COT1_HUMAN
ID COT1_HUMAN Reviewed; 423 AA.
AC P10589;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=COUP transcription factor 1;
DE Short=COUP-TF1;
DE AltName: Full=COUP transcription factor I;
DE Short=COUP-TF I;
DE AltName: Full=Nuclear receptor subfamily 2 group F member 1;
DE AltName: Full=V-erbA-related protein 3;
DE Short=EAR-3;
GN Name=NR2F1; Synonyms=EAR3, ERBAL3, TFCOUP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-423, AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2739739; DOI=10.1038/340163a0;
RA Wang L.-H., Tsai S.Y., Cook R.G., Beattie W.G., Tsai M.-J., O'Malley B.W.;
RT "COUP transcription factor is a member of the steroid receptor
RT superfamily.";
RL Nature 340:163-166(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Lung;
RX PubMed=2905047; DOI=10.1093/nar/16.23.11057;
RA Miyajima N., Kadowaki Y., Fukushige S., Shimizu S., Semba K., Yamanashi Y.,
RA Matsubara K., Toyoshima K., Yamamoto T.;
RT "Identification of two novel members of erbA superfamily by molecular
RT cloning: the gene products of the two are highly related to each other.";
RL Nucleic Acids Res. 16:11057-11074(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH GTF2B.
RX PubMed=1517211; DOI=10.1016/s0021-9258(19)37087-5;
RA Ing N.H., Beekman J.M., Tsai S.Y., Tsai M.J., O'Malley B.W.;
RT "Members of the steroid hormone receptor superfamily interact with TFIIB
RT (S300-II).";
RL J. Biol. Chem. 267:17617-17623(1992).
RN [5]
RP INTERACTION WITH COPS2.
RX PubMed=10207062; DOI=10.1128/mcb.19.5.3383;
RA Dressel U., Thormeyer D., Altincicek B., Paululat A., Eggert M.,
RA Schneider S., Tenbaum S.P., Renkawitz R., Baniahmad A.;
RT "Alien, a highly conserved protein with characteristics of a corepressor
RT for members of the nuclear hormone receptor superfamily.";
RL Mol. Cell. Biol. 19:3383-3394(1999).
RN [6]
RP FUNCTION.
RX PubMed=10644740; DOI=10.1074/jbc.275.4.2763;
RA Zhang Y., Dufau M.L.;
RT "Nuclear orphan receptors regulate transcription of the gene for the human
RT luteinizing hormone receptor.";
RL J. Biol. Chem. 275:2763-2770(2000).
RN [7]
RP FUNCTION, SUBUNIT, AND INDUCTION BY GONADOTROPIN.
RX PubMed=11682620; DOI=10.1210/mend.15.11.0720;
RA Zhang Y., Dufau M.L.;
RT "EAR2 and EAR3/COUP-TFI regulate transcription of the rat LH receptor.";
RL Mol. Endocrinol. 15:1891-1905(2001).
RN [8]
RP STRUCTURE BY NMR OF 84-162.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the zinc finger, C4-type domain of human COUP
RT transcription factor 1.";
RL Submitted (FEB-2008) to the PDB data bank.
RN [9]
RP INVOLVEMENT IN BBSOAS, VARIANTS BBSOAS LYS-112; ARG-113; PRO-115 AND
RP PRO-252, AND CHARACTERIZATION OF VARIANTS BBSOAS LYS-112; ARG-113; PRO-115
RP AND PRO-252.
RX PubMed=24462372; DOI=10.1016/j.ajhg.2014.01.002;
RA Bosch D.G., Boonstra F.N., Gonzaga-Jauregui C., Xu M., de Ligt J.,
RA Jhangiani S., Wiszniewski W., Muzny D.M., Yntema H.G., Pfundt R.,
RA Vissers L.E., Spruijt L., Blokland E.A., Chen C.A., Lewis R.A., Tsai S.Y.,
RA Gibbs R.A., Tsai M.J., Lupski J.R., Zoghbi H.Y., Cremers F.P.,
RA de Vries B.B., Schaaf C.P.;
RT "NR2F1 mutations cause optic atrophy with intellectual disability.";
RL Am. J. Hum. Genet. 94:303-309(2014).
RN [10]
RP VARIANT PHE-110 DEL.
