HSD17B10 (also known as HADH2, SCHAD, SDR5C1, MRPP2, and historically ERAB/ABAD) is a mitochondrial-matrix protein of the short-chain dehydrogenase/reductase (SDR) family that acts as a functional homotetramer and is a genuinely moonlighting, multifunctional enzyme. In its catalytic role it is an NAD+-dependent dehydrogenase whose physiologically important activity is (S)-2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) in L-isoleucine catabolism, oxidizing (2S,3S)-3-hydroxy-2-methylbutanoyl-CoA to 2-methyl-3-oxobutanoyl-CoA. It has broad (S)-3-hydroxyacyl-CoA dehydrogenase activity on short/medium straight-chain acyl-CoAs and weaker intrinsic 17-beta-/3-alpha-hydroxysteroid and alcohol dehydrogenase activities toward steroid hormones (including the neurosteroid allopregnanolone/brexanolone), bile acids and other substrates. Independently of its enzymatic activity, it moonlights as MRPP2, an essential non-catalytic subunit of mitochondrial RNase P (together with the methyltransferase TRMT10C/MRPP1 and the nuclease PRORP/MRPP3), which performs 5'-end processing of mitochondrial tRNAs; the TRMT10C-HSD17B10 subcomplex additionally catalyzes N1-methylation of purine-9 (m1A9/m1G9) of mt-tRNAs and acts as a tRNA-maturation platform that supports downstream 3'-processing by ELAC2 and 3'-CCA addition by TRNT1. It localizes to the mitochondrial matrix and associates with the mitochondrial nucleoid. Loss-of-function mutations in the X-linked HSD17B10 gene cause HSD10 mitochondrial disease (a progressive infantile/childhood neurodegeneration with cardiomyopathy), and disease severity tracks with the RNase P/tRNA-processing and mitochondrial-integrity defect rather than with residual dehydrogenase activity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004303 estradiol 17-beta-dehydrogenase [NAD(P)+] activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetically inferred 17-beta-estradiol dehydrogenase activity. This is a real but weak intrinsic in-vitro activity of HSD17B10 (its k_cat for 17-beta-oestradiol is orders of magnitude below the 3-hydroxyacyl-CoA activity), not its physiological core function. Kept as a valid but non-core side activity. Reason: Confirmed intrinsic activity but of low catalytic efficiency and not the evolved core function; the steroid activities are minor relative to 3-hydroxyacyl-CoA/MHBD chemistry. Supporting Evidence: PMID:10600649 The k(cat) of the ADH activity was three orders of magnitude less than the l-3-hydroxyacyl-CoA dehydrogenase activity but was comparable with that of the enzyme's hydroxysteroid dehydrogenase (HSD) activity for oxidizing 17beta-oestradiol |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of mitochondrial localization, consistent with all experimental data placing HSD17B10 in the mitochondrion (matrix/nucleoid). Supporting Evidence: file:human/HSD17B10/HSD17B10-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0006631 fatty acid metabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Broad fatty-acid metabolic process, phylogenetically inferred. HSD17B10 does act as a (S)-3-hydroxyacyl-CoA dehydrogenase, but the more specific and better supported process annotations are fatty acid beta-oxidation and isoleucine catabolism. Kept as a correct but general, non-core parent. Reason: Correct but too general; more specific child processes (beta-oxidation, isoleucine catabolism) are separately annotated. |
| GO:0008209 androgen metabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Androgen metabolic process inferred phylogenetically. Reflects the weak in-vitro testosterone/androstanediol dehydrogenase side activities; not a demonstrated physiological role. Kept as non-core. Reason: Minor in-vitro steroid side activity, not the evolved core function. |
| GO:0008210 estrogen metabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Estrogen metabolic process inferred phylogenetically; reflects weak in-vitro 17-beta-estradiol dehydrogenase side activity. Kept as non-core. Reason: Minor in-vitro steroid side activity, not the evolved core function. |
| GO:0003857 (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (Rhea/EC 1.1.1.35) assignment of (3S)-3-hydroxyacyl-CoA dehydrogenase activity. This is a genuine, well-established core catalytic activity of HSD17B10, independently supported by multiple experimental annotations below. Accept. Supporting Evidence: PMID:9553139 This NAD+-dependent dehydrogenase catalyzes the reversible oxidation of L-3-hydroxyacyl-CoAs to form 3-ketoacyl-CoAs, but it does not act on the D-isomers. |
| GO:0004022 alcohol dehydrogenase (NAD+) activity | IEA GO_REF:0000116 | MARK AS OVER ANNOTATED | Summary: Generic alcohol dehydrogenase (NAD+) activity assigned electronically from Rhea corticosteroid/steroid reactions. HSD17B10 does have a very weak intrinsic alcohol dehydrogenase activity (e.g. on 2-propanol), but this broad term is an over-annotation of what is really a hydroxysteroid/hydroxyacyl-CoA dehydrogenase; the generic parent is uninformative for this gene. Reason: Over-broad electronic term; the real chemistry is hydroxysteroid/hydroxyacyl-CoA dehydrogenation and the generic ADH activity is trivial and misleading. Supporting Evidence: PMID:10600649 The k(cat) of the ADH activity was three orders of magnitude less than the l-3-hydroxyacyl-CoA dehydrogenase activity |
| GO:0004303 estradiol 17-beta-dehydrogenase [NAD(P)+] activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic (Rhea/EC 1.1.1.62) assignment of 17-beta-estradiol dehydrogenase activity. Real but weak intrinsic side activity; kept as non-core (see the corresponding experimental annotations). Reason: Minor in-vitro steroid side activity, not the evolved core function. |
| GO:0005739 mitochondrion | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic mitochondrial localization, consistent with all experimental data. Supporting Evidence: file:human/HSD17B10/HSD17B10-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion |
| GO:0008709 cholate 7-alpha-dehydrogenase (NAD+) activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic (Rhea/EC 1.1.1.159) assignment of cholate 7-alpha-dehydrogenase activity, matching the in-vitro bile-acid activity characterized for the human enzyme. Real but non-core (in-vitro bile-acid metabolism). Reason: In-vitro bile-acid side activity, not the evolved core function. Supporting Evidence: PMID:12917011 the human orthologue oxidizes the 7alpha-OH of chenodeoxycholic acid (5beta-cholanic acid, 3alpha,7alpha-diol) and cholic acid |
| GO:0016509 long-chain (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity | IEA GO_REF:0000116 | MARK AS OVER ANNOTATED | Summary: Electronic (Rhea:31159, hydroxyhexadecanoyl-CoA) assignment of LONG-chain 3-hydroxyacyl-CoA dehydrogenase activity. HSD17B10 actually PREFERS short- and medium-chain substrates and is a poor long-chain enzyme; this specific long-chain child term over-states its chain-length specificity. Reason: HSD17B10 preferentially accepts straight medium- and short-chain acyl-CoA; the long-chain-specific term misrepresents its substrate preference. Supporting Evidence: file:human/HSD17B10/HSD17B10-uniprot.txt Preferentially accepts straight medium- and short-chain acyl-CoA substrates |
| GO:0042645 mitochondrial nucleoid | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic (UniProt SubCell) mitochondrial-nucleoid localization, supported experimentally: HSD17B10 (as part of the RNase P machinery) associates with mtDNA nucleoids to initiate RNA processing. Supporting Evidence: PMID:24703694 mitochondrial RNA processing enzymes involved in tRNA excision, ribonuclease P (RNase P) and ELAC2, as well as a subset of nascent mitochondrial ribosomal proteins (MRPs) associate with nucleoids to initiate RNA processing and ribosome assembly |
| GO:0044594 17-beta-hydroxysteroid dehydrogenase (NAD+) activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: Electronic (Rhea:41992) assignment of 17-beta-hydroxysteroid dehydrogenase activity; corresponds to the enzyme's name-giving but catalytically weak steroid side activity. Kept as non-core. Reason: Minor in-vitro steroid side activity, not the evolved core function. |
| GO:0047015 3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (Rhea:13281/EC 1.1.1.178) assignment of 2-methyl-3-hydroxybutyryl-CoA (MHBD) dehydrogenase activity. This is the physiologically most important catalytic activity of HSD17B10 (isoleucine catabolism) and is strongly supported experimentally. Accept as a core molecular function. Supporting Evidence: file:human/HSD17B10/HSD17B10-uniprot.txt Reaction=(2S,3S)-3-hydroxy-2-methylbutanoyl-CoA + NAD(+) = 2-methyl-3- |
| GO:0047035 testosterone dehydrogenase (NAD+) activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic (Rhea:14929/EC 1.1.1.239) assignment of testosterone dehydrogenase activity; a demonstrated in-vitro steroid side activity (see IDA below). Kept as non-core. Reason: In-vitro steroid side activity, not the evolved core function. |
| GO:0047044 androstan-3-alpha,17-beta-diol dehydrogenase (NAD+) activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic (Rhea:42004/EC 1.1.1.53) assignment of androstanediol dehydrogenase activity, matching the in-vitro 3-alpha-hydroxysteroid activity. Non-core. Reason: In-vitro steroid side activity, not the evolved core function. |
| GO:0106281 chenodeoxycholate 7-alpha-dehydrogenase (NAD+) activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: Electronic (Rhea:42036) bile-acid 7-alpha-dehydrogenase activity, also supported by IDA (PMID:12917011). Real but non-core in-vitro bile-acid activity. Reason: In-vitro bile-acid side activity, not the evolved core function. |
| GO:0106282 isoursodeoxycholate 7-beta-dehydrogenase (NAD+) activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: Electronic (Rhea:42024) bile-acid 7-beta-dehydrogenase activity, supported by IDA (PMID:12917011). Non-core in-vitro bile-acid activity. Reason: In-vitro bile-acid side activity, not the evolved core function. |
| GO:0106283 ursodeoxycholate 7-beta-dehydrogenase (NAD+) activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: Electronic (Rhea:42028) bile-acid 7-beta-dehydrogenase activity, supported by IDA (PMID:12917011). Non-core in-vitro bile-acid activity. Reason: In-vitro bile-acid side activity, not the evolved core function. |
| GO:0005515 protein binding | IPI PMID:18984158 RNase P without RNA: identification and functional reconstit... | MARK AS OVER ANNOTATED | Summary: IPI protein-binding to TRMT10C (Q7L0Y3), from the study that identified HSD17B10/MRPP2 as a mitochondrial RNase P subunit. The interaction is real and biologically central (MRPP1-MRPP2 subcomplex), but the bare "protein binding" term is uninformative; the functional consequence is captured by the RNase P complex / tRNA-processing annotations. Reason: Uninformative generic protein-binding term; the meaningful TRMT10C interaction is captured by the mitochondrial RNase P complex and tRNA-processing annotations. Supporting Evidence: PMID:18984158 composed of a tRNA methyltransferase, a short-chain dehydrogenase/reductase- family member, and a protein of hitherto unknown functional and evolutionary origin |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: IPI protein-binding to TRMT10C (Q7L0Y3) from a large-scale interactome study. Bare "protein binding" is uninformative; functional meaning captured elsewhere. Reason: Uninformative generic protein-binding term. |
| GO:0005515 protein binding | IPI PMID:29128334 A Map of Human Mitochondrial Protein Interactions Linked to ... | MARK AS OVER ANNOTATED | Summary: IPI protein-binding to EEF2 (P13639) from a mitochondrial neurodegeneration interactome map. Bare "protein binding" is uninformative and this interaction has no established functional role for HSD17B10. Reason: Uninformative generic protein-binding term; interaction of unclear significance. |
