Affinage

NR0B2

Nuclear receptor subfamily 0 group B member 2 · UniProt Q15466

Length
257 aa
Mass
28.1 kDa
Annotated
2026-06-10
100 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NR0B2/SHP is an atypical, inducible nuclear receptor that functions principally as a transcriptional corepressor, lacking a conventional DNA-binding domain while retaining a receptor-interaction region and an autonomous C-terminal repressor domain (PMID:9372944). It silences target genes by directly binding the ligand-binding domains of partner nuclear receptors through LxxLL-related motifs (NR boxes) that occupy the same hydrophobic coactivator groove, thereby competing out coactivators—demonstrated structurally for androgen receptor, where SHP NR Box 2 docks into the AR-LBD groove used by FHL2 and TIF2 (PMID:11735420, PMID:18007036). SHP enforces repression by recruiting histone deacetylases, forming ternary complexes with target receptors and HDAC1/HDAC3 that can be reversed pharmacologically with the HDAC inhibitor TSA (PMID:15835920, PMID:20516075). Beyond classical receptor binding, SHP engages non-receptor partners: a crystal structure with EID1 revealed a second, N-terminal interaction surface mimicking helix H1 of the nuclear receptor LBD, distinct from the C-terminal cofactor site (PMID:24379397), and SHP also partners with SMILE and FOXA1 to modulate repression in a cell-type- and tissue-specific manner (PMID:18657049, PMID:25701738). As an FGF/FXR-inducible factor—its own transcription driven by FXR through chromatin-looping FXR response elements (PMID:20444884)—SHP integrates into bile acid and lipid metabolic control, repressing LRH-1-driven CYP7A1 and bile acid synthesis (PMID:11907135) and suppressing one-carbon and lipid genes (Dnmt1, Pemt, Gnmt) by antagonizing ERRγ, MTF-1, and AhR (PMID:21459093, PMID:22362755, PMID:29416063). SHP additionally possesses a cytoplasmic apoptotic function: upon pharmacological induction it translocates to mitochondria, binds Bcl-2, disrupts Bcl-2/Bid interaction, and triggers cytochrome c release (PMID:20065042). Missense mutations (G93D, R38H, K170N) that impair repressor activity or nuclear translocation establish specific residues required for SHP function (PMID:20516075, PMID:15459958).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1997 High

    Established SHP as a structurally unconventional nuclear receptor—lacking a DNA-binding domain but carrying distinct receptor-interaction and repressor modules—reframing how it could act on transcription.

    Evidence Domain mapping by yeast/mammalian two-hybrid and in vitro binding with transactivation assays

    PMID:9372944

    Open questions at the time
    • Mechanism of repression (cofactor recruitment) not yet defined
    • Physiological target genes unidentified
  2. 1998 High

    Defined the gene's two-exon structure, chromosomal location, and tissue-restricted expression, anchoring SHP in liver, adrenal, and intestinal biology.

    Evidence Genomic library screening, FISH, primer extension, promoter assays

    PMID:9603951

    Open questions at the time
    • Does not establish the upstream signals controlling tissue-specific induction
  3. 2001 High

    Showed SHP represses androgen receptor by competing with coactivators via LxxLL motifs, extending its corepressor role to steroid hormone signaling.

    Evidence Two-hybrid, GST pull-down, Co-IP, reporter and coactivator competition assays

    PMID:11735420

    Open questions at the time
    • Structural basis of competition not yet resolved
    • Did not address downstream effector recruitment
  4. 2002 Medium

    Placed SHP in the FXR-bile acid feedback loop, where it represses LRH-1 to shut down CYP7A1 and bile acid synthesis.

    Evidence Reporter assays and Co-IP summarized in a review of primary data

    PMID:11907135

    Open questions at the time
    • Summarized from review rather than primary data
    • Chromatin-level mechanism on CYP7A1 not detailed here
  5. 2004 Medium

    Demonstrated that a single residue (G93) is required for SHP repression of HNF-4α, linking specific structure to repressor output.

    Evidence Mutation analysis and reporter assays in MIN6-m9 and HepG2 cells

    PMID:15459958

    Open questions at the time
    • Functional assay in cell lines only; in vivo consequence not tested
    • Single lab
  6. 2005 High

    Identified HDAC recruitment as the effector mechanism of SHP repression, mapping repressive subdomains and showing AR/SHP/HDAC1 ternary complex formation reversible by TSA.

