CG4598

id: Q9VL68
gene_symbol: CG4598
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:7227
  label: Drosophila melanogaster
description: >-
  CG4598 is one of a tandem cluster of three Drosophila melanogaster mitochondrial enoyl-CoA delta
  isomerase 1 paralogs (with CG4592 and CG4594), the mitochondrial-type (human ECI1 class)
  delta(3),delta(2)-enoyl-CoA isomerases (EC 5.3.3.8). It is an auxiliary enzyme of unsaturated fatty
  acid beta-oxidation that isomerizes both 3-cis (3Z) and 3-trans (3E) enoyl-CoA double bonds into the
  2-trans (2E) form (with a preference for (3Z)-enoyl-CoAs), regenerating the substrate of the core
  enoyl-CoA hydratase so that unsaturated fatty acids with double bonds at odd-numbered positions can
  be fully degraded. It localizes to the mitochondrial matrix (also supported by organelle proteomics)
  and, unlike the peroxisomal-type isomerase Dci, is a mitochondrial isomerase relevant to the
  mitochondrial unsaturated-FAO cassette. Of the three tandem paralogs, CG4598 uniquely has direct organelle-proteomics localization support (HDA mitochondrion, PMID:19317464).
existing_annotations:
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetically inferred mitochondrial localization, consistent with the mitochondrial ECI1
      family; less specific than the mitochondrial matrix.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct compartment; the mitochondrial matrix (GO:0005759) is the core location.
- term:
    id: GO:0006635
    label: fatty acid beta-oxidation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Phylogenetically inferred participation in fatty acid beta-oxidation - the auxiliary
      delta(3),delta(2)-enoyl-CoA isomerase step for unsaturated fatty acids.
    action: ACCEPT
    reason: >-
      Core biological process for this auxiliary isomerase of (unsaturated) fatty acid beta-oxidation.
- term:
    id: GO:0004165
    label: delta(3)-delta(2)-enoyl-CoA isomerase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    summary: >-
      EC-based electronic assignment of delta(3),delta(2)-enoyl-CoA isomerase activity (EC 5.3.3.8) -
      the defining molecular function of this mitochondrial ECI1-class isomerase.
    action: ACCEPT
    reason: >-
      Core molecular function; concordant with the UniProt name and mitochondrial ECI1 family
      membership.
    supported_by:
    - reference_id: file:DROME/CG4598/CG4598-uniprot.txt
      supporting_text: "Enoyl-CoA delta isomerase 1, mitochondrial"
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic (UniProt subcellular-location) annotation to the mitochondrial matrix - the correct,
      specific compartment for this mitochondrial-type enoyl-CoA isomerase.
    action: ACCEPT
    reason: >-
      The specific, core location; distinguishes CG4598 from the peroxisomal-type isomerase Dci.
    supported_by:
    - reference_id: file:DROME/CG4598/CG4598-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Mitochondrion matrix"
- term:
    id: GO:0004165
    label: delta(3)-delta(2)-enoyl-CoA isomerase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: enables
  review:
    summary: >-
      Orthology-based delta(3),delta(2)-enoyl-CoA isomerase activity, duplicating the core
      molecular-function call.
    action: ACCEPT
    reason: >-
      Core molecular function of CG4598.
    supported_by:
    - reference_id: file:DROME/CG4598/CG4598-uniprot.txt
      supporting_text: "Enoyl-CoA delta isomerase 1, mitochondrial"
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HDA
  original_reference_id: PMID:19317464
  qualifier: located_in
  review:
    summary: >-
      High-throughput organelle-proteomics localization to the mitochondrion, corroborating the
      mitochondrial-matrix assignment.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct compartment from proteomics; the mitochondrial matrix is the specific core location.
references:
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- 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: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: PMID:19317464
  title: Mapping organelle proteins and protein complexes in Drosophila melanogaster.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: "High-throughput organelle proteomics; source of the HDA mitochondrion localization
      for CG4598."
core_functions:
- description: >-
    Mitochondrial delta(3),delta(2)-enoyl-CoA isomerase (EC 5.3.3.8): isomerizes 3Z/3E-enoyl-CoA to
    2E-enoyl-CoA, the auxiliary step that lets unsaturated fatty acids with odd-position double bonds
    re-enter the beta-oxidation spiral. One of three fly mitochondrial ECI1 paralogs (CG4592/CG4594/CG4598).
  supported_by:
  - reference_id: file:DROME/CG4598/CG4598-uniprot.txt
    supporting_text: "Key enzyme of fatty acid beta-oxidation."
  molecular_function:
    id: GO:0004165
    label: delta(3)-delta(2)-enoyl-CoA isomerase activity
  directly_involved_in:
  - id: GO:0006635
    label: fatty acid beta-oxidation
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
proposed_new_terms: []
suggested_questions:
- question: >-
    Do the three tandem mitochondrial enoyl-CoA delta-isomerase paralogs (CG4592/CG4594/CG4598) have
    distinct expression or substrate roles, or are they functionally redundant copies of the
    mitochondrial delta(3),delta(2)-enoyl-CoA isomerase?
suggested_experiments:
- description: >-
    Expression profiling and individual/combined knockouts of CG4592, CG4594 and CG4598 to test
    functional redundancy and confirm the mitochondrial delta(3),delta(2)-enoyl-CoA isomerase step of
    unsaturated fatty acid beta-oxidation in the fly.
  hypothesis: >-
    The CG4592/CG4594/CG4598 cluster provides the mitochondrial delta(3),delta(2)-enoyl-CoA isomerase
    activity (distinct from peroxisomal Dci) required for the mitochondrial unsaturated-FAO cassette.