| GO:0005515 protein binding | IPI PMID:29128334 A Map of Human Mitochondrial Protein Interactions Linked to ... | MARK AS OVER ANNOTATED | Summary: IPI protein-binding to TRAP1 (Q12931) from a mitochondrial interactome map. Bare "protein binding" is uninformative; no established functional role. Reason: Uninformative generic protein-binding term; interaction of unclear significance. |
| GO:0005515 protein binding | IPI PMID:29880640 Structural insight into the human mitochondrial tRNA purine ... | MARK AS OVER ANNOTATED | Summary: IPI protein-binding to TRMT10C (Q7L0Y3) from the structural study of the MRPP1/MRPP2 complex. Real and central, but bare "protein binding" is uninformative; captured by the RNase P/methyltransferase complex annotations. Reason: Uninformative generic protein-binding term; the TRMT10C interaction is captured by the complex/process annotations. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: IPI protein-binding to APP/amyloid-beta (P05067) from a neurodegenerative-disease interactome study. The AΞ² interaction (ABAD/ERAB) is a real disease-association but is non-core; the bare term is uninformative. Reason: Uninformative generic protein-binding term; AΞ² interaction is a disease association, not a core function. |
| GO:0005515 protein binding | IPI PMID:32825572 Study of Biomolecular Interactions of Mitochondrial Proteins... | MARK AS OVER ANNOTATED | Summary: IPI protein-binding to APP/amyloid-beta processed peptide (P05067-PRO_0000000092) from a study of Alzheimer-related mitochondrial protein interactions. Non-core disease association; bare term uninformative. Reason: Uninformative generic protein-binding term; AΞ² interaction is a disease association, not a core function. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: IPI protein-binding to TRMT10C (Q7L0Y3) from a proteome-scale interactome study. Bare "protein binding" uninformative; functional meaning captured elsewhere. Reason: Uninformative generic protein-binding term. |
| GO:0005515 protein binding | IPI PMID:9338779 An intracellular protein that binds amyloid-beta peptide and... | MARK AS OVER ANNOTATED | Summary: IPI protein-binding to APP/amyloid-beta (P05067) from the original ERAB/AΞ² discovery paper. Real disease-association interaction but non-core; the bare term is uninformative. Reason: Uninformative generic protein-binding term; AΞ² interaction is a disease association, not a core function. |
| GO:0006550 L-isoleucine catabolic process | IEA GO_REF:0000041 | ACCEPT | Summary: Electronic (UniPathway) assignment of L-isoleucine catabolism, the pathway in which HSD17B10's MHBD activity acts. Strongly supported experimentally (see IDA annotations). Core biological process. Supporting Evidence: PMID:20077426 the mitochondrial enzyme 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) involved in isoleucine metabolism |
| GO:0006635 fatty acid beta-oxidation | IEA GO_REF:0000041 | ACCEPT | Summary: Electronic (UniPathway) assignment of fatty acid beta-oxidation, where HSD17B10 acts as a short/medium-chain (S)-3-hydroxyacyl-CoA dehydrogenase (third step of the cycle). Supported by IDA (PMID:12917011). Accept. Supporting Evidence: file:human/HSD17B10/HSD17B10-uniprot.txt Acts as (S)-3-hydroxyacyl-CoA dehydrogenase in mitochondrial fatty acid |
| GO:0006699 bile acid biosynthetic process | IEA GO_REF:0000041 | KEEP AS NON CORE | Summary: Electronic (UniPathway) assignment of bile-acid metabolism, reflecting the in-vitro bile-acid (7-alpha/7-beta-hydroxy) dehydrogenase activities. A real but in-vitro, non-core role. Kept as non-core. Reason: Based on in-vitro bile-acid dehydrogenase activities; physiological contribution to bile-acid biosynthesis is not established. |
| GO:0160241 cardiolipin dehydrogenase (NAD+) activity | IDA PMID:26338420 Myxococcus CsgA, Drosophila Sniffer, and human HSD10 are car... | KEEP AS NON CORE | Summary: IDA for a phospholipase C-like / cardiolipin-oxidizing activity, with a preference for cardiolipin bearing oxidized fatty acids, proposed to protect against reactive oxygen species. Experimentally supported in vitro but a distinct, non-core moonlighting activity. Keep as non-core. Reason: Experimentally supported in-vitro activity but a separate moonlighting role, not the evolved core (isoleucine/tRNA) functions. Supporting Evidence: PMID:26338420 HSD10 exhibits a strong preference for cardiolipin with oxidized fatty acids. |
| GO:0047035 testosterone dehydrogenase (NAD+) activity | IDA PMID:28888424 Novel patient missense mutations in the HSD17B10 gene affect... | KEEP AS NON CORE | Summary: IDA testosterone dehydrogenase activity from biochemical characterization of the recombinant enzyme. A demonstrated in-vitro steroid side activity; kept as non-core. Reason: In-vitro steroid side activity, not the evolved core function. |
| GO:0001680 tRNA 3'-terminal CCA addition | IDA PMID:38824131 Structural basis for human mitochondrial tRNA maturation. | KEEP AS NON CORE | Summary: IDA (ComplexPortal) involvement in 3'-CCA addition: cryo-EM shows the TRMT10C/SDR5C1 maturation platform retains the tRNA and presents it to the CCA-adding enzyme TRNT1. HSD17B10 participates as part of the platform rather than catalyzing CCA addition itself. Accept as a valid (non-core) process role. Reason: Real platform role in CCA addition, but ancillary to the core 5'-processing/ RNase P function; HSD17B10 does not itself add CCA. Supporting Evidence: PMID:29040705 presents the nascent tRNA to the mitochondrial CCA-adding enzyme |
| GO:0005739 mitochondrion | NAS PMID:21593607 Involvement of human ELAC2 gene product in 3' end processing... | ACCEPT | Summary: NAS mitochondrial localization; consistent with all experimental evidence. |
| GO:0042780 tRNA 3'-end processing | IDA PMID:39516281 Structural basis of 3'-tRNA maturation by the human mitochon... | KEEP AS NON CORE | Summary: IDA (ComplexPortal) involvement in tRNA 3'-end processing: cryo-EM of the mitochondrial RNase Z complex (ELAC2/SDR5C1/TRMT10C) shows the SDR5C1/TRMT10C platform supports ELAC2-catalyzed 3'-processing. A real, platform-associated role; kept as non-core relative to the 5'-processing core. Reason: Platform-supported 3'-processing role; ancillary to the core RNase P 5'-processing function. Supporting Evidence: PMID:29040705 significantly enhances the efficiency of ELAC2-catalyzed 3'-processing for 17 of the 22 tRNAs |