    Evidence GST pull-down, Co-IP, reporter assays, TSA inhibition, deletion mapping

    PMID:15835920

    Open questions at the time
    • Whether HDAC recruitment is universal across all SHP target receptors not established
    • Additional corepressor partners not excluded
  7. 2006 Medium

    Showed SHP can homodimerize and heterodimerize with DAX1, with ligand-activated ERα dissociating SHP homodimers, adding a dimerization layer to its regulation.

    Evidence Co-IP, mammalian two-hybrid, fractionation, BRET in mammalian cells

    PMID:16709599

    Open questions at the time
    • Functional consequence of homo- vs heterodimer not resolved
    • Single lab
  8. 2008 High

    Identified SMILE as a SHP partner that tunes SHP repression of ERα in a cell-type-specific manner, expanding the non-receptor partner repertoire.

    Evidence Yeast two-hybrid, Co-IP, co-localization, siRNA, reporter, domain mapping

    PMID:18657049

    Open questions at the time
    • Structural basis of SHP-SMILE interaction unresolved
    • In vivo relevance not tested
  9. 2009 High

    Revealed that SHP can indirectly activate gene expression through a dual-inhibitory ERRγ→YY1→AP1 cascade driving miR-206, showing its repression can yield net activation downstream.

    Evidence Microarray, qPCR, RACE, reporter, ChIP, siLP, forced expression

    PMID:19721712

    Open questions at the time
    • Physiological context of miR-206 regulation by SHP not defined
  10. 2010 Medium

    Established a cytoplasmic, mitochondrial apoptotic function for SHP via Bcl-2 binding and cytochrome c release, distinct from its nuclear corepressor role.

    Evidence Co-IP, fractionation, confocal imaging, cytochrome c release, tumor growth assays with AHPN induction

    PMID:20065042

    Open questions at the time
    • Signal triggering nuclear-to-mitochondrial translocation incompletely defined
    • Single lab
  11. 2010 High

    Mapped how disease-associated residues (R38H, K170N, G171A) control SHP nuclear translocation, acetylation, stability, and target-selective repression, connecting residue chemistry to function.

    Evidence Mutant expression, translocation/ubiquitination/acetylation assays, ChIP, reporter, molecular dynamics

    PMID:20516075

    Open questions at the time
    • Why repression of LRH-1 is spared by K170N not mechanistically explained
  12. 2010 High

    Defined how SHP's own transcription is amplified by FXR through two response elements brought together by chromatin looping, explaining its rapid inducibility.

    Evidence ChIP-seq, ChIP-qPCR, reporter, mutagenesis, 3C chromatin conformation capture

    PMID:20444884

    Open questions at the time
    • Looping factors mediating the FXRRE interaction not identified
  13. 2011 High

    Showed SHP controls DNA methylation machinery by repressing Dnmt1 through ERRγ antagonism, confirmed in KO and transgenic mice.

    Evidence Reporter, ChIP, Co-IP, SHP-KO and SHP-transgenic mice, Western blot

    PMID:21459093

    Open questions at the time
    • Downstream methylation targets affected not catalogued
  14. 2012 High

    Extended SHP's Dnmt1 control to antagonism of the metal-responsive factor MTF-1, showing it integrates zinc signaling into epigenetic regulation.

    Evidence Reporter, ChIP, Co-IP, SHP-KO and transgenic mice, Western blot

    PMID:22362755

    Open questions at the time
    • Direct vs indirect repression of MTF-1 not fully separated
  15. 2013 High

    Solved a crystal structure of SHP bound to EID1, revealing a non-canonical N-terminal interaction surface distinct from the classical H12 cofactor site.

    Evidence X-ray crystallography, mutagenesis, in vitro binding, reporter assay

    PMID:24379397

    Open questions at the time
    • Whether other partners use this same N-terminal site not established
  16. 2014 High

    Provided a structural view of how SHP NR Box 2 occupies the AR coactivator groove, explaining coactivator competition at atomic resolution.

    Evidence X-ray crystallography of AR-LBD/SHP peptide complex, structural comparison

    PMID:18007036

    Open questions at the time
    • Contribution of NR Box 1 and N-terminal contacts to full-length binding not captured in peptide co-crystal
  17. 2014 Medium

    Linked SHP to NF-κB-driven apoptosis, showing p65 recruits SHP to the PDCD5 promoter to promote a pro-apoptotic program.

    Evidence ChIP-on-chip, ChIP, Co-IP, reporter, siRNA, overexpression, Western blot

    PMID:24343129

    Open questions at the time
    • Whether SHP activates or represses PDCD5 in this context not fully clarified
    • Single lab
  18. 2014 Medium

    Placed Nr0b2 under hypothalamo-pituitary control via LH/CG-PKA-AMPK signaling in Leydig cells, mediating testosterone repression and germ cell apoptosis.

