Affinage

SH2B1

SH2B adapter protein 1 · UniProt Q9NRF2

Length
756 aa
Mass
79.4 kDa
Annotated
2026-06-10
100 papers in source corpus 44 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SH2B1 is a multidomain adaptor protein that amplifies signaling from receptor and cytoplasmic tyrosine kinases to govern energy balance, glucose homeostasis, and neuronal differentiation (PMID:16098827, PMID:15314154, PMID:10187854). Its SH2 domain docks at a defined phosphotyrosine on its kinase targets — JAK2 pTyr813, recognized through canonical SH2-phosphopeptide contacts that select for Glu at +1 and a hydrophobic residue at +3 (PMID:15121872, PMID:16824542) — and this engagement stimulates kinase activity, whereas a separate pTyr813-independent contact on non-phosphorylated JAK2 holds basal activity in check, giving SH2B1 bidirectional control (PMID:17565041, PMID:16914724). An N-terminal dimerization domain drives homo- and heterodimerization that juxtaposes two JAK2 molecules for transactivation (PMID:15767667), and the same SH2 module enhances the insulin receptor, TrkA, FGFR3, and EPO-R, with SH2B1 acting as a positive regulator of insulin and neurotrophin receptors but a negative regulator of EPO-R (PMID:15314154, PMID:10187854, PMID:11827956, PMID:22669948). Downstream of leptin and insulin, SH2B1 recruits IRS1 and IRS2 into JAK2/receptor complexes and protects them from dephosphorylation, thereby amplifying PI3K/Akt output (PMID:15316008, PMID:19542202). In the central nervous system, neuronal SH2B1 is the critical site for whole-body energy and glucose homeostasis: neuron-specific transgenic rescue corrects the obesity and insulin resistance of SH2B1-null mice in an SH2-domain-dependent manner (PMID:17235396, PMID:20484460), and hypothalamic SH2B1 drives leptin-stimulated sympathetic activation and brown adipose thermogenesis (PMID:32251290). The PH domain is independently required for full metabolic function in vivo (PMID:31439647). Beyond metabolism, SH2B1 promotes neurite outgrowth and filopodium formation through partners including IRSp53 (PMID:25586189), requires constitutive nucleocytoplasmic shuttling for its pro-differentiation activity (PMID:15082760), supports peripheral myelination by maintaining cytohesin-2 Tyr381 phosphorylation in Schwann cells (PMID:35077201), facilitates HSC70-dependent lysosomal degradation of PLIN4 to limit lipid peroxidation (PMID:35390677), and modulates chromatin state and MyoD occupancy during myogenesis (PMID:28039048). Distinct isoforms diverge functionally, with the brain-enriched SH2B1delta localizing to nucleoli (PMID:35019135) and the alpha/delta isoforms regulating food intake through a leptin-independent route (PMID:33214137).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 High

    Established that SH2-Bbeta is a kinase-engaging adaptor in neurotrophin signaling, the first link to neuronal differentiation, answering whether it physically and functionally couples to an activated receptor tyrosine kinase.

    Evidence GST pulldown, Co-IP, and dominant-negative R555E in NGF-stimulated PC12 cells with neurite outgrowth readout

    PMID:10187854

    Open questions at the time
    • Did not define the JAK2 docking site or quantify direct kinase stimulation
    • Mechanism of how binding enhances outgrowth left open
  2. 1999 Medium

    Showed that SH2B1 engagement is not limited to neurotrophin receptors by mapping its insulin receptor interaction to an activation-loop phosphotyrosine, broadening the receptor repertoire.

    Evidence In vitro binding with IR kinase domain phosphopeptides; splice-variant (gamma) characterization

    PMID:10594240

    Open questions at the time
    • No cellular or in vivo confirmation in this study
    • Functional consequence for IR signaling not yet tested
  3. 2001 Medium

    Defined the N-terminal multimerization domain as a structural requirement for kinase enhancement and revealed isoform/paralog selectivity, answering how SH2B proteins might assemble functional units.

    Evidence Gel filtration/native PAGE for pentamer state plus deletion mutants with TrkA autophosphorylation; JAK1/2/3 isoform-selective kinase assays

    PMID:11238898 PMID:11751854

    Open questions at the time
    • Stoichiometry at endogenous levels unresolved
    • Distinct regulatory roles of SH2B1 vs APS on JAKs mechanistically unexplained
  4. 2004 High

    Identified JAK2 pTyr813 as the SH2 docking site and the JAK2/SH2B1/IRS tertiary complex as the mechanism amplifying PI3K/Akt, converting an adaptor observation into a defined molecular circuit.

    Evidence 2D phosphopeptide mapping and JAK2 Y813 mutants; Co-IP, in vitro binding, and KO MEF rescue for IRS1/2 recruitment; tissue-specific KO insulin receptor readouts

    PMID:15121872 PMID:15314154 PMID:15316008

    Open questions at the time
    • How SH2 docking allosterically increases kinase activity not resolved at atomic level
    • Relative contributions across receptors in vivo not separated
  5. 2005 High

    Connected the molecular adaptor function to physiology by showing SH2B1 is an endogenous enhancer of leptin sensitivity, and that dimerization transactivates JAK2 — explaining how loss causes obesity.

    Evidence SH2-B knockout mice with hypothalamic JAK2/STAT3/IRS2 readouts and PTP1B competition; yeast two-hybrid and concentration-dependent JAK2 kinase assays

    PMID:15767667 PMID:16098827

    Open questions at the time
    • Cell type within hypothalamus not yet pinpointed
    • Biphasic concentration dependence of activation not validated in vivo
  6. 2006 High

    Provided structural and mutational definition of the SH2-pTyr813 interface and the dual positive/negative regulation of JAK2, resolving how one adaptor both inhibits basal and enhances activated kinase.

    Evidence 2.35 A crystal structure of SH2 domain with JAK2 pTyr813 peptide; JAK2 truncation/point mutants in kinase assays; biochemical SH2B1 vs APS specificity

    PMID:16824542 PMID:16914724

    Open questions at the time
    • Structure of full-length protein or kinase complex not determined
    • Conformational basis of inhibitory contact not visualized
  7. 2007 High

    Localized the metabolically essential pool of SH2B1 to neurons via genetic rescue, and dissected the two-mode JAK2 regulation in cells, establishing where and how SH2B1 controls energy balance.

