PSMC3 interacting protein (PSMC3IP)

PSMC3 interacting protein (PSMC3IP, also known as HOP2, TBPIP, GT198) is a nuclear protein essential in meiotic homologous recombination, acting with the MND1 subunit to stimulate Rad51/Dmc1 recombinase activity and ensure accurate pairing and exchange of homologous chromosomes during meiosis. Beyond its recombination role, PSMC3IP serves as a tissue-specific coactivator for nuclear hormone receptors—including estrogen, androgen, glucocorticoid, progesterone, and thyroid receptors—by enhancing ligand-dependent transcription via direct interaction with DNA-binding domains. Mutations disrupt reproductive development, causing conditions like XX gonadal dysgenesis, azoospermia, and premature ovarian insufficiency. Aberrant PSMC3IP expression is implicated in cancer (notably ovarian and hepatocellular carcinoma), where it may modulate DNA repair, cancer stem cell properties, and proliferation. It is classified molecularly as a DNA repair protein and nuclear receptor coactivator, but currently lacks approved drugs targeting it directly. Its clinical importance centers on fertility, reproductive development, and cancer biology.

Other names

Homologous-pairing protein 2 homologHOP2TBPIPGT198HUMGT198AODG3Tat-binding protein 1-interacting proteinNuclear receptor coactivator GT198Proteasome 26S ATPase subunit 3-interacting proteinTBP-1-interacting protein

Not established for direct drug interaction. Mechanistically, disruption would theoretically impair homologous recombination or nuclear receptor transcriptional coactivation.