Post-Translational Modifications (PTMs), Identified on Endogenous Huntingtin, Cluster within Proteolytic Domains between HEAT Repeats.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:28653853", "kind": "science-record", "revision": 2, "content_hash": "sha256:54dbfafdb51d09983108cc7223312be2ff0be0ca2a67c7f9787af2fe120607b8", "created_at": "2026-11-01T15:40:26Z", "updated_at": "2026-11-01T18:48:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Post-Translational Modifications (PTMs), Identified on Endogenous Huntingtin, Cluster within Proteolytic Domains between HEAT Repeats.", "doi": "10.1021/acs.jproteome.6b00991", "pmid": "28653853", "authors": ["Tamara Ratovitski", "Robert N O'Meally", "Mali Jiang", "Raghothama Chaerkady", "Ekaterine Chighladze", "Jacqueline C Stewart", "Xiaofang Wang", "Nicolas Arbez", "Elaine Roby", "Athanasios Alexandris", "Wenzhen Duan", "Ravi Vijayvargia", "Ihn Sik Seong", "Daniel J Lavery", "Robert N Cole", "Christopher A Ross"], "journal": "Journal of proteome research", "year": 2017, "abstract": "Post-translational modifications (PTMs) of proteins regulate various cellular processes. PTMs of polyglutamine-expanded huntingtin (Htt) protein, which causes Huntington's disease (HD), are likely modulators of HD pathogenesis. Previous studies have identified and characterized several PTMs on exogenously expressed Htt fragments, but none of them were designed to systematically characterize PTMs on the endogenous full-length Htt protein. We found that full-length endogenous Htt, which was immunoprecipitated from HD knock-in mouse and human post-mortem brain, is suitable for detection of PTMs by mass spectrometry. Using label-free and mass tag labeling-based approaches, we identified near 40 PTMs, of which half are novel (data are available via ProteomeXchange with identifier PXD005753). Most PTMs were located in clusters within predicted unstructured domains rather than within the predicted α-helical structured HEAT repeats. Using quantitative mass spectrometry, we detected significant differences in the stoichiometry of several PTMs between HD and WT mouse brain. The mass-spectrometry identification and quantitation were verified using phospho-specific antibodies for selected PTMs. To further validate our findings, we introduced individual PTM alterations within full-length Htt and identified several PTMs that can modulate its subcellular localization in striatal cells. These findings will be instrumental in further assembling the Htt PTM framework and highlight several PTMs as potential therapeutic targets for HD.", "claims": [{"id": "claim-target-result", "statement": "The study used quantitative mass spectrometry, specifically TMT-based TIMTA analysis, to compare PTM stoichiometry between HD and WT mouse brain, finding significant differences in several PTMs; the source data were deposited in ProteomeXchange under identifier PXD005753.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:28653853", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Using quantitative mass spectrometry, we detected significant differences in the stoichiometry of several PTMs between HD and WT mouse brain."}, {"asset": "source:pmid:28653853", "locator": "sections[1] \"INTRODUCTION\" paragraph 6", "quote": "Using label-free and tandem mass tag (TMT)-based MS techniques, we identified 34 PTMs on the endogenous Htt, including 18 novel PTMs (10 serine and 1 threonine phosphorylation and 7 lysine acetylation sites)."}, {"asset": "source:pmid:28653853", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Using label-free and mass tag labeling-based approaches, we identified near 40 PTMs, of which half are novel (data are available via ProteomeXchange with identifier PXD005753)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The study used quantitative mass spectrometry, specifically TMT-based TIMTA analysis, to compare PTM stoichiometry between HD and WT mouse brain, finding significant differences in several PTMs; the source data were deposited in ProteomeXchange under identifier PXD005753.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:28653853"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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