Protein-coding gene in the species Homo sapiens
More reference expression data |
BioGPS | ![](//upload.wikimedia.org/wikipedia/commons/thumb/f/f7/PBB_GE_FYB_205285_s_at_fs.png/250px-PBB_GE_FYB_205285_s_at_fs.png)
![](//upload.wikimedia.org/wikipedia/commons/thumb/9/9d/PBB_GE_FYB_211795_s_at_fs.png/250px-PBB_GE_FYB_211795_s_at_fs.png)
![](//upload.wikimedia.org/wikipedia/commons/thumb/c/cb/PBB_GE_FYB_211794_at_fs.png/250px-PBB_GE_FYB_211794_at_fs.png) | More reference expression data |
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Gene ontology |
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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 |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | |
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NM_001243093 NM_001465 NM_199335 NM_001349333 NM_018594 |
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RefSeq (protein) | |
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NP_001230022 NP_001456 NP_955367 NP_001336262 NP_061064 |
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Location (UCSC) | Chr 5: 39.11 – 39.27 Mb | Chr 15: 6.55 – 6.69 Mb |
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PubMed search | [3] | [4] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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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]
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]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000082074 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022148 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: FYB FYN binding protein (FYB-120/130)".
- ^ Schraven B, Marie-Cardine A, Koretzky G (June 1997). "Molecular analysis of the fyn-complex: cloning of SKAP55 and SLAP-130, two novel adaptor proteins which associate with fyn and may participate in the regulation of T cell receptor-mediated signaling". Immunology Letters. 57 (1–3): 165–169. doi:10.1016/s0165-2478(97)00053-9. PMID 9232446.
- ^ a b c d Griffiths EK, Penninger JM (June 2002). "Communication between the TCR and integrins: role of the molecular adapter ADAP/Fyb/Slap". Current Opinion in Immunology. 14 (3): 317–322. doi:10.1016/s0952-7915(02)00334-5. PMID 11973129.
- ^ a b c d e f Wang H, Rudd CE (October 2008). "SKAP-55, SKAP-55-related and ADAP adaptors modulate integrin-mediated immune-cell adhesion". Trends in Cell Biology. 18 (10): 486–493. doi:10.1016/j.tcb.2008.07.005. PMC 3512129. PMID 18760924.
- ^ a b c d e Gerbec ZJ, Thakar MS, Malarkannan S (2015-09-16). "The Fyn-ADAP Axis: Cytotoxicity Versus Cytokine Production in Killer Cells". Frontiers in Immunology. 6: 472. doi:10.3389/fimmu.2015.00472. PMC 4584950. PMID 26441977.
- ^ a b c d Zhang Y, Wang H (April 2012). "Integrin signalling and function in immune cells". Immunology. 135 (4): 268–275. doi:10.1111/j.1365-2567.2011.03549.x. PMC 3372743. PMID 22211918.
- ^ a b c d e Dadwal N, Mix C, Reinhold A, Witte A, Freund C, Schraven B, Kliche S (2021-07-06). "The Multiple Roles of the Cytosolic Adapter Proteins ADAP, SKAP1 and SKAP2 for TCR/CD3 -Mediated Signaling Events". Frontiers in Immunology. 12: 703534. doi:10.3389/fimmu.2021.703534. PMC 8290198. PMID 34295339.
Further reading
- da Silva AJ, Janssen O, Rudd CE (December 1993). "T cell receptor zeta/CD3-p59fyn(T)-associated p120/130 binds to the SH2 domain of p59fyn(T)". The Journal of Experimental Medicine. 178 (6): 2107–2113. doi:10.1084/jem.178.6.2107. PMC 2191307. PMID 7504057.
- Musci MA, Hendricks-Taylor LR, Motto DG, Paskind M, Kamens J, Turck CW, Koretzky GA (May 1997). "Molecular cloning of SLAP-130, an SLP-76-associated substrate of the T cell antigen receptor-stimulated protein tyrosine kinases". The Journal of Biological Chemistry. 272 (18): 11674–11677. doi:10.1074/jbc.272.18.11674. PMID 9115214.
- da Silva AJ, Li Z, de Vera C, Canto E, Findell P, Rudd CE (July 1997). "Cloning of a novel T-cell protein FYB that binds FYN and SH2-domain-containing leukocyte protein 76 and modulates interleukin 2 production". Proceedings of the National Academy of Sciences of the United States of America. 94 (14): 7493–7498. Bibcode:1997PNAS...94.7493D. doi:10.1073/pnas.94.14.7493. PMC 23849. PMID 9207119.
- Liu J, Kang H, Raab M, da Silva AJ, Kraeft SK, Rudd CE (July 1998). "FYB (FYN binding protein) serves as a binding partner for lymphoid protein and FYN kinase substrate SKAP55 and a SKAP55-related protein in T cells". Proceedings of the National Academy of Sciences of the United States of America. 95 (15): 8779–8784. Bibcode:1998PNAS...95.8779L. doi:10.1073/pnas.95.15.8779. PMC 21153. PMID 9671755.
- Marie-Cardine A, Hendricks-Taylor LR, Boerth NJ, Zhao H, Schraven B, Koretzky GA (October 1998). "Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130". The Journal of Biological Chemistry. 273 (40): 25789–25795. doi:10.1074/jbc.273.40.25789. PMID 9748251.
