NR2C1_PONAB
ID NR2C1_PONAB Reviewed; 601 AA.
AC Q5RCZ5;
DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 25-MAY-2022, entry version 89.
DE RecName: Full=Nuclear receptor subfamily 2 group C member 1;
GN Name=NR2C1;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
RG The German cDNA consortium;
RL Submitted (NOV-2004) 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. Also activator of OCT4 gene expression. Plays a fundamental
CC role in early embryogenesis and regulates embryonic stem cell
CC proliferation and differentiation. Mediator of retinoic acid-regulated
CC 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-582 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}.
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DR EMBL; CR858123; CAH90362.1; -; mRNA.
DR RefSeq; NP_001127276.1; NM_001133804.2.
DR AlphaFoldDB; Q5RCZ5; -.
DR STRING; 9601.ENSPPYP00000005520; -.
DR GeneID; 100174333; -.
DR KEGG; pon:100174333; -.
DR CTD; 7181; -.
DR eggNOG; KOG3575; Eukaryota.
DR InParanoid; Q5RCZ5; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
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..601
FT /note="Nuclear receptor subfamily 2 group C member 1"
FT /id="PRO_0000369404"
FT DOMAIN 349..591
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 585..601
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 582
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 589
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P13056"
SQ SEQUENCE 601 AA; 67004 MW; 46BE3FE0E856346C CRC64;
MATIEEIAHQ IIEQQMGEIV TEQQTGQKIQ IVTALDHNTQ GKQFILTNHD GSTPSKVILA
RQDSTPGKVF LTTPDAAGVN QLFFTTPDLS AQHLQLLTDN SSPDQGPNKV FDLCVVCGDK
ASGRHYGAVT CEGCKGFFKR SIRKNLVYSC RGSKDCIINK HHRNRCQYCR LQRCIAFGMK
QDSVQCERKP IEVSREKSSN CAASTEKIYI RKDLRSPLTA TPTFVTDSES TRSTGLLDSG
MFVNIHPSGV KTESTVLMTS DKAESCQGDL STLASVVTSL ANLGKTKDLS QNSNEMSMIE
SLSNDDTSLC EFQEMHTNGD VSRAFDTLAK ALNPGESTAC QSSVAGMEGS VHLITGDSSI
NYTEKEGPLL SDSHVAFRLT MPSPMPEYLN VHYIGESASR LLFLSMHWAL SIPSFQALGQ
ENSISLVKAY WNELFTLGLA QCWQVMNVAT ILATFVNCLH NSLQQDKMST ERRKLLMEHI
FKLQEFCNSM VKLCIDGYEY AYLKAIVLFS PDHPGLENME QIEKFQEKAY VEFQDYITKT
YPDDTYRLSR LLLRLPALRL MNATITEELF FKGLIGNIRI DSVIPHILKM EPGQYSKTSS
L