    Evidence Neuron-specific transgenic rescue of KO mice with metabolic phenotyping; JAK2 Y813F and SH2B1 domain mutants by Co-IP; SH2B2beta inhibitory isoform pulldowns

    PMID:17204555 PMID:17235396 PMID:17565041

    Open questions at the time
    • Specific neuronal population not defined
    • Endogenous role of inhibitory SH2B2beta isoform in vivo untested
  8. 2009 High

    Separated the peripheral, insulin-sensitizing arm of SH2B1 function and showed direct stimulation of the insulin receptor plus protection of IRS proteins from phosphatases, refining the in vivo division of labor.

    Evidence Tissue-specific TgKO mice on high-fat diet; reconstituted in vitro IR kinase and dephosphorylation assays with purified SH2B1 and domain mutants

    PMID:19542202

    Open questions at the time
    • Phosphatases protected against not identified
    • Relative weight of central vs peripheral contribution to glucose control not quantified
  9. 2010 High

    Defined the downstream physiological circuit (SNS/BAT/thermogenesis) and showed the SH2 domain is required in vivo, linking the molecular docking mechanism to whole-organism thermogenic output.

    Evidence LepR-neuron-specific KO and hypothalamic AAV overexpression with sympathetic nerve recording; SH2-domain mutant (R555E) transgenic rescue and dominant-negative metabolic phenotyping

    PMID:20484460 PMID:32251290

    Open questions at the time
    • Molecular targets coupling neuronal SH2B1 to SNS output not identified
    • How dominant-negative R555E acts at endogenous loci unclear
  10. 2013 Medium

    Extended SH2B1 function to beta-cell survival, insulin secretion, and lipid/VLDL metabolism, and identified an IRS2 stabilization mechanism, broadening its metabolic mechanism beyond signal amplification.

    Evidence Pancreas- and hepatocyte-specific KO mice; INS-1 knockdown/overexpression; insulin promoter-luciferase and Pdx1 ChIP; SH2B1/IRS2/JAK2 complex Co-IP and IRS2 ubiquitination assay; Drosophila Lnk epistasis and FRET

    PMID:23590848 PMID:24150605 PMID:24358267 PMID:24645678 PMID:27217487

    Open questions at the time
    • Ubiquitin ligase acting on IRS2 not identified
    • Tissue-specific mechanisms not unified into a single model
  11. 2018 Medium

    Resolved domain- and isoform-specific control of SH2B1, including the inhibitory alpha tail and PH domain requirement, explaining how splice variants tune adaptor output.

    Evidence Tyr753 alpha-tail mutant analysis in PC12 cells; PH-domain knockin mice (P322S, deltaPR) with metabolic phenotyping; high-resolution SH2 structure with ITC

    PMID:29127727 PMID:29229648 PMID:31439647

    Open questions at the time
    • PH domain ligand/lipid specificity not defined
    • How conformational plasticity selects ligands in cells untested
  12. 2022 High

    Uncovered kinase-independent and non-metabolic mechanisms — Schwann cell myelination via cytohesin-2 phosphorylation, HSC70-dependent PLIN4 degradation, and nucleolar isoform targeting — expanding SH2B1 beyond receptor signaling.

    Evidence Schwann cell-specific KD and cytohesin-2 Y381F knockin mice with Arf6 assays; SH2B1-HSC70 Co-IP and PLIN4 lysosomal/MPTP models; isoform rescue in KO neurons with nucleolar localization mapping

    PMID:35019135 PMID:35077201 PMID:35390677

    Open questions at the time
    • How SH2B1 directs cytohesin-2 phosphorylation mechanistically unclear
    • Function of nucleolar SH2B1delta localization not defined
  13. 2023 Medium

    Demonstrated cell-type-specific behavioral roles, with hippocampal inhibitory-neuron SH2B1 acting as a negative ERK regulator controlling cognition, refining context-dependent signaling outputs.

    Evidence Cell-type-specific Sh2b1 KO with behavioral battery, single-cell profiling, and ERK-inhibitor pharmacological rescue

    PMID:38434247

    Open questions at the time
    • Direct molecular substrate linking SH2B1 to ERK suppression unidentified
    • Reconciliation with SH2B1's positive role on ERK in neurotrophin signaling unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SH2B1 isoform composition, domain conformation, and ligand selection are integrated to produce opposite (activating vs inhibitory) outputs across tissues and receptors remains the central open question.
  • No full-length structure showing both activating and inhibitory contacts simultaneously
  • Switch determining positive vs negative kinase regulation in vivo undefined
  • Direct substrates/effectors for non-canonical roles (chromatin, nucleolus) not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 5 GO:0042393 histone binding 1
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 2 GO:0005730 nucleolus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1430728 Metabolism 4 R-HSA-162582 Signal Transduction 4
Partners
EPORFGFR3HSPA8IRS1IRS2IRSP53JAK2TRKA

