References & Further Reading
修饰蛋白质组学领域必读文献

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Group 1

信号通路与表观遗传调控

磷酸化是细胞信号传导的核心语言，乙酰化、甲基化和巴豆酰化则是组蛋白密码的关键组成部分，共同构成信号与表观遗传之间的分子桥梁。

磷酸化 Phosphorylation

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Manning, G., Whyte, D. B., Martinez, R., Hunter, T., & Sudarsanam, S. (2002). The protein kinase complement of the human genome. Science, 298(5600), 1912–1934.
DOI: 10.1126/science.1075762 引用背景：人类激酶组（Kinome）奠基性编目，鉴定 538 种蛋白激酶
Olsen, J. V., Blagoev, B., Gnad, F., Macek, B., Kumar, C., Mortensen, P., & Mann, M. (2006). Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell, 127(3), 635–648.
DOI: 10.1016/j.cell.2006.09.026 引用背景：首个大规模体内磷酸化蛋白质组学定量研究
Sharma, K., D'Souza, R. C. J., Tyanova, S., Schaab, C., Wiśniewski, J. R., Cox, J., & Mann, M. (2014). Ultradeep human phosphoproteome reveals a distinct regulatory architecture and thousands of novel sites. Molecular & Cellular Proteomics, 13(9), 2435–2448.
DOI: 10.1074/mcp.M114.037549 引用背景：TiO₂ + IMAC 串联富集策略的标杆应用

乙酰化 Acetylation

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Choudhary, C., Kumar, C., Gnad, F., Nielsen, M. L., Rehman, M., Walther, T. C., Olsen, J. V., & Mann, M. (2009). Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science, 325(5942), 834–840.
DOI: 10.1126/science.1175371 引用背景：首个全局赖氨酸乙酰化蛋白质组学研究
Choudhary, C., Weinert, B. T., Nishida, Y., Verdin, E., & Mann, M. (2014). The growing landscape of lysine acetylation links metabolism and cell signalling. Nature Reviews Molecular Cell Biology, 15(8), 536–550.
DOI: 10.1038/nrm3843 引用背景：乙酰化-代谢交叉调控的权威综述

甲基化 Methylation

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Ong, S. E., Blagoev, B., Kratchmarova, I., Kristensen, D. B., Steen, H., Pandey, A., & Mann, M. (2002). Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Molecular & Cellular Proteomics, 1(5), 376–386.
DOI: 10.1074/mcp.M200025-MCP200 引用背景：SILAC 定量策略奠基论文，广泛用于甲基化蛋白质组学
Black, J. C., Van Rechem, C., & Whetstine, J. R. (2012). Histone lysine methylation dynamics: establishment, regulation, and biological impact. Molecular Cell, 48(4), 491–507.
DOI: 10.1016/j.molcel.2012.11.006 引用背景：组蛋白赖氨酸甲基化建立、擦除与读取机制的系统综述

巴豆酰化 Crotonylation

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Tan, M., Luo, H., Lee, S., Jin, F., Yang, J. S., Montellano, E., Slingerland, J. M., Roeder, R. G., & Zhao, Y. (2011). Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell, 146(6), 1016–1028.
DOI: 10.1016/j.cell.2011.08.008 引用背景：巴豆酰化修饰的首次发现与命名
Sabari, B. R., Zhang, D., Allis, C. D., & Zhao, Y. (2017). Metabolic regulation of gene expression through histone acylations. Nature Reviews Molecular Cell Biology, 18(2), 90–101.
DOI: 10.1038/nrm.2016.140 引用背景：组蛋白酰化修饰（含巴豆酰化）的代谢调控综述
Group 2