RX PubMed=26138355; DOI=10.1111/cge.12636;
RA Dimassi S., Labalme A., Ville D., Calender A., Mignot C., Boutry-Kryza N.,
RA de Bellescize J., Rivier-Ringenbach C., Bourel-Ponchel E., Cheillan D.,
RA Simonet T., Maincent K., Rossi M., Till M., Mougou-Zerelli S., Edery P.,
RA Saad A., Heron D., des Portes V., Sanlaville D., Lesca G.;
RT "Whole-exome sequencing improves the diagnosis yield in sporadic infantile
RT spasm syndrome.";
RL Clin. Genet. 89:198-204(2016).
CC -!- FUNCTION: Coup (chicken ovalbumin upstream promoter) transcription
CC factor binds to the ovalbumin promoter and, in conjunction with another
CC protein (S300-II) stimulates initiation of transcription. Binds to both
CC direct repeats and palindromes of the 5'-AGGTCA-3' motif. Represses
CC transcriptional activity of LHCG. {ECO:0000269|PubMed:10644740,
CC ECO:0000269|PubMed:11682620}.
CC -!- SUBUNIT: Binds DNA as dimer; homodimer and probable heterodimer with
CC NR2F6 (PubMed:11682620). Interacts with GTF2B; this interaction is
CC direct (PubMed:1517211). Interacts with COPS2 (PubMed:10207062).
CC {ECO:0000269|PubMed:10207062, ECO:0000269|PubMed:11682620,
CC ECO:0000269|PubMed:1517211}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- INDUCTION: Inhibited by gonadotropin in granulosa cells.
CC {ECO:0000269|PubMed:11682620}.
CC -!- DISEASE: Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS)
CC [MIM:615722]: An autosomal dominant disorder characterized by optic
CC atrophy associated with developmental delay and intellectual
CC disability. Most patients also have evidence of cerebral visual
CC impairment. {ECO:0000269|PubMed:24462372}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR2
CC subfamily. {ECO:0000305}.
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DR EMBL; X16155; CAA34277.1; -; mRNA.
DR EMBL; X12795; CAA31283.1; -; Genomic_DNA.
DR EMBL; BC004154; AAH04154.1; -; mRNA.
DR EMBL; BC017493; AAH17493.1; -; mRNA.
DR CCDS; CCDS4068.1; -.
DR PIR; S02710; S02710.
DR RefSeq; NP_005645.1; NM_005654.5.
DR PDB; 2EBL; NMR; -; A=84-159.
DR PDBsum; 2EBL; -.
DR AlphaFoldDB; P10589; -.
DR SMR; P10589; -.
DR BioGRID; 112883; 65.
DR DIP; DIP-622N; -.
DR IntAct; P10589; 12.
DR MINT; P10589; -.
DR STRING; 9606.ENSP00000325819; -.
DR BindingDB; P10589; -.
DR ChEMBL; CHEMBL1961789; -.
DR DrugBank; DB06732; beta-Naphthoflavone.
DR iPTMnet; P10589; -.
DR PhosphoSitePlus; P10589; -.
DR BioMuta; NR2F1; -.
DR DMDM; 116959; -.
DR EPD; P10589; -.
DR jPOST; P10589; -.
DR MassIVE; P10589; -.
DR MaxQB; P10589; -.
DR PaxDb; P10589; -.
DR PeptideAtlas; P10589; -.
DR PRIDE; P10589; -.
DR ProteomicsDB; 52615; -.
DR Antibodypedia; 24914; 271 antibodies from 33 providers.
DR DNASU; 7025; -.
DR Ensembl; ENST00000327111.8; ENSP00000325819.3; ENSG00000175745.14.
DR GeneID; 7025; -.
DR KEGG; hsa:7025; -.
DR MANE-Select; ENST00000327111.8; ENSP00000325819.3; NM_005654.6; NP_005645.1.
DR UCSC; uc003kkj.4; human.
DR CTD; 7025; -.
DR DisGeNET; 7025; -.
DR GeneCards; NR2F1; -.
DR HGNC; HGNC:7975; NR2F1.
DR HPA; ENSG00000175745; Low tissue specificity.
DR MalaCards; NR2F1; -.
DR MIM; 132890; gene.
DR MIM; 615722; phenotype.
DR neXtProt; NX_P10589; -.
DR OpenTargets; ENSG00000175745; -.
DR Orphanet; 401777; Optic atrophy-intellectual disability syndrome.
DR PharmGKB; PA31758; -.
DR VEuPathDB; HostDB:ENSG00000175745; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000157876; -.
DR InParanoid; P10589; -.
DR OMA; THLIHAE; -.
DR OrthoDB; 666130at2759; -.
DR PhylomeDB; P10589; -.
DR TreeFam; TF352097; -.
DR PathwayCommons; P10589; -.
DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway.
DR SignaLink; P10589; -.
