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SH2D2A

SH2 domain-containing protein 2A · UniProt Q9NP31

Length
389 aa
Mass
42.9 kDa
Annotated
2026-06-10
38 papers in source corpus 19 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SH2D2A (TSAd) is a catalytically inactive adapter protein that couples antigen- and growth-factor receptor signaling to cytoskeletal remodeling, migration, and transcription through an SH2 domain, a proline-rich region, and multiple phosphorylatable tyrosines (PMID:9468509). In T cells, TSAd expression is induced upon TCR engagement and is regulated both transcriptionally—via a CRE element requiring PKA activity, with cAMP priming cells for rapid protein production—and translationally (PMID:15128801, PMID:18160104). Once expressed and tyrosine-phosphorylated, TSAd engages Lck through three modes (Lck-SH3, Lck-SH2, and the TSAd SH2 domain) and acts as a substrate that drives Lck hyperphosphorylation at Y394 and Y505 to modulate its activity, and promotes Lck phosphorylation of Lck Y192 within the Lck SH2 domain (PMID:15827961, PMID:16839418, PMID:25492967). By bridging Lck to its substrate Itk, TSAd is required for Itk Y511 phosphorylation, and it scaffolds Nck with Lck and SLP-76 via phospho-Y280/Y305 and its proline-rich region to drive actin polymerization and chemokine-induced migration (PMID:20305788, PMID:26163016). These activities underlie TSAd control of CD4+ T cell polarization toward the APC, immunological synapse organization, and effector-versus-central memory differentiation (PMID:30190583). TSAd also undergoes SH2-domain-dependent nuclear import—using VCP/p97 (phosphorylated on Y805) as its phosphotyrosine ligand—where it activates the IL-2 promoter (PMID:11413197, PMID:15752563). In endothelial cells, the TSAd SH2 domain binds VEGFR2 phospho-Y951 while its proline-rich region engages c-Src, bridging the two within a VE-cadherin/VEGFR2/c-Src complex to localize active c-Src to junctions and thereby regulate VE-cadherin turnover, VEGF-induced vascular permeability, and angiogenic sprouting (PMID:15962004, PMID:22689825, PMID:27436360). The breadth of this endothelial role across organs is contested by multi-omics data indicating TSAd is largely absent from endothelial cells (PMID:40080216).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 Medium

    Established TSAd as a non-catalytic adapter, defining the structural toolkit (SH2 domain, phosphotyrosine-binding motifs) through which it would later be shown to act.

    Evidence cDNA cloning, COS-cell expression with immunostaining, and anti-phosphotyrosine immunoprecipitation in PHA-stimulated PBMCs

    PMID:9468509

    Open questions at the time
    • No binding partners identified
    • No functional readout beyond inducible phosphorylation
  2. 2001 Medium

    Showed TSAd has a nuclear, transcriptional function, answering whether this cytoplasmic adapter influences gene expression and linking its SH2 domain to both nuclear import and IL-2 promoter activation.

    Evidence Subcellular fractionation, SH2-mutant transfection, and IL-2 promoter-reporter assays in T cells

    PMID:11413197

    Open questions at the time
    • Identity of the ~95-100 kDa SH2 ligand unknown at this stage
    • Mechanism of transcriptional activation not defined
  3. 2004 Medium

    Identified VCP/p97 as the phosphotyrosine ligand driving TSAd nuclear import and defined how SH2D2A transcription is controlled, connecting receptor signaling to TSAd induction and trafficking.

    Evidence MS identification and endogenous co-IP of VCP, CDC48 mutant yeast complementation (#2); luciferase reporters, EMSA, RT-PCR and PKA inhibition (#3)

    PMID:15128801 PMID:15752563

    Open questions at the time
    • Functional consequence of nuclear TSAd-VCP interaction on specific target genes unresolved
    • Whether VCP-dependent import is required for IL-2 activation not directly tested
  4. 2005 High

    Defined two distinct receptor-proximal roles: TSAd as a multivalent Lck binder and negative regulator of Lck activity in T cells, and as a VEGFR2 pY951 effector required for endothelial migration and tumor vascularization.

