id: Q99714
gene_symbol: HSD17B10
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
alternative_products:
- name: '1'
  id: Q99714-1
- name: '2'
  id: Q99714-2
  sequence_note: VSP_007830
existing_annotations:
- term:
    id: GO:0004303
    label: estradiol 17-beta-dehydrogenase [NAD(P)+] activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:10600649
      supporting_text: >-
        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
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetic inference of mitochondrial localization, consistent with all
      experimental data placing HSD17B10 in the mitochondrion (matrix/nucleoid).
    action: ACCEPT
    supported_by:
    - reference_id: file:human/HSD17B10/HSD17B10-uniprot.txt
      supporting_text: >-
        SUBCELLULAR LOCATION: Mitochondrion
- term:
    id: GO:0006631
    label: fatty acid metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but too general; more specific child processes (beta-oxidation,
      isoleucine catabolism) are separately annotated.
- term:
    id: GO:0008209
    label: androgen metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Minor in-vitro steroid side activity, not the evolved core function.
- term:
    id: GO:0008210
    label: estrogen metabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Estrogen metabolic process inferred phylogenetically; reflects weak in-vitro
      17-beta-estradiol dehydrogenase side activity. Kept as non-core.
    action: KEEP_AS_NON_CORE
    reason: Minor in-vitro steroid side activity, not the evolved core function.
- term:
    id: GO:0003857
    label: (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9553139
      supporting_text: >-
        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.
- term:
    id: GO:0004022
    label: alcohol dehydrogenase (NAD+) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Over-broad electronic term; the real chemistry is hydroxysteroid/hydroxyacyl-CoA
      dehydrogenation and the generic ADH activity is trivial and misleading.
    supported_by:
    - reference_id: PMID:10600649
      supporting_text: >-
        The k(cat) of the ADH activity was three orders of magnitude less than the
        l-3-hydroxyacyl-CoA dehydrogenase activity
- term:
    id: GO:0004303
    label: estradiol 17-beta-dehydrogenase [NAD(P)+] activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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).
    action: KEEP_AS_NON_CORE
    reason: Minor in-vitro steroid side activity, not the evolved core function.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Electronic mitochondrial localization, consistent with all experimental data.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/HSD17B10/HSD17B10-uniprot.txt
      supporting_text: >-
        SUBCELLULAR LOCATION: Mitochondrion
- term:
    id: GO:0008709
    label: cholate 7-alpha-dehydrogenase (NAD+) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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).
    action: KEEP_AS_NON_CORE
    reason: In-vitro bile-acid side activity, not the evolved core function.
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        the human orthologue oxidizes the 7alpha-OH of chenodeoxycholic acid
        (5beta-cholanic acid, 3alpha,7alpha-diol) and cholic acid
- term:
    id: GO:0016509
    label: long-chain (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      HSD17B10 preferentially accepts straight medium- and short-chain acyl-CoA;
      the long-chain-specific term misrepresents its substrate preference.
    supported_by:
    - reference_id: file:human/HSD17B10/HSD17B10-uniprot.txt
      supporting_text: >-
        Preferentially accepts straight medium- and short-chain acyl-CoA substrates
- term:
    id: GO:0042645
    label: mitochondrial nucleoid
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:24703694
      supporting_text: >-
        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
- term:
    id: GO:0044594
    label: 17-beta-hydroxysteroid dehydrogenase (NAD+) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Minor in-vitro steroid side activity, not the evolved core function.
- term:
    id: GO:0047015
    label: 3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/HSD17B10/HSD17B10-uniprot.txt
      supporting_text: >-
        Reaction=(2S,3S)-3-hydroxy-2-methylbutanoyl-CoA + NAD(+) = 2-methyl-3-
- term:
    id: GO:0047035
    label: testosterone dehydrogenase (NAD+) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: In-vitro steroid side activity, not the evolved core function.
- term:
    id: GO:0047044
    label: androstan-3-alpha,17-beta-diol dehydrogenase (NAD+) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Electronic (Rhea:42004/EC 1.1.1.53) assignment of androstanediol dehydrogenase
      activity, matching the in-vitro 3-alpha-hydroxysteroid activity. Non-core.
    action: KEEP_AS_NON_CORE
    reason: In-vitro steroid side activity, not the evolved core function.
- term:
    id: GO:0106281
    label: chenodeoxycholate 7-alpha-dehydrogenase (NAD+) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: In-vitro bile-acid side activity, not the evolved core function.
- term:
    id: GO:0106282
    label: isoursodeoxycholate 7-beta-dehydrogenase (NAD+) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: >-
      Electronic (Rhea:42024) bile-acid 7-beta-dehydrogenase activity, supported by
      IDA (PMID:12917011). Non-core in-vitro bile-acid activity.
    action: KEEP_AS_NON_CORE
    reason: In-vitro bile-acid side activity, not the evolved core function.
- term:
    id: GO:0106283
    label: ursodeoxycholate 7-beta-dehydrogenase (NAD+) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  qualifier: enables
  review:
    summary: >-
      Electronic (Rhea:42028) bile-acid 7-beta-dehydrogenase activity, supported by
      IDA (PMID:12917011). Non-core in-vitro bile-acid activity.
    action: KEEP_AS_NON_CORE
    reason: In-vitro bile-acid side activity, not the evolved core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18984158
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative generic protein-binding term; the meaningful TRMT10C interaction
      is captured by the mitochondrial RNase P complex and tRNA-processing annotations.
    supported_by:
    - reference_id: PMID:18984158
      supporting_text: >-
        composed of a tRNA methyltransferase, a short-chain dehydrogenase/reductase-
        family member, and a protein of hitherto unknown functional and evolutionary
        origin
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding to TRMT10C (Q7L0Y3) from a large-scale interactome study.
      Bare "protein binding" is uninformative; functional meaning captured elsewhere.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative generic protein-binding term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29128334
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative generic protein-binding term; interaction of unclear significance.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29128334
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding to TRAP1 (Q12931) from a mitochondrial interactome map.
