組織蛋白酶E

組織蛋白酶E（英文：Cathepsin E）是一種酶（EC 3.4.23.34），在人體中由CTSE基因編碼。^[5][6][7]該酶又稱慢速蛋白酶、紅細胞膜天冬氨酸蛋白酶、SMP、EMAP、非胃蛋白酶、組織蛋白酶D樣酸性蛋白酶、組織蛋白酶E樣酸性蛋白酶、組織蛋白酶D型蛋白酶。^{[8][9][10][11]}

組織蛋白酶E
已知的結構 PDB 直系同源搜索: PDBe RCSB PDBID列表 1TZS
識別號
別名	CTSE；, Ctse, A430072O03Rik, C920004C08Rik, CE, CatE, cathepsin E
外部ID	OMIM：116890 MGI：107361 HomoloGene：37551 GeneCards：CTSE
基因位置（人類） 染色體 1號染色體[1] 基因座 1q32.1 起始 206,008,535 bp[1] 終止 206,023,909 bp[1]
基因位置（小鼠） 染色體 小鼠1號染色體[2] 基因座 1 E4|1 57.14 cM 起始 131,566,044 bp[2] 終止 131,603,243 bp[2]
RNA表達模式
查閱更多表達數據
基因本體 分子功能 • 肽酶活性 • 水解酶活性 • protein homodimerization activity • aspartic-type endopeptidase activity 細胞組分 • 核內體 生物學過程 • protein autoprocessing • protein catabolic process • antigen processing and presentation of exogenous peptide antigen via MHC class II • 蛋白酶解 Sources:Amigo / QuickGO
直系同源
物種	人類	小鼠
Entrez	1510	13034
Ensembl	ENSG00000196188	ENSMUSG00000004552
UniProt	P14091	P70269
mRNA​序列	NM_001910 ​NM_148964 ​NM_001317331	NM_007799
蛋白序列	NP_001304260 ​NP_001901 ​NP_683865	NP_031825
基因位置​（UCSC）	Chr 1: 206.01 – 206.02 Mb	Chr 1: 131.57 – 131.6 Mb
PubMed​查找	[3]	[4]
維基數據
檢視/編輯人類 檢視/編輯小鼠

Cathepsin E
命名 系統命名 縮寫
識別碼
EC編號	3.4.23.34
CAS號	110910-42-4
數據庫
IntEnz	IntEnz瀏覽
BRENDA（英語：BRENDA）	BRENDA入口
ExPASy（英語：ExPASy）	NiceZyme瀏覽
KEGG	KEGG入口
MetaCyc（英語：MetaCyc）	代謝路徑
PRIAM（英語：PRIAM_enzyme-specific_profiles）	概述
PDB	RCSB PDB PDBj PDBe PDBsum
搜索 PMC 相關文獻 PubMed 相關文獻

組織蛋白酶E是一種在動物以及各種其他生物中發現的蛋白酶，屬於天冬氨酸蛋白酶組。在人類中，它由位於1號染色體1q32。^{[12][13][11][14]}它是一種細胞內非溶酶體糖蛋白，主要存在於皮膚和免疫細胞中。^[15]該蛋白質是作為二硫鍵連接的同源二聚體發揮作用的天冬氨酰蛋白酶，具有高甘露糖型的寡糖鏈。^[16]它是肽酶A1家族的成員，因此它與胃蛋白酶A和組織蛋白酶D有相似的特異性。組織蛋白酶E是一種細胞內酶，並且不參與膳食蛋白質的消化。它在胃的上皮粘液產生細胞表面的豐度最高。它是第一種存在於胎兒胃中的天冬氨酸蛋白酶，存在於超過一半的胃癌中，因此它似乎是一種腫瘤胚胎抗原。該基因存在利用替代多腺苷酸化信號的轉錄變體和編碼不同異構體的兩種轉錄變體。^[14][15]

