SH2D1A explained

SH2 domain–containing protein 1A is a protein that in humans is encoded by the SH2D1A gene.^{[1] [2] [3]} It is often called SLAM-associated protein (symbol SAP), where "SLAM" refers to signaling lymphocytic activation molecules. It is a SH2 domain–containing molecule (part of a family of such molecules) that plays a role in SLAM signaling. A putative function is as an adaptor for Fyn and competitor of phosphatases, leading to modulation of SLAM family function. SAP has been implicated in autoimmunity,^[4] and a mutation of it is associated with X-linked lymphoproliferative disease. At least 32 disease-causing mutations in this gene have been discovered.^[5]

Interactions

SH2D1A has been shown to interact with:

• CD84,^{[6] [7] [8]}
• DOK1,^[9]
• FYN,^{[10] [11]}
• LY9^[7] and
• SLAMF1.^{[12] [13]}

Further reading

• Sumegi J, Seemayer TA, Huang D, Davis JR, Morra M, Gross TG, Yin L, Romco G, Klein E, Terhorst C, Lanyi A . A spectrum of mutations in SH2D1A that causes X-linked lymphoproliferative disease and other Epstein-Barr virus-associated illnesses . Leukemia & Lymphoma . 43 . 6 . 1189–201 . Jun 2002 . 12152986 . 10.1080/10428190290026240 . 44576367 .
• Engel P, Eck MJ, Terhorst C . The SAP and SLAM families in immune responses and X-linked lymphoproliferative disease . Nature Reviews. Immunology . 3 . 10 . 813–21 . Oct 2003 . 14523387 . 10.1038/nri1202 . 1490779 .
• Stern MH, Soulier J, Rosenzwajg M, Nakahara K, Canki-Klain N, Aurias A, Sigaux F, Kirsch IR . MTCP-1: a novel gene on the human chromosome Xq28 translocated to the T cell receptor alpha/delta locus in mature T cell proliferations . Oncogene . 8 . 9 . 2475–83 . Sep 1993 . 8361760 .
• Skare J, Wu BL, Madan S, Pulijaal V, Purtilo D, Haber D, Nelson D, Sylla B, Grierson H, Nitowsky H . Characterization of three overlapping deletions causing X-linked lymphoproliferative disease . Genomics . 16 . 1 . 254–5 . Apr 1993 . 8387453 . 10.1006/geno.1993.1169 . free .
• Nichols KE, Harkin DP, Levitz S, Krainer M, Kolquist KA, Genovese C, Bernard A, Ferguson M, Zuo L, Snyder E, Buckler AJ, Wise C, Ashley J, Lovett M, Valentine MB, Look AT, Gerald W, Housman DE, Haber DA . Inactivating mutations in an SH2 domain-encoding gene in X-linked lymphoproliferative syndrome . Proceedings of the National Academy of Sciences of the United States of America . 95 . 23 . 13765–70 . Nov 1998 . 9811875 . 24894 . 10.1073/pnas.95.23.13765 . 1998PNAS...9513765N . free .
• Poy F, Yaffe MB, Sayos J, Saxena K, Morra M, Sumegi J, Cantley LC, Terhorst C, Eck MJ . Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition . Molecular Cell . 4 . 4 . 555–61 . Oct 1999 . 10549287 . 10.1016/S1097-2765(00)80206-3 . free .
• Li SC, Gish G, Yang D, Coffey AJ, Forman-Kay JD, Ernberg I, Kay LE, Pawson T . Novel mode of ligand binding by the SH2 domain of the human XLP disease gene product SAP/SH2D1A . Current Biology . 9 . 23 . 1355–62 . Dec 1999 . 10607564 . 10.1016/S0960-9822(00)80080-9 . free .
• Sylla BS, Murphy K, Cahir-McFarland E, Lane WS, Mosialos G, Kieff E . The X-linked lymphoproliferative syndrome gene product SH2D1A associates with p62dok (Dok1) and activates NF-kappa B . Proceedings of the National Academy of Sciences of the United States of America . 97 . 13 . 7470–5 . Jun 2000 . 10852966 . 16569 . 10.1073/pnas.130193097 . 2000PNAS...97.7470S . free .
• Benoit L, Wang X, Pabst HF, Dutz J, Tan R . Defective NK cell activation in X-linked lymphoproliferative disease . Journal of Immunology . 165 . 7 . 3549–53 . Oct 2000 . 11034354 . 10.4049/jimmunol.165.7.3549 . free .
• Nagy N, Cerboni C, Mattsson K, Maeda A, Gogolák P, Sümegi J, Lányi A, Székely L, Carbone E, Klein G, Klein E . SH2D1A and SLAM protein expression in human lymphocytes and derived cell lines . International Journal of Cancer . 88 . 3 . 439–47 . Nov 2000 . 11054674 . 10.1002/1097-0215(20001101)88:3<439::AID-IJC17>3.0.CO;2-# . 196589196 .
• Shlapatska LM, Mikhalap SV, Berdova AG, Zelensky OM, Yun TJ, Nichols KE, Clark EA, Sidorenko SP . CD150 association with either the SH2-containing inositol phosphatase or the SH2-containing protein tyrosine phosphatase is regulated by the adaptor protein SH2D1A . Journal of Immunology . 166 . 9 . 5480–7 . May 2001 . 11313386 . 10.4049/jimmunol.166.9.5480 . free .
• Sayós J, Martín M, Chen A, Simarro M, Howie D, Morra M, Engel P, Terhorst C . Cell surface receptors Ly-9 and CD84 recruit the X-linked lymphoproliferative disease gene product SAP . Blood . 97 . 12 . 3867–74 . Jun 2001 . 11389028 . 10.1182/blood.V97.12.3867 . 10530544 . free .
• Morra M, Simarro-Grande M, Martin M, Chen AS, Lanyi A, Silander O, Calpe S, Davis J, Pawson T, Eck MJ, Sumegi J, Engel P, Li SC, Terhorst C . Characterization of SH2D1A missense mutations identified in X-linked lymphoproliferative disease patients . The Journal of Biological Chemistry . 276 . 39 . 36809–16 . Sep 2001 . 11477068 . 10.1074/jbc.M101305200 . free . 2437/230556 . free .
• Latour S, Gish G, Helgason CD, Humphries RK, Pawson T, Veillette A . Regulation of SLAM-mediated signal transduction by SAP, the X-linked lymphoproliferative gene product . Nature Immunology . 2 . 8 . 681–90 . Aug 2001 . 11477403 . 10.1038/90615 . 23206045 .
• Bottino C, Falco M, Parolini S, Marcenaro E, Augugliaro R, Sivori S, Landi E, Biassoni R, Notarangelo LD, Moretta L, Moretta A . NTB-A [correction of GNTB-A], a novel SH2D1A-associated surface molecule contributing to the inability of natural killer cells to kill Epstein-Barr virus-infected B cells in X-linked lymphoproliferative disease . The Journal of Experimental Medicine . 194 . 3 . 235–46 . Aug 2001 . 11489943 . 2193462 . 10.1084/jem.194.3.235 .
• Liu A, Klein G, Bandobashi K, Klein E, Nagy N . SH2D1A expression reflects activation of T and NK cells in cord blood lymphocytes infected with EBV and treated with the immunomodulator PSK . Immunology Letters . 80 . 3 . 181–8 . Mar 2002 . 11803050 . 10.1016/S0165-2478(01)00330-3 .
• Howie D, Simarro M, Sayos J, Guirado M, Sancho J, Terhorst C . Molecular dissection of the signaling and costimulatory functions of CD150 (SLAM): CD150/SAP binding and CD150-mediated costimulation . Blood . 99 . 3 . 957–65 . Feb 2002 . 11806999 . 10.1182/blood.V99.3.957 . free .
• Aoukaty A, Tan R . Association of the X-linked lymphoproliferative disease gene product SAP/SH2D1A with 2B4, a natural killer cell-activating molecule, is dependent on phosphoinositide 3-kinase . The Journal of Biological Chemistry . 277 . 15 . 13331–7 . Apr 2002 . 11815622 . 10.1074/jbc.M112029200 . free .

Notes and References

1. Coffey AJ, Brooksbank RA, Brandau O, Oohashi T, Howell GR, Bye JM, Cahn AP, Durham J, Heath P, Wray P, Pavitt R, Wilkinson J, Leversha M, Huckle E, Shaw-Smith CJ, Dunham A, Rhodes S, Schuster V, Porta G, Yin L, Serafini P, Sylla B, Zollo M, Franco B, Bolino A, Seri M, Lanyi A, Davis JR, Webster D, Harris A, Lenoir G, de St Basile G, Jones A, Behloradsky BH, Achatz H, Murken J, Fassler R, Sumegi J, Romeo G, Vaudin M, Ross MT, Meindl A, Bentley DR . Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene . Nature Genetics . 20 . 2 . 129–35 . Oct 1998 . 9771704 . 10.1038/2424 . 9347438 .
2. Sayos J, Wu C, Morra M, Wang N, Zhang X, Allen D, van Schaik S, Notarangelo L, Geha R, Roncarolo MG, Oettgen H, De Vries JE, Aversa G, Terhorst C . The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM . Nature . 395 . 6701 . 462–9 . Oct 1998 . 9774102 . 10.1038/26683 . 1998Natur.395..462S . 4324402 .
3. Web site: Entrez Gene: SH2D1A SH2 domain protein 1A, Duncan's disease (lymphoproliferative syndrome).
4. Menard M et al . 2014 . Signaling lymphocytic activation molecule (SLAM)/SLAM-associated protein pathway regulates human B-cell tolerance . Journal of Allergy and Clinical Immunology . 133 . 4. 1149–1161 . 10.1016/j.jaci.2013.10.051. 24373350 . 4077428.
5. Šimčíková D, Heneberg P . Refinement of evolutionary medicine predictions based on clinical evidence for the manifestations of Mendelian diseases . Scientific Reports . 9 . 1 . 18577 . December 2019 . 31819097 . 6901466 . 10.1038/s41598-019-54976-4. 2019NatSR...918577S .
6. Tangye SG, Nichols KE, Hare NJ, van de Weerdt BC . Functional requirements for interactions between CD84 and Src homology 2 domain-containing proteins and their contribution to human T cell activation . Journal of Immunology . 171 . 5 . 2485–95 . Sep 2003 . 12928397 . 10.4049/jimmunol.171.5.2485. free .
7. Sayós J, Martín M, Chen A, Simarro M, Howie D, Morra M, Engel P, Terhorst C . Cell surface receptors Ly-9 and CD84 recruit the X-linked lymphoproliferative disease gene product SAP . Blood . 97 . 12 . 3867–74 . Jun 2001 . 11389028 . 10.1182/blood.v97.12.3867. 10530544 . free .
8. Tangye SG, van de Weerdt BC, Avery DT, Hodgkin PD . CD84 is up-regulated on a major population of human memory B cells and recruits the SH2 domain containing proteins SAP and EAT-2 . European Journal of Immunology . 32 . 6 . 1640–9 . Jun 2002 . 12115647 . 10.1002/1521-4141(200206)32:6<1640::AID-IMMU1640>3.0.CO;2-S . free .
9. Sylla BS, Murphy K, Cahir-McFarland E, Lane WS, Mosialos G, Kieff E . The X-linked lymphoproliferative syndrome gene product SH2D1A associates with p62dok (Dok1) and activates NF-kappa B . Proceedings of the National Academy of Sciences of the United States of America . 97 . 13 . 7470–5 . Jun 2000 . 10852966 . 16569 . 10.1073/pnas.130193097 . 2000PNAS...97.7470S . free .
10. Li C, Iosef C, Jia CY, Han VK, Li SS . Dual functional roles for the X-linked lymphoproliferative syndrome gene product SAP/SH2D1A in signaling through the signaling lymphocyte activation molecule (SLAM) family of immune receptors . The Journal of Biological Chemistry . 278 . 6 . 3852–9 . Feb 2003 . 12458214 . 10.1074/jbc.M206649200 . free .
11. Chan B, Lanyi A, Song HK, Griesbach J, Simarro-Grande M, Poy F, Howie D, Sumegi J, Terhorst C, Eck MJ . SAP couples Fyn to SLAM immune receptors . Nature Cell Biology . 5 . 2 . 155–60 . Feb 2003 . 12545174 . 10.1038/ncb920 . 9840321 .
12. Morra M, Simarro-Grande M, Martin M, Chen AS, Lanyi A, Silander O, Calpe S, Davis J, Pawson T, Eck MJ, Sumegi J, Engel P, Li SC, Terhorst C . Characterization of SH2D1A missense mutations identified in X-linked lymphoproliferative disease patients . The Journal of Biological Chemistry . 276 . 39 . 36809–16 . Sep 2001 . 11477068 . 10.1074/jbc.M101305200 . free . 2437/230556 . free .
13. Howie D, Simarro M, Sayos J, Guirado M, Sancho J, Terhorst C . Molecular dissection of the signaling and costimulatory functions of CD150 (SLAM): CD150/SAP binding and CD150-mediated costimulation . Blood . 99 . 3 . 957–65 . Feb 2002 . 11806999 . 10.1182/blood.v99.3.957. free .