| GO:1902494 catalytic complex | IPI PMID:38824131 Structural basis for human mitochondrial tRNA maturation. | KEEP AS NON CORE | Summary: Part_of a catalytic complex (ComplexPortal), a generic parent of the mitochondrial RNase P / tRNA-maturation complexes HSD17B10 belongs to. Correct but very general; more specific complex terms (mitochondrial ribonuclease P complex, endoribonuclease complex) are separately annotated. Reason: Correct but over-general complex term; superseded by specific mitochondrial RNase P complex annotations. |
| GO:1902555 endoribonuclease complex | IDA PMID:39516281 Structural basis of 3'-tRNA maturation by the human mitochon... | KEEP AS NON CORE | Summary: IDA part_of an endoribonuclease complex (the mitochondrial RNase Z / ELAC2-SDR5C1-TRMT10C complex from cryo-EM). Correct but general; the specific mitochondrial RNase P complex term is the core CC. Reason: Correct but general complex term; the specific mitochondrial RNase P complex is the core cellular component. Supporting Evidence: PMID:39516281 cryo-EM structures of the mitochondrial RNase Z complex (ELAC2/SDR5C1/TRMT10C) |
| GO:0005739 mitochondrion | IDA PMID:29880640 Structural insight into the human mitochondrial tRNA purine ... | ACCEPT | Summary: IDA mitochondrial localization from the RNase P structural study. Accept. |
| GO:0030678 mitochondrial ribonuclease P complex | IPI PMID:29880640 Structural insight into the human mitochondrial tRNA purine ... | ACCEPT | Summary: Part_of the mitochondrial RNase P complex, from structural characterization of the MRPP1/MRPP2 (and RNase P) complexes. This is a core cellular component for HSD17B10/MRPP2. Accept. Supporting Evidence: PMID:29040705 The human mitochondrial RNase P is composed of three protein subunits: mitochondrial RNase P proteins 1, 2 and 3 (MRPP1, MRPP2 and MRPP3, respectively) |
| GO:0097745 mitochondrial tRNA 5'-end processing | IDA PMID:29880640 Structural insight into the human mitochondrial tRNA purine ... | ACCEPT | Summary: IDA involvement in mitochondrial tRNA 5'-end processing, the core RNase P function of HSD17B10/MRPP2. Accept as a core biological process. Supporting Evidence: PMID:18984158 extra nucleotides at their 5' ends are removed by an endonuclease called RNase P |
| GO:0003857 (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity | EXP PMID:10600649 Intrinsic alcohol dehydrogenase and hydroxysteroid dehydroge... | ACCEPT | Summary: EXP (3S)-3-hydroxyacyl-CoA dehydrogenase activity, kinetically characterized on the purified enzyme. Core catalytic activity. Accept. Supporting Evidence: PMID:10600649 The k(cat) of the ADH activity was three orders of magnitude less than the l-3-hydroxyacyl-CoA dehydrogenase activity |
| GO:0003857 (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity | EXP PMID:26950678 A novel HSD17B10 mutation impairing the activities of the mi... | ACCEPT | Summary: EXP 3-hydroxyacyl-CoA dehydrogenase activity, assayed together with RNase P activities for the K212E disease mutant. Core catalytic activity. Accept. Supporting Evidence: PMID:26950678 the p.K212E mutation impairs the SDR5C1-dependent mitochondrial RNase P activities |
| GO:0003857 (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity | EXP PMID:9553139 A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is id... | ACCEPT | Summary: EXP 3-hydroxyacyl-CoA dehydrogenase activity from cloning/characterization of the purified human brain enzyme. Core catalytic activity. Accept. Supporting Evidence: PMID:9553139 This NAD+-dependent dehydrogenase catalyzes the reversible oxidation of L-3-hydroxyacyl-CoAs to form 3-ketoacyl-CoAs, but it does not act on the D-isomers. |
| GO:0004303 estradiol 17-beta-dehydrogenase [NAD(P)+] activity | EXP PMID:10600649 Intrinsic alcohol dehydrogenase and hydroxysteroid dehydroge... | KEEP AS NON CORE | Summary: EXP 17-beta-estradiol dehydrogenase activity, kinetically characterized. Real but weak intrinsic steroid activity; kept as non-core. Reason: Weak in-vitro steroid side activity, not the evolved core function. Supporting Evidence: PMID:10600649 comparable with that of the enzyme's hydroxysteroid dehydrogenase (HSD) activity for oxidizing 17beta-oestradiol |
| GO:0004303 estradiol 17-beta-dehydrogenase [NAD(P)+] activity | EXP PMID:12917011 Expanded substrate screenings of human and Drosophila type 1... | KEEP AS NON CORE | Summary: EXP 17-beta-estradiol/hydroxysteroid dehydrogenase activity from the expanded substrate screen. Weak in-vitro steroid activity; non-core. Reason: Weak in-vitro steroid side activity, not the evolved core function. Supporting Evidence: PMID:12917011 3alpha-OH and 17beta-OH activities with sex steroids |
| GO:0005739 mitochondrion | EXP PMID:12917011 Expanded substrate screenings of human and Drosophila type 1... | ACCEPT | Summary: EXP mitochondrial localization by confocal/electron microscopy; the human enzyme carries an N-terminal mitochondrial targeting signal. Accept. Supporting Evidence: PMID:12917011 the human form is localized to mitochondria |
| GO:0005739 mitochondrion | EXP PMID:18984158 RNase P without RNA: identification and functional reconstit... | ACCEPT | Summary: EXP mitochondrial localization from the RNase P identification study. Accept. |
| GO:0047015 3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity | EXP PMID:20077426 A non-enzymatic function of 17beta-hydroxysteroid dehydrogen... | ACCEPT | Summary: EXP 2-methyl-3-hydroxybutyryl-CoA (MHBD) dehydrogenase activity, measured with the substrate 2-methyl-3-hydroxybutyryl-CoA on WT and disease-mutant enzymes. Core physiological catalytic activity (isoleucine catabolism). Accept. Supporting Evidence: PMID:20077426 substrate 2-methyl-3-hydroxybutyryl-CoA |
| GO:0005739 mitochondrion | IDA PMID:23042678 A subcomplex of human mitochondrial RNase P is a bifunctiona... | ACCEPT | Summary: IDA mitochondrial localization. Accept. |