- Marie-Cardine A, Verhagen AM, Eckerskorn C, Schraven B (September 1998). "SKAP-HOM, a novel adaptor protein homologous to the FYN-associated protein SKAP55". FEBS Letters. 435 (1): 55–60. doi:10.1016/S0014-5793(98)01040-0. PMID 9755858. S2CID 37288744.
- Veale M, Raab M, Li Z, da Silva AJ, Kraeft SK, Weremowicz S, et al. (October 1999). "Novel isoform of lymphoid adaptor FYN-T-binding protein (FYB-130) interacts with SLP-76 and up-regulates interleukin 2 production". The Journal of Biological Chemistry. 274 (40): 28427–28435. doi:10.1074/jbc.274.40.28427. PMID 10497204.
- Hamid N, Gustavsson A, Andersson K, McGee K, Persson C, Rudd CE, Fällman M (October 1999). "YopH dephosphorylates Cas and Fyn-binding protein in macrophages". Microbial Pathogenesis. 27 (4): 231–242. doi:10.1006/mpat.1999.0301. PMID 10502464.
- Geng L, Raab M, Rudd CE (December 1999). "Cutting edge: SLP-76 cooperativity with FYB/FYN-T in the Up-regulation of TCR-driven IL-2 transcription requires SLP-76 binding to FYB at Tyr595 and Tyr651". Journal of Immunology. 163 (11): 5753–5757. doi:10.4049/jimmunol.163.11.5753. PMID 10570256. S2CID 29719649.
- Krause M, Sechi AS, Konradt M, Monner D, Gertler FB, Wehland J (April 2000). "Fyn-binding protein (Fyb)/SLP-76-associated protein (SLAP), Ena/vasodilator-stimulated phosphoprotein (VASP) proteins and the Arp2/3 complex link T cell receptor (TCR) signaling to the actin cytoskeleton". The Journal of Cell Biology. 149 (1): 181–194. doi:10.1083/jcb.149.1.181. PMC 2175102. PMID 10747096.
- Kang H, Freund C, Duke-Cohan JS, Musacchio A, Wagner G, Rudd CE (June 2000). "SH3 domain recognition of a proline-independent tyrosine-based RKxxYxxY motif in immune cell adaptor SKAP55". The EMBO Journal. 19 (12): 2889–2899. doi:10.1093/emboj/19.12.2889. PMC 203341. PMID 10856234.
- Asazuma N, Wilde JI, Berlanga O, Leduc M, Leo A, Schweighoffer E, et al. (October 2000). "Interaction of linker for activation of T cells with multiple adapter proteins in platelets activated by the glycoprotein VI-selective ligand, convulxin". The Journal of Biological Chemistry. 275 (43): 33427–33434. doi:10.1074/jbc.M001439200. PMID 10942756.
- Li C, Iosef C, Jia CY, Han VK, Li SS (February 2003). "Dual functional roles for the X-linked lymphoproliferative syndrome gene product SAP/SH2D1A in signaling through the signaling lymphocyte activation molecule (SLAM) family of immune receptors". The Journal of Biological Chemistry. 278 (6): 3852–3859. doi:10.1074/jbc.M206649200. PMID 12458214.
- Brill LM, Salomon AR, Ficarro SB, Mukherji M, Stettler-Gill M, Peters EC (May 2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry". Analytical Chemistry. 76 (10): 2763–2772. doi:10.1021/ac035352d. PMID 15144186.
- Heuer K, Arbuzova A, Strauss H, Kofler M, Freund C (May 2005). "The helically extended SH3 domain of the T cell adaptor protein ADAP is a novel lipid interaction domain". Journal of Molecular Biology. 348 (4): 1025–1035. doi:10.1016/j.jmb.2005.02.069. PMID 15843031.
- Huang Y, Norton DD, Precht P, Martindale JL, Burkhardt JK, Wange RL (June 2005). "Deficiency of ADAP/Fyb/SLAP-130 destabilizes SKAP55 in Jurkat T cells". The Journal of Biological Chemistry. 280 (25): 23576–23583. doi:10.1074/jbc.M413201200. PMID 15849195.
- Koga S, Yogo K, Yoshikawa K, Samori H, Goto M, Uchida T, et al. (September 2005). "Physical and functional association of c-Src and adhesion and degranulation promoting adaptor protein (ADAP) in osteoclastogenesis in vitro". The Journal of Biological Chemistry. 280 (36): 31564–31571. doi:10.1074/jbc.M502703200. PMID 16020549.
- Duke-Cohan JS, Kang H, Liu H, Rudd CE (May 2006). "Regulation and function of SKAP-55 non-canonical motif binding to the SH3c domain of adhesion and degranulation-promoting adaptor protein". The Journal of Biological Chemistry. 281 (19): 13743–13750. doi:10.1074/jbc.M508774200. PMID 16461356.
PDB gallery
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1ri9: Structure of a helically extended SH3 domain of the T cell adapter protein ADAP -
2gtj: Reduced form of ADAP hSH3-N-domain -
2gto: Oxidized form of ADAP hSH3-N |