NR2C1_BOVIN
ID NR2C1_BOVIN Reviewed; 608 AA.
AC A0JNE3;
DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT 12-DEC-2006, sequence version 1.
DT 25-MAY-2022, entry version 93.
DE RecName: Full=Nuclear receptor subfamily 2 group C member 1;
GN Name=NR2C1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Orphan nuclear receptor. Binds the IR7 element in the
CC promoter of its own gene in an autoregulatory negative feedback
CC mechanism. Primarily repressor of a broad range of genes including ESR1
CC and RARB. Together with NR2C2, forms the core of the DRED (direct
CC repeat erythroid-definitive) complex that represses embryonic and fetal
CC globin transcription. Binds to hormone response elements (HREs)
CC consisting of two 5'-AGGTCA-3' half site direct repeat consensus
CC sequences (By similarity). Also activator of OCT4 gene expression.
CC Plays a fundamental role in early embryogenesis and regulates embryonic
CC stem cell proliferation and differentiation. Mediator of retinoic acid-
CC regulated preadipocyte proliferation (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer (By similarity). Heterodimer; with NR2C2 which is
CC required for chromatin remodeling and for binding to promoter regions
CC such as globin DR1 repeats (By similarity). Interacts with ESR1; the
CC interaction prevents homodimerization of ESR1 and suppresses its
CC transcriptional activity and cell growth. Interacts with NRIP1 (via its
CC LXXLL motifs); the interaction provides corepressor activity. Interacts
CC with HDAC3 (via the DNA-binding domain); the interaction recruits
CC phosphorylated NR2C1 to PML bodies for sumoylation. Interacts with
CC HDAC4 (via the DNA-binding domain). Interacts with PIAS1; the
CC interaction is required for sumoylation of NR2C1. Interacts with UBE2I;
CC the interaction is required for sumoylation of NR2C1. Interacts with
CC KAT2B; the interaction acts as a corepressor of gene expression (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00407}.
CC Nucleus, PML body {ECO:0000250}. Note=Recruited by HDAC3, after all-
CC trans retinoic acid stimulated MAPK1-mediated Thr-223 phosphorylation,
CC to PML bodies for subsequent sumoylation. {ECO:0000250}.
CC -!- PTM: Sumoylation requires both PIAS1 and UBE2I. Sumoylation appears to
CC dissociate NR2C1 from the PML nuclear bodies. Enhances the interaction
CC with NRIP1 but inhibits interaction with KAT2B. In proliferating cells,
CC stimulation by all-trans retinoic acid, activation of MAPK1-mediated
CC phosphorylation and recruitment to PML bodies with subsequent
CC sumoylation, suppresses OCT4 expression (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated on several serine and threonine residues.
CC Phosphorylation on Thr-223, stimulated by all-trans retinoic acid
CC (atRA) mediates PML location and sumoylation in proliferating cells
CC which then modulates its association with effector molecules, KAT2B and
CC NRIP1. Phosphorylation on Ser-586 by PKC is important for protein
CC stability and function as activator of RARB (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR2
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC126643; AAI26644.1; -; mRNA.
DR RefSeq; NP_001071372.1; NM_001077904.1.
DR AlphaFoldDB; A0JNE3; -.
DR STRING; 9913.ENSBTAP00000023577; -.
DR PaxDb; A0JNE3; -.
DR PRIDE; A0JNE3; -.
DR GeneID; 511407; -.
DR KEGG; bta:511407; -.
DR CTD; 7181; -.
DR eggNOG; KOG3575; Eukaryota.
DR InParanoid; A0JNE3; -.
DR OrthoDB; 278171at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0004879; F:nuclear receptor activity; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
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:0000122; P:negative 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 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 2: Evidence at transcript level;
KW Activator; DNA-binding; Isopeptide bond; Metal-binding; Nucleus;
KW Phosphoprotein; Receptor; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..608
FT /note="Nuclear receptor subfamily 2 group C member 1"
FT /id="PRO_0000369402"
FT DOMAIN 353..595
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 111..186
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 114..134
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 150..169
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..179
FT /note="Required for interaction with KAT2B"
FT /evidence="ECO:0000250"
FT REGION 589..608
FT /note="Required for interaction with NRIP1"
FT /evidence="ECO:0000250"
FT MOD_RES 198
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q505F1"
FT MOD_RES 216
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13056"
FT MOD_RES 221
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P13056"
FT MOD_RES 223
FT /note="Phosphothreonine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:Q505F1"
FT MOD_RES 586
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:Q505F1"
FT CROSSLNK 251
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 251
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P13056"
FT CROSSLNK 593
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P13056"
SQ SEQUENCE 608 AA; 67714 MW; 49C110AEB8B74BE2 CRC64;
MASIEEIAHQ IIEQQMGEIV TEQPTGQKIQ IVTALDHNTQ GKQFILTNHD GSTPNKVILA
RQDSTPGKVF FTTPDAAGVN QLFFTTPDLS TQQLQFLTDN SSSEQGPNKV FDLCVVCGDK
ASGRHYGEVT CEGCKGFFKR SIRKNLVYSC RGSKDCIINK HHRNRCQYCR LQRCIAFGMK
QDSVQCERKP IEVSREKSSN CAASTEKIYI RKDLRSPLAA TPTFVTDSET ARSAGLLDSG
MFVNIHQSGI KTESTMLMTP DKAVSCQGDL STLASVVTSL ANLGKTKDPA PNSNEVSMIE
SLSNGDTSYT SVCEFHQEMQ TNGDVSRAFD TLAKALNPGE STACQSSGEG MEGNVHLIAG
DSSINYIEKE GPLLSDSHVA FRLTMPSPMP EYLNVHYIGE SASRLLFLSM HWALSIPSFQ
ALGQENSISL VKAYWNELFT LGLAQCWQVM NVATILATFV NCLHSSLQQD KISAERRKLL
MEHIFKLQEF CNSMVKLCID GYEYAYLKAI VLFSPDHPGL ENMEQIEKFQ EKAYVEFQDY
ITKTYPDDTY RLSRLLLRLP ALRLMNATIT EELFFKGLIG NVRIDSVIPH ILKMEPADYN
SQIIGHSI