    Evidence NR0B2-null mice, PKA/AMPK inhibitors, hormone treatment, testosterone measurement, TUNEL

    PMID:25426871

    Open questions at the time
    • Direct SHP target genes in steroidogenesis not mapped
    • Single lab
  19. 2015 High

    Showed SHP interacts with FOXA1 to impose circadian, oscillatory control over homocysteine metabolism genes, protecting against hyperhomocysteinemia.

    Evidence RNA-seq, metabolomics, ChIP, immunoblot, SHP-null mice, time-course sampling

    PMID:25701738

    Open questions at the time
    • Mechanism coupling SHP to circadian clock inputs not detailed
  20. 2018 High

    Demonstrated SHP, induced by FGF15 in the late fed state, antagonizes AhR-driven Pemt/Gnmt one-carbon gene induction, positioning SHP as a temporal switch in hepatic lipid/methyl metabolism.

    Evidence SHP-null mice, adenoviral overexpression/rescue, ChIP, reporter, metabolomics

    PMID:29416063

    Open questions at the time
    • Direct SHP-AhR physical contact vs competition for promoter not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SHP's nuclear corepressor activity and its cytoplasmic mitochondrial pro-apoptotic function are coordinated, and what signals govern its subcellular partitioning, remains unresolved.
  • Translocation signal and trigger not defined
  • Integration of metabolic, apoptotic, and circadian roles within single cells unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0140313 molecular sequestering activity 1
Localization
GO:0005634 nucleus 2 GO:0005739 mitochondrion 1 GO:0005829 cytosol 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-74160 Gene expression (Transcription) 3 GO:0140110 transcription regulator activity 2 R-HSA-5357801 Programmed Cell Death 2
Partners
AREID1ERRGFOXA1HDAC1HNF4ALRH-1RXRA

