Affinage

UBASH3A

Ubiquitin-associated and SH3 domain-containing protein A · UniProt P57075

Length
661 aa
Mass
74.1 kDa
Annotated
2026-06-10
95 papers in source corpus 21 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UBASH3A (STS-2/TULA) is a lymphoid-enriched multi-domain adaptor that negatively regulates proximal T cell receptor signaling and dampens T cell activation (PMID:14738763, PMID:11281453). It restrains TCR-proximal kinases — suppressing ZAP-70 phosphorylation in T cells, with loss of UBASH3A producing hyperresponsive T cells, elevated cytokine output, and increased autoimmune susceptibility (PMID:14738763, PMID:21393235). The protein is built from an SH3 domain that engages CBL-family E3 ligases (c-Cbl and CBL-B) and the phosphatase PTPN22, a UBA domain that binds mono- and poly-ubiquitin, and a histidine-phosphatase (PGM/2H) domain that oligomerizes (PMID:15159412, PMID:31659016, PMID:37240014). Although the PGM domain adopts a catalytically competent fold using a nucleophilic histidine (His366), its intrinsic phosphatase activity is negligible relative to its paralog STS-1/TULA-2, a difference traced to non-conserved active-site residues; consequently UBASH3A acts largely through protein-protein interactions rather than direct catalysis, and can behave as a dominant-negative against STS-1-mediated Syk/ZAP-70 dephosphorylation (PMID:19196006, PMID:21393235, PMID:20670933, PMID:18189269). Mechanistically, UBASH3A attenuates TCR-induced NF-κB signaling by suppressing IKK complex activation through interactions with non-degradative polyubiquitin chains, TAK1, and NEMO, thereby lowering IL-2 expression (PMID:28607106), and it controls TCR-CD3 complex synthesis, surface turnover, and endocytosis — sequestering dynamin via its SH3 domain to inhibit clathrin-dependent and clathrin-independent endocytic pathways (PMID:17382318, PMID:31659016). Through these activities UBASH3A is a genetically validated, T cell-intrinsic risk locus for type 1 diabetes, where risk alleles modulate its expression and splicing to tune IL-2 production (PMID:28607106, PMID:32694640, PMID:29491471), and it limits T cell-driven inflammation in models of arthritis and colitis (PMID:25047644, PMID:28972439).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2001 Medium

    Established UBASH3A as a lymphoid-restricted multi-domain protein, defining the structural toolkit (SH3, UBA, novel domain) and expression pattern that would frame all later mechanistic work.

    Evidence cDNA cloning, RT-PCR tissue expression, and genomic/domain analysis

    PMID:11281453

    Open questions at the time
    • No function assigned to the domains at this stage
    • Subcellular localization beyond a predicted NLS not demonstrated functionally
  2. 2004 High

    Defined the core physiological role: UBASH3A (with its paralog) negatively regulates TCR signaling by suppressing ZAP-70 phosphorylation, with loss producing autoimmunity-prone hyperresponsive T cells.

    Evidence Sts-1/Sts-2 double-knockout mice, T cell stimulation/phospho assays, cytokine measurement, EAE model

    PMID:14738763

    Open questions at the time
    • Double-KO design does not separate UBASH3A-specific from paralog contribution
    • Mechanism of ZAP-70 suppression not resolved
  3. 2004 High

    Mapped the adaptor logic by showing the SH3 domain binds c-Cbl and the UBA domain binds ubiquitin, linking UBASH3A to receptor downregulation machinery.

    Evidence Affinity chromatography/MS, co-expression in 293T, functional assays in Jurkat cells (idx1); domain binding, Co-IP, endocytosis assays, PGM-mediated oligomerization (idx2)

    PMID:15107835 PMID:15159412

    Open questions at the time
    • Effect on Cbl (degradation vs sequestration) directionally inconsistent across studies
    • Largely demonstrated on EGFR rather than TCR cargo
  4. 2007 High

    Showed UBASH3A inhibits endocytosis broadly by sequestering dynamin through its SH3 domain, distinguishing a dynamin-dependent mechanism from the Cbl/ubiquitin EGFR route.

    Evidence Multi-cargo endocytosis assays, reciprocal Co-IP, colocalization, dynamin overexpression rescue

    PMID:17382318

    Open questions at the time
    • Relevance to TCR-CD3 trafficking not directly tested here
    • Stoichiometry of dynamin sequestration unknown
  5. 2007 Medium

    Extended the interactome beyond immune signaling, linking UBASH3A to ABCE-1 and a UBA-dependent block of HIV-1 particle production.

    Evidence MS identification of TULA-associated ABCE-1, HIV-1 production assays, UBA deletion mutants

    PMID:18006034

    Open questions at the time
    • Single-lab finding outside the core T cell context
    • Direct UBASH3A-ABCE-1 binding not validated reciprocally
  6. 2008 Medium

    Reframed UBASH3A as a near-catalytically-inert phosphatase that acts as a dominant-negative on the active paralog, rather than as a direct enzyme.

