Alternative titles; symbols
HGNC Approved Gene Symbol: HDGFL2
Cytogenetic location: 19p13.3 Genomic coordinates (GRCh38): 19:4,472,297-4,502,207 (from NCBI)
HDGFL2 binds to histones associated with transcriptionally silent genes and recruits factors involved in homologous recombination repair to sites of DNA damage (Baude et al., 2016).
Izumoto et al. (1997) cloned mouse Hdgfl2, which they called Hrp2. The deduced 669-amino acid protein has a calculated molecular mass of 74.3 kD. Hrp2 has a significant number of charged residues and is rich in prolines and serines. Hrp2 also shares an approximately 98-residue N-terminal domain with HDGF (600339) and mouse Hrp1 (Hdgfl1). Northern blot analysis of 8 mouse tissues detected highest expression of a major 2.5-kb Hrp2 transcript in testis, with lower expression in all other tissues except spleen, which showed little to no Hrp2 expression. Hrp2 was also expressed as a minor 3.5-kb transcript in all tissues except spleen.
Baude et al. (2016) showed that the 670-amino acid human HDGFL2 protein, which they called HDGFRP2, has an N-terminal PWWP domain, a central AT hook-like motif, and C-terminal integrase-binding domain. Immunohistochemical analysis detected HDGFRP2 in a punctate nuclear pattern in interphase U2OS and HeLa cells. HDGFRP2 dissociated partly from condensed chromosomes in mitotic cells.
Wu et al. (2011) found that the isolated PWWP domain of human HDGF2 showed weak binding to methylated histones.
Using short interfering RNA, Baude et al. (2016) found that depletion of HDGFRP2 in human U2OS and HeLa cells caused spontaneous DNA damage and resulted in cell death. Knockdown of HDGFRP2 impaired DNA damage-induced phosphorylation of RPA2 (179836) and recruitment of RBBP8 (604124) to DNA double-strand breaks. HDGFRP2 preferentially bound histone marks characteristic of transcriptionally silent chromatin in vitro and immunoprecipitated with CBX1 (604511) and POGZ (614787). Baude et al. (2016) concluded that HDGFRP2, possibly in complex with POGZ, recruits factors involved in homologous recombination to damaged silent genes or to active genes silenced upon DNA damage.
Hartz (2018) mapped the HDGFL2 gene to chromosome 19p13.3 based on an alignment of the HDGFL2 sequence (GenBank BC000755) with the genomic sequence (GRCh38).
Baude, A., Aaes, T. L., Zhai, B., Al-Nakouzi, N., Oo, H. Z., Daugaard, M., Rohde, M., Jaattela, M. Hepatoma-derived growth factor-related protein 2 promotes DNA repair by homologous recombination. Nucleic Acids Res. 44: 2214-2226, 2016. [PubMed: 26721387] [Full Text: https://doi.org/10.1093/nar/gkv1526]
Hartz, P. A. Personal Communication. Baltimore, Md. 2/22/2018.
Izumoto, Y., Kuroda, T., Harada, H., Kishimoto, T., Nakamura, H. Hepatoma-derived growth factor belongs to a gene family in mice showing significant homology in the amino terminus. Biochem. Biophys. Res. Commun. 238: 26-32, 1997. [PubMed: 9299445] [Full Text: https://doi.org/10.1006/bbrc.1997.7233]
Wu, H., Zeng, H., Lam, R., Tempel, W., Amaya, M. F., Xu, C., Dombrovski, L., Qiu, W., Wang, Y., Min, J. Structural and histone binding ability characterizations of human PWWP domains. PLoS One 6: e18919, 2011. Note: Electronic Article. [PubMed: 21720545] [Full Text: https://doi.org/10.1371/journal.pone.0018919]