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 SHP (NR0B2) lacks a conventional DNA-binding domain but contains novel receptor interaction and repressor domains. The central region (amino acids 92–148) mediates interaction with RXRα, thyroid hormone receptor, and retinoic acid receptor; the C-terminal region constitutes an autonomous repressor domain distinct from N-CoR-binding sequences. SHP did not interact with N-CoR in yeast or mammalian two-hybrid systems. Mammalian two-hybrid, yeast two-hybrid, in vitro binding (deletion and domain mapping), transient transfection repressor assays Molecular and cellular biology High 9372944
1998 The SHP gene (Nr0b2) is composed of two exons with a single intron; it is located at human chromosome 1p36.1. Tissue-specific expression is highest in fetal liver, fetal adrenal gland, adult spleen, and adult small intestine, and promoter activity is higher in adrenal-derived cells than HeLa cells. Genomic library screening, Southern blot, FISH, primer extension, transient transfection promoter assay The Journal of biological chemistry High 9603951
2001 SHP inhibits androgen receptor (AR)-mediated transcription by up to 97%. Interaction requires AR ligand and is mediated by SHP LxxLL (LXXI/LL) motifs binding the AR ligand-binding domain (AR-LBD). SHP also interacts with the AR N-terminal domain (AR-NTD), stabilizing the overall AR–SHP interaction. SHP competes with AR coactivators (FHL2, TIF2) and inhibits both AR-LBD- and AR-NTD-dependent transactivation. Mammalian two-hybrid, GST pull-down, co-immunoprecipitation, luciferase reporter transactivation assay, competition with coactivators Biochemistry High 11735420
2002 FXR activation induces SHP expression, and increased SHP protein associates with LRH-1 (liver receptor homolog-1), an obligate transcriptional activator of CYP7A1 (cholesterol-7α-hydroxylase), thereby repressing CYP7A1 expression and bile acid synthesis. Transient transfection reporter assays, co-immunoprecipitation, cited functional studies Journal of lipid research Medium 11907135
2005 SHP represses transcription by recruiting histone deacetylases (HDACs). Two core repressive domains were mapped to amino acids 170–210 and 210–240 of SHP. SHP directly interacts with HDAC1, and SHP, AR, and HDAC1 form a ternary complex. HDAC inhibitor trichostatin A (TSA) reverses SHP-mediated repression of both AR and ERα transactivation. GST pull-down, co-immunoprecipitation, luciferase reporter assays, TSA pharmacological inhibition, deletion mapping Biochemistry High 15835920
2005 SHP (NR0B2) acts as an inducible, tissue-specific transcriptional corepressor by directly binding multiple nuclear receptors through its LxxLL-related motifs and suppressing their transactivation. SHP lacks a DNA-binding domain but retains a ligand-binding domain-like region. Review synthesizing two-hybrid, Co-IP, reporter, and in vivo data from multiple primary studies Trends in endocrinology and metabolism: TEM Medium 16275121
2006 DAX1 (NR0B1) and SHP (NR0B2) form individual homodimers as well as DAX1–SHP heterodimers in the nucleus of mammalian cells. DAX1 homodimerization involves LXXLL motifs and the AF-2 domain; SHP homodimers dissociate upon heterodimerization with ligand-activated ERα. DAX1–SHP heterodimerization also involves the LXXLL motifs and AF-2 domain of DAX1. Co-immunoprecipitation, mammalian two-hybrid, subcellular fractionation/localization, BRET assays Molecular endocrinology (Baltimore, Md.) Medium 16709599
2008 SMILE (SHP-interacting leucine zipper protein) was identified as a new SHP-interacting protein. The N-terminus of SHP and the middle region of SMILE-L mediate their interaction. SMILE isoforms regulate SHP-dependent repression of estrogen receptor transactivation in a cell-type-specific manner; in breast cancer cell lines, SMILE enhances SHP repression of ERα and downregulates ERα-target E2F1 expression. Yeast two-hybrid, co-immunoprecipitation, co-localization (immunofluorescence), siRNA knockdown, adenoviral overexpression, reporter assays, domain-mapping mutagenesis The Biochemical journal High 18657049
2009 SHP activates miR-206 expression through a cascade dual-inhibitory mechanism: SHP inhibits ERRγ transcriptional activity, leading to decreased YY1 expression; reduced YY1 de-represses AP1 (c-Jun/c-Fos) activity, which then activates the miR-206 promoter. ChIP confirmed physical association of AP1 (c-Jun), YY1, and ERRγ with respective promoters. Microarray, real-time PCR, RACE, luciferase reporter assay, ChIP, siRNA knockdown, forced expression PloS one High 19721712
2010 SHP (NR0B2) has a cytoplasmic function: it localizes to mitochondria where it binds Bcl-2, disrupts Bcl-2/Bid interaction, and induces cytochrome c release and apoptosis. AHPN promotes SHP translocation from nucleus to mitochondria. SHP activation inhibits peritoneal pancreatic tumor growth. Co-immunoprecipitation, subcellular fractionation, confocal microscopy, cytochrome c release assay, tumor growth assay, pharmacological induction (AHPN) Molecular and cellular biology Medium 20065042
