Evidence map›Paper›PMID 28169289›Full record

ArticleScientific reports2017

The Nedd8 Non-covalent Binding Region in the Smurf HECT Domain is Critical to its Ubiquitn Ligase Function.

Shan He, Yu Cao, Ping Xie, Guanglong Dong, Lingqiang Zhang

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

19 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. SMURF2 in Anticancer Therapy: Dual Role in Carcinogenesis and Theranostics.International journal of molecular sciences · 2026
    Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. SSDraw: Software for generating comparative protein secondary structure diagrams.Protein science : a publication of the Protein Society · 2023
    Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Adaptors as the regulators of HECT ubiquitin ligases.Cell death and differentiation · 2021
    Review
  14. Review
  15. Review
  16. Review
  17. TTC3 contributes to TGF-βCell death & disease · 2019
    Article
  18. Regulating the human HECT E3 ligases.Cellular and molecular life sciences : CMLS · 2018
    Review
  19. Regulation of Ubiquitin Enzymes in the TGF-β Pathway.International journal of molecular sciences · 2017
    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

5 authors at 2 institutions in 1 country.

Shan HeState Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.
Yu CaoState Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.
Ping XieState Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.
Guanglong DongDepartment of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
Lingqiang ZhangState Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Collaborative Innovation Center for Cancer Medicine, Beijing 100850, China.
Beijing Proteome Research Center · CNPeople's Liberation Army No. 150 Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nedd8 is a ubiquitin-like protein that controls vital biological events through conjugation to target proteins. We previously identified the HECT-type ubiquitin ligase Smurf1 which controls diverse cellular processes is activated by Nedd8 through covalent neddylation. However, the effect of non-covalent binding to Nedd8 remains unknown. In this study, we demonstrate that both Smurf1 and its homologue Smurf2 carry a non-covalent Nedd8-binding site within its catalytic HECT domain. Structural analysis reveals that Smurf2 has Nedd8-binding sites within the small sub-domain of N-lobe and the C-lobe of HECT domain. Interestingly, the consensus Nedd8 binding sequence, L(X7)R(X5)F(X)ALQ is conserved in both Smurfs. Mutational studies reveal that all the five residues in the conserved sequence are required for binding to Nedd8. Functional studies suggest that mutations that disrupt Smurf interaction with Nedd8 reduce its neddylation and stabilize the protein. Furthermore, Nedd8 binding site in Smurf is shown to be necessary for its ubiquitin ligase activity towards the substrate and also the self-ubiquitylation. Finally, we show that Nedd8 binding to Smurf plays important roles in the regulation of cell migration and the BMP and TGFβ signaling pathways.

Indexed as

Amino Acid SequenceBone Morphogenetic ProteinsCell MovementHEK293 CellsHumansMolecular Docking SimulationMutationNEDD8 ProteinProtein BindingProtein DomainsSignal TransductionStructure-Activity RelationshipSubstrate SpecificityTransforming Growth Factor betaUbiquitinationUbiquitin-Protein LigasesBone Morphogenetic ProteinsNEDD8 ProteinNEDD8 protein, humanSMURF1 protein, humanSMURF2 protein, humanTransforming Growth Factor betaUbiquitin-Protein Ligases

Identifiers

PMID28169289
PMCPMC5294409
OpenAlexW2587663328

What OpenQuestion 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 OpenQuestion graph.