SKAP1

Last updated
SKAP1
Protein SKAP1 PDB 1u5d.png
Available structures
PDB Ortholog search: PDBe RCSB
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)
Ideogram human chromosome 17.svg
Chr. Chromosome 17 (human) [1]
Human chromosome 17 ideogram.svg
HSR 1996 II 3.5e.svg
Red rectangle 2x18.png
Band 17q21.32Start48,133,442 bp [1]
End48,430,275 bp [1]
RNA expression pattern
PBB GE SKAP1 205790 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

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

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

Contents

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]

Related Research Articles

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Platelet-derived growth factor receptor protein family

Platelet-derived growth factor receptors (PDGF-R) are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor (PDGF) family. PDGF subunits -A and -B are important factors regulating cell proliferation, cellular differentiation, cell growth, development and many diseases including cancer. There are two forms of the PDGF-R, alpha and beta each encoded by a different gene. Depending on which growth factor is bound, PDGF-R homo- or heterodimerizes.

GRB2 protein-coding gene in the species Homo sapiens

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Dystroglycan mammalian protein found in Homo sapiens

Dystroglycan is a protein that in humans is encoded by the DAG1 gene.

ZAP70 protein-coding gene in the species Homo sapiens

ZAP-70 is a protein normally expressed near the surface membrane of T cells and natural killer cells. It is part of the T cell receptor, and plays a critical role in T-cell signaling. Its molecular weight is 70 kDa, and it is a member of the protein-tyrosine kinase family.

Lymphocyte cytosolic protein 2 protein-coding gene in the species Homo sapiens

Lymphocyte cytosolic protein 2, also known as LCP2 or SLP-76, is a gene that encodes a signal-transducing adaptor protein.

Linker for activation of T cells protein-coding gene in the species Homo sapiens

The Linker for activation of T cells, also known as linker of activated T cells or LAT, is a protein which in humans is encoded by the LAT gene. Alternative splicing results in multiple transcript variants encoding different isoforms.

FYN mammalian protein found in Homo sapiens

Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.

CBL (gene) protein-coding gene in the species Homo sapiens

Cbl is a mammalian gene encoding the protein CBL which is an E3 ubiquitin-protein ligase involved in cell signalling and protein ubiquitination. Mutations to this gene have been implicated in a number of human cancers, particularly acute myeloid leukaemia.

NCK1 protein-coding gene in the species Homo sapiens

Cytoplasmic protein NCK1 is a protein that in humans is encoded by the NCK1 gene.

B-cell linker mammalian protein found in Homo sapiens

The B-cell linker protein is encoded by the BLNK gene and is an adaptor protein also known as SLP-65, BASH, and BCA. BLNK is expressed in B cells and macrophages and plays a large role in B cell receptor signalling, in a fashion analogous to the role its paralogue SLP-76 plays in T cell receptor signalling. As it has no known intrinsic enzymatic activity, the function of BLNK is to temporally and spatially coordinate and regulate signalling effectors downstream of the B cell receptor.

TNK2 protein-coding gene in the species Homo sapiens

Activated CDC42 kinase 1, also known as ACK1, is an enzyme that in humans is encoded by the TNK2 gene. TNK2 gene encodes a non-receptor tyrosine kinase, ACK1, that binds to multiple receptor tyrosine kinases e.g. EGFR, MERTK, AXL, HER2 and insulin receptor (IR). ACK1 also interacts with Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activity of Cdc42Hs. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain. The protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation signal transduction pathway. Several alternatively spliced transcript variants have been identified from this gene, but the full-length nature of only two transcript variants has been determined.

GRAP2 protein-coding gene in the species Homo sapiens

GRB2-related adapter protein 2 also known as GRB2-related adaptor downstream of Shc (GADS) is a 37 kDa protein that in humans is encoded by the GRAP2 gene.

Alpha-tubulin 3C protein-coding gene in the species Homo sapiens

Tubulin alpha-3C/D chain is a protein that in humans is encoded by the TUBA3C gene.

NCK2 protein-coding gene in the species Homo sapiens

Cytoplasmic protein NCK2 is a protein that in humans is encoded by the NCK2 gene.

SHB (gene) protein-coding gene in the species Homo sapiens

SH2 domain-containing adapter protein B is a protein that in humans is encoded by the SHB gene.

FYB protein-coding gene in the species Homo sapiens

FYN binding protein (FYB-120/130), also known as FYB, ADAP, and SLAP-130 is a protein that in humans is encoded by the FYB gene.

SKAP2 protein-coding gene in the species Homo sapiens

Src kinase-associated phosphoprotein 2 is an enzyme that in humans is encoded by the SKAP2 gene.

TXK (gene) protein-coding gene in the species Homo sapiens

Tyrosine-protein kinase TXK is an enzyme that in humans is encoded by the TXK gene.

PRAM1 protein-coding gene in the species Homo sapiens

PML-RARA-regulated adapter molecule 1 is a protein that in humans is encoded by the PRAM1 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000141293 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 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. 1 2 "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. 1 2 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

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