Cobalt-zinc-cadmium resistance protein CzcC (VPARA_44910) in Variovorax paradoxus strain TBEA6 is a 445-amino-acid outer-membrane factor (OMF, TC 1.B.17) channel subunit (InterPro IPR003423, InterPro IPR010131, PANTHER PTHR30203) encoded at the 3' end of the tripartite czcA3-czcB-czcC (VPARA_44890-VPARA_44910) heavy-metal efflux operon. Synthesized as a precursor with a 20-residue N-terminal Sec signal peptide (residues 1-20) and a 425-residue mature chain (residues 21-445) containing two tandem outer membrane efflux protein (OEP) repeats (Pfam PF02321), CzcC assembles into a trimeric TolC-like outer-membrane beta-barrel and periplasmic alpha-helical tunnel that docks with the periplasmic adaptor CzcB (VPARA_44900) and the inner-membrane HME-RND antiporter CzcA3 (VPARA_44890) to form a continuous conduit for exporting monoatomic metal cations across the outer membrane.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0015562 efflux transmembrane transporter activity | IEA GO_REF:0000002 | ACCEPT | Summary: Accurate core molecular function of the outer-membrane efflux channel subunit of the tripartite CzcCBA complex. Reason: Unlike the periplasmic membrane-fusion adaptor CzcB (VPARA_44900, which forms no transmembrane pore and acts as a structural intermembrane bridge, GO:0005198), CzcC (VPARA_44910) contains two tandem outer membrane efflux protein repeats (Pfam PF02321, InterPro IPR003423, PANTHER PTHR30203) that assemble into the actual outer-membrane transmembrane beta-barrel pore and periplasmic alpha-helical exit conduit through which metal cations traverse the outer membrane. Supporting Evidence: UniProtKB:A0A0H2M0U4 DR PANTHER; PTHR30203; OUTER MEMBRANE CATION EFFLUX PROTEIN; 1. PMID:10559151 The Czc system of Ralstonia sp. strain CH34 mediates resistance to cobalt, zinc, and cadmium through ion efflux catalyzed by the CzcCB(2)A cation-proton antiporter. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Correct but overly general cellular component; refine to GO:0009279 (cell outer membrane). Reason: VPARA_44910 carries an N-terminal signal peptide (residues 1-20) and two outer membrane efflux protein repeats (Pfam PF02321, InterPro IPR003423, PANTHER PTHR30203) that embed the mature channel (residues 21-445) in the Gram-negative cell outer membrane (GO:0009279). Proposed replacements: cell outer membrane Supporting Evidence: UniProtKB:A0A0H2M0U4 DR PANTHER; PTHR30203; OUTER MEMBRANE CATION EFFLUX PROTEIN; 1. UniProtKB:A0A0H2M0U4 DR Pfam; PF02321; OEP; 2. |
| GO:0022857 transmembrane transporter activity | IEA GO_REF:0000002 | MODIFY | Summary: Correct but overly general molecular function; refine to GO:0015562 (efflux transmembrane transporter activity) and GO:0008324 (monoatomic cation transmembrane transporter activity). Reason: GO:0022857 (transmembrane transporter activity) is a broad parent term; within the tripartite czcA3-czcB-czcC cation-efflux operon, CzcC (PANTHER PTHR30203, OUTER MEMBRANE CATION EFFLUX PROTEIN) mediates efflux transmembrane transporter activity (GO:0015562) and monoatomic cation transmembrane transporter activity (GO:0008324). Proposed replacements: efflux transmembrane transporter activity monoatomic cation transmembrane transporter activity Supporting Evidence: UniProtKB:A0A0H2M0U4 DR PANTHER; PTHR30203; OUTER MEMBRANE CATION EFFLUX PROTEIN; 1. PMID:10559151 The Czc system of Ralstonia sp. strain CH34 mediates resistance to cobalt, zinc, and cadmium through ion efflux catalyzed by the CzcCB(2)A cation-proton antiporter. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: Correct but overly general biological process; refine to GO:0098655 (monoatomic cation transmembrane transport). Reason: GO:0055085 (transmembrane transport) is a generic parent term; CzcC functions as the outer-membrane exit channel of the CzcCBA complex mediating monoatomic cation transmembrane transport (GO:0098655). Proposed replacements: monoatomic cation transmembrane transport Supporting Evidence: UniProtKB:A0A0H2M0U4 DR PANTHER; PTHR30203; OUTER MEMBRANE CATION EFFLUX PROTEIN; 1. PMID:10559151 The Czc system of Ralstonia sp. strain CH34 mediates resistance to cobalt, zinc, and cadmium through ion efflux catalyzed by the CzcCB(2)A cation-proton antiporter. |
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Download this section (compressed HTML)Q: Is CzcC (VPARA_44910) dedicated exclusively to the co-transcribed CzcA3-CzcB (VPARA_44890-VPARA_44900) pump in Variovorax paradoxus TBEA6, or can it also serve as the shared outer-membrane channel for other CzcA/CzcB paralogs lacking an adjacent OMF gene?
Suggested experts: Nies DH, Koronakis V, Luisi BF
Experiment: Construct a ΞczcC (VPARA_44910) deletion mutant in Variovorax paradoxus TBEA6 and compare its sensitivity to Zn2+, Co2+, and Cd2+ with that of a ΞczcA3 (VPARA_44890) mutant.
Hypothesis: Deletion of czcC abolishes outer-membrane export of divalent cations by the CzcA3-CzcB complex, increasing intracellular metal accumulation and metal sensitivity.
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