| GO:0043527 tRNA methyltransferase complex | IPI PMID:23042678 A subcomplex of human mitochondrial RNase P is a bifunctiona... | ACCEPT | Summary: Part_of a tRNA methyltransferase complex: the MRPP1-MRPP2 (TRMT10C-SDR5C1) subcomplex is the m1A9/m1G9 methyltransferase, with HSD17B10 as the required non-catalytic partner. Accept as a valid cellular component (methyltransferase subcomplex of RNase P). Supporting Evidence: PMID:23042678 the human mitochondrial enzyme, moreover, requires a short-chain dehydrogenase as a partner protein |
| GO:0070901 mitochondrial tRNA methylation | IDA PMID:23042678 A subcomplex of human mitochondrial RNase P is a bifunctiona... | ACCEPT | Summary: IDA involvement in mitochondrial tRNA methylation (m1A9/m1G9 formation by the MRPP1-MRPP2 subcomplex). A genuine, experimentally supported role of the RNase P machinery HSD17B10 is part of. Accept. Supporting Evidence: PMID:23042678 is the methyltransferase responsible for m(1)G9 and m(1)A9 formation |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: HTP mitochondrial localization from a high-confidence mitochondrial proteome study. Consistent with all evidence. Accept. |
| GO:0106281 chenodeoxycholate 7-alpha-dehydrogenase (NAD+) activity | IDA PMID:12917011 Expanded substrate screenings of human and Drosophila type 1... | KEEP AS NON CORE | Summary: IDA bile-acid 7-alpha-dehydrogenase activity (chenodeoxycholate/cholate) from the expanded substrate screen. Real in-vitro bile-acid activity; non-core. Reason: In-vitro bile-acid side activity, not the evolved core function. Supporting Evidence: PMID:12917011 the human orthologue oxidizes the 7alpha-OH of chenodeoxycholic acid |
| GO:0106282 isoursodeoxycholate 7-beta-dehydrogenase (NAD+) activity | IDA PMID:12917011 Expanded substrate screenings of human and Drosophila type 1... | KEEP AS NON CORE | Summary: IDA bile-acid 7-beta-dehydrogenase activity on (iso)ursodeoxycholic acid from the substrate screen. Real in-vitro bile-acid activity; non-core. Reason: In-vitro bile-acid side activity, not the evolved core function. Supporting Evidence: PMID:12917011 act as 7beta-OH dehydrogenases of ursodeoxycholic or isoursodeoxycholic acid |
| GO:0106283 ursodeoxycholate 7-beta-dehydrogenase (NAD+) activity | IDA PMID:12917011 Expanded substrate screenings of human and Drosophila type 1... | KEEP AS NON CORE | Summary: IDA bile-acid 7-beta-dehydrogenase activity on ursodeoxycholic acid. Real in-vitro bile-acid activity; non-core. Reason: In-vitro bile-acid side activity, not the evolved core function. Supporting Evidence: PMID:12917011 act as 7beta-OH dehydrogenases of ursodeoxycholic or isoursodeoxycholic acid |
| GO:0006550 L-isoleucine catabolic process | IDA PMID:18996107 Study of patients and carriers with 2-methyl-3-hydroxybutyry... | ACCEPT | Summary: IDA involvement in L-isoleucine catabolism from clinical/biochemical study of MHBD-deficient patients (deficient MHBD activity, isoleucine-pathway metabolites). Core biological process. Accept. Supporting Evidence: PMID:18996107 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency |
| GO:0006550 L-isoleucine catabolic process | IDA PMID:19706438 Mental retardation linked to mutations in the HSD17B10 gene ... | ACCEPT | Summary: IDA involvement in isoleucine catabolism; the disease mutant fails to dehydrogenate 2-methyl-3-hydroxybutyryl-CoA. Core biological process. Accept. Supporting Evidence: PMID:19706438 HSD10(E249Q) was unable to catalyze the dehydrogenation of 2-methyl-3-hydroxybutyryl-CoA |
| GO:0044594 17-beta-hydroxysteroid dehydrogenase (NAD+) activity | IDA PMID:12917011 Expanded substrate screenings of human and Drosophila type 1... | KEEP AS NON CORE | Summary: IDA 17-beta-hydroxysteroid dehydrogenase activity from the expanded substrate screen. Real but weak intrinsic steroid activity; non-core. Reason: Weak in-vitro steroid side activity, not the evolved core function. Supporting Evidence: PMID:12917011 3alpha-OH and 17beta-OH activities with sex steroids |
| GO:0047015 3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity | IDA PMID:18996107 Study of patients and carriers with 2-methyl-3-hydroxybutyry... | ACCEPT | Summary: IDA MHBD activity measured in patient fibroblasts. Core physiological catalytic activity (isoleucine catabolism). Accept. Supporting Evidence: PMID:18996107 MHBD activity was clearly deficient in males |
| GO:0003857 (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity | IDA PMID:12917011 Expanded substrate screenings of human and Drosophila type 1... | ACCEPT | Summary: IDA (3S)-3-hydroxyacyl-CoA dehydrogenase activity from the substrate screen. Core catalytic activity. Accept. Supporting Evidence: PMID:12917011 In addition to the known hydroxyacyl-CoA dehydrogenase |
| GO:0006635 fatty acid beta-oxidation | IDA PMID:12917011 Expanded substrate screenings of human and Drosophila type 1... | ACCEPT | Summary: IDA involvement in fatty acid beta-oxidation (short/medium-chain 3-hydroxyacyl-CoA dehydrogenase step). Accept. Supporting Evidence: file:human/HSD17B10/HSD17B10-uniprot.txt Acts as (S)-3-hydroxyacyl-CoA dehydrogenase in mitochondrial fatty acid |
| GO:0006699 bile acid biosynthetic process | IDA PMID:12917011 Expanded substrate screenings of human and Drosophila type 1... | KEEP AS NON CORE | Summary: IDA involvement in bile-acid metabolism, from the in-vitro bile-acid dehydrogenase activities and bile-acid isomerization proposal. Real but in-vitro; physiological contribution unestablished. Non-core. Reason: Based on in-vitro bile-acid activities; physiological role in bile-acid biosynthesis not established. Supporting Evidence: PMID:12917011 participates in bile acid isomerization |
| GO:0008207 C21-steroid hormone metabolic process | IDA PMID:12917011 Expanded substrate screenings of human and Drosophila type 1... | KEEP AS NON CORE | Summary: IDA involvement in C21-steroid (glucocorticoid/gestagen) metabolism, from the 20-beta/21-OH oxidation activities. In-vitro steroid metabolism; non-core. Reason: In-vitro steroid metabolism, not the evolved core function. Supporting Evidence: PMID:12917011 oxidize the 20beta-OH and 21-OH groups in C21 steroids |
