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FLASH GENE
Symbol SH2D2A contributors: mct - updated : 06-04-2014
HGNC name SH2 domain protein 2A
HGNC id 10821
Location 1q23.1      Physical location : 156.776.034 - 156.786.640
Synonym name
  • T cell specific adaptor protein
  • Rlk/Itk-binding protein
  • Synonym symbol(s) TSAD, F2771, RP11-66D17.12-002, SCAP, RIBP, VRAP
    DNA
    TYPE functioning gene
    STRUCTURE 10.61 kb     9 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    LOC92312 1q22-q23.1 hypothetical protein LOC92312 LMNA 1q21.2-q21.3 lamin A/C FLJ12287 1q22 hypothetical protein FLJ12287 similar to semaphorins LOC388706 1 LOC388706 KIAA0446 1q23.1 KIAA0446 gene product PMF1 1q12-q21.1 polyamine-modulated factor 1 BGLAP 1q25-q31 bone gamma-carboxyglutamate (gla) protein (osteocalcin) PAQR6 1q23.1 progestin and adipoQ receptor family member VI EST1B 1q21.2 Est1p-like protein B MGC13102 1q23.1 hypothetical protein MGC13102 MGC31963 1q23.1 kidney predominant protein NCU-G1 LOC391104 1 similar to Von Hippel-Lindau disease tumor suppressor (pVHL) (G7 protein) CCT3 1q23 chaperonin containing TCP1, subunit 3 (gamma) SSTK-IP 1q23.1 SSTK-interacting protein RHBG 1q21.3 Rhesus blood group, B glycoprotein CROC4 1q12-q25 Rhesus blood group, B glycoprotein MEF2D 1q12-q23 MADS box transcription enhancer factor 2, polypeptide D (myocyte enhancer factor 2D) IQGAP3 1q21.3 IQ motif containing GTPase activating protein 3 LOC164118 1q23.1 similar to RIKEN cDNA A430025D11 APOA1BP 1q21.2 apolipoprotein A-I binding protein FLJ20249 1q22 hypothetical protein FLJ20249 BRAL1 1q22 hypothetical protein FLJ20249 BCAN 1q23-q31 hypothetical protein FLJ20249 NES 1q23.1 nestin CRABP2 1q21.3 cellular retinoic acid binding protein 2 FLJ12671 1q23.1 hypothetical protein FLJ12671 CGI-41 1q23.1 CGI-41 protein MRPL24 1q21-q22 mitochondrial ribosomal protein L24 HDGF Xq25 hepatoma-derived growth factor (high-mobility group protein 1-like) PRCC 1q21.2 papillary renal cell carcinoma (translocation-associated) SH2D2A 1q21 SH2 domain protein 2A INSRR 1q21-q23 insulin receptor-related receptor NTRK1 1q22 neurotrophic tyrosine kinase, receptor, type 1 FLJ00193 1q23.1 FLJ00193 protein FLJ32884 1q23.1 hypothetical protein FLJ32884 ARHGEF11 1q21-q23 Rho guanine nucleotide exchange factor (GEF) 11 LOC246784 1q21.3 homolog of C. elegans smu-1 pseudogene LOC149501 1q23.1 similar to KRT8 protein HCP2 1q22 cytochrome c, somatic pseudogene ETV3 1q21-q23 ets variant gene 3
    regionally located centromeric to the CD1 cluster
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 1630 - 371 - 2004 15300336
    9 - 1661 - 389 - 2004 15300336
    9 - 1691 - 399 - 2004 15300336
    8 - 1540 - 361 - 2004 15300336
    8 - 1445 - 389 - 2004 15300336
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen    
     thymus    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoietic    
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    Lymphoid/ImmuneB cell Mus musculus
    Lymphoid/ImmuneT cell Mus musculusFetal
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal SRC homology 2 domain
  • putative SH3 domain
  • two phosphotyrosine binding sites (NPXY motifs)
  • lacking a catalytic domain
  • conjugated PhosphoP
    HOMOLOGY
    Homologene
    FAMILY T-cell-specific adapter (TSAd) proteins family
    CATEGORY adaptor , signaling
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    basic FUNCTION
  • adaptor protein involved in T cell signaling
  • SH2D2A and HSH2D are adaptors related by structure and sequence, coexpressed in T cells
  • SH2D2A and HSH2D have nonredundant functions in lymphocytes
  • its expression of SH2D2A is important for proper activation of T-cells
  • adapter protein playing key roles in intracellular signal transduction through complex formation with catalytically active signaling molecules
  • promote migration of Jurkat T cells through interaction with the G protein beta subunit
  • required for VEGF-induced, SRC-mediated regulation of endothelial cell junctions and for vascular permeability
  • possible modulatory role for SH2D2A in T cell mediated immune surveillance of cancer
  • modulates signaling downstream of the T cell receptor (TCR)
  • contains several protein interaction domains, and is merging as a modulator of T cell activation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with SMAD2 and SMAD3
  • upon TCR plus integrin costimulation, SH2D2A associates with RPSA and mediates T lymphocyte migration
  • required for tyrosine phosphorylation of the LCK substrate ITK
  • through its interaction with both ITK and LCK, primes ITK for LCK mediated phosphorylation and thereby regulates CXCL12 induced T cell migration and actin cytoskeleton rearrangements
  • KDR induces SRC signaling and vascular permeability in vivo via the adaptor protein SH2D2A
  • novel interactions between the SH2D2A SH2 domain and CD6 phosphotyrosine (pTyr)629 and linker of activated T cells (LAT) pTyr171 , pTyr191 and pTyr226
  • cell & other
    REGULATION
    induced by induced after T cell activation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
  • to Guillain-Barré syndrome
  • multiple sclerosis
  • Variant & Polymorphism other association with a homozygous genotype for a low repeat number of tandem GA in the SH2D2A gene in Guillain-Barré syndrome
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Tsad-deficient murine thymocytes failed to respond to CXCL12 with increased Itk phosphorylation, and displayed reduced actin polymerization and cell migration responses