      Bare "protein binding" is uninformative; no established functional role.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative generic protein-binding term; interaction of unclear significance.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29880640
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative generic protein-binding term; the TRMT10C interaction is captured
      by the complex/process annotations.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding to APP/amyloid-beta (P05067) from a neurodegenerative-disease
      interactome study. The Aβ interaction (ABAD/ERAB) is a real disease-association
      but is non-core; the bare term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative generic protein-binding term; Aβ interaction is a disease
      association, not a core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32825572
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative generic protein-binding term; Aβ interaction is a disease
      association, not a core function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding to TRMT10C (Q7L0Y3) from a proteome-scale interactome study.
      Bare "protein binding" uninformative; functional meaning captured elsewhere.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative generic protein-binding term.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9338779
  qualifier: enables
  review:
    summary: >-
      IPI protein-binding to APP/amyloid-beta (P05067) from the original ERAB/Aβ
      discovery paper. Real disease-association interaction but non-core; the bare
      term is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative generic protein-binding term; Aβ interaction is a disease
      association, not a core function.
- term:
    id: GO:0006550
    label: L-isoleucine catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:20077426
      supporting_text: >-
        the mitochondrial enzyme 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD)
        involved in isoleucine metabolism
- term:
    id: GO:0006635
    label: fatty acid beta-oxidation
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/HSD17B10/HSD17B10-uniprot.txt
      supporting_text: >-
        Acts as (S)-3-hydroxyacyl-CoA dehydrogenase in mitochondrial fatty acid
- term:
    id: GO:0006699
    label: bile acid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Based on in-vitro bile-acid dehydrogenase activities; physiological
      contribution to bile-acid biosynthesis is not established.
- term:
    id: GO:0160241
    label: cardiolipin dehydrogenase (NAD+) activity
  evidence_type: IDA
  original_reference_id: PMID:26338420
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Experimentally supported in-vitro activity but a separate moonlighting role,
      not the evolved core (isoleucine/tRNA) functions.
    supported_by:
    - reference_id: PMID:26338420
      supporting_text: >-
        HSD10 exhibits a strong preference for cardiolipin with oxidized fatty acids.
- term:
    id: GO:0047035
    label: testosterone dehydrogenase (NAD+) activity
  evidence_type: IDA
  original_reference_id: PMID:28888424
  qualifier: enables
  review:
    summary: >-
      IDA testosterone dehydrogenase activity from biochemical characterization of
      the recombinant enzyme. A demonstrated in-vitro steroid side activity; kept as
      non-core.
    action: KEEP_AS_NON_CORE
    reason: In-vitro steroid side activity, not the evolved core function.
- term:
    id: GO:0001680
    label: tRNA 3'-terminal CCA addition
  evidence_type: IDA
  original_reference_id: PMID:38824131
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Real platform role in CCA addition, but ancillary to the core 5'-processing/
      RNase P function; HSD17B10 does not itself add CCA.
    supported_by:
    - reference_id: PMID:29040705
      supporting_text: >-
        presents the nascent tRNA to the mitochondrial CCA-adding enzyme
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: NAS
  original_reference_id: PMID:21593607
  qualifier: located_in
  review:
    summary: NAS mitochondrial localization; consistent with all experimental evidence.
    action: ACCEPT
- term:
    id: GO:0042780
    label: tRNA 3'-end processing
  evidence_type: IDA
  original_reference_id: PMID:39516281
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Platform-supported 3'-processing role; ancillary to the core RNase P
      5'-processing function.
    supported_by:
    - reference_id: PMID:29040705
      supporting_text: >-
        significantly enhances the efficiency of ELAC2-catalyzed 3'-processing for 17
        of the 22 tRNAs
- term:
    id: GO:1902494
    label: catalytic complex
  evidence_type: IPI
  original_reference_id: PMID:38824131
  qualifier: part_of
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but over-general complex term; superseded by specific mitochondrial
      RNase P complex annotations.
- term:
    id: GO:1902555
    label: endoribonuclease complex
  evidence_type: IDA
  original_reference_id: PMID:39516281
  qualifier: part_of
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but general complex term; the specific mitochondrial RNase P complex is
      the core cellular component.
    supported_by:
    - reference_id: PMID:39516281
      supporting_text: >-
        cryo-EM structures of the mitochondrial RNase Z complex
        (ELAC2/SDR5C1/TRMT10C)
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:29880640
  qualifier: located_in
  review:
    summary: IDA mitochondrial localization from the RNase P structural study. Accept.
    action: ACCEPT
- term:
    id: GO:0030678
    label: mitochondrial ribonuclease P complex
  evidence_type: IPI
  original_reference_id: PMID:29880640
  qualifier: part_of
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:29040705
      supporting_text: >-
        The human mitochondrial RNase P is composed of three protein subunits:
        mitochondrial RNase P proteins 1, 2 and 3 (MRPP1, MRPP2 and MRPP3,
        respectively)
- term:
    id: GO:0097745
    label: mitochondrial tRNA 5'-end processing
  evidence_type: IDA
  original_reference_id: PMID:29880640
  qualifier: involved_in
  review:
    summary: >-
      IDA involvement in mitochondrial tRNA 5'-end processing, the core RNase P
      function of HSD17B10/MRPP2. Accept as a core biological process.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:18984158
      supporting_text: >-
        extra nucleotides at their 5' ends are removed by an endonuclease called
        RNase P
- term:
    id: GO:0003857
    label: (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
  evidence_type: EXP
  original_reference_id: PMID:10600649
  qualifier: enables
  review:
    summary: >-
      EXP (3S)-3-hydroxyacyl-CoA dehydrogenase activity, kinetically characterized on
      the purified enzyme. Core catalytic activity. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10600649
      supporting_text: >-
        The k(cat) of the ADH activity was three orders of magnitude less than the
        l-3-hydroxyacyl-CoA dehydrogenase activity
- term:
    id: GO:0003857
    label: (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
  evidence_type: EXP
  original_reference_id: PMID:26950678
  qualifier: enables
  review:
    summary: >-
      EXP 3-hydroxyacyl-CoA dehydrogenase activity, assayed together with RNase P
      activities for the K212E disease mutant. Core catalytic activity. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:26950678
      supporting_text: >-
        the p.K212E mutation impairs the SDR5C1-dependent mitochondrial RNase P
        activities
- term:
    id: GO:0003857
    label: (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
  evidence_type: EXP
  original_reference_id: PMID:9553139
  qualifier: enables
  review:
    summary: >-
      EXP 3-hydroxyacyl-CoA dehydrogenase activity from cloning/characterization of
      the purified human brain enzyme. Core catalytic activity. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:9553139
      supporting_text: >-
        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.