| GO:0008209 androgen metabolic process | IDA PMID:12917011 Expanded substrate screenings of human and Drosophila type 1... | KEEP AS NON CORE | Summary: IDA involvement in androgen metabolism, from testosterone/androstanediol dehydrogenase activities. In-vitro steroid metabolism; non-core. Reason: In-vitro steroid side activity, not the evolved core function. Supporting Evidence: PMID:12917011 3alpha-OH and 17beta-OH activities with sex steroids |
| GO:0008210 estrogen metabolic process | IDA PMID:12917011 Expanded substrate screenings of human and Drosophila type 1... | KEEP AS NON CORE | Summary: IDA involvement in estrogen metabolism, from 17-beta-estradiol dehydrogenase activity. In-vitro steroid metabolism; non-core. Reason: In-vitro steroid side activity, not the evolved core function. Supporting Evidence: PMID:12917011 17beta-OH activities with sex steroids |
| GO:0008709 cholate 7-alpha-dehydrogenase (NAD+) activity | IDA PMID:12917011 Expanded substrate screenings of human and Drosophila type 1... | KEEP AS NON CORE | Summary: IDA cholate 7-alpha-dehydrogenase activity from the substrate screen. Real in-vitro bile-acid activity; non-core. Reason: In-vitro bile-acid side activity, not the evolved core function. Supporting Evidence: PMID:12917011 the human orthologue oxidizes the 7alpha-OH of chenodeoxycholic acid (5beta-cholanic acid, 3alpha,7alpha-diol) and cholic acid |
| GO:0042645 mitochondrial nucleoid | IDA PMID:24703694 Initial steps in RNA processing and ribosome assembly occur ... | ACCEPT | Summary: IDA localization to the mitochondrial nucleoid, where RNase P/ELAC2 initiate tRNA processing and ribosome assembly. Accept. Supporting Evidence: PMID:24703694 associate with nucleoids to initiate RNA processing and ribosome assembly |
| GO:0047015 3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity | IDA PMID:19706438 Mental retardation linked to mutations in the HSD17B10 gene ... | ACCEPT | Summary: IDA MHBD activity; disease mutant loses dehydrogenation of 2-methyl-3-hydroxybutyryl-CoA. Core physiological catalytic activity. Accept. Supporting Evidence: PMID:19706438 HSD10(E249Q) was unable to catalyze the dehydrogenation of 2-methyl-3-hydroxybutyryl-CoA |
| GO:0047035 testosterone dehydrogenase (NAD+) activity | IDA PMID:12917011 Expanded substrate screenings of human and Drosophila type 1... | KEEP AS NON CORE | Summary: IDA testosterone dehydrogenase activity from the substrate screen. In-vitro steroid side activity; non-core. Reason: In-vitro steroid side activity, not the evolved core function. Supporting Evidence: PMID:12917011 3alpha-OH and 17beta-OH activities with sex steroids |
| GO:0062173 brexanolone metabolic process | IDA PMID:19706438 Mental retardation linked to mutations in the HSD17B10 gene ... | KEEP AS NON CORE | Summary: IDA involvement in brexanolone (allopregnanolone) metabolism: HSD17B10 oxidizes the 3-alpha-OH of this neurosteroid GABA-A modulator, and disease mutants lose this activity. A genuine, potentially neurologically relevant side activity; kept as non-core relative to the isoleucine/tRNA core roles. Reason: Real neurosteroid activity of possible pathophysiological relevance, but a side activity rather than the evolved core function. Supporting Evidence: PMID:19706438 the oxidation of allopregnanolone, a positive modulator of the gamma-aminobutyric acid type A receptor |
| GO:0000049 tRNA binding | IDA PMID:29040705 The MRPP1/MRPP2 complex is a tRNA-maturation platform in hum... | ACCEPT | Summary: IDA tRNA binding: the MRPP1/2 (TRMT10C/SDR5C1) complex binds and retains mitochondrial pre-tRNA throughout maturation. tRNA binding is the subunit-level molecular activity underlying HSD17B10/MRPP2's structural role in RNase P/tRNA processing. Accept as a core molecular function. Supporting Evidence: PMID:29040705 it retains the tRNA product from the 5'-processing step |
| GO:0003857 (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity | IDA PMID:25925575 Molecular insights into HSD10 disease: impact of SDR5C1 muta... | ACCEPT | Summary: IDA 3-hydroxyacyl-CoA dehydrogenase activity assayed for disease mutants alongside RNase P/tRNA functions. Core catalytic activity. Accept. Supporting Evidence: PMID:25925575 pathogenic mutations impair SDR5C1-dependent dehydrogenation, tRNA processing and methylation |
| GO:0003857 (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity | IDA PMID:28888424 Novel patient missense mutations in the HSD17B10 gene affect... | ACCEPT | Summary: IDA 3-hydroxyacyl-CoA dehydrogenase activity for the V12L/V176M disease mutants (reduced dehydrogenase activity). Core catalytic activity. Accept. Supporting Evidence: PMID:28888424 Both mutant proteins showed significant reduction in the dehydrogenase, methyltransferase and tRNA processing activities compared to wildtype |
| GO:0005515 protein binding | IPI PMID:29040705 The MRPP1/MRPP2 complex is a tRNA-maturation platform in hum... | MARK AS OVER ANNOTATED | Summary: IPI protein-binding to TRMT10C (Q7L0Y3) from the MRPP1/2 tRNA-maturation platform study. Real and central, but bare "protein binding" is uninformative; functional meaning captured by the RNase P complex/process annotations. Reason: Uninformative generic protein-binding term; TRMT10C interaction captured by complex/process annotations. |
| GO:0030678 mitochondrial ribonuclease P complex | IDA PMID:25925575 Molecular insights into HSD10 disease: impact of SDR5C1 muta... | ACCEPT | Summary: IDA part_of the mitochondrial RNase P complex; disease mutations disrupt complex assembly/interaction with TRMT10C. Core cellular component. Accept. Supporting Evidence: PMID:25925575 moonlighting as a component of human mitochondrial RNase P |
| GO:0030678 mitochondrial ribonuclease P complex | IDA PMID:28888424 Novel patient missense mutations in the HSD17B10 gene affect... | ACCEPT | Summary: IDA part_of the mitochondrial RNase P complex (MRPP1/MRPP2/MRPP3). Core cellular component. Accept. Supporting Evidence: PMID:28888424 in a complex with MRPP1 and MRPP3 (also known as PRORP) proteins for 5'-end processing of mitochondrial precursor tRNA |
