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Q15466 (NR0B2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nuclear receptor subfamily 0 group B member 2
Alternative name(s):
Orphan nuclear receptor SHP
Small heterodimer partner
Gene names
Name:NR0B2
Synonyms:SHP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length257 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts as a transcriptional regulator. Acts as a negative regulator of receptor-dependent signaling pathways. Specifically inhibits transactivation of the nuclear receptor with whom it interacts. Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated trancription complex for NEUROD1. Ref.8

Subunit structure

Interacts with RARA, RXRA, THRB, NR5A1, NR5A2, NR1I3, PPARA, PPARG and EID1. May also interact with HNF4A By similarity. Heterodimer; efficient DNA binding requires dimerization with another bHLH protein. Interacts (via N-terminus) with NEUROD1 (via N-terminus an C-terminus). Interacts with ID2. Ref.8

Subcellular location

Nucleus. Cytoplasm. Note: Colocalizes with NEUROD1 in the nucleus. Ref.8

Tissue specificity

Liver. Low levels of expression were detected in heart and pancreas. Ref.1

Post-translational modification

Arginine methylation by PRMT5 enhances repression activity of metabolic genes in liver in response to bile acid signaling, by increasing interaction with cofactors By similarity.

Involvement in disease

Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.3

Sequence similarities

Belongs to the nuclear hormone receptor family. NR0 subfamily.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Obesity
   Molecular functionReceptor
Repressor
   PTMMethylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcholesterol metabolic process

Traceable author statement PubMed 11030331. Source: ProtInc

gene expression

Traceable author statement. Source: Reactome

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.8. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Traceable author statement PubMed 11030331. Source: ProtInc

organ regeneration

Inferred from electronic annotation. Source: Ensembl

positive regulation of insulin secretion

Inferred from electronic annotation. Source: Ensembl

response to glucose

Inferred from electronic annotation. Source: Ensembl

transcription initiation from RNA polymerase II promoter

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay Ref.8. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.8PubMed 16709599. Source: UniProtKB

protein complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction Ref.8PubMed 15317749PubMed 16709599. Source: UniProtKB

protein domain specific binding

Inferred from physical interaction PubMed 17686645. Source: UniProtKB

protein homodimerization activity

Inferred from physical interaction PubMed 16709599. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

steroid hormone receptor activity

Inferred from electronic annotation. Source: InterPro

transcription corepressor activity

Inferred from direct assay Ref.8. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 257257Nuclear receptor subfamily 0 group B member 2
PRO_0000053752

Regions

Region57 – 228172Ligand-binding By similarity

Amino acid modifications

Modified residue541Symmetric dimethylarginine By similarity
Modified residue571Symmetric dimethylarginine; by PRMT5 By similarity

Natural variations

Natural variant571R → W in early-onset obesity; Japanese population; loss of methylation and repressor activity. Ref.3 Ref.10
VAR_026015
Natural variant1711G → A.
Corresponds to variant rs6659176 [ dbSNP | Ensembl ].
VAR_050584
Natural variant1891G → E in early-onset obesity; Japanese population; strong decrease of repressor activity. Ref.3
Corresponds to variant rs202154574 [ dbSNP | Ensembl ].
VAR_026016
Natural variant1951A → S in early-onset obesity; Japanese population; slight decrease of repressor activity. Ref.3
VAR_026017
Natural variant2131R → C in early-onset obesity; Japanese population; loss of repressor activity. Ref.3
VAR_026018
Natural variant2161R → H No effect on repressor activity. Ref.3
Corresponds to variant rs200475847 [ dbSNP | Ensembl ].
VAR_026019

Secondary structure

..... 257
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q15466 [UniParc].

Last modified December 1, 2000. Version 2.
Checksum: 14BEE2B3FF46154A

FASTA25728,058
        10         20         30         40         50         60 
MSTSQPGACP CQGAASRPAI LYALLSSSLK AVPRPRSRCL CRQHRPVQLC APHRTCREAL 

        70         80         90        100        110        120 
DVLAKTVAFL RNLPSFWQLP PQDQRRLLQG CWGPLFLLGL AQDAVTFEVA EAPVPSILKK 

       130        140        150        160        170        180 
ILLEEPSSSG GSGQLPDRPQ PSLAAVQWLQ CCLESFWSLE LSPKEYACLK GTILFNPDVP 

       190        200        210        220        230        240 
GLQAASHIGH LQQEAHWVLC EVLEPWCPAA QGRLTRVLLT ASTLKSIPTS LLGDLFFRPI 