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 SH2B1 (SH2-B) is an endogenous enhancer of leptin sensitivity: genetic deletion in mice severely impairs leptin-stimulated hypothalamic JAK2 activation and STAT3/IRS2 phosphorylation, resulting in hyperphagia and obesity. Overexpression of SH2-B counteracted PTP1B-mediated inhibition of leptin signaling in cultured cells. SH2-B knockout mouse model; in vitro overexpression/PTP1B competition assay; hypothalamic signaling readouts Cell metabolism High 16098827
2004 SH2-B promotes activation of the PI3-kinase pathway downstream of leptin by directly binding IRS1 and IRS2 (via its PH and SH2 domains) and mediating formation of a JAK2/SH2-B/IRS1(or IRS2) tertiary complex, dramatically enhancing leptin-stimulated tyrosine phosphorylation of IRS1/IRS2 and subsequent Akt activation. Deletion of SH2-B gene impaired this phosphorylation in MEFs. Co-immunoprecipitation; in vitro binding; HEK293 overexpression; MEF knockout rescue; SH2-B domain mutants The Journal of biological chemistry High 15316008
2004 SH2-B is a physiological enhancer of insulin receptor activation: systemic deletion of SH2-B impairs insulin receptor activation and signaling (IRS1/IRS2 phosphorylation, PI3K/Akt, ERK1/2) in liver, muscle, and fat. SH2-B directly enhanced autophosphorylation of insulin receptor and tyrosine phosphorylation of IRS1/IRS2 in an SH2 domain-dependent manner in cultured cells. SH2-B knockout mouse; in vitro kinase assay; cultured cell overexpression with domain mutants Molecular and cellular biology High 15314154
2004 JAK2 autophosphorylation on Tyr813 is the critical docking site for the SH2 domain of SH2-Bbeta; phosphorylation of Tyr813 is required for SH2-Bbeta to bind JAK2 and to enhance JAK2 activity and STAT5B activation. The homologous Tyr785 in JAK3 similarly mediates SH2-Bbeta binding and is autophosphorylated in response to IL-2. 2D phosphopeptide mapping; phosphospecific antibody; JAK2 Tyr813 mutants; in vitro kinase assays; Co-IP Molecular and cellular biology High 15121872
2007 SH2B1 regulates leptin/JAK2 signaling by two mechanisms: (1) constitutive binding via non-SH2 domain regions to non-phosphorylated JAK2 inhibits basal JAK2 activity; (2) leptin-stimulated phosphorylation of JAK2 Tyr813 recruits the SH2 domain of SH2B1, which then enhances JAK2 activity. Additionally, SH2B1-IRS1 interaction (independent of Tyr813) facilitates IRS1 phosphorylation by recruiting IRS1 to JAK2. Co-immunoprecipitation; JAK2 Y813F mutants; overexpression in cells; domain deletion mutants Molecular endocrinology High 17565041
2007 Neuron-specific expression of SH2B1beta (using transgenic rescue of SH2B1 knockout mice) is sufficient to correct metabolic disorders including leptin resistance, hyperphagia, obesity, hyperglycemia, and insulin resistance, demonstrating that neuronal SH2B1 is the critical site for whole-body energy and glucose homeostasis. Neuron-specific transgenic rescue of SH2B1 knockout mice (SH2B1TgKO); metabolic phenotyping; hypothalamic JAK2/leptin signaling readouts The Journal of clinical investigation High 17235396
2009 Peripheral SH2B1 enhances insulin sensitivity by two mechanisms: (1) directly stimulating insulin receptor catalytic activity (the SH2 domain is required and sufficient); (2) binding IRS-1 and IRS-2 and protecting them from tyrosine dephosphorylation. Deletion of peripheral SH2B1 in TgKO mice markedly worsens high-fat diet-induced insulin resistance. Tissue-specific KO (TgKO) mice; in vitro insulin receptor kinase assay with purified SH2B1; in vitro dephosphorylation assay; domain deletion mutants; Co-IP Diabetes High 19542202
1999 SH2-Bbeta is required for NGF-induced neuronal differentiation: it binds to TrkA in an SH2 domain-dependent manner (NGF stimulates binding; SH2-Bbeta R555E mutant cannot bind), and overexpression of SH2-Bbeta enhances NGF-induced neurite outgrowth while dominant-negative R555E blocks it. SH2-Bbeta is tyrosyl-phosphorylated in response to NGF. GST pulldown; Co-IP in PC12 cells; GFP-fusion protein overexpression; neurite outgrowth assay; dominant-negative mutant The Journal of biological chemistry High 10187854
2001 SH2-B and APS exist as homopentamers and/or heteropentamers in cells (independent of Trk activation), mediated by the N-terminal multimerization domain. The N-terminal multimerization domain is required for SH2-B to enhance TrkA autophosphorylation magnitude and duration following NGF, and for TrkA/SH2-B-mediated morphological differentiation of PC12 cells. Gel filtration/native PAGE (multimerization); structure-function analysis with deletion mutants; overexpression in PC12 cells; TrkA autophosphorylation assay Molecular and cellular biology High 11238898
2005 Human SH2-B homodimerizes via a unique N-terminal dimerization domain; dimerization brings two JAK2 molecules into proximity for transactivation. At low SH2-B levels, dimerization activates JAK2 by forming JAK2-(SH2-B)2-JAK2 heterotetramers; at high levels, kinase activation is blocked. SH2-B and APS also heterodimerize. Yeast two-hybrid; cellular transfection; in vitro binding; JAK2 kinase activity assays with varying SH2-B concentrations Molecular and cellular biology High 15767667
2006 Crystal structure (2.35 Å) of the SH2 domain of SH2-B in complex with a phosphopeptide from JAK2 pTyr813 reveals canonical SH2 domain-phosphopeptide binding with specific recognition of Glu at +1 and a hydrophobic residue at +3. Biochemical comparison shows SH2-B SH2 domain binds JAK2 preferentially (monomeric state) while APS SH2 domain has higher affinity for the insulin receptor (dimeric state). X-ray crystallography (2.35 Å); in vitro binding assays comparing SH2-B and APS SH2 domains Journal of molecular biology High 16824542