    Evidence Lck SH2/SH3 pull-downs, kinase assays and deletion mutants in Jurkat cells (#4); VEGFR2 phosphosite mapping, siRNA, Y951F mutation and TSAd-KO mouse tumor implantation (#5)

    PMID:15827961 PMID:15962004

    Open questions at the time
    • How TSAd reconciles opposing roles in two cell types unclear
    • Downstream effectors of VEGFR2-TSAd not yet identified
  5. 2006 Medium

    Mapped the TSAd-Lck interaction to three binding modes and localized the exon 7 region essential for both Lck modulation and nuclear translocation, and reported TSAd binding to Smad2/3.

    Evidence Domain/isoform co-IP in Jurkat and primary CD4+ T cells (#6); yeast two-hybrid, co-IP and GST pull-down for Smad2/3 (#7)

    PMID:16806069 PMID:16839418

    Open questions at the time
    • Functional consequence of TSAd-Smad2/3 interaction never validated
    • Specific tyrosines binding Lck-SH2 not pinpointed
  6. 2007 Medium

    Resolved that SH2D2A is dual-controlled at transcription and translation, explaining how cAMP priming and TCR engagement jointly gate TSAd protein output.

    Evidence RT-PCR, immunoblotting and pharmacological cAMP/TCR modulation in primary T cells

    PMID:18160104

    Open questions at the time
    • Molecular basis of translational control not defined
    • Identity of translation-regulating signals downstream of TCR unknown
  7. 2009 Low

    Implicated TSAd in laminin/integrin-costimulated T cell migration via interaction with the 67 kDa laminin-binding protein.

    Evidence Yeast two-hybrid, co-IP, overexpression and shRNA migration assays in D1.1 T cells

    PMID:19561400

    Open questions at the time
    • No domain-level mapping of the TSAd-LBP interaction
    • Single lab, no reciprocal validation
    • Connection to canonical TSAd-Lck/Nck pathway unestablished
  8. 2010 High

    Demonstrated that TSAd bridges Lck and Itk to enable Itk Y511 phosphorylation, providing a mechanistic basis for TSAd-driven chemokine-induced actin polymerization and migration.

    Evidence Co-IP, phospho-Itk blotting, proline-rich mutants, Jurkat migration assays, and TSAd-deficient mouse thymocyte assays with actin polymerization readouts

    PMID:20305788

    Open questions at the time
    • Stoichiometry of the Lck-TSAd-Itk ternary assembly not defined
    • Whether nuclear and cytoskeletal pools of TSAd are functionally separable unaddressed
  9. 2012 High

    Defined the endothelial TSAd permeability module, showing TSAd assembles a VE-cadherin/VEGFR2/c-Src complex at junctions and is required for VEGF-induced c-Src activation and vascular permeability.

    Evidence Reciprocal endogenous co-IP, phospho-blotting, siRNA with pathway-specific readouts, and tsad-/- mouse permeability assays with confocal junction imaging

    PMID:22689825

    Open questions at the time
    • Selectivity for c-Src over PLCγ/ERK/eNOS mechanistically unexplained
    • Direct contribution of nuclear TSAd functions to EC phenotype untested
  10. 2014 Medium

    Showed TSAd and Itk drive Lck Y192 phosphorylation within the Lck SH2 domain, creating a docking surface that recruits cytoskeletal regulators and supports T cell-APC conjugate formation.

    Evidence Phosphopeptide arrays, biochemical binding, phospho-specific blotting, Lck point mutants and T cell-APC conjugation assays

    PMID:25492967

    Open questions at the time
    • Whether Lck Y192 phosphorylation is direct or indirect not fully resolved
    • Quantitative contribution of TSAd versus Itk to Y192 phosphorylation unclear
  11. 2015 Medium

    Established TSAd as a Nck-recruiting scaffold, linking phospho-Y280/Y305 and the proline-rich region to assembly of Nck-Lck-SLP-76 complexes that drive actin polymerization.

    Evidence SMALI prediction, peptide arrays, pull-down, co-IP, confocal imaging and actin assays in TSAd-deficient Jurkat cells

    PMID:26163016

    Open questions at the time
    • Why Vav1 is excluded from the complex not explained
    • In vivo relevance of the Nck-Lck-SLP-76 assembly not tested in primary cells
  12. 2018 Medium

    Connected TSAd's cytoskeletal scaffolding role to T cell biology, showing it controls synapse polarization, MTOC orientation and effector/central memory differentiation.

