Affinage

MICA

MHC class I polypeptide-related sequence A · UniProt Q29983

Length
383 aa
Mass
42.9 kDa
Annotated
2026-04-28
100 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MICA is a stress-inducible MHC class I-related cell-surface glycoprotein that serves as the principal ligand for the activating immunoreceptor NKG2D on NK cells, γδ T cells, and CD8+ αβ T cells, coupling cellular stress sensing to cytolytic immune surveillance (PMID:10426993). MICA surface expression is transcriptionally regulated by NF-κB/HSF1 at a −130 bp promoter element and repressed by STAT3, while post-translationally it depends on allele-specific N-glycosylation at Asn8 (determined by Thr24) and is directed to the basolateral epithelial membrane via a cytoplasmic tail leucine-valine motif (PMID:22170063, PMID:21257710, PMID:24872415, PMID:11854468). Tumors evade MICA-NKG2D immunity through ADAM10/ADAM17-mediated proteolytic shedding of the MICA ectodomain and through MUC1-C-driven epigenetic silencing and exosomal secretion; soluble MICA impairs NKG2D function by triggering c-Cbl-dependent receptor ubiquitination and degradation (PMID:18676862, PMID:29599246, PMID:36754452, PMID:24846123). A functionally significant MICA-129Met/Val dimorphism determines NKG2D binding affinity and downstream signaling strength, with the Met isoform eliciting stronger but more rapidly self-limiting NK and T cell responses (PMID:26483398).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 High

    Identifying MICA as the ligand for NKG2D established the molecular basis for how stress-induced surface molecules activate innate cytolytic immunity by NK cells and γδ T cells.

    Evidence Receptor-ligand binding assays and functional cytolysis assays with MICA transfectants and epithelial tumor cells

    PMID:10426993

    Open questions at the time
    • Structural basis of MICA–NKG2D interaction not yet defined
    • Downstream NKG2D signaling intermediates uncharacterized
    • Whether other NKG2D ligands are functionally redundant with MICA unclear
  2. 1999 Medium

    Demonstrating cell-type-specific surface expression despite ubiquitous intracellular MICA protein revealed that post-translational trafficking, not transcription alone, controls MICA immunological accessibility.

    Evidence Flow cytometry versus Western blot comparison across endothelial cells, fibroblasts, keratinocytes, and monocytes

    PMID:10363723

    Open questions at the time
    • Mechanism of intracellular retention in non-presenting cell types not identified
    • No trafficking receptor or chaperone implicated
  3. 2002 High

    Identification of a leucine-valine basolateral sorting motif in the MICA cytoplasmic tail explained how polarized epithelial cells direct MICA toward the subepithelial immune compartment, and how the common A5.1 frameshift allele disrupts this targeting.

    Evidence Site-directed mutagenesis in polarized epithelial cells combined with immunofluorescence of native intestinal epithelium

    PMID:11854468

    Open questions at the time
    • Adaptor protein recognizing the LV motif not identified
    • Functional consequence of apical mis-sorting for immune surveillance not tested in vivo
  4. 2004 High

    Showing that gliadin/IL-15-induced MICA expression on gut epithelium drives NKG2D-dependent intraepithelial lymphocyte cytotoxicity linked MICA directly to celiac disease tissue destruction.

    Evidence In vitro gliadin challenge, IL-15 pathway dissection, and NKG2D-blocking antibody experiments with intestinal IEL

    PMID:15357948

    Open questions at the time
    • Whether MICA induction is the primary or redundant NKG2D ligand in celiac lesions not resolved
    • In vivo genetic evidence (MICA polymorphism–disease association) not provided in this study
  5. 2005 Medium

    Discovery that tumor-derived exosomes bearing MICA downregulate NKG2D on effector cells revealed an additional mechanism—beyond shedding—by which tumors co-opt MICA to suppress immune attack.

    Evidence Incubation of PBL with tumor exosomes; flow cytometry for NKG2D; antibody blocking

    PMID:15885603

    Open questions at the time
    • Relative contribution of exosomal versus soluble shed MICA to NKG2D downregulation in vivo not quantified
    • Exosome biogenesis machinery responsible for MICA loading not identified at this point
  6. 2007 High

    Biophysical characterization revealed that MICA undergoes a disorder-to-order conformational transition upon NKG2D binding, with mutations destabilizing the unbound state increasing affinity—establishing an unusual induced-fit recognition mechanism.