| GO:0051289 protein homotetramerization | IDA PMID:25925575 Molecular insights into HSD10 disease: impact of SDR5C1 muta... | ACCEPT | Summary: IDA protein homotetramerization; HSD17B10 functions as a homotetramer and some disease mutations disrupt tetramerization. A genuine, structurally important property. Accept. Supporting Evidence: PMID:25925575 Some mutations disrupt the homotetramerization of SDR5C1 |
| GO:0070901 mitochondrial tRNA methylation | IDA PMID:25925575 Molecular insights into HSD10 disease: impact of SDR5C1 muta... | ACCEPT | Summary: IDA involvement in mitochondrial tRNA methylation (m1A9/m1G9); disease mutations impair methylation. Genuine RNase P subcomplex role. Accept. Supporting Evidence: PMID:25925575 pathogenic mutations impair SDR5C1-dependent dehydrogenation, tRNA processing and methylation |
| GO:0070901 mitochondrial tRNA methylation | IDA PMID:28888424 Novel patient missense mutations in the HSD17B10 gene affect... | ACCEPT | Summary: IDA involvement in mitochondrial tRNA methylation; V12L/V176M mutants show reduced methyltransferase activity. Accept. Supporting Evidence: PMID:28888424 N1-methylation of purines at position 9 of mitochondrial tRNA |
| GO:0097745 mitochondrial tRNA 5'-end processing | IDA PMID:24549042 Mutation or knock-down of 17Ξ²-hydroxysteroid dehydrogenase t... | ACCEPT | Summary: IDA involvement in mitochondrial tRNA 5'-end processing; knock-down / patient mutation impairs heavy-strand transcript processing. Core biological process. Accept. Supporting Evidence: PMID:24549042 evidence of impaired processing of precursor tRNA transcripts of the mitochondrial heavy strand |
| GO:0097745 mitochondrial tRNA 5'-end processing | IDA PMID:25925575 Molecular insights into HSD10 disease: impact of SDR5C1 muta... | ACCEPT | Summary: IDA involvement in mitochondrial tRNA 5'-end processing; disease mutations impair RNase P tRNA processing. Core biological process. Accept. Supporting Evidence: PMID:25925575 the enzyme removing 5'-extensions of tRNAs, an early and crucial step in tRNA maturation |
| GO:0097745 mitochondrial tRNA 5'-end processing | IDA PMID:28888424 Novel patient missense mutations in the HSD17B10 gene affect... | ACCEPT | Summary: IDA involvement in mitochondrial tRNA 5'-end processing; disease mutants show reduced tRNA processing. Core biological process. Accept. Supporting Evidence: PMID:28888424 5'-end processing of mitochondrial precursor tRNA |
| GO:0097745 mitochondrial tRNA 5'-end processing | IDA PMID:29040705 The MRPP1/MRPP2 complex is a tRNA-maturation platform in hum... | ACCEPT | Summary: IDA involvement in mitochondrial tRNA 5'-end processing; MRPP1/2 mediates RNase P 5'-leader removal. Core biological process. Accept. Supporting Evidence: PMID:29040705 MRPP1/2 is not only responsible for mitochondrial RNase P-based 5'-leader removal |
| GO:1990180 mitochondrial tRNA 3'-end processing | IDA PMID:29040705 The MRPP1/MRPP2 complex is a tRNA-maturation platform in hum... | KEEP AS NON CORE | Summary: IDA involvement in mitochondrial tRNA 3'-end processing: the MRPP1/2 platform retains the tRNA after 5'-cleavage and enhances ELAC2-catalyzed 3'-processing. Real platform-associated role; kept as non-core relative to the 5'-processing core (HSD17B10 does not itself perform 3'-cleavage). Reason: Platform-supported 3'-processing role; ancillary to the core RNase P 5'-processing function. Supporting Evidence: PMID:29040705 significantly enhances the efficiency of ELAC2-catalyzed 3'-processing for 17 of the 22 tRNAs |
| GO:0007005 mitochondrion organization | IMP PMID:20077426 A non-enzymatic function of 17beta-hydroxysteroid dehydrogen... | KEEP AS NON CORE | Summary: IMP involvement in mitochondrion organization: knock-down/knock-out and disease mutations disrupt mitochondrial structural integrity (cristae) independently of dehydrogenase activity. This reflects the essential non-enzymatic (RNase P/tRNA-processing) role. A genuine but downstream/pleiotropic process; kept as non-core. Reason: Genuine IMP phenotype but a downstream consequence of the RNase P/tRNA-processing role; more specific molecular roles capture the core function. Supporting Evidence: PMID:20077426 a property of HSD10 independent of its enzymatic activity is essential for structural and functional integrity of mitochondria |
| GO:0003857 (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity | IDA PMID:23042678 A subcomplex of human mitochondrial RNase P is a bifunctiona... | ACCEPT | Summary: IDA 3-hydroxyacyl-CoA dehydrogenase activity (CAFA-assigned) associated with the methyltransferase-subcomplex study. Core catalytic activity. Accept. Supporting Evidence: PMID:23042678 a fatty and amino acid degradation enzyme in tRNA methylation |
| GO:0005515 protein binding | IPI PMID:23042678 A subcomplex of human mitochondrial RNase P is a bifunctiona... | MARK AS OVER ANNOTATED | Summary: IPI protein-binding to TRMT10C (Q7L0Y3), the methyltransferase partner. Real and central, but bare "protein binding" is uninformative; captured by the RNase P / methyltransferase complex annotations. Reason: Uninformative generic protein-binding term; TRMT10C interaction captured by complex annotations. |
