UniProtKB - Q15466 (NR0B2_HUMAN)
Nuclear receptor subfamily 0 group B member 2
NR0B2
Functioni
Transcriptional regulator that acts as a negative regulator of receptor-dependent signaling pathways (By similarity).
Specifically inhibits transactivation of the nuclear receptor with which it interacts (By similarity).
Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated transcription complex for NEUROD1 (PubMed:14752053).
Essential component of the liver circadian clock which via its interaction with NR1D1 and RORG regulates NPAS2-mediated hepatic lipid metabolism (By similarity).
Regulates the circadian expression of cytochrome P450 (CYP) enzymes (By similarity).
Represses: NR5A2 and HNF4A to down-regulate CYP2C38, NFLI3 to up-regulate CYP2A5, BHLHE41/HNF1A axis to up-regulate CYP1A2, CYP2E1 and CYP3A11, and NR1D1 to up-regulate CYP2B10, CYP4A10 and CYP4A14 (By similarity).
By similarity1 PublicationGO - Molecular functioni
- peroxisome proliferator activated receptor binding Source: Ensembl
- protein-containing complex binding Source: Ensembl
- protein domain specific binding Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
- retinoid X receptor binding Source: Ensembl
- thyroid hormone receptor binding Source: Ensembl
- transcription corepressor activity Source: GO_Central
- transcription regulator inhibitor activity Source: MGI
GO - Biological processi
- animal organ regeneration Source: Ensembl
- bile acid and bile salt transport Source: Ensembl
- cholesterol metabolic process Source: ProtInc
- circadian regulation of gene expression Source: UniProtKB
- circadian rhythm Source: UniProtKB
- negative regulation of DNA-binding transcription factor activity Source: UniProtKB
- negative regulation of gene expression Source: UniProtKB
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: GO_Central
- Notch signaling pathway Source: Ensembl
- positive regulation of gene expression Source: UniProtKB
- positive regulation of insulin secretion Source: Ensembl
- positive regulation of transcription, DNA-templated Source: MGI
- response to ethanol Source: Ensembl
- response to glucose Source: Ensembl
- response to organic cyclic compound Source: Ensembl
Keywordsi
Molecular function | Receptor, Repressor |
Biological process | Biological rhythms, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | Q15466 |
Reactomei | R-HSA-383280, Nuclear Receptor transcription pathway |
SignaLinki | Q15466 |
SIGNORi | Q15466 |
Names & Taxonomyi
Protein namesi | Recommended name: Nuclear receptor subfamily 0 group B member 2Alternative name(s): Orphan nuclear receptor SHP Small heterodimer partner |
Gene namesi | Name:NR0B2 Synonyms:SHP |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:7961, NR0B2 |
MIMi | 604630, gene |
neXtProti | NX_Q15466 |
VEuPathDBi | HostDB:ENSG00000131910 |
Subcellular locationi
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Other locations
- chromatin Source: MGI
- cytoplasm Source: UniProtKB
- protein-containing complex Source: Ensembl
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
Obesity (OBESITY)1 Publication
Keywords - Diseasei
Disease variant, ObesityOrganism-specific databases
DisGeNETi | 8431 |
MalaCardsi | NR0B2 |
MIMi | 601665, phenotype |
OpenTargetsi | ENSG00000131910 |
PharmGKBi | PA31747 |
Miscellaneous databases
Pharosi | Q15466, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5603 |
GuidetoPHARMACOLOGYi | 636 |
Genetic variation databases
BioMutai | NR0B2 |
DMDMi | 9978744 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000053752 | 1 – 257 | Nuclear receptor subfamily 0 group B member 2Add BLAST | 257 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 57 | Symmetric dimethylarginine; by PRMT5By similarity | 1 |
Post-translational modificationi
Keywords - PTMi
MethylationProteomic databases
jPOSTi | Q15466 |
MassIVEi | Q15466 |
PaxDbi | Q15466 |
PeptideAtlasi | Q15466 |
PRIDEi | Q15466 |
PTM databases
GlyGeni | Q15466, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q15466 |
PhosphoSitePlusi | Q15466 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000131910, Expressed in right lobe of liver and 90 other tissues |
Genevisiblei | Q15466, HS |
Organism-specific databases
HPAi | ENSG00000131910, Tissue enhanced (intestine, liver) |
Interactioni
Subunit structurei
Interacts (via N-terminus) with NEUROD1 (via N-terminus and C-terminus) (PubMed:14752053).
Interacts with ID2 (PubMed:14752053).
Interacts with RORG, NFIL3, NR1D1 and BHLHE41 (By similarity). Heterodimer; efficient DNA binding requires dimerization with another bHLH protein (PubMed:14752053).
Interacts with RARA, RXRA, THRB, NR5A1, NR5A2, NR1I3, PPARA, PPARG and EID1 (By similarity).