    Evidence RosettaDesign computational mutagenesis validated by surface plasmon resonance kinetics

    PMID:17690100

    Open questions at the time
    • Full crystallographic confirmation of disordered-to-ordered transition not provided
    • Whether allelic MICA variants exploit this mechanism differently not addressed
  7. 2008 High

    Identification of ADAM10 and ADAM17 as the sheddases responsible for proteolytic release of soluble MICA from tumor cells defined the enzymatic basis of a major tumor immune evasion strategy.

    Evidence siRNA knockdown of ADAM10/ADAM17 combined with stalk deletion mutagenesis and ELISA for soluble MICA

    PMID:18676862

    Open questions at the time
    • Precise cleavage site in the MICA stalk not mapped at amino acid resolution
    • Whether additional proteases contribute in vivo not excluded
  8. 2011 High

    Mapping the transcriptional regulation of MICA to direct STAT3 repression and NF-κB/HSF1 activation at defined promoter elements resolved how stress and inflammatory signals converge to control MICA expression in cancer and endothelial cells.

    Evidence ChIP for STAT3 binding to MICA promoter; STAT3 siRNA and pharmacological inhibition; NF-κB/HSF1 promoter deletion mapping at −130 bp with dominant-negative HSF1

    PMID:21257710 PMID:22170063

    Open questions at the time
    • How STAT3 and NF-κB signals are integrated at the same promoter in a single cell not resolved
    • Chromatin remodeling events at the MICA locus not characterized
  9. 2012 Medium

    Implicating ERp5 thiol oxidoreductase in MICA shedding on CLL cells suggested that disulfide bond reduction in the ectodomain is a prerequisite for proteolytic cleavage.

    Evidence Co-localization of ERp5 and GRP78 with MICA on CLL cells; pharmacological ERp5 inhibition reduced sMICA

    PMID:22215138

    Open questions at the time
    • No direct co-IP of MICA–ERp5 complex demonstrated
    • Whether ERp5 acts upstream of or synergistically with ADAMs not tested
    • Single lab finding
  10. 2014 High

    Demonstrating that c-Cbl ubiquitin ligase mediates MICA-triggered NKG2D internalization and degradation explained the molecular feedback loop by which soluble MICA disarms effector cells, and showed ligand-specific differences (MICA vs. ULBP2) in receptor fate.

    Evidence c-Cbl knockdown, ubiquitination assays, and comparative NK cytotoxicity with MICA- versus ULBP2-expressing targets

    PMID:24846123

    Open questions at the time
    • Ubiquitination site on NKG2D/DAP10 not mapped
    • Whether other E3 ligases contribute not excluded
  11. 2014 High

    Discovery of allele-specific N-glycosylation dependence at Asn8 (governed by Thr24) and its exploitation by HHV7 immunoevasin U21 revealed a post-translational checkpoint controlling MICA surface expression that differs across allelic variants.

    Evidence Site-directed mutagenesis of Asn8 and Thr24; U21 overexpression; glycosylation inhibitors; flow cytometry

    PMID:24872415

    Open questions at the time
    • Structural mechanism by which Thr24 controls Asn8 glycosylation not resolved
    • Whether this checkpoint affects shedding susceptibility unknown
  12. 2014 High

    Identification of HCMV US18 and US20 as viral factors that target MICA for lysosomal degradation defined a pathogen evasion strategy distinct from proteolytic shedding.

    Evidence Systematic HCMV genome screen with deletion mutants; lysosomal inhibitor rescue; flow cytometry

    PMID:24787765

    Open questions at the time
    • Host adaptor linking US18/US20 to the lysosomal sorting machinery not identified
    • Whether US18/US20 affect other NKG2D ligands not fully assessed
  13. 2015 High

    Biophysical and functional characterization of the MICA-129Met/Val dimorphism established that a single amino acid switch determines NKG2D binding affinity and sets the balance between effector activation and receptor counter-regulation.

    Evidence Surface plasmon resonance affinity measurements; NK cell degranulation, IFN-γ, and CD8+ T cell costimulation assays; NKG2D downregulation kinetics

    PMID:26483398

    Open questions at the time
    • Crystal structure of Met vs. Val allele bound to NKG2D not compared
    • Clinical outcome correlations not validated prospectively in this study
  14. 2018 High

    Anti-α3-domain antibodies that block MICA shedding restored surface MICA and drove NK cell-dependent tumor rejection in vivo, providing therapeutic proof-of-concept that preventing shedding unleashes NKG2D-mediated immunity.

