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HSD17B10 - hydroxysteroid 17-beta dehydrogenase 10 (human)

Gene
Symbol
Dates
  • Create:
    2016-09-14
  • Modify:
    2025-01-29
Description
This gene encodes 3-hydroxyacyl-CoA dehydrogenase type II, a member of the short-chain dehydrogenase/reductase superfamily. The gene product is a mitochondrial protein that catalyzes the oxidation of a wide variety of fatty acids and steroids, and is a subunit of mitochondrial ribonuclease P, which is involved in tRNA maturation. The protein has been implicated in the development of Alzheimer disease, and mutations in the gene are the cause of 17beta-hydroxysteroid dehydrogenase type 10 (HSD10) deficiency. Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined. [provided by RefSeq, Aug 2014]
Enables oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor and tRNA binding activity. Involved in several processes, including carboxylic acid catabolic process; mitochondrial tRNA processing; and steroid metabolic process. Located in mitochondrial nucleoid. Part of mitochondrial ribonuclease P complex and tRNA methyltransferase complex. Implicated in pheochromocytoma and syndromic X-linked intellectual disability type 10. Biomarker of Alzheimer's disease and osteosarcoma.

The HSD17B10 gene provides instructions for making a protein called HSD10. This protein is located within mitochondria, the energy-producing centers inside cells, where it has several different functions.

The HSD10 protein is important for the production (synthesis) of proteins in mitochondria. (While most protein synthesis occurs in the fluid surrounding the nucleus, called the cytoplasm, a few proteins are synthesized in the mitochondria.) During protein synthesis, whether in the cytoplasm or in mitochondria, molecules called transfer RNAs (tRNAs) help assemble protein building blocks (amino acids) into the chains that form proteins. The HSD10 protein is involved in making functional mitochondrial tRNA. It forms a complex with an enzyme called TRMT10C to modify tRNAs so that they are more stable and can function properly. In addition, the complex interacts with another enzyme called PRORP to perform an enzymatic function called mitochondrial RNase P (mtRNase P) that cuts precursor RNA molecules, which is an essential step to generating tRNA molecules. Normal mitochondrial protein production, which requires tRNAs, is essential for the formation of the protein complexes that convert the energy from food into a form cells can use.

The HSD10 protein also plays an important role in processing several substances in the body. It helps break down the amino acid isoleucine. Specifically, it is responsible for the fifth step in this process, in which 2-methyl-3-hydroxybutyryl-CoA is converted into 2-methylacetoacetyl-CoA. Through a similar mechanism, the HSD10 protein also processes a group of fats called branched-chain fatty acids.

The HSD10 protein is also thought to be involved in chemical reactions involving female sex hormones (estrogens) and male sex hormones (androgens). HSD10 turns off (inactivates) a potent form of estrogen called 17β-estradiol by converting it to a weaker form called estrone. HSD10 also generates a potent androgen called dihydrotestosterone from a weak androgen called 3α-androstanediol. These reactions are critical for maintaining appropriate levels of male and female sex hormones.

The HSD10 protein also plays a role in certain chemical reactions involving neurosteroids, which are substances that regulate the activity of the nervous system. This protein inactivates two neurosteroids called allopregnanolone and allotetrahydrodeoxycorticosterone. These neurosteroids interact with receptors that prevent the brain from being overloaded with too many signals. By regulating the activity of these neurosteroids, the HSD10 protein may help maintain normal brain function. However, other proteins in the body can also carry out these reactions, and the importance of HSD10 in these functions is unclear.

1 Names and Identifiers

1.1 Synonyms

  • 17b-HSD10
  • ABAD
  • CAMR
  • DUPXp11.22
  • ERAB
  • HADH2
  • HCD2
  • HSD10MD
  • MHBD
  • MRPP2
  • MRX17
  • MRX31
  • MRXS10
  • SCHAD
  • SDR5C1
  • 3-hydroxyacyl-CoA dehydrogenase type-2
  • 3-hydroxy-2-methylbutyryl-CoA dehydrogenase
  • AB-binding alcohol dehydrogenase
  • amyloid-beta peptide binding alcohol dehydrogenase
  • endoplasmic reticulum-associated amyloid beta-peptide-binding protein
  • mitochondrial RNase P subunit 2
  • mitochondrial ribonuclease P protein 2
  • short chain L-3-hydroxyacyl-CoA dehydrogenase type 2
  • short chain type dehydrogenase/reductase XH98G2

