JPH3

Junctophilin-3

JPH3
Identifiers
Aliases	JPH3 , CAGL237, HDL2, JP-3, JP3, TNRC22, junctophilin 3
External IDs	OMIM: 605268; MGI: 1891497; HomoloGene: 10762; GeneCards: JPH3; OMA:JPH3 - orthologs
Gene location (Human) Chr. Chromosome 16 (human) [1] Band 16q24.2 Start 87,601,835 bp [1] End 87,698,156 bp [1]
Gene location (Mouse) Chr. Chromosome 8 (mouse) [2] Band 8|8 E1 Start 122,456,362 bp [2] End 122,521,015 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right frontal lobe postcentral gyrus anterior cingulate cortex sural nerve entorhinal cortex superior frontal gyrus nucleus accumbens amygdala dorsolateral prefrontal cortex prefrontal cortex Top expressed in CA3 field entorhinal cortex perirhinal cortex dentate gyrus cingulate gyrus superior frontal gyrus primary visual cortex primary motor cortex Region I of hippocampus proper dentate gyrus of hippocampal formation granule cell More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium-release channel activity molecular function Cellular component plasma membrane endoplasmic reticulum endoplasmic reticulum membrane membrane junctional sarcoplasmic reticulum membrane junctional membrane complex integral component of membrane Biological process regulation of neuronal synaptic plasticity release of sequestered calcium ion into cytosol calcium ion transport into cytosol memory learning exploration behavior locomotion neuromuscular process controlling balance regulation of ryanodine-sensitive calcium-release channel activity regulation of synaptic plasticity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 57338 57340 Ensembl ENSG00000154118 ENSMUSG00000025318 UniProt Q8WXH2 Q9ET77 RefSeq (mRNA) NM_001271604 NM_001271605 NM_020655 NM_020605 RefSeq (protein) NP_001258533 NP_001258534 NP_065706 NP_065630 Location (UCSC) Chr 16: 87.6 – 87.7 Mb Chr 8: 122.46 – 122.52 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. ^[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 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. 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, ^[9] which can aggregate in neurons, leading to the degeneration of neuronal subpopulations. ^[10]

References

1. GRCh38: Ensembl release 89: ENSG00000154118 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000025318 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Takeshima H, Komazaki S, Nishi M, Iino M, Kangawa K (July 2000). "Junctophilins: a novel family of junctional membrane complex proteins". Molecular Cell. 6 (1): 11–22. doi: 10.1016/S1097-2765(05)00005-5 . PMID   10949023.
6. 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. PMID   10891348.
7. 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. PMID   11906164.
8. 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. PMID   22367996. S2CID   6432652.
9. Chen Z, Sequeiros J, Tang B, Jiang H (December 2018). "Genetic modifiers of age-at-onset in polyglutamine diseases". Ageing Research Reviews. 48: 99–108. doi:10.1016/j.arr.2018.10.004. PMID   30355507. S2CID   53027229.
10. Fan HC, Ho LI, Chi CS, Chen SJ, Peng GS, Chan TM, et al. (May 2014). "Polyglutamine (PolyQ) diseases: genetics to treatments". Cell Transplantation. 23 (4–5): 441–458. doi: 10.3727/096368914X678454 . PMID   24816443. S2CID   27522175.

External links

• https://www.omim.org/entry/605268?search=junctophilin-3&highlight=%28junctophilin%7Cjunctophilin3%29
• nih.gov
• 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, et al. (July 1997). "cDNAs with long CAG trinucleotide repeats from human brain". Human Genetics. 100 (1): 114–122. doi:10.1007/s004390050476. PMID   9225980. S2CID   25999127.
• Olin KL, Potter-Perigo S, Barrett PH, Wight TN, Chait A (January 2001). "Biglycan, a vascular proteoglycan, binds differently to HDL2 and HDL3: role of apoE". Arteriosclerosis, Thrombosis, and Vascular Biology. 21 (1): 129–135. doi: 10.1161/01.ATV.21.1.129 . PMID   11145944.
• 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. PMID   11694876. S2CID   23976552.
• 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. PMID   11914418. S2CID   34200149.
• Grimsby S, Jaensson H, Dubrovska A, Lomnytska M, Hellman U, Souchelnytskyi S (November 2004). "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. doi: 10.1016/j.febslet.2004.09.069 . PMID   15527767. S2CID   82568.
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC   1847948 . PMID   17353931.