    Evidence Rational antibody design; in vitro shedding assays; multiple syngeneic and humanized mouse tumor models; NK cell depletion

    PMID:29599246

    Open questions at the time
    • Whether antibody-bound MICA alters NKG2D signaling quality not addressed
    • Long-term resistance mechanisms not evaluated
  15. 2023 High

    MUC1-C was shown to orchestrate MICA silencing at three levels—EZH2/DNMT-mediated promoter methylation, ERp5-dependent shedding, and RAB27A-dependent exosomal secretion—unifying epigenetic, proteolytic, and vesicular evasion into a single oncogenic hub.

    Evidence Genetic and pharmacological MUC1-C targeting; H3K27me3 and DNA methylation assays; co-IP of MUC1-C with ERp5 and RAB27A; NK cytotoxicity assays

    PMID:36754452

    Open questions at the time
    • Whether MUC1-C regulation of MICA is direct or operates through intermediate transcription factors not fully delineated
    • Generalizability across tumor types not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • The precise protease cleavage site in the MICA stalk, the structural basis for allele-specific shedding susceptibility, and the identity of the host adaptor that sorts MICA to lysosomes during viral immune evasion remain undefined.
  • Amino acid-resolution cleavage site not mapped
  • No structural comparison of shed-susceptible vs. shed-resistant alleles
  • Adaptor linking viral proteins US18/US20 to lysosomal machinery unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005576 extracellular region 3 GO:0005764 lysosome 1
Pathway
R-HSA-1643685 Disease 5 R-HSA-168256 Immune System 5
Partners
ADAM10ADAM17CBLKLRK1MUC1PDIA6STAT3