2010 Two novel missense mutations of SHP (R38H, K170N) impair nuclear translocation. K170N makes SHP more susceptible to ubiquitin-mediated degradation, blocks SHP acetylation, and abolishes repressive activity on ERRγ and HNF4α but not LRH-1. G171A stabilizes nuclear receptor boxes. K170N impairs recruitment of SHP, HNF4α, HDAC1, and HDAC3 to the apoCIII promoter. Molecular dynamics simulations show G171A stabilizes and K170N destabilizes structural elements of the receptor. Mutant expression, nuclear translocation assay, ubiquitination assay, acetylation assay, reporter assays, ChIP, molecular dynamics simulation The Journal of biological chemistry High 20516075
2010 FXR activates SHP (Nr0b2) transcription through two FXR response elements (FXRREs): one in the proximal promoter and a novel one in the 3'-enhancer region. These two FXRREs interact via head-to-tail chromatin looping to increase SHP transcription efficiency. ChIP-seq, ChIP-qPCR, luciferase reporter assay, site-directed mutagenesis, chromatin conformation capture (3C) assay Molecular endocrinology (Baltimore, Md.) High 20444884
2011 SHP represses Dnmt1 expression by inhibiting ERRγ transactivation; ERRγ binds directly to ERE1/ERE2 response elements in the Dnmt1 promoter and activates transcription, while SHP diminishes ERRγ recruitment and shifts local chromatin to an inactive conformation. SHP-knockout mice show increased Dnmt1 expression; SHP-transgenic mice show decreased Dnmt1. Reporter assays, ChIP, co-immunoprecipitation, SHP-KO and SHP-transgenic mouse models, Western blot FEBS letters High 21459093
2012 SHP inhibits zinc-induced Dnmt1 expression by antagonizing MTF-1 (metal-responsive transcription factor-1). Zinc induces MTF-1 occupancy on the Dnmt1 promoter; SHP represses MTF-1 expression and abolishes zinc-mediated chromatin changes at the Dnmt1 promoter. SHP-KO mice have increased Dnmt1; SHP-transgenic mice have decreased Dnmt1. Reporter assays, ChIP, co-immunoprecipitation, SHP-KO and SHP-transgenic mice, Western blot Nucleic acids research High 22362755
2013 Crystal structure of SHP in complex with EID1 reveals an unexpected binding site at the N-terminus of the receptor (mimicking helix H1 of the nuclear receptor LBD), distinct from the classical C-terminal H12 cofactor-binding site. Mutations at the SHP–EID1 interface diminish their interaction and reduce SHP repressor activity. X-ray crystallography, mutagenesis, in vitro binding, reporter assay Proceedings of the National Academy of Sciences of the United States of America High 24379397
2004 G93D missense mutation of SHP (NR0B2) shows reduced in vitro inhibition of HNF-4α transactivation of the HNF-1α promoter when expressed in MIN6-m9 and HepG2 cells, demonstrating that the G93 residue contributes to SHP repressor function. SSCP/heteroduplex mutation analysis, transient transfection reporter assay in MIN6-m9 and HepG2 cells Human mutation Medium 15459958
2007 Crystal structure of the AR ligand-binding domain in complex with a 14-mer peptide from SHP NR Box 2 (LKKIL motif) reveals that SHP binds the same hydrophobic groove on AR used by coactivators. Only NR Box 2 of SHP formed a crystal complex with AR-LBD under the conditions tested, and SHP inhibits AR by competing with coactivators at this site. X-ray crystallography (AR-LBD/SHP peptide co-crystal), structural comparison with coactivator-bound AR complexes Acta crystallographica. Section D, Biological crystallography High 18007036
2015 SHP interacts with FOXA1 to oscillatorily regulate homocysteine metabolism genes (Bhmt, cystathionine γ-lyase). SHP inhibits FOXA1-mediated transcriptional activation of Bhmt and cystathionine γ-lyase, controlling oscillatory production of S-adenosylmethionine, betaine, and related metabolites. SHP-null mice have altered circadian timing of homocysteine metabolism gene expression and are protected from ethanol- and homocysteine-induced hyperhomocysteinemia. RNA-seq, metabolomics, ChIP, immunoblot, SHP-null mouse model, gene expression (qPCR), 24-h light-dark cycle sampling Gastroenterology High 25701738
2018 AhR activates Pemt and Gnmt (one-carbon cycle genes regulating PC/SAM levels) in the early fed state; SHP, activated by FGF15 signaling in the late fed state, blocks this AhR-mediated induction. SHP-null mice fail to suppress AhR-driven Pemt/Gnmt expression, altering PC and SAM levels. Adenoviral AhR in obese mice exacerbates steatosis, and co-expression of SHP blunts this effect. SHP-null mouse model, adenoviral overexpression, ChIP, reporter assays, metabolomic analysis, immunoblot Nature communications High 29416063
2014 NF-κB p65 recruits SHP (NR0B2) to the PDCD5 gene promoter; a SHP/NF-κB p65 complex is found on the PDCD5 gene, and 3-Cl-AHPC-mediated apoptosis increases SHP mRNA/protein and the SHP/p65 interaction. PDCD5 induction triggers apoptosis via increased Bax and cytochrome c release. ChIP-on-chip, ChIP, co-immunoprecipitation, reporter assay, siRNA knockdown, overexpression, Western blot Apoptosis : an international journal on programmed cell death Medium 24343129
2014 LH/CG represses Nr0b2 (SHP) expression in testicular Leydig cells through the protein kinase A–AMP protein kinase (PKA–AMPK) pathway. NR0B2 mediates the repression of testosterone synthesis and subsequent germ cell apoptosis induced by anti-GnRH compounds, establishing a functional link between the hypothalamo-pituitary axis and NR0B2 in testicular androgen metabolism. Transgenic NR0B2-null mouse model, pharmacological pathway inhibitors (PKA, AMPK), hormone treatment, testosterone measurement, TUNEL assay Endocrinology Medium 25426871

