Enhancer of Zeste Homologs Inhibitory Protein (EZHIP)

Enhancer of Zeste Homologs Inhibitory Protein (EZHIP), also known as CXorf67 or CATACOMB, is a nuclear protein encoded on the X chromosome in humans. It directly binds and competitively inhibits the Polycomb Repressive Complex 2 (PRC2), specifically blocking the methyltransferase activity of EZH1/EZH2, leading to genome-wide reduction in H3K27 trimethylation. EZHIP is functionally and mechanistically analogous to the H3K27M oncohistone; both block PRC2 and thus reduce repressive histone marks, contributing to oncogenesis in distinct pediatric brain tumor types including PFA ependymoma and diffuse intrinsic pontine glioma (DIPG). The protein acts via a conserved "K27M-like" peptide motif at its C-terminus and is intrinsically disordered. EZHIP is expressed predominantly in certain tissues, most notably in the testis, placenta, and various tumors. Its dysregulation or mutation is associated with clinically and molecularly defined cancers, with a proposed role both in diagnosis and in understanding epigenetic oncogenic mechanisms[1][2][3][7]. **Note:** No approved therapeutic agents currently modulate EZHIP directly; it is primarily a mechanistic biomarker and a research focus in PRC2-related oncogenesis[1][2].

Other names

EZHIPCXorf67CATACOMBKIP75K27M-like inhibitor of PRC2catalytic antagonist of Polycombchromosome X open reading frame 67

Not applicable; EZHIP itself is an endogenous competitive inhibitor of PRC2, acting through a K27M-like C-terminal motif that blocks enzymatic activity of PRC2/EZH2