Карс (ген)

Карс1
Доступные структуры
PDB	Поиск ортолога: PDBE RCSB
showСписок кодов идентификаторов PDB
	3BJU, 4DPG, 4YCU, 4YCW
Идентификаторы
Псевдонимы	Kars1 , Kars2, Cmtrib, лизил-тРНК-синтетаза 1, KRS, лизил-тРНК-синтетаза, KARS, DFNB89, Lepid, Deaple
Внешние идентификаторы	Омим : 601421 ; MGI : 1934754 ; Гомологен : 4053 ; Genecards : Kars1 ; OMA : Kars1 - ортологи
showМестоположение гена ( человек )
Chr.	Chromosome 16 (human)
End	75,648,643 bp
showМестоположение гена ( мышь )
Chr.	Chromosome 8 (mouse)
End	112,737,955 bp
showРНК -паттерн экспрессии
	Top expressed in
	gingival epithelium; ; parietal pleura; ; visceral pleura; ; epithelium of nasopharynx; ; skin of hip; ; parotid gland; ; endothelial cell; ; Skeletal muscle tissue of biceps brachii; ; tibialis anterior muscle; ; deltoid muscle;
	Top expressed in
	primitive streak; ; epiblast; ; yolk sac; ; otic vesicle; ; ventricular zone; ; tail of embryo; ; otic placode; ; embryo; ; embryo; ; fetal liver hematopoietic progenitor cell;
	More reference expression data
	More reference expression data
showДжин Онтология
Molecular function	aminoacyl-tRNA ligase activity; nucleotide binding; amino acid binding; tRNA binding; lysine-tRNA ligase activity; ligase activity; protein binding; nucleic acid binding; ATP binding; ATP adenylyltransferase activity; protein homodimerization activity; transferase activity; identical protein binding;
Cellular component	membrane; plasma membrane; extracellular region; mitochondrial matrix; mitochondrion; extracellular space; aminoacyl-tRNA synthetase multienzyme complex; nucleus; cytoplasm; cytosol;
Biological process	protein biosynthesis; tRNA processing; tRNA aminoacylation for protein translation; lysyl-tRNA aminoacylation; viral process; basophil activation involved in immune response; negative regulation of cell population proliferation; positive regulation of macrophage chemotaxis; tumor necrosis factor-mediated signaling pathway; positive regulation of macrophage activation; positive regulation of transcription, DNA-templated; ERK1 and ERK2 cascade; positive regulation of ERK1 and ERK2 cascade; positive regulation of cytokine production involved in inflammatory response; positive regulation of p38MAPK cascade; positive regulation of metallopeptidase activity; diadenosine tetraphosphate biosynthetic process; response to X-ray;
	Sources:Amigo / QuickGO
hideОртологи
	3735
	85305
	ENSG00000065427
	ENSMUSG00000031948
	Q15046
	Q99MN1
	NM_005548; NM_001130089; NM_001378148
	NM_001130868; NM_001286384; NM_053092; NM_001363429; NM_001363430
	NP_001123561; NP_005539; NP_001365077
	NP_001124340; NP_001273313; NP_444322; NP_001350358; NP_001350359
	Wikidata
View/Edit Human	View/Edit Mouse

Лизил-тРНК-синтетаза является ферментом , который у людей кодируется Карса геном . ^{[ 5 ]}^{[ 6 ]}^{[ 7 ]}

Функция

Аминоацил-тРНК-синтетазы представляют собой класс ферментов, которые заряжаются тРНК с их родственными аминокислотами. Лизил-тРНК-синтетаза представляет собой гомодимер, локализованный в цитоплазме, которая принадлежит семейству тРНК-синтетаз класса II. Было показано, что он является мишенью для аутоантител при аутоиммунных заболеваниях человека, полимиозите или дерматомиозите ^{[ 7 ]}

Помимо его роли в трансляции, лизил-тРНК-синтетаза участвует в сигнальном пути, ведущем к активации генов. ^{[ 8 ]} После физиологической стимуляции различных клеток лизил-тРНК-синтетаза связывается с факторами транскрипции MITF ^{[ 9 ]} и USF2 ^{[ 10 ]} и затем может повлиять на их транскрипционную деятельность. Такая физиологическая стимуляция включает иммунологическую активацию тучных клеток, поэтому этот путь может быть связан с аллергическим ответом.

