CzcA3 (VPARA_44890) in Variovorax paradoxus is a 1067-amino-acid predicted inner-membrane Heavy-Metal Efflux Resistance-Nodulation-Division (HME-RND) transporter subunit (NCBIfam TIGR00914, InterPro IPR004763, PANTHER PTHR32063:SF24) containing 12 transmembrane alpha-helices and two large periplasmic porter loops. Based on HME-RND family membership, CzcA3 functions as the inner-membrane proton/cation antiporter component that partners with a periplasmic membrane-fusion adaptor protein and an outer-membrane factor channel to drive transmembrane export of monoatomic metal cations.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Reason: CzcA3 (VPARA_44890) is a 1067-residue integral inner-membrane RND transporter subunit with 12 transmembrane helices anchored in the bacterial plasma membrane. Supporting Evidence: UniProtKB:A0A0H2MBF7 FT TRANSMEM 12..31 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" |
| GO:0006812 monoatomic cation transport | IEA GO_REF:0000002 | TOO GENERAL | Reason: The broad term monoatomic cation transport (GO:0006812) is true of CzcA3 but subsumed by the specific child term monoatomic cation transmembrane transport (GO:0098655) already accepted on this record. Supporting Evidence: UniProtKB:A0A0H2MBF7 DR NCBIfam; TIGR00914; 2A0601; 1. |
| GO:0008324 monoatomic cation transmembrane transporter activity | IEA GO_REF:0000002 | ACCEPT | Reason: VPARA_44890 belongs to the HME-RND (Heavy Metal Efflux) CzcA/CusA family (NCBIfam TIGR00914, InterPro IPR004763) that catalyzes proton-driven transmembrane transport of monoatomic metal cations. Supporting Evidence: UniProtKB:A0A0H2MBF7 DR InterPro; IPR004763; CusA-like. |
| GO:0016020 membrane | IEA GO_REF:0000002 | TOO GENERAL | Reason: Generic membrane (GO:0016020) is true of CzcA3 but subsumed by the more specific term plasma membrane (GO:0005886) already accepted on this record. Supporting Evidence: UniProtKB:A0A0H2MBF7 FT TRANSMEM 12..31 FT /note="Helical" FT /evidence="ECO:0000256|SAM:Phobius" |
| GO:0022857 transmembrane transporter activity | IEA GO_REF:0000002 | TOO GENERAL | Reason: Generic transmembrane transporter activity (GO:0022857) is true of CzcA3 but subsumed by monoatomic cation transmembrane transporter activity (GO:0008324) already accepted on this record. Supporting Evidence: UniProtKB:A0A0H2MBF7 DR InterPro; IPR004763; CusA-like. |
| GO:0042908 xenobiotic transport | IEA GO_REF:0000108 | REMOVE | Reason: VPARA_44890 (CzcA3) is a member of the Heavy Metal Efflux (HME-RND) CzcA/CusA family (NCBIfam TIGR00914, InterPro IPR004763, PANTHER PTHR32063:SF24 CATION EFFLUX SYSTEM), not the Hydrophobe/Amphiphile Efflux (HAE-RND) AcrB multidrug/xenobiotic family. Xenobiotic transport (GO:0042908) is a logical over-propagation from the erroneous TreeGrafter xenobiotic transporter annotation. Supporting Evidence: UniProtKB:A0A0H2MBF7 DR NCBIfam; TIGR00914; 2A0601; 1. |
| GO:0042910 xenobiotic transmembrane transporter activity | IEA GO_REF:0000118 | REMOVE | Reason: TreeGrafter over-propagated xenobiotic transmembrane transporter activity (GO:0042910) from the parent RND family PTHR32063 (which includes AcrB/AcrD/AcrF multidrug pumps). VPARA_44890 specifically matches subfamily PTHR32063:SF24 (CATION EFFLUX SYSTEM), NCBIfam TIGR00914 (2A0601 heavy-metal RND pump), and InterPro IPR004763 (CusA-like), which export inorganic metal cations rather than organic xenobiotics. Supporting Evidence: UniProtKB:A0A0H2MBF7 DR PANTHER; PTHR32063:SF24; CATION EFFLUX SYSTEM (ACRB_ACRD_ACRF FAMILY); 1. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | TOO GENERAL | Reason: The broad term transmembrane transport (GO:0055085) is true of CzcA3 but subsumed by the specific child term monoatomic cation transmembrane transport (GO:0098655) already accepted on this record. Supporting Evidence: UniProtKB:A0A0H2MBF7 DR NCBIfam; TIGR00914; 2A0601; 1. |
| GO:0098655 monoatomic cation transmembrane transport | IEA GO_REF:0000108 | ACCEPT | Reason: CzcA3 (VPARA_44890) catalyzes proton-motive-force-driven transmembrane efflux of monoatomic metal cations across the inner membrane. Supporting Evidence: UniProtKB:A0A0H2MBF7 DR NCBIfam; TIGR00914; 2A0601; 1. |
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Download this section (compressed HTML)Q: What are the specific metal cation substrates (e.g., Co2+/Zn2+/Cd2+ vs Cu+/Ag+ or Ni2+) of VPARA_44890 (CzcA3) relative to other HME-RND paralogs in Variovorax paradoxus?
Experiment: Measure minimum inhibitory concentrations (MICs) and intracellular metal accumulation by ICP-MS for Zn2+, Cd2+, Co2+, Ni2+, and Cu2+ in a Variovorax paradoxus delta-czcA3 mutant.
Hypothesis: CzcA3 mediates selective efflux of inorganic transition-metal cations and does not transport organic xenobiotics.
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