InterPro domain: IPR003034

The SAP motif is a 35-residue motif, which has been named after SAF-A/B,Acinus and PIAS, three proteins known to contain it. The SAP motif is found ina variety of nuclear proteins involved in transcription, DNA repair, RNAprocessing or apoptotic chromatin degradation. As the sap motif of SAF-A hasbeen shown to be essential for specific DNA binding activity, it has beenproposed that it could be a DNA-binding motif [ 1 ].

A multiple alignment of the SAP motif reveals a bipartite distribution ofstrongly conserved hydrophobic, polar and bulky amino acids separated by aregion that contains a glycine. Secondary structure predictions suggest thatthe SAP motif could form two alpha helices separated by a turn [ 2 ].

Some proteins known to contain a SAP motif are listed below:

• Vertebrate scaffold attachment factors A and B (SAF-A/B). These two proteins are heterogeneous nuclear ribonucleoproteins (hnRNPs) that bind to AT-rich chromosomal region. It has been proposed that they couple RNA metabolism to nuclear organisation [ 2 , 3 ]. The SAF-A protein is cleaved by caspase-3 during apoptosis [ 4 ].
• Mammalian Acinus, a protein which induces apoptotic chromatin condensation after cleavage by caspase-3 [ 5 ]. Acinus also contains a RNA-recognition motif.
• Eukaryotic proteins of the PIAS (protein inhibitor of activated STAT) family. These proteins interact with phosphorylated STAT dimers and inhibit STAT mediated gene activation. Deletion of the first 50 amino acid residues containing the SAP domain allows the interaction of PIAS1 with STAT1 monomer [ 6 ].
• Plant poly(ADP-ribose) polymerase (PARP). PARP is a nuclear protein that catalyzes the poly(ADP-ribosyl)ation of proteins. It is involved in responses to mild and severe oxidative stresses, by mediating DNA repair and programmed cell death processes, respectively [ 7 ]. PARP is tightly bound to chromatin or nuclear matrix.
• Arabidopsis thaliana Arp, an apurinic endonuclease-redox protein.
• Yeast THO1 protein. It could be involved in the regulation of transcriptional elongation by RNA polymerase II [ 8 ].
• Animal Ku70. Together with Ku86, it forms a DNA ends binding complex that is involved in repairing DNA double-strand breaks.
• Yeast RAD18, a protein involved in DNA repair.
• Neurospora crassa UVS-2, the homologue of RAD18.

1. SAP - a putative DNA-binding motif involved in chromosomal organization. Trends Biochem. Sci. 25, 112-4
2. A novel hnRNP protein (HAP/SAF-B) enters a subset of hnRNP complexes and relocates in nuclear granules in response to heat shock. J. Cell. Sci. 112 ( Pt 10), 1465-76
3. SAF-B protein couples transcription and pre-mRNA splicing to SAR/MAR elements. Nucleic Acids Res. 26, 3542-9
4. Apoptotic cleavage of scaffold attachment factor A (SAF-A) by caspase-3 occurs at a noncanonical cleavage site. J. Biol. Chem. 275, 5031-6
5. Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation. Nature 401, 168-73
6. Distinct roles of the NH2- and COOH-terminal domains of the protein inhibitor of activated signal transducer and activator of transcription (STAT) 1 (PIAS1) in cytokine-induced PIAS1-Stat1 interaction. Proc. Natl. Acad. Sci. U.S.A. 97, 5267-72
7. The involvement of poly(ADP-ribose) polymerase in the oxidative stress responses in plants. FEBS Lett. 440, 1-7
8. A novel yeast gene, THO2, is involved in RNA pol II transcription and provides new evidence for transcriptional elongation-associated recombination. EMBO J. 17, 4859-72