Evidence map›Paper›PMID 42584645›Full record

ArticleJournal of the American Chemical Society2026

Chemical Proteomic Profiling of the Histaminylation Proteome in Cancer Cells Unveils Uncharted Epigenetic Marks on Core Histones.

Xingyu Ma, Anne A Leaman, Zeng Lin, Huapeng Li, Zhengjun Cai, Qianyue Wang, Kaiwaan Dalal, Md Shahadat Hossain, Venkatesh P Thirumalaikumar, Zhihong Wang and 3 more

Abstract read
In one paragraph

Article in Journal of the American Chemical Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Xingyu MaDepartment of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana47907, United States.
Anne A LeamanDepartment of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana47907, United States.ORCID 0009-0003-1521-2401
Zeng LinDepartment of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana47907, United States.ORCID 0009-0005-5159-5168
Huapeng LiDepartment of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana47907, United States.
Zhengjun CaiDepartment of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana47907, United States.
Qianyue WangDepartment of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana47907, United States.
Kaiwaan DalalDepartment of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana47907, United States.
Md Shahadat HossainDepartment of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana47907, United States.
Venkatesh P ThirumalaikumarPurdue Proteomics Facility, Bindley Bioscience Center, Purdue University, West Lafayette, Indiana47907, United States.
Zhihong WangDepartment of Chemistry and Biochemistry, Rowan University, Glassboro, New Jersey08028, United States.ORCID 0000-0003-1667-3536
Valerie P O'BrienDepartment of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana47907, United States.
W Andy TaoDepartment of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana47907, United States.ORCID 0000-0002-5535-5517
Qingfei ZhengDepartment of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, West Lafayette, Indiana47907, United States.ORCID 0000-0002-8397-3507

Funding

Development of a Chemical Biology Toolbox to Investigate Histone MonoaminylationR35GM150676 · NIGMS · PURDUE UNIVERSITY · PI Qingfei Zheng · 2023 to 2026
$1.6M
Division of Chemistry CHE-2404098NIGMS NIH HHS R35 GM150676Purdue University NA
6 · The paper itself

Abstract

Histamine is a key signaling molecule in pathophysiology that can exhibit significant regulatory roles in diverse health and disease states. Besides the well-studied noncovalent interactions between histamine and its receptors, protein histaminylation is a recently discovered mechanism of action through which histamine regulates cellular signaling pathways in a covalent modification manner. Histaminylation is an emerging protein post-translational modification (PTM), where an isopeptide bond is formed between the histamine primary amine and the γ-carboxyl group of glutamine through a transamidation reaction catalyzed by transglutaminase 2 (TGM2). However, due to the lack of efficient pan-specific antibodies targeting histaminylated glutamine, the histaminylation proteome in cells remains poorly explored. Here, we report the design and development of a novel Nτ-propargylated histamine (Nτ-PH) probe as well as its successful application in chemical proteomic profiling of the histaminylation proteome in cancer cells. Notably, new TGM2-catalyzed epigenetic marks on core histones, e.g., H2AX-Q84 and Q104 histaminylation, have been identified from cancer cells and verified. Lastly, the crosstalk between H2AX histaminylation and γH2AX formation was discovered in this study, suggesting that TGM2-mediated histaminylation plays a critical role in DNA damage responses.

Indexed as

Epigenesis, GeneticHistamineHistonesProteomeProteomicsHumansProtein Glutamine gamma Glutamyltransferase 2Protein Processing, Post-TranslationalTransglutaminasesHistamineHistonesProtein Glutamine gamma Glutamyltransferase 2ProteomeTransglutaminases

Identifiers

PMID42584645
PMCPMC13530330

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.