NR0B2 (nuclear receptor subfamily 0 group B member 2)

Gene

• Entrez ID: 8431
• Gene name: Nuclear receptor subfamily 0 group B member 2
• Gene symbol: NR0B2
• Synonyms: SHP, SHP1
• Chromosome: 1
• Chromosome location: 1p36.11
• Summary: The protein encoded by this gene is an unusual orphan receptor that contains a putative ligand-binding domain but lacks a conventional DNA-binding domain. The gene product is a member of the nuclear hormone receptor family, a group of transcription factors regulated by small hydrophobic hormones, a subset of which do not have known ligands and are referred to as orphan nuclear receptors. The protein has been shown to interact with retinoid and thyroid hormone receptors, inhibiting their ligand-dependent transcriptional activation. In addition, interaction with estrogen receptors has been demonstrated, leading to inhibition of function. Studies suggest that the protein represses nuclear hormone receptor-mediated transactivation via two separate steps: competition with coactivators and the direct effects of its transcriptional repressor function. [provided by RefSeq, Jul 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT006718	hsa-miR-141-3p	Luciferase reporter assay	22314666
MIRT028990	hsa-miR-26b-5p	Microarray	19088304
MIRT030414	hsa-miR-24-3p	Microarray	19748357

Transcription factors

Transcription factor	Regulation	Reference
ATF6	Activation	18450959
CLOCK	Activation	20674862
EP300	Activation	18842595
SREBF1	Activation	15123650

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IBA	21873635
GO:0000785	Component	Chromatin	IDA	27471003
GO:0000785	Component	Chromatin	ISA
GO:0003714	Function	Transcription corepressor activity	IBA	21873635
GO:0003714	Function	Transcription corepressor activity	IDA	14752053
GO:0003714	Function	Transcription corepressor activity	TAS	11030331
GO:0005515	Function	Protein binding	IPI	14752053, 15317749, 16709599, 17895379, 20375098, 22504882, 22575647, 28128295, 32296183, 32814053
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	IDA	14752053, 16709599, 28797635
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005737	Component	Cytoplasm	IDA	14752053
GO:0006367	Process	Transcription initiation from RNA polymerase II promoter	TAS
GO:0007219	Process	Notch signaling pathway	IEA
GO:0007623	Process	Circadian rhythm	IBA	21873635
GO:0007623	Process	Circadian rhythm	IDA	28797635
GO:0008134	Function	Transcription factor binding	IBA	21873635
GO:0008203	Process	Cholesterol metabolic process	TAS	11030331
GO:0009749	Process	Response to glucose	IEA
GO:0010628	Process	Positive regulation of gene expression	IMP	19085950
GO:0010629	Process	Negative regulation of gene expression	IMP	19085950
GO:0014070	Process	Response to organic cyclic compound	IEA
GO:0015721	Process	Bile acid and bile salt transport	IEA
GO:0019904	Function	Protein domain specific binding	IPI	17686645
GO:0031100	Process	Animal organ regeneration	IEA
GO:0032024	Process	Positive regulation of insulin secretion	IEA
GO:0032922	Process	Circadian regulation of gene expression	ISS
GO:0032991	Component	Protein-containing complex	IEA
GO:0042803	Function	Protein homodimerization activity	IPI	16709599
GO:0042975	Function	Peroxisome proliferator activated receptor binding	IEA
GO:0043433	Process	Negative regulation of DNA-binding transcription factor activity	IBA	21873635
GO:0043433	Process	Negative regulation of DNA-binding transcription factor activity	IDA	14752053
GO:0044877	Function	Protein-containing complex binding	IEA
GO:0045471	Process	Response to ethanol	IEA
GO:0045892	Process	Negative regulation of transcription, DNA-templated	ISS
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	27471003
GO:0046965	Function	Retinoid X receptor binding	IEA
GO:0046966	Function	Thyroid hormone receptor binding	IEA
GO:0140416	Function	Transcription regulator inhibitor activity	IDA	27471003

Other IDs

• MIM: 604630
• HGNC: 7961
• e!Ensembl: ENSG00000131910

Protein

• UniProt ID: Q15466
• Protein name: Nuclear receptor subfamily 0 group B member 2 (Orphan nuclear receptor SHP) (Small heterodimer partner)
• Protein function: 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).
• PDB: 1YUC, 2Q3Y, 2Z4J, 4DOR, 4ONI, 5UFS, 6W9M
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00104	Hormone_recep	50 → 237	Ligand-binding domain of nuclear hormone receptor	Domain

• Sequence:

  MSTSQPGACPCQGAASRPAILYALLSSSLKAVPRPRSRCLCRQHRPVQLCAPHRTCREAL
  DVLAKTVAFLRNLPSFWQLPPQDQRRLLQGCWGPLFLLGLAQDAVTFEVAEAPVPSILKK
  ILLEEPSSSGGSGQLPDRPQPSLAAVQWLQCCLESFWSLELSPKEYACLKGTILFNPDVP
  GLQAASHIGHLQQEAHWVLCEVLEPWCPAAQGRLTRVLLTASTLKSIPTSLLGDLFFRPI
  IGDVDIAGLLGDMLLLR

• Sequence length: 257

Pathways

KEGG:

Bile secretion

Reactome:

Nuclear Receptor transcription pathway

Associated diseases

Disease name	Disease term	References
	Cognition Disorders	29382564
	Fatty Liver	27664470
	Steatohepatitis	27664470
	Lipoidosis	17175557, 16919414, 15342952
	Liver carcinoma	23811326
	Obesity