Ech1

id: Q9W5W8
gene_symbol: Ech1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:7227
  label: Drosophila melanogaster
description: >-
  Ech1 (CG9577) is a Drosophila melanogaster delta(3,5),delta(2,4)-dienoyl-CoA isomerase
  (EC 5.3.3.21), an auxiliary enzyme of the beta-oxidation of polyunsaturated fatty acids that have a
  double bond at an odd-numbered carbon. It isomerizes 3-trans,5-cis-dienoyl-CoA (3E,5Z-dienoyl-CoA)
  to 2-trans,4-trans-dienoyl-CoA (2E,4E-dienoyl-CoA), which is then reduced by 2,4-dienoyl-CoA
  reductase and re-isomerized by the delta(3),delta(2)-enoyl-CoA isomerase to rejoin the core
  beta-oxidation spiral. Ech1 is the ortholog of human ECH1; its subcellular localization is not fully
  resolved in the fly - UniProt names it mitochondrial and phylogenetic/orthology evidence places it
  in the mitochondrion, while an electronic and a targeting-signal prediction also assign it to the
  peroxisome (human ECH1 is peroxisomal), so a dual or organism-specific localization is plausible.
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 UniProt "mitochondrial"
      naming of Ech1 and with a role in the mitochondrial beta-oxidation of polyunsaturated fatty acids.
    action: ACCEPT
    reason: >-
      Mitochondrion is the primary annotated compartment for fly Ech1; retained as the core location
      (see the peroxisome annotations for the alternative/dual localization).
- term:
    id: GO:0051750
    label: delta(3,5)-delta(2,4)-dienoyl-CoA isomerase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetically inferred delta(3,5),delta(2,4)-dienoyl-CoA isomerase activity (EC 5.3.3.21) -
      the defining molecular function of Ech1 and the auxiliary step for polyunsaturated fatty acid
      beta-oxidation.
    action: ACCEPT
    reason: >-
      Core molecular function of Ech1, concordant with the EC/UniProt name and the IEA evidence.
    supported_by:
    - reference_id: file:DROME/Ech1/Ech1-uniprot.txt
      supporting_text: "Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial"
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: >-
      ARBA electronic cytoplasm annotation. Ech1 is an organellar (mitochondrial/peroxisomal)
      beta-oxidation enzyme; "cytoplasm" is an over-general parent that does not capture the compartment.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Uninformative over-general term superseded by the specific mitochondrion/peroxisome localization
      annotations.
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic (UniProt subcellular-location) peroxisome annotation. Human ECH1 is peroxisomal, so a
      peroxisomal pool of fly Ech1 is plausible, but the fly protein is primarily annotated
      mitochondrial; the localization is unresolved.
    action: KEEP_AS_NON_CORE
    reason: >-
      Possible dual/alternative localization; retained as non-core relative to the mitochondrion pending
      direct evidence resolving the mitochondrion-vs-peroxisome assignment.
- term:
    id: GO:0016853
    label: isomerase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro electronic annotation to the parent isomerase class. Correct but a high-level parent of
      the specific dienoyl-CoA isomerase activity.
    action: KEEP_AS_NON_CORE
    reason: >-
      Accurate parent term subsumed by the specific delta(3,5),delta(2,4)-dienoyl-CoA isomerase activity.
- term:
    id: GO:0051750
    label: delta(3,5)-delta(2,4)-dienoyl-CoA isomerase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  qualifier: enables
  review:
    summary: >-
      Electronic assignment of the EC 5.3.3.21 dienoyl-CoA isomerase activity, duplicating the core
      molecular-function call.
    action: ACCEPT
    reason: >-
      Core molecular function of Ech1.
    supported_by:
    - reference_id: file:DROME/Ech1/Ech1-uniprot.txt
      supporting_text: "Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial"
- term:
    id: GO:0006635
    label: fatty acid beta-oxidation
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    summary: >-
      Electronic annotation to fatty acid beta-oxidation - specifically the auxiliary dienoyl-CoA
      isomerase step required to fully degrade polyunsaturated fatty acids.
    action: ACCEPT
    reason: >-
      Core biological process for Ech1 as an auxiliary enzyme of (polyunsaturated) fatty acid
      beta-oxidation.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: >-
      Orthology-based mitochondrial localization, concordant with the UniProt mitochondrial naming and
      the IBA mitochondrion call.
    action: ACCEPT
    reason: >-
      Mitochondrion is the primary annotated compartment for fly Ech1; core location.