- term:
    id: GO:0004303
    label: estradiol 17-beta-dehydrogenase [NAD(P)+] activity
  evidence_type: EXP
  original_reference_id: PMID:10600649
  qualifier: enables
  review:
    summary: >-
      EXP 17-beta-estradiol dehydrogenase activity, kinetically characterized. Real
      but weak intrinsic steroid activity; kept as non-core.
    action: KEEP_AS_NON_CORE
    reason: Weak in-vitro steroid side activity, not the evolved core function.
    supported_by:
    - reference_id: PMID:10600649
      supporting_text: >-
        comparable with that of the enzyme's hydroxysteroid dehydrogenase (HSD)
        activity for oxidizing 17beta-oestradiol
- term:
    id: GO:0004303
    label: estradiol 17-beta-dehydrogenase [NAD(P)+] activity
  evidence_type: EXP
  original_reference_id: PMID:12917011
  qualifier: enables
  review:
    summary: >-
      EXP 17-beta-estradiol/hydroxysteroid dehydrogenase activity from the expanded
      substrate screen. Weak in-vitro steroid activity; non-core.
    action: KEEP_AS_NON_CORE
    reason: Weak in-vitro steroid side activity, not the evolved core function.
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        3alpha-OH and 17beta-OH activities with sex steroids
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: EXP
  original_reference_id: PMID:12917011
  qualifier: located_in
  review:
    summary: >-
      EXP mitochondrial localization by confocal/electron microscopy; the human
      enzyme carries an N-terminal mitochondrial targeting signal. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        the human form is localized to mitochondria
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: EXP
  original_reference_id: PMID:18984158
  qualifier: located_in
  review:
    summary: EXP mitochondrial localization from the RNase P identification study. Accept.
    action: ACCEPT
- term:
    id: GO:0047015
    label: 3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity
  evidence_type: EXP
  original_reference_id: PMID:20077426
  qualifier: enables
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:20077426
      supporting_text: >-
        substrate 2-methyl-3-hydroxybutyryl-CoA
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:23042678
  qualifier: located_in
  review:
    summary: IDA mitochondrial localization. Accept.
    action: ACCEPT
- term:
    id: GO:0043527
    label: tRNA methyltransferase complex
  evidence_type: IPI
  original_reference_id: PMID:23042678
  qualifier: part_of
  review:
    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).
    action: ACCEPT
    supported_by:
    - reference_id: PMID:23042678
      supporting_text: >-
        the human mitochondrial enzyme, moreover, requires a short-chain
        dehydrogenase as a partner protein
- term:
    id: GO:0070901
    label: mitochondrial tRNA methylation
  evidence_type: IDA
  original_reference_id: PMID:23042678
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:23042678
      supporting_text: >-
        is the methyltransferase responsible for m(1)G9 and m(1)A9 formation
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: >-
      HTP mitochondrial localization from a high-confidence mitochondrial proteome
      study. Consistent with all evidence. Accept.
    action: ACCEPT
- term:
    id: GO:0106281
    label: chenodeoxycholate 7-alpha-dehydrogenase (NAD+) activity
  evidence_type: IDA
  original_reference_id: PMID:12917011
  qualifier: enables
  review:
    summary: >-
      IDA bile-acid 7-alpha-dehydrogenase activity (chenodeoxycholate/cholate) from
      the expanded substrate screen. Real in-vitro bile-acid activity; non-core.
    action: KEEP_AS_NON_CORE
    reason: In-vitro bile-acid side activity, not the evolved core function.
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        the human orthologue oxidizes the 7alpha-OH of chenodeoxycholic acid
- term:
    id: GO:0106282
    label: isoursodeoxycholate 7-beta-dehydrogenase (NAD+) activity
  evidence_type: IDA
  original_reference_id: PMID:12917011
  qualifier: enables
  review:
    summary: >-
      IDA bile-acid 7-beta-dehydrogenase activity on (iso)ursodeoxycholic acid from
      the substrate screen. Real in-vitro bile-acid activity; non-core.
    action: KEEP_AS_NON_CORE
    reason: In-vitro bile-acid side activity, not the evolved core function.
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        act as 7beta-OH dehydrogenases of ursodeoxycholic or isoursodeoxycholic acid
- term:
    id: GO:0106283
    label: ursodeoxycholate 7-beta-dehydrogenase (NAD+) activity
  evidence_type: IDA
  original_reference_id: PMID:12917011
  qualifier: enables
  review:
    summary: >-
      IDA bile-acid 7-beta-dehydrogenase activity on ursodeoxycholic acid. Real
      in-vitro bile-acid activity; non-core.
    action: KEEP_AS_NON_CORE
    reason: In-vitro bile-acid side activity, not the evolved core function.
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        act as 7beta-OH dehydrogenases of ursodeoxycholic or isoursodeoxycholic acid
- term:
    id: GO:0006550
    label: L-isoleucine catabolic process
  evidence_type: IDA
  original_reference_id: PMID:18996107
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:18996107
      supporting_text: >-
        2-Methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency
- term:
    id: GO:0006550
    label: L-isoleucine catabolic process
  evidence_type: IDA
  original_reference_id: PMID:19706438
  qualifier: involved_in
  review:
    summary: >-
      IDA involvement in isoleucine catabolism; the disease mutant fails to
      dehydrogenate 2-methyl-3-hydroxybutyryl-CoA. Core biological process. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:19706438
      supporting_text: >-
        HSD10(E249Q) was unable to catalyze the dehydrogenation of
        2-methyl-3-hydroxybutyryl-CoA
- term:
    id: GO:0044594
    label: 17-beta-hydroxysteroid dehydrogenase (NAD+) activity
  evidence_type: IDA
  original_reference_id: PMID:12917011
  qualifier: enables
  review:
    summary: >-
      IDA 17-beta-hydroxysteroid dehydrogenase activity from the expanded substrate
      screen. Real but weak intrinsic steroid activity; non-core.
    action: KEEP_AS_NON_CORE
    reason: Weak in-vitro steroid side activity, not the evolved core function.
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        3alpha-OH and 17beta-OH activities with sex steroids
- term:
    id: GO:0047015
    label: 3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity
  evidence_type: IDA
  original_reference_id: PMID:18996107
  qualifier: enables
  review:
    summary: >-
      IDA MHBD activity measured in patient fibroblasts. Core physiological catalytic
      activity (isoleucine catabolism). Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:18996107
      supporting_text: >-
        MHBD activity was clearly deficient in males
- term:
    id: GO:0003857
    label: (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
  evidence_type: IDA
  original_reference_id: PMID:12917011
  qualifier: enables
  review:
    summary: >-
      IDA (3S)-3-hydroxyacyl-CoA dehydrogenase activity from the substrate screen.
      Core catalytic activity. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        In addition to the known hydroxyacyl-CoA dehydrogenase
- term:
    id: GO:0006635
    label: fatty acid beta-oxidation
  evidence_type: IDA
  original_reference_id: PMID:12917011
  qualifier: involved_in
  review:
    summary: >-
      IDA involvement in fatty acid beta-oxidation (short/medium-chain
      3-hydroxyacyl-CoA dehydrogenase step). Accept.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/HSD17B10/HSD17B10-uniprot.txt
      supporting_text: >-
        Acts as (S)-3-hydroxyacyl-CoA dehydrogenase in mitochondrial fatty acid
- term:
    id: GO:0006699
    label: bile acid biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:12917011
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Based on in-vitro bile-acid activities; physiological role in bile-acid
      biosynthesis not established.
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        participates in bile acid isomerization
- term:
    id: GO:0008207
    label: C21-steroid hormone metabolic process
  evidence_type: IDA
  original_reference_id: PMID:12917011
  qualifier: involved_in
  review:
    summary: >-
      IDA involvement in C21-steroid (glucocorticoid/gestagen) metabolism, from the
      20-beta/21-OH oxidation activities. In-vitro steroid metabolism; non-core.
    action: KEEP_AS_NON_CORE
    reason: In-vitro steroid metabolism, not the evolved core function.
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        oxidize the 20beta-OH and 21-OH groups in C21 steroids
- term:
    id: GO:0008209
    label: androgen metabolic process
  evidence_type: IDA
  original_reference_id: PMID:12917011
  qualifier: involved_in
  review:
    summary: >-
      IDA involvement in androgen metabolism, from testosterone/androstanediol
      dehydrogenase activities. In-vitro steroid metabolism; non-core.
    action: KEEP_AS_NON_CORE
    reason: In-vitro steroid side activity, not the evolved core function.
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        3alpha-OH and 17beta-OH activities with sex steroids
- term:
    id: GO:0008210
    label: estrogen metabolic process
  evidence_type: IDA
  original_reference_id: PMID:12917011
  qualifier: involved_in
  review:
    summary: >-
      IDA involvement in estrogen metabolism, from 17-beta-estradiol dehydrogenase
      activity. In-vitro steroid metabolism; non-core.
    action: KEEP_AS_NON_CORE
    reason: In-vitro steroid side activity, not the evolved core function.
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        17beta-OH activities with sex steroids
- term:
    id: GO:0008709
    label: cholate 7-alpha-dehydrogenase (NAD+) activity
  evidence_type: IDA
  original_reference_id: PMID:12917011
  qualifier: enables
  review:
    summary: >-
      IDA cholate 7-alpha-dehydrogenase activity from the substrate screen. Real
      in-vitro bile-acid activity; non-core.
    action: KEEP_AS_NON_CORE
    reason: In-vitro bile-acid side activity, not the evolved core function.
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        the human orthologue oxidizes the 7alpha-OH of chenodeoxycholic acid
        (5beta-cholanic acid, 3alpha,7alpha-diol) and cholic acid
- term:
    id: GO:0042645
    label: mitochondrial nucleoid
  evidence_type: IDA
  original_reference_id: PMID:24703694
  qualifier: located_in
  review:
    summary: >-
      IDA localization to the mitochondrial nucleoid, where RNase P/ELAC2 initiate
      tRNA processing and ribosome assembly. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:24703694
      supporting_text: >-
        associate with nucleoids to initiate RNA processing and ribosome assembly
- term:
    id: GO:0047015
    label: 3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity
  evidence_type: IDA
  original_reference_id: PMID:19706438
  qualifier: enables
  review:
    summary: >-
      IDA MHBD activity; disease mutant loses dehydrogenation of
      2-methyl-3-hydroxybutyryl-CoA. Core physiological catalytic activity. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:19706438
      supporting_text: >-
        HSD10(E249Q) was unable to catalyze the dehydrogenation of
        2-methyl-3-hydroxybutyryl-CoA
- term:
    id: GO:0047035
    label: testosterone dehydrogenase (NAD+) activity
  evidence_type: IDA
  original_reference_id: PMID:12917011
  qualifier: enables
  review:
    summary: >-
      IDA testosterone dehydrogenase activity from the substrate screen. In-vitro
      steroid side activity; non-core.
    action: KEEP_AS_NON_CORE
    reason: In-vitro steroid side activity, not the evolved core function.
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        3alpha-OH and 17beta-OH activities with sex steroids
- term:
    id: GO:0062173
    label: brexanolone metabolic process
  evidence_type: IDA
  original_reference_id: PMID:19706438
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: >-
      Real neurosteroid activity of possible pathophysiological relevance, but a side
      activity rather than the evolved core function.
    supported_by:
    - reference_id: PMID:19706438
      supporting_text: >-
        the oxidation of allopregnanolone, a positive modulator of the
        gamma-aminobutyric acid type A receptor
- term:
    id: GO:0000049
    label: tRNA binding
  evidence_type: IDA
  original_reference_id: PMID:29040705
  qualifier: enables
  review:
    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.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:29040705
      supporting_text: >-
        it retains the tRNA product from the 5'-processing step
- term:
    id: GO:0003857
    label: (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
  evidence_type: IDA
  original_reference_id: PMID:25925575
  qualifier: enables
  review:
    summary: >-
      IDA 3-hydroxyacyl-CoA dehydrogenase activity assayed for disease mutants
      alongside RNase P/tRNA functions. Core catalytic activity. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:25925575
      supporting_text: >-
        pathogenic mutations impair SDR5C1-dependent dehydrogenation, tRNA processing
        and methylation
- term:
    id: GO:0003857
    label: (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
  evidence_type: IDA
  original_reference_id: PMID:28888424
  qualifier: enables
  review:
    summary: >-
      IDA 3-hydroxyacyl-CoA dehydrogenase activity for the V12L/V176M disease mutants
      (reduced dehydrogenase activity). Core catalytic activity. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:28888424
      supporting_text: >-
        Both mutant proteins showed significant reduction in the dehydrogenase,
        methyltransferase and tRNA processing activities compared to wildtype
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:29040705
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative generic protein-binding term; TRMT10C interaction captured by
      complex/process annotations.
- term:
    id: GO:0030678
    label: mitochondrial ribonuclease P complex
  evidence_type: IDA
  original_reference_id: PMID:25925575
  qualifier: part_of
  review:
    summary: >-
      IDA part_of the mitochondrial RNase P complex; disease mutations disrupt
      complex assembly/interaction with TRMT10C. Core cellular component. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:25925575
      supporting_text: >-
        moonlighting as a component of human mitochondrial RNase P
- term:
    id: GO:0030678
    label: mitochondrial ribonuclease P complex
  evidence_type: IDA
  original_reference_id: PMID:28888424
  qualifier: part_of
  review:
    summary: >-
      IDA part_of the mitochondrial RNase P complex (MRPP1/MRPP2/MRPP3). Core
      cellular component. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:28888424
      supporting_text: >-
        in a complex with MRPP1 and MRPP3 (also known as PRORP) proteins for 5'-end
        processing of mitochondrial precursor tRNA
- term:
    id: GO:0051289
    label: protein homotetramerization
  evidence_type: IDA
  original_reference_id: PMID:25925575
  qualifier: involved_in
  review:
    summary: >-
      IDA protein homotetramerization; HSD17B10 functions as a homotetramer and some
      disease mutations disrupt tetramerization. A genuine, structurally important
      property. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:25925575
      supporting_text: >-
        Some mutations disrupt the homotetramerization of SDR5C1
- term:
    id: GO:0070901
    label: mitochondrial tRNA methylation
  evidence_type: IDA
  original_reference_id: PMID:25925575
  qualifier: involved_in
  review:
    summary: >-
      IDA involvement in mitochondrial tRNA methylation (m1A9/m1G9); disease mutations
      impair methylation. Genuine RNase P subcomplex role. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:25925575
      supporting_text: >-
        pathogenic mutations impair SDR5C1-dependent dehydrogenation, tRNA processing
        and methylation
- term:
    id: GO:0070901
    label: mitochondrial tRNA methylation
  evidence_type: IDA
  original_reference_id: PMID:28888424
  qualifier: involved_in
  review:
    summary: >-
      IDA involvement in mitochondrial tRNA methylation; V12L/V176M mutants show
      reduced methyltransferase activity. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:28888424
      supporting_text: >-
        N1-methylation of purines at position 9 of mitochondrial tRNA
- term:
    id: GO:0097745
    label: mitochondrial tRNA 5'-end processing
  evidence_type: IDA
  original_reference_id: PMID:24549042
  qualifier: involved_in
  review:
    summary: >-
      IDA involvement in mitochondrial tRNA 5'-end processing; knock-down / patient
      mutation impairs heavy-strand transcript processing. Core biological process.
      Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:24549042
      supporting_text: >-
        evidence of impaired processing of precursor tRNA transcripts of the
        mitochondrial heavy strand
- term:
    id: GO:0097745
    label: mitochondrial tRNA 5'-end processing
  evidence_type: IDA
  original_reference_id: PMID:25925575
  qualifier: involved_in
  review:
    summary: >-
      IDA involvement in mitochondrial tRNA 5'-end processing; disease mutations
      impair RNase P tRNA processing. Core biological process. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:25925575
      supporting_text: >-
        the enzyme removing 5'-extensions of tRNAs, an early and crucial step in tRNA
        maturation
- term:
    id: GO:0097745
    label: mitochondrial tRNA 5'-end processing
  evidence_type: IDA
  original_reference_id: PMID:28888424
  qualifier: involved_in
  review:
    summary: >-
      IDA involvement in mitochondrial tRNA 5'-end processing; disease mutants show
      reduced tRNA processing. Core biological process. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:28888424
      supporting_text: >-
        5'-end processing of mitochondrial precursor tRNA
- term:
    id: GO:0097745
    label: mitochondrial tRNA 5'-end processing
  evidence_type: IDA
  original_reference_id: PMID:29040705
  qualifier: involved_in
  review:
    summary: >-
      IDA involvement in mitochondrial tRNA 5'-end processing; MRPP1/2 mediates
      RNase P 5'-leader removal. Core biological process. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:29040705
      supporting_text: >-
        MRPP1/2 is not only responsible for mitochondrial RNase P-based 5'-leader
        removal
- term:
    id: GO:1990180
    label: mitochondrial tRNA 3'-end processing
  evidence_type: IDA
  original_reference_id: PMID:29040705
  qualifier: involved_in
  review:
    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).
    action: KEEP_AS_NON_CORE
    reason: >-
      Platform-supported 3'-processing role; ancillary to the core RNase P
      5'-processing function.
    supported_by:
    - reference_id: PMID:29040705
      supporting_text: >-
        significantly enhances the efficiency of ELAC2-catalyzed 3'-processing for 17
        of the 22 tRNAs
- term:
    id: GO:0007005
    label: mitochondrion organization
  evidence_type: IMP
  original_reference_id: PMID:20077426
  qualifier: involved_in
  review:
    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.
    action: KEEP_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.
    supported_by:
    - reference_id: PMID:20077426
      supporting_text: >-
        a property of HSD10 independent of its enzymatic activity is essential for
        structural and functional integrity of mitochondria
- term:
    id: GO:0003857
    label: (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
  evidence_type: IDA
  original_reference_id: PMID:23042678
  qualifier: enables
  review:
    summary: >-
      IDA 3-hydroxyacyl-CoA dehydrogenase activity (CAFA-assigned) associated with the
      methyltransferase-subcomplex study. Core catalytic activity. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:23042678
      supporting_text: >-
        a fatty and amino acid degradation enzyme in tRNA methylation
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23042678
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative generic protein-binding term; TRMT10C interaction captured by
      complex annotations.