2006 SH2-Bbeta binds JAK2 at multiple sites; binding to pTyr813 is essential for APS (and SH2-Bbeta) to enhance active JAK2. Binding to a pTyr813-independent site on JAK2 inhibits JAK2. SH2-Bbeta-induced increases in JAK2 activity require only the SH2 domain and only one SH2-Bbeta bound to a JAK2 dimer. Residues 809-811 in JAK2 are critical for a regulatory region required for SH2-Bbeta activation. JAK2 truncation and point mutants; in vitro kinase assays; domain deletion analysis Molecular and cellular biology High 16914724
2001 SH2-Bbeta specifically activates JAK2 but not JAK1 or JAK3 when overexpressed. APS negatively regulates JAK2 and JAK1. Endogenous APS is tyrosyl-phosphorylated in response to GH and interferon-gamma. Both SH2-Bbeta and APS bind all three JAKs, but their regulatory roles on JAK activity are distinct. Overexpression in cells; JAK1/2/3 kinase activity assays; endogenous tyrosyl-phosphorylation detection; 3T3-F442A adipocytes The Journal of biological chemistry Medium 11751854
1999 NGF stimulates phosphorylation of SH2-B on multiple serine/threonine residues via kinases downstream of MEK/ERK (ERK1/2 phosphorylate SH2-Bbeta on Ser96 in vitro); MEK inhibitor PD98059 dramatically reduces NGF-promoted serine/threonine phosphorylation. An intact SH2 domain (but not Ser96 alone) is required for full NGF-stimulated serine/threonine phosphorylation. In vitro kinase assay with ERK1/2; MEK inhibitor PD98059; phosphatase treatment; SH2-Bbeta point mutants (S96A, R555E) The Journal of biological chemistry Medium 10473609
1999 SH2-B (SH2-Bgamma isoform) interacts specifically with the insulin receptor, requiring phosphorylation of Tyr1146 in the activation loop triple-tyrosine motif of the IR kinase domain. In vitro binding with phosphopeptides and IR kinase domain; alternative splice variant characterization Mammalian genome Medium 10594240
2002 SH2-Bbeta interacts with FGFR3 via its SH2 domain; two FGFR3 phosphotyrosines (Tyr724 and Tyr760) are required for optimal SH2 domain binding. SH2-Bbeta is tyrosyl-phosphorylated by activated FGFR3. Overexpression of SH2-Bbeta increases FGFR3-stimulated STAT5 phosphorylation and nuclear translocation. Yeast two-hybrid; Co-IP; FGFR3 mutants (N540K, K650E); STAT5 phosphorylation/localization assays The Journal of biological chemistry Medium 11827956
2000 SH2-Bbeta is required for GH-induced actin reorganization (membrane ruffling and pinocytosis) in 3T3-F442A cells. SH2-Bbeta co-localizes with F-actin in GH-induced membrane ruffles. This function requires the SH2 domain and N-terminal regions but is discrete from SH2-Bbeta's role as a JAK2 kinase activator. Cell fractionation; confocal microscopy; overexpression of wild-type and mutant SH2-Bbeta; ruffling and pinocytosis assays The Journal of biological chemistry Medium 10777618
2004 SH2-Bbeta undergoes constitutive nucleocytoplasmic shuttling; a nuclear export sequence (amino acids 224-233) is required for cytoplasmic/plasma membrane access. Nuclear export-defective SH2-Bbeta (L231A/L233A) accumulates in the nucleus and loses the ability to enhance NGF-induced neurite outgrowth, without altering ERK1/2 phosphorylation, indicating cytoplasmic/plasma membrane localization is required for its pro-differentiation function. Leptomycin B nuclear export inhibitor; truncation/point mutants with NES deletion; confocal imaging of GFP-SH2-Bbeta; stable PC12 cell lines; neurite outgrowth assay Molecular and cellular biology High 15082760
2003 SH2-Bbeta positively regulates NGF-mediated activation of the Akt/Forkhead pathway: PC12 cells overexpressing SH2-Bbeta show enhanced and prolonged NGF-induced Akt phosphorylation (Ser473) and activity, and increased phosphorylation of GSK-3 and FKHR/FOXO. Dominant-negative R555E blocks NGF-induced redistribution of FKHR to the cytoplasm and Akt activation. Stable PC12 cell overexpression; Akt kinase activity assay; immunolocalization of FKHR; SH2 domain mutant (R555E) The Journal of biological chemistry Medium 14565960
2007 SH2B2beta, a novel SH2B2 isoform lacking an SH2 domain, forms heterodimers with SH2B1 and SH2B2alpha (demonstrated by GST pulldown and Co-IP). SH2B2beta markedly attenuates SH2B1-promoted JAK2 activation and IRS-1 phosphorylation by JAK2, acting as an endogenous inhibitor of SH2B1. GST fusion protein pulldown; Co-IP; JAK2 kinase activation assay; IRS-1 phosphorylation assay Endocrinology Medium 17204555
2010 SH2B1 in neuronal SH2B1 deletion mice (LepR neuron-specific Sh2b1 deletion) abrogates leptin-stimulated sympathetic nerve activation and impairs BAT thermogenic programs, revealing an SH2B1/SNS/BAT/thermogenesis axis. Hypothalamic overexpression of human SH2B1 has opposite effects (increased SNS activity, thermogenesis) and protects against diet-induced obesity. LepR neuron-specific Sh2b1 KO; adeno-associated virus-mediated hypothalamic overexpression; sympathetic nerve recording; BAT thermogenesis assays; metabolic phenotyping Nature communications High 32251290
2010 The SH2 domain of neuronal SH2B1 is required for maintenance of normal body weight and glucose metabolism in vivo: SH2 domain-defective (R555E) or SH2 domain-alone (DeltaN503) transgenes fail to rescue obesity/insulin resistance in SH2B1 null mice. Neuron-specific expression of R555E in wild-type mice promotes obesity and insulin resistance (dominant negative). Neuron-specific transgenic rescue with SH2-domain mutants; metabolic phenotyping Endocrinology High 20484460
2013 SH2B1 in pancreatic beta-cells promotes beta-cell survival and proliferation via the PI3K/Akt pathway: knockdown attenuates insulin/IGF-1-stimulated PI3K/Akt activation and increases apoptosis; pancreas-specific SH2B1 KO on HFD leads to increased beta-cell apoptosis, decreased beta-cell mass, impaired insulin secretion, and exacerbated glucose intolerance. INS-1 cell knockdown/overexpression; pancreas-specific KO mice (PKO); streptozotocin challenge; beta-cell mass/apoptosis/proliferation assays; HFD metabolic phenotyping Diabetes High 24150605