1.2 Other Identifiers

1.2.1 HGNC ID

1.2.2 Ensembl ID

1.2.3 Alliance Gene ID

1.2.4 Bgee Gene ID

1.2.5 Enzyme Commission (EC) Number

1.2.6 GenCC ID

1.2.7 KEGG Gene

1.2.8 MIM Number

1.2.9 Open Targets ID

1.2.10 PharmGKB ID

1.2.11 Pharos Target

1.2.12 VEuPathDB ID

1.2.13 Wikidata

3 Proteins

3.1 Protein Function

Mitochondrial dehydrogenase involved in pathways of fatty acid, branched-chain amino acid and steroid metabolism (PMID: 10600649, PMID: 12917011, PMID: 18996107, PMID: 19706438, PMID: 20077426, PMID: 25925575, PMID: 26950678, PMID: 28888424, PMID: 9553139). Acts as (S)-3-hydroxyacyl-CoA dehydrogenase in mitochondrial fatty acid beta-oxidation, a major degradation pathway of fatty acids. Catalyzes the third step in the beta-oxidation cycle, namely the reversible conversion of (S)-3-hydroxyacyl-CoA to 3-ketoacyl-CoA. Preferentially accepts straight medium- and short-chain acyl-CoA substrates with highest efficiency for (3S)-hydroxybutanoyl-CoA (PMID: 10600649, PMID: 12917011, PMID: 25925575, PMID: 26950678, PMID: 9553139). Acts as 3-hydroxy-2-methylbutyryl-CoA dehydrogenase in branched-chain amino acid catabolic pathway. Catalyzes the oxidation of 3-hydroxy-2-methylbutanoyl-CoA into 2-methyl-3-oxobutanoyl-CoA, a step in isoleucine degradation pathway (PMID: 18996107, PMID: 19706438, PMID: 20077426). Has hydroxysteroid dehydrogenase activity toward steroid hormones and bile acids. Catalyzes the oxidation of 3alpha-, 17beta-, 20beta- and 21-hydroxysteroids and 7alpha- and 7beta-hydroxy bile acids (PMID: 10600649, PMID: 12917011). Oxidizes allopregnanolone/brexanolone at the 3alpha-hydroxyl group, which is known to be critical for the activation of gamma-aminobutyric acid receptors (GABAARs) chloride channel (PMID: 19706438, PMID: 28888424). Has phospholipase C-like activity toward cardiolipin and its oxidized species. Likely oxidizes the 2'-hydroxyl in the head group of cardiolipin to form a ketone intermediate that undergoes nucleophilic attack by water and fragments into diacylglycerol, dihydroxyacetone and orthophosphate. Has higher affinity for cardiolipin with oxidized fatty acids and may degrade these species during the oxidative stress response to protect cells from apoptosis (PMID: 26338420). By interacting with intracellular amyloid-beta, it may contribute to the neuronal dysfunction associated with Alzheimer disease (AD) (PMID: 9338779). Essential for structural and functional integrity of mitochondria (PMID: 20077426).

In addition to mitochondrial dehydrogenase activity, moonlights as a component of mitochondrial ribonuclease P, a complex that cleaves tRNA molecules in their 5'-ends (PMID: 18984158, PMID: 24549042, PMID: 25925575, PMID: 26950678, PMID: 28888424). Together with TRMT10C/MRPP1, forms a subcomplex of the mitochondrial ribonuclease P, named MRPP1-MRPP2 subcomplex, which displays functions that are independent of the ribonuclease P activity (PMID: 23042678, PMID: 29040705). The MRPP1-MRPP2 subcomplex catalyzes the formation of N(1)-methylguanine and N(1)-methyladenine at position 9 (m1G9 and m1A9, respectively) in tRNAs; HSD17B10/MRPP2 acting as a non-catalytic subunit (PMID: 23042678, PMID: 25925575, PMID: 28888424). The MRPP1-MRPP2 subcomplex also acts as a tRNA maturation platform: following 5'-end cleavage by the mitochondrial ribonuclease P complex, the MRPP1-MRPP2 subcomplex enhances the efficiency of 3'-processing catalyzed by ELAC2, retains the tRNA product after ELAC2 processing and presents the nascent tRNA to the mitochondrial CCA tRNA nucleotidyltransferase TRNT1 enzyme (PMID: 29040705). Associates with mitochondrial DNA complexes at the nucleoids to initiate RNA processing and ribosome assembly.

