PIAS1 gene is composed of 14 exons and spans approximately 134,8 kb of genomic DNA.

PIAS1 gene encodes a 2309 bp mRNA transcript.

No pseudogenes have been reported.

The human PIAS1 protein is composed of 651 amino acids, with a predicted molecular weight of 71,85 kDa. PIAS1 has five distinct functional domains, with different functions: the SAP (scaffold attachment factor-A/B, Acinus and PIAS), the PINIT motif, the RING-type zinc-binding domain, the SBD (SUMO binding domain, also indicated as SIM, SUMO interacting motif) and a C-terminal serine/threonine rich region. The SAP domain contains a LXXLL motif which is involved in direct-DNA binding or in physical interaction with other proteins involved in DNA-binding, such as transcription factors, co-regulators and nuclear receptors (Aravind and Koonin, 2000). The PINIT motif is involved in the sub-cellular organization of PIAS1 (Duval et al., 2003). The RING domain is essential for the E3 SUMO-ligase activity of PIAS1 and also mediates protein-protein interactions (Hochstrasser, 2001). The SBD domain interact in a non-covalently way with SUMO proteins (Rytinki et al., 2009). The C-terminal portion of PIAS1 is a serine/threonine rich region: this is the most variable region within the PIAS proteins family. PIAS1 undergoes several post-translational modifications, including phosphorylation, acetylation, methylation, SUMOylation and ubiquitination (Liu et al., 2005; Depaux et al., 2007; Rytinki et al., 2009; Stehmeier and Muller, 2009; Weber et al., 2009).

PIAS1 is ubiquitously expressed.

Nuclear.

PIAS1 has been implicated in several cellular functions and most of them have been associated to its SUMO E3-ligase activity (Schimdt and Müller, 2003; Shuai and Liu, 2005; Rytinki et al., 2009).
Transcriptional regulation: PIAS1 is a negative regulator of several transcription factors. PIAS1 was initially described as a negative regulator of the STAT1 signal by blocking the DNA-binding activity of STAT1 (Liu et al., 1998). PIAS1 SUMOylates the TP53 tumor suppressor, inhibiting its activity (Kahyo et al., 2001; Schmidt and Müller, 2002). PIAS1 SUMOylates the androgen receptor (AR) repressing the AR-dependent transcription (Nishida and Yasuda, 2002). PIAS1 also regulates the homeoprotein Msx1 by regulating its subnuclear localization and its DNA-binding specificity in a SUMO E3-ligase independent manner (Lee et al., 2006). PIAS1 SUMOylates the progesterone receptor (PR), and cAMP attenuates ligand-dependent SUMOylation of PR (Jones et al., 2006).
Inflammation and immunity: upon various inflammatory stimuli, IKKa phosphorylates PIAS1 associating it with the promoter of NF-κB target genes (Liu et al., 2007). PIAS1 regulates the natural T regulatory cells by restricting their differentiation through the recruitment of the protein DNA-methyltransferase and CBX5 at the FOXP3 promoter (Liu et al., 2010).
DNA damage: PIAS1 co-operates with PIAS4 promoting double-strand DNA breaks repair (Galanty et al., 2009).
Cancer: PIAS1 SUMOylates the promyelocytic leukemia (PML) gene and promotes its ubiquitin/proteasome-dependent degradation, inhibiting its tumor suppressor functions. PIAS1 also SUMOylates the PML-RARA oncoprotein of acute promyelocytic leukemia (APL); in this case, PIAS1-dependent SUMOylation is required for the degradation of PML-RARA in APL cells treated with arsenic trioxide (Rabellino et al., 2012).

PIAS1 belongs to the PIAS proteins family and is evolutionary conserved from yeast to man. PIAS1 can be found in Saccharomyces cerevisiae, in plants (Arabidopis thaliana and Oryza sativa), Caernorhabditis elegans, Drosophila melanogaster, Danio renio, Xenopus laevis, Gallus gallus and mammals. All PIAS1 orthologues share a high degree of homology. The human PIAS family consists of at least 5 different members: PIAS1, PIAS2 (with two variants called PIASxα and PIASxβ), PIAS3 and PIAS4 (also known as PIASy). All family members share high protein homology, except for the C-terminus (Shuai and Liu, 2005; Rytinki et al., 2009).

No translocations involving PIAS1 gene have been reported so far.

No germinal mutations of PIAS1 have been reported.

At least 25 different somatic mutations have been described in different tumor types. All the informations in this regard can be found at the COSMIC website.