PGLYRP1

PGLYRP1
已知的结构
PDB	直系同源搜索: PDBe RCSB
PDBID列表
	1YCK
识别号
别名	PGLYRP1；, PGLYRP, PGRP, PGRP-S, PGRPS, TAG7, TNFSF3L, peptidoglycan recognition protein 1
外部ID	OMIM：604963 MGI：1345092 HomoloGene：74539 GeneCards：PGLYRP1
基因位置（人类）
染色体	19号染色体
终止	46,023,053 bp
基因位置（小鼠）
染色体	小鼠7号染色体
终止	18,624,384 bp
RNA表达模式
	查阅更多表达数据
基因本体
分子功能	• 锌离子结合; • peptidoglycan immune receptor activity; • N-acetylmuramoyl-L-alanine amidase activity; • peptidoglycan binding;
细胞组分	• 外排体; • 细胞外区域; • specific granule lumen; • phagocytic vesicle lumen; • tertiary granule lumen; • 细胞外空间;
生物学过程	• peptidoglycan catabolic process; • negative regulation of natural killer cell differentiation involved in immune response; • negative regulation of interferon-gamma production; • 先天免疫系统; • negative regulation of inflammatory response; • defense response to bacterium; • 免疫反应; • detection of bacterium; • immune system process; • defense response to Gram-positive bacterium; • pattern recognition receptor signaling pathway; • antimicrobial humoral response; • neutrophil degranulation; • positive regulation of cytolysis in other organism; • antimicrobial humoral immune response mediated by antimicrobial peptide; • response to bacterium; • killing of cells of other organism;
	Sources:Amigo / QuickGO
直系同源
	8993
	21946
	ENSG00000008438
	ENSMUSG00000030413
	O75594
	O88593
	NM_005091
	NM_009402
	NP_005082
	NP_033428
	维基数据
查看/编辑人类	查看/编辑小鼠

肽聚糖识别蛋白1（Peptidoglycan Recognition Protein 1），也被称为 TAG7、PGRP-S，是在人类PGLYRP1基因编码的蛋白。^[5]^[6]^[7]

肽聚糖识别蛋白（Peptidoglycan Recognition Proteins, PGRPs）是近几年来，在昆虫和哺乳动物体内所发现的一种先天性免疫激活蛋白。哺乳动物具有四种PGRPs，分别命名为PGRP-S、PGRP-L、PGRP-Iα以及PGRP-Iβ（也称为PGLYRP-1、PGLYRP-2、PGLYRP-3与PGLYRP-4）。^[8]

其中，PGRP-S为哺乳动物PGRP中最早克隆得到的。在过去的试验发现PGRP-S会激活生物体的淋巴免疫细胞而诱发体内生成干扰素（IFN-γ）、肿瘤坏死因子（TNF-α），^[9]而展现出抗病毒的效果，且受到PGRP-S激活的淋巴免疫细胞并不会对正常的健康细胞产生危害。^[10]

组织分布与分泌

该PGLYRP-1基因会高度表现在骨髓、循环型多形核白细胞（PMLs），以及角膜上皮细胞。主要在颗粒多型核白细胞（PML）可以发现PGLYRP1蛋白。

结构

如同大多数肽聚糖识别蛋白，PGLYRP-1有一个羧基端第2型酰胺域（也称为PGRP域）并包括三个α-螺旋，五个β股，螺旋，并具有能形成三个双硫键的三对保守半胱氨酸。^[11] PGLYRP1会形成二聚体，以表现出抗微生物活性，并且可以与热休克蛋白70形成复合体，而表现出其毒性。

功能

PGLYRP-1蛋白在先天免疫反应中扮演着极为重要的脚色。此蛋白针对革兰氏阳性菌，例如金黄色葡萄球菌、表皮葡萄球菌以及李斯特菌，且通常具有促炎的影响，会诱发组织中肿瘤坏死因子-α（TNF-a）和干扰素伽玛（IFN-γ）的生成，对于猪PRRS病毒、流感病毒以及肠病毒在研究中也能产生出抑制的效果。^[10]^[12]^[13]^[14]^[15]

在过去的研究中，我们也知道PGLYRP-1能与热休克蛋白70形成具有细胞毒性的复合体，这表示了它也许能作为抗癌症的脚色。^[16] 身为一个具有抗菌属性的识别病原蛋白，PGLYRP-1也许在维持肠道中微生物菌丛中扮演着重要脚色。

机制

作为抗微生物剂，PGLYRP-1结合到其目标细胞，并不会像防御素和其他抗菌肽一样，穿透细菌细胞壁。相反地，PGLYRP-1的结合激活了细菌的压抑反应，而导致细菌关闭转录和翻译作用，以及诱导氧化反应。作为一个细胞毒性剂，PGLYRP1-热休克蛋白70复合体

可能的病理学作用

在人体上，PGLYRP-1基因的单核苷酸多态性与溃疡性结肠炎的发生有关。^[17]

在小鼠，缺乏PGLYRP1会增加感染传染性疾病的几率，但也减少了自身免疫性疾病的侵扰。当感染绿脓杆菌时，缺乏 PGLYRP1会增加角膜感染的风险性，减少角膜创伤的愈合能力，并且增加了角膜刮伤。^[18] 但PGLYRP1缺陷的小鼠同时也减缓了过敏性皮肤炎和接触性皮肤炎的严重性，且对于哮喘的发生也有所影响。

参考文献

^ ^1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000008438 - Ensembl, May 2017
^ ^2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000030413 - 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.
^ A peptidoglycan recognition protein in innate immunity conserved from insects to humans. Proc Natl Acad Sci U S A. Sep 1998, 95 (17): 10078–82. PMC 21464  . PMID 9707603. doi:10.1073/pnas.95.17.10078.
^ [Expression analysis of proteins encoded by genes of the tag7/tagL (PGRP-S,L) family in human peripheral blood cells]. Genetika. Apr 2003, 39 (2): 244–9. PMID 12669421.
^ Entrez Gene: PGLYRP1 peptidoglycan recognition protein 1.
^ 郭, 睿; 王, 银. 哺乳动物肽聚糖识别蛋白抗菌作用及其机制的研究进展. 吉林农业大学学报. 2013, 35 (02): 236–240 [2019-01-15]. ISSN 1000-5684. doi:10.13327/j.jjlau.2013.02.023. （原始内容存档于2019-01-15）.
^ Osanai, Arihiro; Sashinami, Hiroshi; Asano, Krisana; Li, Sheng-Jun; Hu, Dong-Liang; Nakane, Akio. Mouse Peptidoglycan Recognition Protein PGLYRP-1 Plays a Role in the Host Innate Immune Response againstListeria monocytogenesInfection. Infection and Immunity. 2010-12-06, 79 (2): 858–866. ISSN 0019-9567. doi:10.1128/iai.00466-10.
^ ^10.0 ^10.1 Sharapova, Tatiana N.; Ivanova, Olga K.; Prasolov, Vladimir S.; Romanova, Elena A.; Sashchenko, Lidia P.; Yashin, Denis V. Innate immunity protein Tag7 (PGRP-S) activates lymphocytes capable of Fasl-Fas-dependent contact killing of virus-infected cells. IUBMB Life. 2017-10-30, 69 (12): 971–977. ISSN 1521-6543. doi:10.1002/iub.1688.
^ Crystal structure of human peptidoglycan recognition protein I alpha bound to a muramyl pentapeptide from Gram-positive bacteria. Protein Sci. 2006, 15 (5): 1199–206. PMC 2242522  . PMID 16641493. doi:10.1110/ps.062077606.
^ López-Fuertes, L; Campos, E; Doménech, N; Ezquerra, A; Castro, J.M; Domı́nguez, J; Alonso, F. Porcine reproductive and respiratory syndrome (PRRS) virus down-modulates TNF-α production in infected macrophages. Virus Research. 2000-08, 69 (1): 41–46. ISSN 0168-1702. doi:10.1016/s0168-1702(00)00172-6.
^ Bautista, E. M.; Molitor, T. W. IFNγ inhibits porcine reproductive and respiratory syndrome virus replication in macrophages. Archives of Virology. 1999-06, 144 (6): 1191–1200. ISSN 0304-8608. doi:10.1007/s007050050578.
^ Weiss, Ido D.; Wald, Ori; Wald, Hanna; Beider, Katia; Abraham, Michal; Galun, Eithan; Nagler, Arnon; Peled, Amnon. IFN-γ Treatment at Early Stages of Influenza Virus Infection Protects Mice from Death in a NK Cell-Dependent Manner. Journal of Interferon & Cytokine Research. 2010-06, 30 (6): 439–449. ISSN 1079-9907. doi:10.1089/jir.2009.0084.
^ Hoshino, Akinori; Takenaka, Hiroshi; Mizukoshi, Osamu; Imanishi, Jiro; Kishida, Tsunataro; Tovey, Michael G. Effect of anti-interferon serum of influenza virus infection in mice. Antiviral Research. 1983-03, 3 (1): 59–65. ISSN 0166-3542. doi:10.1016/0166-3542(83)90015-3.
^ Peptidoglycan recognition protein tag7 forms a cytotoxic complex with heat shock protein 70 in solution and in lymphocytes. J. Biol. Chem. 2004, 279 (3): 2117–24. PMID 14585845. doi:10.1074/jbc.M307513200.
^ Genetic Association of Peptidoglycan Recognition Protein Variants with Inflammatory Bowel Disease. PLoS ONE. 2013, 8 (6): e67393. PMC 3686734  . PMID 23840689. doi:10.1371/journal.pone.0067393.
^ A novel antimicrobial peptidoglycan recognition protein in the cornea. Invest. Ophthalmol. Vis. Sci. 2009, 50 (9): 4185–91. PMC 3052780  . PMID 19387073. doi:10.1167/iovs.08-3040.

相关阅读

Cho JH, Fraser IP, Fukase K, et al. Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity.. Blood. 2005, 106 (7): 2551–8. PMC 1895263  . PMID 15956276. doi:10.1182/blood-2005-02-0530.
Guan R, Wang Q, Sundberg EJ, Mariuzza RA. Crystal structure of human peptidoglycan recognition protein S (PGRP-S) at 1.70 A resolution.. J. Mol. Biol. 2005, 347 (4): 683–91. PMID 15769462. doi:10.1016/j.jmb.2005.01.070.
Guan R, Roychowdhury A, Ember B, et al. Structural basis for peptidoglycan binding by peptidoglycan recognition proteins.. Proc. Natl. Acad. Sci. U.S.A. 2005, 101 (49): 17168–73. PMC 535381  . PMID 15572450. doi:10.1073/pnas.0407856101.
Gerhard DS, Wagner L, Feingold EA, et al. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).. Genome Res. 2004, 14 (10B): 2121–7. PMC 528928  . PMID 15489334. doi:10.1101/gr.2596504.
Guan R, Malchiodi EL, Wang Q, et al. Crystal structure of the C-terminal peptidoglycan-binding domain of human peptidoglycan recognition protein Ialpha.. J. Biol. Chem. 2004, 279 (30): 31873–82. PMID 15140887. doi:10.1074/jbc.M404920200.
Grimwood J, Gordon LA, Olsen A, et al. The DNA sequence and biology of human chromosome 19.. Nature. 2004, 428 (6982): 529–35. PMID 15057824. doi:10.1038/nature02399.
Sashchenko LP, Dukhanina EA, Yashin DV, et al. Peptidoglycan recognition protein tag7 forms a cytotoxic complex with heat shock protein 70 in solution and in lymphocytes.. J. Biol. Chem. 2004, 279 (3): 2117–24. PMID 14585845. doi:10.1074/jbc.M307513200.
Wang ZM, Li X, Cocklin RR, et al. Human peptidoglycan recognition protein-L is an N-acetylmuramoyl-L-alanine amidase.. J. Biol. Chem. 2004, 278 (49): 49044–52. PMID 14506276. doi:10.1074/jbc.M307758200.
Clark HF, Gurney AL, Abaya E, et al. The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.. Genome Res. 2003, 13 (10): 2265–70. PMC 403697  . PMID 12975309. doi:10.1101/gr.1293003.
Strausberg RL, Feingold EA, Grouse LH, et al. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.. Proc. Natl. Acad. Sci. U.S.A. 2003, 99 (26): 16899–903. PMC 139241  . PMID 12477932. doi:10.1073/pnas.242603899.
Liu C, Xu Z, Gupta D, Dziarski R. Peptidoglycan recognition proteins: a novel family of four human innate immunity pattern recognition molecules.. J. Biol. Chem. 2001, 276 (37): 34686–94. PMID 11461926. doi:10.1074/jbc.M105566200.

[refGRCh38Ensembl-1] 1.0 ^1.1 ^1.2 GRCh38: Ensembl release 89: ENSG00000008438 - Ensembl, May 2017

[refGRCm38Ensembl-2] 2.0 ^2.1 ^2.2 GRCm38: Ensembl release 89: ENSMUSG00000030413 - 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.

[pmid9707603-5] A peptidoglycan recognition protein in innate immunity conserved from insects to humans. Proc Natl Acad Sci U S A. Sep 1998, 95 (17): 10078–82. PMC 21464  . PMID 9707603. doi:10.1073/pnas.95.17.10078.

[pmid12669421-6] [Expression analysis of proteins encoded by genes of the tag7/tagL (PGRP-S,L) family in human peripheral blood cells]. Genetika. Apr 2003, 39 (2): 244–9. PMID 12669421.

[entrez-7] Entrez Gene: PGLYRP1 peptidoglycan recognition protein 1.

[8] 郭, 睿; 王, 银. 哺乳动物肽聚糖识别蛋白抗菌作用及其机制的研究进展. 吉林农业大学学报. 2013, 35 (02): 236–240 [2019-01-15]. ISSN 1000-5684. doi:10.13327/j.jjlau.2013.02.023. （原始内容存档于2019-01-15）.

[9] Osanai, Arihiro; Sashinami, Hiroshi; Asano, Krisana; Li, Sheng-Jun; Hu, Dong-Liang; Nakane, Akio. Mouse Peptidoglycan Recognition Protein PGLYRP-1 Plays a Role in the Host Innate Immune Response againstListeria monocytogenesInfection. Infection and Immunity. 2010-12-06, 79 (2): 858–866. ISSN 0019-9567. doi:10.1128/iai.00466-10.

[:0-10] 10.0 ^10.1 Sharapova, Tatiana N.; Ivanova, Olga K.; Prasolov, Vladimir S.; Romanova, Elena A.; Sashchenko, Lidia P.; Yashin, Denis V. Innate immunity protein Tag7 (PGRP-S) activates lymphocytes capable of Fasl-Fas-dependent contact killing of virus-infected cells. IUBMB Life. 2017-10-30, 69 (12): 971–977. ISSN 1521-6543. doi:10.1002/iub.1688.

[pmid16641493-11] Crystal structure of human peptidoglycan recognition protein I alpha bound to a muramyl pentapeptide from Gram-positive bacteria. Protein Sci. 2006, 15 (5): 1199–206. PMC 2242522  . PMID 16641493. doi:10.1110/ps.062077606.

[12] López-Fuertes, L; Campos, E; Doménech, N; Ezquerra, A; Castro, J.M; Domı́nguez, J; Alonso, F. Porcine reproductive and respiratory syndrome (PRRS) virus down-modulates TNF-α production in infected macrophages. Virus Research. 2000-08, 69 (1): 41–46. ISSN 0168-1702. doi:10.1016/s0168-1702(00)00172-6.

[13] Bautista, E. M.; Molitor, T. W. IFNγ inhibits porcine reproductive and respiratory syndrome virus replication in macrophages. Archives of Virology. 1999-06, 144 (6): 1191–1200. ISSN 0304-8608. doi:10.1007/s007050050578.

[14] Weiss, Ido D.; Wald, Ori; Wald, Hanna; Beider, Katia; Abraham, Michal; Galun, Eithan; Nagler, Arnon; Peled, Amnon. IFN-γ Treatment at Early Stages of Influenza Virus Infection Protects Mice from Death in a NK Cell-Dependent Manner. Journal of Interferon & Cytokine Research. 2010-06, 30 (6): 439–449. ISSN 1079-9907. doi:10.1089/jir.2009.0084.

[15] Hoshino, Akinori; Takenaka, Hiroshi; Mizukoshi, Osamu; Imanishi, Jiro; Kishida, Tsunataro; Tovey, Michael G. Effect of anti-interferon serum of influenza virus infection in mice. Antiviral Research. 1983-03, 3 (1): 59–65. ISSN 0166-3542. doi:10.1016/0166-3542(83)90015-3.

[pmid14585845-16] Peptidoglycan recognition protein tag7 forms a cytotoxic complex with heat shock protein 70 in solution and in lymphocytes. J. Biol. Chem. 2004, 279 (3): 2117–24. PMID 14585845. doi:10.1074/jbc.M307513200.

[pmid23840689-17] Genetic Association of Peptidoglycan Recognition Protein Variants with Inflammatory Bowel Disease. PLoS ONE. 2013, 8 (6): e67393. PMC 3686734  . PMID 23840689. doi:10.1371/journal.pone.0067393.

[pmid19387073-18] A novel antimicrobial peptidoglycan recognition protein in the cornea. Invest. Ophthalmol. Vis. Sci. 2009, 50 (9): 4185–91. PMC 3052780  . PMID 19387073. doi:10.1167/iovs.08-3040.

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