InterPro domain: IPR033658

This entry represents a glutaredoxin (GRX) domain found in PICOT (also known as glutaredoxin-3 or PKC-interacting cousin of thioredoxin) and GRX-PICOT-like proteins. The non-PICOT members of this group contain only the GRX-like domain, whereas PICOT contains an N-terminal TRX-like domain followed by one to three GRX-like domains. It is interesting to note that PICOT from plants contain three repeats of the GRX-like domain, metazoan proteins (except for insect) have two repeats, while fungal sequences contain only one copy of the domain. PICOT is a protein that interacts with protein kinase C (PKC) theta, a calcium independent PKC isoform selectively expressed in skeletal muscle and T lymphocytes. PICOT inhibits the activation of c-Jun N-terminal kinase and the transcription factors, AP-1 and NF-kB, induced by PKC theta or T-cell activating stimuli. Both GRX and TRX domains of PICOT are required for its activity [ 1 , 2 , 3 ]. Characterized non-PICOT proteins with this domain include CXIP1, a CAX-interacting protein in Arabidopsis thaliana, and PfGLP-1, a GRX-like protein from Plasmodium falciparum [ 4 , 5 ].

1. Inhibition of the c-Jun N-terminal kinase/AP-1 and NF-kappaB pathways by PICOT, a novel protein kinase C-interacting protein with a thioredoxin homology domain. J. Biol. Chem. 275, 1902-9
2. PICOT-HD: a highly conserved protein domain that is often associated with thioredoxin and glutaredoxin modules. Trends Biochem. Sci. 25, 537-9
3. Glutaredoxins: glutathione-dependent redox enzymes with functions far beyond a simple thioredoxin backup system. Antioxid. Redox Signal. 6, 63-74
4. Cloning and characterization of CXIP1, a novel PICOT domain-containing Arabidopsis protein that associates with CAX1. J. Biol. Chem. 278, 6503-9
5. Plasmodium falciparum possesses a classical glutaredoxin and a second, glutaredoxin-like protein with a PICOT homology domain. J. Biol. Chem. 276, 37133-40