SKAP1

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SKAP1
Protein SKAP1 PDB 1u5d.png
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
Gene location (Human)
Chromosome 17 (human)
Chr.Chromosome 17 (human)[1]
Chromosome 17 (human)
Genomic location for SKAP1
Genomic location for SKAP1
Band17q21.32Start48,133,442 bp[1]
End48,430,275 bp[1]
RNA expression pattern
PBB GE SKAP1 205790 at fs.png
More reference expression data
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: 96.46 – 96.76 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[edit]

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

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000141293 - Ensembl, May 2017
  2. ^ a b c 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. ^ 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.
  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. doi:10.1073/pnas.95.15.8779. PMC 21153. PMID 9671755.

Further reading[edit]