PAXIP1-associated glutamate-rich protein 1 (PAGR1)

PAXIP1-associated glutamate-rich protein 1 (PAGR1, also historically known as PA1, C16orf53, among other names) is a nuclear chromatin-associated protein that functions as a transcriptional cofactor and is an integral part of histone methyltransferase complexes, such as those containing MLL3/4. PAGR1 regulates gene expression through modulation of chromatin structure by facilitating H3K4 methylation, a key epigenetic mark for transcriptional activation. Beyond its role in epigenetic regulation, PAGR1 participates in the DNA damage response, being recruited to sites of DNA breaks in cooperation with PAXIP1, and is essential for maintaining genomic stability. PAGR1 can modulate the activity of nuclear hormone receptors—including estrogen, glucocorticoid, androgen, and PPARG—by acting as a competitive cofactor, influencing receptor-mediated gene transcription and cell cycle progression. In vivo, loss of the mouse homolog Pagr1a leads to embryonic developmental defects, most notably in extraembryonic tissues, at least in part through impaired BMP signaling. Clinically, PAGR1/PA1 is noted as a prognostic marker in breast cancer and has been associated with multiple cancer types and other disease states in expression studies. There are no known drugs that directly target PAGR1, nor associated mechanisms of drug action or specific safety concerns reported in the available literature.

Other names

PA1C16orf53PTIP-associated protein 1PAXIP1-associated protein 1Glutamate-rich coactivator interacting with SRC1GASMGC4606PTIP-associated 1 protein