    Evidence Imaging flow cytometry of Sh2d2a-/- T cells with APC, polarity-marker localization and in vitro differentiation assays

    PMID:30190583

    Open questions at the time
    • Molecular link between polarity defects and memory skewing not defined
    • Single-cell heterogeneity of the phenotype unaddressed
  13. 2020 Medium

    Placed TSAd downstream of an epigenetic regulatory axis, showing Myo9b loss silences TSAd via H3K27me3 and that TSAd controls TH1/TH17 balance with disease relevance in pleural effusion.

    Evidence ChIP for H3K27me3 at the TSAd promoter, TSAd siRNA differentiation assays, and in vivo siRNA in a malignant pleural effusion model

    PMID:33046503

    Open questions at the time
    • Direct transcriptional targets of TSAd in TH differentiation unidentified
    • Mechanism coupling TSAd adapter activity to lineage commitment unclear
  14. 2025 Medium

    Expanded the TSAd SH2 interactome to negative-signaling phosphatases/adapters DOK2 and PTPN11, recasting TSAd as a potential negative signaling node in T cells.

    Evidence Affinity-purification mass spectrometry, phosphopeptide mapping and CRISPR/Cas9 TSAd/DOK2 knockouts in Jurkat cells (preprint)

    PMID:bio_10.1101_2025.02.11.636929

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Functional consequence of DOK2/PTPN11 recruitment on specific pathways not resolved
    • Reconciliation with TSAd's positive scaffolding roles unaddressed
  15. 2025 Medium

    Challenged the universality of the endothelial TSAd model by showing TSAd transcripts and protein are largely absent from endothelial cells across organs.

    Evidence Mining of public scRNA-seq, bulk RNA-seq, chromatin accessibility and MS proteomics datasets from endothelial cells across multiple organs

    PMID:40080216

    Open questions at the time
    • Does not exclude regulated or context-specific EC expression
    • Discordance with functional KO permeability phenotypes unresolved
    • Single study, detection-sensitivity limits not fully addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TSAd integrates its opposing positive (Lck/Itk/Nck scaffolding, IL-2 activation) and negative (Lck inhibition, DOK2/PTPN11 recruitment) functions, and in which cell types the VEGFR2 module is physiologically operative, remains unresolved.
  • No unified model reconciling positive and negative signaling roles
  • Definitive cell-type-resolved expression map of TSAd lacking
  • No structural model of TSAd in any signaling complex

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-1500931 Cell-Cell communication 2
Partners
DOK2ITKLCKNCK1PTPN11SRCVCPVEGFR2
Complex memberships
Nck-Lck-SLP-76 complexVE-cadherin/VEGFR2/c-Src junctional complex