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 MICA functions as a ligand for the activating immunoreceptor NKG2D, expressed on most γδ T cells, CD8+ αβ T cells, and NK cells. Ligation of NKG2D by MICA activates cytolytic responses of γδ T cells and NK cells against MICA-expressing transfectants and epithelial tumor cells. NKG2D receptor identification by receptor-ligand binding assays; functional cytolysis assays with MICA transfectants and tumor cell lines Science High 10426993
2002 MICA contains a basolateral sorting signal encoded by a leucine-valine dihydrophobic tandem in its cytoplasmic tail. Full-length MICA is sorted to the basolateral membrane of polarized epithelial cells, whereas the naturally occurring A5.1 allele (which has a frameshift causing premature stop and loss of the 42-aa cytoplasmic tail) is aberrantly transported to the apical surface. Site-directed mutagenesis of cytoplasmic tail; subcellular localization in polarized epithelial cells; immunofluorescence and Western blot of native human intestinal epithelium Proceedings of the National Academy of Sciences of the United States of America High 11854468
2004 MICA/NKG2D interaction directly drives intraepithelial T lymphocyte (IEL)-mediated cytotoxicity toward intestinal epithelial cells in celiac disease. MICA expression on gut epithelium is induced by gliadin (or its p31-49 peptide) via IL-15, triggering innate-like cytotoxicity and enhanced TCR-dependent CD8 T cell responses through NKG2D engagement. In vitro gliadin challenge of intestinal epithelial cells; IL-15 pathway dissection; NKG2D-blocking antibody experiments; functional cytotoxicity assays with IEL Immunity High 15357948
2008 MICA is shed from the tumor cell surface by proteolytic cleavage in the stalk of the MICA ectodomain, and ADAM10 and ADAM17 are the primary sheddases responsible. Silencing of ADAM10 and ADAM17 inhibited MICA shedding by tumor cells; deletions (but not alanine substitutions) in the stalk impeded shedding. siRNA knockdown of ADAM10 and ADAM17; small molecule ADAM inhibitors/stimulators; deletion and alanine substitution mutagenesis of the MICA stalk; ELISA measurement of soluble MICA Cancer research High 18676862
1999 MICA is differentially expressed on the cell surface of endothelial cells and fibroblasts but not on the membrane of keratinocytes and monocytes, despite all four cell types expressing the 62 kDa MICA protein by Western blot. This indicates cell-type-specific regulation of MICA surface expression. Western blot; flow cytometry; immunoprecipitation; peptide neutralization assays with MICA-specific rabbit sera Human immunology Medium 10363723
2005 Tumor-derived exosomes bearing NKG2D ligands including MICA reduce the proportion of NKG2D-positive CD8+ T cells and NK cells in a dose-dependent manner, impairing NKG2D-mediated cytotoxic function. Antibody blocking of NKG2D ligands on exosomes reversed this effect. Incubation of peripheral blood leukocytes with tumor exosomes; flow cytometry for NKG2D expression; in vitro cytotoxicity assays; antibody blocking experiments Blood cells, molecules & diseases Medium 15885603
2011 STAT3 directly binds the MICA promoter and negatively regulates MICA transcription in cancer cells. STAT3 neutralization (pharmacological inhibitors or siRNA) increases MICA expression and NK cell activation via NKG2D. STAT3 also suppresses MICA expression under genotoxic stress (irradiation, heat shock). STAT3 siRNA knockdown and pharmacological inhibition; chromatin immunoprecipitation (direct STAT3-MICA promoter interaction); NK cell functional assays (degranulation, IFN-γ); NKG2D-neutralizing antibody rescue experiments Cancer research High 21257710
2011 NF-κB mediates TNFα-induced MICA upregulation in human endothelial cells through a regulatory control site at -130 bp upstream of the MICA transcription start site, which overlaps with a heat shock response element integrating NF-κB and HSF1 pathway inputs. A dominant-negative truncated HSF1 delivered by lentivirus inhibited the MICA response to TNFα. Promoter analysis/deletion mapping; lentivirus-mediated gene delivery of dominant-negative HSF1; NF-κB pathway inhibition; reporter assays; immunohistochemistry of atherosclerotic lesions The Journal of biological chemistry High 22170063
2014 HCMV US18 and US20 (members of the US12 gene family) independently promote MICA degradation via the lysosomal pathway, with the greatest effect when both act together. HCMV IE2 (but not IE1) activates MICA/B expression, while US18 and US20 counteract this by targeting MICA to lysosomes. Systematic HCMV genome screen; viral deletion mutants (US18, US20); lysosomal inhibitor experiments; flow cytometry for MICA surface expression; co-infection and epistasis analysis PLoS pathogens High 24787765
2014 c-Cbl ubiquitin ligase directs MICA-induced (but not ULBP2-induced) NKG2D internalization and degradation in human NK cells, via the ubiquitin pathway. MICA promotes stronger NKG2D down-modulation than ULBP2, leading to greater impairment of NKG2D-dependent NK cytotoxicity. c-Cbl knockdown; ubiquitination assays; flow cytometry for NKG2D surface expression; NK cell cytotoxicity assays with MICA- vs. ULBP2-expressing targets European journal of immunology High 24846123
2015 The MICA-129Met isoform binds NKG2D with higher affinity than MICA-129Val, triggering stronger NKG2D signaling, more NK cell degranulation, more IFN-γ production, and faster CD8+ T cell costimulation. However, MICA-129Met also induces faster and stronger NKG2D downregulation on NK and CD8+ T cells than MICA-129Val. Surface plasmon resonance for binding affinity; NK cell degranulation assays; IFN-γ ELISA; CD8+ T cell proliferation; flow cytometry for NKG2D surface expression EMBO molecular medicine High 26483398
2007 MICA undergoes a structural transition from disorder to order in the region that contacts NKG2D upon binding. Mutations designed to destabilize this region increased NKG2D association rate and affinity (by 0.9-1.8 kcal/mol), while mutations predicted to stabilize the receptor-bound conformation did not enhance affinity, revealing an unusual binding mechanism. RosettaDesign computational design followed by surface plasmon resonance kinetics/thermodynamics; mutational analysis of the disordered MICA region The Journal of biological chemistry High 17690100
