fae

id: Q9FA38
gene_symbol: fae
product_type: PROTEIN
taxon:
  id: NCBITaxon:272630
  label: Methylorubrum extorquens AM1
description: "fae encodes the formaldehyde-activating enzyme (5,6,7,8-tetrahydromethanopterin\
  \ hydro-lyase, EC 4.2.1.147), which catalyzes the first and critical step in formaldehyde\
  \ detoxification and metabolism. The enzyme condenses formaldehyde with tetrahydromethanopterin\
  \ (H4MPT) to form 5,10-methylenetetrahydromethanopterin, channeling formaldehyde\
  \ into the central C1 metabolic pathway. While this reaction proceeds spontaneously,\
  \ Fae catalyzes it at a substantially higher rate. The protein forms a homopentamer\
  \ in the cytoplasm and is essential for growth on methanol, as it both detoxifies\
  \ the highly reactive formaldehyde produced by methanol dehydrogenases and provides\
  \ the substrate for downstream C1 metabolism. Crystal structure has been solved\
  \ at 1.9 \xC5 resolution, revealing the mechanism of H4MPT binding and formaldehyde\
  \ activation. The enzyme exhibits optimal activity at pH 7-7.5 with a KM of 0.2\
  \ mM for formaldehyde."
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: 'Correct - Fae is localized to the cytoplasm where it catalyzes formaldehyde
      activation [file:METEA/fae/fae-uniprot.txt, "SUBCELLULAR LOCATION: Cytoplasm"].'
    action: ACCEPT
- term:
    id: GO:0006730
    label: one-carbon metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Correct - Fae is central to C1 metabolism, catalyzing the first step
      in formaldehyde processing [file:METEA/fae/fae-uniprot.txt, "One-carbon metabolism"
      and "essential enzyme for methylotrophic energy metabolism"].
    action: ACCEPT
- term:
    id: GO:0009636
    label: response to toxic substance
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Correct - Fae detoxifies formaldehyde, a highly reactive and toxic metabolite
      [file:METEA/fae/fae-uniprot.txt, "essential enzyme for...formaldehyde detoxification"].
    action: ACCEPT
- term:
    id: GO:0016051
    label: carbohydrate biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: Incorrect - While Fae works with H4MPT (which contains a pterin moiety),
      it does not participate in carbohydrate biosynthesis. Its function is formaldehyde
      activation for C1 metabolism.
    action: REMOVE
- term:
    id: GO:0016829
    label: lyase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Correct - Fae is classified as a hydro-lyase (EC 4.2.1.147) [file:METEA/fae/fae-uniprot.txt,
      "5,6,7,8-tetrahydromethanopterin hydro-lyase"].
    action: ACCEPT
- term:
    id: GO:0016840
    label: carbon-nitrogen lyase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: Incorrect - Fae is a hydro-lyase, not a carbon-nitrogen lyase. It catalyzes
      addition of formaldehyde to H4MPT with elimination of water, not cleavage of
      C-N bonds.
    action: REMOVE
- term:
    id: GO:0046294
    label: formaldehyde catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  review:
    summary: 'Correct - Fae catalyzes the first step in formaldehyde degradation via
      the H4MPT route [file:METEA/fae/fae-uniprot.txt, "One-carbon metabolism; formaldehyde
      degradation; formate from formaldehyde (H4MPT route): step 1/5"].'
    action: ACCEPT
core_functions:
- description: 'Fae catalyzes the critical first step in formaldehyde metabolism by
    condensing formaldehyde with tetrahydromethanopterin (H4MPT) to form 5,10-methylenetetrahydromethanopterin.
    This reaction serves dual purposes: (1) detoxifying the highly reactive formaldehyde
    produced by methanol dehydrogenases, and (2) channeling the C1 unit into central
    metabolism for biosynthesis and energy generation. The enzyme functions as a homopentamer
    and is absolutely essential for growth on methanol. While the reaction proceeds
    spontaneously, Fae accelerates it substantially, with optimal activity at pH 7-7.5
    and a KM of 0.2 mM for formaldehyde.'
  molecular_function:
    id: GO:0016829
    label: lyase activity
  directly_involved_in:
  - id: GO:0046294
    label: formaldehyde catabolic process
  - id: GO:0006730
    label: one-carbon metabolic process
  - id: GO:0009636
    label: response to toxic substance
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:METEA/fae/fae-uniprot.txt
    supporting_text: Catalyzes the condensation of formaldehyde with tetrahydromethanopterin
      (H4MPT) to 5,10-methylenetetrahydromethanopterin... Is an essential enzyme for
      methylotrophic energy metabolism and formaldehyde detoxification... Homopentamer...Optimum
      pH is 7-7.5...KM=0.2 mM for formaldehyde
references:
- id: file:METEA/fae/fae-uniprot.txt
  title: UniProt entry for fae formaldehyde-activating enzyme
  findings: []
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms.
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping.
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword 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: []
status: COMPLETE
tags:
- metea