Details for: SH2B2

Gene ID: 10603

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SH2B2

Ensembl ID: ENSG00000160999

Description: SH2B adaptor protein 2

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • precursor B cell CL0000817
    CSI 3.52
    rCSI 3.08%
    PRS 96.36
  • astrocyte of the cerebral cortex CL0002605
    CSI 3.11
    rCSI 6.97%
    PRS 84.52
  • plasmablast CL0000980
    CSI 2.97
    rCSI 2.34%
    PRS 95.06
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.86
    rCSI 2.2%
    PRS 96.18
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 2.42
    rCSI 3.01%
    PRS 82.19
  • mature B cell CL0000785
    CSI 2.03
    rCSI 1.77%
    PRS 97.68
  • intermediate monocyte CL0002393
    CSI 1.83
    rCSI 2.77%
    PRS 96.75
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.83
    rCSI 3.07%
    PRS 84.44
  • extravillous trophoblast CL0008036
    CSI 1.79
    rCSI 2.21%
    PRS 92.49
  • germinal center B cell CL0000844
    CSI 1.16
    rCSI 3.45%
    PRS 95.62
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.82
    rCSI 2.58%
    PRS 85.28

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [SH2B2](/details-gene/10603) (SH2B adaptor protein 2), also known as APS, is a protein-coding gene located on chromosome 7q22.1. It functions as a critical signaling adaptor protein, containing both a pleckstrin homology (PH) and an SH2 domain. These domains enable it to participate in a wide array of intracellular signaling cascades, particularly those initiated by receptor tyrosine kinases and cytokine receptors. **Overall**, expression data reveals that [SH2B2](/details-gene/10603) is a significant marker in hematopoietic cells, especially those of the B cell lineage, such as [precursor B cell](/details-cell/CL0000817)s and [plasmablast](/details-cell/CL0000980)s. It also shows notable expression in specific myeloid and neuronal cell types, suggesting a multifaceted role in both the immune and nervous systems. Its function is central to processes like the [B cell receptor signaling pathway](/details-ontology/GO:0050853), [cytokine-mediated signaling](/details-ontology/GO:0019221), and the organization of the [actin cytoskeleton](/details-ontology/GO:0030036). ## Cellular Roles and Expression Landscape The expression profile of [SH2B2](/details-gene/10603) highlights its prominent role in the hematopoietic system. The gene shows its highest significance in B-lineage cells across various developmental stages, including [precursor B cell](/details-cell/CL0000817) (CSI: 3.52), [plasmablast](/details-cell/CL0000980) (CSI: 2.97), [mature B cell](/details-cell/CL0000785) (CSI: 2.03), and [germinal center B cell](/details-cell/CL0000844) (CSI: 1.16). This pattern is consistent with early research identifying its tyrosine phosphorylation upon B-cell receptor stimulation, positioning it as a key mediator in B-cell activation and homeostasis ([Link](https://doi.org/10.1038/sj.onc.1201163)). Beyond the B-cell lineage, [SH2B2](/details-gene/10603) is also significantly expressed in myeloid cells, including [CD14-low, CD16-positive monocyte](/details-cell/CL0002396) (CSI: 2.86) and [intermediate monocyte](/details-cell/CL0002393) (CSI: 1.83). This suggests a broader role in innate immune signaling. Intriguingly, [SH2B2](/details-gene/10603) also demonstrates a distinct expression signature within the central nervous system. It is a highly significant marker in [astrocyte of the cerebral cortex](/details-cell/CL0002605) (CSI: 3.11) and specific neuronal subtypes, such as [pvalb GABAergic cortical interneuron](/details-cell/CL4023018)s (CSI: 2.42) and [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011)s (CSI: 1.83). This dual expression pattern in both immune and neural cells points towards a conserved role in modulating complex signal transduction pathways across different tissues. ## Pathways and Molecular Function Functionally, [SH2B2](/details-gene/10603) acts as a signaling scaffold, primarily through its [signaling adaptor activity](/details-ontology/GO:0035591) and [transmembrane receptor protein tyrosine kinase adaptor activity](/details-ontology/GO:0005068). It is deeply integrated into [Signal transduction](/details-pathway/R-HSA-162582) and specifically [Signaling by Receptor Tyrosine Kinases](/details-pathway/R-HSA-9006934). Its involvement in the [B cell receptor signaling pathway](/details-ontology/GO:0050853) directly corresponds to its high expression in B cells. Furthermore, its role in pathways such as [Signaling by scf-kit](/details-pathway/R-HSA-1433557) ([Link](https://doi.org/10.1016/j.bbrc.2005.08.055)) and [Factors involved in megakaryocyte development and platelet production](/details-pathway/R-HSA-983231) underscores its importance in hematopoiesis beyond the B-cell lineage. The protein's function extends to metabolic regulation, as evidenced by its participation in the [Insulin receptor signaling pathway](/details-ontology/GO:0008286). Studies have also shown that [SH2B2](/details-gene/10603) can inhibit the JAK-STAT pathway ([Link](https://doi.org/10.1038/sj.leu.2401397)) and PDGF-induced mitogenesis ([Link](https://doi.org/10.1038/sj.onc.1202326)), highlighting its capacity to both positively and negatively regulate signaling outputs. At the subcellular level, [SH2B2](/details-gene/10603) localizes to the [cytoplasm](/details-ontology/GO:0005737) and [plasma membrane](/details-ontology/GO:0005886) and is involved in [actin cytoskeleton organization](/details-ontology/GO:0030036), linking extracellular signals to changes in cell morphology and motility. ## Research Directions The diverse expression pattern and multiple signaling roles of [SH2B2](/details-gene/10603) present several avenues for future investigation. Its dual significance in both the immune and nervous systems is particularly compelling. **Proposed Hypotheses:** 1. Given its high expression in [precursor B cell](/details-cell/CL0000817)s and its role as an adaptor for receptor tyrosine kinases like KIT, [SH2B2](/details-gene/10603) may act as a critical checkpoint in early B cell development, integrating survival and differentiation signals from the bone marrow microenvironment. Dysregulation of [SH2B2](/details-gene/10603) could therefore contribute to developmental blocks or the pathogenesis of B-cell malignancies. 2. The pronounced expression of [SH2B2](/details-gene/10603) in [astrocyte of the cerebral cortex](/details-cell/CL0002605) suggests it may function as a key regulator of astrocyte-neuron communication. It could modulate glial responses to neuronal activity or injury by integrating signals from neurotrophic factors or inflammatory cytokines, thereby influencing synaptic plasticity or neuroinflammatory processes. **Experimental Approach:** To test the first hypothesis regarding its role in B-cell development, a conditional knockout mouse model could be generated, deleting [SH2B2](/details-gene/10603) specifically in the B-cell lineage (e.g., using a CD19-Cre driver). Subsequent analysis via multi-parameter flow cytometry of bone marrow, spleen, and peripheral blood would reveal any specific blockade in B-cell maturation from the pro-B to mature B-cell stage. Furthermore, B cells isolated from these mice could be functionally assessed for their proliferative and signaling responses to B-cell receptor (BCR) cross-linking and cytokine stimulation (e.g., IL-7 or SCF) by analyzing phosphorylation cascades and gene expression changes via phosphoflow cytometry and RNA-seq. **Therapeutic Potential:** As an intracellular adaptor protein, [SH2B2](/details-gene/10603) is not a direct target for antibody-based therapies. However, its crucial role in mediating signals from oncoproteins (e.g., receptor tyrosine kinases) makes it a potential target for small molecule inhibitors designed to disrupt its key protein-protein interactions, such as binding via its SH2 domain. Given its high expression in B-lineage cells, developing inhibitors of [SH2B2](/details-gene/10603) function could represent a novel therapeutic strategy for B-cell acute lymphoblastic leukemia or other B-cell malignancies where receptor tyrosine kinase signaling is aberrantly activated. Inhibition, rather than activation, would be the therapeutic goal to blunt pro-survival and proliferative signaling pathways.