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 TSAd (F2771/SH2D2A) was identified as a novel adapter protein containing an SH2 domain and putative SH3/phosphotyrosine-binding motifs but no catalytic domains. The protein is expressed in activated T cells, localizes to the cytoplasm when expressed in COS cells, and is itself tyrosine-phosphorylated (~52 kDa) upon PHA stimulation of peripheral blood mononuclear cells. cDNA cloning, transfection in COS cells with localization by immunostaining, immunoprecipitation with anti-phosphotyrosine antibody The Journal of biological chemistry Medium 9468509
2001 TSAd localizes to the T cell nucleus via an active import process that requires a functional SH2 domain recognizing a phosphotyrosine-containing ligand (~95-100 kDa). TSAd acts as a transcriptional activator in T cells and upregulates IL-2 promoter activity in a manner dependent on an intact SH2 domain, but does not modulate NF-κB, NFAT, or AP-1 activity. Subcellular fractionation, nuclear import assays, SH2 domain mutant transfection in T cells, IL-2 promoter-reporter cotransfection assays The Journal of experimental medicine Medium 11413197
2004 The TSAd SH2 domain ligand involved in nuclear import was identified as p97 Valosin-containing protein (VCP), which is phosphorylated on Y805 by TCR-activated tyrosine kinases. Direct interaction between endogenous TSAd and VCP was demonstrated in T cells. VCP/CDC48 (yeast homolog) is required for TSAd nuclear transport, established using CDC48 mutant yeast. Microchemical identification (mass spectrometry), co-immunoprecipitation of endogenous proteins, direct interaction assay, CDC48 mutant yeast complementation Immunology letters Medium 15752563
2004 Transcriptional activation of SH2D2A in T cells requires a cAMP response element (CRE) centered at position -117 bp from the first coding ATG. CD3 stimulation-induced SH2D2A expression requires cAMP-dependent protein kinase activity, and cAMP analogs potently induce SH2D2A mRNA. Reporter gene assays (luciferase), EMSA with nuclear extracts, real-time RT-PCR, PKA inhibitor treatment Journal of immunology Medium 15128801
2005 TSAd interacts with Lck through Lck's SH2 and SH3 domains, and TSAd is a substrate for Lck phosphorylation. The TSAd C-terminus (proline-rich region and five tyrosines) is both necessary and sufficient for interaction with and phosphorylation by Lck. TSAd expression causes hyperphosphorylation of Lck at Y394 and Y505, reducing the Y394/Y505 ratio, thereby inhibiting Lck activity. The C-terminus alone is sufficient to inhibit the hyperactive Lck Y505F mutant. Co-immunoprecipitation, Lck SH2/SH3 domain pull-down, Lck kinase activity assays, TSAd deletion mutant transfection in Jurkat T cells, phosphospecific immunoblotting European journal of immunology High 15827961
2005 VEGFR-2 phosphorylation at Y951 (within the kinase insert domain) creates a binding site for TSAd. TSAd is expressed in tumor vessels, and Y951-TSAd signaling is required for VEGF-A-induced actin stress fiber formation and endothelial cell migration (but not mitogenesis). TSAd-deficient mice show reduced tumor vascularization and growth. Pan-phosphorylation site mapping of VEGFR-2, phosphopeptide binding assays, TSAd siRNA in endothelial cells, Y951F VEGFR-2 mutation, TSAd knockout mice with tumor implantation The EMBO journal High 15962004