2013 SH2B1 in beta-cells promotes insulin gene expression and glucose-stimulated insulin secretion at least in part by enhancing JAK2 activation of the insulin promoter and increasing Pdx1 expression and its recruitment to the insulin promoter. INS-1 cell knockdown/overexpression; insulin promoter-luciferase assay; Pdx1 chromatin immunoprecipitation; islet insulin content measurement Molecular endocrinology Medium 24645678
2012 SH2B1beta associates with the erythropoietin receptor (EPO-R) at pTyr343 and pTyr401 via its SH2 domain (pYXXL motif), as shown by COLT screening and Co-IP. In hematopoietic cells, SH2B1beta preferentially associates with EPO-R over JAK2. Constitutive SH2B1-EPO-R association is needed for optimal SH2-dependent recruitment. In the absence of SH2B1, EPO-R downstream signaling is enhanced, indicating SH2B1 is a negative regulator of EPO signaling. COLT screening; Co-IP; in vitro mixing; domain-dependency experiments; SH2B1 knockdown with EPO signaling readouts The Journal of biological chemistry Medium 22669948
2007 SH2-B promotes adipocyte differentiation by enhancing insulin/IGF-I receptor-Akt-Foxo1 signaling, leading to increased PPARgamma mRNA levels. SH2-B deficient MEFs show reduced adipogenesis and PPARgamma levels in response to insulin; this upregulation of PPARgamma is blocked by PI3K inhibition but not MEK inhibition. SH2-B KO MEFs; 3T3-L1 retroviral overexpression; adipogenesis assays; PI3K/MEK inhibitors; PPARgamma mRNA/protein measurement; Akt and FKHR/Foxo1 phosphorylation assays Molecular endocrinology Medium 17312274
2013 In Drosophila, Lnk (SH2B ortholog) acts upstream of PI3K at the same level as Chico (IRS), downstream of InR. FRET analysis reveals in vivo binding among InR, Chico, and Lnk. Lnk ensures Chico plasma membrane localization (via both Chico PH domain and Lnk interaction) and recruits an intracellular InR fragment to the membrane, providing a fail-safe mechanism for IIS activation. Genetic epistasis in Drosophila; FRET analysis in vivo; membrane localization assays; double mutant analysis Cell communication and signaling Medium 23590848
2009 Drosophila Lnk (SH2B ortholog) acts in the IIS pathway downstream of InR and upstream of PI3K, in parallel to the IRS ortholog Chico. Lnk and Chico double mutants are synthetically lethal, indicating partially redundant functions. Loss of Lnk function also extends lifespan and improves stress survival via effects on both IIS and Ras/MAPK pathways. Drosophila genetic epistasis; PIP3 reporter localization; PKB phosphorylation assay; double mutant synthetic lethality PLoS genetics Medium 19680438
2008 PSM/SH2B1 splice variants (gamma > delta > alpha > beta) directly potentiate Src tyrosine kinase catalytic activity (increasing Vmax and decreasing Km for ATP) and are Src substrates. SH2B1 and Src co-immunoprecipitate. SH2B1 domain-specific peptide mimetics (SH2 or PH domains) inhibit Src activity and Src-mediated STAT3s activation and phenotypic cell transformation. Co-IP with Src; in vitro kinase assay (Vmax/Km determination); herbimycin inhibitor; dominant-negative peptide mimetics; STAT3 phosphorylation assay; transformation assay Journal of cellular biochemistry Medium 18247337
2013 SH2B1 promotes beta-cell mass by preventing IRS2 ubiquitination: 4E-BP2 deletion induces translation of SH2B1, which forms a complex with IRS2 and JAK2 that prevents IRS2 ubiquitination, thereby increasing IRS2 levels, Akt signaling, and beta-cell proliferation and survival. 4E-BP2 KO mice; Co-IP of SH2B1/IRS2/JAK2 complex; IRS2 ubiquitination assay; beta-cell mass/proliferation/survival assays Diabetes Medium 27217487
2015 SH2B1 interacts with IRSp53 via its N-terminal proline-rich domains in hippocampal neurons. SH2B1-IRSp53 complexes co-localize at the plasma membrane and in the Triton X-100-insoluble fraction. Overexpressing both SH2B1beta and IRSp53 significantly enhances filopodium formation, neurite outgrowth, and branching. Co-IP in hippocampal neurons and 293T cells; confocal co-localization; subcellular fractionation; overexpression assays; filopodium/neurite quantification The Journal of biological chemistry Medium 25586189
2013 SH2B1 promotes BDNF-induced neurite outgrowth in PC12/TrkB cells by enhancing MEK-ERK1/2 and PI3K-AKT signaling. SH2B1beta also enhances BDNF-stimulated STAT3 phosphorylation on Ser727. The SH2 domain and tyrosine phosphorylation of SH2B1beta are required for these BDNF signaling effects. Stable PC12 (TrkB) cell overexpression; kinase inhibitor experiments; SH2 domain and phosphorylation mutants; neurite outgrowth assay; western blotting PloS one Medium 24260264
2018 The unique C-terminal alpha tail of SH2B1alpha inhibits SH2B1 functions (nuclear cycling, NGF-mediated neurite outgrowth, TrkA autophosphorylation, Akt and PLC-gamma phosphorylation) via TrkA-mediated phosphorylation of Tyr753 in the alpha tail. Mutation Y753F restores these functions. SH2B1alpha also inhibits SH2B1beta-mediated neurite outgrowth in a Tyr753-dependent manner. PC12 cell overexpression; TrkA co-expression; Tyr753Phe mutant analysis; Akt/PLC-gamma phosphorylation assays; neurite outgrowth quantification Molecular and cellular biology Medium 29229648
2022 SH2B1 promotes phosphorylation of cytohesin-2 at Tyr381 in Schwann cells, which is required for cytohesin-2 Arf6 GEF activity and peripheral nervous system myelination. Schwann cell-specific loss of SH2B1 reduces cytohesin-2 Tyr381 phosphorylation and myelin thickness in sciatic nerve. PTP4A1 dephosphorylates the same site, acting antagonistically to SH2B1. Schwann cell-specific SH2B1 knockdown mice; cytohesin-2 Y381F knockin mice; Arf6 activity assay; myelin thickness measurement; HEK293T co-expression with PTP4A1 Science signaling High 35077201
