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Protein

Nuclear receptor subfamily 2 group C member 2

Gene

NR2C2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear receptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during the late phase of spermatogenesis. Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior (By similarity). Activates transcriptional activity of LHCG. Antagonist of PPARA-mediated transactivation.By similarity5 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi114 – 189Nuclear receptorPROSITE-ProRule annotationAdd BLAST76
Zinc fingeri117 – 137NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri153 – 177NR C4-typePROSITE-ProRule annotationAdd BLAST25

GO - Molecular functioni

  • DNA binding transcription factor activity Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
  • sequence-specific DNA binding Source: UniProtKB
  • signaling receptor activity Source: ProtInc
  • steroid hormone receptor activity Source: InterPro
  • transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: NTNU_SB
  • transcription coactivator activity Source: ProtInc
  • zinc ion binding Source: InterPro

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • nervous system development Source: ProtInc
  • positive regulation of transcription by RNA polymerase II Source: UniProtKB
  • regulation of transcription, DNA-templated Source: ProtInc
  • spermatogenesis Source: UniProtKB-KW
  • transcription initiation from RNA polymerase II promoter Source: Reactome

Keywordsi

Molecular functionActivator, DNA-binding, Receptor, Repressor
Biological processDifferentiation, Spermatogenesis, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-383280 Nuclear Receptor transcription pathway
SignaLinkiP49116
SIGNORiP49116

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear receptor subfamily 2 group C member 2
Alternative name(s):
Orphan nuclear receptor TAK1
Orphan nuclear receptor TR4
Testicular receptor 4
Gene namesi
Name:NR2C2
Synonyms:TAK1, TR4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000177463.15
HGNCiHGNC:7972 NR2C2
MIMi601426 gene
neXtProtiNX_P49116

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi576I → N: Reduces interaction with JAZF1. 1 Publication1

Organism-specific databases

DisGeNETi7182
OpenTargetsiENSG00000177463
PharmGKBiPA31755

Chemistry databases

ChEMBLiCHEMBL5716
GuidetoPHARMACOLOGYi614

Polymorphism and mutation databases

BioMutaiNR2C2
DMDMi1351190

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000535881 – 596Nuclear receptor subfamily 2 group C member 2Add BLAST596

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19Phosphoserine; by MAPKCombined sources1
Modified residuei46PhosphoserineCombined sources1
Modified residuei55Phosphoserine; by MAPKBy similarity1
Modified residuei68Phosphoserine; by MAPKCombined sources1
Modified residuei98PhosphoserineCombined sources1
Cross-linki192Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei219PhosphoserineCombined sources1
Modified residuei231N6-acetyllysineBy similarity1

Post-translational modificationi

Phosphorylation on Ser-19 and Ser-68 is an important regulator of NR2C2-mediated transcriptional activity. Phosphorylation on these residues recruits the corepressor, NRIP1, leading to transcripional repression, whereas the non-phosphorylated form preferentially recruits the coactivator, PCAF (By similarity).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP49116
MaxQBiP49116
PaxDbiP49116
PeptideAtlasiP49116
PRIDEiP49116
TopDownProteomicsiP49116-2 [P49116-2]

PTM databases

iPTMnetiP49116
PhosphoSitePlusiP49116

Expressioni

Developmental stagei

Transiently repressed during the meiotic phase of spermatogenesis.

Inductioni

Induced by oxidative stress via FOXO3 activation.1 Publication

Gene expression databases

BgeeiENSG00000177463
CleanExiHS_NR2C2
ExpressionAtlasiP49116 baseline and differential
GenevisibleiP49116 HS

Organism-specific databases

HPAiHPA006313

Interactioni

Subunit structurei

Homodimer; can bind DNA as homodimer (By similarity). Heterodimer; binds DNA as a heterodimer with NR2C1 required for chromatin remodeling and for binding to promoter regions such as globin DR1 repeats. Interacts with PCAF; the interaction preferentially occurs on the non-phosphorylated form and induces NR2C2-mediated transactivation activity and does not require the ligand-binding domain (By similarity). Interacts (MAPK-mediated phosphorylated form) with NRIP1; the interaction promotes repression of NR2C2-mediated activity (PubMed:9556573). Interacts with NR2C2AP; the interaction represses selective NR2C2-mediated transcriptional activity (PubMed:12486131). Interacts with NLRP10 (PubMed:22672233). Interacts (via ligand-binding region) with transcriptional corepressor JAZF1; the interaction promotes NR2C2-mediated transcriptional repression (PubMed:15302918).By similarity4 Publications

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi113034, 46 interactors
DIPiDIP-5999N
IntActiP49116, 19 interactors
MINTiP49116
STRINGi9606.ENSP00000320447

Chemistry databases

BindingDBiP49116

Structurei

Secondary structure

1596
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi354 – 357Combined sources4
Helixi386 – 402Combined sources17
Turni405 – 407Combined sources3
Helixi408 – 410Combined sources3
Helixi412 – 420Combined sources9
Helixi423 – 433Combined sources11
Turni434 – 436Combined sources3
Helixi468 – 484Combined sources17
Helixi489 – 500Combined sources12
Helixi512 – 532Combined sources21
Turni533 – 535Combined sources3
Helixi539 – 544Combined sources6
Helixi547 – 551Combined sources5
Helixi555 – 562Combined sources8
Helixi567 – 570Combined sources4
Helixi572 – 579Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3P0UX-ray3.00A/B348-596[»]
ProteinModelPortaliP49116
SMRiP49116
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP49116

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini341 – 583NR LBDPROSITE-ProRule annotationAdd BLAST243