Interacts with HNF4A; the resulting heterodimer is transcriptionnally inactive (PubMed:28128295).
Interacts with DDX3X; this interaction disrupts the interaction between HNF4 and NR0B2/SHP that forms inactive heterodimers and enhances the formation of active HNF4 homodimers (PubMed:28128295).
By similarity2 PublicationsBinary interactionsi
Q15466
GO - Molecular functioni
- peroxisome proliferator activated receptor binding Source: Ensembl
- protein domain specific binding Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
- retinoid X receptor binding Source: Ensembl
- thyroid hormone receptor binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 114012, 70 interactors |
CORUMi | Q15466 |
DIPi | DIP-46313N |
IntActi | Q15466, 30 interactors |
MINTi | Q15466 |
STRINGi | 9606.ENSP00000254227 |
Miscellaneous databases
RNActi | Q15466, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q15466 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q15466 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 16 – 257 | NR LBDPROSITE-ProRule annotationAdd BLAST | 242 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG3575, Eukaryota |
GeneTreei | ENSGT00390000015719 |
HOGENOMi | CLU_093194_0_0_1 |
InParanoidi | Q15466 |
OMAi | PHRCNCE |
OrthoDBi | 1474731at2759 |
PhylomeDBi | Q15466 |
TreeFami | TF332386 |
Family and domain databases
Gene3Di | 1.10.565.10, 1 hit |
IDEALi | IID00081 |
InterProi | View protein in InterPro IPR035500, NHR-like_dom_sf IPR033544, NR0B1/2 IPR000536, Nucl_hrmn_rcpt_lig-bd IPR001723, Nuclear_hrmn_rcpt |
PANTHERi | PTHR24081, PTHR24081, 1 hit |
Pfami | View protein in Pfam PF00104, Hormone_recep, 1 hit |
PRINTSi | PR00398, STRDHORMONER |
SMARTi | View protein in SMART SM00430, HOLI, 1 hit |
SUPFAMi | SSF48508, SSF48508, 1 hit |
PROSITEi | View protein in PROSITE PS51843, NR_LBD, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MSTSQPGACP CQGAASRPAI LYALLSSSLK AVPRPRSRCL CRQHRPVQLC
60 70 80 90 100
APHRTCREAL DVLAKTVAFL RNLPSFWQLP PQDQRRLLQG CWGPLFLLGL
110 120 130 140 150
AQDAVTFEVA EAPVPSILKK ILLEEPSSSG GSGQLPDRPQ PSLAAVQWLQ
160 170 180 190 200
CCLESFWSLE LSPKEYACLK GTILFNPDVP GLQAASHIGH LQQEAHWVLC
210 220 230 240 250
EVLEPWCPAA QGRLTRVLLT ASTLKSIPTS LLGDLFFRPI IGDVDIAGLL
GDMLLLR
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_026015 | 57 | R → W in early-onset obesity; Japanese population; loss of methylation and repressor activity. 2 PublicationsCorresponds to variant dbSNP:rs777291973Ensembl. | 1 | |
Natural variantiVAR_050584 | 171 | G → A. Corresponds to variant dbSNP:rs6659176EnsemblClinVar. | 1 | |
Natural variantiVAR_026016 | 189 | G → E in early-onset obesity; Japanese population; strong decrease of repressor activity. 1 PublicationCorresponds to variant dbSNP:rs202154574Ensembl. | 1 | |
Natural variantiVAR_026017 | 195 | A → S in early-onset obesity; Japanese population; slight decrease of repressor activity. 1 PublicationCorresponds to variant dbSNP:rs74315350EnsemblClinVar. | 1 | |
Natural variantiVAR_026018 | 213 | R → C in early-onset obesity; Japanese population; loss of repressor activity. 1 PublicationCorresponds to variant dbSNP:rs199976415Ensembl. | 1 | |
Natural variantiVAR_026019 | 216 | R → H No effect on repressor activity. 1 PublicationCorresponds to variant dbSNP:rs200475847Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L76571 Genomic DNA Translation: AAC41998.1 AB058644 Genomic DNA Translation: BAB68530.1 HQ692833 mRNA Translation: ADZ17344.1 AL356390 Genomic DNA No translation available. CH471059 Genomic DNA Translation: EAX07781.1 BC030207 mRNA Translation: AAH30207.1 |
CCDSi | CCDS291.1 |
RefSeqi | NP_068804.1, NM_021969.2 |
Genome annotation databases
Ensembli | ENST00000254227; ENSP00000254227; ENSG00000131910 |
GeneIDi | 8431 |
KEGGi | hsa:8431 |