- term:
    id: GO:0005777
    label: peroxisome
  evidence_type: ISM
  original_reference_id: PMID:22758915
  qualifier: located_in
  review:
    summary: >-
      Sequence-model (targeting-signal) prediction of peroxisomal localization from the Drosophila
      peroxisomal-proteome inventory. Consistent with the peroxisomal localization of human ECH1 but
      in tension with the mitochondrial naming; localization remains unresolved.
    action: KEEP_AS_NON_CORE
    reason: >-
      Possible dual/alternative localization; retained as non-core relative to the mitochondrion pending
      experimental resolution.
    supported_by:
    - reference_id: PMID:22758915
      supporting_text: "The subcellular localization of five of \nthese predicted peroxisomal proteins was confirmed."
      full_text_unavailable: true
- term:
    id: GO:0006635
    label: fatty acid beta-oxidation
  evidence_type: NAS
  original_reference_id: PMID:22758915
  qualifier: involved_in
  review:
    summary: >-
      Author statement associating Ech1 with fatty acid beta-oxidation in the peroxisomal-proteome
      inventory, concordant with its dienoyl-CoA isomerase role.
    action: ACCEPT
    reason: >-
      Core biological process for Ech1 in (polyunsaturated) fatty acid beta-oxidation.
    supported_by:
    - reference_id: PMID:22758915
      supporting_text: "An inventory of peroxisomal proteins and pathways in Drosophila melanogaster"
      full_text_unavailable: true
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- 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: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:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:22758915
  title: An inventory of peroxisomal proteins and pathways in Drosophila melanogaster.
  findings:
  - statement: Ech1 is associated with peroxisomal fatty acid beta-oxidation in the Drosophila
      peroxisomal-proteome inventory (targeting-signal prediction).
    supporting_text: "An inventory of peroxisomal proteins and pathways in Drosophila melanogaster"
    full_text_unavailable: true
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: "Computational peroxisomal-proteome inventory; source of the ISM peroxisome
      prediction and the NAS beta-oxidation call. Contributes to the unresolved mito-vs-peroxisome
      localization of fly Ech1 (human ECH1 is peroxisomal). Abstract-only in cache."
core_functions:
- description: >-
    delta(3,5),delta(2,4)-dienoyl-CoA isomerase (EC 5.3.3.21): isomerizes 3E,5Z-dienoyl-CoA to
    2E,4E-dienoyl-CoA, the auxiliary step that allows beta-oxidation of polyunsaturated fatty acids
    with a double bond at an odd-numbered position to proceed (feeding into 2,4-dienoyl-CoA reductase
    and the delta(3),delta(2)-enoyl-CoA isomerase).
  supported_by:
  - reference_id: file:DROME/Ech1/Ech1-uniprot.txt
    supporting_text: "Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase, mitochondrial"
  molecular_function:
    id: GO:0051750
    label: delta(3,5)-delta(2,4)-dienoyl-CoA isomerase activity
  directly_involved_in:
  - id: GO:0006635
    label: fatty acid beta-oxidation
  locations:
  - id: GO:0005739
    label: mitochondrion
proposed_new_terms: []
suggested_questions:
- question: >-
    Is Drosophila Ech1 mitochondrial (as its UniProt name and phylogenetic annotation indicate),
    peroxisomal (as for human ECH1 and the targeting-signal prediction), or dually localized - and
    which pool supports the mitochondrial polyunsaturated-FAO cassette?
suggested_experiments:
- description: >-
    Tagged-protein localization / organelle fractionation of Ech1 to resolve its mitochondrial versus
    peroxisomal distribution, and an in-vitro assay of recombinant Ech1 on 3E,5Z-dienoyl-CoA to
    confirm the delta(3,5),delta(2,4)-dienoyl-CoA isomerase activity.
  hypothesis: >-
    Fly Ech1 provides the dienoyl-CoA isomerase step of polyunsaturated fatty acid beta-oxidation, with
    a mitochondrial pool serving the mitochondrial cassette even if a peroxisomal pool also exists.