SKAP1

Protein-coding gene in the species Homo sapiens

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; OMA:SKAP1 - orthologs

Gene location (Human)

Chr.	Chromosome 17 (human)^[1]

Band	17q21.32	Start	48,133,442 bp^[1]
Band	17q21.32	End	48,430,275 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 11 (mouse)^[2]

Band	11\|11 D	Start	96,355,419 bp^[2]
Band	11\|11 D	End	96,649,956 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

granulocyte

right lobe of liver

right uterine tube

lymph node

blood

pituitary gland

right testis

left testis

anterior pituitary

right adrenal cortex

Top expressed in

thymus

zygote

secondary oocyte

primary oocyte

mesenteric lymph nodes

blood

islet of Langerhans

seminal vesicula

embryo

lumbar subsegment of spinal cord

More reference expression data

BioGPS


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

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: 96.36 – 96.65 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]

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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000141293 – Ensembl, May 2017
^ ^a ^b ^c 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.
^ ^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.
^ ^a ^b "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.
^ ^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.
^ 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.