FYB1: Fyn Binding Protein 1 (ADAP)
A key scaffold protein in T-cell receptor signaling and integrin activation
Gene Information Card
| Symbol | FYB1 |
|---|---|
| Full Name | FYN binding protein 1 |
| Gene Type | protein coding |
| Chromosomal Location | 5p13.1 |
| NCBI Gene ID | 2533 ncbi.nlm.nih.gov/gene/2533 |
| Ensembl ID | ENSG00000113520 |
| UniProt ID | O75569 |
| OMIM ID | 602731 |
| HGNC ID | 4036 |
| Aliases | ADAP, SLAP-130, SLAP130, PRO0823 |
Description
FYB1 (FYN binding protein 1), also known as ADAP (adhesion and degranulation-promoting adaptor protein), encodes a scaffold protein that links T-cell receptor (TCR) signaling to integrin activation. It is essential for T-cell adhesion, migration, and immune synapse formation. FYB1 is phosphorylated by FYN and SLP-76, and it recruits VASP and Ena/VASP proteins to regulate actin cytoskeleton dynamics.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Systemic lupus erythematosus (SLE) | FYB1 polymorphisms may alter T-cell adhesion and signaling, contributing to autoimmunity. | PMID: 23291587 |
| Immunodeficiency (T-cell dysfunction) | Loss-of-function mutations impair integrin activation and T-cell adhesion. | PMID: 17442905 |
| Cancer (lymphoma, leukemia) | Dysregulated FYB1 expression affects T-cell trafficking and anti-tumor immunity. | COSMIC: FYB1 mutations in hematopoietic malignancies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 45.2 | High |
| Spleen | 38.7 | High |
| Bone marrow | 22.1 | Medium |
| Thymus | 18.5 | Medium |
| Whole blood | 12.3 | Medium |
| Lung | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 58.4 | High expression; used in functional studies |
| Raji (Burkitt lymphoma) | 2.1 | Low expression |
| HEK293 (embryonic kidney) | 0.8 | Very low; not endogenous |
| K562 (chronic myeloid leukemia) | 15.6 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1123C>T (p.Arg375Trp) | Missense | 0.01% (gnomAD) | Impaired phosphorylation and VASP binding |
| c.1456_1457del (p.Leu486fs) | Frameshift | <0.001% | Loss of function; truncated protein |
| c.789G>A (p.Trp263*) | Nonsense | <0.001% | Premature stop; likely loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein or disrupt key interaction domains (e.g., SH3 domain, proline-rich region) lead to loss of adapter function in T-cell signaling.
Gain of Function (GOF)
Not well documented; no known activating mutations in FYB1.
Dominant Negative (DN)
Missense mutations that retain binding but fail to recruit downstream effectors (e.g., VASP) may act in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• T-cell receptor signaling pathway (KEGG: hsa04660)
• Integrin signaling pathway (PID: integrin1_pathway)
• Fc epsilon RI signaling pathway (KEGG: hsa04664)
• Rap1 signaling pathway (KEGG: hsa04015)
Protein Summary
FYB1 (ADAP) is a 783-amino-acid scaffold protein with multiple interaction domains: an N-terminal SH3 domain, a central proline-rich region, and a C-terminal Ena/VASP homology 1 (EVH1) binding motif. It is predominantly expressed in hematopoietic cells. Upon TCR stimulation, FYB1 is phosphorylated by FYN and SLP-76, leading to recruitment of VASP and Ena/VASP proteins, which promote actin polymerization and integrin clustering. This process is critical for T-cell adhesion, migration, and immune synapse formation. FYB1 also interacts with SKAP1 and SKAP2 to modulate inside-out integrin signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FYB1 Knockout HEK293 Cell Line | EDJ-KQ1308 | Human | 2533 | Details Get a Quote |
| FYB1 Knockout A-549 Cell Line | EDJ-KQ20732 | Human | 2533 | Details Get a Quote |
| FYB1 Knockout HeLa Cell Line | EDJ-KQ53282 | Human | 2533 | Details Get a Quote |
| FYB1 Knockout HCT 116 Cell Line | EDJ-KQ70246 | Human | 2533 | Details Get a Quote |
