Affinage

MICB

MHC class I polypeptide-related sequence B · UniProt Q29980

Length
383 aa
Mass
42.6 kDa
Annotated
2026-04-28
100 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MICB is a stress-induced MHC class I-related surface glycoprotein that serves as a ligand for the NKG2D activating receptor, triggering cytotoxic responses by NK cells, γδ T cells, and CD8+ T cells against transformed and infected cells (PMID:10359807, PMID:11491531). MICB expression is controlled at multiple levels: transcriptionally by NF-Y, Sp1, STAT3, and RXRA through a polymorphic promoter whose activity is modulated by chromatin remodeling via histone acetylation and DNA methylation (PMID:17557375, PMID:17625602, PMID:18395517, PMID:29); post-transcriptionally by cellular and viral miRNAs targeting both the 3′UTR and 5′UTR, and by RNA-binding proteins including vigilin and IMP3 (PMID:19380116, PMID:28850101, PMID:28356383, PMID:26982091); and at the protein level by metalloprotease-mediated ectodomain shedding (ADAM15, ADAM17) counteracted by the endogenous inhibitor TIMP3 (PMID:16698441, PMID:23314034, PMID:28404876). MICB induction is linked to the DNA damage response through ATM/ATR–Chk1/Chk2 signaling (PMID:18644891, PMID:30483783), and surface MICB is targeted for immune evasion by herpesvirus proteins such as HCMV UL16, which binds the MICB platform domain at a glutamine-169-dependent site to retain it intracellularly, with allelic variation at positions 98 and 113 modulating this interaction (PMID:20090832, PMID:23625227). A common MICB missense variant (D136N) reduces surface expression and NKG2D-mediated NK killing and is associated with reduced acute lung injury severity (PMID:37878820).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 High

    Establishing that MICB functions as a stress-induced antigen recognized by γδ T cells resolved the question of how innate-like lymphocytes detect transformed cells independently of classical peptide–MHC presentation.

    Evidence Cytotoxicity assays with Vδ1 γδ T cell lines against autologous and heterologous tumors expressing MICA/B

    PMID:10359807

    Open questions at the time
    • NKG2D had not yet been identified as the receptor
    • mechanism of stress-induced MICB upregulation unknown
  2. 2001 High

    Demonstrating that NKG2D homodimers directly bind monomeric MICA/MICB in solution defined the receptor–ligand pair and revealed that allelic polymorphism at position 129 in the α2 domain governs binding affinity.

    Evidence Solution binding assays with soluble NKG2D and MICA, cell surface binding with MICB, allelic mutagenesis

    PMID:11491531

    Open questions at the time
    • Structural basis of NKG2D–MICB interaction not yet resolved
    • downstream signaling consequences of affinity differences not explored
  3. 2003 Medium

    Transgenic expression of human MICB in mice producing skin hyperkeratosis and leukocytosis provided the first in vivo evidence that MICB drives inflammatory tissue responses.

    Evidence Transgenic mice with ubiquitous MICB expression, histopathology and blood cell counts in two independent lines

    PMID:12753668

    Open questions at the time
    • Whether phenotype is NKG2D-dependent was not tested
    • relevance to endogenous stress-induced expression levels uncertain
  4. 2006 High

    Two studies established that surface MICB undergoes metalloprotease-mediated shedding to produce a soluble form and that MICB engagement at the NK immunological synapse drives NKG2D clustering, bidirectional receptor–ligand transfer, and subsequent attenuation of NK cytotoxicity.

    Evidence Metalloprotease inhibitor experiments with ELISA/flow cytometry for shedding; live-cell imaging and cytotoxicity assays for synapse dynamics

    PMID:16698441 PMID:16849432

    Open questions at the time
    • Identity of the specific sheddase(s) not yet determined
    • relative contribution of shedding vs. trogocytosis to immune evasion unresolved
  5. 2007 High

    Characterization of the MICB promoter identified NF-Y (CCAAT box) and Sp1 (GC box) as essential transcription factors and revealed that a natural 2-bp deletion polymorphism causes an 18-fold reduction in promoter activity, while HDAC inhibition upregulates MICB via increased histone H3 acetylation at the promoter.

    Evidence Luciferase reporter/EMSA for promoter elements; ChIP for histone acetylation and HDAC1 occupancy at MICB promoter in leukemic cells

    PMID:17557375 PMID:17625602

    Open questions at the time
    • In vivo relevance of the promoter polymorphism not established
    • full set of transcription factors regulating MICB promoter not mapped
  6. 2008 High

    Placing MICB induction downstream of ATM/ATR–Chk1 DNA damage signaling—demonstrated via Dicer knockdown and 5-aza-dC treatment with kinase inhibitor epistasis—established the DNA damage response as a central pathway for MICB upregulation.

    Evidence Pharmacological and genetic inhibition of ATM/ATR/Chk1, bisulfite sequencing for DNA methylation, flow cytometry and RT-PCR

    PMID:18395517 PMID:18644891

    Open questions at the time
    • Direct transcription factor linking ATM/ATR to MICB promoter activation not identified
    • contribution of DNA demethylation vs. damage signaling not fully separated
  7. 2009 High

    Discovery that miRNAs from three divergent herpesviruses (HCMV, KSHV, EBV) convergently target the MICB 3′UTR to suppress expression revealed a conserved viral immune evasion strategy operating at the post-transcriptional level.