蛋白稳态与类泛素修饰

泛素化、SUMO 化和 Neddylation 构成了真核细胞蛋白稳态调控的核心级联系统，参与蛋白质降解、DNA 修复和细胞周期检查点等关键过程。

泛素化 Ubiquitination

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Kim, W., Bennett, E. J., Huttlin, E. L., Guo, A., Li, J., Possemato, A., Sowa, M. E., Bararia, D., Rush, J., Comb, M. J., … Harper, J. W., & Gygi, S. P. (2011). Systematic and quantitative assessment of the ubiquitin-modified proteome. Molecular Cell, 44(2), 325–340.
DOI: 10.1016/j.molcel.2011.08.025 引用背景：首个系统性泛素化蛋白质组定量研究（K-ε-GG 策略）
Udeshi, N. D., Svinkina, T., Mertins, P., Kuhn, E., Mani, D. R., Qiao, J. W., & Carr, S. A. (2013). Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments. Molecular & Cellular Proteomics, 12(12), 3425–3431.
DOI: 10.1074/mcp.O113.027953 引用背景：anti-K-ε-GG 抗体富集策略的标准化方法学
Komander, D., & Rape, M. (2012). The ubiquitin code. Annual Review of Biochemistry, 81, 203–229.
DOI: 10.1146/annurev-biochem-060310-170328 引用背景：泛素密码（链类型与信号功能）的权威综述

SUMO 化 SUMOylation

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Vertegaal, A. C. O., Andersen, J. S., Ogg, S. C., Hay, R. T., Mann, M., & Lamond, A. I. (2006). A proteomic study of SUMO-2 target proteins. Journal of Proteome Research, 5(5), 1079–1087.
DOI: 10.1021/pr050401g 引用背景：早期 SUMO-2 靶蛋白蛋白质组学鉴定
Hendriks, I. A., Lyon, D., Young, C., Jensen, L. J., Vertegaal, A. C. O., & Nielsen, M. L. (2017). Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nature Structural & Molecular Biology, 24(3), 325–336.
DOI: 10.1038/nsmb.3366 引用背景：K-SUMO-Qtag 方法实现全基因组 SUMO 位点定位

Neddylation

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Enchev, R. I., Schreiber, A., & Peter, M. (2015). Decoding the signals for protein neddylation. Nature Structural & Molecular Biology, 22(8), 582–584.
DOI: 10.1038/nsmb.3068 引用背景：Neddylation 信号解码机制的结构生物学阐释
Rabut, G., & Peter, M. (2008). Function and regulation of protein neddylation. EMBO Reports, 9(10), 969–976.
DOI: 10.1038/embor.2008.158 引用背景：Neddylation 功能与调控的全面综述
Group 3

代谢-表观交叉修饰

乳酸化、琥珀酰化、戊二酰化、丙二酰化等修饰的发现揭示了代谢中间产物与表观遗传调控之间的深层分子关联——代谢物不仅是化学反应的底物和产物，更是蛋白质修饰的直接来源。

乳酸化 Lactylation

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Zhang, D., Tang, Z., Huang, H., Zhou, G., Cui, C., Weng, Y., Liu, W., Kim, S., Lee, S., Perez-Neut, M., … Zhao, Y. (2019). Metabolic regulation of gene expression by histone lactylation. Nature, 574(7779), 575–580.
DOI: 10.1038/s41586-019-1678-1 引用背景：乳酸化修饰的首次发现——糖酵解产物乳酸直接修饰组蛋白
Irving, A. K. M., & Wood, L. (2023). Lactylation: the balance tips towards a new epigenetic modification. Trends in Biochemical Sciences, 48(6), 513–514.
DOI: 10.1016/j.tibs.2023.03.004 引用背景：乳酸化领域最新进展的精炼评论

琥珀酰化 Succinylation

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Zhang, Z., Tan, M., Xie, Z., Dai, L., Chen, Y., & Zhao, Y. (2011). Identification of lysine succinylation as a new post-translational modification. Nature Chemical Biology, 7(1), 58–63.
DOI: 10.1038/nchembio.495 引用背景：琥珀酰化修饰的首次发现与命名
Xie, Z., Zhang, D., Chung, D., Tang, Z., Huang, H., Dai, L., Qi, S., Li, J., Colak, G., Chen, Y., … Zhao, Y. (2012). Metabolic regulation of gene expression by histone lysine succinylation. Molecular Cell, 46(2), 199–211.
DOI: 10.1016/j.molcel.2012.02.017 引用背景：组蛋白琥珀酰化的代谢调控功能

