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ノイラミニダーゼ1
識別子
EC番号	3.2.1.18
データベース
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB構造	RCSB PDB PDBj PDBe PDBsum
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PubMed	articles
NCBI	proteins
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NEU1
識別子
記号	NEU1, NANH, NEU, SIAL1, neuraminidase 1 (lysosomal sialidase), neuraminidase 1
外部ID	OMIM: 608272 MGI: 97305 HomoloGene: 375 GeneCards: NEU1
遺伝子の位置 (ヒト)
染色体	6番染色体 (ヒト)
終点	31,862,905 bp
遺伝子の位置 (マウス)
染色体	17番染色体 (マウス)
終点	35,154,929 bp
遺伝子オントロジー
分子機能	• exo-alpha-(2->3)-sialidase activity; • exo-alpha-(2->8)-sialidase activity; • exo-alpha-(2->6)-sialidase activity; • 加水分解酵素活性; • hydrolase activity, acting on glycosyl bonds; • exo-alpha-sialidase activity; • 血漿タンパク結合; • alpha-sialidase activity;
細胞の構成要素	• cytoplasmic vesicle; • intracellular membrane-bounded organelle; • lysosomal membrane; • エキソソーム; • リソソーム; • 細胞膜; • lysosomal lumen; • 細胞結合; • 膜; • 細胞外領域; • specific granule lumen; • 細胞質;
生物学的プロセス	• ganglioside catabolic process; • 脂質異化プロセス; • 脂質代謝; • 代謝; • オリゴ糖異化プロセス; • glycosphingolipid metabolic process; • 好中球脱顆粒; • 炭水化物代謝;
	出典:Amigo / QuickGO
オルソログ
	4758
	18010
ENSG00000227129; ENSG00000184494; ENSG00000223957; ENSG00000234846; ENSG00000204386;
	ENSG00000234343; ENSG00000227315; ENSG00000228691
	ENSMUSG00000007038
	Q99519
	O35657
	NM_000434
	NM_010893
	NP_000425
	NP_035023
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

NEU1としても知られるシアリダーゼ1（リソソームシアリダーゼ）ノイラミニダーゼ1 (ノイラミニダーゼワン、Neuraminidase 1、EC3.2.1.18）は、シアル酸残基と他の分子とのグリコシド結合を加水分解するエキソグリコシダーゼである。哺乳類細胞のリソソーム内にカテプシンAと複合体を形成して存在する。

哺乳類のリソソームノイラミニダーゼ酵素であり、ヒトではNEU1遺伝子によってコードされている ^[5] ^[6]。

概要

動物細胞のリソソーム内にて、糖タンパク質や糖脂質から末端シアル酸残基を加水分解により除去するエキソグリコシダーゼである。ヒトノイラミニダーゼ1は他のノイラミニダーゼ(NEU2、NEU3、NEU4)とは異なり、単独では活性がない。ヒトノイラミニダーゼ1は、他のノイラミニダーゼアイソザイムとは異なり、アスパラギン結合型糖鎖をもつ^[7]。哺乳類の培養細胞にCMVプロモーターなどの強力なプロモーターで過剰発現させると細胞内で結晶化する^[8]。

相互作用

カテプシンAと相互作用する。ノイラミニダーゼ1は単独では活性がなく、カテプシンAと会合することで活性化される。また、粗面小胞体内腔で生合成されるが、単独ではリソソームへあまり輸送されず、カテプシンAとの会合により輸送が促進される^[14]。

