SKAP1

Src kinase associated phosphoprotein 1
PDB rendering based on 1u5d.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1U5D​
Identifiers
Symbols	SKAP1 ; HEL-S-81p; SCAP1; SKAP55
External IDs	OMIM: 604969 MGI: 1925723 HomoloGene: 2764 GeneCards: SKAP1 Gene
Gene ontology Molecular function • SH3/SH2 adaptor activity • protein binding • SH3 domain binding • protein kinase binding • protein phosphatase binding • protein complex binding • SH2 domain binding Cellular component • nucleus • cytoplasm • cytosol • plasma membrane • cell-cell junction • T cell receptor complex Biological process • adaptive immune response • positive regulation of signal transduction • positive regulation of cell adhesion • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • T cell receptor signaling pathway • protein localization to plasma membrane Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8631	78473
Ensembl	ENSG00000141293	ENSMUSG00000057058
UniProt	Q86WV1	Q3UUV5
RefSeq (mRNA)	NM_001075099	NM_001033186
RefSeq (protein)	NP_001068567	NP_001028358
Location (UCSC)	Chr 17: 48.13 – 48.43 Mb	Chr 11: 96.46 – 96.76 Mb
PubMed search

Src kinase-associated phosphoprotein 1 is an adapter protein that in humans is encoded by the SKAP1 gene.^[1][2]

This gene encodes a T cell adapter protein, a class of intracellular molecules with modular domains capable of recruiting additional proteins but that exhibit no intrinsic enzymatic activity. The encoded protein contains a unique N-terminal region followed by a PH domain and C-terminal SH3 domain. Along with the adhesion and degranulation-promoting adapter protein, the encoded protein plays a critical role in inside-out signaling by coupling T-cell antigen receptor stimulation to the activation of integrins.^[2]

The demonstration that SKAP1 regulates LFA-1 adhesion was made by retroviral infection ^[3] and by the SKAP1 deficient mouse.^[4] Additional work has implicated SKAP1 in binding to the exchange factor RasGRP1 and in regulating ERK activation in T-cells.^[5][6]

Interactions

SKAP1 has been shown to interact with FYN,^[1][7][8] PTPRC^[9] and FYB.^[8][10]

References

1. Marie-Cardine A, Bruyns E, Eckerskorn C, Kirchgessner H, Meuer SC, Schraven B (July 1997). "Molecular cloning of SKAP55, a novel protein that associates with the protein tyrosine kinase p59fyn in human T-lymphocytes". J Biol Chem 272 (26): 16077–80. doi:10.1074/jbc.272.26.16077. PMID 9195899.
2. "Entrez Gene: SKAP1 src kinase associated phosphoprotein 1".
3. Wang H, Moon EY, Azouz A, et al. (2003). "SKAP-55 regulates integrin adhesion and formation of T cell-APC conjugates". Nat. Immunol. 4 (4): 366–74. doi:10.1038/ni913. PMID 12652296.
4. Wang H, Liu H, Lu Y, Lovatt M, Wei, B, Rudd CE Functional defects of SKAP-55 deficient T-cells identify a regulatory role for the adaptor in LFA-1 adhesion, Mol. Cell. Biol. 2007 27, 6863-75.
5. • Kosco KA, Cerignoli F, Williams S, et al. (2008). "SKAP55 modulates T cell antigen receptor-induced activation of the Ras-Erk-AP1 pathway by binding RasGRP1". Mol. Immunol. 45 (2): 510–22. doi:10.1016/j.molimm.2007.05.024. PMID 17658605.
6. Schneider H., Wang H., Raab M., Valk E., Smith X. , Lovatt M., Wu Z., Strebhardt K, Rudd, CE. Adaptor SKAP55 binds RasGRP1 and negatively regulates p21ras and the ERK pathway in T-cells. (2008) PLoS ONE. 3, 1718.
7. Wu, Liangtang; Yu Zhenbao; Shen Shi-Hsiang (October 2002). "SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation". J. Biol. Chem. (United States) 277 (43): 40420–7. doi:10.1074/jbc.M206023200. ISSN 0021-9258. PMID 12171928.
8. Marie-Cardine, A; Hendricks-Taylor L R; Boerth N J; Zhao H; Schraven B; Koretzky G A (October 1998). "Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130". J. Biol. Chem. (UNITED STATES) 273 (40): 25789–95. doi:10.1074/jbc.273.40.25789. ISSN 0021-9258. PMID 9748251.
9. Wu, Liangtang; Fu Jun; Shen Shi-Hsiang (April 2002). "SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription". Mol. Cell. Biol. (United States) 22 (8): 2673–86. doi:10.1128/MCB.22.8.2673-2686.2002. ISSN 0270-7306. PMC 133720. PMID 11909961.
10. Liu, J; Kang H; Raab M; da Silva A J; Kraeft S K; Rudd C E (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". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 95 (15): 8779–84. doi:10.1073/pnas.95.15.8779. ISSN 0027-8424. PMC 21153. PMID 9671755.

