Evidence map›Paper›PMID 32973038›Full record

ArticleJournal of lipid research2020

Characterization of essential domains in HSD17B13 for cellular localization and enzymatic activity.

Yanling Ma, Suman Karki, Philip M Brown, Dennis D Lin, Maren C Podszun, Wenchang Zhou, Olga V Belyaeva, Natalia Y Kedishvili, Yaron Rotman

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of lipid research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 18% 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, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.

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  18. HSD17B13: A Potential Therapeutic Target for NAFLD.Frontiers in molecular biosciences · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Yanling MaLiver and Energy Metabolism Section, National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, Bethesda, MD, USA.
Suman KarkiDepartment of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama, Birmingham, Birmingham, AL, USA.
Philip M BrownLiver and Energy Metabolism Section, National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, Bethesda, MD, USA.
Dennis D LinLiver and Energy Metabolism Section, National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, Bethesda, MD, USA.
Maren C PodszunLiver and Energy Metabolism Section, National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, Bethesda, MD, USA.
Wenchang ZhouTheoretical Molecular Biophysics Laboratory, National Heart, Lung, and Blood Institute, the National Institutes of Health, Bethesda, MD, USA.
Olga V BelyaevaDepartment of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama, Birmingham, Birmingham, AL, USA.
Natalia Y KedishviliDepartment of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama, Birmingham, Birmingham, AL, USA.ORCID 0000-0001-6917-4891
Yaron RotmanLiver and Energy Metabolism Section, National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, Bethesda, MD, USA rotmany@niddk.nih.gov.ORCID 0000-0002-7549-8216
National Institutes of Health · USUniversity of Alabama at Birmingham · US

Funding

SHORT-CHAIN DEHYDROGENASES IN RETINOL/STEROL METABOLISMR01AA012153 · NIAAA · UNIVERSITY OF MISSOURI KANSAS CITY · PI KEDISHVILI, NATALIA Y · 2000 to 2017
$5.1M
Short-Chain Dehydrogenases in Retinol/Sterol MetabolismR01AR076924 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KEDISHVILI, NATALIA Y · 2020 to 2024
$2.2M
NIAAA NIH HHS R01 AA012153NIAMS NIH HHS R01 AR076924
6 · The paper itself

Abstract

Human genetic studies recently identified an association of SNPs in the 17-β hydroxysteroid dehydrogenase 13 (HSD17B13) gene with alcoholic and nonalcoholic fatty liver disease development. Mutant HSD17B13 variants devoid of enzymatic function have been demonstrated to be protective from cirrhosis and liver cancer, supporting the development of HSD17B13 as a promising therapeutic target. Previous studies have demonstrated that HSD17B13 is a lipid droplet (LD)-associated protein. However, the critical domains that drive LD targeting or determine the enzymatic activity have yet to be defined. Here we used mutagenesis to generate multiple truncated and point-mutated proteins and were able to demonstrate in vitro that the N-terminal hydrophobic domain, PAT-like domain, and a putative α-helix/β-sheet/α-helix domain in HSD17B13 are all critical for LD targeting. Similarly, we characterized the predicted catalytic, substrate-binding, and homodimer interaction sites and found them to be essential for the enzymatic activity of HSD17B13, in addition to our previous identification of amino acid P260 and cofactor binding site. In conclusion, we identified critical domains and amino acid sites that are essential for the LD localization and protein function of HSD17B13, which may facilitate understanding of its function and targeting of this protein to treat chronic liver diseases.

Indexed as

17-Hydroxysteroid DehydrogenasesCells, CulturedChronic DiseaseHumansLiver DiseasesSmall Molecule Libraries17-Hydroxysteroid DehydrogenasesHSD17B13 protein, humanSmall Molecule Librariesalcoholic liver diseaseenzyme regulationlipid dropletsnonalcoholic fatty liver diseaseprotein structureretinoids

Identifiers

PMID32973038
PMCPMC7604732
OpenAlexW3089284732

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.