    Evidence In vivo/in vitro phospho assays, dominant-negative overexpression, co-transfection (Syk readout)

    PMID:18189269

    Open questions at the time
    • Dominant-negative mechanism inferred from overexpression
    • Endogenous relevance not established
  7. 2009 High

    Provided the structural and mechanistic basis for the phosphatase domain, identifying His366 as the catalytic nucleophile and the specific non-conserved residues that explain low activity versus STS-1.

    Evidence X-ray structures (apo, tungstate, phosphate, phospho-intermediate, vanadate), active-site mutagenesis, enzymatic assays

    PMID:19196006 PMID:19627098

    Open questions at the time
    • Physiological substrate of UBASH3A PGM domain not defined
    • In-cell catalytic relevance unclear given low activity
  8. 2010 High

    Confirmed by unbiased screening that UBASH3A has no detectable intrinsic phosphatase activity, cementing that its function is interaction-driven.

    Evidence Combinatorial phosphotyrosyl peptide library screen with kinetics

    PMID:20670933

    Open questions at the time
    • Cannot exclude activity on non-peptide or conformational substrates
    • Does not address whether catalysis matters in any cellular context
  9. 2011 High

    Pinned the weak residual activity and ZAP-70 phospho-regulation to specific specificity-determinant residues (Glu481/Ser552/Ser582), bridging structure to T cell phosphoregulation.

    Evidence In vitro phosphatase assays with phosphosubstrates, active-site mutagenesis, cell-based phospho analysis

    PMID:21393235

    Open questions at the time
    • Whether weak activity contributes meaningfully to TCR signaling in vivo unresolved
  10. 2017 High

    Identified a distinct NF-κB-suppressing mechanism in human T cells and connected UBASH3A expression to T1D risk alleles and IL-2 output.

    Evidence Co-IP, ubiquitin-binding assays, siRNA, TCR stimulation and IL-2 analysis in primary CD4+ T cells; eQTL of risk alleles

    PMID:28607106

    Open questions at the time
    • Direct binding partner among TAK1/NEMO/polyUb not biochemically dissected
    • How SH3/UBA domains engage the IKK complex unmapped
  11. 2017 High

    Confirmed in human protein that the histidine-phosphatase domain has much lower activity than STS-1 and that STS-1 (not STS-2) robustly dephosphorylates ZAP-70.

    Evidence Crystal structures of Sts-1HP/Sts-2HP, steady-state kinetics, cell-based ZAP-70 assay, inhibitor testing

    PMID:28759203

    Open questions at the time
    • Reinforces that UBASH3A catalytic contribution to ZAP-70 control is minor
    • No direct UBASH3A enzymatic activity on ZAP-70 shown
  12. 2014 Medium

    Demonstrated in vivo that UBASH3A limits T cell-driven mucosal inflammation, with deletion exacerbating colitis via ZAP-70 phospho-regulation.

    Evidence Single/double KO mice, TNBS colitis model, T cell activation and ZAP-70 phospho analysis

    PMID:25047644

    Open questions at the time
    • Single-lab in vivo study
    • UBASH3A-specific contribution partly confounded by paralog co-deletion
  13. 2017 Medium

    Showed the autoimmune phenotype is driven by enhanced effector T cell IL-2 production rather than Treg failure, in a collagen-induced arthritis model.

    Evidence CIA in STS-2 KO mice, intracellular cytokine staining, Treg suppression co-cultures

    PMID:28972439

    Open questions at the time
    • Mechanism linking UBASH3A loss to IL-2 elevation not fully resolved at molecular level
  14. 2018 Medium

    Functionally validated a non-coding T1D variant as an expression/splicing regulator, showing reduced UBASH3A protein raises IL-2 secretion.

    Evidence Haplotype/allele-specific expression, RNA-seq, intron-retention quantification, TCR-stimulated IL-2 assays in primary CD4+ T cells

    PMID:29491471

    Open questions at the time
    • Causal SNP among linked variants not isolated
    • Mechanism of intron-9 retention unknown
  15. 2019 High

    Established UBASH3A control over TCR-CD3 complex synthesis and surface turnover, and mapped CBL-B binding to the SH3 domain, broadening the adaptor interactome via MS.

    Evidence Expression modulation in Jurkat, flow cytometry of surface receptors, MS, Co-IP, domain mapping

    PMID:31659016

    Open questions at the time
    • Mechanism connecting CBL-B binding to CD3 turnover not dissected
    • New MS associations (ERAD, recycling) not functionally validated
  16. 2020 High

    Proved the autoimmune effect is T cell-intrinsic by showing UBASH3A-deficient T cell transfer is sufficient to accelerate diabetes in NOD mice.