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 The 'Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends in biochemical sciences 1015 12826400
1997 Deletion of SHIP or SHP-1 reveals two distinct pathways for inhibitory signaling. Cell 380 9244303
1998 Protein-tyrosine phosphatase Shp-2 regulates cell spreading, migration, and focal adhesion. The Journal of biological chemistry 343 9694867
2009 Activation of PKC-delta and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy. Nature medicine 326 19881493
2009 SHP-1 and SHP-2 in T cells: two phosphatases functioning at many levels. Immunological reviews 304 19290938
1999 Shp-2 tyrosine phosphatase: signaling one cell or many. Experimental cell research 245 10579910
2003 The function of the protein tyrosine phosphatase SHP-1 in cancer. Gene 237 12657462
2006 SHP-2 phosphatase negatively regulates the TRIF adaptor protein-dependent type I interferon and proinflammatory cytokine production. Immunity 207 17157040
2007 The Src homology 2 domain tyrosine phosphatases SHP-1 and SHP-2: diversified control of cell growth, inflammation, and injury. Histology and histopathology 203 17647198
2010 Role of nuclear receptor SHP in metabolism and cancer. Biochimica et biophysica acta 197 20970497
1999 The myeloid-specific sialic acid-binding receptor, CD33, associates with the protein-tyrosine phosphatases, SHP-1 and SHP-2. The Journal of biological chemistry 153 10206955
2020 Interaction of SHP-2 SH2 domains with PD-1 ITSM induces PD-1 dimerization and SHP-2 activation. Communications biology 146 32184441
2005 A SHPing tale: perspectives on the regulation of SHP-1 and SHP-2 tyrosine phosphatases by the C-terminal tail. Cellular signalling 144 16084691
1997 Src kinase activity is regulated by the SHP-1 protein-tyrosine phosphatase. The Journal of biological chemistry 141 9261115
2000 The SHP-2 tyrosine phosphatase: signaling mechanisms and biological functions. Cell research 138 11191350
2002 Regulation of cholesterol-7alpha-hydroxylase: BAREly missing a SHP. Journal of lipid research 130 11907135
2007 Control of CNS cell-fate decisions by SHP-2 and its dysregulation in Noonan syndrome. Neuron 128 17442246
2013 Capillarisin inhibits constitutive and inducible STAT3 activation through induction of SHP-1 and SHP-2 tyrosine phosphatases. Cancer letters 124 24333736
1999 SHP-1 regulates Lck-induced phosphatidylinositol 3-kinase phosphorylation and activity. The Journal of biological chemistry 122 10488096
2005 Transcriptional corepression by SHP: molecular mechanisms and physiological consequences. Trends in endocrinology and metabolism: TEM 118 16275121
1997 Novel receptor interaction and repression domains in the orphan receptor SHP. Molecular and cellular biology 115 9372944
2006 The SHP-1 protein tyrosine phosphatase negatively modulates glucose homeostasis. Nature medicine 112 16617349
2002 Role of the SHP-2 tyrosine phosphatase in cytokine-induced signaling and cellular response. Biochimica et biophysica acta 109 12421673
2013 SHP-1 phosphatase activity counteracts increased T cell receptor affinity. The Journal of clinical investigation 104 23391724
2000 Cytoplasmic protein tyrosine phosphatases SHP-1 and SHP-2: regulators of B cell signal transduction. Current opinion in immunology 103 10781410
1998 Structural determinants of SHP-2 function and specificity in Xenopus mesoderm induction. Molecular and cellular biology 99 9418864
2001 Requirement of Shp-2 tyrosine phosphatase in lymphoid and hematopoietic cell development. Blood 97 11159516
2005 Receptor-stimulated oxidation of SHP-2 promotes T-cell adhesion through SLP-76-ADAP. The EMBO journal 95 15933714
1999 Regulation of acidification and apoptosis by SHP-1 and Bcl-2. The Journal of biological chemistry 95 10506221
2003 Identification of Shp-2 as a Stat5A phosphatase. The Journal of biological chemistry 94 12615921
2004 SHP-2 and myeloid malignancies. Current opinion in hematology 93 14676626
1998 Regulation of angiotensin II-induced JAK2 tyrosine phosphorylation: roles of SHP-1 and SHP-2. The American journal of physiology 93 9814969
1998 Structure and expression of the orphan nuclear receptor SHP gene. The Journal of biological chemistry 90 9603951
2011 Substrate specificity of protein tyrosine phosphatases 1B, RPTPα, SHP-1, and SHP-2. Biochemistry 87 21291263
2010 Nuclear receptor SHP, a death receptor that targets mitochondria, induces apoptosis and inhibits tumor growth. Molecular and cellular biology 85 20065042