2022 SH2B1delta is the predominant brain-specific isoform that localizes primarily to nucleoli (driven by two highly basic regions unique to delta), with some at plasma membrane/nucleus. All four SH2B1 isoforms rescue decreased neurite complexity in Sh2b1 KO neurons; SH2B1delta also increases total neurite length and BDNF-induced expression of Egr1, Arc and FosL1. Human obesity variants in SH2B1delta alter neurite branching, linking nucleolar function to neurobehavioral phenotypes. Primary hippocampal neuron KO rescue with individual isoforms; confocal localization; deletion/mutation of basic regions; BDNF-induced gene expression assay; neurite complexity quantification Journal of cell science Medium 35019135
2022 SH2B1 promotes PLIN4 lysosomal degradation by binding to HSC70, facilitating HSC70-mediated PLIN4 recognition and lysosomal translocation, thereby suppressing lipid peroxidation and protecting against neurodegeneration in an MPTP Parkinson's disease mouse model. Co-IP (SH2B1-HSC70); Sh2b1 KO and neuron-specific Sh2b1 overexpression mice; AAV-HSC70 rescue; PLIN4 lysosomal translocation assay; lipid peroxidation measurement; behavioral assays Redox biology Medium 35390677
2016 SH2B1 modulates chromatin state during myogenesis: it interacts with histone H1 and is required for removal of histone H1 from active transcription sites, enabling H3K4me3 induction and H3K9me3 reduction at IGF2 and MYOG promoters/enhancers. SH2B1 knockdown delays chromatin condensation and decreases myotube formation. SH2B1 is also required for MyoD occupancy at IGF2 and MYOG enhancer/promoter regions. SH2B1 knockdown in myoblasts; Co-IP with histone H1; chromatin immunoprecipitation (H3K4me3, H3K9me3, MyoD); myotube formation assay Biochimica et biophysica acta. Gene regulatory mechanisms Medium 28039048
2023 Selective deletion of Sh2b1 in hippocampal inhibitory (but not excitatory) neurons impairs working memory, short-term object recognition, and behavioral flexibility in mice. Sh2b1 deletion in these neurons leads to aberrantly enhanced ERK signaling; pharmacological ERK inhibition reverses the behavioral impairment, placing hippocampal SH2B1 as a negative regulator of ERK in inhibitory neurons controlling fluid intelligence. Cell-type-specific Sh2b1 KO (inhibitory vs. excitatory neurons); behavioral battery; single-cell RNA/protein profiling; ERK inhibitor pharmacological rescue Research Medium 38434247
2019 The PH domain of SH2B1 is crucial for energy balance: a two-amino acid deletion (ΔPR, residues 317-318) in the PH domain causes obesity and insulin resistance beyond that attributable to adiposity in mice. A human variant P322S/+ causes late-onset glucose intolerance. The PH domain is thus required for full SH2B1 metabolic function in vivo. SH2B1 PH domain knockin mouse models (P322S, ΔPR); metabolic phenotyping; glucose/insulin tolerance tests Diabetes Medium 31439647
2017 The SH2 domain of SH2B1 recognizes diverse phosphopeptides (from JAK2 pTyr813, insulin receptor, IRS-1/2) with distinct thermodynamic signatures. Key residues K575 and R578 play distinct roles in binding chemically disparate ligands (+3 hydrophobic vs. +1 acidic). High-resolution structure of the SH2B1 SH2 domain reveals conformationally plastic loops enabling recognition of dissimilar ligands. X-ray crystallography (high-resolution); isothermal titration calorimetry; site-directed mutagenesis of SH2 domain residues Proteins High 29127727
2020 Deletion of brain-specific SH2B1alpha and SH2B1delta isoforms (αδKO mice) decreases food intake and protects from weight gain on standard and high-fat diets, with adiposity-dependent improvement in glucose homeostasis. This lean phenotype does not require enhanced leptin sensitivity (αδKO mice show normal leptin sensitivity), suggesting the alpha/delta isoforms regulate energy balance via a leptin-independent mechanism. SH2B1 alpha/delta brain-specific KO mice; metabolic phenotyping; leptin sensitivity assays Diabetes Medium 33214137
2015 SH2B1 is a positive mediator of pathological cardiac hypertrophy: cardiac-specific overexpression of SH2B1 exacerbates pressure overload-induced hypertrophy, fibrosis, and dysfunction, while SH2B1 KO produces the opposite phenotype. The pro-hypertrophic effects are mediated through activation of the JAK2/STAT3 signaling cascade; pharmacological JAK2 inactivation rescues abnormalities in SH2B1-overexpressing transgenic mice. Cardiac-specific SH2B1 transgenic mice; global SH2B1 KO rat; aortic banding model; JAK2 inhibitor rescue; JAK2/STAT3 signaling assays Cardiovascular research Medium 26077624
2013 Hepatic SH2B1 adult-onset deletion attenuates HFD-induced hepatic steatosis by decreasing DGAT2 expression and increasing ATGL expression. Deletion of liver SH2B1 in SH2B2 null mice attenuates VLDL secretion. However, hepatic SH2B1 is not required for normal insulin sensitivity or glucose metabolism. Hepatocyte-specific SH2B1 KO mice (HKO); adult-onset liver deletion; DGAT2/ATGL expression; VLDL secretion assay; metabolic phenotyping PloS one Medium 24358267
2018 Neural deletion of Sh2b1 decreases brain weight and causes pathological reactive aggression in mice. Brain-specific restoration of Sh2b1 normalizes brain size and reverses aggression and aberrant activation of amygdala/periaqueductal gray circuits. At the molecular level, Sh2b1 enhances neurotrophin-stimulated neuronal differentiation and protects against oxidative stress-induced neuronal death. Brain-specific Sh2b1 KO; AAV-mediated restoration; resident-intruder assay; c-fos immunoreactivity; neuronal differentiation and survival assays FASEB journal Medium 29180441

