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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004601 peroxidase activity | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | 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. |
| GO:0004602 glutathione peroxidase activity | IEA GO_REF:0000120 | ACCEPT | 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. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | 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. |
| GO:0006979 response to oxidative stress | IEA GO_REF:0000002 | KEEP AS NON CORE | 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. |
| GO:0098869 cellular oxidant detoxification | IEA GO_REF:0000120 | ACCEPT | 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. |
Loading supporting content…
Download this section (compressed HTML)Q: 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.
Suggested experts: Filarial nematode redox biochemists
Loading supporting content…
Download this section (compressed HTML)