    Evidence 3′UTR reporter assays with mutagenesis, miRNA mimics/inhibitors, authentic viral infection, NK cytotoxicity assays

    PMID:19380116

    Open questions at the time
    • Full repertoire of cellular miRNAs targeting MICB not known
    • quantitative contribution of miRNA-mediated suppression relative to other evasion mechanisms unclear
  8. 2010 High

    The 1.8 Å crystal structure of HCMV UL16 bound to MICB revealed that UL16 mimics NKG2D binding geometry on the MICB platform domain and that glutamine-169 is the critical determinant for UL16 engagement, explaining why MICA (arginine-169) escapes UL16 retention.

    Evidence X-ray crystallography, surface plasmon resonance, site-directed mutagenesis

    PMID:20090832

    Open questions at the time
    • How UL16 retains MICB intracellularly (trafficking mechanism) not resolved
    • structure of UL16–MICB in membrane context unknown
  9. 2013 Medium

    Identification of ADAM15 as a MICB sheddase and of allelic variation at MICB positions 98 and 113 as determinants of UL16 binding specificity provided molecular explanations for differential immune evasion across MICB alleles.

    Evidence siRNA knockdown of ADAM15 with surface/soluble MICB quantification; Fc-fusion UL16 binding to MICB allelic cell lines

    PMID:23314034 PMID:23625227

    Open questions at the time
    • Relative contributions of ADAM15 vs. other ADAMs to shedding in different tissues not determined
    • MICB allele-specific UL16 binding not validated structurally
  10. 2014 High

    Unbiased RNA pull-down/mass spectrometry identified six RNA-binding proteins regulating MICB, at least two functioning during genotoxic stress, establishing post-transcriptional control as a major regulatory axis beyond miRNAs.

    Evidence RNA pull-down with MICB UTRs, mass spectrometry, RBP knockdown with MICB expression readout under genotoxic stress

    PMID:24924487

    Open questions at the time
    • Precise binding sites and mechanism for most identified RBPs not characterized
    • whether RBPs and miRNAs act cooperatively or redundantly unknown
  11. 2017 Medium

    Three discoveries refined the post-transcriptional and post-translational regulation of MICB: vigilin was identified as a 5′UTR-binding repressor, ADAM17 was shown to be the principal sheddase inhibitable by TIMP3, and novel miRNAs targeting both the 3′UTR and 5′UTR were validated.

    Evidence RNA pull-down/MS for vigilin; ADAM17 inhibition and TIMP3 siRNA with shedding assays; luciferase reporters with UTR mutagenesis

    PMID:28356383 PMID:28404876 PMID:28850101

    Open questions at the time
    • Structural basis for vigilin–5′UTR interaction unknown
    • relative importance of ADAM15 vs. ADAM17 across cell types not compared
    • functional redundancy among UTR-targeting miRNAs not assessed
  12. 2018 High

    Antibodies targeting the MICA/MICB α3 domain that block proteolytic shedding demonstrated therapeutic proof-of-concept by maintaining surface NKG2D ligand density and inhibiting tumor growth through NK cell activation via NKG2D and CD16.

    Evidence Antibody engineering, surface MICA/B quantification, multiple syngeneic mouse tumor models with NK depletion

    PMID:29599246

    Open questions at the time
    • Whether anti-shedding antibodies affect MICB and MICA equally not fully resolved
    • contribution of adaptive immune components beyond NK cells not characterized
  13. 2024 High

    A common MICB missense variant (D136N) was shown to reduce surface expression and NKG2D-mediated NK killing, with clinical validation linking homozygosity to reduced acute lung injury severity, directly connecting MICB genetic variation to human disease outcomes.

    Evidence Variant protein expression in cells, flow cytometry, NK coculture, two independent clinical cohorts

    PMID:37878820

    Open questions at the time
    • Structural basis for D136N effect on surface expression unknown
    • whether D136N also affects UL16 or other viral immunoevasin binding not tested
  14. 2024 Medium

    The lncRNA Linc-ROR was found to suppress MICB by promoting UBE4B-mediated ubiquitination and degradation of the transcription factor RXRA, adding a new upstream regulatory layer to MICB transcriptional control.