2012 ERp5 (a thiol oxidoreductase) and GRP78 co-localize with MICA on the surface of chronic lymphocytic leukemia (CLL) cells and are involved in soluble MICA shedding. Pharmacological inhibition of ERp5 activity reduced sMICA shedding in B cell lines and CLL cells. Elevated sMICA correlated with NKG2D downregulation on CD8 T cells. Immunofluorescence co-localization; flow cytometry; pharmacological ERp5 inhibition; ELISA for soluble MICA; correlation analysis Cancer immunology, immunotherapy Medium 22215138
2018 Antibodies targeting the MICA α3 domain (site of proteolytic shedding) prevent loss of cell-surface MICA and MICB by human cancer cells. This inhibits tumor growth in immunocompetent mouse models and reduces melanoma metastases in a humanized mouse model, with antitumor immunity mediated mainly by NK cells through NKG2D and CD16 Fc receptors. Rational antibody design targeting α3 domain; in vitro shedding assays; multiple in vivo mouse tumor models; NK cell depletion experiments; humanized mouse model Science High 29599246
2013 The miR-25-93-106b cluster suppresses MICA expression in hepatocellular carcinoma cells. Overexpression of this cluster significantly reduced MICA protein levels, while silencing of the cluster enhanced MICA expression. These changes were functionally significant in NKG2D-binding assays and an in vivo cell-killing model. miRNA overexpression and silencing; Western blot for MICA protein; NKG2D-binding assays; in vivo cell-killing model Scientific reports Medium 24061441
2014 N-glycosylation at asparagine 8 (Asn8) is required for cell-surface expression of MICA018 but not MICA008, identifying allele-specific N-glycosylation regulation. A single amino acid (Thr24) in the extracellular domain determines the N-glycosylation dependence. The HHV7 immunoevasin U21 inhibits MICA018 surface expression by affecting N-glycosylation at this site, and the T24A substitution rescues surface expression. Site-directed mutagenesis of N-glycosylation sites and Thr24; flow cytometry for surface expression; U21 overexpression; glycosylation inhibitors The Journal of biological chemistry High 24872415
2017 Active glycolytic metabolism and purine nucleotide synthesis regulate MICA expression. Glucose transport into cells and glycolysis are necessary to upregulate MICA, and increases in purine nucleotide levels are sufficient to induce MICA expression. Metabolic induction of MICA directly influences NKG2D-dependent cytotoxicity. Metabolic interventions (glucose transport inhibitors, glycolysis inhibitors, purine synthesis inhibitors); metabolomic analysis; MICA surface expression by flow cytometry; NKG2D-mediated cytotoxicity assays The Journal of biological chemistry Medium 29279329
2019 High glucose suppresses MICA/B expression in pancreatic cancer cells through the AMPK-Bmi1-GATA2 axis. High glucose inhibits AMPK signaling, leading to elevated Bmi1, which promotes GATA2 expression to suppress MICA/B, enabling cancer cells to evade NK cell-mediated killing. qPCR, Western blot, flow cytometry, immunofluorescence for pathway components; Bmi1 and GATA2 knockdown/overexpression; LDH cytotoxicity assays; in vivo diabetic mouse model Journal of experimental & clinical cancer research Medium 31088566
2018 ADAM17 is the primary sheddase for MICA in hepatocellular carcinoma cells. ADAM17 knockdown reduced soluble MICA levels and increased membrane-bound MICA. Lomofungin (an antifungal drug) was identified as an ADAM17 enzymatic inhibitor that increases membrane MICA and decreases sMICA production in a dose-dependent, ADAM17-dependent manner. siRNA knockdown of ADAMs and MMPs; ELISA for sMICA; flow cytometry for membrane MICA; FDA-approved drug library screen; in vitro ADAM17 enzymatic inhibition assay; lomofungin analog structure-activity analysis International journal of cancer High 29873070
2002 CD3 or CD28 engagement (with PMA) induces MICA expression on T lymphocytes, including CD4+ and CD8+ T cells activated by allogeneic stimulation. This activation-induced MICA expression may participate in NKG2D-mediated cytotoxicity toward activated T cells to maintain immune homeostasis. Western blot; RT-PCR; flow cytometry for MICA expression; activation with anti-CD3, anti-CD28 mAbs, PMA; blocking antibodies to HLA class I, HLA-DR, CD86 Journal of leukocyte biology Medium 11994503
2005 MICA can mediate NKG2D-independent suppression of T cell proliferation. This suppressive effect requires IL-10 and involves a receptor other than NKG2D, demonstrating that MICA has dual roles as both an activating and a suppressive signal depending on cytokine context. T cell proliferation assays with H60 and MICA stimulation; NKG2D-blocking antibodies; IL-10 neutralization; receptor identification by blocking Proceedings of the National Academy of Sciences of the United States of America Medium 16091471
2008 Estradiol upregulates MICA expression on human uterine epithelial cells in an estrogen receptor-dependent manner, with greater MICA protein detected in secretory-phase endometrium by immunohistochemistry. RT-PCR; protein expression assays; estrogen receptor antagonist experiments; immunohistochemistry of endometrial tissue from different menstrual cycle phases Clinical immunology Medium 18728002
2023 MUC1-C represses MICA and MICB expression through an NF-κB→EZH2-mediated and DNMT-mediated methylation of the MICA/B promoter regions. MUC1-C also regulates ERp5 thiol oxidoreductase (necessary for MICA/B protease digestion and shedding) and interacts with RAB27A (required for exosome formation), thereby controlling exosomal MICA/B secretion. Targeting MUC1-C increases MICA/B surface expression and promotes NK cell killing. Genetic and pharmacological (GO-203 inhibitor) MUC1-C targeting; H3K27 and DNA methylation assays of MICA/B promoters; co-immunoprecipitation and direct binding of MUC1-C with ERp5 and RAB27A; ELISA for shedding; exosome isolation; NK cell cytotoxicity assays Journal for immunotherapy of cancer High 36754452

