SKAP1

Src kinase-associated phosphoprotein 1 is an adapter protein that in humans is encoded by the SKAP1 gene.[5][6]

SKAP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1U5D
Identifiers
Aliases	SKAP1, HEL-S-81p, SCAP1, SKAP55, src kinase associated phosphoprotein 1
External IDs	OMIM: 604969 MGI: 1925723 HomoloGene: 2764 GeneCards: SKAP1
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q21.32 Start 48,133,442 bp[1] End 48,430,275 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 D Start 96,464,593 bp[2] End 96,759,130 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • SH3 domain binding • SH2 domain binding • GO:0001948 protein binding • protein phosphatase binding • protein kinase binding • GO:0032403 macromolecular complex binding • protein homodimerization activity • microtubule plus-end binding Cellular component • cytoplasm • membrane • intercellular junction • cell membrane • T cell receptor complex • cell nucleus • cytosol • ruffle • immunological synapse • microtubule plus-end • plasma membrane raft Biological process • adaptive immune response • immune system process • positive regulation of transcription, DNA-templated • protein localization to plasma membrane • T cell receptor signaling pathway • positive regulation of cell adhesion • positive regulation of transcription from RNA polymerase II promoter • positive regulation of signal transduction • microtubule cytoskeleton organization • positive regulation of cell-matrix adhesion • positive regulation of adaptive immune response • cell migration • positive regulation of integrin activation • positive regulation of cell-cell adhesion mediated by integrin • positive regulation of heterotypic cell-cell adhesion • cellular response to epidermal growth factor stimulus • positive regulation of leukocyte cell-cell adhesion Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	8631	78473
Ensembl	ENSG00000141293	ENSMUSG00000057058
UniProt	Q86WV1	Q3UUV5
RefSeq (mRNA)	NM_001075099 NM_003726	NM_001033186 NM_001177898 NM_001177899
RefSeq (protein)	NP_001068567 NP_003717	NP_001028358 NP_001171369 NP_001171370
Location (UCSC)	Chr 17: 48.13 – 48.43 Mb	Chr 11: 96.46 – 96.76 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[6]

The demonstration that SKAP1 regulates LFA-1 adhesion was made by retroviral infection [7] and by the SKAP1 deficient mouse.[8] Additional work has implicated SKAP1 in binding to the exchange factor RasGRP1 and in regulating ERK activation in T-cells.[9][10]

Interactions

SKAP1 has been shown to interact with FYN,[5][11][12] PTPRC[13] and FYB.[12][14]

References

1. GRCh38: Ensembl release 89: ENSG00000141293 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000057058 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Marie-Cardine A, Bruyns E, Eckerskorn C, Kirchgessner H, Meuer SC, Schraven B (June 1997). "Molecular cloning of SKAP55, a novel protein that associates with the protein tyrosine kinase p59fyn in human T-lymphocytes". The Journal of Biological Chemistry. 272 (26): 16077–80. doi:10.1074/jbc.272.26.16077. PMID 9195899.
6. "Entrez Gene: SKAP1 src kinase associated phosphoprotein 1".
7. Wang H, Moon EY, Azouz A, Wu X, Smith A, Schneider H, Hogg N, Rudd CE (April 2003). "SKAP-55 regulates integrin adhesion and formation of T cell-APC conjugates". Nature Immunology. 4 (4): 366–74. doi:10.1038/ni913. PMID 12652296.
8. 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.
9. • Kosco KA, Cerignoli F, Williams S, Abraham RT, Mustelin T (January 2008). "SKAP55 modulates T cell antigen receptor-induced activation of the Ras-Erk-AP1 pathway by binding RasGRP1". Molecular Immunology. 45 (2): 510–22. doi:10.1016/j.molimm.2007.05.024. PMID 17658605.
10. 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.
11. Wu L, Yu Z, Shen SH (October 2002). "SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation". The Journal of Biological Chemistry. 277 (43): 40420–7. doi:10.1074/jbc.M206023200. PMID 12171928.
12. 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): 25789–95. doi:10.1074/jbc.273.40.25789. PMID 9748251.
13. Wu L, Fu J, Shen SH (April 2002). "SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription". Molecular and Cellular Biology. 22 (8): 2673–86. doi:10.1128/MCB.22.8.2673-2686.2002. PMC 133720. PMID 11909961.
14. 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): 8779–84. doi:10.1073/pnas.95.15.8779. PMC 21153. PMID 9671755.

Further reading

• 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): 165–9. 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". Annual Review of Immunology. 17: 89–108. doi:10.1146/annurev.immunol.17.1.89. PMID 10358754.
• 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): 8779–84. 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): 25789–95. doi:10.1074/jbc.273.40.25789. PMID 9748251.
• Kouroku Y, Soyama A, Fujita E, Urase K, Tsukahara T, Momoi T (November 1998). "RA70 is a src kinase-associated protein expressed ubiquitously". Biochemical and Biophysical Research Communications. 252 (3): 738–42. doi:10.1006/bbrc.1998.9637. PMID 9837776.
• 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): 2889–99. doi:10.1093/emboj/19.12.2889. PMC 203341. PMID 10856234.
• Wu L, Fu J, Shen SH (April 2002). "SKAP55 coupled with CD45 positively regulates T-cell receptor-mediated gene transcription". Molecular and Cellular Biology. 22 (8): 2673–86. doi:10.1128/MCB.22.8.2673-2686.2002. PMC 133720. PMID 11909961.
• Wu L, Yu Z, Shen SH (October 2002). "SKAP55 recruits to lipid rafts and positively mediates the MAPK pathway upon T cell receptor activation". The Journal of Biological Chemistry. 277 (43): 40420–7. doi:10.1074/jbc.M206023200. PMID 12171928.
• 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): 23576–83. doi:10.1074/jbc.M413201200. PMID 15849195.
• Jo EK, Wang H, Rudd CE (June 2005). "An essential role for SKAP-55 in LFA-1 clustering on T cells that cannot be substituted by SKAP-55R". The Journal of Experimental Medicine. 201 (11): 1733–9. doi:10.1084/jem.20042577. PMC 2213273. PMID 15939789.
• 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): 13743–50. doi:10.1074/jbc.M508774200. PMID 16461356.
• Kliche S, Breitling D, Togni M, Pusch R, Heuer K, Wang X, Freund C, Kasirer-Friede A, Menasche G, Koretzky GA, Schraven B (October 2006). "The ADAP/SKAP55 signaling module regulates T-cell receptor-mediated integrin activation through plasma membrane targeting of Rap1". Molecular and Cellular Biology. 26 (19): 7130–44. doi:10.1128/MCB.00331-06. PMC 1592884. PMID 16980616.