Alternative titles; symbols
HGNC Approved Gene Symbol: RPH3A
Cytogenetic location: 12q24.13 Genomic coordinates (GRCh38): 12:112,575,236-112,898,881 (from NCBI)
Exocytosis of neurotransmitters and hormones is fundamental to synaptic neurotransmission and cell-cell communication. RAB3A (179490) is a small G protein that is thought to act at late stages of exocytosis, and RPH3A is a RAB3A effector (Lin et al., 2007).
By sequencing clones obtained from a size-fractionated brain cDNA library, Nagase et al. (1999) cloned RPH3A, which they designated KIAA0985. The deduced 694-amino acid protein shares 86.9% identity over 703 amino acids with rat Rph3a. RT-PCR ELISA detected highest expression in fetal brain, followed by adult spinal cord and whole brain. Much lower expression was detected in adult lung, testis, and spleen. Expression was high in all specific adult brain regions tested, with highest abundance in subthalamic nuclei and thalamus.
Inagaki et al. (1994) cloned mouse Rph3a, which encodes a deduced 681-amino acid protein with an N-terminal Rab3a-binding region and 2 C-terminal internal repeats homologous to the regulatory domain (C2 domain) of protein kinase C (see PRKCZ; 176982). Northern blot analysis detected Rph3a highly expressed in brain and in several mammalian endocrine and hormone-secreting cell lines.
Lin et al. (2007) found that direct interaction with rabphilin was required for hydrolysis of GTP by Rab3a in stimulated rat pheochromocytoma cells and for dissociation of Rab3a from vesicles and exocytosis.
Smith et al. (2007) stated that the amount of Rph3a protein was reduced in different brain regions in a transgenic mouse model of Huntington disease (HD; 143100) and that Rph3a interacted with the SNARE synaptic complex via Snap25 (600322). Western blot and immunohistochemical analysis showed that levels of both SNAP25 and RPH3A were reduced in human HD cortex. SNAP25 protein levels were lower even in HD brains with limited neuropathology; the level of RPH3A deceased in HD brains with higher neuropathologic grade and higher CAG repeats. The loss of SNAP25 and RPH3A was not due to general loss of synapses in HD cortex, since the levels of other synapse-related proteins, including RAB3A, were unaltered in the same patient samples.
By radiation hybrid analysis, Nagase et al. (1999) mapped the RPH3A gene to chromosome 12.
Inagaki, N., Mizuta, M., Seino, S. Cloning of a mouse rabphilin-3A expressed in hormone-secreting cells. J. Biochem. 116: 239-242, 1994. [PubMed: 7822236] [Full Text: https://doi.org/10.1093/oxfordjournals.jbchem.a124512]
Lin, C.-C., Huang, C.-C., Lin, K.-H., Cheng, K.-H., Yang, D.-M., Tsai, Y.-S., Ong, R.-Y., Huang, Y.-N., Kao, L.-S. Visualization of Rab3A dissociation during exocytosis: a study by total internal reflection microscopy. J. Cell. Physiol. 211: 316-326, 2007. [PubMed: 17149709] [Full Text: https://doi.org/10.1002/jcp.20938]
Nagase, T., Ishikawa, K., Suyama, M., Kikuno, R., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 6: 63-70, 1999. [PubMed: 10231032] [Full Text: https://doi.org/10.1093/dnares/6.1.63]
Smith, R., Klein, P., Koc-Schmitz, Y., Waldvogel, H. J., Faull, R. L. M., Brundin, P., Plomann, M., Li, J.-Y. Loss of SNAP-25 and rabphilin 3a in sensory-motor cortex in Huntington's disease. J. Neurochem. 103: 115-123, 2007. [PubMed: 17877635] [Full Text: https://doi.org/10.1111/j.1471-4159.2007.04703.x]