    Evidence ZFN KO in NOD mice, insulitis scoring, diabetes incidence, adoptive T cell transfer into NOD.Rag1−/−

    PMID:32694640

    Open questions at the time
    • Does not identify which T cell subset/mechanism dominates the transferred phenotype
  17. 2022 Medium

    Defined upstream epigenetic control of UBASH3A via a super-enhancer (BACH2/MED1/BRD4, eRNAs) in disease-context CD4+ T cells, linking its dysregulation to TCR-induced IL-6.

    Evidence ChIP, LNA-mediated eRNA knockdown, RT-PCR/WB, overexpression, cytokine bead array in RA CD4+ T cells

    PMID:36324153

    Open questions at the time
    • Causal chain from enhancer state to IL-6 not fully mapped
    • Single-lab disease-cohort study
  18. 2023 Medium

    Identified PTPN22 as a direct SH3-domain partner cooperating with UBASH3A to regulate IL-2, integrating two autoimmunity risk genes into one phospho-regulatory node.

    Evidence SH3-mediated Co-IP, domain mapping, RNA-seq of primary CD8+ T cells, statistical interaction analysis

    PMID:37240014

    Open questions at the time
    • Functional consequence of the complex on specific substrates not shown
    • Cooperative IL-2 effect is correlative/transcriptomic
  19. 2024 Medium

    Extended UBASH3A function beyond lymphocytes to a tumor-suppressor role in erythroleukemia, controlled transcriptionally by an FLI1-GATA2 axis and acting in part through HSPA1B.

    Evidence shRNA knockdown, luciferase promoter assays, ChIP, RNA-seq, proliferation/apoptosis assays

    PMID:38461240

    Open questions at the time
    • Mechanism by which UBASH3A induces HSPA1B unknown
    • Relationship to T cell adaptor function unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How UBASH3A's distinct activities (NF-κB/IKK suppression, dynamin-dependent endocytosis, CD3 turnover, PTPN22/CBL-B scaffolding) are coordinated through its domains, and whether residual phosphatase activity matters physiologically, remains unresolved.
  • No integrated structural model of full-length UBASH3A engaging the IKK/ubiquitin machinery
  • Direct cellular substrate(s) of the PGM domain undefined
  • Domain-resolved dissection of which interaction drives the autoimmune IL-2 phenotype lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0031386 protein tag activity 3 GO:0016787 hydrolase activity 2
Localization
GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-5653656 Vesicle-mediated transport 3
Partners
ABCE1CBLCBLBDNM1NEMOPTPN22STS-1TAK1
Complex memberships
IKK complex (NEMO/TAK1-associated)