MANE-Selecti | ENST00000254227.4; ENSP00000254227.3; NM_021969.3; NP_068804.1 |
UCSCi | uc001bnf.4, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L76571 Genomic DNA Translation: AAC41998.1 AB058644 Genomic DNA Translation: BAB68530.1 HQ692833 mRNA Translation: ADZ17344.1 AL356390 Genomic DNA No translation available. CH471059 Genomic DNA Translation: EAX07781.1 BC030207 mRNA Translation: AAH30207.1 |
CCDSi | CCDS291.1 |
RefSeqi | NP_068804.1, NM_021969.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1YUC | X-ray | 1.90 | C/D | 15-28 | [»] | |
2Q3Y | X-ray | 2.40 | B | 18-27 | [»] | |
2Z4J | X-ray | 2.60 | B | 115-124 | [»] | |
4DOR | X-ray | 1.90 | C/D | 15-28 | [»] | |
4ONI | X-ray | 1.80 | C/D | 12-30 | [»] | |
5UFS | X-ray | 2.12 | C/D | 18-27 | [»] | |
6W9M | X-ray | 1.59 | B | 17-27 | [»] | |
SMRi | Q15466 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 114012, 70 interactors |
CORUMi | Q15466 |
DIPi | DIP-46313N |
IntActi | Q15466, 30 interactors |
MINTi | Q15466 |
STRINGi | 9606.ENSP00000254227 |
Chemistry databases
ChEMBLi | CHEMBL5603 |
GuidetoPHARMACOLOGYi | 636 |
PTM databases
GlyGeni | Q15466, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q15466 |
PhosphoSitePlusi | Q15466 |
Genetic variation databases
BioMutai | NR0B2 |
DMDMi | 9978744 |
Proteomic databases
jPOSTi | Q15466 |
MassIVEi | Q15466 |
PaxDbi | Q15466 |
PeptideAtlasi | Q15466 |
PRIDEi | Q15466 |
Protocols and materials databases
Antibodypediai | 16231, 419 antibodies from 34 providers |
DNASUi | 8431 |
Genome annotation databases
Ensembli | ENST00000254227; ENSP00000254227; ENSG00000131910 |
GeneIDi | 8431 |
KEGGi | hsa:8431 |
MANE-Selecti | ENST00000254227.4; ENSP00000254227.3; NM_021969.3; NP_068804.1 |
UCSCi | uc001bnf.4, human |
Organism-specific databases
CTDi | 8431 |
DisGeNETi | 8431 |
GeneCardsi | NR0B2 |
HGNCi | HGNC:7961, NR0B2 |
HPAi | ENSG00000131910, Tissue enhanced (intestine, liver) |
MalaCardsi | NR0B2 |
MIMi | 601665, phenotype 604630, gene |
neXtProti | NX_Q15466 |
OpenTargetsi | ENSG00000131910 |
PharmGKBi | PA31747 |
VEuPathDBi | HostDB:ENSG00000131910 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3575, Eukaryota |
GeneTreei | ENSGT00390000015719 |
HOGENOMi | CLU_093194_0_0_1 |
InParanoidi | Q15466 |
OMAi | PHRCNCE |
OrthoDBi | 1474731at2759 |
PhylomeDBi | Q15466 |
TreeFami | TF332386 |
Enzyme and pathway databases
PathwayCommonsi | Q15466 |
Reactomei | R-HSA-383280, Nuclear Receptor transcription pathway |
SignaLinki | Q15466 |
SIGNORi | Q15466 |
Miscellaneous databases
BioGRID-ORCSi | 8431, 19 hits in 1057 CRISPR screens |
ChiTaRSi | NR0B2, human |
EvolutionaryTracei | Q15466 |
GeneWikii | Small_heterodimer_partner |
GenomeRNAii | 8431 |
Pharosi | Q15466, Tchem |
PROi | PR:Q15466 |
RNActi | Q15466, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000131910, Expressed in right lobe of liver and 90 other tissues |
Genevisiblei | Q15466, HS |
Family and domain databases
Gene3Di | 1.10.565.10, 1 hit |
IDEALi | IID00081 |
InterProi | View protein in InterPro IPR035500, NHR-like_dom_sf IPR033544, NR0B1/2 IPR000536, Nucl_hrmn_rcpt_lig-bd IPR001723, Nuclear_hrmn_rcpt |
PANTHERi | PTHR24081, PTHR24081, 1 hit |
Pfami | View protein in Pfam PF00104, Hormone_recep, 1 hit |
PRINTSi | PR00398, STRDHORMONER |
SMARTi | View protein in SMART SM00430, HOLI, 1 hit |
SUPFAMi | SSF48508, SSF48508, 1 hit |
PROSITEi | View protein in PROSITE PS51843, NR_LBD, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NR0B2_HUMAN | |
Accessioni | Q15466Primary (citable) accession number: Q15466 Secondary accession number(s): F1D8P5, Q5QP36 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | December 1, 2000 | |
Last modified: | February 23, 2022 | |
This is version 195 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families