gp29

id: P67877
gene_symbol: gp29
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:6279
  label: Brugia malayi
description: Bm-gp29 is the major soluble cuticular glycoprotein (also known as gp29/gp30
  and a major surface antigen) of the lymphatic filarial nematode Brugia malayi and
  related Brugia species. It is a secreted glutathione peroxidase (EC 1.11.1.9) of the
  glutathione peroxidase family in which the catalytic selenocysteine of mammalian
  GPX enzymes is replaced by a cysteine, making it a non-selenium GPX. The mature
  protein is N-glycosylated and assembles into a homotetramer. Functionally it reduces
  hydroperoxides using glutathione; filarial gp29 has been reported to act preferentially
  on fatty-acid and phospholipid hydroperoxides (phospholipid-hydroperoxide glutathione
  peroxidase-type activity), protecting membranes and the cuticle from lipid peroxidation. It is secreted into the cuticular matrix
  and released into the surrounding medium, where it is positioned to detoxify oxidative
  species and neutralize lipid-peroxidation products generated by host immune effector
  cells, contributing to parasite survival at the host-parasite interface. It may
  also participate in cross-linking of cuticular collagen (e.g. dityrosine formation).
  Expression is developmentally regulated, being up-regulated in infective third-stage
  larvae and maintained through the adult stage but absent from microfilariae.
existing_annotations:
- term:
    id: GO:0004601
    label: peroxidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: gp29 is a peroxidase, so this parent term is not wrong. However it is
      an over-general ancestor of the more specific, well-supported glutathione
      peroxidase activity (GO:0004602) that this protein carries out. Because a more
      specific and accurate child MF term is available, this generic term is an
      over-annotation.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0004602
    label: glutathione peroxidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: gp29 is a member of the glutathione peroxidase family and the EC 1.11.1.9
      / RHEA:16833 mapping (2 glutathione + H2O2 = glutathione disulfide + 2 H2O) is
      consistent with the UniProt catalytic activity annotation; the catalytic
      selenocysteine of mammalian GPX is replaced by cysteine (non-selenium GPX).
      Accept this as the well-supported core molecular function. Filarial gp29 enzymes
      have been reported to act preferentially on fatty-acid/phospholipid hydroperoxides
      (i.e. phospholipid-hydroperoxide GPX activity, GO:0047066), but that
      substrate-specificity refinement is not directly demonstrated for B. malayi
      P67877 in a citable primary reference here, so it is recorded as a suggested
      refinement (see suggested_questions) rather than asserted as a MODIFY.
    action: ACCEPT
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Consistent with UniProt subcellular location (Secreted; secreted into
      the cuticle and ultimately released into the medium) and with the protein's
      identity as the major soluble cuticular glycoprotein and a surface antigen.
      The signal peptide supports secretion. Accept as a correct, if general, location.
    action: ACCEPT
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: Biologically reasonable; as a secreted glutathione peroxidase gp29 acts
      in the response to oxidative attack, plausibly detoxifying host-derived oxidants
      and lipid-peroxidation products at the parasite surface. This is a broad process
      term rather than the protein's core molecular activity, so retain as non-core
      context.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0098869
    label: cellular oxidant detoxification
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: This is the operative biological process for a glutathione peroxidase
      and is well supported by the enzyme's reduction of (phospho)lipid hydroperoxides
      and peroxides, protecting membranes and the cuticle from oxidative damage. Accept.
    action: ACCEPT
core_functions:
- description: Non-selenium (cysteine-containing) glutathione peroxidase that reduces
    hydroperoxides using glutathione, protecting membranes and the parasite cuticle
    from oxidative/lipid-peroxidation damage; secreted into the cuticular matrix and
    the extracellular environment at the host-parasite interface. Filarial gp29 is
    reported to prefer fatty-acid/phospholipid hydroperoxides (phospholipid-hydroperoxide
    GPX-type activity), but the core MF is annotated at the well-supported glutathione
    peroxidase level pending a citable primary reference for B. malayi substrate specificity.
  molecular_function:
    id: GO:0004602
    label: glutathione peroxidase activity
  supported_by:
  - reference_id: GO_REF:0000120
  locations:
  - id: GO:0005576
    label: extracellular region
suggested_questions:
- question: >-
    Does B. malayi gp29 (P67877) preferentially reduce fatty-acid/phospholipid hydroperoxides
    over hydrogen peroxide, i.e. does it have phospholipid-hydroperoxide glutathione peroxidase
    activity (GO:0047066)? If demonstrated for this protein, the core MF could be refined from
    glutathione peroxidase activity to the more specific PHGPx term.
  experts:
  - Filarial nematode redox biochemists
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  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:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []