Alternative titles; symbols
HGNC Approved Gene Symbol: HSPA4
Cytogenetic location: 5q31.1 Genomic coordinates (GRCh38): 5:133,052,013-133,106,449 (from NCBI)
Heat-shock proteins (HSPs) act as molecular chaperones by assisting folding of nascent and misfolded proteins, preventing their aggregation. HSPA4 is a ubiquitously expressed member of the HSP110 family of HSPs. HSP110 family members act as cochaperones for HSP70 chaperones (see 140550) (summary by Mohamed et al., 2014).
Fathallah et al. (1993) reported the cloning of a human heat-shock protein (hsp), which they designated hsp70 RY. The cDNA was isolated from an EBV-transformed B-cell line from a patient with leukocyte adhesion molecule deficiency. The predicted 701-amino acid protein has an N-terminal ATP-binding domain and a C-terminal peptide-binding domain characteristic of hsp proteins. Northern blot analysis detected a 3.0-kb RNA in the patient's EBV cell line.
Nonoguchi et al. (1999) cloned HSPA4, which they called APG2, from a human testis cDNA library. The predicted protein contains 840 amino acids and has an N-terminal ATP-binding motif. Human APG2 shares 95.5% amino acid identity with is 841-amino acid mouse ortholog. Northern blot analysis of human tissues detected APG2 transcripts of 5.4 and 3.0 kb in all human tissues examined, including brain, testis, and ovary.
Using immunoblot analysis, Mohamed et al. (2014) showed that Hspa4 was expressed in pulmonary epithelial cells throughout mouse lung development.
Fathallah et al. (1993) used in situ hybridization to map the HSPA4 gene to chromosome 5q31.1-q31.2.
By FISH, Nonoguchi et al. (1999) mapped the HSPA4 gene to chromosome 5q23.3-q31.1.
Gross (2020) mapped the HSPA4 gene to chromosome 5q31.1 based on an alignment of the HSPA4 sequence (GenBank BC002526) with the genomic sequence (GRCh38).
Nonoguchi et al. (1999) found that heat shock did not induce APG2 expression in ECV304 human endothelial cells.
Mohamed et al. (2014) found that mice lacking both Hspa4l (619077) and Hspa4 had pulmonary hypoplasia that resulted in neonatal lethality due to impaired maturation of alveolar epithelium. Histologic analysis showed that Hspa4l -/- Hspa4 -/- embryos developed hypercellularity of mesenchymal septa in lungs because of accelerated cell proliferation and diminished apoptosis, leading to disrupted distal lung morphogenesis. In addition, loss of both Hspa4l and Hspa4 interrupted maturation of type I and type II pneumocytes and increased accumulation of ubiquitinated proteins in lungs of Hspa4l -/- Hspa4 -/- mice.
Fathallah, D. M., Cherif, D., Dellagi, K., Arnaout, M. A. Molecular cloning of a novel human hsp70 from a B cell line and its assignment to chromosome 5. J. Immun. 151: 810-813, 1993. Note: Erratum: J. Immun. 151: 6616 only, 1993. [PubMed: 8335910]
Gross, M. B. Personal Communication. Baltimore, Md. 10/22/2020.
Mohamed, B. A., Barakat, A. Z., Held, T., Elkenani, M., Muhlfeld, C., Manner, J., Adham, I. M. Respiratory distress and early neonatal lethality in Hspa4l/Hspa4 double-mutant mice. Am. J. Resp. Cell Molec. Biol. 50: 817-824, 2014. [PubMed: 23980576] [Full Text: https://doi.org/10.1165/rcmb.2013-0132OC]
Nonoguchi, K., Itoh, K., Xue, J.-H., Tokuchi, H., Nishiyama, H., Kaneko, Y., Tatsumi, K., Okuno, H., Tomiwa, K., Fujita, J. Cloning of human cDNAs for Apg-1 and Apg-2, members of the Hsp110 family, and chromosomal assignment of their genes. Gene 237: 21-28, 1999. [PubMed: 10524232] [Full Text: https://doi.org/10.1016/s0378-1119(99)00325-x]