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Sts-1 and Sts-2 (UBASH3A/STS-2 and its paralog) negatively regulate TCR signaling by suppressing ZAP-70 phosphorylation and activation; T cells from Sts-1/Sts-2 double-knockout mice are hyperresponsive to TCR stimulation with increased ZAP-70 phosphorylation, elevated cytokine production, and increased susceptibility to autoimmunity in a mouse EAE model. Genetic knockout (double KO mice), T cell stimulation assays, phosphorylation analysis, cytokine production measurement, EAE model Immunity High 14738763
2004 TULA (UBASH3A/STS-2) binds to c-Cbl via its SH3 domain and to ubiquitin via its UBA domain; TULA inhibits c-Cbl-mediated downregulation of EGF receptor and upregulates ZAP-70 activity and NF-AT transcription factor activity in Jurkat T cells; the inhibitory effect on c-Cbl appears to involve TULA-induced ubiquitylation and degradation of c-Cbl. Affinity chromatography, mass spectrometry identification, co-expression in 293T cells, functional assays in Jurkat cells, modulation of TULA concentration Oncogene Medium 15107835
2004 Sts-2 (UBASH3A) contains an SH3 domain that interacts with Cbl, a UBA domain that binds directly to mono-ubiquitin or EGFR/Ub chimera, and a phosphoglycerate mutase (PGM) domain that mediates oligomerization; ligand-induced recruitment of Sts-2 into activated EGFR complexes inhibits receptor internalization, reduces EGFR-containing endocytic vesicles, and blocks receptor degradation, leading to prolonged mitogenic signaling. Co-immunoprecipitation, domain binding assays, endocytosis assays, fluorescence microscopy, dominant-negative interference The Journal of biological chemistry High 15159412
2001 UBASH3A encodes a 661-amino-acid protein containing SH3, UBA, and a novel domain with a nuclear localization signal; it is expressed primarily in spleen, peripheral blood leukocytes, and bone marrow; the gene spans 40 kb and is divided into 15 exons. cDNA cloning, RT-PCR expression analysis, sequence/domain analysis, genomic characterization Human genetics Medium 11281453
2009 The PGM/2H-phosphatase domain of Sts-2 (UBASH3A) is an acid-dependent phosphatase with a crystal structure remarkably similar to Sts-1; the catalytic mechanism involves a transiently phosphorylated nucleophilic histidine; non-conserved active site residues Gln372, Ala446, Glu481, Ser552, and Ser582 account for the substantially lower activity of Sts-2 compared to Sts-1. X-ray crystallography (apo, tungstate-bound, phosphate-bound structures), active site mutagenesis, enzymatic activity assays Biochemistry High 19196006
2009 The phosphorylated intermediate and vanadate transition-state analogue structures of the Sts-2 PGM domain confirm His366 as the nucleophilic catalytic residue; the reaction mechanism is partially associative; Glu476 activates a uniquely positioned water molecule; the active site conformation does not change during dephosphorylation. X-ray crystallography of phosphorylated and VO3-bound enzyme forms Biochemistry High 19627098
2011 Sts-2 (UBASH3A) regulates tyrosine phosphorylation levels in T cells including on ZAP-70; the PGM domain of Sts-2 has clear but weak phosphatase activity; residues Glu-481, Ser-552, and Ser-582 are specificity determinants — mutation of these three residues to their Sts-1 counterparts substantially increases Sts-2(PGM) phosphatase activity. In vitro phosphatase assays with new phosphorylated substrates, active site mutagenesis, cell-based phosphorylation analysis The Journal of biological chemistry High 21393235
2008 TULA (UBASH3A/STS-2) has negligible phosphatase activity compared to TULA-2 (STS-1); overexpression of TULA increases Syk tyrosine phosphorylation in cells, acting as a dominant-negative inhibitor of endogenous TULA-2-mediated Syk dephosphorylation rather than as a direct phosphatase. In vivo and in vitro phosphorylation assays, dominant-negative overexpression, co-transfection experiments Journal of cellular biochemistry Medium 18189269
2010 TULA-1 (UBASH3A/STS-2) showed no detectable phosphatase activity toward any phosphotyrosyl peptides in a combinatorial library screen, confirming that its intrinsic enzymatic activity is negligible. TULA-2 (STS-1) showed clear substrate selectivity with two substrate classes. Combinatorial phosphotyrosyl peptide library screening, kinetic analysis The Journal of biological chemistry High 20670933
2007 TULA (UBASH3A) inhibits clathrin-dependent endocytosis (transferrin, LDL uptake) and clathrin-independent but dynamin-dependent endocytosis (CD59, MHC-I) by co-immunoprecipitating with and functionally sequestering dynamin via its SH3 domain binding proline-rich sequences in dynamin; overexpression of dynamin counteracted TULA-mediated inhibition of these pathways but did not rescue EGFR endocytosis (which operates via a distinct Cbl/ubiquitination mechanism). Endocytosis assays (transferrin, LDL, CD59, MHC-I, ricin uptake), co-immunoprecipitation, colocalization microscopy, dynamin overexpression rescue experiments Experimental cell research High 17382318
2017 UBASH3A attenuates NF-κB signal transduction upon TCR stimulation in human T cells by specifically suppressing activation of the IκB kinase (IKK) complex; UBASH3A interacts with non-degradative polyubiquitin chains, TAK1, and NEMO, suggesting ubiquitin-dependent regulation of the NF-κB pathway; T1D risk alleles at rs11203203 and rs80054410 increase UBASH3A expression in primary CD4+ T cells upon TCR stimulation, thereby inhibiting NF-κB and reducing IL-2 expression. Protein-protein interaction studies (Co-IP), ubiquitin-binding assays, siRNA knockdown, TCR stimulation assays, IL-2 expression analysis in primary human CD4+ T cells Diabetes High 28607106