3.2 Protein Isoforms

Isoform
Isoform 1
UniProt ID
RefSeq Accession
Isoform
Isoform 2
UniProt ID
RefSeq Accession

3.3 Protein 3D Structures

3.3.1 PDB Structures

3.3.2 NCBI Protein Structures

3.3.3 AlphaFold Structures

Highly accurate protein structure prediction with AlphaFold. Nature. 2021 Aug;596(7873):583-589. DOI:10.1038/s41586-021-03819-2. PMID:34265844; PMCID:PMC8371605

3.4 Protein Targets

4 Chemicals and Bioactivities

4.1 Tested Compounds

5 BioAssays

5.1 Small-Molecule BioAssays

5.2 RNAi BioAssays

6 Diseases and Phenotypes

6.1 GHR Health Conditions

6.2 KEGG Diseases

6.3 OMIM Phenotypes

6.4 MedGen Diseases

6.5 Gene-Disease Associations

7 Interactions and Pathways

7.1 Chemical-Gene Interactions

7.2 Interactions

7.3 Pathways

8 Biochemical Reactions

9 Cell Lines

10 Expression

11 Target Development Level

12 Literature

12.1 Consolidated References

12.2 Gene-Chemical Co-Occurrences in Literature

12.3 Gene-Gene Co-Occurrences in Literature

12.4 Gene-Disease Co-Occurrences in Literature

13 Patents

13.1 Gene-Chemical Co-Occurrences in Patents

13.2 Gene-Gene Co-Occurrences in Patents

13.3 Gene-Disease Co-Occurrences in Patents

14 Classification

14.1 Gene Family

14.2 Gene Ontology: Biological Process

14.3 Gene Ontology: Cellular Component

14.4 Gene Ontology: Molecular Function

14.5 ChEMBL Target Tree

15 Information Sources

  1. NCBI Gene
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  2. PubChem
  3. Alliance of Genome Resources
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    https://www.alliancegenome.org/privacy-warranty-licensing
  4. MedlinePlus Genetics
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    https://medlineplus.gov/about/using/usingcontent/
  5. BioGRID
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    The MIT License (MIT); Copyright Mike Tyers Lab
    https://wiki.thebiogrid.org/doku.php/terms_and_conditions
  6. STRING: functional protein association networks
  7. Comparative Toxicogenomics Database (CTD)
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    http://ctdbase.org/about/legal.jsp
  8. Drug Gene Interaction database (DGIdb)
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    http://www.dgidb.org/downloads
  9. DrugBank
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    https://www.drugbank.ca/legal/terms_of_use
  10. Open Targets
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    https://platform-docs.opentargets.org/licence
  11. Dependency Map (DepMap)
  12. Gene Curation Coalition (GenCC)
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    The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication.
    https://thegencc.org/terms.html
    HSD17B10
  13. HUGO Gene Nomenclature Committee (HGNC)
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  14. KEGG
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  15. NCBI Gene Expression Omnibus (GEO)
  16. NCBI MedGen
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  17. NCBI Structure
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  18. Online Mendelian Inheritance in Man (OMIM)
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    https://omim.org/help/copyright
  19. PharmGKB
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    https://www.pharmgkb.org/page/policies
  20. Pharos
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    https://pharos.nih.gov/about
  21. RCSB Protein Data Bank (RCSB PDB)
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    https://www.rcsb.org/pages/policies
  22. Swiss Institute of Bioinformatics Bgee
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    https://www.bgee.org/about/
  23. UniProt
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    https://www.uniprot.org/help/license
  24. VEuPathDB: The Eukaryotic Pathogen, Vector and Host Informatics Resource
    LICENSE
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    https://veupathdb.org/veupathdb/app/static-content/about.html
  25. Wikidata
  26. ChEMBL
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    http://www.ebi.ac.uk/Information/termsofuse.html
  27. Gene Ontology (GO)
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    http://geneontology.org/docs/go-citation-policy/
  28. AlphaFold DB
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    All of the data provided is freely available for both academic and commercial use under Creative Commons Attribution 4.0 (CC-BY 4.0) licence terms.
    https://alphafold.ebi.ac.uk/faq
  29. Rhea - annotated reactions database
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