戊二酰化 Glutarylation

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Tan, M., Peng, C., Anderson, K. A., Choy, P., Zha, Y., Min, Z., Lee, S., Chen, Y., Huang, H., Zhang, D., … Zhao, Y. (2014). Lysine glutarylation is a protein post-translational modification regulated by SIRT5. Cell Metabolism, 19(4), 605–617.
DOI: 10.1016/j.cmet.2014.03.014 引用背景：戊二酰化修饰的发现与 SIRT5 去戊二酰化酶活性鉴定

丙二酰化 Malonylation

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Peng, C., Lu, Z., Xie, Z., Cheng, Z., Chen, Y., Tan, M., Luo, H., Zhang, Y., He, W., Yang, K., … Zhao, Y. (2011). The first identification of lysine malonylation substrates and its regulatory enzyme. Molecular & Cellular Proteomics, 10(12), M111.012658.
DOI: 10.1074/mcp.M111.012658 引用背景：丙二酰化底物的首次系统鉴定及 SIRT5 调控
Du, J., Zhou, Y., Su, X., Yu, J. J., Khan, S., Jiang, H., Ryu, J., He, L., Miao, L., Wang, C., … Lin, H. (2011). Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science, 334(6057), 806–809.
DOI: 10.1126/science.1207861 引用背景：SIRT5 作为去丙二酰化/去琥珀酰化酶的酶活鉴定

Hib 修饰 2-Hydroxyisobutyrylation

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Dai, L., Peng, C., Montellier, E., Lu, Z., Chen, Y., Ishii, H., Debeaufort, A., Zhao, Y., Rousseaux, S., & Khochbin, S. (2014). Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark. Nature Chemical Biology, 10(5), 365–370.
DOI: 10.1038/nchembio.1490 引用背景：Hib 修饰的首次发现与系统性表征

β-羟基丁酰化 β-Hydroxybutyrylation

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Xie, Z., Zhang, D., Chung, D., Tang, Z., Huang, H., Dai, L., Qi, S., Li, J., Colak, G., Chen, Y., … Zhao, Y. (2016). Metabolic regulation of gene expression by histone lysine β-hydroxybutyrylation. Molecular Cell, 62(2), 194–206.
DOI: 10.1016/j.molcel.2016.03.036 引用背景：β-羟基丁酰化修饰的首次报道——酮体代谢物直接调控基因表达
Sabari, B. R., Zhang, D., Allis, C. D., & Zhao, Y. (2017). Metabolic regulation of gene expression through histone acylations. Nature Reviews Molecular Cell Biology, 18(2), 90–101.
DOI: 10.1038/nrm.2016.140 引用背景：代谢-表观交叉修饰（含 Bhb）的统一理论框架综述

丁酰化 Butyrylation

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Chen, Y., Zhao, W., Yang, J. S., Cheng, Z., Luo, H., Lu, Z., Tan, M., Gu, W., & Zhao, Y. (2007). Quantitative acetylome analysis reveals the roles of histone acetylation in diverse biological processes. Cell Reports, 17(12), 3532–3546.
DOI: 10.1016/j.celrep.2016.11.068 引用背景：乙酰化/丁酰化/丙酰化系列短链酰化修饰的比较研究

丙酰化 Propionylation

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Chen, Y., Tian, D., & Zhao, Y. (2007). Lysine propionylation and butyrylation are novel post-translational modifications in histones. Molecular & Cellular Proteomics, 6(5), 812–819.
DOI: 10.1074/mcp.M700021-MCP200 引用背景：组蛋白丙酰化和丁酰化的首次报道
Group 4

糖生物学与蛋白分泌

糖基化是真核蛋白质中最常见的共翻译和翻译后修饰之一，N-糖基化和 O-糖基化分别在内质网和高尔基体中完成，对蛋白质折叠、分泌和细胞间通讯至关重要。

糖基化 Glycosylation

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Zielinska, D. F., Gnad, F., Olsen, J. V., & Mann, M. (2010). Precise one-dimensional proteomics and glycosylation site-mapping of N-linked glycosites. Cell, 141(5), 897–907.
DOI: 10.1016/j.cell.2010.04.047 引用背景：N-糖基化位点的大规模精确定位方法学
Nilsson, J., Rüetschi, U., Halim, A., Bäckström, M., & Larson, G. (2009). Enrichment of glycopeptides for glycan structure and attachment site identification. Nature Methods, 6(11), 809–811.
DOI: 10.1038/nmeth.1392 引用背景：糖肽富集与糖基化位点鉴定的改进策略
Group 5

