SH2 Domain Containing Protein 1A (SH2D1A)

IMD5; LYP; XLP; MTCP1; DSHP; XLPD; EBVS; SAP; Duncan disease SH2-protein; Lymphoproliferative Syndrome; Signaling lymphocytic activation molecule-associated protein

SPN	K399
HGNC	10820
MGI	1328352
PubMed	20926771
RGD	1562408
UniProt	O60880
Wiki	SH2D1A

SH2D1A plays a major role in the bidirectional stimulation of T and B cells. This protein contains an SH2 domain and a short tail. It associates with the signaling lymphocyte-activation molecule, thereby acting as an inhibitor of this transmembrane protein by blocking the recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to its docking site. This protein can also bind to other related surface molecules that are expressed on activated T, B and NK cells, thereby modifying signal transduction pathways in these cells. Mutations in this gene cause lymphoproliferative syndrome X-linked type 1 or Duncan disease, a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus, with symptoms including severe mononucleosis and malignant lymphoma.

Reference

"Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene."
Nat. Genet. 20:129-135(1998) [PubMed] [Europe PMC] [Abstract]

"The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM."
Nature 395:462-469(1998) [PubMed] [Europe PMC] [Abstract]

"Decreased expression of signaling lymphocytic-activation molecule-associated protein (SAP) transcripts in T cells from patients with rheumatoid arthritis."
Int. Immunol. 13:559-565(2001) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence of the human X chromosome."
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Cell surface receptors Ly-9 and CD84 recruit the X-linked lymphoproliferative disease gene product SAP."
Blood 97:3867-3874(2001) [PubMed] [Europe PMC] [Abstract]

"CD84 is up-regulated on a major population of human memory B cells and recruits the SH2 domain containing proteins SAP and EAT-2."
Eur. J. Immunol. 32:1640-1649(2002) [PubMed] [Europe PMC] [Abstract]

"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]

"Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition."
Mol. Cell 4:555-561(1999) [PubMed] [Europe PMC] [Abstract]

"A 'three-pronged' binding mechanism for the SAP/SH2D1A SH2 domain: structural basis and relevance to the XLP syndrome."
EMBO J. 21:314-323(2002) [PubMed] [Europe PMC] [Abstract]

"SAP couples Fyn to SLAM immune receptors."
Nat. Cell Biol. 5:155-160(2003) [PubMed] [Europe PMC] [Abstract]

"SH2D1A mutation analysis for diagnosis of XLP in typical and atypical patients."
Hum. Genet. 105:501-505(1999) [PubMed] [Europe PMC] [Abstract]

"Correlation of mutations of the SH2D1A gene and Epstein-Barr virus infection with clinical phenotype and outcome in X-linked lymphoproliferative disease."
Blood 96:3118-3125(2000) [PubMed] [Europe PMC] [Abstract]

"Defective NK cell activation in X-linked lymphoproliferative disease."
J. Immunol. 165:3549-3553(2000) [PubMed] [Europe PMC] [Abstract]

"SH2D1A mutations in Japanese males with severe Epstein-Barr virus-associated illnesses."
Blood 98:1268-1270(2001) [PubMed] [Europe PMC] [Abstract]

"Characterization of SH2D1A missense mutations identified in X-linked lymphoproliferative disease patients."
J. Biol. Chem. 276:36809-36816(2001) [PubMed] [Europe PMC] [Abstract]

"Disease-causing SAP mutants are defective in ligand binding and protein folding."
Biochemistry 42:14885-14892(2003) [PubMed] [Europe PMC] [Abstract]

"Fatal hemophagocytic lymphohistiocytosis associated with Epstein-Barr virus infection in a patient with a novel mutation in the signaling lymphocytic activation molecule-associated protein."
Clin. Infect. Dis. 37:E136-E141(2003) [PubMed] [Europe PMC] [Abstract]

"Characterization of a new disease-causing mutation of SH2D1A in a family with X-linked lymphoproliferative disease."
Hum. Mutat. 25:506-506(2005) [PubMed] [Europe PMC] [Abstract]

"Missense mutations in SH2D1A identified in patients with X-linked lymphoproliferative disease differentially affect the expression and function of SAP."
Int. Immunol. 18:1055-1065(2006) [PubMed] [Europe PMC] [Abstract]