2019 UBASH3A regulates TCR-CD3 complex synthesis and turnover in T cells: modulation of UBASH3A levels in Jurkat cells alters total cellular CD3 chains and cell-surface TCR-CD3 complexes (but not CD28 levels); upon TCR engagement, UBASH3A enhances TCR-CD3 downmodulation from the cell surface; mass spectrometry revealed novel UBASH3A associations with components of ER-associated protein degradation, cell motility, endocytosis, and endocytic recycling pathways; the SH3 domain of UBASH3A mediates binding to CBL-B E3 ubiquitin ligase. Modulation of UBASH3A expression in Jurkat cells, flow cytometry for surface receptor levels, mass spectrometry, protein-protein interaction studies, domain-mapping experiments Journal of immunology High 31659016
2007 TULA (UBASH3A) binds to ABCE-1 (RLI/HP68), a host factor of HIV-1 assembly, as identified by mass spectrometry; TULA proteins substantially inhibit production of both sub-genomic and full-length HIV-1 viral particles in a UBA domain-dependent manner; ABCE-1 recruits TULA to HIV-1 assembly sites where it interferes with late steps of HIV-1 life cycle. Mass spectrometry identification of TULA-associated proteins, HIV-1 production assays, UBA domain deletion mutant analysis Virology Medium 18006034
2017 The histidine phosphatase domains of human Sts-1 and Sts-2 were crystallized; Sts-2HP has significantly lower phosphatase activity than Sts-1HP in steady-state kinetic assays; Sts-1HP is a functional surrogate for full-length Sts-1; the SHP-1 inhibitor PHPS1 inhibits Sts-1 with Ki = 1.05 μM; human Sts-1 has robust phosphatase activity against ZAP-70 in cell-based assays. X-ray crystallography (Sts-1HP apo and sulfate-bound to 2.5/1.9 Å; Sts-2HP sulfate-bound to 2.4 Å), steady-state kinetics, cell-based ZAP-70 phosphatase assay, inhibitor testing Biochemistry High 28759203
2014 Deletion of either or both TULA-family members (TULA/UBASH3A and TULA-2) in mice leads to exacerbated T-cell responses and inflammation in TNBS-induced colitis; both single and double KO exacerbate inflammation, with double KO having a greater effect; the mechanism involves regulation of ZAP-70 phosphorylation in T cells. Single and double knockout mice, TNBS-induced colitis model, T-cell activation assays, TCR signaling analysis (ZAP-70 phosphorylation) Immunology and cell biology Medium 25047644
2017 STS-2 (UBASH3A) KO mice immunized with collagen develop arthritis more frequently than WT mice; STS-2 KO CD4+ T cells show increased IL-2 production upon TCR stimulation; STS-2 KO Tregs normally suppress T cell proliferation, suggesting the pro-arthritis phenotype is mediated by enhanced IL-2 production from effector T cells rather than impaired Treg function. Collagen-induced arthritis model in KO mice, intracellular cytokine staining, co-culture Treg suppression assays Modern rheumatology Medium 28972439
2020 UBASH3A deficiency in NOD mice accelerates type 1 diabetes development and enhances salivary gland inflammation; adoptive transfer of UBASH3A-deficient splenic T cells into NOD.Rag1−/− mice was sufficient to promote T1D development, demonstrating that the UBASH3A effect is T cell-intrinsic. Zinc-finger nuclease-mediated KO in NOD mice, insulitis scoring, diabetes incidence monitoring, adoptive T cell transfer, flow cytometry Scientific reports High 32694640
2022 In CD4+ T cells from rheumatoid arthritis patients, UBASH3A transcription is suppressed via epigenetic regulation of a super-enhancer, involving accumulation of the silencing transcription factor BACH2 and absence of MED1/BRD4 at UBASH3A loci; knockdown of enhancer RNAs (eRNA_1 and eRNA_3) reduces UBASH3A mRNA; overexpression of UBASH3A in RA CD4+ T cells significantly inhibits TCR-induced IL-6 production. ChIP analysis, locked nucleic acid-mediated eRNA knockdown, RT-PCR/western blotting, UBASH3A plasmid overexpression, cytometric bead array for cytokines Inflammation and regeneration Medium 36324153
2023 UBASH3A physically interacts with PTPN22 via its SH3 domain in T cells; this interaction is not altered by the T1D risk coding variant rs2476601 in PTPN22; UBASH3A and PTPN22 transcript levels exert a cooperative effect on IL2 expression in human primary CD8+ T cells. Co-immunoprecipitation (SH3 domain-mediated), domain mapping, RNA-seq analysis of primary T cells, statistical interaction analysis International journal of molecular sciences Medium 37240014
2024 UBASH3A knockdown in erythroleukemic cells increases proliferation, associated with induction of HSPA1B (HSP70); UBASH3A acts as a tumor suppressor in erythroleukemia in part through activation of HSPA1B; FLI1 indirectly inhibits UBASH3A transcription via GATA2; UBASH3A is transcriptionally distinct from UBASH3B in the context of FLI1-driven leukemia. shRNA knockdown, luciferase promoter assays, ChIP, RNAseq, MTT proliferation assays, flow cytometry apoptosis assays BMC cancer Medium 38461240
2024 CD6 regulates UBASH3A expression in CD4+ T cells during murine coronavirus infection; CD6-deficient mice showed reduced infection-induced upregulation of UBASH3A in lymph nodes, associated with intensified TCR signal strength and greater T cell activation, suggesting that CD6 suppresses T cell activation in part by promoting UBASH3A expression. CD6 KO mouse model, gene expression analysis, TCR signal strength measurement, T cell activation assays bioRxiv (preprint)preprint Low
2018 A non-coding T1D-associated variant rs1893592 in UBASH3A affects disease risk; its minor allele is associated with reduced overall UBASH3A mRNA levels and increased proportion of a low-abundance intron-9-retaining transcript that cannot produce full-length protein; this reduction leads to increased IL-2 secretion upon TCR stimulation in primary CD4+ T cells. Haplotype analysis, allele-specific expression in primary human CD4+ T cells, RNA-seq, TCR stimulation assays, IL-2 measurement European journal of human genetics Medium 29491471

