FYB

This article is about the protein-coding gene. For the Poppy song, see Stagger (EP).

FYN binding protein (FYB-120/130), also known as FYB, ADAP (Adhesion and degranulation-promoting adapter protein), and SLAP-130 (SLP-76-associated phosphoprotein) is a protein that is encoded by the FYB gene in humans.^[5] The protein is expressed in T cells, monocytes, mast cells, macrophages, NK cells, but not B cells.^[6][7][8][9] FYB is a multifunctional protein involved in post-activation T cell signaling, lymphocyte cytokine production, cell adhesion, and actin remodeling.^{[7][8][9][10][11]}

FYB1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1RI9, 2GTJ, 2GTO
Identifiers
Aliases	FYB1
External IDs	OMIM: 602731; MGI: 1346327; HomoloGene: 22664; GeneCards: FYB1; OMA:FYB1 - orthologs
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5p13.1 Start 39,105,252 bp[1] End 39,274,528 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15|15 A1 Start 6,552,334 bp[2] End 6,692,794 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte blood lymph node bone marrow cell trabecular bone appendix granulocyte spleen epithelium of colon epithelium of nasopharynx Top expressed in granulocyte thymus spleen lymph node spermatid mesenteric lymph nodes blood stroma of bone marrow tibiofemoral joint morula More reference expression data BioGPS More reference expression data
Gene ontology Molecular function signaling receptor binding protein binding lipid binding protein-containing complex binding Cellular component cytoplasm cytosol nucleus actin cytoskeleton plasma membrane cell junction Biological process protein phosphorylation intracellular signal transduction protein localization to plasma membrane T cell receptor signaling pathway immune response signal transduction NLS-bearing protein import into nucleus biological process integrin-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2533 23880 Ensembl ENSG00000082074 ENSMUSG00000022148 UniProt O15117 O35601 RefSeq (mRNA) NM_001243093 NM_001465 NM_199335 NM_001349333 NM_018594 NM_001278269 NM_011815 RefSeq (protein) NP_001230022 NP_001456 NP_955367 NP_001336262 NP_061064 NP_001265198 NP_035945 Location (UCSC) Chr 5: 39.11 – 39.27 Mb Chr 15: 6.55 – 6.69 Mb PubMed search [3] [4]
Wikidata
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Structure

Two isoforms of FYB with different lengths of 120 and 130 kDa (FYB-120 and FYB-130) exist.^[8] The 130kDa version has an extra insertion of 46 amino acids and is preferentially expressed in peripheral T cells.^[8] The FYB protein has a variety of binding domains: a non-structured N-terminal region, a proline-rich region, two SH3 domains, a FPPP-motif which binds the ENA/VASP protein family, and other tyrosine-based signaling motifs.^[11]

Function

FYB is critical for activation and proliferation of T-helper cells (CD4+) and required for chemokine signal transduction in T-helper cells and cytotoxic T cells (CD8+).^[11]

FYB regulates cytokine production in T cells as well as in activated NK cells through the FYN-ADAP axis.^[9] In T cells, after TCR stimulation, a unique region of FYB, pYDGI, allows phosphorylation of the protein by FYN.^[9] After being phosphorylated, ADAP can bind to Carma1, causing NF-κB translocation into the nucleus and cytokine production.^[9]

In mast cells, FYB regulates cell adhesion as well as degranulation.^[7] In T cells, FYB allows for cell adhesion and migration through blood vessels through the SLP-76-FYB-SKAP1 complex.^[10] After being phosphorylated by FYN, FYB can bind to SLP-76.^[7] This binding of FYB and SLP-76 regulates "outside-in signaling" or the transfer of signals from outside the cell to inside the cell by integrin.^[10] FYB can also bind to SKAP1, which allows SKAP1 to upregulate integrin activity through interactions with Rap1.^[8][10] The bacteria Yersinia can interfere with this pathway in macrophages through the secretion of YopH (Yersinia protein tyrosine phosphatase) into the macrophage, which de-phosphorylates FYB and SKAP1, leading to a decrease in integrin activity that results in an inhibition of adhesion, phagocytosis, and cytotoxicity.^[8]

FYB is also an important protein for actin remodeling of immune cells.^[11] This is thought to occur through the binding of proteins of the ENA/VASP protein family to the FPPPP-motif of the FYB protein.^[11]