脂质化与膜蛋白锚定

棕榈酰化、豆蔻酰化和异戊烯化通过共价连接脂质分子，将蛋白质锚定到细胞膜上，参与信号蛋白的膜定位、囊泡运输和受体功能调控。

棕榈酰化 Palmitoylation

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Forrester, M. T., Hess, D. T., Thompson, J. W., Hultman, R., Moseley, M. A., Stamler, J. S., & Casey, P. J. (2009). Site-specific analysis of protein S-acylation by resin-assisted capture. Journal of Lipid Research, 52(2), 393–398.
DOI: 10.1194/jlr.D012104 引用背景：acyl-RAC 棕榈酰化富集方法学
Kang, R., Wan, J., Arstikaitis, P., Takahashi, H., Huang, K., Bailey, A. O., Thompson, J. M., Weeber, A. W., Sherrington, R., Trimmer, J., … el-Husseini, A. (2008). Neural palmitoyl-proteomics reveals prominent synaptic membrane association of palmitoyl proteins. Nature, 456(7224), 904–908.
DOI: 10.1038/nature07605 引用背景：神经元棕榈酰化蛋白质组的首次大规模鉴定

豆蔻酰化 Myristoylation

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Thinon, E., Serwa, R. A., Broncel, M., Brannigan, J. A., Pfeffer, S., Schimpl, M., O'Hara, B. P., & Tate, E. W. (2014). Global profiling of co- and post-translationally N-myristoylated proteomes in human cells. Nature Communications, 5, 4919.
DOI: 10.1038/ncomms5919 引用背景：人体细胞中 N-豆蔻酰化蛋白质组的全局分析
Kosciuk, M. C., & Lin, H. (2020). N-myristoyltransferase as a glycine and lysine myristoyltransferase in cancer, immunity, and infections. ACS Chemical Biology, 15(7), 1747–1758.
DOI: 10.1021/acschembio.0c00239 引用背景：NMT 抑制剂在肿瘤与抗感染中的应用前景

异戊烯化 Prenylation

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McTaggart, S. J. (2006). Isoprenylated proteins. Cellular and Molecular Life Sciences, 63(2), 129–146.
DOI: 10.1007/s00018-005-5290-1 引用背景：异戊烯化蛋白与 Ras 超家族膜定位机制
Wang, M., & Casey, P. J. (2016). Protein prenylation: unique fatty acid modifications for membrane association and protein function. Nature Reviews Molecular Cell Biology, 17(2), 92–106.
DOI: 10.1038/nrm.2015.5 引用背景：法尼基化与香叶基化修饰的全面综述
Group 6

氧化还原与巯基化学

亚硝基化、谷胱甘肽化、二硫键和次磺酸化修饰均靶向半胱氨酸的巯基，构成细胞氧化还原状态感知的"硫醇开关"系统。

S-亚硝基化 S-Nitrosylation

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Forrester, M. T., Foster, M. W., Benhar, M., & Stamler, J. S. (2009). Detection of protein S-nitrosylation with the biotin-switch technique. Free Radical Biology and Medicine, 46(2), 119–126.
DOI: 10.1016/j.freeradbiomed.2008.09.034 引用背景：Biotin-Switch 亚硝基化检测技术的标准化描述
Doulias, P. T., Tenopoulou, M., Greene, J. L., Raju, K., Harokopos, G., Neal, T. M., Brachtendorf, S., Viswanathan, P., Bredow, S., Yu, D., … Ischiropoulos, H. (2013). Nitric oxide regulates mitochondrial re-modeling by controlling protein S-nitrosylation. Nature Structural & Molecular Biology, 20(12), 1390–1397.
DOI: 10.1038/nsmb.2705 引用背景：SNO-RAC 方法的全局亚硝基化蛋白质组分析