    Evidence Co-transfection, ubiquitination assays, RXRA protein quantification, flow cytometry for MICB, NK-92 coculture

    PMID:38205878

    Open questions at the time
    • Whether RXRA binds the MICB promoter directly not demonstrated by ChIP
    • generalizability beyond gastric cancer cells not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The precise transcription factor cascade linking ATM/ATR activation to MICB promoter induction remains unidentified, and a unified model integrating transcriptional, post-transcriptional (miRNA/RBP), and post-translational (shedding/lysosomal degradation) control of MICB surface density has not been established.
  • No transcription factor directly connecting ATM/ATR kinase activity to MICB promoter has been identified
  • Quantitative contributions of shedding, trogocytosis, and miRNA suppression to MICB surface levels in physiological contexts are unknown
  • Full structural basis of allelic MICB variation on NKG2D vs. viral immunoevasin binding not comprehensively mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4
Localization
GO:0005886 plasma membrane 6
Pathway
R-HSA-168256 Immune System 6 R-HSA-73894 DNA Repair 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
ADAM15ADAM17HDAC1KLRK1

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 MICA and MICB are stress-induced antigens recognized by gamma delta T cells expressing Vdelta1 variable region, acting as tumor-associated antigens that trigger cytotoxic responses without peptide antigen constraints. T cell recognition assays using tumor-derived Vdelta1 gamma delta T cell lines and clones against autologous and heterologous tumor cells expressing MICA/B Proceedings of the National Academy of Sciences of the United States of America High 10359807
2001 NKG2D homodimers form stable complexes with monomeric MICA in solution without requiring additional components; NKG2D also binds cell surface MICB; MICA glycosylation enhances but is not essential for complex formation; allelic variants of MICA show large differences in NKG2D binding associated with a single amino acid substitution at position 129 in the alpha2 domain. Solution binding assays (soluble NKG2D and MICA), cell surface binding with soluble NKG2D, allelic mutagenesis analysis Immunogenetics High 11491531
2006 MICB is shed by metalloproteases from tumor cell surfaces in soluble form; cell-bound MICB causes downregulation of surface NKG2D on NK cells, whereas soluble MICB did not alter NKG2D expression on NK cells in vitro, suggesting shedding impairs tumor immunogenicity primarily by reducing NKG2D-ligand density on malignant cells. Metalloprotease inhibitor experiments, NK cell NKG2D expression assays by flow cytometry, ELISA for soluble MICB in patient sera Human immunology High 16698441
2006 NKG2D and MICB undergo bidirectional intercellular transfer at the cytotoxic NK cell immune synapse (cNK-IS); MICB on target cells induces NKG2D clustering at the central supramolecular activation cluster (cSMAC) surrounded by F-actin at the peripheral SMAC; membrane-connective structures at cNK-IS contain F-actin, perforin, and NKG2D; brief NK–MICB+ target cell interactions reduce NKG2D-dependent NK cytotoxicity. Live cell imaging, immunofluorescence microscopy, cytotoxicity assays with MICB-expressing target cells Proceedings of the National Academy of Sciences of the United States of America High 16849432
2007 HDAC inhibitor trichostatin A (TsA) increases MICA and MICB expression on leukemic cells by increasing histone H3 acetylation and decreasing HDAC1 association at MICA and MICB promoters, leading to enhanced NKG2D-mediated cytotoxicity against leukemic cells. Chromatin immunoprecipitation (ChIP) assay, flow cytometry, cytotoxicity assays Leukemia High 17625602
2007 The MICB promoter is polymorphic; a 2-bp deletion near the CCAAT box (-70) and GC box (-86) dramatically reduces MICB transcriptional activity (18-fold decrease) by diminishing Sp1 transcriptional activation; the minimal MICB promoter contains NF-Y binding (CCAAT box) and Sp1/Sp3/Sp4 binding (GC box) elements. Luciferase reporter assays, promoter deletion analysis, electrophoretic mobility shift assay (EMSA), functional transcription analysis European journal of immunology High 17557375
2008 Knockdown of Dicer in human cells induces DNA damage and upregulates MICA and MICB expression; this upregulation is prevented by pharmacological or genetic inhibition of ATM kinase, ATR kinase, or Chk1, establishing that MICB upregulation following Dicer knockdown is mediated through the DNA damage response pathway. RNAi knockdown of Dicer, pharmacological inhibition (ATM, ATR, Chk1 inhibitors), genetic inhibition, flow cytometry/RT-PCR for MICA/B expression The Journal of cell biology High 18644891
2008 5-aza-2'-deoxycytidine (5-aza-dC) upregulates MICB expression through promoter DNA demethylation combined with DNA damage; ATM kinase inhibition partially prevents this upregulation, indicating that both DNA demethylation and ATM-mediated DNA damage signaling contribute to MICB induction. Bisulfite sequencing for DNA methylation, pharmacological ATM inhibition, RT-PCR/flow cytometry for MICB expression Biochemical and biophysical research communications Medium 18395517