Source papers

Stage 0 corpus · 95 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Tula virus: a newly detected hantavirus carried by European common voles. Journal of virology 176 7966573
2004 Regulation of ZAP-70 activation and TCR signaling by two related proteins, Sts-1 and Sts-2. Immunity 153 14738763
2004 Suppressors of T-cell receptor signaling Sts-1 and Sts-2 bind to Cbl and inhibit endocytosis of receptor tyrosine kinases. The Journal of biological chemistry 120 15159412
2007 Tula and Puumala hantavirus NSs ORFs are functional and the products inhibit activation of the interferon-beta promoter. Journal of medical virology 117 17705180
1996 Isolation and characterization of Tula virus, a distinct serotype in the genus Hantavirus, family Bunyaviridae. The Journal of general virology 117 9000098
2010 Electron cryotomography of Tula hantavirus suggests a unique assembly paradigm for enveloped viruses. Journal of virology 111 20219926
1999 Recombination in Tula hantavirus evolution: analysis of genetic lineages from Slovakia. Journal of virology 87 9847372
1996 Inhibition of puumala and tula hantaviruses in Vero cells by MxA protein. Virology 82 8862399
1995 Genetic variation in Tula hantaviruses: sequence analysis of the S and M segments of strains from Central Europe. Virus research 79 8837887
2004 TULA: an SH3- and UBA-containing protein that binds to c-Cbl and ubiquitin. Oncogene 78 15107835
2011 Sts-2 is a phosphatase that negatively regulates zeta-associated protein (ZAP)-70 and T cell receptor signaling pathways. The Journal of biological chemistry 68 21393235
2010 A novel histidine tyrosine phosphatase, TULA-2, associates with Syk and negatively regulates GPVI signaling in platelets. Blood 61 20585042
2005 Tula hantavirus triggers pro-apoptotic signals of ER stress in Vero E6 cells. Virology 57 15708603
1997 Puumala virus and two genetic variants of Tula virus are present in Austrian rodents. Journal of medical virology 57 9334930
2017 UBASH3A Mediates Risk for Type 1 Diabetes Through Inhibition of T-Cell Receptor-Induced NF-κB Signaling. Diabetes 55 28607106
2008 TULA proteins regulate activity of the protein tyrosine kinase Syk. Journal of cellular biochemistry 52 18189269
2001 Isolation and characterization of the UBASH3A gene on 21q22.3 encoding a potential nuclear protein with a novel combination of domains. Human genetics 50 11281453
2010 Determination of the substrate specificity of protein-tyrosine phosphatase TULA-2 and identification of Syk as a TULA-2 substrate. The Journal of biological chemistry 49 20670933
2019 UBASH3A Regulates the Synthesis and Dynamics of TCR-CD3 Complexes. Journal of immunology (Baltimore, Md. : 1950) 45 31659016
2003 Non-covalent interaction between nucleocapsid protein of Tula hantavirus and small ubiquitin-related modifier-1, SUMO-1. Virus research 45 12606074
2012 Tula virus infections in the Eurasian water vole in Central Europe. Vector borne and zoonotic diseases (Larchmont, N.Y.) 43 22225425
2013 Tula hantavirus infection in immunocompromised host, Czech Republic. Emerging infectious diseases 42 24209605
2004 Tula hantavirus infection of Vero E6 cells induces apoptosis involving caspase 8 activation. The Journal of general virology 42 15483239
2002 Transfection-mediated generation of functionally competent Tula hantavirus with recombinant S RNA segment. The EMBO journal 40 11889055
1996 Characterization of Tula virus antigenic determinants defined by monoclonal antibodies raised against baculovirus-expressed nucleocapsid protein. Virus research 39 8896239
2016 High genetic structuring of Tula hantavirus. Archives of virology 38 26831932
2013 TULA-family proteins: a new class of cellular regulators. Journal of cellular physiology 38 22689384
2012 Once phosphorylated, tyrosines in carboxyl terminus of protein-tyrosine kinase Syk interact with signaling proteins, including TULA-2, a negative regulator of mast cell degranulation. The Journal of biological chemistry 37 22267732
2003 Mapping of the regions involved in homotypic interactions of Tula hantavirus N protein. Journal of virology 35 14512541
2012 TULA-2, a novel histidine phosphatase, regulates bone remodeling by modulating osteoclast function. Cellular and molecular life sciences : CMLS 33 23149425
2011 The C-terminal 42 residues of the Tula virus Gn protein regulate interferon induction. Journal of virology 33 21367904
2007 The Cbl-interacting protein TULA inhibits dynamin-dependent endocytosis. Experimental cell research 33 17382318
2013 Evidence of new risk genetic factor to systemic lupus erythematosus: the UBASH3A gene. PloS one 30 23565265