| GO:0030678 mitochondrial ribonuclease P complex | TAS PMID:23042678 A subcomplex of human mitochondrial RNase P is a bifunctiona... | ACCEPT | Summary: TAS part_of the mitochondrial RNase P complex. Core cellular component, independently supported by IDA. Accept. Supporting Evidence: PMID:23042678 a subcomplex of human mitochondrial RNase P |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | MARK AS OVER ANNOTATED | Summary: HDA RNA binding from a global mRNA-interactome capture screen. HSD17B10 does bind tRNA (specifically captured by GO:0000049), but this high-throughput generic "RNA binding" from a poly(A)-mRNA capture experiment is a non-specific over-annotation for a protein whose relevant RNA ligand is tRNA. Reason: Non-specific high-throughput RNA-binding capture; the specific and relevant activity (tRNA binding) is separately and better annotated. |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-508369 | ACCEPT | Summary: TAS (Reactome) mitochondrial-matrix localization for the isoleucine-catabolism reaction. Consistent with the authoritative matrix localization. Accept. Supporting Evidence: file:human/HSD17B10/HSD17B10-uniprot.txt Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-6787591 | ACCEPT | Summary: TAS (Reactome) mitochondrial-matrix localization for the tRNA m1G9 methylation reaction. Consistent with authoritative matrix localization. Accept. Supporting Evidence: file:human/HSD17B10/HSD17B10-uniprot.txt Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-6787594 | ACCEPT | Summary: TAS (Reactome) mitochondrial-matrix localization for the tRNA m1A9 methylation reaction. Accept. Supporting Evidence: file:human/HSD17B10/HSD17B10-uniprot.txt Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-70837 | ACCEPT | Summary: TAS (Reactome) mitochondrial-matrix localization for the isoleucine-catabolism (MHBD) reaction. Accept. Supporting Evidence: file:human/HSD17B10/HSD17B10-uniprot.txt Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-9838081 | ACCEPT | Summary: TAS (Reactome) mitochondrial-matrix localization (LONP1 matrix-protein degradation context). Localization consistent with authoritative matrix localization. Accept. Supporting Evidence: file:human/HSD17B10/HSD17B10-uniprot.txt Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-9838093 | ACCEPT | Summary: TAS (Reactome) mitochondrial-matrix localization (LONP1 matrix-protein binding context). Accept. Supporting Evidence: file:human/HSD17B10/HSD17B10-uniprot.txt Mitochondrion matrix |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: ISS mitochondrial localization by orthology to mouse (O08756). Consistent with all experimental data. Accept. |
| GO:0005737 cytoplasm | TAS PMID:9338779 An intracellular protein that binds amyloid-beta peptide and... | MARK AS OVER ANNOTATED | Summary: TAS cytoplasm from the 1997 ERAB discovery paper, which reported an ER/plasma-membrane-associated AΞ²-binding protein. This localization is a legacy mis-assignment superseded by all subsequent work establishing the protein as mitochondrial (matrix/nucleoid). Over-annotated. Reason: Legacy mislocalization from the original ERAB paper; superseded by mitochondrial matrix/nucleoid localization in all later studies. Supporting Evidence: PMID:12917011 the human form is localized to mitochondria |
| GO:0005886 plasma membrane | TAS PMID:9338779 An intracellular protein that binds amyloid-beta peptide and... | MARK AS OVER ANNOTATED | Summary: TAS plasma membrane from the 1997 ERAB discovery paper. A legacy mis-assignment; the protein is a mitochondrial-matrix enzyme with no established plasma-membrane role. Over-annotated. Reason: Legacy mislocalization from the original ERAB paper; superseded by mitochondrial localization. Supporting Evidence: PMID:12917011 the human form is localized to mitochondria |
| GO:0006629 lipid metabolic process | TAS PMID:9338779 An intracellular protein that binds amyloid-beta peptide and... | KEEP AS NON CORE | Summary: TAS broad "lipid metabolic process" from the 1997 ERAB paper. HSD17B10 does have fatty-acid/cardiolipin/steroid-lipid activities, so a lipid-metabolism parent is not wrong, but this is a very general term captured better by fatty acid beta-oxidation. Kept as non-core. Reason: Over-general parent; more specific lipid processes are separately annotated. |
| GO:0008709 cholate 7-alpha-dehydrogenase (NAD+) activity | TAS PMID:9338779 An intracellular protein that binds amyloid-beta peptide and... | KEEP AS NON CORE | Summary: TAS cholate 7-alpha-dehydrogenase activity attributed to the 1997 ERAB paper, which did NOT establish bile-acid activity (it described an AΞ²-binding dehydrogenase); the bile-acid activity was actually characterized later (PMID:12917011, separately annotated by IDA). The activity itself is a real but non-core in-vitro side activity, so this is kept as non-core; note that the 1997 citation is a legacy mis-attribution and the true support is PMID:12917011. Reason: Real but non-core in-vitro bile-acid side activity; the cited 1997 paper does not actually support it (true support is the later IDA, PMID:12917011). Supporting Evidence: PMID:12917011 the human orthologue oxidizes the 7alpha-OH of chenodeoxycholic acid (5beta-cholanic acid, 3alpha,7alpha-diol) and cholic acid |
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Download this section (compressed HTML)Q: Which of HSD17B10's catalytic activities (isoleucine-pathway MHBD, general 3-hydroxyacyl-CoA, neurosteroid/allopregnanolone, cardiolipin phospholipase) are physiologically significant in vivo versus in-vitro artifacts of a broad-specificity SDR active site?
Q: How does the non-catalytic RNase P/tRNA-processing role mechanistically account for HSD10 disease severity, and can it be uncoupled therapeutically from the metabolic (isoleucine) role?
Q: Does the neurosteroid (allopregnanolone/brexanolone) oxidation activity contribute to the neurological phenotype of HSD10 disease independently of tRNA processing?
Experiment: Separation-of-function mutants that selectively abolish either dehydrogenase activity or RNase P/TRMT10C-binding, tested in patient-derived and knockout cells for mitochondrial tRNA processing, respiratory chain assembly, and viability.
Experiment: Quantitative in-vivo metabolic flux analysis of isoleucine catabolism and neurosteroid (allopregnanolone) levels in HSD10-deficient models to define which metabolic defects contribute to neuropathology.
Experiment: Structural and biochemical dissection of how the HSD17B10 homotetramer scaffolds TRMT10C and pre-tRNA across the sequential 5'-processing, methylation, 3'-processing and CCA-addition steps.
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