2011 SHP-2/PTPN11 mediates gliomagenesis driven by PDGFRA and INK4A/ARF aberrations in mice and humans. The Journal of clinical investigation 75 21393858
2002 Gab1 and SHP-2 promote Ras/MAPK regulation of epidermal growth and differentiation. The Journal of cell biology 75 12370245
2022 SHP-2 and PD-1-SHP-2 signaling regulate myeloid cell differentiation and antitumor responses. Nature immunology 74 36581713
2018 SHP-1 Acts as a Tumor Suppressor in Hepatocarcinogenesis and HCC Progression. Cancer research 73 29776962
2001 Characterization of the interaction between androgen receptor and a new transcriptional inhibitor, SHP. Biochemistry 70 11735420
1997 Downregulated expression of SHP-1 in Burkitt lymphomas and germinal center B lymphocytes. The Journal of experimental medicine 62 9348315
2011 SHP-1 in cell-cycle regulation. Anti-cancer agents in medicinal chemistry 61 21291405
2005 Heme transfer from streptococcal cell surface protein Shp to HtsA of transporter HtsABC. Infection and immunity 60 16041024
2002 SHP-1 regulates Fcgamma receptor-mediated phagocytosis and the activation of RAC. Blood 59 12176909
2000 The protein-tyrosine phosphatase SHP-1 binds to and dephosphorylates p120 catenin. The Journal of biological chemistry 58 10835420
2006 Sequence specificity of SHP-1 and SHP-2 Src homology 2 domains. Critical roles of residues beyond the pY+3 position. The Journal of biological chemistry 56 16702225
2018 AhR and SHP regulate phosphatidylcholine and S-adenosylmethionine levels in the one-carbon cycle. Nature communications 53 29416063
2018 Large-Scale Phosphoproteomics Reveals Shp-2 Phosphatase-Dependent Regulators of Pdgf Receptor Signaling. Cell reports 53 29514104
2018 SHP-1 regulates hematopoietic stem cell quiescence by coordinating TGF-β signaling. The Journal of experimental medicine 51 29669741
2014 SHP-1 plays a crucial role in CD40 signaling reciprocity. Journal of immunology (Baltimore, Md. : 1950) 51 25187664
2017 Alteration of SHP-1/p-STAT3 Signaling: A Potential Target for Anticancer Therapy. International journal of molecular sciences 48 28594363
2015 Interactions Between Nuclear Receptor SHP and FOXA1 Maintain Oscillatory Homocysteine Homeostasis in Mice. Gastroenterology 48 25701738
2005 SHP represses transcriptional activity via recruitment of histone deacetylases. Biochemistry 47 15835920
2019 SHP-2 in Lymphocytes' Cytokine and Inhibitory Receptor Signaling. Frontiers in immunology 46 31708921
2014 SHP-1 is a target of regorafenib in colorectal cancer. Oncotarget 46 25071018
2020 Nrf2-SHP Cascade-Mediated STAT3 Inactivation Contributes to AMPK-Driven Protection Against Endotoxic Inflammation. Frontiers in immunology 44 32210977
2009 Nuclear receptor SHP activates miR-206 expression via a cascade dual inhibitory mechanism. PloS one 44 19721712
2016 SHP-1: the next checkpoint target for cancer immunotherapy? Biochemical Society transactions 43 27068940
2008 SMILE, a new orphan nuclear receptor SHP-interacting protein, regulates SHP-repressed estrogen receptor transactivation. The Biochemical journal 43 18657049
2010 Novel polymorphisms of nuclear receptor SHP associated with functional and structural changes. The Journal of biological chemistry 42 20516075
2012 Intravenous immunoglobulins modulate neutrophil activation and vascular injury through FcγRIII and SHP-1. Circulation research 39 22415018
2010 Deficient SOCS3 and SHP-1 expression in psoriatic T cells. The Journal of investigative dermatology 37 20130595
2010 Farnesoid X receptor activation mediates head-to-tail chromatin looping in the Nr0b2 gene encoding small heterodimer partner. Molecular endocrinology (Baltimore, Md.) 37 20444884
2009 SHP-2 expression negatively regulates NK cell function. Journal of immunology (Baltimore, Md. : 1950) 37 19915046
2004 FLT3/ITD mutation signaling includes suppression of SHP-1. The Journal of biological chemistry 37 15574429
1999 Tyrosine phosphorylation and association of BIT with SHP-2 induced by neurotrophins. Journal of neurochemistry 37 10098842
2023 Diosgenin attenuates nonalcoholic hepatic steatosis through the hepatic FXR-SHP-SREBP1C/PPARα/CD36 pathway. European journal of pharmacology 36 37263401
2021 Luteolin alleviates ulcerative colitis through SHP-1/STAT3 pathway. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 36 34014331