- term:
    id: GO:0030678
    label: mitochondrial ribonuclease P complex
  evidence_type: TAS
  original_reference_id: PMID:23042678
  qualifier: part_of
  review:
    summary: >-
      TAS part_of the mitochondrial RNase P complex. Core cellular component,
      independently supported by IDA. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:23042678
      supporting_text: >-
        a subcomplex of human mitochondrial RNase P
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22681889
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Non-specific high-throughput RNA-binding capture; the specific and relevant
      activity (tRNA binding) is separately and better annotated.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-508369
  qualifier: located_in
  review:
    summary: >-
      TAS (Reactome) mitochondrial-matrix localization for the isoleucine-catabolism
      reaction. Consistent with the authoritative matrix localization. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/HSD17B10/HSD17B10-uniprot.txt
      supporting_text: >-
        Mitochondrion matrix
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6787591
  qualifier: located_in
  review:
    summary: >-
      TAS (Reactome) mitochondrial-matrix localization for the tRNA m1G9 methylation
      reaction. Consistent with authoritative matrix localization. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/HSD17B10/HSD17B10-uniprot.txt
      supporting_text: >-
        Mitochondrion matrix
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-6787594
  qualifier: located_in
  review:
    summary: >-
      TAS (Reactome) mitochondrial-matrix localization for the tRNA m1A9 methylation
      reaction. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/HSD17B10/HSD17B10-uniprot.txt
      supporting_text: >-
        Mitochondrion matrix
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-70837
  qualifier: located_in
  review:
    summary: >-
      TAS (Reactome) mitochondrial-matrix localization for the isoleucine-catabolism
      (MHBD) reaction. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/HSD17B10/HSD17B10-uniprot.txt
      supporting_text: >-
        Mitochondrion matrix
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9838081
  qualifier: located_in
  review:
    summary: >-
      TAS (Reactome) mitochondrial-matrix localization (LONP1 matrix-protein
      degradation context). Localization consistent with authoritative matrix
      localization. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/HSD17B10/HSD17B10-uniprot.txt
      supporting_text: >-
        Mitochondrion matrix
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9838093
  qualifier: located_in
  review:
    summary: >-
      TAS (Reactome) mitochondrial-matrix localization (LONP1 matrix-protein binding
      context). Accept.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/HSD17B10/HSD17B10-uniprot.txt
      supporting_text: >-
        Mitochondrion matrix
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      ISS mitochondrial localization by orthology to mouse (O08756). Consistent with
      all experimental data. Accept.
    action: ACCEPT
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: TAS
  original_reference_id: PMID:9338779
  qualifier: located_in
  review:
    summary: >-
      TAS cytoplasm from the 1997 ERAB discovery paper, which reported an
      ER/plasma-membrane-associated Aβ-binding protein. This localization is a legacy
      mis-assignment superseded by all subsequent work establishing the protein as
      mitochondrial (matrix/nucleoid). Over-annotated.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Legacy mislocalization from the original ERAB paper; superseded by mitochondrial
      matrix/nucleoid localization in all later studies.
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        the human form is localized to mitochondria
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: PMID:9338779
  qualifier: located_in
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Legacy mislocalization from the original ERAB paper; superseded by mitochondrial
      localization.
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        the human form is localized to mitochondria
- term:
    id: GO:0006629
    label: lipid metabolic process
  evidence_type: TAS
  original_reference_id: PMID:9338779
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Over-general parent; more specific lipid processes are separately annotated.
- term:
    id: GO:0008709
    label: cholate 7-alpha-dehydrogenase (NAD+) activity
  evidence_type: TAS
  original_reference_id: PMID:9338779
  qualifier: enables
  review:
    summary: >-
      TAS cholate 7-alpha-dehydrogenase activity attributed to the 1997 ERAB paper,
      which did NOT establish bile-acid activity (it described an Aβ-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.
    action: KEEP_AS_NON_CORE
    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).
    supported_by:
    - reference_id: PMID:12917011
      supporting_text: >-
        the human orthologue oxidizes the 7alpha-OH of chenodeoxycholic acid
        (5beta-cholanic acid, 3alpha,7alpha-diol) and cholic acid
core_functions:
- description: >-
    NAD+-dependent (S)-2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) acting in
    the mitochondrial matrix in L-isoleucine catabolism, oxidizing
    (2S,3S)-3-hydroxy-2-methylbutanoyl-CoA to 2-methyl-3-oxobutanoyl-CoA; the enzyme
    also has broad short/medium-chain (S)-3-hydroxyacyl-CoA dehydrogenase activity in
    fatty acid beta-oxidation. Deficiency of this activity causes the MHBD organic
    aciduria.
  molecular_function:
    id: GO:0047015
    label: 3-hydroxy-2-methylbutyryl-CoA dehydrogenase activity
  directly_involved_in:
  - id: GO:0006550
    label: L-isoleucine catabolic process
  - id: GO:0006635
    label: fatty acid beta-oxidation
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
  supported_by:
  - reference_id: PMID:19706438
    supporting_text: >-
      HSD10(E249Q) was unable to catalyze the dehydrogenation of
      2-methyl-3-hydroxybutyryl-CoA
  - reference_id: PMID:20077426
    supporting_text: >-
      the mitochondrial enzyme 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD)
      involved in isoleucine metabolism
  - reference_id: PMID:9553139
    supporting_text: >-
      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.
