JPH2

JPH2
Identifikatori
Aliasi	JPH2
Vanjski ID-jevi	OMIM: 605267 MGI: 1891496 HomoloGene: 10714 GeneCards: JPH2
Lokacija gena (čovjek)
Hrom.	Hromosom 20 (čovjek)
Kraj	44,187,188 bp
Lokacija gena (miš)
Hrom.	Hromosom 2 (miš)
Kraj	163,239,913 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• phosphatidic acid binding; • phosphatidylinositol-4-phosphate binding; • phosphatidylinositol-5-phosphate binding; • phosphatidylserine binding; • phosphatidylinositol-3,4,5-trisphosphate binding; • GO:0001948, GO:0016582 vezivanje za proteine; • phosphatidylinositol-3,5-bisphosphate binding; • phosphatidylinositol-4,5-bisphosphate binding; • phosphatidylinositol-3-phosphate binding; • calcium-release channel activity; • vezivanje sa DNK;
Ćelijska komponenta	• integral component of membrane; • Sarkoplazmatski retikulum; • sarcoplasmic reticulum membrane; • junctional membrane complex; • membrana; • Endoplazmatski retikulum; • ćelijska membrana; • junctional sarcoplasmic reticulum membrane; • Z discdkac; • endoplasmic reticulum membrane; • jedro;
Biološki proces	• regulation of cardiac muscle tissue development; • calcium ion transport into cytosol; • positive regulation of cytosolic calcium ion concentration; • positive regulation of ryanodine-sensitive calcium-release channel activity; • calcium ion homeostasis; • regulation of ryanodine-sensitive calcium-release channel activity; • release of sequestered calcium ion into cytosol; • multicellular organism development;
	Izvori:Amigo / QuickGO
Ortolozi
	57158
	59091
	ENSG00000149596
	ENSMUSG00000017817
	Q9BR39
	Q9ET78
	NM_020433; NM_175913
	NM_001205076; NM_021566; NM_197984
	NP_065166; NP_787109
	NP_001192005; NP_067541
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Junktofilin 2, znan i kao JPH2, jest protein koji je kod ljudi kodiran genom JPH2.^[5]^[6]^[7] Na ovom lokusu uočena je alternativna prerada i opisane su dvije varijante koje kodiraju različite izoforme.

Funkcija

Spojni kompleksi između plazmatske membrane i endoplazmatskog / sarkoplazmatskog retikuluma su zajednička karakteristika svih tipova pobudljivih ćelija i posreduju u unakrsnom razgovoru između površine ćelije i unutarćelijskog ionskog kanala . Protein koji kodira ovaj gen komponenta je spojnih kompleksa i sastoji se od C-krajevi hidrofobnog segmenta, koji se protežu kroz membranu endoplazmatskog / sarkoplazmatskog retikuluma i preostalog pokrivanja i prepoznavanja citoplazmatske ledene membrane nexus (MORN) domena, pokazuju specifični afinitet za plazmatsku membranu. JPH2 je član porodice junktofilinskih gena (ostali članovi su JPH1, JPH3 i JPH4) i dominantna je izoforma u srčanom tkivu, ali se također eksprimnira i sa JPH1 u skeletnim mišićima.^[8] Proteinski proizvod JPH2 ima presudnu ulogu u održavanju razmaka geometrije srčane dijade - prostora između plazmamembrane i sarkoplazmatskog retikuluma.^[5] Ove srčane dijade također su poznate, budući da se smatra da spojni membranski kompleksi ili jedinice za oslobađanje kalcija imaju ključnu ulogu u oslobađanju kalcija induciranom približavanjem kalcija kalcijskim kanalima L-tipa na plazemamembrani i receptora ryanodine tipa 2 na sarkoplazmatskom retikulumu. JPH2 također sadrži evolucijski konzervirani signal jedarne lokalizacije i domen koja veže DNK. Tokom (srčane) bolesti, kalpain aktiviran stresom , pretvara JPH2 pune dužine u fragmente. N-terminalni fragment (uključujući signal nuklearne lokalizacije i domen koji veže DNK) premješta se u jedro i reguliraju transkripciju gena.^[9]

Uloga u bolesti

Mutacije u JPH2 identificirane su u kohorti pacijenata s hipertrofijskom kardiomiopatijom kojima nedostaju uobičajene mutacije u proteinima sarkomera.^[10] Pokazalo se da je JPH2 reguliran u nekoliko životinjskih modela srčanog zatajenja. Model nokautiranog miša JPH2 smrtonosan je u 10,5. danu embrionskog razvoja, što je otprilike vrijeme kada bi srčana kontraktilnost trebala započeti. Ovi miševi pokazali su abnormalan promet srčanog kalcija, kardiomiopatiju i promijenjeno stvaranje kompleksa spojnih membrana.

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000149596 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000017817 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: JPH2 junctophilin 2".
^ Takeshima H, Komazaki S, Nishi M, Iino M, Kangawa K (juli 2000). "Junctophilins: a novel family of junctional membrane complex proteins". Mol. Cell. 6 (1): 11–22. doi:10.1016/S1097-2765(05)00005-5. PMID 10949023.
^ Nishi M, Mizushima A, Nakagawara K, Takeshima H (juli 2000). "Characterization of human junctophilin subtype genes". Biochem. Biophys. Res. Commun. 273 (3): 920–7. doi:10.1006/bbrc.2000.3011. PMID 10891348.
^ Garbino A, van Oort RJ, et al. (2009). "Molecular evolution of the junctophilin gene family". Physiol Genomics. 37 (3): 175–86. doi:10.1152/physiolgenomics.00017.2009. PMC 2685503. PMID 19318539.
^ Guo A, Wang Y, et al. (2018). "E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcription regulator". Science. 362 (6421): eaan3303. doi:10.1126/science.aan3303. PMC 6336677. PMID 30409805.
^ Landstrom AP, Weisleder N, et al. (2007). "Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans". J Mol Cell Cardiol. 42 (6): 1026–35. doi:10.1016/j.yjmcc.2007.04.006. PMC 4318564. PMID 17509612.

Dopunska literatura

Nishi M, Mizushima A, Nakagawara K, Takeshima H (2000). "Characterization of human junctophilin subtype genes". Biochem. Biophys. Res. Commun. 273 (3): 920–7. doi:10.1006/bbrc.2000.3011. PMID 10891348.
Takeshima H, Komazaki S, Nishi M, et al. (2000). "Junctophilins: a novel family of junctional membrane complex proteins". Mol. Cell. 6 (1): 11–22. doi:10.1016/S1097-2765(05)00005-5. PMID 10949023.
Deloukas P, Matthews LH, Ashurst J, et al. (2002). "The DNA sequence and comparative analysis of human chromosome 20". Nature. 414 (6866): 865–71. doi:10.1038/414865a. PMID 11780052.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Minamisawa S, Oshikawa J, Takeshima H, et al. (2005). "Junctophilin type 2 is associated with caveolin-3 and is down-regulated in the hypertrophic and dilated cardiomyopathies". Biochem. Biophys. Res. Commun. 325 (3): 852–6. doi:10.1016/j.bbrc.2004.10.107. PMID 15541368.
Kim J, Bhinge AA, Morgan XC, Iyer VR (2005). "Mapping DNA-protein interactions in large genomes by sequence tag analysis of genomic enrichment". Nat. Methods. 2 (1): 47–53. doi:10.1038/nmeth726. PMID 15782160.
Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.02. PMID 17081983.
Matsushita Y, Furukawa T, Kasanuki H, et al. (2007). "Mutation of junctophilin type 2 associated with hypertrophic cardiomyopathy". J. Hum. Genet. 52 (6): 543–8. doi:10.1007/s10038-007-0149-y. PMID 17476457.
Landstrom AP, Weisleder N, Batalden KB, et al. (2007). "Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans". J. Mol. Cell. Cardiol. 42 (6): 1026–35. doi:10.1016/j.yjmcc.2007.04.006. PMC 4318564. PMID 17509612.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000149596 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000017817 - Ensembl, maj 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.

[entrez-5] "Entrez Gene: JPH2 junctophilin 2".

[pmid10949023-6] Takeshima H, Komazaki S, Nishi M, Iino M, Kangawa K (juli 2000). "Junctophilins: a novel family of junctional membrane complex proteins". Mol. Cell. 6 (1): 11–22. doi:10.1016/S1097-2765(05)00005-5. PMID 10949023.

[pmid10891348-7] Nishi M, Mizushima A, Nakagawara K, Takeshima H (juli 2000). "Characterization of human junctophilin subtype genes". Biochem. Biophys. Res. Commun. 273 (3): 920–7. doi:10.1006/bbrc.2000.3011. PMID 10891348.

[8] Garbino A, van Oort RJ, et al. (2009). "Molecular evolution of the junctophilin gene family". Physiol Genomics. 37 (3): 175–86. doi:10.1152/physiolgenomics.00017.2009. PMC 2685503. PMID 19318539.

[9] Guo A, Wang Y, et al. (2018). "E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcription regulator". Science. 362 (6421): eaan3303. doi:10.1126/science.aan3303. PMC 6336677. PMID 30409805.

[10] Landstrom AP, Weisleder N, et al. (2007). "Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans". J Mol Cell Cardiol. 42 (6): 1026–35. doi:10.1016/j.yjmcc.2007.04.006. PMC 4318564. PMID 17509612.

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