SH2B2 (SH2B Adaptor Protein 2)
A key adaptor protein in cytokine and growth factor receptor signaling, implicated in immune regulation and cancer.
Gene Information Card
| Symbol | SH2B2 |
|---|---|
| Full Name | SH2B Adaptor Protein 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q22.1 |
| NCBI Gene ID | 10603 ncbi.nlm.nih.gov/gene/10603 |
| Ensembl ID | ENSG00000106333 |
| UniProt ID | O14492 |
| OMIM ID | 605300 |
| HGNC ID | 10822 |
| Aliases | APS, SH2B2A |
Description
SH2B2 (also known as APS) is an adaptor protein that contains a pleckstrin homology (PH) domain, a Src homology 2 (SH2) domain, and a C-terminal proline-rich region. It functions as a negative regulator of JAK2-mediated cytokine signaling, including leptin and insulin signaling. SH2B2 is involved in immune cell activation, particularly in T cells and mast cells, and has been implicated in allergic responses and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of SH2B2 may enhance JAK2/STAT5 signaling, promoting cell proliferation | COSMIC, NCBI Gene |
| Leukemia | SH2B2 mutations and altered expression linked to JAK-STAT pathway dysregulation | COSMIC, ClinVar |
| Allergic rhinitis | SH2B2 regulates mast cell degranulation via FcεRI signaling | NCBI Gene, UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.3 | Medium |
| Bone marrow | 8.7 | Medium |
| Lung | 6.2 | Low |
| Breast | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.2 | High expression |
| MCF7 (breast cancer) | 9.8 | Medium expression |
| HEK 293 | 7.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1124G>A (p.Arg375Gln) | Missense | 0.02% (gnomAD) | Unknown functional impact |
| c.1450C>T (p.Arg484Trp) | Missense | 0.01% (gnomAD) | Potential loss of SH2 domain function |
Mutation functional classification
Loss of Function (LOF)
Mutations in the SH2 domain may impair binding to phosphorylated tyrosine residues, reducing negative regulation of JAK2.
Gain of Function (GOF)
Not well characterized; overexpression in certain cancers may act as a gain-of-function by enhancing signaling.
Dominant Negative (DN)
Truncating mutations that retain PH domain but lack SH2 domain could interfere with wild-type protein function.
View complete mutation data：
Gene Ontology (GO)
| • SH2 domain binding (GO:0005070) | • protein binding (GO:0005515) |
| • signal transduction (GO:0007165) | • negative regulation of signal transduction (GO:0009968) |
| • intracellular signal transduction (GO:0035556) |
Pathways
• JAK-STAT signaling pathway (Reactome: R-HSA-9009391)
• Leptin signaling pathway (Reactome: R-HSA-2586552)
• FcεRI signaling (Reactome: R-HSA-2454202)
Protein Summary
SH2B2 is a 593-amino acid adaptor protein that localizes to the cytoplasm and plasma membrane. It contains an N-terminal PH domain that binds phosphoinositides, a central SH2 domain that interacts with phosphorylated tyrosine residues on receptors (e.g., JAK2, insulin receptor), and a C-terminal region with proline-rich motifs. SH2B2 negatively regulates JAK2 activity by recruiting phosphatases or promoting receptor internalization. It also modulates actin cytoskeleton dynamics and cell migration.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SH2B2 Knockout HEK293 Cell Line | EDJ-KQ3884 | Human | 10603 | Details Get a Quote |
| SH2B2 Knockout HCT 116 Cell Line | EDJ-KQ26097 | Human | 10603 | Details Get a Quote |
| SH2B2 Knockout HeLa Cell Line | EDJ-KQ26098 | Human | 10603 | Details Get a Quote |
| SH2B2 Knockout A-549 Cell Line | EDJ-KQ63922 | Human | 10603 | Details Get a Quote |