2013 Expression of SHP-1 induced by hyperglycemia prevents insulin actions in podocytes. American journal of physiology. Endocrinology and metabolism 33 23531619
2023 Macrophage-derived SHP-2 inhibits the metastasis of colorectal cancer via Tie2-PI3K signals. Oncology research 32 37304233
2013 Expression and clinical significance of tyrosine phosphatase SHP-2 in colon cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 32 24439672
2011 Nuclear receptor SHP inhibition of Dnmt1 expression via ERRγ. FEBS letters 32 21459093
2010 Overexpression of nuclear receptor SHP in adipose tissues affects diet-induced obesity and adaptive thermogenesis. American journal of physiology. Endocrinology and metabolism 32 20124506
2005 RNA interference targeting SHP-1 attenuates myocardial infarction in rats. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 32 16223786
2019 Targeting PDGFRα-activated glioblastoma through specific inhibition of SHP-2-mediated signaling. Neuro-oncology 31 31232447
2019 Regulation of peripheral and central immunity: Understanding the role of Src homology 2 domain-containing tyrosine phosphatases, SHP-1 & SHP-2. Immunobiology 31 31561841
2007 SHP-2 is required for the maintenance of cardiac progenitors. Development (Cambridge, England) 30 17928416
2003 SHP-1: a regulator of neutrophil apoptosis. Seminars in immunology 30 14563118
2021 Dynamic variability in SHP-1 abundance determines natural killer cell responsiveness. Science signaling 29 34752140
2016 Protein kinase D regulates positive selection of CD4+ thymocytes through phosphorylation of SHP-1. Nature communications 29 27670070
2012 Zinc-induced Dnmt1 expression involves antagonism between MTF-1 and nuclear receptor SHP. Nucleic acids research 29 22362755
2011 Ligand-independent actions of the orphan receptors/corepressors DAX-1 and SHP in metabolism, reproduction and disease. The Journal of steroid biochemistry and molecular biology 28 21550402
2006 Dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX1) (NR0B1) and small heterodimer partner (SHP) (NR0B2) form homodimers individually, as well as DAX1-SHP heterodimers. Molecular endocrinology (Baltimore, Md.) 28 16709599
2012 The tyrosine phosphatase SHP-1 dampens murine Th17 development. Blood 27 22438258
2022 SKAP2 suppresses inflammation-mediated tumorigenesis by regulating SHP-1 and SHP-2. Oncogene 26 35034964
2021 SHP-1/STAT3 Interaction Is Related to Luteolin-Induced Myocardial Ischemia Protection. Inflammation 26 34460026
2013 Structural insights into gene repression by the orphan nuclear receptor SHP. Proceedings of the National Academy of Sciences of the United States of America 26 24379397
2003 Gab1, SHP-2 and other novel regulators of Ras: targets for anticancer drug discovery? Current cancer drug targets 26 12769687
1997 Regulation of cell signaling by the protein tyrosine phosphatases, CD45 and SHP-1. Immunologic research 25 9048211
2014 NF-κB p65 recruited SHP regulates PDCD5-mediated apoptosis in cancer cells. Apoptosis : an international journal on programmed cell death 24 24343129
2023 Epiberberine regulates lipid synthesis through SHP (NR0B2) to improve non-alcoholic steatohepatitis. Biochimica et biophysica acta. Molecular basis of disease 23 36638873
2018 ChREBP Rather Than SHP Regulates Hepatic VLDL Secretion. Nutrients 23 29518948
2016 Akt and SHP-1 are DC-intrinsic checkpoints for tumor immunity. JCI insight 23 27812544
2001 SHP-2 complex formation with the SHP-2 substrate-1 during C2C12 myogenesis. Journal of cell science 23 11493654
2020 Regulation of autoimmune arthritis by the SHP-1 tyrosine phosphatase. Arthritis research & therapy 22 32586377
2012 The protein tyrosine phosphatase SHP-1 regulates phagolysosome biogenesis. Journal of immunology (Baltimore, Md. : 1950) 22 22826316
2004 Mutation analysis of NR0B2 among 1545 Danish men identifies a novel c.278G>A (p.G93D) variant with reduced functional activity. Human mutation 22 15459958
2014 SHP-2 regulates growth factor dependent vascular signalling and function. Mini reviews in medicinal chemistry 21 22512561
2014 Identification of the link between the hypothalamo-pituitary axis and the testicular orphan nuclear receptor NR0B2 in adult male mice. Endocrinology 21 25426871
2007 Interaction between the androgen receptor and a segment of its corepressor SHP. Acta crystallographica. Section D, Biological crystallography 21 18007036

Missed literature

Know a paper Affinage missed for NR0B2? Flag it for the maintainers and the community.

No submissions yet.