Further reading

• Schraven B, Marie-Cardine A, Koretzky G (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". Immunol. Lett. 57 (1–3): 165–9. doi:10.1016/S0165-2478(97)00053-9. PMID 9232446.
• Clements JL, Boerth NJ, Lee JR, Koretzky GA (1999). "Integration of T cell receptor-dependent signaling pathways by adapter proteins". Annu. Rev. Immunol. 17: 89–108. doi:10.1146/annurev.immunol.17.1.89. PMID 10358754.
• Liu J, Kang H, Raab M, et al. (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". Proc. Natl. Acad. Sci. U.S.A. 95 (15): 8779–84. doi:10.1073/pnas.95.15.8779. PMC 21153. PMID 9671755.
• Marie-Cardine A, Hendricks-Taylor LR, Boerth NJ, et al. (1998). "Molecular interaction between the Fyn-associated protein SKAP55 and the SLP-76-associated phosphoprotein SLAP-130". J. Biol. Chem. 273 (40): 25789–95. doi:10.1074/jbc.273.40.25789. PMID 9748251.
• Kouroku Y, Soyama A, Fujita E, et al. (1999). "RA70 is a src kinase-associated protein expressed ubiquitously". Biochem. Biophys. Res. Commun. 252 (3): 738–42. doi:10.1006/bbrc.1998.9637. PMID 9837776.
• Kang H, Freund C, Duke-Cohan JS, et al. (2000). "SH3 domain recognition of a proline-independent tyrosine-based RKxxYxxY motif in immune cell adaptor SKAP55". EMBO J. 19 (12): 2889–99. doi:10.1093/emboj/19.12.2889. PMC 203341. PMID 10856234.
• Wu L, Fu J, Shen SH (2002). "SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription". Mol. Cell. Biol. 22 (8): 2673–86. doi:10.1128/MCB.22.8.2673-2686.2002. PMC 133720. PMID 11909961.
• Wu L, Yu Z, Shen SH (2002). "SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation". J. Biol. Chem. 277 (43): 40420–7. doi:10.1074/jbc.M206023200. PMID 12171928.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Huang Y, Norton DD, Precht P, et al. (2005). "Deficiency of ADAP/Fyb/SLAP-130 destabilizes SKAP55 in Jurkat T cells". J. Biol. Chem. 280 (25): 23576–83. doi:10.1074/jbc.M413201200. PMID 15849195.
• Jo EK, Wang H, Rudd CE (2005). "An essential role for SKAP-55 in LFA-1 clustering on T cells that cannot be substituted by SKAP-55R". J. Exp. Med. 201 (11): 1733–9. doi:10.1084/jem.20042577. PMC 2213273. PMID 15939789.
• Duke-Cohan JS, Kang H, Liu H, Rudd CE (2006). "Regulation and function of SKAP-55 non-canonical motif binding to the SH3c domain of adhesion and degranulation-promoting adaptor protein". J. Biol. Chem. 281 (19): 13743–50. doi:10.1074/jbc.M508774200. PMID 16461356.
• Kliche S, Breitling D, Togni M, et al. (2006). "The ADAP/SKAP55 signaling module regulates T-cell receptor-mediated integrin activation through plasma membrane targeting of Rap1". Mol. Cell. Biol. 26 (19): 7130–44. doi:10.1128/MCB.00331-06. PMC 1592884. PMID 16980616.