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science (New York, N.Y.) 2373 10426993
2004 A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease. Immunity 538 15357948
2018 Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity. Science (New York, N.Y.) 378 29599246
2008 Tumor-associated MICA is shed by ADAM proteases. Cancer research 305 18676862
1996 DNA binding to mica correlates with cationic radius: assay by atomic force microscopy. Biophysical journal 238 8785352
2003 Adsorption of DNA to mica mediated by divalent counterions: a theoretical and experimental study. Biophysical journal 148 14507713
1999 Differential surface expression of MICA by endothelial cells, fibroblasts, keratinocytes, and monocytes. Human immunology 122 10363723
2005 Exosomes and the MICA-NKG2D system in cancer. Blood cells, molecules & diseases 120 15885603
2014 Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation. PLoS pathogens 119 24787765
1997 AFM analysis of DNA-protamine complexes bound to mica. Nucleic acids research 119 9153324
2020 NKG2D and MICA/B shedding: a 'tag game' between NK cells and malignant cells. Clinical & translational immunology 113 33363734
2001 MICA polymorphism is associated with type 1 diabetes in the Korean population. Diabetes care 111 11194237
2002 A basolateral sorting motif in the MICA cytoplasmic tail. Proceedings of the National Academy of Sciences of the United States of America 104 11854468
2011 Novel role for STAT3 in transcriptional regulation of NK immune cell targeting receptor MICA on cancer cells. Cancer research 96 21257710
2010 MicA sRNA links the PhoP regulon to cell envelope stress. Molecular microbiology 90 20345657
2007 Sigma E controls biogenesis of the antisense RNA MicA. Nucleic acids research 90 17267407
2010 MICA polymorphism: biology and importance in immunity and disease. Trends in molecular medicine 83 20153697
1999 MIC-A polymorphism in Japanese and a MIC-A-MIC-B null haplotype. Immunogenetics 78 10369920
1999 Association of MICA gene and HLA-B*5101 with Behçet's disease in Greece. Investigative ophthalmology & visual science 76 10440244
2014 MICA polymorphism: biology and importance in cancer. Carcinogenesis 73 25330802
2015 The MICA-129 dimorphism affects NKG2D signaling and outcome of hematopoietic stem cell transplantation. EMBO molecular medicine 69 26483398
2002 Activation-induced expression of MICA on T lymphocytes involves engagement of CD3 and CD28. Journal of leukocyte biology 68 11994503
2010 Regulation of the small regulatory RNA MicA by ribonuclease III: a target-dependent pathway. Nucleic acids research 66 21138960
2001 Two distinct MICA gene markers discriminate major autoimmune diabetes types. The Journal of clinical endocrinology and metabolism 66 11502807
2000 Age-related association of MHC class I chain-related gene A (MICA) with type 1 (insulin-dependent) diabetes mellitus. Human immunology 62 10825591
2002 MICA rather than MICB, TNFA, or HLA-DRB1 is associated with susceptibility to psoriatic arthritis. The Journal of rheumatology 58 12022360
2005 Imaging DNA molecules on mica surface by atomic force microscopy in air and in liquid. Microscopy research and technique 55 15889427
2011 NF-κB regulates MICA gene transcription in endothelial cell through a genetically inhibitable control site. The Journal of biological chemistry 54 22170063
2006 Diversity of MICA and linkage disequilibrium with HLA-B in two North American populations. Human immunology 52 16698437
2019 High glucose promotes pancreatic cancer cells to escape from immune surveillance via AMPK-Bmi1-GATA2-MICA/B pathway. Journal of experimental & clinical cancer research : CR 50 31088566
2004 Amyloidosis in familial Mediterranean fever patients: correlation with MEFV genotype and SAA1 and MICA polymorphisms effects. BMC medical genetics 50 15018633
2019 Imaging DNA Equilibrated onto Mica in Liquid Using Biochemically Relevant Deposition Conditions. ACS nano 48 30938988
2001 Diversity of MICA (PERB11.1) and HLA haplotypes in Northeastern Thais. Tissue antigens 45 11696220
2016 Impact of the MICA-129Met/Val Dimorphism on NKG2D-Mediated Biological Functions and Disease Risks. Frontiers in immunology 43 28018354
2013 HLA and MICA allosensitization patterns among patients supported by ventricular assist devices. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 43 24075503
