Affinage

HCST

Hematopoietic cell signal transducer · UniProt Q9UBK5

Round 2 corrected
Length
93 aa
Mass
9.5 kDa
Annotated
2026-04-28
82 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HCST (DAP10) is a transmembrane adaptor protein that couples activating immunoreceptors—primarily NKG2D, but also Ly49H, MDL-1, TREM2, RAGE, and CD200AR—to intracellular signaling cascades in NK cells, T cells, osteoclasts, and keratinocytes (PMID:10426994, PMID:19251634, PMID:25002577, PMID:33829411). Its cytoplasmic YINM motif simultaneously recruits the p85 subunit of PI3K and a Grb2–Vav1 complex; both interactions are required for full downstream activation of Akt, ERK, calcium flux, cytoskeletal polarization at the immunological synapse, and cytotoxic granule release (PMID:16582911, PMID:16887996, PMID:26508790). DAP10 surface expression is regulated transcriptionally by TGF-β1 (which excludes RNA Pol II from the DAP10 promoter) and IL-21, and post-transcriptionally by γc cytokines that promote DAP10 protein synthesis and glycosylation required for NKG2D association and stabilization (PMID:21816829, PMID:16424177). Ligand-induced ubiquitylation of DAP10 drives receptor endocytosis that is itself required for ERK signaling and effector function, while DAP10-deficient mice develop osteopetrosis and display altered NKT/Treg activation thresholds, revealing roles beyond lymphocyte cytotoxicity (PMID:26508790, PMID:17785813, PMID:19251634).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1999 High

    Identification of DAP10 as a transmembrane adaptor that pairs with NKG2D and recruits PI3K via its YINM motif established the first non-ITAM activation mechanism for NK receptors, answering how NKG2D signals without Syk-family kinases.

    Evidence Co-immunoprecipitation, transfection, and PI3K recruitment assays in NK/T cell lines; independent cloning and Grb2 binding demonstration

    PMID:10426994 PMID:10528161

    Open questions at the time
    • Relative contributions of PI3K vs. Grb2 recruitment unresolved
    • In vivo requirement not yet tested
  2. 2000 High

    Transmembrane domain swap experiments demonstrated that DAP10 and DAP12 achieve receptor specificity through their transmembrane regions and activate distinct signaling pathways (PI3K vs. ITAM/Syk), resolving how structurally similar adaptors partition among activating receptors.

    Evidence TM domain chimeras with NK cytotoxicity and cytokine assays

    PMID:11015446

    Open questions at the time
    • Structural basis of TM-mediated specificity undefined
    • Stoichiometry of receptor–adaptor complexes unknown
  3. 2003 High

    Mutational dissection of the YINM motif showed it couples NKG2D to PI3K, Vav1, Rho GTPases, and PLC independently of Syk kinases, defining the complete proximal signaling module downstream of DAP10.

    Evidence YINM point mutations with NK killing assays and multi-pathway signaling analysis

    PMID:12740575

    Open questions at the time
    • Whether both PI3K and Grb2 branches are co-required or redundant was unresolved
    • Kinase(s) phosphorylating YINM not identified
  4. 2006 High

    Simultaneous binding of both Grb2–Vav1 and p85-PI3K to the same DAP10 YINM motif was shown to be required for full calcium flux and cytotoxicity, resolving the non-redundancy of the two signaling arms and establishing Vav1 as the specific Vav family member mediating DAP10-dependent cytoskeletal polarization and synapse maturation.

    Evidence Dominant-negative constructs and YINM point mutations with calcium, Co-IP, and cytotoxicity assays; Vav1/2/3 single and combinatorial KO mice with NK killing assays and cytoskeletal imaging

    PMID:15365099 PMID:16582911 PMID:16887996

    Open questions at the time
    • Structural basis for simultaneous Grb2 and p85 occupancy of one motif unclear
    • How Vav1 specificity over Vav2/3 is achieved molecularly not defined
  5. 2009 High

    DAP10 was found to extend beyond NKG2D pairing to form signaling complexes with MDL-1 (via DAP12-dependent recruitment) and Ly49H, and DAP10-deficient mice developed osteopetrosis, broadening DAP10's biological role to osteoclastogenesis and antiviral NK responses.