2009 MicroRNAs from diverse herpesviruses (HCMV, KSHV, EBV) directly target MICB mRNA at different but adjacent sites in its 3'UTR to repress MICB expression and enable NK cell evasion; despite lacking sequence homology, these viral miRNAs are functionally conserved in targeting MICB during authentic viral infection. Reporter assays with MICB 3'UTR, miRNA mimic/inhibitor experiments, authentic viral infection, NK cell cytotoxicity assays Cell host & microbe High 19380116
2010 Crystal structure of HCMV UL16 in complex with MICB at 1.8 Å resolution reveals that UL16 uses a three-stranded beta-sheet to engage the alpha-helical surface of the MICB MHC class I-like platform domain, mimicking the NKG2D binding mode; UL16 binds MICB, ULBP1, and ULBP2 with nanomolar affinity (12–66 nM); binding requires glutamine at position 169 of MICB, and an arginine at this position (as in MICA or ULBP3) causes steric clashes preventing UL16 binding. X-ray crystallography (1.8 Å), surface plasmon resonance, mutagenesis PLoS pathogens High 20090832
2011 HHV-7 U21 immunoevasin binds to NK-activating ligands MICA and MICB and downregulates their surface expression, resulting in reduced NK-mediated cytotoxicity; this is mechanistically distinct from U21's known downregulation of class I MHC. Flow cytometry for MICB/MICA surface expression in U21-expressing cells, NK cytotoxicity assays PLoS pathogens Medium 22102813
2012 miR-10b directly binds to the 3'UTR of MICB mRNA and downregulates MICB surface expression; antagonizing miR-10b enhanced NKG2D-mediated NK cell killing of tumor cells in vitro and reduced tumor growth in vivo; overexpression of miR-10b impaired tumor cell elimination through MICB downregulation. 3'UTR reporter assays, miRNA mimic/inhibitor, flow cytometry for MICB surface expression, in vitro and in vivo NK cytotoxicity assays Cancer research High 22915757
2013 ADAM15 mediates MICB ectodomain shedding in pancreatic cancer cells; knockdown of ADAM15 increases cell surface MICB and reduces soluble MICB in conditioned media; gemcitabine suppresses ADAM15 expression, leading to decreased MICB shedding and increased surface MICB without altering MICB mRNA levels. siRNA knockdown of ADAM15, ELISA for soluble MICB, flow cytometry for surface MICB, RT-PCR for mRNA levels, immunohistochemistry on patient tissue Molecular medicine reports Medium 23314034
2013 HBsAg overexpression in hepatoma cells induces cellular miRNAs that directly repress MICA and MICB expression via their 3'UTRs, reducing surface MICA/B and decreasing NK cell-mediated cytolysis of HCC cells. miRNA profiling, 3'UTR reporter assays, miRNA inhibitor experiments, flow cytometry, NK cytotoxicity assays Carcinogenesis Medium 23917076
2014 Six RNA-binding proteins (RBPs) bind and regulate MICB expression; at least two RBPs function during genotoxic stress; RBP binding was identified through unbiased RNA pull-down combined with mass spectrometry, establishing post-transcriptional regulation of MICB by RBPs. RNA pull-down assay, mass spectrometry, functional validation of RBP knockdown on MICB expression, genotoxic stress conditions Nature communications High 24924487
2014 Valproic acid (HDAC inhibitor) upregulates MICA and MICB expression on pancreatic cancer cells via the PI3K/Akt signaling pathway; this effect is blocked by PI3K inhibitor LY294002 or PI3K siRNA, and enhances NK cell-mediated cytotoxicity both in vitro and in vivo. Flow cytometry, qRT-PCR, PI3K inhibitor/siRNA epistasis, xenograft mouse model NK cytotoxicity assays BMC cancer Medium 24885711
2016 The RNA-binding protein IMP3 indirectly targets MICB expression through a mechanism functionally distinct from its direct interaction with ULBP2 mRNA (which causes transcript destabilization); IMP3-mediated regulation of MICB leads to impaired NK cell recognition of transformed cells. RIP assay, mRNA stability assays, IMP3 knockdown/overexpression, flow cytometry, NK cell cytotoxicity assays eLife Medium 26982091
2017 Vigilin, an RNA-binding protein, binds to the 5'UTR of MICB mRNA and negatively regulates MICB expression; vigilin downregulation in target cells increases MICB surface expression and significantly enhances NK cell activation against those cells. RNA pull-down assay, mass spectrometry, RNAi knockdown of vigilin, flow cytometry for MICB, NK activation assays Journal of immunology Medium 28356383
2017 ADAM17 (activated by ADAM17) mediates shedding of MICB, MICA, and ULBP2 from AML cell surfaces; hypomethylating agents (AZA, DAC) increase TIMP3 expression by demethylating the TIMP3 gene, and TIMP3 (an ADAM17 inhibitor) reduces soluble MICB shedding, thereby enhancing NKG2D-mediated NK cell recognition. ADAM17 inhibition, TIMP3 siRNA knockdown, bisulfite sequencing, ELISA for soluble MICB, flow cytometry for NKG2D receptor, NK cytotoxicity assays Oncotarget High 28404876
2017 STAT3 inhibition by STA21 increases cell surface MICB expression and soluble MICB secretion from gastric adenocarcinoma cells; recombinant soluble MICB decreases NKG2D receptor levels on NK and CD8+ T cells, impairing their cytolytic activity. STA21 pharmacological inhibition, flow cytometry, ELISA for soluble MICB, NKG2D receptor expression, NK cytotoxicity assays Immunobiology Medium 28578917
