Junctophilin-3 (JPH3) is a protein in humans that is encoded by the JPH3 gene. The gene is approximately 97 kilobases long and is located at chromosomal position 16q24.2. Junctophilin proteins are associated with the formation of junctional membrane complexes, linking the plasma membrane with the endoplasmic reticulum in excitable cells.[5] JPH3 is localized to the brain and is associated with motor coordination and memory neurons.[6]
The protein contains 748 residues and is composed of a C-terminal hydrophobic segment that spans the endoplasmic/sarcoplasmic reticulum membrane and a cytoplasmic domain that displays specific affinity for the plasma membrane, as well as several membrane occupation and recognition nexus repeats involved in plasma membrane binding through interactions with phospholipids.
JPH3 is primarily expressed in the brain, specifically in the dorsolateral prefrontal cortex. Although the precise function of the protein has not been determined, it has been shown to play a role in motor coordination and memory through efficient calcium ion signaling[7] and the stabilization of neuronal cellular architecture.[8]
The JPH3 gene contains a CAG/CTG trinucleotide repeat segment. Expansion of this segment in various genes can cause polyglutamine diseases. Expansion of the CAG repeat in JPH3 is associated with the HDL2 type of Huntington's disease-like syndrome. The pathological expansion of the CAG repeat region leads to an expanded polyglutamine tract,[9] which can aggregate in neurons, leading to the degeneration of neuronal subpopulations.[10]
^Nishi M, Mizushima A, Nakagawara K, Takeshima H (July 2000). "Characterization of human junctophilin subtype genes". Biochemical and Biophysical Research Communications. 273 (3): 920–927. doi:10.1006/bbrc.2000.3011. PMID10891348.
^Nishi M, Hashimoto K, Kuriyama K, Komazaki S, Kano M, Shibata S, Takeshima H (March 2002). "Motor discoordination in mutant mice lacking junctophilin type 3". Biochemical and Biophysical Research Communications. 292 (2): 318–324. doi:10.1006/bbrc.2002.6649. PMID11906164.
^Seixas AI, Holmes SE, Takeshima H, Pavlovich A, Sachs N, Pruitt JL, et al. (February 2012). "Loss of junctophilin-3 contributes to Huntington disease-like 2 pathogenesis". Annals of Neurology. 71 (2): 245–257. doi:10.1002/ana.22598. PMID22367996. S2CID6432652.
Margolis RL, Abraham MR, Gatchell SB, Li SH, Kidwai AS, Breschel TS, et al. (July 1997). "cDNAs with long CAG trinucleotide repeats from human brain". Human Genetics. 100 (1): 114–122. doi:10.1007/s004390050476. PMID9225980. S2CID25999127.
Holmes SE, O'Hearn E, Rosenblatt A, Callahan C, Hwang HS, Ingersoll-Ashworth RG, et al. (December 2001). "A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2". Nature Genetics. 29 (4): 377–378. doi:10.1038/ng760. PMID11694876. S2CID23976552.
Stevanin G, Camuzat A, Holmes SE, Julien C, Sahloul R, Dodé C, et al. (March 2002). "CAG/CTG repeat expansions at the Huntington's disease-like 2 locus are rare in Huntington's disease patients". Neurology. 58 (6): 965–967. doi:10.1212/wnl.58.6.965. PMID11914418. S2CID34200149.
