called isoforms. PIAS1 is the only gene of this family that does not encode any isoforms. Homologues Homologues of PIAS proteins have been found in other eukaryotes, and several are listed below: Zimp/dPIAS in Drosophila melanogaster zfPIAS4a in zebrafish SIZ1 and SIZ2 in yeast Function PIAS proteins contribute to the control of gene expression, and may be considered transcriptional co-regulators. While PIAS proteins interact with at least 60 different proteins involved in transcription, they are known to act as E3 SUMO-protein ligases. In essence, the RING-finger-like zinc-binding domain of the PIAS protein assists in the attachment of a SUMO protein to the target transcription factor. Attachment of a SUMO protein to the target allows for protein–protein interaction between PIAS and the transcription factor. This interaction can either upregulate or downregulate transcription. For example, the activity of transcription factor p53 was stimulated after it was SUMOylated by PIASy. In contrast, the activity of transcription factor p73 was repressed after it was SUMOylated by PIAS1. One function of PIAS proteins is to relocate transcriptional regulators to different compartments within the nucleus of the cell. PIAS proteins also play a key role in double-stranded break DNA repair. Exposure to UV light, chemicals, and ionizing radiation can cause DNA damage, and the most detrimental type of DNA damage is a double-stranded break. PIAS1, PIAS3, and PIAS4 have been shown to recruit proteins to the site of the damage and promote repair. Additionally, PIAS proteins are important transcriptional co-regulators of the JAK/STAT signaling pathway. PIAS protein's interaction with STAT signaling requires tyrosine phosphorylation of STAT proteins. Additionally, PIAS1 binds preferentially to un-methylated STAT1. Although the exact mechanism isn't clear, PIAS1 and PIASy both inhibit STAT1 signaling. PIAS3 was found to specifically inhibit STAT3 signaling after stimulation by the cytokine IL-6. Also, it is known that PIAS1 can inhibit NF-κB activity upon stimulation by the cytokine TNF and the LPS endotoxin. Structure The three-dimensional protein structures of PIAS2, PIAS3, and PIAS-like protein SIZ1 were recently solved using X-ray crystallography. The structures of PIAS2 and PIAS3 were listed in the Structural Genomics Consortium in 2012 and 2013, respectively, by A. Dong et al. Details of the SIZ1 structure were published by Ali A. Yunus and Christopher D. Lima in 2009. Four PIAS domains and two PIAS motifs have been identified. They include the N-terminal scaffold attachment factor-A/B, acinus and PIAS (SAP) domain, the Pro-Ile-Asn-Ile-Thr (PINIT) motif, the