2018 Antibodies targeting the MICB/MICA alpha3 domain prevent proteolytic shedding of MICA and MICB from human cancer cells, maintaining surface expression; this inhibits tumor growth in immunocompetent mouse models primarily through NK cell activation via NKG2D and CD16 Fc receptors. Antibody engineering, cell surface MICA/B quantification, multiple syngeneic mouse tumor models, NK cell depletion experiments Science (New York, N.Y.) High 29599246
2018 miR-34a has a dual role in MICB regulation: it upregulates ATR kinase (promoting MICB expression) and downregulates E2F1 transcription factor (reducing MICB expression); the net effect on MICB depends on endogenous E2F1 levels, with miR-34a promoting MICB expression in cells with low E2F1. miR-34a overexpression/inhibition, ATR and E2F1 protein expression analysis, MICB flow cytometry, NK cell cytotoxicity assays Carcinogenesis Medium 30256916
2018 MG132 (proteasome inhibitor) selectively upregulates MICB transcription in A549 lung cancer cells via the DNA damage response, specifically through activation of ATM kinase and Chk2 phosphorylation; MG132 increases MICB promoter activity (~1.77-fold) and this is blocked by ATM kinase inhibitor KU-55933. Luciferase promoter reporter assay, ATM inhibitor epistasis, Chk2 phosphorylation western blot, flow cytometry, NK cytotoxicity assays Molecular medicine reports Medium 30483783
2019 LXR (Liver X Receptor) activation regulates MICA and MICB expression through distinct mechanisms: MICA is regulated at the transcriptional level (enhanced mica promoter activity), whereas MICB is regulated by inhibiting its lysosomal degradation; both effects increase surface MICA/B and render multiple myeloma cells more susceptible to NK cell killing. Promoter reporter assays for MICA, lysosomal pathway inhibitors for MICB, flow cytometry, NK degranulation and killing assays FASEB journal Medium 31125275
2020 HDAC inhibitor panobinostat and anti-MICA/B antibody (blocking shedding) synergistically enhance MICB surface expression on tumor cells: panobinostat enhances MICB gene expression, while the antibody stabilizes synthesized protein on the cell surface; the combination reduces pulmonary metastases in humanized NK cell mouse models. Drug combination assays, flow cytometry, MICB mRNA/protein quantification, humanized NOD/SCID gamma mouse model with human NK cells Cancer immunology research Medium 32209637
2013 Allelic MICB polymorphisms differentially affect binding to HCMV UL16 protein; MICB*008 (containing methionine at position 98 and asparagine at position 113 in the alpha2 domain) shows decreased binding to UL16 compared to MICB*003, *004, and *00502 (containing isoleucine at 98 and aspartic acid at 113), suggesting MICB*008 may be a protective allele for HCMV immune surveillance. Flow cytometry binding assay using soluble Fc-fusion UL16 proteins and stable cell lines expressing specific MICB alleles Journal of microbiology (Seoul, Korea) Medium 23625227
2003 Transgenic mice ubiquitously expressing human MICB show transient neonatal skin hyperkeratosis with epidermal hyperkeratosis, thickened granular layer, and mild inflammatory cell infiltration in the dermis, as well as ~50% leukocytosis, demonstrating an in vivo role for MICB in skin inflammation. Transgenic mouse generation with ubiquitous MICB promoter, histopathological analysis of skin, blood cell counting Tissue antigens Medium 12753668
2024 A common missense MICB variant (MICBD136N) results in reduced surface MICB expression and reduced NKG2D ligation; cells expressing MICBD136N are less susceptible to NK cell killing, and coculture with NK cells shows less NKG2D activation; in clinical cohorts, MICB variant homozygosity is associated with reduced severity of acute lung injury. Missense variant protein expression in cultured cells, flow cytometry for surface MICB, NK cell coculture cytotoxicity, BAL NK cell characterization in human subjects, clinical cohort analysis American journal of respiratory and critical care medicine High 37878820
2020 MICB amino acid position 98 (MICB98) is a key polymorphic residue involved in UL16 binding; mismatches at MICB98 in unrelated-donor hematopoietic cell transplantation are associated with increased acute and chronic GVHD and higher CMV infection/reactivation, establishing MICB98 as a functionally critical position linking UL16 interaction to clinical immune outcomes. Retrospective clinical study of 943 HCT pairs, MICB98 genotyping, hazard ratio analysis for GVHD and CMV outcomes Bone marrow transplantation Medium 32286503
2024 Linc-ROR promotes ubiquitination and degradation of RXRA (retinoid X receptor alpha) via E3 ligase UBE4B, reducing RXRA availability; since RXRA is a transcription factor for MICB, its degradation leads to reduced MICB surface expression and impaired NK cell-mediated cytotoxicity against gastric cancer cells. Co-transfection, ubiquitination assays, Linc-ROR overexpression, RXRA protein quantification, flow cytometry for surface MICB, NK-92 cell coculture cytotoxicity assays Journal of cellular biochemistry Medium 38205878
2017 Novel miRNAs binding to both the 3'UTR and 5'UTR of MICB mRNA reduce MICB expression; mutation of miRNA binding sites in either UTR restores luciferase activity in reporter assays; overexpression of candidate miRNAs reduces and inhibition increases MICB protein surface expression. Luciferase reporter assays with MICB 3'UTR and 5'UTR constructs, miRNA mimic/inhibitor experiments, flow cytometry Genes Medium 28850101

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB. Proceedings of the National Academy of Sciences of the United States of America 831 10359807
2009 Diverse herpesvirus microRNAs target the stress-induced immune ligand MICB to escape recognition by natural killer cells. Cell host & microbe 383 19380116
2018 Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity. Science (New York, N.Y.) 378 29599246
2001 Interactions of human NKG2D with its ligands MICA, MICB, and homologs of the mouse RAE-1 protein family. Immunogenetics 377 11491531
2003 Expression and role of MICA and MICB in human hepatocellular carcinomas and their regulation by retinoic acid. International journal of cancer 195 12569559
2011 Genome-wide association study identifies susceptibility loci for dengue shock syndrome at MICB and PLCE1. Nature genetics 169 22001756
2001 MICA and MICB genes: can the enigma of their polymorphism be resolved? Trends in immunology 160 11429322
2006 Release of MICB molecules by tumor cells: mechanism and soluble MICB in sera of cancer patients. Human immunology 121 16698441
1999 Microsatellite polymorphism of the MHC class I chain-related (MIC-A and MIC-B) genes marks the risk for autoimmune Addison's disease. The Journal of clinical endocrinology and metabolism 120 10523017
2012 MiR-10b downregulates the stress-induced cell surface molecule MICB, a critical ligand for cancer cell recognition by natural killer cells. Cancer research 108 22915757
2020 Inhibition of MICA and MICB Shedding Elicits NK-Cell-Mediated Immunity against Tumors Resistant to Cytotoxic T Cells. Cancer immunology research 107 32209637
2006 Soluble MICB in malignant diseases: analysis of diagnostic significance and correlation with soluble MICA. Cancer immunology, immunotherapy : CII 104 16636811
2007 Regulation of the expression of MHC class I-related chain A, B (MICA, MICB) via chromatin remodeling and its impact on the susceptibility of leukemic cells to the cytotoxicity of NKG2D-expressing cells. Leukemia 99 17625602
2017 MHC class I chain-related protein A and B (MICA and MICB) are predominantly expressed intracellularly in tumour and normal tissue. British journal of cancer 92 28334733
2007 In vivo expression pattern of MICA and MICB and its relevance to auto-immunity and cancer. PloS one 83 17565371
2006 Transfer of NKG2D and MICB at the cytotoxic NK cell immune synapse correlates with a reduction in NK cell cytotoxic function. Proceedings of the National Academy of Sciences of the United States of America 74 16849432
1997 Allelic variants of the human MHC class I chain-related B gene (MICB). Immunogenetics 74 9321430
2008 Decreased Dicer expression elicits DNA damage and up-regulation of MICA and MICB. The Journal of cell biology 68 18644891
2001 Competence repression under oxygen limitation through the two-component MicAB signal-transducing system in Streptococcus pneumoniae and involvement of the PAS domain of MicB. Journal of bacteriology 62 11443095
2002 MICA rather than MICB, TNFA, or HLA-DRB1 is associated with susceptibility to psoriatic arthritis. The Journal of rheumatology 58 12022360
2007 Transcriptional regulation of MICA and MICB: a novel polymorphism in MICB promoter alters transcriptional regulation by Sp1. European journal of immunology 57 17557375
2014 Valproic acid sensitizes pancreatic cancer cells to natural killer cell-mediated lysis by upregulating MICA and MICB via the PI3K/Akt signaling pathway. BMC cancer 55 24885711
2008 Induction of MHC class I-related chain B (MICB) by 5-aza-2'-deoxycytidine. Biochemical and biophysical research communications 53 18395517
2006 Expression of MHC class I-related Chain B (MICB) molecules on renal transplant biopsies. Transplantation 45 16641608
2016 The RNA binding protein IMP3 facilitates tumor immune escape by downregulating the stress-induced ligands ULPB2 and MICB. eLife 44 26982091
2001 MICA, MICB and C1_4_1 polymorphism in Crohn's disease and ulcerative colitis. Tissue antigens 44 11782275
2010 Structure of the HCMV UL16-MICB complex elucidates select binding of a viral immunoevasin to diverse NKG2D ligands. PLoS pathogens 43 20090832
2011 The human herpesvirus-7 (HHV-7) U21 immunoevasin subverts NK-mediated cytoxicity through modulation of MICA and MICB. PLoS pathogens 41 22102813
2001 Wide distribution of the MICA-MICB null haplotype in East Asians. Tissue antigens 41 11169252
2017 Increasing TIMP3 expression by hypomethylating agents diminishes soluble MICA, MICB and ULBP2 shedding in acute myeloid leukemia, facilitating NK cell-mediated immune recognition. Oncotarget 39 28404876
2013 Hepatitis B surface antigen inhibits MICA and MICB expression via induction of cellular miRNAs in hepatocellular carcinoma cells. Carcinogenesis 39 23917076
2006 MHC class I chain-related gene B (MICB) is associated with rheumatoid arthritis susceptibility. Rheumatology (Oxford, England) 37 17003176
2000 On the MICA deleted-MICB null, HLA-B*4801 haplotype. Tissue antigens 37 11034563
2002 High resolution molecular phototyping of MICA and MICB alleles using sequence specific primers. Human immunology 35 12175734
2011 Association of MICA and MICB alleles with symptomatic dengue infection. Human immunology 34 21762746
2007 Polymorphisms in MICB are associated with human herpes virus seropositivity and schizophrenia risk. Schizophrenia research 34 17561376
1998 Microsatellite polymorphism within the MICB gene among Japanese patients with Behçet's disease. Human immunology 34 9712354
2006 Variation in MICA and MICB genes and enhanced susceptibility to paucibacillary leprosy in South India. Human molecular genetics 33 16923796
1998 Sequencing-based typing reveals six novel MHC class I chain-related gene B (MICB) alleles. Tissue antigens 32 9694358
2011 Expression of MICA, MICB and NKG2D in human leukemic myelomonocytic and cervical cancer cells. Journal of experimental & clinical cancer research : CR 28 21477352
2010 Soluble MICB serum levels correlate with disease stage and survival rate in patients with oral squamous cell carcinoma. Anticancer research 28 21036725
2003 MICB typing by PCR amplification with sequence specific primers. Immunogenetics 28 12671735
2014 A replication study confirms the association of GWAS-identified SNPs at MICB and PLCE1 in Thai patients with dengue shock syndrome. BMC medical genetics 27 24884822
2014 RNA-binding proteins regulate the expression of the immune activating ligand MICB. Nature communications 27 24924487
2011 Characterization of the major histocompatibility complex class I chain-related gene B (MICB) polymorphism in a northern Chinese Han population: the identification of a new MICB allele, MICB*023. Human immunology 26 21664939
2005 The haplotype block, NFKBIL1-ATP6V1G2-BAT1-MICB-MICA, within the class III-class I boundary region of the human major histocompatibility complex may control susceptibility to hepatitis C virus-associated dilated cardiomyopathy. Tissue antigens 26 16101831
2019 Activation of liver X receptor up-regulates the expression of the NKG2D ligands MICA and MICB in multiple myeloma through different molecular mechanisms. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25 31125275
2010 HIF-1alpha accumulation upregulates MICA and MICB expression on human cardiomyocytes and enhances NK cell cytotoxicity during hypoxia-reoxygenation. Life sciences 25 20566410
2004 Association of MHC class I related gene B (MICB) to celiac disease. The American journal of gastroenterology 25 15089901
2002 Alu polymorphism within the MICB gene and association with HLA-B alleles. Immunogenetics 24 11862397
2008 Genetic influence of the nonclassical major histocompatibility complex class I molecule MICB in multiple sclerosis susceptibility. Tissue antigens 22 18588574
2017 5'-UTR and 3'-UTR Regulation of MICB Expression in Human Cancer Cells by Novel microRNAs. Genes 21 28850101
2016 MICA, MICB Polymorphisms and Linkage Disequilibrium with HLA-B in a Chinese Mongolian Population. Scandinavian journal of immunology 21 27028549
2014 Diversity and characterization of polymorphic 5' promoter haplotypes of MICA and MICB genes. Tissue antigens 21 24962621
2008 Associations of MICB with cervical cancer in north-eastern Thais: identification of major histocompatibility complex class I chain-related gene B motifs influencing natural killer cell activation. Clinical and experimental immunology 21 18505429
2011 MICB polymorphisms and haplotypes with MICA and HLA alleles in Koreans. Tissue antigens 20 21554252
2002 High frequency of MIC null haplotype (HLA-B48-MICA-del-MICB*0107 N) in the Angaite Amerindian community in Paraguay. Immunogenetics 20 12242594
2001 MICA and MICB microsatellite alleles in HLA extended haplotypes. European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics 20 11881819
2000 Three novel MICB alleles. Tissue antigens 19 10746790
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
2017 STAT3 inhibition by STA21 increases cell surface expression of MICB and the release of soluble MICB by gastric adenocarcinoma cells. Immunobiology 17 28578917
2012 MICB polymorphism in a southern Chinese Han population: the identification of two new MICB alleles, MICB*005:06 and MICB*026. Human immunology 17 22609444
2001 The nucleotide diversity of MICA and MICB suggests the effect of overdominant selection. Tissue antigens 17 11929594
2001 Linkage disequilibria between HLA-B, C1_4_1, MICA and MICB. Tissue antigens 14 11929593
2017 Soluble MICB in Plasma and Urine Explains Population Expansions of NKG2D+CD4 T Cells Inpatients with Juvenile-Onset Systemic Lupus Erythematosus. Open journal of immunology 13 28944101
2013 Distribution of MICB diversity in the Zhejiang Han population: PCR sequence-based typing for exons 2-6 and identification of five novel MICB alleles. Immunogenetics 13 23549730
2004 Study on the haplotypes of MICA and MICB microsatellite and HLA-B locus in the Guangzhou Han population. Tissue antigens 13 15304009
2020 Compatibility at amino acid position 98 of MICB reduces the incidence of graft-versus-host disease in conjunction with the CMV status. Bone marrow transplantation 12 32286503
2002 Alternatively spliced forms of MICA and MICB lacking exon 3 in a human cell line and evidence of presence of similar RNA in human peripheral blood mononuclear cells. Immunogenetics 12 12466900
