SKAP1

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]
End	48,430,275 bp[1]
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)[2]
End	96,649,956 bp[2]
RNA expression pattern
	Top expressed in
	right lobe of liver; ; right uterine tube; ; lymph node; ; blood; ; pituitary gland; ; anterior pituitary; ; spleen; ; kidney; ; bone marrow cells; ; appendix;
	Top expressed in
	thymus; ; secondary oocyte; ; blood; ; islet of Langerhans; ; seminal vesicula; ; spleen; ; subcutaneous adipose tissue; ; spermatid; ; neural tube; ; spermatocyte;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	SH3 domain binding; SH2 domain binding; protein binding; protein phosphatase binding; protein kinase binding; protein-containing complex binding; protein homodimerization activity; microtubule plus-end binding;
Cellular component	cytoplasm; membrane; cell-cell junction; plasma membrane; T cell receptor complex; 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 by RNA polymerase II; 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
	8631
	78473
	ENSG00000141293
	ENSMUSG00000057058
	Q86WV1
	Q3UUV5
	NM_001075099; NM_003726
	NM_001033186; NM_001177898; NM_001177899
	NP_001068567; NP_003717
	NP_001028358; NP_001171369; NP_001171370
	Wikidata
View/Edit Human	View/Edit Mouse

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

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

GRCh38: Ensembl release 89: ENSG00000141293 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000057058 - 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.
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.
"Entrez Gene: SKAP1 src kinase associated phosphoprotein 1".
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. S2CID 11810379.
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.
- 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.
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.
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.
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.
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.
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. Bibcode:1998PNAS...95.8779L. doi:10.1073/pnas.95.15.8779. PMC 21153. PMID 9671755.

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. 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): 25789–95. 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.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000141293 - Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid9195899-5] 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.

[entrez-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. S2CID 11810379.

[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] 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.

[pmid12171928-11] 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.

[pmid9748251-12] 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.

[pmid11909961-13] 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.

[pmid9671755-14] 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. Bibcode:1998PNAS...95.8779L. doi:10.1073/pnas.95.15.8779. PMC 21153. PMID 9671755.

SKAP1

Interactions

References

Further reading