Alternative titles; symbols
HGNC Approved Gene Symbol: HPCAL4
Cytogenetic location: 1p34.2 Genomic coordinates (GRCh38): 1:39,678,648-39,691,433 (from NCBI)
HPCAL4 is a neural calcium sensor that may contribute to pain and itch processing (Alvaro et al., 2020).
Kobayashi et al. (1998) cloned HPCAL4, which they termed HLP4, from a human hippocampus cDNA library. The deduced 191-amino acid protein has a calculated molecular mass of 22 kD and contains 4 EF-hand calcium-binding motifs. HLP4 shares 68% and 99% amino acid identity with human hippocalcin (HPCA; 142622) and rat Nvp2, respectively. Northern blot analysis of human tissues detected a 5.0-kb HLP4 transcript in brain only, with highest expression in cerebral cortex and cerebellum.
Using in situ hybridization, Alvaro et al. (2020) showed that Hpcal4 was expressed in adult mouse spinal cord, predominantly in substantia gelatinosa, where most nociceptors terminate.
Gross (2021) mapped the HPCAL4 gene to chromosome 1p34.2 based on an alignment of the HPCAL4 sequence (GenBank BC030827) with the genomic sequence (GRCh38).
Using in situ hybridization, Alvaro et al. (2020) showed that Tr4 (NR2C2; 601426) -/- mice, which exhibit major pain and itch deficits, had strongly reduced Hpcal4 expression in spinal cord. Similarly, Hpcal4 -/- mice had reduced heat response, but mechanical pain responses were normal. Examination of injury-induced mechanical hypersensitivity in Hpcal4 -/- mice revealed that Hpcal4 was not required for development or maintenance of inflammation- or peripheral nerve injury-induced mechanical hypersensitivity. However, Hpcal4 expression was required to evoke scratching behavior in response to peripheral injection of pruritogens.
Alvaro, C. G., Braz, J. M., Bernstein, M., Hamel, K. A., Craik, V., Yamanaka, H., Basbaum, A. I. Hippocalcin-like 4, a neural calcium sensor, has a limited contribution to pain and itch processing. PLoS One 15: e0226289, 2020. Note: Electronic Article. [PubMed: 32015563] [Full Text: https://doi.org/10.1371/journal.pone.0226289]
Gross, M. B. Personal Communication. Baltimore, Md. 2/25/2021.
Kobayashi, M., Sakai, E., Furuta, Y., Takamatsu, K. Isolation of two human cDNAs, HLP3 and HLP4, homologous to the neuron-specific calcium-binding protein genes. DNA Seq. 9: 171-176, 1998. [PubMed: 10520747] [Full Text: https://doi.org/10.3109/10425179809072192]