Alternative titles; symbols
HGNC Approved Gene Symbol: HELZ2
Cytogenetic location: 20q13.33 Genomic coordinates (GRCh38) : 20:63,558,086-63,574,239 (from NCBI)
PRIC285 is a nuclear transcriptional coactivator for PPAR-alpha (PPARA; 170998) and PPAR-gamma (PPARG; 601487), as well as various other nuclear receptors (Surapureddi et al., 2002; Tomaru et al., 2006).
By screening for cDNAs with the potential to encode large proteins expressed in human brain, Nagase et al. (2000) identified partial PRIC285, which they designated KIAA1769. RT-PCR analysis detected moderate expression in most all human tissues and specific brain regions tested, except for low expression in testis and cerebellum.
Surapureddi et al. (2002) purified a multiprotein PPAR-alpha-interacting cofactor (PRIC) protein complex from rat liver nuclear extract isolated 1 hour after a dose of ciprofibrate, a synthetic PPARA ligand. By database analysis using sequences from gel-separated PRIC complex proteins, the authors identified PRIC285. The deduced 2,080-amino acid protein has a calculated molecular mass of 285 kD and contains 5 LLXLL motifs and a helicase motif. Northern blot analysis of human tissues detected a 9.5-kb transcript in skeletal muscle, colon, spleen, liver, kidney, lung, peripheral blood, and placenta, as well as several cancer cell lines. In HEK293 cells, PRIC285 colocalized with PPARA to the nucleus.
Tomaru et al. (2006) independently isolated PRIC285, which they called PDIP1. They identified a 2,080-amino acid isoform with a calculated molecular mass of 231 kD, which they called PDIP1-alpha, and a 2,649-amino acid isoform with a calculated molecular mass of 295 kD, which they called PDIP1-beta, resulting from an N-terminal extension of 576 amino acids. Northern blot analysis of human tissues detected ubiquitous expression of a 10-kb transcript, with highest expression in heart, liver, skeletal muscle, and pancreas.
Using GST pull-down assays, Surapureddi et al. (2002) showed that PRIC285 displays ligand-dependent interaction with PPARA as well as PPARG, TR-beta-1 (THRB; 190160), ER-alpha (133430), and RXR-alpha (180245). By cotransfection of PRIC285 and PPARA with a PPRE reporter, Surapureddi et al. (2002) showed that PRIC285 coactivated PPARA transcriptional activity.
By yeast 2-hybrid analysis and GST pull-down assay, Tomaru et al. (2006) demonstrated that the C-terminal portion of PDIP1 mediated interaction with PPAR-gamma. Both PDIP1-alpha and PDIP1-beta enhanced PPAR-gamma-mediated transactivation, and the 5 LXXLL motifs were not required for this enhancement. RNAi knockdown of PDIP1 reduced ligand-dependent activation by PPARG. PDIP1-alpha and PDIP1-beta similarly augmented transactivation by PPAR-alpha, PPAR-delta (PPARD; 600409), TR-alpha-1 (THRA; 190120), TR-beta-1, and RXR-alpha. PDIP1-alpha also enhanced AR (313700)- and ER-alpha-mediated transactivation, whereas PDIP1-beta did not. PDIP1-alpha showed receptor-specific synergism with CBP (CREBBP; 600140) but not with SRC1 (NCOA1; 602691) or PCAF (602303) in PPARG- and TR-beta-1-mediated transactivation.
Surapureddi et al. (2002) determined that the PRIC285 gene contains 18 exons.
By radiation hybrid analysis, Nagase et al. (2000) mapped the PRIC285 gene to chromosome 20. By genomic sequence analysis, Surapureddi et al. (2002) mapped the PRIC285 gene to chromosome 20q13.3.
Nagase, T., Kikuno, R., Hattori, A., Kondo, Y., Okumura, K., Ohara, O. Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 347-355, 2000. [PubMed: 11214970] [Full Text: https://doi.org/10.1093/dnares/7.6.347]
Surapureddi, S., Yu, S., Bu, H., Hashimoto, T., Yeldandi, A. V., Kashireddy, P., Cherkaoui-Malki, M., Qi, C., Zhu, Y.-J., Rao, M. S., Reddy, J. K. Identification of a transcriptionally active peroxisome proliferator-activated receptor alpha-interacting cofactor complex in rat liver and characterization of PRIC285 as a coactivator. Proc. Nat. Acad. Sci. 99: 11836-11841, 2002. [PubMed: 12189208] [Full Text: https://doi.org/10.1073/pnas.182426699]
Tomaru, T., Satoh, T., Yoshino, S., Ishizuka, T., Hashimoto, K., Monden, T., Yamada, M., Mori, M. Isolation and characterization of a transcriptional cofactor and its novel isoform that bind the deoxyribonucleic acid-binding domain of peroxisome proliferator-activated receptor-gamma. Endocrinology 147: 377-388, 2006. [PubMed: 16239304] [Full Text: https://doi.org/10.1210/en.2005-0450]