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Protein

Nuclear receptor subfamily 0 group B member 2

Gene

NR0B2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 NEUROD1.1 Publication

GO - Molecular functioni

  1. DNA binding Source: InterPro
  2. protein domain specific binding Source: UniProtKB
  3. protein homodimerization activity Source: UniProtKB
  4. sequence-specific DNA binding transcription factor activity Source: InterPro
  5. steroid hormone receptor activity Source: InterPro
  6. transcription corepressor activity Source: UniProtKB

GO - Biological processi

  1. cholesterol metabolic process Source: ProtInc
  2. gene expression Source: Reactome
  3. negative regulation of gene expression Source: UniProtKB
  4. negative regulation of sequence-specific DNA binding transcription factor activity Source: UniProtKB
  5. negative regulation of transcription from RNA polymerase II promoter Source: ProtInc
  6. organ regeneration Source: Ensembl
  7. positive regulation of gene expression Source: UniProtKB
  8. positive regulation of insulin secretion Source: Ensembl
  9. response to glucose Source: Ensembl
  10. transcription initiation from RNA polymerase II promoter Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Receptor, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiREACT_15525. Nuclear Receptor transcription pathway.
SignaLinkiQ15466.

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear receptor subfamily 0 group B member 2
Alternative name(s):
Orphan nuclear receptor SHP
Small heterodimer partner
Gene namesi
Name:NR0B2
Synonyms:SHP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:7961. NR0B2.

Subcellular locationi

Nucleus 1 Publication. Cytoplasm 1 Publication
Note: Colocalizes with NEUROD1 in the nucleus.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleoplasm Source: Reactome
  3. nucleus Source: UniProtKB
  4. protein complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Obesity1 Publication

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:601665

Keywords - Diseasei

Disease mutation, Obesity

Organism-specific databases

MIMi601665. phenotype.
PharmGKBiPA31747.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 257257Nuclear receptor subfamily 0 group B member 2PRO_0000053752Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei54 – 541Symmetric dimethylarginineBy similarity
Modified residuei57 – 571Symmetric dimethylarginine; by PRMT5By similarity

Post-translational modificationi

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

Keywords - PTMi

Methylation

Proteomic databases

PaxDbiQ15466.
PRIDEiQ15466.

PTM databases

PhosphoSiteiQ15466.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ15466.
CleanExiHS_NR0B2.
GenevestigatoriQ15466.

Interactioni

Subunit structurei

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.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MDM2Q009874EBI-3910729,EBI-389668
SIRT1Q96EB66EBI-3910729,EBI-1802965
TP53P046373EBI-3910729,EBI-366083

Protein-protein interaction databases

BioGridi114012. 58 interactions.
DIPiDIP-46313N.
IntActiQ15466. 18 interactions.
MINTiMINT-8150838.
STRINGi9606.ENSP00000254227.

Structurei

Secondary structure

1
257
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi19 – 268Combined sources
Helixi118 – 1225Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1YUCX-ray1.90C/D15-28[»]
2Q3YX-ray2.40B18-27[»]
2Z4JX-ray2.60B115-124[»]
4DORX-ray1.90C/D15-28[»]
ProteinModelPortaliQ15466.
SMRiQ15466. Positions 51-257.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15466.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni57 – 228172Ligand-bindingBy similarityAdd
BLAST

Sequence similaritiesi

Phylogenomic databases

eggNOGiNOG235713.
GeneTreeiENSGT00390000015719.
HOGENOMiHOG000231151.
HOVERGENiHBG008136.
InParanoidiQ15466.
KOiK08563.
OMAiDRPQPSL.
OrthoDBiEOG7NSB35.
PhylomeDBiQ15466.
TreeFamiTF332386.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
InterProiIPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
[Graphical view]
PRINTSiPR00398. STRDHORMONER.
SMARTiSM00430. HOLI. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.

Sequencei

Sequence statusi: Complete.