1999 Novel intronic variants of MICB (MHC class I chain-related gene B). European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics 12 10583461
2018 MicroRNA-34a promotes MICB expression in hepatocytes. Carcinogenesis 11 30256916
2018 MG132 selectively upregulates MICB through the DNA damage response pathway in A549 cells. Molecular medicine reports 11 30483783
2016 MMP9 Promoter Polymorphism (-1562 C/T) Does not Affect the Serum Levels of Soluble MICB and MICA in Breast Cancer. Iranian journal of immunology : IJI 11 27026046
2013 ADAM15 is involved in MICB shedding and mediates the effects of gemcitabine on MICB shedding in PANC-1 pancreatic cancer cells. Molecular medicine reports 11 23314034
2006 MICB microsatellite polymorphism is associated with ulcerative colitis in Chinese population. Clinical immunology (Orlando, Fla.) 11 16679067
2024 MICB Genomic Variant Is Associated with NKG2D-mediated Acute Lung Injury and Death. American journal of respiratory and critical care medicine 9 37878820
2021 High-throughput genotyping of HLA-G, HLA-F, MICA, and MICB and analysis of frequency distributions in healthy blood donors from Catalonia. HLA 9 33599111
2021 Associations of high-resolution-typing-defined MICA and MICB polymorphisms, and the levels of soluble MICA and MICB with Oral Squamous Cell Carcinoma in Bulgarian patients. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 9 33835601
2021 Single-Nucleotide Polymorphisms in MICA and MICB Genes Could Play a Role in the Outcome in AML Patients after HSCT. Journal of clinical medicine 9 34682758
2017 Vigilin Regulates the Expression of the Stress-Induced Ligand MICB by Interacting with Its 5' Untranslated Region. Journal of immunology (Baltimore, Md. : 1950) 9 28356383
2013 Metastamir-mediated immune evasion: miR-10b downregulates the stress-induced molecule MICB, hence avoid recognition by NKG2D receptor. Oncoimmunology 9 23479551
2004 Eight novel MICB alleles, including a null allele, identified in gastric MALT lymphoma patients. Tissue antigens 9 15304008
2011 Impact of MICA-TM, MICB-C1_2_A and C1_4_1 microsatellite polymorphisms on the susceptibility to chronic periodontitis in Germany. Tissue antigens 8 21388352
2019 Inhibiting exosomal MIC-A and MIC-B shedding of cancer cells to overcome immune escape: new insight of approved drugs. Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences 7 31435903
2013 Characterization of 3'untranslated region (3'UTR) of the MICB gene. Human immunology 7 23380144
2023 Associations between MICA and MICB Genetic Variants, Protein Levels, and Colorectal Cancer: Atherosclerosis Risk in Communities (ARIC). Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 6 36958849
2020 Major Histocompatibility Complex Class I Chain-Related A and B (MICA and MICB) Gene, Allele, and Haplotype Associations With Dengue Infections in Ethnic Thais. The Journal of infectious diseases 6 32737971
2016 In silico transcriptional regulation and functional analysis of dengue shock syndrome associated SNPs in PLCE1 and MICB genes. Functional & integrative genomics 6 27038471
2013 Allelic MHC class I chain related B (MICB) molecules affect the binding to the human cytomegalovirus (HCMV) unique long 16 (UL16) protein: implications for immune surveillance. Journal of microbiology (Seoul, Korea) 6 23625227
2018 MICB*002 and MICB*014 protect against rheumatoid arthritis, whereas MICA*009 and MICA*A6 are associated with rheumatoid arthritis in a Hainan Han Chinese population. International journal of rheumatic diseases 5 29665245
2016 Polymorphism rs3828903 within MICB Is Associated with Susceptibility to Systemic Lupus Erythematosus in a Northern Han Chinese Population. Journal of immunology research 5 27433477
2015 Soluble MICB protein levels and platelet counts during hepatitis B virus infection and response to hepatocellular carcinoma treatment. BMC infectious diseases 5 25626490
2003 Hyperkeratosis and leukocytosis in transgenic mice carrying MHC class I chain-related gene B (MICB). Tissue antigens 5 12753668
2024 Linc-ROR inhibits NK cell-killing activity by promoting RXRA ubiquitination and reducing MICB expression in gastric cancer patients. Journal of cellular biochemistry 4 38205878
2022 HLA class I chain-related MICA and MICB genes polymorphism in healthy individuals from the Bulgarian population. Human immunology 4 35525711
2018 Correction: Increasing TIMP3 expression by hypomethylating agents diminishes soluble MICA, MICB and ULBP2 shedding in acute myeloid leukemia, facilitating NK cell-mediated immune recognition. Oncotarget 4 30214691
2018 Single-Nucleotide Polymorphisms in NOD1, RIPK2, MICB, PLCE1, TNF, and IKBKE Genes Associated with Symptomatic Dengue in Children from Colombia. Viral immunology 4 30332343
2018 Diversity and characterisation of polymorphic 3' untranslated region haplotypes of MICA and MICB genes. HLA 4 30471210
2005 [Effect of hypoxia/reoxygenation (H/R) on expression of MICA and MICB in human hepatocytes]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 4 15807254
2025 Identification of Novel MICB Alleles in Haematopoietic Stem Cell Donors of Indian Origin. HLA 3 39871443