- description: >-
    Broad-substrate NAD+-dependent (S)-3-hydroxyacyl-CoA dehydrogenase catalyzing the
    third step of mitochondrial fatty acid beta-oxidation, with NAD+ as the required
    cofactor bound in a Rossmann fold. This is the family-defining SDR catalytic
    activity underlying the MHBD and other hydroxyacyl-CoA/hydroxysteroid activities.
  molecular_function:
    id: GO:0003857
    label: (3S)-3-hydroxyacyl-CoA dehydrogenase (NAD+) activity
  directly_involved_in:
  - id: GO:0006635
    label: fatty acid beta-oxidation
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
  supported_by:
  - reference_id: PMID:9553139
    supporting_text: >-
      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.
  - reference_id: PMID:12917011
    supporting_text: >-
      In addition to the known hydroxyacyl-CoA dehydrogenase
- description: >-
    Essential non-catalytic (moonlighting) structural subunit MRPP2 of mitochondrial
    RNase P. As a homotetramer it binds mitochondrial pre-tRNA and, together with the
    methyltransferase TRMT10C/MRPP1 and the nuclease PRORP/MRPP3, carries out 5'-end
    processing of mitochondrial tRNAs; the TRMT10C-HSD17B10 subcomplex also acts as a
    tRNA-maturation platform and enables N1-methylation of purine-9 (m1A9/m1G9). This
    role is independent of the enzyme's dehydrogenase activity, and its loss underlies
    the severity of HSD10 mitochondrial disease.
  molecular_function:
    id: GO:0000049
    label: tRNA binding
  directly_involved_in:
  - id: GO:0097745
    label: mitochondrial tRNA 5'-end processing
  - id: GO:0070901
    label: mitochondrial tRNA methylation
  in_complex:
    id: GO:0030678
    label: mitochondrial ribonuclease P complex
  supported_by:
  - reference_id: PMID:18984158
    supporting_text: >-
      human mitochondrial RNase P is a protein enzyme that does not require a
      trans-acting RNA component for catalysis
  - reference_id: PMID:29040705
    supporting_text: >-
      it retains the tRNA product from the 5'-processing step
  - reference_id: PMID:23042678
    supporting_text: >-
      the human mitochondrial enzyme, moreover, requires a short-chain dehydrogenase
      as a partner protein
  - reference_id: PMID:20077426
    supporting_text: >-
      a property of HSD10 independent of its enzymatic activity is essential for
      structural and functional integrity of mitochondria
proposed_new_terms: []
suggested_questions:
- question: >-
    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?
- question: >-
    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?
- question: >-
    Does the neurosteroid (allopregnanolone/brexanolone) oxidation activity contribute
    to the neurological phenotype of HSD10 disease independently of tRNA processing?
suggested_experiments:
- description: >-
    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.
- description: >-
    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.
- description: >-
    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.
references:
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:9338779
  title: An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity
    in Alzheimer's disease.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      The original ERAB/Aβ discovery paper. Establishes the Aβ (APP) interaction, but
      its cytoplasm/plasma-membrane/ER localization and bile-acid TAS assignments are
      legacy mis-assignments superseded by later mitochondrial-matrix work.
- id: PMID:9553139
  title: A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is identical to an
    amyloid beta-peptide-binding protein involved in Alzheimer's disease.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Cloning and biochemical characterization establishing the core NAD+-dependent
      (3S)-3-hydroxyacyl-CoA dehydrogenase activity; identical to ERAB.
- id: PMID:10600649
  title: Intrinsic alcohol dehydrogenase and hydroxysteroid dehydrogenase activities
    of human mitochondrial short-chain L-3-hydroxyacyl-CoA dehydrogenase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Kinetic characterization showing the alcohol/hydroxysteroid activities are orders
      of magnitude weaker than the 3-hydroxyacyl-CoA activity, supporting non-core status
      of the steroid/ADH side activities.
- id: PMID:12917011
  title: 'Expanded substrate screenings of human and Drosophila type 10 17beta-hydroxysteroid
    dehydrogenases (HSDs) reveal multiple specificities in bile acid and steroid hormone
    metabolism: characterization of multifunctional 3alpha/7alpha/7beta/17beta/20beta/21-HSD.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Definitive substrate screen and mitochondrial localization; source of most steroid
      and bile-acid MF/BP annotations (in-vitro, non-core).
- id: PMID:18984158
  title: 'RNase P without RNA: identification and functional reconstitution of the
    human mitochondrial tRNA processing enzyme.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Identified HSD17B10/MRPP2 as an essential subunit of the protein-only mitochondrial
      RNase P; foundational for the tRNA-processing core function.
- id: PMID:18996107
  title: 'Study of patients and carriers with 2-methyl-3-hydroxybutyryl-CoA dehydrogenase
    (MHBD) deficiency: difficulties in the diagnosis.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Patient/carrier study of MHBD deficiency supporting the isoleucine-catabolism role.
- id: PMID:19706438
  title: Mental retardation linked to mutations in the HSD17B10 gene interfering with
    neurosteroid and isoleucine metabolism.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Links disease mutations to loss of both MHBD (isoleucine) and allopregnanolone
      (neurosteroid) oxidation; source of the brexanolone metabolic process annotation.
- id: PMID:20077426
  title: A non-enzymatic function of 17beta-hydroxysteroid dehydrogenase type 10 is
    required for mitochondrial integrity and cell survival.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Key evidence that disease severity is independent of enzymatic activity and driven
      by an essential non-enzymatic mitochondrial-integrity function; also the 1.2 A
      crystal structure.
- id: PMID:21593607
  title: Involvement of human ELAC2 gene product in 3' end processing of mitochondrial
    tRNAs.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      ELAC2 mitochondrial 3'-processing study; source of a NAS mitochondrion
      localization for HSD17B10 in the context of the tRNA-processing machinery.