2006 TSAd interacts with Lck through three modes: (1) TSAd aa239-256 binds the Lck-SH3 domain; (2) one or more tyrosines within TSAd aa239-334 (exon 7) bind the Lck-SH2 domain; (3) the TSAd SH2 domain also interacts with Lck. The exon 7-encoded region (aa239-334) is essential for Lck modulation and for TSAd nuclear translocation. TSAd-Lck interaction was confirmed in human CD4+ T cells ex vivo. Co-immunoprecipitation with TSAd isoform/deletion mutants in Jurkat cells and primary CD4+ T cells, domain-binding assays BMC immunology Medium 16839418
2006 TSAd interacts with Smad2 and Smad3, primarily through the TSAd type I SH2 domain. Both Smad2 and Smad3 also interact with the Lck type I SH2 domain but not the PI3K type III SH2 domain. Yeast two-hybrid, co-immunoprecipitation, GST pull-down assays Biochemical and biophysical research communications Low 16806069
2007 SH2D2A expression is regulated at both transcriptional and translational levels. cAMP signaling alone induces TSAd mRNA but not protein. TCR engagement is required for both transcription and translation of TSAd. cAMP signaling primes T cells for more rapid TSAd protein expression upon TCR stimulation. RT-PCR for mRNA quantification, immunoblotting for protein levels, pharmacological modulation of cAMP and TCR signaling in primary T cells Molecular immunology Medium 18160104
2009 TSAd interacts with the 67 kDa laminin-binding protein (LBP) as identified by yeast two-hybrid and confirmed by co-immunoprecipitation in D1.1 T cells. TSAd-LBP interaction occurs upon TCR plus laminin or TCR plus integrin α6 costimulation. Overexpression of TSAd enhances TCR+laminin-induced T cell migration, while dominant-negative TSAd or TSAd shRNA disrupts this migration. Yeast two-hybrid screening, co-immunoprecipitation, overexpression and shRNA knockdown in D1.1 T cells with migration assays Experimental & molecular medicine Low 19561400
2010 TSAd is required for tyrosine phosphorylation of the Lck substrate Itk (at Y511). TSAd promotes Itk phosphorylation by Lck by bridging the two kinases. TSAd interaction with Itk through its proline-rich region is necessary for TSAd to enhance CXCL12-induced actin polymerization and migration of Jurkat T cells. TSAd-deficient murine thymocytes show reduced Itk phosphorylation, actin polymerization, and migration in response to CXCL12. Co-immunoprecipitation, Itk phospho-specific immunoblotting, TSAd proline-rich region mutants, Jurkat migration assays, TSAd-deficient mouse thymocyte assays, actin polymerization (flow cytometry) PloS one High 20305788
2012 VEGFR2 Y951 phosphorylation facilitates binding of VEGFR2 to the SH2 domain of TSAd. TSAd in turn regulates VEGF-induced c-Src activation (increased pY418, reduced pY527). TSAd silencing blocked VEGF-induced c-Src activation but not PLCγ, ERK, or eNOS pathways. TSAd forms a complex with VE-cadherin, VEGFR2, and c-Src at endothelial junctions. TSAd-deficient mice show impaired VEGF-induced vascular permeability (Evans blue, dextran, microsphere extravasation) but normal histamine-induced permeability. Co-immunoprecipitation of endogenous proteins, phospho-specific immunoblotting, Tsad siRNA in endothelial cells, tsad-/- mice with permeability assays (Evans blue, dextran, microspheres), confocal microscopy of VE-cadherin junctions The Journal of experimental medicine High 22689825
2014 Itk and TSAd promote TCR-dependent phosphorylation of Lck at Tyr192 within the Lck SH2 domain. Phospho-Tyr192 of Lck preferentially recruits actin cytoskeleton regulators (including Itk and TSAd) compared to unphosphorylated Lck. Lck Y192 phosphorylation is required for proper T cell activation and T cell–APC conjugate formation. Phosphopeptide arrays, biochemical binding assays, phospho-specific immunoblotting, T cell–APC conjugation assay, Lck point mutant transfection Science signaling Medium 25492967
