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Q15466

- NR0B2_HUMAN

UniProt

Q15466 - NR0B2_HUMAN

Protein

Nuclear receptor subfamily 0 group B member 2

Gene

NR0B2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 138 (01 Oct 2014)
      Sequence version 2 (01 Dec 2000)
      Previous versions | rss
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    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 binding Source: UniProtKB
    3. protein domain specific binding Source: UniProtKB
    4. protein homodimerization activity Source: UniProtKB
    5. sequence-specific DNA binding transcription factor activity Source: InterPro
    6. steroid hormone receptor activity Source: InterPro
    7. transcription corepressor activity Source: UniProtKB

    GO - Biological processi

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

    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

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    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.1 Publication
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

    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

    ArrayExpressiQ15466.
    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. 57 interactions.
    DIPiDIP-46313N.
    IntActiQ15466. 17 interactions.
    MINTiMINT-8150838.
    STRINGi9606.ENSP00000254227.

    Structurei

    Secondary structure

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

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    HOGENOMiHOG000231151.
    HOVERGENiHBG008136.
    InParanoidiQ15466.
    KOiK08563.
    OMAiHIGHLQQ.
    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

    MSTSQPGACP CQGAASRPAI LYALLSSSLK AVPRPRSRCL CRQHRPVQLC    50
    APHRTCREAL DVLAKTVAFL RNLPSFWQLP PQDQRRLLQG CWGPLFLLGL 100
    AQDAVTFEVA EAPVPSILKK ILLEEPSSSG GSGQLPDRPQ PSLAAVQWLQ 150
    CCLESFWSLE LSPKEYACLK GTILFNPDVP GLQAASHIGH LQQEAHWVLC 200
    EVLEPWCPAA QGRLTRVLLT ASTLKSIPTS LLGDLFFRPI IGDVDIAGLL 250
    GDMLLLR 257
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS291.1.
    RefSeqi NP_068804.1. NM_021969.2.
    UniGenei Hs.427055.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    ProteinModelPortali Q15466.
    SMRi Q15466. Positions 51-257.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114012. 57 interactions.
    DIPi DIP-46313N.
    IntActi Q15466. 17 interactions.
    MINTi MINT-8150838.
    STRINGi 9606.ENSP00000254227.

    Chemistry

    ChEMBLi CHEMBL5603.

    PTM databases

    PhosphoSitei Q15466.

    Polymorphism databases

    DMDMi 9978744.

    Proteomic databases

    PaxDbi Q15466.
    PRIDEi Q15466.

    Protocols and materials databases

    DNASUi 8431.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000254227 ; ENSP00000254227 ; ENSG00000131910 .
    GeneIDi 8431.
    KEGGi hsa:8431.
    UCSCi uc001bnf.3. human.

    Organism-specific databases

    CTDi 8431.
    GeneCardsi GC01M027237.
    HGNCi HGNC:7961. NR0B2.
    MIMi 601665. phenotype.
    604630. gene.
    neXtProti NX_Q15466.
    PharmGKBi PA31747.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG235713.
    HOGENOMi HOG000231151.
    HOVERGENi HBG008136.
    InParanoidi Q15466.
    KOi K08563.
    OMAi HIGHLQQ.
    OrthoDBi EOG7NSB35.
    PhylomeDBi Q15466.
    TreeFami TF332386.

    Enzyme and pathway databases

    Reactomei REACT_15525. Nuclear Receptor transcription pathway.
    SignaLinki Q15466.

    Miscellaneous databases

    EvolutionaryTracei Q15466.
    GeneWikii Small_heterodimer_partner.
    GenomeRNAii 8431.
    NextBioi 31546.
    PROi Q15466.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q15466.
    Bgeei Q15466.
    CleanExi HS_NR0B2.
    Genevestigatori Q15466.

    Family and domain databases

    Gene3Di 1.10.565.10. 1 hit.
    InterProi IPR008946. Nucl_hormone_rcpt_ligand-bd.
    IPR000536. Nucl_hrmn_rcpt_lig-bd_core.
    IPR001723. Str_hrmn_rcpt.
    [Graphical view ]
    Pfami PF00104. Hormone_recep. 1 hit.
    [Graphical view ]
    PRINTSi PR00398. STRDHORMONER.
    SMARTi SM00430. HOLI. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48508. SSF48508. 1 hit.
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 138 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