Genular Protein ID: 2435315940

Symbol: SH2B2_HUMAN

Name: SH2B adapter protein 2

UniProtKB Accession Codes:

O14492 A0A0A0MTI2 A6ND74

Database IDs:

AGR 1 AlphaFoldDB 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 4 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 21 Gene3D 3 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 3 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 3 SignaLink 1 UCSC 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9233773

Title: Cloning and characterization of APS, an adaptor molecule containing PH and SH2 domains that is tyrosine phosphorylated upon B-cell receptor stimulation.

PubMed ID: 9233773

DOI: 10.1038/sj.onc.1201163

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

PubMed ID: 10374881

Title: APS, an adaptor protein containing pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl.

PubMed ID: 10374881

DOI: 10.1038/sj.leu.2401397

PubMed ID: 9989826

Title: APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis.

PubMed ID: 9989826

DOI: 10.1038/sj.onc.1202326

PubMed ID: 12400014

Title: Adaptor protein APS binds the NH2-terminal autoinhibitory domain of guanine nucleotide exchange factor Vav3 and augments its activity.

PubMed ID: 12400014

DOI: 10.1038/sj.onc.1205927

PubMed ID: 16129412

Title: Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor.

PubMed ID: 16129412

DOI: 10.1016/j.bbrc.2005.08.055

PubMed ID: 15378031

Title: A phenylalanine zipper mediates APS dimerization.

PubMed ID: 15378031

DOI: 10.1038/nsmb829

Sequence Information:

  • Length: 632
  • Mass: 67738
  • Checksum: 823DF1699D404227
  • Sequence:
    • MNGAGPGPAA AAPVPVPVPV PDWRQFCELH AQAAAVDFAH KFCRFLRDNP AYDTPDAGAS 
FSRHFAANFL DVFGEEVRRV LVAGPTTRGA AVSAEAMEPE LADTSALKAA PYGHSRSSED 
VSTHAATKAR VRKGFSLRNM SLCVVDGVRD MWHRRASPEP DAAAAPRTAE PRDKWTRRLR 
LSRTLAAKVE LVDIQREGAL RFMVADDAAA GSGGSAQWQK CRLLLRRAVA EERFRLEFFV 
PPKASRPKVS IPLSAIIEVR TTMPLEMPEK DNTFVLKVEN GAEYILETID SLQKHSWVAD 
IQGCVDPGDS EEDTELSCTR GGCLASRVAS CSCELLTDAV DLPRPPETTA VGAVVTAPHS 
RGRDAVRESL IHVPLETFLQ TLESPGGSGS DSNNTGEQGA ETDPEAEPEL ELSDYPWFHG 
TLSRVKAAQL VLAGGPRNHG LFVIRQSETR PGEYVLTFNF QGKAKHLRLS LNGHGQCHVQ 
HLWFQSVLDM LRHFHTHPIP LESGGSADIT LRSYVRAQDP PPEPGPTPPA APASPACWSD 
SPGQHYFSSL AAAACPPASP SDAAGASSSS ASSSSAASGP APPRPVEGQL SARSRSNSAE 
RLLEAVAATA AEEPPEAAPG RARAVENQYS FY