       250 
IGDVDIAGLL GDMLLLR 

« Hide

References

« Hide 'large scale' references
[1]"An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors."
Seol W., Choi H.-S., Moore D.D.
Science 272:1336-1339(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[2]"Structure and expression of the orphan nuclear receptor SHP gene."
Lee H.-K., Lee Y.-K., Park S.-H., Kim Y.-S., Park S.H., Lee J.W., Kwon H.-B., Soh J., Moore D.D., Choi H.-S.
J. Biol. Chem. 273:14398-14402(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects."
Nishigori H., Tomura H., Tonooka N., Kanamori M., Yamada S., Sho K., Inoue I., Kikuchi N., Onigata K., Kojima I., Kohama T., Yamagata K., Yang Q., Matsuzawa Y., Miki T., Seino S., Kim M.-Y., Choi H.-S. expand/collapse author list , Lee Y.-K., Moore D.D., Takeda J.
Proc. Natl. Acad. Sci. U.S.A. 98:575-580(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS EARLY-ONSET OBESITY TRP-57; GLU-189; SER-195 AND CYS-213, VARIANT HIS-216, CHARACTERIZATION OF VARIANTS EARLY-ONSET OBESITY TRP-57; GLU-189; SER-195 AND CYS-213, CHARACTERIZATION OF VARIANT HIS-216.
[4]"Isolation of cDNA coding for multiple human nuclear receptor clones."
Kaighin V.A., Martin A.L., Aronstam R.S.
Submitted (DEC-2010) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.
[5]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Pancreas and Spleen.
[8]"Orphan nuclear receptor small heterodimer partner, a novel corepressor for a basic helix-loop-helix transcription factor BETA2/neuroD."
Kim J.Y., Chu K., Kim H.J., Seong H.A., Park K.C., Sanyal S., Takeda J., Ha H., Shong M., Tsai M.J., Choi H.S.
Mol. Endocrinol. 18:776-790(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, HETERODIMERIZATION, INTERACTION WITH ID2 AND NEUROD1, SUBCELLULAR LOCATION.
[9]"Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP."
Ortlund E.A., Lee Y., Solomon I.H., Hager J.M., Safi R., Choi Y., Guan Z., Tripathy A., Raetz C.R.H., McDonnell D.P., Moore D.D., Redinbo M.R.
Nat. Struct. Mol. Biol. 12:357-363(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 15-28 IN COMPLEX WITH NR5A2.
[10]"Arginine methylation by PRMT5 at a naturally occurring mutation site is critical for liver metabolic regulation by small heterodimer partner."
Kanamaluru D., Xiao Z., Fang S., Choi S.E., Kim D.H., Veenstra T.D., Kemper J.K.
Mol. Cell. Biol. 31:1540-1550(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TRP-57.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L76571 Genomic DNA. Translation: AAC41998.1.
AB058644 Genomic DNA. Translation: BAB68530.1.
HQ692833 mRNA. Translation: ADZ17344.1.
AL356390 Genomic DNA. Translation: CAI13562.1.
CH471059 Genomic DNA. Translation: EAX07781.1.
BC030207 mRNA. Translation: AAH30207.1.
CCDSCCDS291.1.
RefSeqNP_068804.1. NM_021969.2.
UniGeneHs.427055.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1YUCX-ray1.90C/D15-28[»]
2Q3YX-ray2.40B18-27[»]
2Z4JX-ray2.60B115-124[»]
4DORX-ray1.90C/D15-28[»]
ProteinModelPortalQ15466.
SMRQ15466. Positions 51-257.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114012. 57 interactions.
DIPDIP-46313N.
IntActQ15466. 17 interactions.
MINTMINT-8150838.
STRING9606.ENSP00000254227.

Chemistry

ChEMBLCHEMBL5603.

PTM databases

PhosphoSiteQ15466.

Polymorphism databases

DMDM9978744.

Proteomic databases

PaxDbQ15466.
PRIDEQ15466.

Protocols and materials databases

DNASU8431.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000254227; ENSP00000254227; ENSG00000131910.
GeneID8431.
KEGGhsa:8431.
UCSCuc001bnf.3. human.

Organism-specific databases

CTD8431.
GeneCardsGC01M027237.
HGNCHGNC:7961. NR0B2.
MIM601665. phenotype.
604630. gene.
neXtProtNX_Q15466.
PharmGKBPA31747.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG235713.
HOGENOMHOG000231151.
HOVERGENHBG008136.
InParanoidQ15466.
KOK08563.
OMAHIGHLQQ.
OrthoDBEOG7NSB35.
PhylomeDBQ15466.
TreeFamTF332386.

Enzyme and pathway databases

ReactomeREACT_71. Gene Expression.
SignaLinkQ15466.

Gene expression databases

ArrayExpressQ15466.
BgeeQ15466.
CleanExHS_NR0B2.
GenevestigatorQ15466.

Family and domain databases

Gene3D1.10.565.10. 1 hit.
InterProIPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
[Graphical view]
PfamPF00104. Hormone_recep. 1 hit.
[Graphical view]
PRINTSPR00398. STRDHORMONER.
SMARTSM00430. HOLI. 1 hit.
[Graphical view]
SUPFAMSSF48508. SSF48508. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ15466.
GeneWikiSmall_heterodimer_partner.
GenomeRNAi8431.
NextBio31546.
PROQ15466.
SOURCESearch...

Entry information

Entry nameNR0B2_HUMAN
AccessionPrimary (citable) accession number: Q15466
Secondary accession number(s): F1D8P5, Q5QP36
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 1, 2000
Last modified: July 9, 2014
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM