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FLASH GENE
Symbol SH2D1A contributors: mct/npt - updated : 16-02-2016
HGNC name SH2 domain protein 1A, Duncan's disease (lymphoproliferative syndrome)
HGNC id 10820
Corresponding disease
LYP lymphoproliferative syndrome
Location Xq25      Physical location : 123.480.131 - 123.507.008
Synonym name
  • SLAM associated protein
  • T cell signal transduction molecule SAP
  • Duncan disease SH2-protein
  • signaling lymphocytic activation molecule-associated protein
  • Synonym symbol(s) SAP, DSHP, MTCP1, SH2A, EBVS, IMD5, LYP, XLP, XLPD, FLJ92177, FLJ18687
    DNA
    TYPE functioning gene
    STRUCTURE 26.86 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Physical map
    CUL4B Xq23 cullin 4B MCTS1 Xq22-24 malignant T cell amplified sequence 1 C1GALT2 Xq25 core 1 UDP-galactose:N-acetylgalactosamine-alpha-R beta 1,3-galactosyltransferase 2 LOC392531 X similar to RIKEN cDNA 2900070E19 LOC389884 X similar to Proliferation-associated protein 2G4 (Cell cycle protein p38-2G4 homolog) (hG4-1) LOC255313 Xq25 hypothetical protein LOC255313 GLUD2 Xq25 glutamate dehydrogenase 2 LOC158714 Xq25 heat shock 70kDa protein 8 pseudogene LOC392532 X similar to Translationally controlled tumor protein (TCTP) (p23) (Histamine-releasing factor) (HRF) LOC139397 Xq25 similar to ribosomal protein L3; 60S ribosomal protein L3; HIV-1 TAR RNA-binding protein B LOC286423 Xq25 similar to mitochondrial ribosome recycling factor isoform 1 GRIA3 Xq25-q26 glutamate receptor, ionotrophic, AMPA 3 LOC392533 X similar to Histone H3.3 LOC392534 X similar to tubulin beta-4 chain - mouse THOC2 Xq25-q26.3 THO complex 2 BIRC4 Xq25 baculoviral IAP repeat-containing 4 STAG2 Xq25 stromal antigen 2 LOC389885 X similar to R28830_1 LOC392535 X similar to Heat shock cognate 71 kDa protein LOC139116 Xq25 similar to testis expressed sequence 13A SH2D1A Xq25-q26 SH2 domain protein 1A, Duncan's disease (lymphoproliferative syndrome) ODZ1 Xq25 odz, odd Oz/ten-m homolog 1(Drosophila) LOC139263 Xq25 similar to testis expressed sequence 13A LOC392536 X similar to filamin-binding LIM protein-1; migfilin LOC340578 Xq25 similar to KIAA1892-like KIAA1892L Xq25 KIAA1892-like
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 splicing 2518 14.2 128 - 2012 23165210
    4 splicing 2498 - 125 - 2012 23165210
    - splicing 470 6.4 58 - 2012 23165210
    - splicing 530 14 125 - 2012 23165210
    - splicing 460 8.4 76 - 2012 23165210
    - splicing 420 6.9 62 - 2012 23165210
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen    
     thymus    
    Digestiveliver    
    Respiratorylung    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte
    Lymphoid/Immunenatural killer
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines EBV transformed B cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • small protein containing a 5 AA terminal sequence SH2 domain
  • a single src-homology-2 domain
  • a 25 AA C terminus tail, highly homologous to INPP5D, required fo its binding to ARHGEF6 and ARHGEF7
  • HOMOLOGY
    interspecies homolog to murine Sh2d1a
    homolog to C.elegans Y51H7BR.5
    intraspecies homolog to INPP5D
    Homologene
    FAMILY
    CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • putative regulator of the signal transduction pathways initiated by interactions between the SLAM molecules at the interface between T and B cells
  • sustaining the immune response by blocking inhibitory signal A mediated by INPP5D
  • compelling for binding of phosphotyrosine to FCgammaRIIB (FCGR2B)
  • may be involved in regulation of B-cell differentiation via switching of SLAMF1-mediated signaling pathways
  • required for the recruitment of ARHGEF6, ARHGEF7 to the SLAM-family receptors
  • may serving as a negative regulator of TRK receptor activation and downstream signaling
  • acting as an intracellular adaptor protein by recruiting the protein tyrosine kinase FYN to the cytoplasmic domains of some of these receptors, which results in the initiation of specific downstream signal transduction pathways
  • may play an important role in balancing positive versus negative immune responses (Li 2008)
  • intracellular adaptor molecule expressed in T cells, natural killer (NK) cells, and some B cells (Li 2008)
  • playing a role in the development of innate-like T cell lineages including natural killer T cells and in the regulation of interactions between B cells and T cells that are required for germinal center formation and long-term humoral immunity (Schwartzberg 2009)
  • playing a novel role in B cells and extends its function to inhibitory immunoreceptor signaling and calcium mobilization (Ostrakhovitch 2009)
  • is pivotal for nearly all phases, but not for maintenance, of T cell-driven B cell humoral immunity
  • regulate T cell proliferation through the MAP-kinase Erk (Li 2009)
  • plays essential roles during invariant NKT cell cytotoxicity and lytic synapse formation
  • plays an essential role in collagen-induced arthritis (CIA) because of FYN-independent and FYN-dependent effects on follicular T helper (TFH) cells and, possibly, other T cell types
  • small cytosolic adaptor protein expressed in hematopoietic lineages whose main function is to regulate intracellular signaling pathways induced by the triggering of members of the SLAM receptor family
  • plays an essential role in the immune system mediating the function of several members of the SLAM family (SLAMF) of receptors, whose expression is essential for T, NK, and B-cell responses
  • is essential for the development of type II NKT cells, and is critical for regulating type II NKT cell responses
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • lymphocyte-activation molecule
  • SLAM-SH2D1A signaling pathway
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • SLAM (signaling lymphocytic activation molecule)/CD150
  • binding to p62dok (DOK1) and activating NFkappaB
  • 2B4/CD244 interaction dependent of PI3K
  • CD84
  • CD229/LY-9
  • associating with the PAK-interacting exchange factor (PIX), a guanine nucleotide exchange factor (GEF) specific for Rac/Cdc42 GTPases, and participating in T cell activation
  • interacted with NTRK1, NTRK2, NTRK3 receptors
  • associates with several other cell-surface receptors including 2B4 (CD244), Ly9 (CD229), CD84 and SLAMF6
  • binding to the inhibitory immunoreceptor CD22 that regulates calcium mobilization in B cells (Ostrakhovitch 2009)
  • interacting with NCK1 (NCK1 is a novel physiological partner for SH2D1A and a direct regulator of TCR signaling and T cell proliferation (Li 2009)
  • is a target of TP53 in T cells
  • directly and specifically interacts with the cytosolic tyrosine 686 of PECAM1
  • SH2D1A facilitates recruitment and activation of LCK at SLAMF6 receptors during restimulation-induced cell death
  • cell & other
    REGULATION
    activated by NFKB
    ASSOCIATED DISORDERS
    corresponding disease(s) LYP
    related resource SH2D1Abase: Mutation registry for X-linked lymphoproliferative syndrome (XLP)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in fatal mononucleoses
    constitutional     --low  
    associated with a major defect in humoral immunity, resulting from a lack of T cell help for B cells
    Susceptibility to systemic lupus erythematosus (SLE)
    Variant & Polymorphism SNP
  • intronic SNP of SH2D1A is associated with SLE
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Sap deficient mice were protected from systemic lupus erythematosus (SLE)
  • mice deficient in the adaptor protein SAP (Sh2d1a) have a major defect in humoral immunity