NCK2: A Key Adaptor Protein in Signal Transduction
Comprehensive genomic and proteomic overview of NCK2, including expression, mutations, and disease associations.
Gene Information Card
| Symbol | NCK2 |
|---|---|
| Full Name | NCK adaptor protein 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q12.3 |
| NCBI Gene ID | 8440 ncbi.nlm.nih.gov/gene/8440 |
| Ensembl ID | ENSG00000115966 |
| UniProt ID | O43639 |
| OMIM ID | 604930 |
| HGNC ID | 7665 |
| Aliases | GRB4, NCKbeta, SH2/SH3 adaptor protein NCK-2 |
Description
NCK2 encodes a member of the NCK family of adaptor proteins, which contain one SH2 domain and three SH3 domains. The protein functions as a scaffold in tyrosine kinase signaling pathways, linking cell surface receptors to downstream effectors such as PAK1 and WASP. NCK2 is involved in cytoskeletal reorganization, cell migration, and growth factor responses. Alternative splicing generates multiple transcript variants.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of NCK2 enhances EGFR signaling and cell migration | PMID: 21502514 |
| Prostate cancer | NCK2 promotes androgen receptor-independent growth via Src/FAK pathway | PMID: 23542167 |
| Colorectal cancer | NCK2 amplification correlates with poor prognosis and metastasis | PMID: 27323851 |
| Nephrotic syndrome | NCK2 mutations disrupt podocyte slit diaphragm signaling | PMID: 21147949 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Kidney | 15.2 | Medium |
| Liver | 6.1 | Low |
| Lung | 10.7 | Medium |
| Breast | 14.8 | Medium |
| Prostate | 18.3 | High |
| Colon | 11.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 22.1 | High expression |
| PC3 (prostate cancer) | 19.5 | High expression |
| HCT116 (colorectal cancer) | 16.8 | Medium expression |
| HEK293 (embryonic kidney) | 9.4 | Low expression |
| A549 (lung cancer) | 13.2 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.437C>T (p.Pro146Leu) | Missense | 0.02% | Alters SH2 domain binding affinity |
| c.689G>A (p.Arg230Gln) | Missense | 0.01% | Reduced interaction with PAK1 |
| c.1123_1124insA (p.Thr375Asnfs*12) | Frameshift | <0.01% | Loss of C-terminal SH3 domain |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Complete loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Frameshift and start-loss mutations lead to truncated or absent protein, impairing adaptor function in signaling.
Gain of Function (GOF)
Missense mutations in the SH2 domain may enhance binding to phosphorylated receptors, increasing oncogenic signaling.
Dominant Negative (DN)
Mutations that retain SH2 but disrupt SH3 domains can sequester receptors without activating downstream effectors.
View complete mutation data：
Gene Ontology (GO)
| • SH3/SH2 adaptor activity (GO:0005070) | • signal transduction (GO:0007165) |
| • actin cytoskeleton organization (GO:0030036) | • neurotrophin TRK receptor signaling pathway (GO:0048011) |
| • plasma membrane (GO:0005886) | • cytoplasm (GO:0005737) |
Pathways
• EGFR signaling pathway (Reactome: R-HSA-177929)
• PAK pathway (Reactome: R-HSA-5626467)
• NGF signaling via TRKA (Reactome: R-HSA-187037)
• Signaling by Rho GTPases (Reactome: R-HSA-194315)
Protein Summary
NCK2 is a 380-amino-acid adaptor protein with one N-terminal SH2 domain and three C-terminal SH3 domains. It binds phosphorylated tyrosine residues on activated receptor tyrosine kinases (e.g., EGFR, PDGFR) via its SH2 domain and recruits proline-rich effectors such as PAK1, WASP, and SOS through its SH3 domains. This scaffolding activity regulates actin dynamics, cell motility, and mitogenic signaling. NCK2 is widely expressed, with highest levels in prostate, breast, and brain tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NCK2 Knockout HEK293 Cell Line | EDJ-KQ6241 | Human | 8440 | Details Get a Quote |
| NCK2 Knockout A-549 Cell Line | EDJ-KQ30092 | Human | 8440 | Details Get a Quote |
| NCK2 Knockout HCT 116 Cell Line | EDJ-KQ30093 | Human | 8440 | Details Get a Quote |
| NCK2 Knockout HeLa Cell Line | EDJ-KQ30094 | Human | 8440 | Details Get a Quote |
