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PsychedeliaDokholyan Laboratory
TargetEnzymes

3-hydroxyacyl-CoA dehydrogenase type-2

Named enzymes, including the metabolising cytochromes and the monoamine oxidases.

Measurements
17
Compounds
9
Binding constants
0
Median pX
—

I · Identity

What this target is

Its function as UniProt states it, where in a cell the protein is found, and which cell types and tissues transcribe its gene.

Protein

HCD2_HUMANHSD17B10Homo sapiens

3-hydroxyacyl-CoA dehydrogenase type-2

Mitochondrial dehydrogenase involved in pathways of fatty acid, branched-chain amino acid and steroid metabolism10600649,12917011,18996107,19706438,20077426,25925575,26950678,28888424,9553139. 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-CoA10600649,12917011,25925575,26950678,9553139. 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 pathway18996107,19706438,20077426. 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 acids10600649,12917011. Oxidizes allopregnanolone/brexanolone at the 3alpha-hydroxyl group, which is known to be critical for the activation of gamma-aminobutyric acid receptors (GABAARs) chloride channel19706438,28888424. 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 apoptosis26338420. By interacting with intracellular amyloid-beta, it may contribute to the neuronal dysfunction associated with Alzheimer disease (AD)9338779. Essential for structural and functional integrity of mitochondria20077426
In addition to mitochondrial dehydrogenase activity, moonlights as a component of mitochondrial ribonuclease P, a complex that cleaves tRNA molecules in their 5'-ends18984158,24549042,25925575,26950678,28888424. 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 activity23042678,29040705. 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 subunit23042678,25925575,28888424. 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 enzyme29040705. Associates with mitochondrial DNA complexes at the nucleoids to initiate RNA processing and ribosome assembly

Quoted from UniProt’s FUNCTION annotation for Q99714 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

PartnerCombinedExperimentDatabaseText mining
TRMT10C0.9990.9770.9000.996
PRORP0.9990.9360.9000.993
ECHS10.9960.0650.9490.582
FSIP10.9820.0000.0000.982
ACAA20.9800.1870.9530.429
HUWE10.9750.2920.0000.964
HADHA0.9730.1520.9370.444
HADHB0.9710.1310.9250.423
ACAA10.9690.0000.9460.384
EHHADH0.9650.0650.9370.389

Where it sits in the cell

UniProt, curated Mitochondrion · Mitochondrion matrix, mitochondrion nucleoid

Expression by cell type

Single cell type RNA, the 5 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

  • Hepatocytes513.5 nCPM
  • Esophageal suprabasal cells430.1 nCPM
  • Esophageal basal cells262.8 nCPM
  • Extravillous trophoblasts262.8 nCPM
  • Esophageal apical cells262.4 nCPM

II · Anatomy

Where the gene is transcribed

The same two atlases the compound plates use, asked about this gene alone. Brain on the left, peripheral and autonomic tissues on the right.

Brain

cerebral cortex — 39.9 nTPM, from HSD17B10cerebellum — 25.5 nTPM, from HSD17B10hippocampal formation — 42.7 nTPM, from HSD17B10amygdala — 47.1 nTPM, from HSD17B10hypothalamus — 50.4 nTPM, from HSD17B10thalamus — no resolved target expressed herebasal ganglia — 52.1 nTPM, from HSD17B10medulla oblongata — no resolved target expressed here

basal ganglia: drawn as the caudate nucleus, putamen and globus pallidus.

Measured but not drawn — this anatomogram has no outline for them: pituitary gland 61.7, midbrain 60.6, spinal cord 55.4, retina 9.4.

Body

heart — 96.9 nTPM, from HSD17B10smooth muscle — 56.4 nTPM, from HSD17B10lung — 45.7 nTPM, from HSD17B10liver — 240.8 nTPM, from HSD17B10kidney — 97.4 nTPM, from HSD17B10stomach — 62.1 nTPM, from HSD17B10duodenum — 52.6 nTPM, from HSD17B10small intestine — 46.1 nTPM, from HSD17B10colon — 58.7 nTPM, from HSD17B10adrenal gland — 103.9 nTPM, from HSD17B10thyroid gland — 61.3 nTPM, from HSD17B10pancreas — 70.3 nTPM, from HSD17B10urinary bladder — 50.6 nTPM, from HSD17B10skeletal muscle — 85.8 nTPM, from HSD17B10spleen — 48.1 nTPM, from HSD17B10salivary gland — 51.2 nTPM, from HSD17B10
0241 nTPM

Square-root ramp · shared scale across both plates

Shading is transcript level — not affinity, and not affinity combined with expression. Outlined but unshaded organs hold none of HSD17B10 transcript above the atlas’s detection threshold. Anatomy from EMBL-EBI Anatomogram (Apache License 2.0); regions identified by Uberon (uberon.org), CC BY 3.0.

Brain · 10

  • pituitary gland61.7 nTPM
  • midbrain60.6 nTPM
  • spinal cord55.4 nTPM
  • basal ganglia52.1 nTPM
  • hypothalamus50.4 nTPM
  • amygdala47.1 nTPM
  • hippocampal formation42.7 nTPM
  • cerebral cortex39.9 nTPM
  • cerebellum25.5 nTPM
  • retina9.4 nTPM

Peripheral and autonomic · 16

  • liver240.8 nTPM
  • adrenal gland103.9 nTPM
  • kidney97.4 nTPM
  • heart muscle96.9 nTPM
  • skeletal muscle85.8 nTPM
  • pancreas70.3 nTPM
  • stomach 162.1 nTPM
  • thyroid gland61.3 nTPM
  • colon58.7 nTPM
  • smooth muscle56.4 nTPM
  • duodenum52.6 nTPM
  • salivary gland51.2 nTPM
  • urinary bladder50.6 nTPM
  • spleen48.1 nTPM
  • small intestine46.1 nTPM
  • lung45.7 nTPM

Transcript is not protein. These are RNA levels for HSD17B10, shaded on √nTPM so that a three-order range stays legible — on a linear ramp every region but the strongest would read as blank, which looks like absence rather than less. A region carrying no shading is one the atlas reports no consensus value for, not one where the gene is silent. And a gene being transcribed somewhere is not evidence that any compound reaches it. Human Protein Atlas, RNA expression, nTPM (normalized transcripts per million), consensus tissue dataset.

IV · Evidence

Every measurement at this target

Each row links to the ChEMBL assay it came from.

Functional readouts 17

IC₅₀, EC₅₀, AC₅₀ and potency. Assay-dependent, and not interchangeable with a binding constant.

TargetClassTypeValue (nM)pXOrganismAssay
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613910
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613910
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613910
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613910
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613910
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613910
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613910
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613910
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613910
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613910
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613910
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613910
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1613910
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614227
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614227
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614227
3-hydroxyacyl-CoA dehydrogenase type-2EnzymesPotency— no normalized value— value does not convert to pXHomo sapiensCHEMBL1614227
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