RING-finger-like zinc-binding domain (RLD), the highly acidic domain (AD), the SUMO-interacting motif (SIM), and the serine/threonine-rich C-terminal region (S/T). SAP The N-terminal scaffold attachment factor-A/B, acinus and PIAS (SAP) domain is found in all PIAS proteins. It is composed of four alpha helices. It binds to areas of chromatin that are rich in adenine (A) and thymine (T). These A/T rich regions are known as matrix-attachment regions. Once bound, the matrix-attachment regions anchor loops of chromatin to the nuclear matrix. The nuclear matrix is a structure within the nucleus where it is thought that transcription regulation takes place. SAP also binds to p53. Each SAP domain contains an LXXLL amino acid motif. L = leucine, and X = any amino acid. This motif is used to bind to nuclear receptors. Nuclear receptors are transcription factors that regulate transcription upon ligand binding. PINIT The Pro-Ile-Asn-Ile-Thr (PINIT) motif was discovered in PIAS3L, an isoform of PIAS3. PIAS proteins tend to go back and forth between the nucleus and cytosol as they carry out their activities. PINIT is needed to localize PIAS3 and PIAS3L to the nucleus. PIASy has a slight difference in its PINIT motif: leucine is in place of the second isoleucine (PINLT). Furthermore, the PINIT motif is not found in PIASy isoform PIASyE6-. This isoform, lacking exon 6, is still retained in the nucleus despite lacking the PINIT motif. The reason for this is unknown. RLD The RING-finger-like zinc-binding domain is present in all PIAS proteins. RLD is essential for PIAS proteins to function as E3 SUMO-protein ligases. It is also needed for successful interaction with other proteins. Its three dimensional structure is thought to be similar to typical RING finger domains. It contains one histidine residue and five cysteine residues AD and SIM The highly acidic domain (AD), present in all PIAS proteins, contains a SUMO-interacting motif (SIM). The SIM motif may be needed for PIAS proteins to accurately recognize and interact with other SUMO proteins. However, it is not needed for E3 SUMO-protein ligase activity to occur. The function of the highly acidic domain is unknown. S/T The Serine/threonine-rich C-terminal (S/T) region is not found in all PIAS proteins. PIASy and PIASyE6- are the only members of the PIAS protein family that lack this region. Furthermore, the length of this region varies among PIAS protein isoforms. The function of the S/T region is unknown. Potential applications Defects in