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Identification of SH2-B as a key regulator of leptin sensitivity, energy balance, and body weight in mice. Cell metabolism 186 16098827
2007 Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. The Journal of clinical investigation 165 17235396
2010 Recurrent 200-kb deletions of 16p11.2 that include the SH2B1 gene are associated with developmental delay and obesity. Genetics in medicine : official journal of the American College of Medical Genetics 150 20808231
2004 SH2-B promotes insulin receptor substrate 1 (IRS1)- and IRS2-mediated activation of the phosphatidylinositol 3-kinase pathway in response to leptin. The Journal of biological chemistry 149 15316008
2012 Human SH2B1 mutations are associated with maladaptive behaviors and obesity. The Journal of clinical investigation 143 23160192
2004 Disruption of the SH2-B gene causes age-dependent insulin resistance and glucose intolerance. Molecular and cellular biology 105 15314154
2006 SH2B1 (SH2-B) and JAK2: a multifunctional adaptor protein and kinase made for each other. Trends in endocrinology and metabolism: TEM 95 17140804
2004 Tyrosine 813 is a site of JAK2 autophosphorylation critical for activation of JAK2 by SH2-B beta. Molecular and cellular biology 95 15121872
2007 SH2B1 enhances leptin signaling by both Janus kinase 2 Tyr813 phosphorylation-dependent and -independent mechanisms. Molecular endocrinology (Baltimore, Md.) 90 17565041
2018 Hsa_circ_0136666 promotes the proliferation and invasion of colorectal cancer through miR-136/SH2B1 axis. Journal of cellular physiology 84 30370521
1999 SH2-B is required for nerve growth factor-induced neuronal differentiation. The Journal of biological chemistry 78 10187854
2016 MicroRNA-361-3p suppresses tumor cell proliferation and metastasis by directly targeting SH2B1 in NSCLC. Journal of experimental & clinical cancer research : CR 77 27164951
2014 SH2B1 regulation of energy balance, body weight, and glucose metabolism. World journal of diabetes 76 25126397
2009 SH2B1 enhances insulin sensitivity by both stimulating the insulin receptor and inhibiting tyrosine dephosphorylation of insulin receptor substrate proteins. Diabetes 73 19542202
2010 Regulation of lifespan, metabolism, and stress responses by the Drosophila SH2B protein, Lnk. PLoS genetics 70 20333234
2001 SH2-B and APS are multimeric adapters that augment TrkA signaling. Molecular and cellular biology 70 11238898
1999 Alternative splicing, gene localization, and binding of SH2-B to the insulin receptor kinase domain. Mammalian genome : official journal of the International Mammalian Genome Society 69 10594240
2009 The Drosophila SH2B family adaptor Lnk acts in parallel to chico in the insulin signaling pathway. PLoS genetics 67 19680438
2013 Regulation of insulin and type 1 insulin-like growth factor signaling and action by the Grb10/14 and SH2B1/B2 adaptor proteins. The FEBS journal 63 23190452
2002 Interaction of fibroblast growth factor receptor 3 and the adapter protein SH2-B. A role in STAT5 activation. The Journal of biological chemistry 59 11827956
2020 Leptin receptor-expressing neuron Sh2b1 supports sympathetic nervous system and protects against obesity and metabolic disease. Nature communications 58 32251290
2005 Kinase activation through dimerization by human SH2-B. Molecular and cellular biology 52 15767667
2002 SH2-B is required for both male and female reproduction. Molecular and cellular biology 52 11940664
2003 Adapter protein with a pleckstrin homology (PH) and an Src homology 2 (SH2) domain (APS) and SH2-B enhance insulin-receptor autophosphorylation, extracellular-signal-regulated kinase and phosphoinositide 3-kinase-dependent signalling. The Biochemical journal 50 12521378
2000 SH2-B is required for growth hormone-induced actin reorganization. The Journal of biological chemistry 48 10777618
2001 SH2-B family members differentially regulate JAK family tyrosine kinases. The Journal of biological chemistry 47 11751854
2010 Effect of FTO, SH2B1, LEP, and LEPR polymorphisms on weight gain associated with antipsychotic treatment. Journal of clinical psychopharmacology 44 21105276
2006 Differential role of SH2-B and APS in regulating energy and glucose homeostasis. Endocrinology 42 16455776
1999 SH2-B, a membrane-associated adapter, is phosphorylated on multiple serines/threonines in response to nerve growth factor by kinases within the MEK/ERK cascade. The Journal of biological chemistry 41 10473609
2007 The SH2B gene is associated with serum leptin and body fat in normal female twins. Obesity (Silver Spring, Md.) 39 17228025
2014 Functional characterization of obesity-associated variants involving the α and β isoforms of human SH2B1. Endocrinology 37 24971614
2010 Critical role of the Src homology 2 (SH2) domain of neuronal SH2B1 in the regulation of body weight and glucose homeostasis in mice. Endocrinology 37 20484460
2007 Identification of SH2B2beta as an inhibitor for SH2B1- and SH2B2alpha-promoted Janus kinase-2 activation and insulin signaling. Endocrinology 36 17204555
2006 Binding of SH2-B family members within a potential negative regulatory region maintains JAK2 in an active state. Molecular and cellular biology 36 16914724
2013 New function of the adaptor protein SH2B1 in brain-derived neurotrophic factor-induced neurite outgrowth. PloS one 35 24260264
2022 BBOX1-AS1 contributes to colorectal cancer progression by sponging hsa-miR-361-3p and targeting SH2B1. FEBS open bio 34 31984680
2001 Functional effects of APS and SH2-B on insulin receptor signalling. Biochemical Society transactions 33 11498022
2012 Mutation screen in the GWAS derived obesity gene SH2B1 including functional analyses of detected variants. BMC medical genomics 31 23270367
2004 Adapter protein SH2-B beta undergoes nucleocytoplasmic shuttling: implications for nerve growth factor induction of neuronal differentiation. Molecular and cellular biology 29 15082760
2000 SH2-B and SIRP: JAK2 binding proteins that modulate the actions of growth hormone. Recent progress in hormone research 29 11036942
2013 SH2B1 in β-cells regulates glucose metabolism by promoting β-cell survival and islet expansion. Diabetes 28 24150605
2007 Adaptor protein SH2-B linking receptor-tyrosine kinase and Akt promotes adipocyte differentiation by regulating peroxisome proliferator-activated receptor gamma messenger ribonucleic acid levels. Molecular endocrinology (Baltimore, Md.) 28 17312274
2006 Structural basis for phosphotyrosine recognition by the Src homology-2 domains of the adapter proteins SH2-B and APS. Journal of molecular biology 28 16824542
2003 SH2-B is a positive regulator of nerve growth factor-mediated activation of the Akt/Forkhead pathway in PC12 cells. The Journal of biological chemistry 28 14565960
2015 SH2B1 is critical for the regulation of cardiac remodelling in response to pressure overload. Cardiovascular research 27 26077624
2013 Hepatic SH2B1 and SH2B2 regulate liver lipid metabolism and VLDL secretion in mice. PloS one 24 24358267
2004 Roles of a conserved family of adaptor proteins, Lnk, SH2-B, and APS, for mast cell development, growth, and functions: APS-deficiency causes augmented degranulation and reduced actin assembly. Biochemical and biophysical research communications 24 14766215
2022 Neuronal SH2B1 attenuates apoptosis in an MPTP mouse model of Parkinson's disease via promoting PLIN4 degradation. Redox biology 23 35390677
2019 Crucial Role of the SH2B1 PH Domain for the Control of Energy Balance. Diabetes 22 31439647
2015 SH2B1 and IRSp53 proteins promote the formation of dendrites and dendritic branches. The Journal of biological chemistry 22 25586189