Interactions

KARS (gene) has been shown to interact with Multisynthetase complex auxiliary component p38.^[11]^[12] Physiological trigger such as immunological activation results in the phosphorylation of LysRS on its serine residues. It separates from the multisynthetase complex and initiates Ap4A production.^[8]

References

^ Jump up to: ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000065427 – Ensembl, May 2017
^ Jump up to: ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000031948 – Ensembl, May 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.
^ Nichols RC, Blinder J, Pai SI, Ge Q, Targoff IN, Plotz PH, Liu P (Aug 1996). "Assignment of two human autoantigen genes-isoleucyl-tRNA synthetase locates to 9q21 and lysyl-tRNA synthetase locates to 16q23-q24". Genomics. 36 (1): 210–3. doi:10.1006/geno.1996.0449. PMID 8812440.
^ Shiba K, Stello T, Motegi H, Noda T, Musier-Forsyth K, Schimmel P (Sep 1997). "Human lysyl-tRNA synthetase accepts nucleotide 73 variants and rescues Escherichia coli double-defective mutant". The Journal of Biological Chemistry. 272 (36): 22809–16. doi:10.1074/jbc.272.36.22809. PMID 9278442.
^ Jump up to: ^a ^b "Entrez Gene: KARS lysyl-tRNA synthetase".
^ Jump up to: ^a ^b Yannay-Cohen N, Carmi-Levy I, Kay G, Yang CM, Han JM, Kemeny DM, Kim S, Nechushtan H, Razin E (Jun 2009). "LysRS serves as a key signaling molecule in the immune response by regulating gene expression". Molecular Cell. 34 (5): 603–11. doi:10.1016/j.molcel.2009.05.019. PMID 19524539.
^ Lee YN, Nechushtan H, Figov N, Razin E (Feb 2004). "The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells". Immunity. 20 (2): 145–51. doi:10.1016/S1074-7613(04)00020-2. PMID 14975237. S2CID 36723485.
^ Lee YN, Razin E (Oct 2005). "Nonconventional involvement of LysRS in the molecular mechanism of USF2 transcriptional activity in FcepsilonRI-activated mast cells". Molecular and Cellular Biology. 25 (20): 8904–12. doi:10.1128/MCB.25.20.8904-8912.2005. PMC 1265770. PMID 16199869.
^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
^ Quevillon S, Robinson JC, Berthonneau E, Siatecka M, Mirande M (Jan 1999). "Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein". Journal of Molecular Biology. 285 (1): 183–95. doi:10.1006/jmbi.1998.2316. PMID 9878398.

Yannay-Cohen N, Razin E (Oct 2006). "Translation and transcription: the dual functionality of LysRS in mast cells". Molecules and Cells. 22 (2): 127–32. doi:10.1016/S1016-8478(23)17400-0. PMID 17085962.
Carmi-Levy I, Yannay-Cohen N, Kay G, Razin E, Nechushtan H (Sep 2008). "Diadenosine tetraphosphate hydrolase is part of the transcriptional regulation network in immunologically activated mast cells". Molecular and Cellular Biology. 28 (18): 5777–84. doi:10.1128/MCB.00106-08. PMC 2546939. PMID 18644867.
Carmi-Levy I, Motzik A, Ofir-Birin Y, Yagil Z, Yang CM, Kemeny DM, Han JM, Kim S, Kay G, Nechushtan H, Suzuki R, Rivera J, Razin E (May 2011). "Importin beta plays an essential role in the regulation of the LysRS-Ap(4)A pathway in immunologically activated mast cells". Molecular and Cellular Biology. 31 (10): 2111–21. doi:10.1128/MCB.01159-10. PMC 3133347. PMID 21402779.
Kleiman L, Halwani R, Javanbakht H (Apr 2004). "The selective packaging and annealing of primer tRNALys3 in HIV-1". Current HIV Research. 2 (2): 163–75. doi:10.2174/1570162043484988. PMID 15078180.
Kino T, Pavlakis GN (Apr 2004). "Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1". DNA and Cell Biology. 23 (4): 193–205. doi:10.1089/104454904773819789. PMID 15142377.
Kleiman L, Cen S (Sep 2004). "The tRNALys packaging complex in HIV-1". The International Journal of Biochemistry & Cell Biology. 36 (9): 1776–86. doi:10.1016/j.biocel.2004.02.022. PMID 15183344.
Norcum MT (Aug 1991). "Structural analysis of the high molecular mass aminoacyl-tRNA synthetase complex. Effects of neutral salts and detergents". The Journal of Biological Chemistry. 266 (23): 15398–405. doi:10.1016/S0021-9258(18)98629-1. PMID 1651330.
Nomura N, Nagase T, Miyajima N, Sazuka T, Tanaka A, Sato S, Seki N, Kawarabayasi Y, Ishikawa K, Tabata S (1995). "Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1". DNA Research. 1 (5): 223–9. doi:10.1093/dnares/1.5.223. PMID 7584044.
Stark LA, Hay RT (Apr 1998). "Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) interacts with Lys-tRNA synthetase: implications for priming of HIV-1 reverse transcription". Journal of Virology. 72 (4): 3037–44. doi:10.1128/JVI.72.4.3037-3044.1998. PMC 109751. PMID 9525626.
Quevillon S, Robinson JC, Berthonneau E, Siatecka M, Mirande M (Jan 1999). "Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein". Journal of Molecular Biology. 285 (1): 183–95. doi:10.1006/jmbi.1998.2316. PMID 9878398.
Tolkunova E, Park H, Xia J, King MP, Davidson E (Nov 2000). "The human lysyl-tRNA synthetase gene encodes both the cytoplasmic and mitochondrial enzymes by means of an unusual alternative splicing of the primary transcript". The Journal of Biological Chemistry. 275 (45): 35063–9. doi:10.1074/jbc.M006265200. PMID 10952987.
Cen S, Khorchid A, Javanbakht H, Gabor J, Stello T, Shiba K, Musier-Forsyth K, Kleiman L (Jun 2001). "Incorporation of lysyl-tRNA synthetase into human immunodeficiency virus type 1". Journal of Virology. 75 (11): 5043–8. doi:10.1128/JVI.75.11.5043-5048.2001. PMC 114908. PMID 11333884.
Sang Lee J, Gyu Park S, Park H, Seol W, Lee S, Kim S (февраль 2002 г.). «Сеть взаимодействия аминоацил-тРНК-синтетаз человека и субъединицы комплекса фактора удлинения 1». Биохимическая и биофизическая исследовательская коммуникация . 291 (1): 158–64. doi : 10.1006/bbrc.2002.6398 . PMID 11829477 .
Ahn HC, Kim S, Lee BJ (май 2003 г.). «Структура раствора и связывание p43 мотива лейцина P38: взаимодействия с спиральной катушкой опосредуют связь между p38 и p43» . Письма Febs . 542 (1–3): 119–24. doi : 10.1016/s0014-5793 (03) 00362-4 . PMID 12729910 . S2CID 39222196 .
Javanbakht H, Halwani R, Cen S, Saadatmand J, Musier-Forsith K, Gottlinger H, Kleiman L (июль 2003 г.). «Взаимодействие между GAG ВИЧ-1 и лизил-тРНК-синтетазой во время вирусной сборки» . Журнал биологической химии . 278 (30): 27644–51. doi : 10.1074/jbc.m301840200 . PMID 12756246 .
Ким М.Дж., Парк Б.Дж., Кан Ю.С., Ким Х.Дж., Парк Дж.Х., Кан Дж.В., Ли С.В., Хан Дж. М., Ли Х.В., Ким С. (июль 2003). «Понижающая регуляция предохранительного белка и C-Myc с помощью кофактора синтетазы тРНК P38 необходимо для дифференцировки клеток легких». Природа генетика . 34 (3): 330–6. doi : 10.1038/ng1182 . PMID 12819782 . S2CID 41006480 .
Di Y, Li J, Zhang Y, He X, Lu H, Xu D, Ling J, Huo K, Wan D, Li Yy, Gu J (Jun 2003). «HCC-ассоциированный белок HCAP1, вариант Gemin4, взаимодействует с белками с цинком». Журнал биохимии . 133 (6): 713–8. doi : 10.1093/jb/mvg091 . PMID 12869526 .