2006 The predictive value of soluble major histocompatibility complex class I chain-related molecule A (MICA) levels on heart allograft rejection. Transplantation 43 16906033
2017 Major Histocompatibility Complex Class I Chain-Related A (MICA) Molecules: Relevance in Solid Organ Transplantation. Frontiers in immunology 42 28293239
2014 c-Cbl regulates MICA- but not ULBP2-induced NKG2D down-modulation in human NK cells. European journal of immunology 42 24846123
2016 A bispecific protein rG7S-MICA recruits natural killer cells and enhances NKG2D-mediated immunosurveillance against hepatocellular carcinoma. Cancer letters 41 26791237
2018 MICA-129 Dimorphism and Soluble MICA Are Associated With the Progression of Multiple Myeloma. Frontiers in immunology 40 29765374
2013 Regulation of the expression of the liver cancer susceptibility gene MICA by microRNAs. Scientific reports 38 24061441
2012 Expression of ERp5 and GRP78 on the membrane of chronic lymphocytic leukemia cells: association with soluble MICA shedding. Cancer immunology, immunotherapy : CII 38 22215138
2011 Role of the MICA polymorphism in systemic lupus erythematosus. Arthritis and rheumatism 37 21702010
2011 RSV infection modulates IL-15 production and MICA levels in respiratory epithelial cells. The European respiratory journal 37 21852331
2010 Possible origin of life between mica sheets. Journal of theoretical biology 37 20558181
2000 Polymorphism of transmembrane region of MICA gene and Kawasaki disease. Experimental and clinical immunogenetics 37 10899738
2022 The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation. Nature medicine 36 35288692
2018 Dynamic Behavior of RNA Nanoparticles Analyzed by AFM on a Mica/Air Interface. Langmuir : the ACS journal of surfaces and colloids 36 29669419
2020 High-Throughput MICA/B Genotyping of Over Two Million Samples: Workflow and Allele Frequencies. Frontiers in immunology 35 32153595
2019 Catalytic, kinetic and thermodynamic properties of free and immobilized caseinase on mica glass-ceramics. Heliyon 35 31193050
2011 Association of MICA and MICB alleles with symptomatic dengue infection. Human immunology 34 21762746
2020 Tumor-Derived Soluble MICA Obstructs the NKG2D Pathway to Restrain NK Cytotoxicity. Aging and disease 33 32010486
2006 Variation in MICA and MICB genes and enhanced susceptibility to paucibacillary leprosy in South India. Human molecular genetics 33 16923796
1998 MICA gene polymorphism in Takayasu's arteritis and Buerger's disease. International journal of cardiology 32 9951809
2011 Functional MICA-129 polymorphism and serum levels of soluble MICA are correlated with ulcerative colitis in Chinese patients. Journal of gastroenterology and hepatology 31 21155878
2010 Role of MICA in the immune response to transplants. Tissue antigens 31 20696027
2007 Epitopes of the HLA-A, B, C, DR, DQ and MICA antigens. Clinical transplants 31 18637469
2018 Enzymatic inhibition of MICA sheddase ADAM17 by lomofungin in hepatocellular carcinoma cells. International journal of cancer 30 29873070
2002 Further polymorphism of the MICA gene. European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics 30 11841487
2010 Compartmental localization and clinical relevance of MICA antibodies after renal transplantation. Transplantation 29 20145522
2005 NKG2D-independent suppression of T cell proliferation by H60 and MICA. Proceedings of the National Academy of Sciences of the United States of America 29 16091471
2013 Role of HLA, KIR, MICA, and cytokines genes in leprosy. BioMed research international 28 23936864
2010 Interleukin 10 decreases MICA expression on melanoma cell surface. Immunology and cell biology 28 20714339
2023 MUC1-C is a master regulator of MICA/B NKG2D ligand and exosome secretion in human cancer cells. Journal for immunotherapy of cancer 27 36754452
2015 Study of DNA adsorption on mica surfaces using a surface force apparatus. Scientific reports 26 25676333
2014 N-glycosylation of asparagine 8 regulates surface expression of major histocompatibility complex class I chain-related protein A (MICA) alleles dependent on threonine 24. The Journal of biological chemistry 26 24872415
1999 MICA gene polymorphism and the risk to develop cervical intraepithelial neoplasia. Human immunology 26 10566597
2017 Purine nucleotide metabolism regulates expression of the human immune ligand MICA. The Journal of biological chemistry 25 29279329