    Evidence Reciprocal Co-IP of MDL-1–DAP12–DAP10 trimolecular complex; DAP10 KO mouse bone histology and osteoclast assays; DAP10/DAP12 single/double KO MCMV infection model with ERK, IFN-γ, and viral titer readouts

    PMID:17785813 PMID:19251634 PMID:19332875

    Open questions at the time
    • Whether DAP10 signals autonomously or only through DAP12-containing complexes with MDL-1 not clarified
    • Functional significance of DAP10–Ly49D association disputed between labs
  6. 2011 High

    The opposing transcriptional regulation of DAP10 was elucidated: TGF-β1 excludes RNA Pol II from the DAP10 promoter to suppress expression, while γc cytokines promote post-transcriptional DAP10 synthesis and glycosylation required for NKG2D association, explaining how the tumor/infection microenvironment tunes NKG2D–DAP10 surface levels.

    Evidence ChIP for RNA Pol II at DAP10 promoter with TGF-β1 treatment; glycosylation inhibitor experiments showing loss of NKG2D–DAP10 co-IP; IL-21 promoter reporter assay

    PMID:16424177 PMID:21816829

    Open questions at the time
    • Transcription factors mediating TGF-β1's exclusion of Pol II not identified
    • Specific glycosylation sites on DAP10 required for NKG2D binding unknown
  7. 2014 Medium

    Discovery that DAP10 pairs with RAGE in keratinocytes to switch RAGE signaling from apoptotic (caspase-8) to pro-survival (Akt) extended DAP10 function beyond hematopoietic cells.

    Evidence Co-IP of RAGE–DAP10, Akt phosphorylation and caspase-8 assays, DAP10 blocking antibody in transformed keratinocytes

    PMID:25002577

    Open questions at the time
    • Physiological relevance of RAGE–DAP10 in vivo not tested
    • Whether the YINM motif mediates PI3K recruitment in the RAGE context not shown
    • Single lab observation
  8. 2015 High

    Ligand-induced ubiquitylation of DAP10 was shown to drive NKG2D–DAP10 endocytosis, and this endosomal trafficking was required for ERK activation and effector functions (granule release, IFN-γ), revealing that DAP10 signals from endosomes, not only from the plasma membrane.

    Evidence Ubiquitylation biochemistry, dominant-negative ubiquitin, confocal endocytosis imaging, ERK and effector function assays in human NK cells

    PMID:26508790

    Open questions at the time
    • E3 ligase responsible for DAP10 ubiquitylation not identified
    • Specific ubiquitin chain type (K48 vs. K63) not determined
    • Whether endosomal signaling applies to non-NKG2D complexes unknown
  9. 2019 High

    EVL was identified as a DAP10-recruited actin regulator at the NK synapse, binding through the same Grb2/Vav1 site, and required for F-actin generation and target cell killing, adding a direct cytoskeletal effector to the DAP10 signaling module.

    Evidence Co-IP of EVL–DAP10–Grb2–Vav1, siRNA knockdown with synapse imaging and cytotoxicity assays

    PMID:31235500

    Open questions at the time
    • How EVL, Grb2, and Vav1 are coordinated at a single DAP10 motif structurally unresolved
    • Whether EVL is required for non-NKG2D DAP10 complexes untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the identity of the E3 ubiquitin ligase that ubiquitylates DAP10, the structural basis for simultaneous occupancy of the YINM motif by PI3K-p85 and Grb2–Vav1–EVL, the kinase(s) that phosphorylate the YINM tyrosine in different receptor contexts, and whether DAP10's role in osteoclastogenesis and RAGE signaling involves the same downstream effectors as in NK cells.
  • E3 ligase for DAP10 ubiquitylation unidentified
  • No structural model of DAP10 signalosome
  • YINM kinase identity context-dependent and undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005768 endosome 2
Pathway
R-HSA-168256 Immune System 6 R-HSA-162582 Signal Transduction 5
Partners
AGEREVLGRB2KLRK1PIK3R1TREM2TYROBPVAV1
Complex memberships
MDL-1–DAP12–DAP10NKG2D–DAP10TREM2–DAP12–DAP10

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 DAP10 (HCST/KAP10) was identified as a transmembrane adaptor protein that forms an activating immunoreceptor complex with NKG2D on NK and T cells, recognizing the stress-inducible MHC molecule MICA. The cytoplasmic YINM (YxxM) motif of DAP10 recruits the p85 subunit of PI3-kinase, providing NKG2D-dependent signal transduction. Co-immunoprecipitation, transfection/expression studies, PI3K recruitment assay, cell surface expression analysis Science High 10426994
1999 DAP10 (KAP10) is genetically linked to DAP12 on human chromosome 19 and, unlike ITAM-containing adaptors, signals via phosphorylation of its cytoplasmic YINM motif to activate PI3K and downstream Akt, rather than recruiting Syk-family kinases. DAP10 can also bind the adaptor protein Grb2. Molecular cloning, sequence analysis, transfection, PI3K/Akt activation assays, Grb2 binding assay Journal of immunology High 10528161
2000 Despite high similarity between DAP10 and DAP12, their transmembrane regions are sufficient to confer specific association with distinct ligand-binding receptor partners. DAP10 signals via the PI3K pathway (YxNM motif), while DAP12 signals via Syk/ZAP70 through its ITAM motif. Cross-linking of either DAP10- or DAP12-associated receptors alone can trigger NK cytotoxicity, but synergy occurs in cytokine production when both are co-engaged. Transfection with transmembrane domain swap mutants, NK cell cytotoxicity assays, cytokine production assays, co-immunoprecipitation The Journal of experimental medicine High 11015446
2001 Pig DAP10 contains conserved structural features including an aspartic acid in the transmembrane domain, two cysteines in the extracellular domain, and a PI3K-binding YxxM motif in the cytoplasmic region. Pig NKG2D requires DAP10 for cell surface expression when transiently transfected into COS-7 cells, demonstrating the conserved requirement for DAP10 in NKG2D surface trafficking. cDNA cloning, sequence analysis, transient transfection in COS-7 cells, cell surface expression by flow cytometry Immunogenetics Medium 11398969
2003 A critical YINM amino acid motif in the DAP10 cytoplasmic tail couples NKG2D receptor stimulation to activation of PI3K, Vav1, Rho family GTPases, and phospholipase C, triggering NK cell killing independently of Syk family tyrosine kinases. This defines a Syk-independent activation pathway for ITAM-lacking receptor complexes. Mutational analysis of DAP10 cytoplasmic YINM motif, NK cell killing assays, signaling pathway analysis (PI3K, Vav1, Rho GTPase, PLC activation), Syk kinase inhibition Nature immunology High 12740575
2003 SIRPβ1 can associate with DAP10 in transfected RBL-2H3 cells, but engagement of SIRPβ1–DAP10 complexes alone does not trigger serotonin release or TNF secretion; instead, DAP10 provides co-stimulatory activity that enhances FcεRI-mediated effector functions under sub-optimal stimulation conditions, demonstrating that DAP10's signaling output is context-dependent. Transfection of RBL-2H3 cells, co-immunoprecipitation, serotonin release assay, TNF secretion assay, FcεRI co-stimulation assay European journal of immunology Medium 14635062
2004 Using mice lacking one, two, or all three Vav family proteins, Vav1 deficiency alone is sufficient to disrupt DAP10-mediated NK cell cytotoxicity, whereas Vav2 and Vav3 are preferentially required for FcRγ- and DAP12-mediated cytotoxicity. This places Vav1 specifically downstream of DAP10 in NK cell activation. Genetic epistasis using Vav1/2/3 single, double, and triple knockout mice; NK cell cytotoxicity assays The Journal of experimental medicine High 15365099
2005 Stable RNA interference-mediated silencing of DAP10 (and NKG2D or DAP12) in human CD8+ T cells and NK cells reduces cytolysis of tumor cells including autologous ovarian cancer cells, and abolishes in vivo antitumor activity, demonstrating that DAP10 is required for effector cell function. Lentiviral stable shRNA knockdown, in vitro tumor cytolysis assays, in vivo antitumor model Journal of immunology High 16339517
2006 For NKG2D-DAP10-mediated cytotoxicity, both Grb2–Vav1 binding and p85 PI3K binding to the DAP10 YINM motif are required. Grb2–Vav1 binding to DAP10 is sufficient to initiate tyrosine phosphorylation events, but full calcium release and cytotoxicity require the simultaneous recruitment of both Grb2–Vav1 and p85 to the same DAP10 motif. Dominant-negative constructs, point mutations of DAP10 YINM motif, co-immunoprecipitation, calcium flux assays, NK cell cytotoxicity assays Nature immunology High 16582911
2006 Vav1 is a critical signaling mediator downstream of DAP10 in NK cells, required for DAP10-induced cytoskeletal polarization involving both actin and microtubule networks, maturation of the cytolytic synapse, and target cell lysis. Vav1 interacts with DAP10 YINM motifs through the adaptor Grb2 and is required for activation of PI3K-dependent Akt signaling downstream of DAP10. Vav1/DAP12 double-knockout mice, NK cell cytoskeletal polarization assays (imaging), synapse maturation analysis, cytotoxicity assays, Co-IP of Vav1–Grb2–DAP10 Journal of immunology High 16887996
2006 IL-21 down-regulates NKG2D–DAP10 surface expression on human NK and CD8+ T cells by markedly reducing DAP10 transcription, as demonstrated by reduced DAP10 promoter activity in a luciferase reporter assay. This functional loss of DAP10 correlates with impaired NKG2D-mediated NK cell cytotoxicity and degranulation. Primary NK/CD8+ T cell culture with cytokines, flow cytometry, DAP10 luciferase reporter assay, redirected lysis assay, degranulation assay Journal of immunology High 16424177
2007 DAP10-deficient mice develop osteopetrosis with age due to reduced osteoclast numbers, revealing a physiological role for DAP10 in bone remodeling. DAP10 deficiency also results in hyperactive NKT cell functions and impaired regulatory T cell (Treg) activation, showing that constitutive DAP10 signaling regulates immune tolerance by adjusting the activation threshold of NKT cells and Tregs. DAP10 knockout mouse analysis, bone histology, NK/NKT cell functional assays (cytotoxicity, cytokine), Treg activation assays (IL-2, IL-10, IFN-γ production) Journal of immunology Medium 17785813
2008 LGLL cells express elevated DAP10 and DAP12 with constitutively activated downstream targets. Expression of dominant-negative DAP10 dramatically reduces the lytic capacity of LGLL CD8+CD28null T cells against pulmonary artery endothelial and synovial cells, demonstrating that DAP10 signaling is required for enhanced cytotoxicity in this leukemia. Dominant-negative DAP10 expression, cytotoxicity assays against endothelial and synovial target cells, western blot for constitutive downstream signaling Blood Medium 19075187
2009 DAP10 associates with the myeloid receptor MDL-1, which also associates with DAP12. In osteoclasts and bone marrow-derived macrophages, MDL-1 forms trimolecular complexes with both DAP12 and DAP10 (ITAM/YINM motifs), and DAP10 association with MDL-1 depends almost entirely on DAP12, suggesting DAP12-dependent recruitment of DAP10 into the complex. DAP10-deficient mice become osteopetrotic, confirming DAP10's role in osteoclastogenesis. Co-immunoprecipitation of MDL-1–DAP12–DAP10 complexes, DAP10 knockout mouse bone phenotype analysis, in vitro osteoclastogenesis assay Proceedings of the National Academy of Sciences High 19251634
2009 During NK cell activation, exposure to MICB-expressing target cells causes lysosomal degradation of DAP10, with approximately 50% of total NKG2D protein degraded. DAP10 traffics to secretory lysosomes in activated NK cells upon interaction with MICB-expressing targets, and polarization of DAP10-containing secretory lysosomes to the cytotoxic immune synapse is observed, suggesting that rapid DAP10/NKG2D degradation upon synapse formation explains receptor down-regulation after chronic ligand exposure. Confocal microscopy, lysosomal inhibitor treatment, subcellular fractionation, flow cytometry for NKG2D surface expression kinetics in NKL cells and primary NK cells The Journal of biological chemistry Medium 19329438
2009 Ly49H must associate with and signal via both DAP10 and DAP12 for optimal NK cell function during MCMV infection. In the absence of DAP12, DAP10 enables Ly49H-mediated target cell killing and proliferation. DAP10-deficient Ly49H+ NK cells show diminished ERK1/2 activation, reduced IFN-γ production, and impaired control of MCMV infection, demonstrating that DAP10 contributes distinct signaling outputs (ERK activation, cytokine production) to the Ly49H receptor complex. DAP10 and DAP12 single/double knockout mice, MCMV infection model, NK cell cytotoxicity assays, proliferation assays, ERK1/2 phosphorylation, IFN-γ production, viral titer measurement The Journal of experimental medicine High 19332875
2009 DAP10 associates with Ly49H and Ly49D in primary mouse NK cells, slightly contributing to their cell surface expression, but this association has no significant impact on Ly49H-mediated control of MCMV infection in physiological conditions, indicating that functional consequences of DAP10 association vary widely among activating NK receptors. Co-immunoprecipitation from primary NK cells, flow cytometry for receptor surface expression, MCMV infection model in DAP10-deficient mice European journal of immunology Medium 19247984
2010 TREM2/DAP12-dependent activation of PI3K requires DAP10 as a co-signaling adaptor. Ligation of TREM2 activates PI3K, ERK1/2, and Vav3; induces Ca2+ mobilization and actin reorganization; and prevents apoptosis. DAP10 is essential for recruitment of PI3K to the TREM2–DAP12 signaling complex. SHIP1 inhibits this pathway by binding DAP12 via its SH2 domain, preventing PI3K recruitment to DAP12. TREM2 ligation assays, PI3K recruitment assays, ERK/Vav3/Ca2+ activation assays, actin reorganization microscopy, DAP10-deficient cells, SHIP1 SH2 domain mutant experiments, co-immunoprecipitation Science signaling High 20484116
2010 DAP10 contributes to CD8+ T cell-mediated cytotoxicity during Mycobacterium tuberculosis infection. DAP10-deficient mice show significantly reduced CD8 T cell-mediated cytotoxicity during Mtb infection, associated with impaired cytotoxic granule release, without affecting CD8 T cell recruitment, activation, or IFN-γ production frequency. DAP10 knockout mouse aerosol Mtb infection model, CD8 T cell cytotoxicity assays, granule release assay, flow cytometry for T cell activation markers and IFN-γ Immunobiology Medium 21122940
2011 IL-2 and γc cytokines up-regulate DAP10 expression primarily at the posttranscriptional level, increasing DAP10 protein synthesis. Newly synthesized DAP10 undergoes glycosylation that is required for its association with NKG2D and stabilization of NKG2D surface expression. TGF-β1 exerts an opposing dominant effect by inhibiting RNA polymerase II association with the DAP10 promoter, decreasing DAP10 mRNA, which causes secondary loss of NKG2D protein. NK cell cytokine stimulation, qRT-PCR, immunoblotting, chromatin immunoprecipitation (RNA Pol II at DAP10 promoter), co-immunoprecipitation of DAP10–NKG2D, glycosylation inhibitor treatment Blood High 21816829
2011 In rodents (rat and mouse), DAP10 and DAP12 associate not with NKG2C/E but with CD94, via a transmembrane lysine residue unique to rodent CD94. This represents a phylogenetic transfer of adaptor-binding capacity from NKG2C/E to the CD94 chain, demonstrating that DAP10 association with NK receptor complexes is mediated by specific transmembrane charged residue interactions. Transfection with NKG2C mutant constructs, flow cytometry, biochemical co-immunoprecipitation from primary rat NK cells, redirected lysis assays Journal of immunology Medium 22084441
2012 TGF-β1 down-regulates both DAP10 and NKG2D surface expression on NK cells from HBV-infected patients, impairing NK cell cytotoxicity and IFN-γ production. In vitro, TGF-β1 treatment recapitulates this down-regulation, and anti-TGF-β1 antibodies restore NKG2D and DAP10 expression, placing TGF-β1 as a key negative regulator of the NKG2D–DAP10 pathway during chronic viral infection. Flow cytometry of NK cells from HBV patients and healthy controls, in vitro TGF-β1 treatment, anti-TGF-β1 antibody restoration experiments, NK cell cytotoxicity and IFN-γ assays PLoS pathogens Medium 22438812
2014 DAP10 associates with the receptor for advanced glycation end products (RAGE) in human keratinocytes. RAGE–DAP10 heterodimer formation markedly enhances Akt activation (pro-survival signaling), whereas homomultimeric RAGE interaction leads to caspase-8 activation and apoptosis. Functional blocking of DAP10 in transformed keratinocyte lines abrogates Akt phosphorylation from S100A8/A9-activated RAGE, leading to increased apoptosis. Artificial oligomerization assay, co-immunoprecipitation of RAGE–DAP10, Akt phosphorylation assay, caspase-8 activation assay, DAP10 functional blocking antibody, DAP10-overexpressing cell lines The Journal of biological chemistry Medium 25002577
2015 Ligand-induced endocytosis of NKG2D–DAP10 complexes in human NK cells depends on ubiquitylation of DAP10. This ubiquitin-dependent endocytosis is required not only for degradation of internalized receptor complexes but also for activation of ERK and NK cell effector functions including cytotoxic granule secretion and IFN-γ production, demonstrating that endosomal DAP10 signaling is functionally critical. Biochemical ubiquitylation assays, dominant-negative ubiquitin constructs, confocal microscopy of receptor endocytosis, ERK activation assays, cytotoxic granule secretion assay, IFN-γ production assay in human NK cells Science signaling High 26508790
2019 EVL (Ena/VASP-like), an actin regulatory protein, is recruited to the NK cell cytotoxic synapse via NKG2D–DAP10 signaling, through the same binding site on DAP10 previously implicated in Vav1 and Grb2 recruitment. EVL interacts with WASP and VASP and is required for F-actin generation at the synapse, NK cell–target cell adhesion, and cytotoxicity. Co-immunoprecipitation of EVL with DAP10/Grb2/Vav1, confocal microscopy of synapse recruitment, siRNA knockdown of EVL, F-actin quantification at synapse, NK cell adhesion and cytotoxicity assays Journal of cell science High 31235500
2021 CD33 (Siglec-3) preferentially inhibits NKG2D/DAP10-mediated NK cell cytotoxicity. CD33-mediated inhibition of NKG2D-triggered cytotoxicity involves dephosphorylation of Vav1, placing Vav1 as a convergence point between the DAP10 activating pathway and CD33 inhibitory signaling. NK cell and NKL cell cytotoxicity assays with CD33 co-engagement, phospho-Vav1 western blot, comparison with ILT-2/CD94-NKG2A inhibitory receptors Journal of immunology research Medium 31143782
2021 CD200AR-L/CD200AR binding signals through DAP10 (not DAP12) to control anti-glioma tumor immunity in vivo. The CD200AR–DAP10 pathway shows initial activation followed by transient decrease and reactivation via a positive feedback loop. In vivo studies using DAP10/DAP12 knockout mice confirm that DAP10, but not DAP12, is required for tumor control by this immune checkpoint receptor pathway. Transcription, protein, and phosphorylation analysis in vitro; DAP10/DAP12 double-KO mouse glioma model; pharmacological inhibitor studies; intracranial GBM model survival assay Neurotherapeutics Medium 33829411
2025 ACLY-deficient NK cells show decreased DAP12 and increased DAP10 transcript and protein levels. Epigenetic profiling demonstrates altered histone acetylation at the DAP10 and DAP12 gene loci in ACLY KO cells. Acetate supplementation restores DAP10/DAP12 expression and activating receptor function, demonstrating that cytosolic acetyl-CoA generated by ACLY controls DAP10 and DAP12 expression through histone acetylation. Inducible ACLY knockout mouse model, RNA-seq, western blot, epigenetic/histone acetylation profiling (ChIP), acetate supplementation rescue, NK cell functional assays (cytotoxicity, cytokine) bioRxiv (preprint)preprint Medium bio_10.1101_2025.03.05.639198

Source papers

Stage 0 corpus · 82 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
1996 The I.M.A.G.E. Consortium: an integrated molecular analysis of genomes and their expression. Genomics 1095 8617505
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2020 A reference map of the human binary protein interactome. Nature 849 32296183
1999 An activating immunoreceptor complex formed by NKG2D and DAP10. Science (New York, N.Y.) 791 10426994
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2010 TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1. Science signaling 340 20484116
2012 Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. PloS one 312 23251661
2003 NKG2D-DAP10 triggers human NK cell-mediated killing via a Syk-independent regulatory pathway. Nature immunology 278 12740575
2003 The DNA sequence and analysis of human chromosome 6. Nature 242 14574404
2018 Mapping the Genetic Landscape of Human Cells. Cell 225 30033366
2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes. Genomics 222 17207965
2006 NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural killer cells. Nature immunology 217 16582911
2000 DAP10 and DAP12 form distinct, but functionally cooperative, receptor complexes in natural killer cells. The Journal of experimental medicine 190 11015446
2012 TGF-β1 down-regulation of NKG2D/DAP10 and 2B4/SAP expression on human NK cells contributes to HBV persistence. PLoS pathogens 167 22438812
2008 Systematic identification of mRNAs recruited to argonaute 2 by specific microRNAs and corresponding changes in transcript abundance. PloS one 148 18461144
1996 Expression cloning of the Golgi CMP-sialic acid transporter. Proceedings of the National Academy of Sciences of the United States of America 141 8755516
2004 Genetic complementation reveals a novel human congenital disorder of glycosylation of type II, due to inactivation of the Golgi CMP-sialic acid transporter. Blood 117 15576474
2005 Silencing human NKG2D, DAP10, and DAP12 reduces cytotoxicity of activated CD8+ T cells and NK cells. Journal of immunology (Baltimore, Md. : 1950) 106 16339517
2011 Complex regulation of human NKG2D-DAP10 cell surface expression: opposing roles of the γc cytokines and TGF-β1. Blood 97 21816829
2006 IL-21 down-regulates NKG2D/DAP10 expression on human NK and CD8+ T cells. Journal of immunology (Baltimore, Md. : 1950) 96 16424177
2004 Differential requirements for Vav proteins in DAP10- and ITAM-mediated NK cell cytotoxicity. The Journal of experimental medicine 93 15365099
2020 Systematic mapping of genetic interactions for de novo fatty acid synthesis identifies C12orf49 as a regulator of lipid metabolism. Nature metabolism 92 32694731
1999 Cutting edge: KAP10, a novel transmembrane adapter protein genetically linked to DAP12 but with unique signaling properties. Journal of immunology (Baltimore, Md. : 1950) 83 10528161
1996 Molecular cloning and characterization of a novel isoform of the human UDP-galactose transporter, and of related complementary DNAs belonging to the nucleotide-sugar transporter gene family. Journal of biochemistry 82 9010752
2006 Vav1 controls DAP10-mediated natural cytotoxicity by regulating actin and microtubule dynamics. Journal of immunology (Baltimore, Md. : 1950) 76 16887996
2009 Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection. The Journal of experimental medicine 65 19332875
2017 Systematic protein-protein interaction mapping for clinically relevant human GPCRs. Molecular systems biology 58 28298427
2009 Signal adaptor DAP10 associates with MDL-1 and triggers osteoclastogenesis in cooperation with DAP12. Proceedings of the National Academy of Sciences of the United States of America 58 19251634
2014 Systematic identification of pathological lamin A interactors. Molecular biology of the cell 56 24623722
2015 Ubiquitin-dependent endocytosis of NKG2D-DAP10 receptor complexes activates signaling and functions in human NK cells. Science signaling 53 26508790
2013 Intellectual disability and bleeding diathesis due to deficient CMP--sialic acid transport. Neurology 47 23873973
2003 Substrate recognition by nucleotide sugar transporters: further characterization of substrate recognition regions by analyses of UDP-galactose/CMP-sialic acid transporter chimeras and biochemical analysis of the substrate specificity of parental and chimeric transporters. The Journal of biological chemistry 45 12682060
2019 Genome-wide CRISPR screening reveals genetic modifiers of mutant EGFR dependence in human NSCLC. eLife 42 31741433
2018 A mutation in the gene coding for the sialic acid transporter SLC35A1 is required for platelet life span but not proplatelet formation. Haematologica 42 30115659
2006 The CMP-sialic acid transporter is localized in the medial-trans Golgi and possesses two specific endoplasmic reticulum export motifs in its carboxyl-terminal cytoplasmic tail. The Journal of biological chemistry 40 16923816
2009 The traffic of the NKG2D/Dap10 receptor complex during natural killer (NK) cell activation. The Journal of biological chemistry 38 19329438
1998 Functional expression of human golgi CMP-sialic acid transporter in the Golgi complex of a transporter-deficient Chinese hamster ovary cell mutant. Journal of biochemistry 35 9644260
2008 A critical role for DAP10 and DAP12 in CD8+ T cell-mediated tissue damage in large granular lymphocyte leukemia. Blood 34 19075187
2014 DNAX-activating protein 10 (DAP10) membrane adaptor associates with receptor for advanced glycation end products (RAGE) and modulates the RAGE-triggered signaling pathway in human keratinocytes. The Journal of biological chemistry 33 25002577