[refGRCh38Ensembl-1] Jump up to: ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000065427 – Ensembl, May 2017

[refGRCm38Ensembl-2] Jump up to: ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000031948 – 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.

[pmid8812440-5] Nichols RC, Blinder J, Pai SI, Ge Q, Targoff IN, Plotz PH, Liu P (Aug 1996). "Assignment of two human autoantigen genes-isoleucyl-tRNA synthetase locates to 9q21 and lysyl-tRNA synthetase locates to 16q23-q24". Genomics. 36 (1): 210–3. doi:10.1006/geno.1996.0449. PMID 8812440.

[pmid9278442-6] Shiba K, Stello T, Motegi H, Noda T, Musier-Forsyth K, Schimmel P (Sep 1997). "Human lysyl-tRNA synthetase accepts nucleotide 73 variants and rescues Escherichia coli double-defective mutant". The Journal of Biological Chemistry. 272 (36): 22809–16. doi:10.1074/jbc.272.36.22809. PMID 9278442.

[entrez-7] Jump up to: ^a ^b "Entrez Gene: KARS lysyl-tRNA synthetase".

[pmid19524539-8] Jump up to: ^a ^b Yannay-Cohen N, Carmi-Levy I, Kay G, Yang CM, Han JM, Kemeny DM, Kim S, Nechushtan H, Razin E (Jun 2009). "LysRS serves as a key signaling molecule in the immune response by regulating gene expression". Molecular Cell. 34 (5): 603–11. doi:10.1016/j.molcel.2009.05.019. PMID 19524539.

[pmid14975237-9] Lee YN, Nechushtan H, Figov N, Razin E (Feb 2004). "The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells". Immunity. 20 (2): 145–51. doi:10.1016/S1074-7613(04)00020-2. PMID 14975237. S2CID 36723485.

[pmid16199869-10] Lee YN, Razin E (Oct 2005). "Nonconventional involvement of LysRS in the molecular mechanism of USF2 transcriptional activity in FcepsilonRI-activated mast cells". Molecular and Cellular Biology. 25 (20): 8904–12. doi:10.1128/MCB.25.20.8904-8912.2005. PMC 1265770. PMID 16199869.

[pmid16189514-11] Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.

[pmid9878398-12] Quevillon S, Robinson JC, Berthonneau E, Siatecka M, Mirande M (Jan 1999). "Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein". Journal of Molecular Biology. 285 (1): 183–95. doi:10.1006/jmbi.1998.2316. PMID 9878398.

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Функция

Interactions

References

Further reading