Alternative titles; symbols
HGNC Approved Gene Symbol: THAP12
Cytogenetic location: 11q13.5 Genomic coordinates (GRCh38): 11:76,349,956-76,381,132 (from NCBI)
Gale et al. (1998) searched for cDNAs encoding regulators of P58(IPK) (601184) function. They identified P52(rIPK) as a 1,479-bp cDNA encoding a protein of 492 amino acids. The protein contains a region (amino acids 86 to 200) of limited homology (24% identity) to the charged domain of HSP90 (140571).
By searching databases, Roussigne et al. (2003) identified several proteins containing an N-terminal THAP domain, including PRKRIR, which they designated THAP0. The THAP domain of the deduced 761-amino acid THAP0 protein includes a C2CH signature, an AVPTIF box, and several other conserved amino acids.
P58(IPK) functions to repress PKR (176871)-mediated phosphorylation of the eukaryotic initiation factor-2 alpha subunit (EIF2-alpha; 603907) through direct interaction, thereby relieving the PKR-imposed block on mRNA translation and cell growth. Gale et al. (1998) demonstrated that P52(rIPK) and P58(IPK) interacted in a yeast 2-hybrid assay and were recovered as a complex from mammalian cell extracts. When coexpressed with PKR in yeast, P58(IPK) repressed PKR-mediated EIF2-alpha phosphorylation, inhibiting the normally toxic and growth-suppressive effects associated with PKR function. Conversely, introduction of P52(rIPK) into these strains resulted in restoration of both PKR activity and EIF2-alpha phosphorylation, concomitant with growth suppression due to inhibition of P58(IPK) function. Furthermore, Gale et al. (1998) showed that P52(rIPK) inhibited P58(IPK) function in a reconstituted in vitro PKR-regulatory assay. Gale et al. (1998) concluded that P58(IPK) is inhibited through a direct interaction with P52(rIPK), which in turn results in upregulation of PKR activity. Gale et al. (1998) concluded that their data described a protein kinase-regulatory system that encompasses an intersection of interferon- (see 147660), stress-, and growth-regulatory pathways.
Gross (2014) mapped the PRKRIR gene to chromosome 11q13.5 based on an alignment of the PRKRIR sequence (GenBank AF007393) with the genomic sequence (GRCh37).
Gale, M., Jr., Blakely, C. M., Hopkins, D. A., Melville, M. W., Wambach, M., Romano, P. R., Katze, M. G. Regulation of interferon-induced protein kinase PKR: modulation of P58(IPK) inhibitory function by a novel protein, P52(rIPK). Molec. Cell. Biol. 18: 859-871, 1998. [PubMed: 9447982] [Full Text: https://doi.org/10.1128/MCB.18.2.859]
Gross, M. B. Personal Communication. Baltimore, Md. 5/29/2014.
Roussigne, M., Kossida, S., Lavigne, A.-C., Clouaire, T., Ecochard, V., Glories, A., Amalric, F., Girard, J.-P. The THAP domain: a novel protein motif with similarity to the DNA-binding domain of P element transposase. Trends Biochem. Sci. 28: 66-69, 2003. [PubMed: 12575992] [Full Text: https://doi.org/10.1016/S0968-0004(02)00013-0]