Q15466-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:257
Mass (Da):28,058
Last modified:December 1, 2000 - v2
Checksum:i14BEE2B3FF46154A
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti57 – 571R → W in early-onset obesity; Japanese population; loss of methylation and repressor activity. 2 Publications
VAR_026015
Natural varianti171 – 1711G → A.
Corresponds to variant rs6659176 [ dbSNP | Ensembl ].
VAR_050584
Natural varianti189 – 1891G → E in early-onset obesity; Japanese population; strong decrease of repressor activity. 1 Publication
Corresponds to variant rs202154574 [ dbSNP | Ensembl ].
VAR_026016
Natural varianti195 – 1951A → S in early-onset obesity; Japanese population; slight decrease of repressor activity. 1 Publication
VAR_026017
Natural varianti213 – 2131R → C in early-onset obesity; Japanese population; loss of repressor activity. 1 Publication
VAR_026018
Natural varianti216 – 2161R → H No effect on repressor activity. 1 Publication
Corresponds to variant rs200475847 [ dbSNP | Ensembl ].
VAR_026019

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. Translation: CAI13562.1.
CH471059 Genomic DNA. Translation: EAX07781.1.
BC030207 mRNA. Translation: AAH30207.1.
CCDSiCCDS291.1.
RefSeqiNP_068804.1. NM_021969.2.
UniGeneiHs.427055.

Genome annotation databases

EnsembliENST00000254227; ENSP00000254227; ENSG00000131910.
GeneIDi8431.
KEGGihsa:8431.
UCSCiuc001bnf.3. human.

Polymorphism databases

DMDMi9978744.

Keywords - Coding sequence diversityi

Polymorphism

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. Translation: CAI13562.1.
CH471059 Genomic DNA. Translation: EAX07781.1.
BC030207 mRNA. Translation: AAH30207.1.
CCDSiCCDS291.1.
RefSeqiNP_068804.1. NM_021969.2.
UniGeneiHs.427055.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1YUCX-ray1.90C/D15-28[»]
2Q3YX-ray2.40B18-27[»]
2Z4JX-ray2.60B115-124[»]
4DORX-ray1.90C/D15-28[»]
ProteinModelPortaliQ15466.
SMRiQ15466. Positions 51-257.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114012. 58 interactions.
DIPiDIP-46313N.
IntActiQ15466. 18 interactions.
MINTiMINT-8150838.
STRINGi9606.ENSP00000254227.

Chemistry

ChEMBLiCHEMBL5603.

PTM databases

PhosphoSiteiQ15466.

Polymorphism databases

DMDMi9978744.

Proteomic databases

PaxDbiQ15466.
PRIDEiQ15466.

Protocols and materials databases

DNASUi8431.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000254227; ENSP00000254227; ENSG00000131910.
GeneIDi8431.
KEGGihsa:8431.
UCSCiuc001bnf.3. human.

Organism-specific databases

CTDi8431.
GeneCardsiGC01M027237.
HGNCiHGNC:7961. NR0B2.
MIMi601665. phenotype.
604630. gene.
neXtProtiNX_Q15466.
PharmGKBiPA31747.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG235713.
GeneTreeiENSGT00390000015719.
HOGENOMiHOG000231151.
HOVERGENiHBG008136.
InParanoidiQ15466.
KOiK08563.
OMAiDRPQPSL.
OrthoDBiEOG7NSB35.
PhylomeDBiQ15466.
TreeFamiTF332386.

Enzyme and pathway databases

ReactomeiREACT_15525. Nuclear Receptor transcription pathway.
SignaLinkiQ15466.

Miscellaneous databases

EvolutionaryTraceiQ15466.
GeneWikiiSmall_heterodimer_partner.
GenomeRNAii8431.
NextBioi31546.
PROiQ15466.
SOURCEiSearch...

Gene expression databases

BgeeiQ15466.
CleanExiHS_NR0B2.
GenevestigatoriQ15466.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
InterProiIPR008946. Nucl_hormone_rcpt_ligand-bd.
IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
IPR001723. Str_hrmn_rcpt.
[Graphical view]
PfamiPF00104. Hormone_recep. 1 hit.
[Graphical view]
PRINTSiPR00398. STRDHORMONER.
SMARTiSM00430. HOLI. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. 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.
    , 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. 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. 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.

Entry informationi

Entry nameiNR0B2_HUMAN
AccessioniPrimary (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: March 4, 2015
This is version 142 of the entry and version 2 of the sequence. [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 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.