2015 TSAd binds Nck via Nck SH2 domain interaction with TSAd phospho-Tyr280 and phospho-Tyr305, and via Nck SH3 domains interacting with TSAd's proline-rich region. TSAd promotes Nck interaction with Lck and SLP-76 (but not Vav1) in T cells. TSAd expression increases polymerized actin in a manner dependent on TSAd exon 7 (which encodes Nck and Lck interaction sites). TSAd and Nck co-localize in Jurkat cells. SMALI algorithm prediction, peptide array, pull-down, co-immunoprecipitation, confocal microscopy, imaging flow cytometry, actin polymerization assay in TSAd-deficient Jurkat cells Cell communication and signaling Medium 26163016
2016 The SH2 and proline-rich domains of TSAd bridge VEGFR2 and c-Src, and this bridging is required for localization of activated c-Src to endothelial junctions and elongation of growing angiogenic sprouts. TSAd-deficient embryoid bodies fail to sprout in response to VEGF; TSAd-deficient mice show impaired tracheal vessel development and reduced sprouting in VEGF-Matrigel plugs (but not FGF-Matrigel plugs). TSAd-deficient embryoid bodies fail to phosphorylate/turn over VE-cadherin at junctions. Domain deletion mutants in endothelial cells, tsad-/- embryoid body sprouting assay, tsad-/- mouse tracheal and retinal vasculature analysis, VEGF/FGF Matrigel plugs, c-Src localization by immunofluorescence Science signaling High 27436360
2018 TSAd modulates polarization of CD4+ T cells towards the APC. Sh2d2a-/- CD4+ T cells show impaired polarization of F-actin and TCR to the immunological synapse, and defective polarization of PKCξ, PAR3, and the MTOC. TSAd-deficient T cells preferentially differentiate toward effector memory (Tem) rather than central memory (Tcm) phenotype. Imaging flow cytometry of Sh2d2a-/- T cells with APC, F-actin/TCR/PKCξ/PAR3/MTOC localization, in vitro T cell differentiation assay Scientific reports Medium 30190583
2020 TSAd is regulated epigenetically downstream of Myo9b: Myo9b deficiency causes H3K27me3 enrichment at the TSAd promoter, reducing TSAd expression. TSAd knockdown in naive T cells recapitulates the Myo9b-/- phenotype of reduced TH1 and increased TH17 differentiation. TSAd siRNA in vivo suppresses malignant pleural effusion development and shifts TH1/TH17 balance. Chromatin immunoprecipitation (ChIP) for H3K27me3 at TSAd promoter, TSAd siRNA in primary T cells with TH1/TH17 differentiation assay, in vivo siRNA delivery with pleural effusion model Journal of immunology Medium 33046503
2025 Affinity-purification mass spectrometry identified DOK2 and PTPN11 as novel ligands of the TSAd SH2 domain. The specific phosphotyrosines on DOK2 and PTPN11 responsible for TSAd SH2 interaction were determined. CRISPR/Cas9 ablation of TSAd and DOK2 in Jurkat T cells resulted in altered tyrosine phosphorylation, suggesting TSAd functions as a negative signaling node via DOK2 and PTPN11. Affinity-purification mass spectrometry (AP-MS), phosphopeptide mapping, CRISPR/Cas9 knockouts in Jurkat T cells, phosphotyrosine immunoblotting bioRxivpreprint Medium bio_10.1101_2025.02.11.636929
2025 Multi-omics data (single-cell RNA-seq, bulk RNA-seq, epigenomic/ATAC, mass spectrometry-based proteomics) from multiple organs indicate that TSAd transcripts are largely absent from endothelial cells, the TSAd promoter resides in closed chromatin in ECs, and TSAd protein is typically undetected in EC proteomes. This challenges the proposed universal role of TSAd in VEGFR2-mediated vascular permeability signaling in ECs. Mining of public scRNA-seq, bulk RNA-seq, epigenomic (chromatin accessibility), and MS proteomics datasets from endothelial cells across multiple organs Angiogenesis Medium 40080216

