SmcY Background Information SmcY, also known as JARID1D (Jumonji/ARID domain-containing protein 1D), HY, HYA or KDM5D, is a nuclear protein that belongs to the JARID1 histone demethylase family. Encoded by a gene on the Y chromosome, SmcY is expressed only in male tissues where it functions as a histone demethylase that removes specific methyl residues from Histone H3, thereby playing a role in the histone code. SmcY uses ascorbate (vitamin C) and iron as cofactors and contains several domains, including one JMJC domain, through which it conveys its enzymatic activity. In addition to its demethylase activity, SmcY can be cleaved into a small peptide that functions as a minor histocompatibility antigen (termed HY or HYA) that rejects female tissue and may be involved in male development and fertility. Multiple isoforms of SmcY exist due to alternative splicing events.