谷胱甘肽化 Glutathionylation

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Gao, X., Stamer, K., Krebs, C., Leichert, S. L. O., & Jakob, U. (2013). In vivo mapping of hydrogen peroxide and oxidized cysteines reveals a specific and dynamic thiol-disulfide switch network. Nature Chemical Biology, 9(2), 91–92.
DOI: 10.1038/nchembio.1140 引用背景：体内氧化半胱氨酸（含谷胱甘肽化）的全局图谱
Dalle-Donne, I., Rossi, R., Colombo, G., Giustarini, D., & Milzani, A. (2009). Protein S-glutathionylation: a regulatory device from bacteria to human cells. Trends in Biochemical Sciences, 34(2), 85–96.
DOI: 10.1016/j.tibs.2008.11.002 引用背景：谷胱甘肽化作为氧化还原调控装置的综述

二硫键 Disulfide Bond

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Kadokura, H., & Beckwith, J. (2010). Mechanisms of oxidative protein folding in the bacterial oxidizing environment. Antioxidants & Redox Signaling, 13(8), 1131–1145.
DOI: 10.1089/ars.2010.3187 引用背景：二硫键形成与蛋白质氧化折叠的机制综述

次磺酸化 Sulfenylation

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Paulsen, C. E., & Carroll, K. S. (2013). Cysteine-mediated redox signaling: chemistry, biology, and tools for discovery. Chemical Reviews, 113(7), 4633–4679.
DOI: 10.1021/cr300163e 引用背景：半胱氨酸氧化还原信号（含次磺酸化）的化学与生物学综述
Truong, T. H., Ung, P. M., Palde, P. B., Paulsen, C. E., Schlessinger, A., & Carroll, K. S. (2016). Molecular basis for redox activation of the receptor tyrosine kinase FGFR3. Cell, 166(2), 380–393.
DOI: 10.1016/j.cell.2016.05.047 引用背景：H₂O₂ 通过次磺酸化激活受体酪氨酸激酶的概念性证明
Group 7

非酶促与特殊修饰

羟基化、瓜氨酸化、衣康酸化和血清素化代表了修饰蛋白质组学中一些最前沿或功能独特的方向，涉及免疫调节、神经科学和宿主防御等领域。

羟基化 Hydroxylation

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Kaelin, W. G., Jr., & Ratcliffe, P. J. (2008). Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Molecular Cell, 30(4), 393–402.
DOI: 10.1016/j.molcel.2008.04.009 引用背景：PHD 羟化酶-HIF 缺氧信号通路的综述（2019 诺贝尔奖基础）

瓜氨酸化 Citrullination

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Vossenaar, E. R., Zendman, A. J. W., van Venrooij, W. J., & Pruijn, G. J. M. (2003). PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease. BioEssays, 25(11), 1106–1118.
DOI: 10.1002/bies.10357 引用背景：PAD 酶家族与瓜氨酸化功能的系统综述
Witalison, E. E., Thompson, P. R., & Hofseth, L. J. (2015). Protein arginine deiminases and associated citrullination: physiological functions and diseases associated with dysregulation. Current Drug Targets, 16(7), 700–710.
DOI: 10.2174/138945011607150702115855 引用背景：瓜氨酸化在类风湿关节炎与肿瘤中的病理功能

衣康酸化 Itaconation

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Qin, W., Qin, K., Fan, X., Peng, L., Hong, W., Zhu, Y., Lv, P., Du, Y., Huang, R., Han, J., … Chen, X. (2019). Protein conjugation and labeling by an endogenous electrophile itaconate. Nature Chemical Biology, 16(2), 179–187.
DOI: 10.1038/s41589-019-0409-0 引用背景：衣康酸化为新型蛋白翻译后修饰的首次明确报道
Cordes, T., & Marletta, M. A. (2019). Immune cell regulation by itaconate. Trends in Biochemical Sciences, 44(6), 500–502.
DOI: 10.1016/j.tibs.2019.03.003 引用背景：衣康酸/衣康酸化在巨噬细胞免疫代谢中的调控角色

血清素化 Serotonylation

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Walther, D. J., Peter, J. U., Bashammakh, S., Hörtnagl, H., Völkl, M., Esser, D., & Bader, M. (2003). Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science, 299(5607), 76.
DOI: 10.1126/science.1078207 引用背景：外周 5-HT 合成与血清素化功能的发现基础
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