2009 Structural and functional characterization of the 2H-phosphatase domain of Sts-2 reveals an acid-dependent phosphatase activity. Biochemistry 30 19196006
2004 Tula hantavirus L protein is a 250 kDa perinuclear membrane-associated protein. The Journal of general virology 30 15105534
2002 Identification of Tula hantavirus in Pitymys subterraneus captured in the Cacak region of Serbia-Yugoslavia. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 30 12044299
2015 Tula hantavirus infection in a hospitalised patient, France, June 2015. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 29 26691901
2008 Tula hantavirus isolate with the full-length ORF for nonstructural protein NSs survives for more consequent passages in interferon-competent cells than the isolate having truncated NSs ORF. Virology journal 29 18190677
2016 TULA-2 Protein Phosphatase Suppresses Activation of Syk through the GPVI Platelet Receptor for Collagen by Dephosphorylating Tyr(P)346, a Regulatory Site of Syk. The Journal of biological chemistry 28 27609517
1998 Completion of the Tula hantavirus genome sequence: properties of the L segment and heterogeneity found in the 3' termini of S and L genome RNAs. The Journal of general virology 28 9820136
1996 Quasispecies in wild-type tula hantavirus populations. Journal of virology 28 8971044
2014 Members of the novel UBASH3/STS/TULA family of cellular regulators suppress T-cell-driven inflammatory responses in vivo. Immunology and cell biology 26 25047644
2008 Multidomain STS/TULA proteins are novel cellular regulators. IUBMB life 26 18344182
2016 TULA-2 (T-Cell Ubiquitin Ligand-2) Inhibits the Platelet Fc Receptor for IgG IIA (FcγRIIA) Signaling Pathway and Heparin-Induced Thrombocytopenia in Mice. Arteriosclerosis, thrombosis, and vascular biology 23 27765766
2018 Molecular-genetic characterization of common, noncoding UBASH3A variants associated with type 1 diabetes. European journal of human genetics : EJHG 22 29491471
2007 TULA proteins bind to ABCE-1, a host factor of HIV-1 assembly, and inhibit HIV-1 biogenesis in a UBA-dependent fashion. Virology 20 18006034
2009 Tula hantavirus NSs protein accumulates in the perinuclear area in infected and transfected cells. Archives of virology 19 19956987
2019 TULA proteins as signaling regulators. Cellular signalling 18 31639493
2013 Evidence of recombination in Tula virus strains from Serbia. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 18 24008094
2020 UBASH3A deficiency accelerates type 1 diabetes development and enhances salivary gland inflammation in NOD mice. Scientific reports 17 32694640
2018 TULA-family proteins: Jacks of many trades and then some. Journal of cellular physiology 17 30076707
2009 Structures of the phosphorylated and VO(3)-bound 2H-phosphatase domain of Sts-2. Biochemistry 16 19627098
2008 First detection of Tula hantaviruses in Microtus arvalis voles in Hungary. Archives of virology 16 18836679
2015 Association of UBASH3A gene polymorphisms and systemic lupus erythematosus in a Chinese population. Gene 15 25843625
2008 New Genetic Lineage of Tula Hantavirus in Microtus arvalis obscurus in Eastern Kazakhstan. The open virology journal 15 19440462
2022 IL-6 production through repression of UBASH3A gene via epigenetic dysregulation of super-enhancer in CD4+ T cells in rheumatoid arthritis. Inflammation and regeneration 13 36324153
2020 miR-25-3p promotes endothelial cell angiogenesis in aging mice via TULA-2/SYK/VEGFR-2 downregulation. Aging 13 33201836
2017 Association of UBASH3A gene polymorphism and atopic dermatitis in the Chinese Han population. Genes and immunity 13 28747736
2017 Structural and Functional Characterization of the Histidine Phosphatase Domains of Human Sts-1 and Sts-2. Biochemistry 13 28759203
2009 Degradation and aggresome formation of the Gn tail of the apathogenic Tula hantavirus. The Journal of general virology 13 19675185
2021 CRKL, AIFM3, AIF, BCL2, and UBASH3A during Human Kidney Development. International journal of molecular sciences 12 34502088
2020 The RNA Replication Site of Tula Orthohantavirus Resides within a Remodelled Golgi Network. Cells 12 32605035
2018 TULA-2 Deficiency Enhances Platelet Functional Responses to CLEC-2 Agonists. TH open : companion journal to thrombosis and haemostasis 12 31249969
1996 Unique and conserved features of Tula hantavirus M gene encoding envelope glycoproteins G1 and G2. Virus genes 12 8883363
2019 Puumala and Tula Virus Differ in Replication Kinetics and Innate Immune Stimulation in Human Endothelial Cells and Macrophages. Viruses 11 31540120
