MICB Gene - MHC class I polypeptide-related sequence B

MICB (MHC class I polypeptide-related sequence B) is a highly polymorphic gene located in the MHC class I region on chromosome 6. It encodes a stress-induced cell surface glycoprotein that serves as a ligand for the NKG2D receptor expressed on natural killer (NK) cells, CD8+ T cells, and γδ T cells. MICB is not associated with β2-microglobulin or peptide presentation; instead, its expression is upregulated in response to cellular stress, infection, or transformation, facilitating immune recognition and elimination of damaged or malignant cells. Alternative splicing generates multiple transcript variants.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• NKG2D signaling in NK cells (Reactome: R-HSA-199043)

• Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (Reactome: R-HSA-198933)

• Antigen processing and presentation (KEGG: hsa04612)

MICB is a type I transmembrane protein with three extracellular alpha domains (α1, α2, α3) homologous to MHC class I molecules, but it does not bind β2-microglobulin or present peptides. The α1α2 platform forms the binding site for the NKG2D receptor. The protein is anchored in the membrane via a transmembrane domain and has a short cytoplasmic tail. Stress-induced expression is regulated by heat shock elements and transcription factors such as HSF1. Proteolytic shedding by matrix metalloproteinases (e.g., MMP-14) releases soluble MICB, which can downregulate NKG2D and impair immune function.