2014 Common variants in BDNF, FAIM2, FTO, MC4R, NEGR1, and SH2B1 show association with obesity-related variables in Spanish Roma population. American journal of human biology : the official journal of the Human Biology Council 22 24948161
2011 Computed tomography analysis of the association between the SH2B1 rs7498665 single-nucleotide polymorphism and visceral fat area. Journal of human genetics 22 21796141
2023 Chromosomal deletions on 16p11.2 encompassing SH2B1 are associated with accelerated metabolic disease. Cell reports. Medicine 21 37586323
2019 Genome-Wide DNA Methylation Analysis Reveals Epigenetic Pattern of SH2B1 in Chinese Monozygotic Twins Discordant for Autism Spectrum Disorder. Frontiers in neuroscience 20 31379474
2011 The SH2B1 obesity locus is associated with myocardial infarction in diabetic patients and with NO synthase activity in endothelial cells. Atherosclerosis 20 21907990
2020 SH2B1 protects cardiomyocytes from ischemia/reperfusion injury via the activation of the PI3K/AKT pathway. International immunopharmacology 19 32222636
2018 Neural deletion of Sh2b1 results in brain growth retardation and reactive aggression. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 19 29180441
2013 The Lnk/SH2B adaptor provides a fail-safe mechanism to establish the Insulin receptor-Chico interaction. Cell communication and signaling : CCS 19 23590848
2013 Screening for coding variants in FTO and SH2B1 genes in Chinese patients with obesity. PloS one 19 23825611
2014 SH2B1 CpG-SNP is associated with body weight reduction in obese subjects following a dietary restriction program. Annals of nutrition & metabolism 18 25471250
2012 The joint effect of cigarette smoking and polymorphisms on LRP5, LEPR, near MC4R and SH2B1 genes on metabolic syndrome susceptibility in Taiwan. Molecular biology reports 18 23054017
2018 SH2B1 promotes NSCLC cell proliferation through PI3K/Akt/mTOR signaling cascade. Cancer cell international 17 30202243
2012 The SH2B1 adaptor protein associates with a proximal region of the erythropoietin receptor. The Journal of biological chemistry 16 22669948
2019 Distal chromosome 16p11.2 duplications containing SH2B1 in patients with scoliosis. Journal of medical genetics 15 30803986
2018 SH2B1 promotes epithelial-mesenchymal transition through the IRS1/β-catenin signaling axis in lung adenocarcinoma. Molecular carcinogenesis 15 29380446
2011 Replication of the SH2B1 rs7498665 association with obesity in a Belgian study population. Obesity facts 14 22248999
2020 Association of the SH2B1 rs7359397 Gene Polymorphism with Steatosis Severity in Subjects with Obesity and Non-Alcoholic Fatty Liver Disease. Nutrients 13 32365683
2018 SH2B1 protects against OGD/R‑induced apoptosis in PC12 cells via activation of the JAK2/STAT3 signaling pathway. Molecular medicine reports 13 30015896
2014 SH2B1 in β-cells promotes insulin expression and glucose metabolism in mice. Molecular endocrinology (Baltimore, Md.) 13 24645678
2018 The Effect of SH2B1 Variants on Expression of Leptin- and Insulin-Induced Pathways in Murine Hypothalamus. Obesity facts 12 29631267
2016 4E-BP2/SH2B1/IRS2 Are Part of a Novel Feedback Loop That Controls β-Cell Mass. Diabetes 12 27217487
2014 Signaling adaptor protein SH2B1 enhances neurite outgrowth and accelerates the maturation of human induced neurons. Stem cells translational medicine 12 24736401
2009 SH2-B beta expression in alveolar macrophages in BAL fluid of asthmatic guinea pigs and its role in NGF-TrkA-mediated asthma. Respirology (Carlton, Vic.) 12 19144050
2020 Hsa_circ_0075960 Serves as a Sponge for miR-361-3p/SH2B1 in Endometrial Carcinoma. Technology in cancer research & treatment 11 33356989
2008 PSM/SH2B1 splice variants: critical role in src catalytic activation and the resulting STAT3s-mediated mitogenic response. Journal of cellular biochemistry 11 18247337
2019 New perspective on SH2B1: An accelerator of cancer progression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 10 31739166
2017 SH2B1 is Involved in the Accumulation of Amyloid-β42 in Alzheimer's Disease. Journal of Alzheimer's disease : JAD 10 27802221
2017 Discordant phenotypes in monozygotic twins with 16p11.2 microdeletions including the SH2B1 gene. American journal of medical genetics. Part A 10 28544142
2015 Genetic and structural variation in the SH2B1 gene in the Belgian population. Molecular genetics and metabolism 10 26031769
2021 Genetic Obesity in Children: Overview of Possible Diagnoses with a Focus on SH2B1 Deletion. Hormone research in paediatrics 9 34689140
2018 Phosphorylation of the Unique C-Terminal Tail of the Alpha Isoform of the Scaffold Protein SH2B1 Controls the Ability of SH2B1α To Enhance Nerve Growth Factor Function. Molecular and cellular biology 9 29229648
2013 Analyses of non-synonymous obesity risk alleles in SH2B1 (rs7498665) and APOB48R (rs180743) in obese children and adolescents undergoing a 1-year lifestyle intervention. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association 9 23519644
2022 The adaptor SH2B1 and the phosphatase PTP4A1 regulate the phosphorylation of cytohesin-2 in myelinating Schwann cells in mice. Science signaling 8 35077201
2022 The nucleolar δ isoform of adapter protein SH2B1 enhances morphological complexity and function of cultured neurons. Journal of cell science 7 35019135
2021 Differential response to a 6-month energy-restricted treatment depending on SH2B1 rs7359397 variant in NAFLD subjects: Fatty Liver in Obesity (FLiO) Study. European journal of nutrition 7 33474638
2014 Implication of SH2B1 gene polymorphism studies in gestational diabetes mellitus in Saudi pregnant women. Saudi journal of biological sciences 7 25473371
2013 [Expression of SH2B1 adaptor protein in oesophageal cancer and its clinical significance]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 7 23456070
2008 Association of genetic variants of MAOA and SH2B1 with bone mineral density in community-dwelling Japanese women. Molecular medicine reports 7 21479408
2002 Association of SH2-B to phosphorylated tyrosine residues in the activation loop of TrkB. Research communications in molecular pathology and pharmacology 7 14632312
2023 SH2B1 Tunes Hippocampal ERK Signaling to Influence Fluid Intelligence in Humans and Mice. Research (Washington, D.C.) 6 38434247
2022 SH2B1 variants as potential causes of non-syndromic monogenic obesity in a Brazilian cohort. Eating and weight disorders : EWD 6 36436143
2014 SH2B1 increases the numbers of IRSp53-induced filopodia. Biochimica et biophysica acta 6 25175559
2020 Deletion of the Brain-Specific α and δ Isoforms of Adapter Protein SH2B1 Protects Mice From Obesity. Diabetes 5 33214137
2018 Circulating SH2B1 is associated with an increased risk of gastric cancer. Oncology letters 5 29849792
2017 Diversity in peptide recognition by the SH2 domain of SH2B1. Proteins 5 29127727
2015 SH2B1 orchestrates signaling events to filopodium formation during neurite outgrowth. Communicative & integrative biology 5 26479731
2013 The SH2B1 obesity locus and abnormal glucose homeostasis: lack of evidence for association from a meta-analysis in individuals of European ancestry. Nutrition, metabolism, and cardiovascular diseases : NMCD 5 24103803
2024 Gene-Environment Interactions Significantly Alter the Obesity Risk of SH2B1 rs7498665 Carriers. Journal of obesity & metabolic syndrome 4 39098052
2016 Evidence for Association between SH2B1 Gene Variants and Glycated Hemoglobin in Nondiabetic European American Young Adults: The Add Health Study. Annals of human genetics 4 27530450
2016 SH2B1 modulates chromatin state and MyoD occupancy to enhance expressions of myogenic genes. Biochimica et biophysica acta. Gene regulatory mechanisms 4 28039048

Missed literature

Know a paper Affinage missed for SH2B1? Flag it for the maintainers and the community.

No submissions yet.