DR SIGNOR; P10589; -.
DR BioGRID-ORCS; 7025; 15 hits in 1094 CRISPR screens.
DR ChiTaRS; NR2F1; human.
DR EvolutionaryTrace; P10589; -.
DR GeneWiki; COUP-TFI; -.
DR GenomeRNAi; 7025; -.
DR Pharos; P10589; Tbio.
DR PRO; PR:P10589; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P10589; protein.
DR Bgee; ENSG00000175745; Expressed in ventricular zone and 181 other tissues.
DR ExpressionAtlas; P10589; baseline and differential.
DR Genevisible; P10589; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0044323; F:retinoic acid-responsive element binding; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0048856; P:anatomical structure development; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
DR InterPro; IPR035500; NHR-like_dom_sf.
DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd.
DR InterPro; IPR001723; Nuclear_hrmn_rcpt.
DR InterPro; IPR001628; Znf_hrmn_rcpt.
DR InterPro; IPR013088; Znf_NHR/GATA.
DR Pfam; PF00104; Hormone_recep; 1.
DR Pfam; PF00105; zf-C4; 1.
DR PRINTS; PR00398; STRDHORMONER.
DR PRINTS; PR00047; STROIDFINGER.
DR SMART; SM00430; HOLI; 1.
DR SMART; SM00399; ZnF_C4; 1.
DR SUPFAM; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Direct protein sequencing; Disease variant;
KW DNA-binding; Metal-binding; Nucleus; Receptor; Reference proteome;
KW Repressor; Transcription; Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..423
FT /note="COUP transcription factor 1"
FT /id="PRO_0000053602"
FT DOMAIN 184..410
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 83..158
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 86..106
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 122..146
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 39..53
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 110
FT /note="Missing (probable disease-associated variant found
FT in a patient with early infantile epileptic
FT encephalopathy)"
FT /evidence="ECO:0000269|PubMed:26138355"
FT /id="VAR_078708"
FT VARIANT 112
FT /note="R -> K (in BBSOAS; decreases transcriptional
FT activity; dbSNP:rs587777277)"
FT /evidence="ECO:0000269|PubMed:24462372"
FT /id="VAR_071319"
FT VARIANT 113
FT /note="S -> R (in BBSOAS; decreases transcriptional
FT activity; dbSNP:rs587777275)"
FT /evidence="ECO:0000269|PubMed:24462372"
FT /id="VAR_071320"
FT VARIANT 115
FT /note="R -> P (in BBSOAS; decreases transcriptional
FT activity; dbSNP:rs587777274)"
FT /evidence="ECO:0000269|PubMed:24462372"
FT /id="VAR_071321"
FT VARIANT 252
FT /note="L -> P (in BBSOAS; decreases transcriptional
FT activity; dbSNP:rs587777276)"
FT /evidence="ECO:0000269|PubMed:24462372"
FT /id="VAR_071322"
FT TURN 87..89
FT /evidence="ECO:0007829|PDB:2EBL"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:2EBL"
FT HELIX 104..114
FT /evidence="ECO:0007829|PDB:2EBL"
FT TURN 115..117
FT /evidence="ECO:0007829|PDB:2EBL"
FT STRAND 132..136
FT /evidence="ECO:0007829|PDB:2EBL"
FT HELIX 140..149
FT /evidence="ECO:0007829|PDB:2EBL"
FT HELIX 153..156
FT /evidence="ECO:0007829|PDB:2EBL"
SQ SEQUENCE 423 AA; 46156 MW; 6EE634BE96242731 CRC64;
MAMVVSSWRD PQDDVAGGNP GGPNPAAQAA RGGGGGAGEQ QQQAGSGAPH TPQTPGQPGA
PATPGTAGDK GQGPPGSGQS QQHIECVVCG DKSSGKHYGQ FTCEGCKSFF KRSVRRNLTY
TCRANRNCPI DQHHRNQCQY CRLKKCLKVG MRREAVQRGR MPPTQPNPGQ YALTNGDPLN
GHCYLSGYIS LLLRAEPYPT SRYGSQCMQP NNIMGIENIC ELAARLLFSA VEWARNIPFF
PDLQITDQVS LLRLTWSELF VLNAAQCSMP LHVAPLLAAA GLHASPMSAD RVVAFMDHIR
IFQEQVEKLK ALHVDSAEYS CLKAIVLFTS DACGLSDAAH IESLQEKSQC ALEEYVRSQY
PNQPSRFGKL LLRLPSLRTV SSSVIEQLFF VRLVGKTPIE TLIRDMLLSG SSFNWPYMSI
QCS