出典

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000227129、ENSG00000184494、ENSG00000223957、ENSG00000234846、ENSG00000204386、ENSG00000234343、ENSG00000227315、ENSG00000228691 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000007038 - Ensembl, May 2017
^ Human PubMed Reference:
^ Mouse PubMed Reference:
^ “Entrez Gene: NEU1 sialidase 1 (lysosomal sialidase)”. 2017年9月5日閲覧。
^ “Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis”. Nat. Genet. 15 (3): 316–20. (March 1997). doi:10.1038/ng0397-316. PMID 9054950.
^ Tsukimoto, Jun; Takeuchi, Yoshie; Horii, Yuto; Iniwa, Toshiki; Fukushi, Yuri; Nishioka, So-Ichiro; Itoh, Kohji (2022-01-17). “In Cellulo Crystallization of Human Neuraminidase 1 and Biological Roles of N-Glycans”. ACS applied bio materials 5 (1): 205–213. doi:10.1021/acsabm.1c01043. ISSN 2576-6422. PMID 35014832.
^ Koiwai, Kotaro; Tsukimoto, Jun; Higashi, Tetsuya; Mafuné, Fumitaka; Miyajima, Ken; Nakane, Takanori; Matsugaki, Naohiro; Kato, Ryuichi et al. (2019-11-18). “Improvement of Production and Isolation of Human Neuraminidase-1 in Cellulo Crystals”. ACS applied bio materials 2 (11): 4941–4952. doi:10.1021/acsabm.9b00686. ISSN 2576-6422. PMID 35021494.
^ Oheda, Yukako; Kotani, Masaharu; Murata, Mai; Sakuraba, Hitoshi; Kadota, Yoshito; Tatano, Yutaka; Kuwahara, Jun; Itoh, Kohji (2006-04). “Elimination of abnormal sialylglycoproteins in fibroblasts with sialidosis and galactosialidosis by normal gene transfer and enzyme replacement”. Glycobiology 16 (4): 271–280. doi:10.1093/glycob/cwj069. ISSN 0959-6658. PMID 16361247.
^ Naganawa, Y.; Itoh, K.; Shimmoto, M.; Takiguchi, K.; Doi, H.; Nishizawa, Y.; Kobayashi, T.; Kamei, S. et al. (2000). “Molecular and structural studies of Japanese patients with sialidosis type 1”. Journal of Human Genetics 45 (4): 241–249. doi:10.1007/s100380070034. ISSN 1434-5161. PMID 10944856.
^ Itoh, K.; Miharu, N.; Ohama, K.; Mizoguchi, N.; Sakura, N.; Sakuraba, H. (1997-10-31). “Fetal diagnosis of galactosialidosis (protective protein/cathepsin A deficiency)”. Clinica Chimica Acta; International Journal of Clinical Chemistry 266 (2): 75–82. doi:10.1016/s0009-8981(97)00141-1. ISSN 0009-8981. PMID 9437536.
^ Nakajima, Hideki; Ueno, Miki; Adachi, Kaori; Nanba, Eiji; Narita, Aya; Tsukimoto, Jun; Itoh, Kohji; Kawakami, Atushi (2019). “A new heterozygous compound mutation in the CTSA gene in galactosialidosis”. Human Genome Variation 6: 22. doi:10.1038/s41439-019-0054-x. ISSN 2054-345X. PMC 6486599. PMID 31044084.
^ Horii, Yuto; Iniwa, Toshiki; Onitsuka, Masayoshi; Tsukimoto, Jun; Tanaka, Yuki; Ike, Hironobu; Fukushi, Yuri; Ando, Haruna et al. (2022-06-09). “Reversal of neuroinflammation in novel GS model mice by single i.c.v. administration of CHO-derived rhCTSA precursor protein”. Molecular Therapy. Methods & Clinical Development 25: 297–310. doi:10.1016/j.omtm.2022.04.001. ISSN 2329-0501. PMC 9062439. PMID 35573044.
^ Bonten, Erik J.; Campos, Yvan; Zaitsev, Viateslav; Nourse, Amanda; Waddell, Brett; Lewis, William; Taylor, Garry; d'Azzo, Alessandra (2009-10-09). “Heterodimerization of the sialidase NEU1 with the chaperone protective protein/cathepsin A prevents its premature oligomerization”. The Journal of Biological Chemistry 284 (41): 28430–28441. doi:10.1074/jbc.M109.031419. ISSN 1083-351X. PMC 2788892. PMID 19666471.

参考文献

“The biochemistry and clinical features of galactosialidosis”. Biochim. Biophys. Acta 1225 (3): 244–54. (1994). doi:10.1016/0925-4439(94)90002-7. PMID 8312369.
“Molecular pathology of NEU1 gene in sialidosis”. Hum. Mutat. 22 (5): 343–52. (2004). doi:10.1002/humu.10268. PMID 14517945.
“Purification and partial characterization of lysosomal neuraminidase from human placenta”. Eur. J. Biochem. 162 (1): 63–7. (1987). doi:10.1111/j.1432-1033.1987.tb10542.x. PMID 3102233.
“Human placental neuraminidase. Activation, stabilization and association with beta-galactosidase and its protective protein”. Eur. J. Biochem. 149 (2): 315–21. (1985). doi:10.1111/j.1432-1033.1985.tb08928.x. PMID 3922758.
“Infectivities of human and other primate lentiviruses are activated by desialylation of the virion surface”. J. Virol. 70 (11): 7462–70. (1996). doi:10.1128/JVI.70.11.7462-7470.1996. PMC 190813. PMID 8892864.
“Association of N-acetylgalactosamine-6-sulfate sulfatase with the multienzyme lysosomal complex of beta-galactosidase, cathepsin A, and neuraminidase. Possible implication for intralysosomal catabolism of keratan sulfate”. J. Biol. Chem. 271 (45): 28359–65. (1996). doi:10.1074/jbc.271.45.28359. PMID 8910459.
“Characterization of human lysosomal neuraminidase defines the molecular basis of the metabolic storage disorder sialidosis”. Genes Dev. 10 (24): 3156–69. (1997). doi:10.1101/gad.10.24.3156. PMID 8985184. * “Identification of a sialidase encoded in the human major histocompatibility complex”. J. Biol. Chem. 272 (7): 4549–58. (1997). doi:10.1074/jbc.272.7.4549. PMID 9020182.
“Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis”. Nat. Genet. 15 (3): 316–20. (1997). doi:10.1038/ng0397-316. PMID 9054950.
“Molecular mechanism of lysosomal sialidase deficiency in galactosialidosis involves its rapid degradation”. Biochem. J. 330 ( Pt 2) (Pt 2): 641–50. (1998). doi:10.1042/bj3300641. PMC 1219185. PMID 9480870.
“Transport of human lysosomal neuraminidase to mature lysosomes requires protective protein/cathepsin A”. EMBO J. 17 (6): 1588–97. (1998). doi:10.1093/emboj/17.6.1588. PMC 1170506. PMID 9501080.
“Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex”. Hum. Mol. Genet. 9 (7): 1075–85. (2000). doi:10.1093/hmg/9.7.1075. PMID 10767332.
“Molecular and structural studies of Japanese patients with sialidosis type 1”. J. Hum. Genet. 45 (4): 241–9. (2000). doi:10.1007/s100380070034. PMID 10944856.
“Novel mutations in lysosomal neuraminidase identify functional domains and determine clinical severity in sialidosis”. Hum. Mol. Genet. 9 (18): 2715–25. (2000). doi:10.1093/hmg/9.18.2715. PMID 11063730.
“Mutations in sialidosis impair sialidase binding to the lysosomal multienzyme complex”. J. Biol. Chem. 276 (20): 17286–90. (2001). doi:10.1074/jbc.M100460200. PMID 11279074.
“Splice donor site mutation in the lysosomal neuraminidase gene causing exon skipping and complete loss of enzyme activity in a sialidosis patient”. FEBS Lett. 501 (2–3): 135–8. (2001). doi:10.1016/S0014-5793(01)02645-X. PMID 11470272. * “Intracellular distribution of lysosomal sialidase is controlled by the internalization signal in its cytoplasmic tail”. J. Biol. Chem. 276 (49): 46172–81. (2002). doi:10.1074/jbc.M104547200. PMID 11571282.
“Prenatal diagnosis and fetal pathology in a Turkish family harboring a novel nonsense mutation in the lysosomal alpha-N-acetyl-neuraminidase (sialidase) gene”. Hum. Genet. 109 (4): 421–8. (2001). doi:10.1007/s004390100592. PMID 11702224.
“Novel missense mutations in the human lysosomal sialidase gene in sialidosis patients and prediction of structural alterations of mutant enzymes”. J. Hum. Genet. 47 (1): 29–37. (2002). doi:10.1007/s10038-002-8652-7. PMID 11829139.