JPH3 explained

Junctophilin-3 (JPH3) is a protein residing 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, which link the plasma membrane with the endoplasmic reticulum in excitable cells.^[1] JPH3 is localized to the brain and is associated with motor coordination and memory neurons.^[2]

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 calcium ion signaling^[3] and the stabilization of neuronal cellular architecture.^[4]

The JPH3 gene contains a CAG/CTG trinucleotide repeat segment. Expansion of this segment in various genes can cause polyglutamine diseases. The expansion of the CAG tandem repeat in JPH3 is associated with the HDL2's type of Huntington's disease-like syndrome. The pathological expansion of the CAG repeat region leads to an expanded polyglutamine tract,^[5] which can aggregate in neurons, leading to the degeneration of neuronal subpopulations.^[6]

External links

• https://www.omim.org/entry/605268?search=junctophilin-3&highlight=%28junctophilin%7Cjunctophilin3%29
• https://www.ncbi.nlm.nih.gov/gene/57338
• https://alphafold.ebi.ac.uk/entry/Q8WXH2
• GeneReviews/NCBI/NIH/UW entry on Huntington Disease-Like 2

Further reading

• Margolis RL, Abraham MR, Gatchell SB, Li SH, Kidwai AS, Breschel TS, Stine OC, Callahan C, McInnis MG, Ross CA . 6 . cDNAs with long CAG trinucleotide repeats from human brain . Human Genetics . 100 . 1 . 114–122 . July 1997 . 9225980 . 10.1007/s004390050476 . 25999127 .
• Olin KL, Potter-Perigo S, Barrett PH, Wight TN, Chait A . Biglycan, a vascular proteoglycan, binds differently to HDL2 and HDL3: role of apoE . Arteriosclerosis, Thrombosis, and Vascular Biology . 21 . 1 . 129–135 . January 2001 . 11145944 . 10.1161/01.ATV.21.1.129 . free .
• Holmes SE, O'Hearn E, Rosenblatt A, Callahan C, Hwang HS, Ingersoll-Ashworth RG, Fleisher A, Stevanin G, Brice A, Potter NT, Ross CA, Margolis RL . 6 . A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2 . Nature Genetics . 29 . 4 . 377–378 . December 2001 . 11694876 . 10.1038/ng760 . 23976552 .
• Stevanin G, Camuzat A, Holmes SE, Julien C, Sahloul R, Dodé C, Hahn-Barma V, Ross CA, Margolis RL, Durr A, Brice A . 6 . CAG/CTG repeat expansions at the Huntington's disease-like 2 locus are rare in Huntington's disease patients . Neurology . 58 . 6 . 965–967 . March 2002 . 11914418 . 10.1212/wnl.58.6.965 . 34200149 .
• Grimsby S, Jaensson H, Dubrovska A, Lomnytska M, Hellman U, Souchelnytskyi S . Proteomics-based identification of proteins interacting with Smad3: SREBP-2 forms a complex with Smad3 and inhibits its transcriptional activity . FEBS Letters . 577 . 1–2 . 93–100 . November 2004 . 15527767 . 10.1016/j.febslet.2004.09.069 . 82568 . free .
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . 6 . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .

Notes and References

1. Takeshima H, Komazaki S, Nishi M, Iino M, Kangawa K . Junctophilins: a novel family of junctional membrane complex proteins . Molecular Cell . 6 . 1 . 11–22 . July 2000 . 10949023 . 10.1016/S1097-2765(05)00005-5 . free .
2. Nishi M, Mizushima A, Nakagawara K, Takeshima H . Characterization of human junctophilin subtype genes . Biochemical and Biophysical Research Communications . 273 . 3 . 920–927 . July 2000 . 10891348 . 10.1006/bbrc.2000.3011 .
3. Nishi M, Hashimoto K, Kuriyama K, Komazaki S, Kano M, Shibata S, Takeshima H . Motor discoordination in mutant mice lacking junctophilin type 3 . Biochemical and Biophysical Research Communications . 292 . 2 . 318–324 . March 2002 . 11906164 . 10.1006/bbrc.2002.6649 .
4. Seixas AI, Holmes SE, Takeshima H, Pavlovich A, Sachs N, Pruitt JL, Silveira I, Ross CA, Margolis RL, Rudnicki DD . 6 . Loss of junctophilin-3 contributes to Huntington disease-like 2 pathogenesis . Annals of Neurology . 71 . 2 . 245–257 . February 2012 . 22367996 . 10.1002/ana.22598 . 6432652 .
5. Chen Z, Sequeiros J, Tang B, Jiang H . Genetic modifiers of age-at-onset in polyglutamine diseases . Ageing Research Reviews . 48 . 99–108 . December 2018 . 30355507 . 10.1016/j.arr.2018.10.004 . 53027229 .
6. Fan HC, Ho LI, Chi CS, Chen SJ, Peng GS, Chan TM, Lin SZ, Harn HJ . 6 . Polyglutamine (PolyQ) diseases: genetics to treatments . Cell Transplantation . 23 . 4–5 . 441–458 . May 2014 . 24816443 . 10.3727/096368914X678454 . 27522175 . free .