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri117 – 137NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri153 – 177NR C4-typePROSITE-ProRule annotationAdd BLAST25

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575 Eukaryota
ENOG410XRZC LUCA
GeneTreeiENSGT00760000118948
HOGENOMiHOG000013058
HOVERGENiHBG008596
InParanoidiP49116
KOiK08544
OMAiREKPTNC
PhylomeDBiP49116
TreeFamiTF316650

Family and domain databases

Gene3Di3.30.50.10, 1 hit
InterProiView protein in InterPro
IPR035500 NHR_like_dom_sf
IPR000536 Nucl_hrmn_rcpt_lig-bd
IPR001723 Nuclear_hrmn_rcpt
IPR001628 Znf_hrmn_rcpt
IPR013088 Znf_NHR/GATA
PfamiView protein in Pfam
PF00104 Hormone_recep, 1 hit
PF00105 zf-C4, 1 hit
PRINTSiPR00398 STRDHORMONER
PR00047 STROIDFINGER
SMARTiView protein in SMART
SM00430 HOLI, 1 hit
SM00399 ZnF_C4, 1 hit
SUPFAMiSSF48508 SSF48508, 2 hits
PROSITEiView protein in PROSITE
PS51843 NR_LBD, 1 hit
PS00031 NUCLEAR_REC_DBD_1, 1 hit
PS51030 NUCLEAR_REC_DBD_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P49116-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTSPSPRIQI ISTDSAVASP QRIQIVTDQQ TGQKIQIVTA VDASGSPKQQ
60 70 80 90 100
FILTSPDGAG TGKVILASPE TSSAKQLIFT TSDNLVPGRI QIVTDSASVE
110 120 130 140 150
RLLGKTDVQR PQVVEYCVVC GDKASGRHYG AVSCEGCKGF FKRSVRKNLT
160 170 180 190 200
YSCRSNQDCI INKHHRNRCQ FCRLKKCLEM GMKMESVQSE RKPFDVQREK
210 220 230 240 250
PSNCAASTEK IYIRKDLRSP LIATPTFVAD KDGARQTGLL DPGMLVNIQQ
260 270 280 290 300
PLIREDGTVL LATDSKAETS QGALGTLANV VTSLANLSES LNNGDTSEIQ
310 320 330 340 350
PEDQSASEIT RAFDTLAKAL NTTDSSSSPS LADGIDTSGG GSIHVISRDQ
360 370 380 390 400
STPIIEVEGP LLSDTHVTFK LTMPSPMPEY LNVHYICESA SRLLFLSMHW
410 420 430 440 450
ARSIPAFQAL GQDCNTSLVR ACWNELFTLG LAQCAQVMSL STILAAIVNH
460 470 480 490 500
LQNSIQEDKL SGDRIKQVME HIWKLQEFCN SMAKLDIDGY EYAYLKAIVL
510 520 530 540 550
FSPDHPGLTS TSQIEKFQEK AQMELQDYVQ KTYSEDTYRL ARILVRLPAL
560 570 580 590
RLMSSNITEE LFFTGLIGNV SIDSIIPYIL KMETAEYNGQ ITGASL
Length:596
Mass (Da):65,414
Last modified:February 1, 1996 - v1
Checksum:i5180BDC3F3C8BD79
GO
Isoform 2 (identifier: P49116-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     24-24: Q → QGSEPASGPLSVFTSLNKEK

Show »
Length:615
Mass (Da):67,345
Checksum:i5D557E04602C1BAB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti108V → A in BAH02299 (PubMed:18619963).Curated1
Sequence conflicti156N → S in AAA21474 (PubMed:8016112).Curated1
Sequence conflicti326S → F in BAH02299 (PubMed:18619963).Curated1
Sequence conflicti400W → R in AAA21474 (PubMed:8016112).Curated1
Sequence conflicti409A → G in AAA21474 (PubMed:8016112).Curated1
Sequence conflicti484 – 485KL → NW in AAA21474 (PubMed:8016112).Curated2
Sequence conflicti594A → V in AAA21474 (PubMed:8016112).Curated1
Sequence conflicti594A → V in BAH02299 (PubMed:18619963).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03952224Q → QGSEPASGPLSVFTSLNKEK in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U10990 mRNA Translation: AAC50118.1
L27586 mRNA Translation: AAA21474.1
AB307708 mRNA Translation: BAH02299.1
AK290590 mRNA Translation: BAF83279.1
AC090937 Genomic DNA No translation available.
AC090954 Genomic DNA No translation available.
CH471055 Genomic DNA Translation: EAW64215.1
CCDSiCCDS2621.1 [P49116-2]
CCDS74905.1 [P49116-1]
PIRiA57031
I59309
RefSeqiNP_001278623.1, NM_001291694.1 [P49116-1]
NP_003289.2, NM_003298.4 [P49116-2]
XP_016862609.1, XM_017007120.1 [P49116-1]
UniGeneiHs.555973

Genome annotation databases

EnsembliENST00000323373; ENSP00000320447; ENSG00000177463 [P49116-2]
ENST00000393102; ENSP00000376814; ENSG00000177463 [P49116-1]
ENST00000406272; ENSP00000384463; ENSG00000177463 [P49116-1]
ENST00000425241; ENSP00000388387; ENSG00000177463 [P49116-1]
ENST00000617312; ENSP00000483059; ENSG00000177463 [P49116-2]
GeneIDi7182
KEGGihsa:7182
UCSCiuc003bzi.4 human [P49116-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiNR2C2_HUMAN
AccessioniPrimary (citable) accession number: P49116
Secondary accession number(s): A8K3H5, B6ZGT8, P55092
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: May 23, 2018
This is version 176 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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