- id: PMID:22681889
  title: The mRNA-bound proteome and its global occupancy profile on protein-coding
    transcripts.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Global mRNA-interactome capture screen; source of the non-specific HDA "RNA
      binding" annotation, marked over-annotated (the relevant ligand is tRNA).
- id: PMID:23042678
  title: A subcomplex of human mitochondrial RNase P is a bifunctional methyltransferase--extensive
    moonlighting in mitochondrial tRNA biogenesis.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Establishes the MRPP1-MRPP2 subcomplex as the m1A9/m1G9 methyltransferase requiring
      HSD17B10 as a non-catalytic partner.
- id: PMID:24549042
  title: Mutation or knock-down of 17β-hydroxysteroid dehydrogenase type 10 cause
    loss of MRPP1 and impaired processing of mitochondrial heavy strand transcripts.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Shows HSD17B10 maintains MRPP1 levels and that its loss impairs heavy-strand
      mitochondrial tRNA processing; disease-relevant.
- id: PMID:24703694
  title: Initial steps in RNA processing and ribosome assembly occur at mitochondrial
    DNA nucleoids.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Localizes RNase P/ELAC2 to mtDNA nucleoids; supports the mitochondrial-nucleoid
      localization annotation.
- id: PMID:25575635
  title: Mitochondrial energy failure in HSD10 disease is due to defective mtDNA transcript
    processing.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Supports that HSD10 disease pathology stems from defective mtDNA transcript (tRNA)
      processing rather than the metabolic defect. Cited in notes; not an existing GOA
      annotation source.
- id: PMID:25925575
  title: 'Molecular insights into HSD10 disease: impact of SDR5C1 mutations on the
    human mitochondrial RNase P complex.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Shows disease mutations impair dehydrogenation, tRNA processing, methylation,
      homotetramerization and TRMT10C interaction; source of several core annotations.
- id: PMID:26338420
  title: Myxococcus CsgA, Drosophila Sniffer, and human HSD10 are cardiolipin phospholipases.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Establishes the cardiolipin phospholipase C-like (cardiolipin dehydrogenase)
      activity, inhibited by Aβ; a distinct in-vitro moonlighting activity (non-core).
- id: PMID:26950678
  title: A novel HSD17B10 mutation impairing the activities of the mitochondrial RNase
    P complex causes X-linked intractable epilepsy and neurodevelopmental regression.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      K212E patient mutation impairing SDR5C1-dependent RNase P activities; source of an
      EXP dehydrogenase annotation.
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      High-throughput interactome study; source of a bare protein-binding (TRMT10C) IPI,
      marked over-annotated.
- id: PMID:28888424
  title: Novel patient missense mutations in the HSD17B10 gene affect dehydrogenase
    and mitochondrial tRNA modification functions of the encoded protein.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      V12L/V176M patient mutations reduce dehydrogenase, methyltransferase and tRNA
      processing; clean statement of the dual catalytic/non-catalytic functions.
- id: PMID:29040705
  title: The MRPP1/MRPP2 complex is a tRNA-maturation platform in human mitochondria.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Shows MRPP1/2 retains tRNA after 5'-cleavage, enhances ELAC2 3'-processing and
      presents tRNA to the CCA-adding enzyme; source of tRNA-binding and processing
      annotations.
- id: PMID:29128334
  title: A Map of Human Mitochondrial Protein Interactions Linked to Neurodegeneration
    Reveals New Mechanisms of Redox Homeostasis and NF-κB Signaling.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Mitochondrial interactome map; source of bare protein-binding IPIs (EEF2, TRAP1)
      of unclear functional significance, marked over-annotated.
- id: PMID:29880640
  title: Structural insight into the human mitochondrial tRNA purine N1-methyltransferase
    and ribonuclease P complexes.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Structural study of the MRPP1/MRPP2 and RNase P complexes; source of RNase P
      complex, mitochondrion and 5'-processing annotations.
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Neurodegeneration interactome; source of a bare protein-binding (APP/Aβ) IPI,
      marked over-annotated.
- id: PMID:32825572
  title: 'Study of Biomolecular Interactions of Mitochondrial Proteins Related to
    Alzheimer''s Disease: Toward Multi-Interaction Biomolecular Processes.'
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Alzheimer-related mitochondrial interaction study; source of a bare protein-binding
      (Aβ peptide) IPI, marked over-annotated.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Proteome-scale interactome; source of a bare protein-binding (TRMT10C) IPI, marked
      over-annotated.
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics
    in cellular context.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: High-confidence mitochondrial proteome; supports mitochondrion localization.
- id: PMID:38824131
  title: Structural basis for human mitochondrial tRNA maturation.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Cryo-EM of the four mt-tRNA maturation steps; supports the maturation-platform,
      CCA-addition and catalytic-complex annotations.
- id: PMID:39516281
  title: Structural basis of 3'-tRNA maturation by the human mitochondrial RNase Z
    complex.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Cryo-EM of the mitochondrial RNase Z (ELAC2/SDR5C1/TRMT10C) complex; supports the
      3'-processing and endoribonuclease-complex annotations.
- id: Reactome:R-HSA-508369
  title: alpha-methylacetoacetyl-CoA + NADH + H+ <=> alpha-methyl-beta-hydroxybutyryl-CoA
    + NAD+
  findings: []
- id: Reactome:R-HSA-6787591
  title: TRMT10C:HSD17B10 (TRMT10C:SDR5C1) of mitochondrial RNase P methylates guanosine-9
    in tRNA yielding 1-methylguanosine-9
  findings: []
- id: Reactome:R-HSA-6787594
  title: TRMT10C:HSD17B10 (TRMT10C:SDR5C1) methylates adenosine-9 in tRNA yielding
    1-methyladenosine-9
  findings: []
- id: Reactome:R-HSA-70837
  title: alpha-methyl-beta-hydroxybutyryl-CoA + NAD+ <=> alpha-methylacetoacetyl-CoA
    + NADH + H+
  findings: []
- id: Reactome:R-HSA-9838081
  title: LONP1 degrades mitochondrial matrix proteins
  findings: []
- id: Reactome:R-HSA-9838093
  title: LONP1 binds mitochondrial matrix proteins
  findings: []