2010 Specific DNA-protein interactions on mica investigated by atomic force microscopy. Langmuir : the ACS journal of surfaces and colloids 25 19791748
2010 MICA polymorphism in a northern Chinese Han population: The identification of a new MICA allele, MICA*059. Human immunology 25 20097244
2007 Mutations designed to destabilize the receptor-bound conformation increase MICA-NKG2D association rate and affinity. The Journal of biological chemistry 25 17690100
2007 MICA gene polymorphism in the pathogenesis of type 1 diabetes. Annals of the New York Academy of Sciences 25 17911424
2006 Post-transplant soluble MICA and MICA antibodies predict subsequent heart graft outcome. Transplant immunology 25 17157214
2020 Restoration of antitumor immunity through anti-MICA antibodies elicited with a chimeric protein. Journal for immunotherapy of cancer 24 32518090
2017 A new MHC-linked susceptibility locus for primary Sjögren's syndrome: MICA. Human molecular genetics 23 28379387
2004 Polymorphism of the MICA gene and risk for oral submucous fibrosis. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 23 14675133
2003 Distribution of MICA alleles and haplotypes associated with HLA in the Korean population. Human immunology 22 12590984
2019 Molecular-Scale Investigations Reveal Noncovalent Bonding Underlying the Adsorption of Environmental DNA on Mica. Environmental science & technology 21 31478650
2014 Diversity and characterization of polymorphic 5' promoter haplotypes of MICA and MICB genes. Tissue antigens 21 24962621
2009 Expression of HLA-G and MICA mRNA in renal allograft. Transplant immunology 21 19193353
2008 Estradiol regulates MICA expression in human endometrial cells. Clinical immunology (Orlando, Fla.) 21 18728002
2008 Polymorphisms of MICA recognized by human alloantibodies. Immunogenetics 21 19066881
2019 LINC01149 variant modulates MICA expression that facilitates hepatitis B virus spontaneous recovery but increases hepatocellular carcinoma risk. Oncogene 20 31754211
2011 MICB polymorphisms and haplotypes with MICA and HLA alleles in Koreans. Tissue antigens 20 21554252
2009 Identification of epitopes and immunodominant regions on the MICA protein defined by alloantibodies from kidney transplant patients. Transplantation 20 19667965
2004 MICA and recovery from hepatitis C virus and hepatitis B virus infections. Genes and immunity 20 15029237
2020 Leukotriene receptor antagonists enhance HCC treatment efficacy by inhibiting ADAMs and suppressing MICA shedding. Cancer immunology, immunotherapy : CII 18 32683508
2013 Role of MICA antibodies in solid organ transplantation. Clinical transplantation 18 24372774
2009 MICA polymorphisms and haplotypes with HLA-B and HLA-DRB1 in Koreans. Tissue antigens 18 19895570
2007 MICA and MICB overexpression in oral squamous cell carcinoma. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 18 17181741
2004 The increase of MICA gene A9 allele associated with gastric cancer and less schirrous change. British journal of cancer 18 15150599
2003 Up-regulated expression of MICA and proinflammatory cytokines in skin biopsies from patients with seborrhoeic dermatitis. Clinical immunology (Orlando, Fla.) 17 12584051
2018 NKG2D Immunoligand rG7S-MICA Enhances NK Cell-mediated Immunosurveillance in Colorectal Carcinoma. Journal of immunotherapy (Hagerstown, Md. : 1997) 16 29528990
2018 5-Methoxyindole-2-carboxylic acid (MICA) suppresses Aβ-mediated pathology in C. elegans. Experimental gerontology 16 29709515
2017 Transcriptional activation of the MICA gene with an engineered CRISPR-Cas9 system. Biochemical and biophysical research communications 16 28322797
2015 Associations of MICA Polymorphisms with Inflammatory Rheumatic Diseases. The open rheumatology journal 16 26862354
2011 Deposition of colloid particles on protein layers: fibrinogen on mica. Journal of colloid and interface science 16 21316698
2005 Distinct pattern of human Vdelta1 gammadelta T cells recognizing MICA. Cellular & molecular immunology 16 16274622
2022 αVEGFR2-MICA fusion antibodies enhance immunotherapy effect and synergize with PD-1 blockade. Cancer immunology, immunotherapy : CII 15 36227341
2002 The increase in the frequency of MICA gene A6 allele in oral squamous cell carcinoma. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 15 12190814