GRAP2: GRB2-Related Adaptor Protein 2
A key adaptor protein in T-cell receptor signaling and immune regulation
Gene Information Card
| Symbol | GRAP2 |
|---|---|
| Full Name | GRB2-related adaptor protein 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 17p11.2 |
| NCBI Gene ID | 9402 ncbi.nlm.nih.gov/gene/9402 |
| Ensembl ID | ENSG00000100368 |
| UniProt ID | O75791 |
| OMIM ID | 604518 |
| HGNC ID | 4563 |
| Aliases | GADS, GRID, GRAP-2, GRB2L, GRBLG, Mona |
Description
GRAP2 (GRB2-related adaptor protein 2) encodes a member of the GRB2 family of adaptor proteins. It contains an SH2 domain flanked by two SH3 domains. GRAP2 is predominantly expressed in hematopoietic cells and plays a critical role in T-cell receptor (TCR) signaling by linking the TCR to downstream signaling pathways, including the Ras-MAPK cascade. It interacts with proteins such as LAT, SLP-76, and PLC-gamma1.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| T-cell immunodeficiency | Impaired TCR signaling due to GRAP2 loss-of-function mutations | PMID: 24631077 |
| Autoimmune lymphoproliferative syndrome (ALPS) | Defective apoptosis and lymphocyte homeostasis | PMID: 24631077 |
| Acute myeloid leukemia (AML) | Altered GRAP2 expression may contribute to leukemogenesis | PMID: 23563269 |
| Breast cancer | Potential role in tumor progression via signaling modulation | PMID: 21947068 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.3 | Medium |
| Lymph node | 10.8 | Medium |
| Bone marrow | 8.5 | Medium |
| Thymus | 7.2 | Low |
| Whole blood | 6.1 | Low |
| Lung | 2.4 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 15.2 | High expression |
| Raji (B-cell lymphoma) | 9.8 | Medium expression |
| K562 (chronic myeloid leukemia) | 7.5 | Low expression |
| HEK293 (embryonic kidney) | 1.2 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.226C>T (p.Arg76Trp) | Missense | Rare | Impaired SH2 domain binding |
| c.487G>A (p.Gly163Arg) | Missense | Rare | Reduced interaction with LAT |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in the SH2 domain (e.g., p.Arg76Trp) disrupt phosphotyrosine binding, impairing TCR signaling.
Gain of Function (GOF)
No gain-of-function mutations reported in GRAP2.
Dominant Negative (DN)
Not described for GRAP2.
View complete mutation data：
Gene Ontology (GO)
| • SH3/SH2 adaptor activity (GO:0005070) | • signaling receptor binding (GO:0005102) |
| • signal transduction (GO:0007165) | • chemical synaptic transmission (GO:0007268) |
| • cell differentiation (GO:0030154) | • positive regulation of T cell proliferation (GO:0042102) |
Pathways
• T-cell receptor signaling pathway (KEGG: hsa04660)
• Fc epsilon RI signaling pathway (KEGG: hsa04664)
• Ras signaling pathway (KEGG: hsa04014)
• MAPK signaling pathway (KEGG: hsa04010)
Protein Summary
GRAP2 is a 330-amino-acid adaptor protein with a molecular weight of approximately 37 kDa. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The SH2 domain binds phosphorylated tyrosine residues on activated receptors, while the SH3 domains interact with proline-rich motifs in downstream effectors. GRAP2 is essential for linking the T-cell receptor to the Ras-MAPK pathway, thereby regulating T-cell activation, proliferation, and differentiation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GRAP2 Knockout HEK293 Cell Line | EDJ-KQ6574 | Human | 9402 | Details Get a Quote |
| GRAP2 Knockout HeLa Cell Line | EDJ-KQ55154 | Human | 9402 | Details Get a Quote |
| GRAP2 Knockout A-549 Cell Line | EDJ-KQ63634 | Human | 9402 | Details Get a Quote |
| GRAP2 Knockout HCT 116 Cell Line | EDJ-KQ72096 | Human | 9402 | Details Get a Quote |
