGGACCCACTGCCCTTCCCGGGCCCCTTCCCTGCTGGGCCC
CTGGCAGTCGCTGGAGGCCCCCGGAAGACAGCAGCCCCAGTGAATGCACTGGTGTCTCAT
CTGCTGGTGGTTGAGCCTGAGAAGCTCTATGCCATGCCTGACCCCGCAGGCCCTGATGGG
CACCTCCCAGCCGTGGCTACCCTCTGTGACCTCTTTGACCGAGAGATTGTGGTCACCATC
AGCTGGGCCAAGAGCATCCCAGGCTTCTCATCGCTGTCGCTGTCTGACCAGATGTCAGTA
CTGCAGAGCGTGTGGATGGAGGTGCTGGTGCTGGGTGTGGCCCAGCGCTCACTGCCACTG
CAGGATGAGCTGGCCTTCGCTGAGGACTTAGTCCTGGATGAAGAGGGGGCACGGGCAGCT
GGCCTGGGGGAACTGGGGGCTGCCCTGCTGCAACTAGTGCGGCGGCTGCAGGCCCTGCGG
CTGGAGCGAGAGGAGTATGTTCTACTAAAGGCCTTGGCCCTTGCCAATTCAGACTCTGTG
CACATCGAAGATGCCGAGGCTGTGGAGCAGCTGCGAGAAGCTCTGCACGAGGCCCTGCTG
GAGTATGAAGCCGGCCGGGCTGGCCCCGGAGGGGGTGCTGAGCGGCGGCGGGCGGGCAGG
CTGCTGCTCACGCTACCGCTCCTCCGCCAGACAGCGGGCAAAGTGCTGGCCCATTTCTAT
GGGGTGAAGCTGGAGGGCAAGGTGCCCATGCACAAGCTGTTCTTGGAGATGCTCGAGGCC
ATGATGGACTGA
Chromosome Location
11
Locus
11q13
External Identifiers
ResourceLink
UniProtKB IDP11474
UniProtKB Entry NameERR1_HUMAN
GenBank Protein ID36609
GenBank Gene IDX51416
HGNC IDHGNC:3471
General References
  1. Giguere V, Yang N, Segui P, Evans RM: Identification of a new class of steroid hormone receptors. Nature. 1988 Jan 7;331(6151):91-4. [PubMed:3267207]
  2. Yang N, Shigeta H, Shi H, Teng CT: Estrogen-related receptor, hERR1, modulates estrogen receptor-mediated response of human lactoferrin gene promoter. J Biol Chem. 1996 Mar 8;271(10):5795-804. [PubMed:8621448]
  3. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [PubMed:16554811]
  4. Wiley SR, Kraus RJ, Zuo F, Murray EE, Loritz K, Mertz JE: SV40 early-to-late switch involves titration of cellular transcriptional repressors. Genes Dev. 1993 Nov;7(11):2206-19. [PubMed:8224847]
  5. Sladek R, Bader JA, Giguere V: The orphan nuclear receptor estrogen-related receptor alpha is a transcriptional regulator of the human medium-chain acyl coenzyme A dehydrogenase gene. Mol Cell Biol. 1997 Sep;17(9):5400-9. [PubMed:9271417]
  6. Schreiber SN, Knutti D, Brogli K, Uhlmann T, Kralli A: The transcriptional coactivator PGC-1 regulates the expression and activity of the orphan nuclear receptor estrogen-related receptor alpha (ERRalpha). J Biol Chem. 2003 Mar 14;278(11):9013-8. Epub 2003 Jan 8. [PubMed:12522104]
  7. Barry JB, Laganiere J, Giguere V: A single nucleotide in an estrogen-related receptor alpha site can dictate mode of binding and peroxisome proliferator-activated receptor gamma coactivator 1alpha activation of target promoters. Mol Endocrinol. 2006 Feb;20(2):302-10. Epub 2005 Sep 8. [PubMed:16150865]
  8. Vu EH, Kraus RJ, Mertz JE: Phosphorylation-dependent sumoylation of estrogen-related receptor alpha1. Biochemistry. 2007 Aug 28;46(34):9795-804. Epub 2007 Aug 4. [PubMed:17676930]
  9. Tremblay AM, Wilson BJ, Yang XJ, Giguere V: Phosphorylation-dependent sumoylation regulates estrogen-related receptor-alpha and -gamma transcriptional activity through a synergy control motif. Mol Endocrinol. 2008 Mar;22(3):570-84. Epub 2007 Dec 6. [PubMed:18063693]
  10. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648]
  11. Wilson BJ, Tremblay AM, Deblois G, Sylvain-Drolet G, Giguere V: An acetylation switch modulates the transcriptional activity of estrogen-related receptor alpha. Mol Endocrinol. 2010 Jul;24(7):1349-58. doi: 10.1210/me.2009-0441. Epub 2010 May 19. [PubMed:20484414]
  12. Cho Y, Hazen BC, Russell AP, Kralli A: Peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1)- and estrogen-related receptor (ERR)-induced regulator in muscle 1 (Perm1) is a tissue-specific regulator of oxidative capacity in skeletal muscle cells. J Biol Chem. 2013 Aug 30;288(35):25207-18. doi: 10.1074/jbc.M113.489674. Epub 2013 Jul 8. [PubMed:23836911]
  13. Kallen J, Schlaeppi JM, Bitsch F, Filipuzzi I, Schilb A, Riou V, Graham A, Strauss A, Geiser M, Fournier B: Evidence for ligand-independent transcriptional activation of the human estrogen-related receptor alpha (ERRalpha): crystal structure of ERRalpha ligand binding domain in complex with peroxisome proliferator-activated receptor coactivator-1alpha. J Biol Chem. 2004 Nov 19;279(47):49330-7. Epub 2004 Aug 26. [PubMed:15337744]
  14. Greschik H, Althage M, Flaig R, Sato Y, Chavant V, Peluso-Iltis C, Choulier L, Cronet P, Rochel N, Schule R, Stromstedt PE, Moras D: Communication between the ERRalpha homodimer interface and the PGC-1alpha binding surface via the helix 8-9 loop. J Biol Chem. 2008 Jul 18;283(29):20220-30. doi: 10.1074/jbc.M801920200. Epub 2008 Apr 25. [PubMed:18441008]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00197Troglitazoneapproved, investigational, withdrawnnoinverse agonistDetails
DB068331-CYCLOHEXYL-N-{[1-(4-METHYLPHENYL)-1H-INDOL-3-YL]METHYL}METHANAMINEexperimentalunknownDetails
DB06732beta-NaphthoflavoneexperimentalunknownDetails
DB00255Diethylstilbestrolapproved, investigationalunknownDetails
DB07776Flavoneapproved, experimentalunknownagonistDetails
DB01645GenisteininvestigationalunknownagonistDetails
DB04468AfimoxifeneinvestigationalunknowninhibitorDetails