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Protein

Nuclear receptor subfamily 2 group C member 1

Gene

NR2C1

Organism
Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at transcript leveli

Functioni

Orphan nuclear receptor. Binds the IR7 element in the promoter of its own gene in an autoregulatory negative feedback mechanism. Primarily repressor of a broad range of genes including ESR1 and RARB. Together with NR2C2, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Also activator of OCT4 gene expression. Plays a fundamental role in early embryogenesis and regulates embryonic stem cell proliferation and differentiation. Mediator of retinoic acid-regulated preadipocyte proliferation (By similarity).By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi111 – 186Nuclear receptorPROSITE-ProRule annotationAdd BLAST76
Zinc fingeri114 – 134NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri150 – 169NR C4-typePROSITE-ProRule annotationAdd BLAST20

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Receptor, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear receptor subfamily 2 group C member 1
Gene namesi
Name:NR2C1
OrganismiPongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii)
Taxonomic identifieri9601 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePongo
Proteomesi
  • UP000001595 Componenti: Unplaced

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation
  • NucleusPML body By similarity

  • Note: Recruited by HDAC3, after all-trans retinoic acid stimulated MAPK1-mediated Thr-223 phosphorylation, to PML bodies for subsequent sumoylation.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003694041 – 601Nuclear receptor subfamily 2 group C member 1Add BLAST601

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei198PhosphoserineBy similarity1
Modified residuei216PhosphoserineBy similarity1
Modified residuei221PhosphothreonineBy similarity1
Modified residuei223Phosphothreonine; by MAPK1By similarity1
Cross-linki251Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei582Phosphoserine; by PKCBy similarity1

Post-translational modificationi

Sumoylation requires both PIAS1 and UBE2I. Sumoylation appears to dissociate NR2C1 from the PML nuclear bodies. Enhances the interaction with NRIP1 but inhibits interaction with KAT2B. In proliferating cells, stimulation by all-trans retinoic acid, activation of MAPK1-mediated phosphorylation and recruitment to PML bodies with subsequent sumoylation, suppresses OCT4 expression (By similarity).By similarity
Phosphorylated on several serine and threonine residues. Phosphorylation on Thr-223, stimulated by all-trans retinoic acid (atRA) mediates PML location and sumoylation in proliferating cells which then modulates its association with effector molecules, KAT2B and NRIP1. Phosphorylation on Ser-582 by PKC is important for protein stability and function as activator of RARB (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

Homodimer (By similarity). Heterodimer; with NR2C2 which is required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats (By similarity). Interacts with ESR1; the interaction prevents homodimerization of ESR1 and suppresses its transcriptional activity and cell growth. Interacts with NRIP1 (via its LXXLL motifs); the interaction provides corepressor activity. Interacts with HDAC3 (via the DNA-binding domain); the interaction recruits phosphorylated NR2C1 to PML bodies for sumoylation. Interacts with HDAC4 (via the DNA-binding domain). Interacts with PIAS1; the interaction is required for sumoylation of NR2C1. Interacts with UBE2I; the interaction is required for sumoylation of NR2C1. Interacts with KAT2B; the interaction acts as a corepressor of gene expression (By similarity).By similarity

Protein-protein interaction databases

STRINGi9601.ENSPPYP00000005520.

Structurei

3D structure databases

ProteinModelPortaliQ5RCZ5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 179Required for interaction with KAT2BBy similarityAdd BLAST179
Regioni585 – 601Required for interaction with NRIP1By similarityAdd BLAST17

Sequence similaritiesi

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri114 – 134NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri150 – 169NR C4-typePROSITE-ProRule annotationAdd BLAST20

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
HOGENOMiHOG000013058.
InParanoidiQ5RCZ5.
KOiK08543.

Family and domain databases

Gene3Di1.10.565.10. 3 hits.
3.30.50.10. 1 hit.
InterProiIPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 3 hits.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q5RCZ5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATIEEIAHQ IIEQQMGEIV TEQQTGQKIQ IVTALDHNTQ GKQFILTNHD
60 70 80 90 100
GSTPSKVILA RQDSTPGKVF LTTPDAAGVN QLFFTTPDLS AQHLQLLTDN
110 120 130 140 150
SSPDQGPNKV FDLCVVCGDK ASGRHYGAVT CEGCKGFFKR SIRKNLVYSC
160 170 180 190 200
RGSKDCIINK HHRNRCQYCR LQRCIAFGMK QDSVQCERKP IEVSREKSSN
210 220 230 240 250
CAASTEKIYI RKDLRSPLTA TPTFVTDSES TRSTGLLDSG MFVNIHPSGV
260 270 280 290 300
KTESTVLMTS DKAESCQGDL STLASVVTSL ANLGKTKDLS QNSNEMSMIE
310 320 330 340 350
SLSNDDTSLC EFQEMHTNGD VSRAFDTLAK ALNPGESTAC QSSVAGMEGS
360 370 380 390 400
VHLITGDSSI NYTEKEGPLL SDSHVAFRLT MPSPMPEYLN VHYIGESASR
410 420 430 440 450
LLFLSMHWAL SIPSFQALGQ ENSISLVKAY WNELFTLGLA QCWQVMNVAT
460 470 480 490 500
ILATFVNCLH NSLQQDKMST ERRKLLMEHI FKLQEFCNSM VKLCIDGYEY
510 520 530 540 550
AYLKAIVLFS PDHPGLENME QIEKFQEKAY VEFQDYITKT YPDDTYRLSR
560 570 580 590 600
LLLRLPALRL MNATITEELF FKGLIGNIRI DSVIPHILKM EPGQYSKTSS

L
Length:601
Mass (Da):67,004
Last modified:December 21, 2004 - v1
Checksum:i46BE3FE0E856346C
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CR858123 mRNA. Translation: CAH90362.1.
RefSeqiNP_001127276.1. NM_001133804.2.
UniGeneiPab.13925.

Genome annotation databases

GeneIDi100174333.
KEGGipon:100174333.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CR858123 mRNA. Translation: CAH90362.1.
RefSeqiNP_001127276.1. NM_001133804.2.
UniGeneiPab.13925.

3D structure databases

ProteinModelPortaliQ5RCZ5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9601.ENSPPYP00000005520.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100174333.
KEGGipon:100174333.

Organism-specific databases

CTDi7181.

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
HOGENOMiHOG000013058.
InParanoidiQ5RCZ5.
KOiK08543.

Family and domain databases

Gene3Di1.10.565.10. 3 hits.
3.30.50.10. 1 hit.
InterProiIPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 3 hits.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNR2C1_PONAB
AccessioniPrimary (citable) accession number: Q5RCZ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 14, 2009
Last sequence update: December 21, 2004
Last modified: October 5, 2016
This is version 68 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.