2021 Slc35a1 deficiency causes thrombocytopenia due to impaired megakaryocytopoiesis and excessive platelet clearance in the liver. Haematologica 32 32303557
2020 A Humanized Lym-1 CAR with Novel DAP10/DAP12 Signaling Domains Demonstrates Reduced Tonic Signaling and Increased Antitumor Activity in B-Cell Lymphoma Models. Clinical cancer research : an official journal of the American Association for Cancer Research 32 32273277
2011 HMBOX1 negatively regulates NK cell functions by suppressing the NKG2D/DAP10 signaling pathway. Cellular & molecular immunology 32 21706044
2020 T-cells expressing a chimeric-PD1-Dap10-CD3zeta receptor reduce tumour burden in multiple murine syngeneic models of solid cancer. Immunology 27 32144940
2000 DAP12 and KAP10 (DAP10)-novel transmembrane adapter proteins of the CD3zeta family. Immunologic research 27 10945225
2017 Adoptive transfer of murine T cells expressing a chimeric-PD1-Dap10 receptor as an immunotherapy for lymphoma. Immunology 26 28670716
2001 Molecular cloning and characterization of pig immunoreceptor DAP10 and NKG2D. Immunogenetics 26 11398969
2017 TGF-β1 improving abnormal pregnancy outcomes induced by Toxoplasma gondii infection: Regulating NKG2D/DAP10 and killer subset of decidual NK cells. Cellular immunology 22 28438315
2020 A novel bispecific chimeric PD1-DAP10/NKG2D receptor augments NK92-cell therapy efficacy for human gastric cancer SGC-7901 cell. Biochemical and biophysical research communications 21 31952789
2019 NKG2D-DAP10 signaling recruits EVL to the cytotoxic synapse to generate F-actin and promote NK cell cytotoxicity. Journal of cell science 20 31235500
2019 CD33 (Siglec-3) Inhibitory Function: Role in the NKG2D/DAP10 Activating Pathway. Journal of immunology research 18 31143782
2006 Physiological roles of murine DAP10 adapter protein in tumor immunity and autoimmunity. Immunological reviews 18 17100879
2020 Inclusion of Dap10 or 4-1BB costimulation domains in the chPD1 receptor enhances anti-tumor efficacy of T cells in murine models of lymphoma and melanoma. Cellular immunology 17 32106933
2024 Deciphering the molecular and clinical characteristics of TREM2, HCST, and TYROBP in cancer immunity: A comprehensive pan-cancer study. Heliyon 16 38468942
2022 DAP10 integration in CAR-T cells enhances the killing of heterogeneous tumors by harnessing endogenous NKG2D. Molecular therapy oncolytics 16 35784403
2020 CSF1R and HCST: Novel Candidate Biomarkers Predicting the Response to Immunotherapy in Non-Small Cell Lung Cancer. Technology in cancer research & treatment 15 33153411
2011 A possible mechanism of impaired NK cytotoxicity in cancer patients: down-regulation of DAP10 by TGF-beta1. Tumori 15 21789015
2011 Rat and mouse CD94 associate directly with the activating transmembrane adaptor proteins DAP12 and DAP10 and activate NK cell cytotoxicity. Journal of immunology (Baltimore, Md. : 1950) 15 22084441
2015 Decreased expression of pSTAT, IRF-1 and DAP10 signalling molecules in peripheral blood lymphocytes of patients with metastatic melanoma. Journal of clinical pathology 14 26442832
2009 DAP10 associates with Ly49 receptors but contributes minimally to their expression and function in vivo. European journal of immunology 14 19247984
2007 DAP10 deficiency breaks the immune tolerance against transplantable syngeneic melanoma. Journal of immunology (Baltimore, Md. : 1950) 13 17785813
2022 TCR extracellular domain genetically linked to CD28, 2B4/41BB and DAP10/CD3ζ -engineered NK cells mediates antitumor effects. Cancer immunology, immunotherapy : CII 12 35988132
2022 Combination of 4-1BB and DAP10 promotes proliferation and persistence of NKG2D(bbz) CAR-T cells. Frontiers in oncology 11 35965586
2021 CD200 Immune-Checkpoint Peptide Elicits an Anti-glioma Response Through the DAP10 Signaling Pathway. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 10 33829411
2007 Cloning, sequencing, and cell surface expression pattern of bovine immunoreceptor NKG2D and adaptor molecules DAP10 and DAP12. Immunogenetics 10 17530242
2003 Contrasting roles of DAP10 and KARAP/DAP12 signaling adaptors in activation of the RBL-2H3 leukemic mast cell line. European journal of immunology 9 14635062
2010 DAP10 contributes to CD8(+) T cell-mediated cytotoxic effector mechanisms during Mycobacterium tuberculosis infection. Immunobiology 8 21122940
2025 HCST Expression Distinguishes Immune-hot and Immune-cold Subtypes in Pancreatic Ductal Adenocarcinoma. Current gene therapy 5 37475556
2021 DAP10 Predicted the Outcome of Pediatric B-Cell Acute Lymphoblastic Leukemia and Was Associated with the T-Cell Exhaustion. Journal of oncology 5 34868314
2017 Age-Based Reproductive Healthcare Stereotype Threat (HCST) as a Stressor Affecting Prenatal Mental Health in Pregnant Women of Advanced Maternal Age: Measurement, Process, Outcomes, and Interactions with Ethnicity/Race, SES, and Other Social Identities. Current epidemiology reports 3 30345220
2022 A chimeric switch-receptor PD1-DAP10-41BB augments NK92-cell activation and killing for human lung Cancer H1299 Cell. Biochemical and biophysical research communications 2 35217362
2026 cGAMP Enhances Microglial/Macrophage Phagocytosis in Ischemic Stroke Via Activation of the TREM2-DAP10-PI3K Pathway. Inflammation 1 41495583
2020 The impact of chimerism on DNA-based human identification from skin surface cells of post-allogenic hematopoietic stem cell transplantation (HCST) patients. Forensic science international 1 33307474
2025 Dap10 co-stimulation enhances the anti-HCC efficacy of NKp30 chimeric antigen receptor T cells. Translational oncology 0 40393250
2024 A girl with a novel nonsense mutation in Chediak-Higashi syndrome was relieved successfully by treatment with HCST and UCBT: a case report. Annals of hematology 0 39412658