Evidence map›Paper›PMID 28653853›Full record

ArticleJournal of proteome research2017

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

Tamara Ratovitski, Robert N O'Meally, Mali Jiang, Raghothama Chaerkady, Ekaterine Chighladze, Jacqueline C Stewart, Xiaofang Wang, Nicolas Arbez, Elaine Roby, Athanasios Alexandris and 6 more

Open access · greenAbstract read
In one paragraph

Article in Journal of proteome research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.3field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Regulation of Mutant Huntingtin Mitochondrial Toxicity by Phosphomimetic Mutations within Its N-Terminal Region.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
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  9. Review
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  11. Article
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  14. Article
  15. Amyotrophic Lateral Sclerosis Genes inInternational journal of molecular sciences · 2021
    Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 1 country.

Tamara RatovitskiDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine , 600 North Wolfe Street, CMSC 8-121, Baltimore, Maryland 21287, United States.ORCID 0000-0003-4020-5644
Robert N O'MeallyMass Spectrometry and Proteomics Facility, Department of Biological Chemistry, Johns Hopkins University School of Medicine , 733 North Broadway Street, Suite 371 BRB, Baltimore, Maryland 21287, United States.
Mali JiangDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine , 600 North Wolfe Street, CMSC 8-121, Baltimore, Maryland 21287, United States.
Raghothama ChaerkadyMass Spectrometry and Proteomics Facility, Department of Biological Chemistry, Johns Hopkins University School of Medicine , 733 North Broadway Street, Suite 371 BRB, Baltimore, Maryland 21287, United States.
Ekaterine ChighladzeDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine , 600 North Wolfe Street, CMSC 8-121, Baltimore, Maryland 21287, United States.
Jacqueline C StewartDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine , 600 North Wolfe Street, CMSC 8-121, Baltimore, Maryland 21287, United States.
Xiaofang WangDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine , 600 North Wolfe Street, CMSC 8-121, Baltimore, Maryland 21287, United States.
Nicolas ArbezDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine , 600 North Wolfe Street, CMSC 8-121, Baltimore, Maryland 21287, United States.
Elaine RobyDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine , 600 North Wolfe Street, CMSC 8-121, Baltimore, Maryland 21287, United States.
Athanasios AlexandrisDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine , 600 North Wolfe Street, CMSC 8-121, Baltimore, Maryland 21287, United States.
Wenzhen DuanDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine , 600 North Wolfe Street, CMSC 8-121, Baltimore, Maryland 21287, United States.
Ravi VijayvargiaCenter for Human Genetic Research, Massachusetts General Hospital , Boston, Massachusetts 02114, United States.
Ihn Sik SeongCenter for Human Genetic Research, Massachusetts General Hospital , Boston, Massachusetts 02114, United States.
Daniel J LaveryCHDI Foundation/CHDI Management, Inc. , Princeton, New Jersey 08540, United States.
Robert N ColeMass Spectrometry and Proteomics Facility, Department of Biological Chemistry, Johns Hopkins University School of Medicine , 733 North Broadway Street, Suite 371 BRB, Baltimore, Maryland 21287, United States.
Christopher A RossDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine , 600 North Wolfe Street, CMSC 8-121, Baltimore, Maryland 21287, United States.
Johns Hopkins University · USHarvard University · USCHDI Foundation · US

Funding

Validation of Novel Pathogenic Post-Translational Modifications of Huntingtin, and of Modifying Enzymes as Therapeutic Targets for Huntington's DiseaseR01NS086452 · NINDS · JOHNS HOPKINS UNIVERSITY · PI ROSS, CHRISTOPHER A · 2014 to 2023
$6.2M
Genomic and functional analysis of transcriptome changes in Huntington's DiseaseR01NS076631 · NINDS · UNIVERSITY OF IOWA · PI DAVIDSON, BEVERLY L., ROSS, CHRISTOPHER A · 2013 to 2017
$3.2M
Huntington's Disease biomarkers and therapeuticsR01NS082338 · NINDS · JOHNS HOPKINS UNIVERSITY · PI DUAN, WENZHEN · 2013 to 2017
$2.0M
Mitochondrial SIRT3 in Huntington's diseaseR21NS099670 · NINDS · JOHNS HOPKINS UNIVERSITY · PI DUAN, WENZHEN · 2016 to 2017
$449k
NG2 cells in Huntington's diseaseR21NS094886 · NINDS · JOHNS HOPKINS UNIVERSITY · PI DUAN, WENZHEN · 2016 to 2017
$446k
NINDS NIH HHS R01 NS076631NINDS NIH HHS R01 NS082338NINDS NIH HHS R01 NS086452NINDS NIH HHS R21 NS094886NINDS NIH HHS R21 NS099670
6 · The paper itself

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.

Indexed as

Protein Processing, Post-TranslationalAnimalsBrainBrain ChemistryCorpus StriatumHumansHuntingtin ProteinHuntington DiseaseMass SpectrometryMiceNerve Tissue ProteinsPeptide HydrolasesPhosphorylationProtein DomainsHTT protein, humanHtt protein, mouseHuntingtin ProteinNerve Tissue ProteinsPeptide Hydrolaseshuman brainHuntington’s diseasemass spectrometryneurodegenerative disorderpost-translational modificationsTMT

Identifiers

PMID28653853
PMCPMC5560079
OpenAlexW2728504653

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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 OpenQuestion graph.