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   24-JAN-2024, entry version 225.
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; 66.
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; 9606-ENSP00000325819; -.
DR   PeptideAtlas; P10589; -.
DR   ProteomicsDB; 52615; -.
DR   Pumba; P10589; -.
DR   Antibodypedia; 24914; 300 antibodies from 33 providers.
DR   DNASU; 7025; -.
DR   Ensembl; ENST00000327111.8; ENSP00000325819.3; ENSG00000175745.15.
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   AGR; HGNC:7975; -.
DR   CTD; 7025; -.
DR   DisGeNET; 7025; -.
DR   GeneCards; NR2F1; -.
DR   GeneReviews; 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; 5400963at2759; -.
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; 22 hits in 1175 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 183 other cell types or tissues.
DR   ExpressionAtlas; P10589; baseline and differential.
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:0007165; P:signal transduction; TAS:ProtInc.
DR   CDD; cd06958; NR_DBD_COUP_TF; 1.
DR   CDD; cd06948; NR_LBD_COUP-TF; 1.
DR   Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1.
DR   Gene3D; 1.10.565.10; Retinoid X Receptor; 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   PANTHER; PTHR24083:SF168; COUP TRANSCRIPTION FACTOR 1; 1.
DR   PANTHER; PTHR24083; NUCLEAR HORMONE RECEPTOR; 1.
DR   Pfam; PF00104; Hormone_recep; 1.
DR   Pfam; PF00105; zf-C4; 1.
DR   PRINTS; PR01282; COUPTNFACTOR.
DR   PRINTS; PR00398; STRDHORMONER.
DR   PRINTS; PR00047; STROIDFINGER.
DR   SMART; SM00430; HOLI; 1.
DR   SMART; SM00399; ZnF_C4; 1.
DR   SUPFAM; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1.
DR   SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1.
DR   PROSITE; PS51843; NR_LBD; 1.
DR   PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR   PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
DR   Genevisible; P10589; HS.
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 (found in a patient with early infantile
FT                   epileptic encephalopathy; likely pathogenic)"
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
//