SKAP1

SKAP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesSKAP1, HEL-S-81p, SCAP1, SKAP55, src kinase associated phosphoprotein 1
External IDsOMIM: 604969; MGI: 1925723; HomoloGene: 2764; GeneCards: SKAP1; OMA:SKAP1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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 MbChr 11: 96.36 – 96.65 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000141293Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000057058Ensembl, 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. ^ a b 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. ^ a b "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. ^ 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. ^ a b 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. Bibcode:1998PNAS...95.8779L. doi:10.1073/pnas.95.15.8779. PMC 21153. PMID 9671755.

Further reading