Source papers

Stage 0 corpus · 38 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis. The EMBO journal 221 15962004
2012 VEGFR2 induces c-Src signaling and vascular permeability in vivo via the adaptor protein TSAd. The Journal of experimental medicine 195 22689825
1998 Molecular cloning of a T cell-specific adapter protein (TSAd) containing an Src homology (SH) 2 domain and putative SH3 and phosphotyrosine binding sites. The Journal of biological chemistry 59 9468509
2001 The T cell regulator gene SH2D2A contributes to the genetic susceptibility of multiple sclerosis. Genes and immunity 43 11528519
2018 The structure of the TsaB/TsaD/TsaE complex reveals an unexpected mechanism for the bacterial t6A tRNA-modification. Nucleic acids research 33 29741707
2016 The endothelial adaptor molecule TSAd is required for VEGF-induced angiogenic sprouting through junctional c-Src activation. Science signaling 33 27436360
2001 A transcription function for the T cell-specific adapter (TSAd) protein in T cells: critical role of the TSAd Src homology 2 domain. The Journal of experimental medicine 30 11413197
2008 Susceptibility to chronic inflammatory demyelinating polyradiculoneuropathy is associated to polymorphic GA repeat in the SH2D2A gene. Journal of neuroimmunology 25 18533279
2014 The kinase Itk and the adaptor TSAd change the specificity of the kinase Lck in T cells by promoting the phosphorylation of Tyr192. Science signaling 24 25492967
2004 Genetic association between juvenile rheumatoid arthritis and polymorphism in the SH2D2A gene. Genes and immunity 24 15129233
2005 The C terminus of T cell-specific adapter protein (TSAd) is necessary for TSAd-mediated inhibition of Lck activity. European journal of immunology 22 15827961
2010 T cell specific adapter protein (TSAd) interacts with Tec kinase ITK to promote CXCL12 induced migration of human and murine T cells. PloS one 21 20305788
2006 Structure function analysis of SH2D2A isoforms expressed in T cells reveals a crucial role for the proline rich region encoded by SH2D2A exon 7. BMC immunology 20 16839418
2004 The p95-100 kDa ligand of the T cell-specific adaptor (TSAd) protein Src-homology-2 (SH2) domain implicated in TSAd nuclear import is p97 Valosin-containing protein (VCP). Immunology letters 18 15752563
2020 Specificity in the biosynthesis of the universal tRNA nucleoside N6-threonylcarbamoyl adenosine (t6A)-TsaD is the gatekeeper. RNA (New York, N.Y.) 17 32385138
2009 The T-cell-specific adapter protein family: TSAd, ALX, and SH2D4A/SH2D4B. Immunological reviews 17 19909368
2007 Expression of SH2D2A in T-cells is regulated both at the transcriptional and translational level. Molecular immunology 16 18160104
2015 T cell specific adaptor protein (TSAd) promotes interaction of Nck with Lck and SLP-76 in T cells. Cell communication and signaling : CCS 15 26163016
2011 Polymorphism of CD1 and SH2D2A genes in inflammatory neuropathies. Journal of the peripheral nervous system : JPNS 15 21696499
2020 TSAd Plays a Major Role in Myo9b-Mediated Suppression of Malignant Pleural Effusion by Regulating TH1/TH17 Cell Response. Journal of immunology (Baltimore, Md. : 1950) 14 33046503
2018 Polarity of CD4+ T cells towards the antigen presenting cell is regulated by the Lck adapter TSAd. Scientific reports 14 30190583
2012 SH2D2A modulates T cell mediated protection to a B cell derived tumor in transgenic mice. PloS one 13 23144743
2004 Transcriptional activation of the SH2D2A gene is dependent on a cyclic adenosine 5'-monophosphate-responsive element in the proximal SH2D2A promoter. Journal of immunology (Baltimore, Md. : 1950) 13 15128801
2000 The SH2D2A gene encoding the T-cell-specific adapter protein (TSAd) is localized centromeric to the CD1 gene cluster on human Chromosome 1. Immunogenetics 13 10752626
2019 Bacillus subtilis YlxR, Which Is Involved in Glucose-Responsive Metabolic Changes, Regulates Expression of tsaD for Protein Quality Control of Pyruvate Dehydrogenase. Frontiers in microbiology 12 31118925
2008 The SH2D2A gene and susceptibility to multiple sclerosis. Journal of neuroimmunology 12 18554728
2023 Downregulation of lncRNA XIST may promote Th17 differentiation through KDM6A-TSAd pathway in neuromyelitis optica spectrum disorders. Multiple sclerosis and related disorders 11 37315471
2004 cDNA cloning of a rat orthologue of SH2D2A encoding T-cell-specific adaptor protein (TSAd): expression in T and NK cells. Immunogenetics 11 15300336
2004 The emerging role of the T cell-specific adaptor (TSAd) protein as an autoimmune disease-regulator in mouse and man. Immunology letters 10 15752554
2023 Structure-function analysis of an ancient TsaD-TsaC-SUA5-TcdA modular enzyme reveals a prototype of tRNA t6A and ct6A synthetases. Nucleic acids research 7 37427786
2009 The adaptor protein LAD/TSAd mediates laminin-dependent T cell migration via association with the 67 kDa laminin binding protein. Experimental & molecular medicine 7 19561400
2006 TSAd interacts with Smad2 and Smad3. Biochemical and biophysical research communications 6 16806069
2023 The NADH recycling enzymes TsaC and TsaD regenerate reducing equivalents for Rieske oxygenase chemistry. The Journal of biological chemistry 5 37673337
2012 Variants in the Signaling Protein TSAd are Associated with Susceptibility to Ovarian Cancer in BRCA1/2 Negative High Risk Families. Biomarker insights 5 23300341
2015 Reduced MCMV Δm157 viral clearance in the absence of TSAd. Scientific reports 4 25783199
2009 The effector functions of mature T lymphocytes are impaired in transgenic mice expressing the SH2 domain of TSAd/Lad. Molecules and cells 3 19756394
2025 Endothelial transcriptomic, epigenomic and proteomic data challenge the proposed role for TSAd in vascular permeability. Angiogenesis 1 40080216
2025 The Impacts of Essential Gcp/TsaD Protein on Cell Morphology, Virulence Expression, and Antibiotic Susceptibility in Staphylococcus aureus. Microorganisms 0 41011442

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