Curation Notes for Variovorax paradoxus S110 fetP (C5CNX5, FETP_VARPS, Vapar_2982)

Overview

• UniProt Accession: C5CNX5 (FETP_VARPS)
• Ordered Locus Name: Vapar_2982
• Gene Symbol: fetP
• Organism: Variovorax paradoxus S110 (NCBITaxon:543728)
• Protein Function: Probable cytosolic $\text{Fe}^{2+}$-trafficking protein (FetP / YggX, 90 aa) predicted via HAMAP rule MF_00686 (InterPro:IPR007457) to mediate intracellular iron transactions between iron acquisition and iron-requiring processes such as synthesis and repair of [Fe-S] clusters.
• Disambiguation Note: Vapar_2982 (C5CNX5) bears the entry name FETP_VARPS via the YggX Fe(2+)-trafficking family rule (HAMAP-Rule:MF_00686) and is distinct from the uncurated periplasmic FetP-like cupredoxin (Vapar_3862 / C5CUI1) encoded adjacent to the variobactin siderophore locus.

Literature & Domain Evidence

1. Genomic Context in Variovorax paradoxus S110 (PMID:21183664, UniProtKB:C5CNX5):
2. Encoded at locus Vapar_2982 on Chromosome 1 of Variovorax paradoxus S110 (PMID:21183664), adjacent to the alkanesulfonate utilization cluster (Vapar_2976 ssuD).
3. Conserved YggX/FetP Domain Architecture & Essential Cys7 (UniProtKB:C5CNX5, PMID:12670952, PMID:11416172):
4. C5CNX5 (FETP_VARPS) is a 90-aa Swiss-Prot reviewed entry curated under HAMAP:MF_00686 (InterPro:IPR007457, Pfam:PF04362, PANTHER:PTHR36965:SF1), annotated with KW Iron., CC -!- SIMILARITY: Belongs to the Fe(2+)-trafficking protein family. {ECO:0000255|HAMAP-Rule:MF_00686}., and CC -!- FUNCTION: Could be a mediator in iron transactions between iron acquisition and iron-requiring processes, such as synthesis and/or repair of Fe-S clusters in biosynthetic enzymes. {ECO:0000255|HAMAP-Rule:MF_00686}. (UniProtKB:C5CNX5).
5. Direct inspection of the C5CNX5 sequence (MARMVQCIKL... in SQ) confirms conservation of Cys7, the invariant N-terminal cysteine demonstrated in Salmonella enterica YggX to be essential for intracellular $\text{Fe}^{2+}$ chelation/trafficking and protection against Fenton-mediated hydroxyl radical DNA damage (PMID:12670952; PMID:12670952) and superoxide inactivation of [Fe-S] clusters (PMID:11416172).

Review of Existing GOA Annotations

• GO:0005506 (iron ion binding, IEA via GO_REF:0000120: InterPro:IPR007457, InterPro:IPR036766, UniRule:UR000033441) -> ACCEPT (core molecular function supported by HAMAP:MF_00686 / InterPro:IPR007457 YggX-family classification, KW Iron., and conservation of the essential Cys7 residue in C5CNX5, PMID:12670952).
• GO:0005829 (cytosol, IEA via TreeGrafter GO_REF:0000118 / PANTHER:PTN002863974) -> ACCEPT (90-aa soluble cytoplasmic YggX-family protein lacking signal peptides or transmembrane helices, UniProtKB:C5CNX5).
• GO:0034599 (cellular response to oxidative stress, IEA via TreeGrafter GO_REF:0000118 / PANTHER:PTN002863974) -> KEEP_AS_NON_CORE (downstream cellular protection against superoxide and Fenton-mediated hydroxyl radical damage resulting from cytosolic $\text{Fe}^{2+}$ trafficking, characterized in S. enterica YggX in PMID:11416172 and PMID:12670952).

Proposed New Annotations

• GO:0006879 (intracellular iron ion homeostasis) — involved_in (ISS from characterized Salmonella enterica YggX in PMID:12670952 and PMID:11416172), supported by conservation of the essential Cys7 residue in C5CNX5 (MARMVQCIKL...) and the HAMAP:MF_00686 annotation (PE 3, Probable Fe(2+)-trafficking protein: "Could be a mediator in iron transactions between iron acquisition and iron-requiring processes, such as synthesis and/or repair of Fe-S clusters in biosynthetic enzymes", UniProtKB:C5CNX5).