Alternative titles; symbols
HGNC Approved Gene Symbol: HDGFL3
Cytogenetic location: 15q25.2 Genomic coordinates (GRCh38): 15:83,112,738-83,207,823 (from NCBI)
Hepatoma-derived growth factor (HDGF; 600339) and HDGF-related proteins, such as HRP3, share a highly conserved HATH region near the N terminus as well as putative nuclear localizing signals (NLSs) outside of the HATH region (summary by Ikegame et al., 1999).
By EST database analysis and PCR of Jurkat, PBL, and testis cDNA libraries, Ikegame et al. (1999) identified and cloned HRP3. The deduced 203-amino acid protein has a predicted molecular mass of 22.6 kD. It contains a HATH region at the N terminus and a bipartite NLS near the C terminus. The human HRP3 protein shares 98% conservation with mouse Hrp3. Northern blot analysis showed that HRP3 is highly expressed throughout the central nervous system and in testis, moderately expressed in heart, and minimally expressed in several other tissues. Transient transfection experiments in HEK293 cells localized HRP3 to the nucleus.
El-Tahir et al. (2009) identified an NLS in the N-terminal HATH region of mouse Hrp3 in addition to the bipartite NLS near the C terminus.
Ikegame et al. (1999) mapped the HRP3 gene to chromosome 15q25 by FISH.
Ikegame et al. (1999) found that overexpression of HRP in HEK293 cells had a growth-stimulating effect.
El-Tahir et al. (2009) observed that Hrp3 is strongly expressed in mouse neurons during development. In cultured mouse neurons from 14.5-day old embryos, Hrp3 was initially expressed in neurites and gradually became exclusively expressed in the nucleus in mature neurons. The C-terminal bipartite NLS was sufficient for nuclear localization in transfected HEK293 cells. Reduction of Hrp3 levels in mouse cortical neurons by siRNA reduced the number and length of neurites, whereas overexpression of the protein increased the number and length of newly formed neurites. El-Tahir et al. (2009) showed that Hrp3 interacts and colocalizes with tubulin in cortical mouse brain and neurons. The binding site of Hrp3 for tubulin is located in the HATH region. Hrp3 protein promotes tubulin assembly into microtubules and stabilizes microtubules once they are formed.
Yun et al. (2013) found that HRP3 is upregulated in lung cancer-derived A549 cells, which are radio- and chemoresistant. siRNA knockdown of HRP3 caused A549 cells to become susceptible to radiation and treatment with doxorubicin and vinblastine, suggesting that HRP3 is a biomarker for radio- and chemoresistance. Knockdown of HRP3 induced an increase in reactive oxygen species (ROS) generation that was attributed to inhibition of the NRF2 (600492)/HO1 (141250) antioxidant pathway and enhancement of ROS-dependent p53 (191170) activation and expression of PUMA (605854).
El-Tahir, H. M., Abouzied, M. M., Gallitzendoerfer, R., Gieselmann, V., Franken, S. Hepatoma-derived growth factor-related protein-3 interacts with microtubules and promotes neurite outgrowth in mouse cortical neurons. J. Biol. Chem. 284: 11637-11651, 2009. [PubMed: 19237540] [Full Text: https://doi.org/10.1074/jbc.M901101200]
Ikegame, K., Yamamoto, M., Kishima, Y., Enomoto, H., Yoshida, K., Suemura, M., Kishimoto, T., Nakamura, H. A new member of a hepatoma-derived growth factor gene family can translocate to the nucleus. Biochem. Biophys. Res. Commun. 266: 81-87, 1999. [PubMed: 10581169] [Full Text: https://doi.org/10.1006/bbrc.1999.1733]
Yun, H. S., Hong, E.-H., Lee, S.-J., Baek, J.-H., Lee, C.-W., Yim, J.-H., Um, H.-D., Hwang, S.-G. Depletion of hepatoma-derived growth factor-related protein-3 induces apoptotic sensitization of radioresistant A549 cells via reactive oxygen species-dependent p53 activation. Biochem. Biophys. Res. Commun. 439: 333-339, 2013. [PubMed: 24012673] [Full Text: https://doi.org/10.1016/j.bbrc.2013.08.086]