Structural highlights
Disease
FYB1_HUMAN Congenital autosomal recessive small-platelet thrombocytopenia. The disease is caused by variants affecting the gene represented in this entry.
Function
FYB1_HUMAN Acts as an adapter protein of the FYN and LCP2 signaling cascades in T-cells (By similarity). May play a role in linking T-cell signaling to remodeling of the actin cytoskeleton (PubMed:10747096, PubMed:16980616). Modulates the expression of IL2 (By similarity). Involved in platelet activation (By similarity). Prevents the degradation of SKAP1 and SKAP2 (PubMed:15849195). May be involved in high affinity immunoglobulin epsilon receptor signaling in mast cells (By similarity).[UniProtKB:D3ZIE4][UniProtKB:O35601][1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The adapter protein ADAP (FYB/SLAP-130) provides a critical link between T cell receptor (TCR) signaling and cell adhesion via the activation of integrins. The C-terminal 70 residues of ADAP show homology to SH3 domains; however, conserved residues of the fold are absent. An alignment and annotation of this domain has therefore been elusive. We have solved the three-dimensional structure of the ADAP C-terminal domain by NMR spectroscopy and show that it represents an altered SH3 domain fold. An N-terminal, amphipathic helix makes extensive contacts to residues of the regular SH3 domain fold, and thereby a composite surface with unusual surface properties is created. We propose this SH3 domain variant to be classified as a helically extended SH3 domain (hSH3 domain) and show that the ADAP-hSH3 domain can no longer bind conventional proline-rich peptides.
Structure of a helically extended SH3 domain of the T cell adapter protein ADAP.,Heuer K, Kofler M, Langdon G, Thiemke K, Freund C Structure. 2004 Apr;12(4):603-10. PMID:15062083[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Krause M, Sechi AS, Konradt M, Monner D, Gertler FB, Wehland J. 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. J Cell Biol. 2000 Apr 3;149(1):181-94. PMID:10747096
- ↑ Huang Y, Norton DD, Precht P, Martindale JL, Burkhardt JK, Wange RL. Deficiency of ADAP/Fyb/SLAP-130 destabilizes SKAP55 in Jurkat T cells. J Biol Chem. 2005 Jun 24;280(25):23576-83. Epub 2005 Apr 22. PMID:15849195 doi:http://dx.doi.org/10.1074/jbc.M413201200
- ↑ Kliche S, Breitling D, Togni M, Pusch R, Heuer K, Wang X, Freund C, Kasirer-Friede A, Menasche G, Koretzky GA, Schraven B. The ADAP/SKAP55 signaling module regulates T-cell receptor-mediated integrin activation through plasma membrane targeting of Rap1. Mol Cell Biol. 2006 Oct;26(19):7130-44. PMID:16980616 doi:http://dx.doi.org/26/19/7130
- ↑ Heuer K, Kofler M, Langdon G, Thiemke K, Freund C. Structure of a helically extended SH3 domain of the T cell adapter protein ADAP. Structure. 2004 Apr;12(4):603-10. PMID:15062083 doi:10.1016/j.str.2004.02.021