體內缺乏組織蛋白酶E可能導致炎症性皮膚病（如異位性皮炎），對此的治療將依賴於固定體內蛋白質的功能和水平。^[17]與腎素和組織蛋白酶D一樣，組織蛋白酶E是少數已知的在消化道和生殖道以外的人體組織中產生的天冬氨酸蛋白酶之一。^[18]

結構

組織蛋白酶E的結構與組織蛋白酶D和Β分泌酶1的結構非常相似，並且它們都具有幾乎相同的活性位點區域。它們之間的區別在於它們活性位點周圍的微環境。殘基DTG 96-98和DTG 281-283有助於酶活性位點的形成。在殘基Cys 272-276和Cys 314-351處也有兩對二硫鍵。氨基酸鏈上第109位和第114位的另外兩個Cys殘基在三維空間中彼此靠近，但是它們的硫原子之間的距離為3.53Å，這對於形成適當的二硫鍵來說太大了。該結構在活性位點的 Asp殘基和周圍的殘基之間也有四個氫鍵。與組織蛋白酶D和Β分泌酶1的結構相比，組織蛋白酶E的一個區別因素可以看出，在Asp 96和Ser 99殘基之間形成了額外的氫鍵，並且在Asp 281處沒有與Leu/Met形成氫鍵。^[17]

在生物體內的分佈

組織蛋白酶E分佈在消化道、淋巴組織、血細胞、泌尿器官和小膠質細胞中。它在不同哺乳動物細胞中的細胞內定位與其類似的組織蛋白酶D不同。組織蛋白酶E與胃壁細胞的胞內小管、肝細胞的膽小管、腎臟的近端腎小管細胞、腸、氣管和支氣管的上皮細胞、破骨細胞甚至紅細胞中的膜組織結合。它在內體結構中的定位可見於許多不同的細胞類型，例如抗原呈遞B細胞淋巴母細胞、胃細胞和小膠質細胞。在細胞內質網的扁囊中也檢測到它的存在。^[16][19]

功能

組織蛋白酶E在蛋白質降解、通過MHCII類分子途徑加工的抗原^[14]和生物活性蛋白的產生中起着至關重要的作用。該酶還被認為與年齡誘導的神經元死亡途徑的執行以及興奮毒素對穀氨酸受體的過度刺激和短暫的前腦缺血有關。在對老鼠進行的一項實驗中，在年輕老鼠的腦組織中幾乎沒有檢測到組織蛋白酶E，但在老年大鼠的新紋狀體和大腦皮質中其水平大大增加。在短暫的前腦缺血一周後，該酶還在海馬體CA1區的活化小膠質細胞和退化的神經元中高水平表達。^[19]組織蛋白酶E可能在腸化生分化良好的腺癌的發展中發揮作用。^[16]該酶還與樹突狀細胞有關，在樹突狀細胞中它產生CD4庫以響應自身和外來蛋白質。^[20]

後翻譯修飾

該酶被糖基化。不同的細胞類型導致碳水化合物鏈的性質不同。在成纖維細胞中的酶原中觀察到高甘露糖型寡糖，然而在複合型寡糖中可以看到成熟酶。在紅細胞膜中，成熟酶和酶原均具有複合型寡糖。自催化裂解產生兩種形式的酶，形式1從殘基Ile 54開始，形式2在Thr 57開始。^[21]

參見

• 組織蛋白酶

參考文獻

1. GRCh38: Ensembl release 89: ENSG00000196188 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000004552 - 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. Couvreur JM, Azuma T, Miller DA, Rocchi M, Mohandas TK, Boudi FA, Taggart RT. Assignment of cathepsin E (CTSE) to human chromosome region 1q31 by in situ hybridization and analysis of somatic cell hybrids. Cytogenetics and Cell Genetics. Aug 1990, 53 (2–3): 137–9. PMID 2369841. doi:10.1159/000132914.
6. Azuma T, Pals G, Mohandas TK, Couvreur JM, Taggart RT. Human gastric cathepsin E. Predicted sequence, localization to chromosome 1, and sequence homology with other aspartic proteinases. The Journal of Biological Chemistry. October 1989, 264 (28): 16748–53. PMID 2674141. doi:10.1016/S0021-9258(19)84768-3 .
7. Entrez Gene: CTSE cathepsin E. [2022-10-17]. （原始內容存檔於2010-12-05）.
8. Lapresle C, Puizdar V, Porchon-Bertolotto C, Joukoff E, Turk V. Structural differences between rabbit cathepsin E and cathepsin D. Biological Chemistry Hoppe-Seyler. June 1986, 367 (6): 523–6. PMID 3741628. doi:10.1515/bchm3.1986.367.1.523.
9. Yonezawa S, Fujii K, Maejima Y, Tamoto K, Mori Y, Muto N. Further studies on rat cathepsin E: subcellular localization and existence of the active subunit form. Archives of Biochemistry and Biophysics. November 1988, 267 (1): 176–83. PMID 3058036. doi:10.1016/0003-9861(88)90021-5.
10. Jupp RA, Richards AD, Kay J, Dunn BM, Wyckoff JB, Samloff IM, Yamamoto K. Identification of the aspartic proteinases from human erythrocyte membranes and gastric mucosa (slow-moving proteinase) as catalytically equivalent to cathepsin E. The Biochemical Journal. September 1988, 254 (3): 895–8. PMC 1135167 . PMID 3058118. doi:10.1042/bj2540895.
11. Azuma T, Pals G, Mohandas TK, Couvreur JM, Taggart RT. Human gastric cathepsin E. Predicted sequence, localization to chromosome 1, and sequence homology with other aspartic proteinases. The Journal of Biological Chemistry. October 1989, 264 (28): 16748–53. PMID 2674141. doi:10.1016/S0021-9258(19)84768-3 .
12. CTSE cathepsin E [Homo sapiens (human)] - Gene - NCBI. www.ncbi.nlm.nih.gov. [2016-10-16]. （原始內容存檔於2020-07-26）.
13. Couvreur JM, Azuma T, Miller DA, Rocchi M, Mohandas TK, Boudi FA, Taggart RT. Assignment of cathepsin E (CTSE) to human chromosome region 1q31 by in situ hybridization and analysis of somatic cell hybrids. Cytogenetics and Cell Genetics. 1990, 53 (2–3): 137–9. PMID 2369841. doi:10.1159/000132914.
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15. Yasuda Y, Kageyama T, Akamine A, Shibata M, Kominami E, Uchiyama Y, Yamamoto K. Characterization of new fluorogenic substrates for the rapid and sensitive assay of cathepsin E and cathepsin D. Journal of Biochemistry. June 1999, 125 (6): 1137–43. PMID 10348917. doi:10.1093/oxfordjournals.jbchem.a022396.
16. Saku T, Sakai H, Shibata Y, Kato Y, Yamamoto K. An immunocytochemical study on distinct intracellular localization of cathepsin E and cathepsin D in human gastric cells and various rat cells. Journal of Biochemistry. December 1991, 110 (6): 956–64. PMID 1794985. doi:10.1093/oxfordjournals.jbchem.a123696.
17. Chou KC. Modeling the tertiary structure of human cathepsin-E. Biochemical and Biophysical Research Communications. May 2005, 331 (1): 56–60. PMID 15845357. doi:10.1016/j.bbrc.2005.03.123.
18. Lees WE, Kalinka S, Meech J, Capper SJ, Cook ND, Kay J. Generation of human endothelin by cathepsin E. FEBS Letters. October 1990, 273 (1–2): 99–102. PMID 2226872. doi:10.1016/0014-5793(90)81060-2 .
19. Tsukuba T, Okamoto K, Yasuda Y, Morikawa W, Nakanishi H, Yamamoto K. New functional aspects of cathepsin D and cathepsin E. Molecules and Cells. December 2000, 10 (6): 601–11. PMID 11211863. S2CID 20761872. doi:10.1007/s10059-000-0601-8.
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21. CTSE - Cathepsin E precursor - Homo sapiens (Human) - CTSE gene & protein. www.uniprot.org. [2016-10-16]. （原始內容存檔於2020-11-09）.

拓展閱讀

• Tsukuba T, Yamamoto K. [Atopic dermatitis and cathepsin E]. Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica. July 2003, 122 (1): 15–20. PMID 12843568. doi:10.1254/fpj.122.15 .
• Flynn TJ, Deshmukh DS, Pieringer RA. Effects of altered thyroid function on galactosyl diacylglycerol metabolism in myelinating rat brain. The Journal of Biological Chemistry. August 1977, 252 (16): 5864–70. PMID 195962. doi:10.1016/S0021-9258(17)40103-7 .
• Azuma T, Liu WG, Vander Laan DJ, Bowcock AM, Taggart RT. Human gastric cathepsin E gene. Multiple transcripts result from alternative polyadenylation of the primary transcripts of a single gene locus at 1q31-q32. The Journal of Biological Chemistry. January 1992, 267 (3): 1609–14. PMID 1370478. doi:10.1016/S0021-9258(18)45989-3 .
• Saku T, Sakai H, Shibata Y, Kato Y, Yamamoto K. An immunocytochemical study on distinct intracellular localization of cathepsin E and cathepsin D in human gastric cells and various rat cells. Journal of Biochemistry. December 1991, 110 (6): 956–64. PMID 1794985. doi:10.1093/oxfordjournals.jbchem.a123696.
• Athauda SB, Takahashi T, Inoue H, Ichinose M, Takahashi K. Proteolytic activity and cleavage specificity of cathepsin E at the physiological pH as examined towards the B chain of oxidized insulin. FEBS Letters. November 1991, 292 (1–2): 53–6. PMID 1959628. doi:10.1016/0014-5793(91)80832-N .
• Lees WE, Kalinka S, Meech J, Capper SJ, Cook ND, Kay J. Generation of human endothelin by cathepsin E. FEBS Letters. October 1990, 273 (1–2): 99–102. PMID 2226872. doi:10.1016/0014-5793(90)81060-2 .
• Athauda SB, Matsuzaki O, Kageyama T, Takahashi K. Structural evidence for two isozymic forms and the carbohydrate attachment site of human gastric cathepsin E. Biochemical and Biophysical Research Communications. April 1990, 168 (2): 878–85. PMID 2334440. doi:10.1016/0006-291X(90)92403-M.
• Fowler SD, Kay J, Dunn BM, Tatnell PJ. Monomeric human cathepsin E. FEBS Letters. June 1995, 366 (1): 72–4. PMID 7789521. S2CID 38970367. doi:10.1016/0014-5793(95)00501-Y.
• Finley EM, Kornfeld S. Subcellular localization and targeting of cathepsin E. The Journal of Biological Chemistry. December 1994, 269 (49): 31259–66. PMID 7983070. doi:10.1016/S0021-9258(18)47417-0 .
• Takeda-Ezaki M, Yamamoto K. Isolation and biochemical characterization of procathepsin E from human erythrocyte membranes. Archives of Biochemistry and Biophysics. August 1993, 304 (2): 352–8. PMID 8346912. doi:10.1006/abbi.1993.1361.
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• Azuma T, Hirai M, Ito S, Yamamoto K, Taggart RT, Matsuba T, Yasukawa K, Uno K, Hayakumo T, Nakajima M. Expression of cathepsin E in pancreas: a possible tumor marker for pancreas, a preliminary report. International Journal of Cancer. August 1996, 67 (4): 492–7. PMID 8759606. doi:10.1002/(SICI)1097-0215(19960807)67:4<492::AID-IJC5>3.0.CO;2-N.
• Sealy L, Mota F, Rayment N, Tatnell P, Kay J, Chain B. Regulation of cathepsin E expression during human B cell differentiation in vitro. European Journal of Immunology. August 1996, 26 (8): 1838–43. PMID 8765029. S2CID 29006370. doi:10.1002/eji.1830260826.
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外部連結

• The MEROPS online database for peptidases and their inhibitors: A01.010 （頁面存檔備份，存於互聯網檔案館）
• 醫學主題詞表（MeSH）：Cathepsin+E