2017 Suppressor of TCR signaling-2 (STS-2) suppresses arthritis development in mice. Modern rheumatology 11 28972439
2014 Adler hantavirus, a new genetic variant of Tula virus identified in Major's pine voles (Microtus majori) sampled in southern European Russia. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 11 25433134
2019 Identification and characterization of a novel subtype of Tula virus in Microtus arvalis obscurus voles sampled from Xinjiang, China. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 10 31446137
2018 A novel genetic lineage of Tula orthohantavirus in Altai voles (Microtus obscurus) from Turkey. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 10 30465911
2024 FLI1 induces erythroleukemia through opposing effects on UBASH3A and UBASH3B expression. BMC cancer 8 38461240
2023 TULA Proteins in Men, Mice, Hens, and Lice: Welcome to the Family. International journal of molecular sciences 8 37298079
2017 Evaluation of the association of UBASH3A and SYNGR1 with rheumatoid arthritis and disease activity and severity in Han Chinese. Oncotarget 8 29262569
2013 Air pollutant characterization in Tula industrial corridor, Central Mexico, during the MILAGRO study. BioMed research international 8 23484131
2023 UBASH3A Interacts with PTPN22 to Regulate IL2 Expression and Risk for Type 1 Diabetes. International journal of molecular sciences 7 37240014
2021 T Cell Receptor Genotype and Ubash3a Determine Susceptibility to Rat Autoimmune Diabetes. Genes 7 34205929
2010 Different cross-reactivity of human and rodent sera to Tula virus and Puumala virus. Comparative immunology, microbiology and infectious diseases 7 20116854
2007 Chemokine production predominates in human monocytes infected with Tula virus. Viral immunology 7 17425435
2021 Spatial and Temporal Dynamics and Molecular Evolution of Tula orthohantavirus in German Vole Populations. Viruses 6 34208398
2005 Recombinant Tula hantavirus shows reduced fitness but is able to survive in the presence of a parental virus: analysis of consecutive passages in a cell culture. Virology journal 6 15725355
2024 Roles of TULA-family proteins in T cells and autoimmune diseases. Genes and immunity 4 39558087
2022 Molecular Characterisation and Phylogeny of Tula Virus in Kazakhstan. Viruses 4 35746729
2021 FREQUENT LEPTOSPIRA SPP. DETECTION BUT ABSENCE OF TULA ORTHOHANTAVIRUS IN MICROTUS SPP. VOLES, NORTHWESTERN SPAIN. Journal of wildlife diseases 4 34320644
2019 Molecular evidence of Tula virus in Microtus obscurus in the region of Yili, Xinjiang, China. BMC infectious diseases 4 31200661
2019 Tula orthohantavirus nucleocapsid protein is cleaved in infected cells and may sequester activated caspase-3 during persistent infection to suppress apoptosis. The Journal of general virology 4 31268416
2014 Enhanced response of T cells from murine gammaherpesvirus 68-infected mice lacking the suppressor of T cell receptor signaling molecules Sts-1 and Sts-2. PloS one 4 24587276
2014 Lack of association between polymorphisms in the UBASH3A gene and autoimmune thyroid disease: a case control study. Arquivos brasileiros de endocrinologia e metabologia 4 25211447
2023 STS-1 and STS-2, Multi-Enzyme Proteins Equipped to Mediate Protein-Protein Interactions. International journal of molecular sciences 3 37298164
2022 TULA-Family Regulators of Platelet Activation. International journal of molecular sciences 3 36499237
2024 Genome-wide support for incipient Tula hantavirus species within a single rodent host lineage. Virus evolution 2 38361825
2026 Higher Promoter Methylation of the Ubiquitin-Associated and SH3 Domain Containing A (UBASH3A) Gene Is Associated With T-Lymphocyte Ontogeny and Reduced Susceptibility to Early-Onset Sepsis. The Journal of infectious diseases 0 41408597
2025 Exploring UBASH3A: from immune regulation to autoimmune diseases. Journal of translational medicine 0 40707988
2024 Role of Tula-Family Proteins in Cell Signaling and Activation: Advances and Challenges. International journal of molecular sciences 0 38674019
2015 [TULA HANTAVIRUS IN CRIMEA]. Molekuliarnaia genetika, mikrobiologiia i virusologiia 0 27192820
2014 [Detection of Babesia canis (Piroplasmida) DNA in the blood samples and lysates of the ticks Dermacentor reticulatus (Ixodidae) collected in the Tula and Moscow Regions]. Meditsinskaia parazitologiia i parazitarnye bolezni 0 24738223
2003 Human papillomavirus 16/18 types among young women from tula (Russia). Journal of lower genital tract disease 0 17051036

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