omcZ (GSU2076, UniProt Q74BG5) — Geobacter sulfurreducens PCA

Starting point

• UniProt Q74BG5 is an unreviewed (TrEMBL) entry named only "Cytochrome c",
  473 aa, PE 1 (two cryo-EM structures: PDB 7LQ5, residues 25-282, and 8D9M).
  SignalP signal peptide 1-24; Pfam IPT/TIG domain 392-455 (in the part that is
  later cut off). No PANTHER family is assigned in the UniProt record.
• GOA has no annotations at all for this protein (omcZ-goa.tsv is header only,
  checked 2026-11-09). Every annotation in the review is therefore a NEW row.
• No provider deep-research file was generated for this gene; the literature search
  below was done by hand from PubMed (query OmcZ[Title/Abstract] AND Geobacter,
  41 hits on 2026-11-09) plus the paper supplied by the user,
  Wissink et al. 2026 (DOI:10.1038/s41467-026-78976-x, not yet indexed in PubMed;
  cached from the CC-BY PDF as publications/DOI_10.1038_s41467-026-78976-x.md).

Residue numbering — read before quoting a residue

The structure papers (Gu et al. 2023 PMID:36732469; Wissink et al. 2026) number
residues on the mature protein, i.e. UniProt position minus 24 (the SignalP
signal peptide). Checked against the Q74BG5 sequence:

The 258-residue nanowire-forming OmcZ30 (Gu 2023, Wissink 2026) corresponds to
UniProt 25-282, matching the PDB 7LQ5 chain range. The review YAML avoids stating
residue numbers for this reason.

Biology, with provenance

Identity, hemes and processing

• OmcZ is made as a 50 kDa precursor (OmcZL) and a 30 kDa mature form (OmcZS);
  OmcZS keeps all eight hemes, one bound by an unusual CX14CH motif
  PMID:20400562.
• OmcZS is very thermostable (Tm 94.2 °C) and its hemes span -420 to -60 mV, midpoint
  about -220 mV vs SHE PMID:20400562.
• Cleavage is done by the subtilisin-like serine protease OzpA (GSU2075, immediately
  downstream); ozpA mutants accumulate OmcZL, make no OmcZS and produce as little
  current as omcZ mutants
  PMID:33837010.
  Cleavage activity is found only in the culture supernatant fraction, so maturation
  happens outside the cell PMID:33837010.
• omcZ, ozpA and a peptidyl-prolyl cis-trans isomerase gene (GSU2074) form an operon;
  OzpA cleaves native and recombinant OmcZ50 into OmcZ30, which self-assembles into
  filaments indistinguishable from native ones
  PMID:36732469.
• AlphaFold models of the cleaved C-terminal region show Ig-like beta-sandwich domains
  (two in OmcZ of G. sulfurreducens), which agrees with the Pfam IPT/TIG hit at 392-455
  [DOI:10.1038/s41467-026-78976-x "the cleaved C-terminal regions adopt β-sandwich folds resembling immunoglobulin-like domains, with three such domains in OmcZ2Mv and two in OmcZGs"].
  Gu 2023 describes the same extra domain as resembling a sugar-binding domain and
  proposes that it blocks polymerization until it is removed.

Structure of the filament

• Two independent cryo-EM structures of OmcZ filaments: Wang et al. 2022
  (PMID:36062910, Bond/Egelman labs, PDB 8D9M) and Gu et al. 2023 (PMID:36732469,
  Malvankar lab, PDB 7LQ5, 3.5 Å). Both are helical homopolymers of OmcZ30 with eight
  hemes per subunit. Hemes I-V and VII form a linear chain and heme VI branches off,
  fully exposed to solvent
  PMID:36732469.
• Unlike OmcS and OmcE, there is no heme coordination between subunits, and the heme
  packing differs, which led Wang et al. to propose that cytochrome polymers evolved
  more than once PMID:36062910.
• The heme II CX14CH loop is solvent exposed. Deleting it from reconstituted OmcZ
  lowers the rate of electron transfer to extracellular acceptors (PMID:36732469).
• Both structures were solved at pH 10.5 in ethanolamine buffer to stop the filaments
  aggregating; the archaeal OmcZ2 structure in Wissink 2026 was the first one solved
  at near-neutral pH [DOI:10.1038/s41467-026-78976-x "Previous structural studies of OmcZGs required alkaline conditions (ethanolamine buffer, pH 10.5) to prevent extensive filament aggregation in vitro27,28."].
  Gu 2023 report that CD spectra at pH 7 and pH 10.5 are similar.

Function: long-range electron transfer to electrodes

• omcZ deletion cuts maximum current about ten-fold (14.4 to 1.3 mA), and plasmid
  complementation restores it (13.4 mA)
  PMID:19461962.
  The mutant did not adapt even after more than 50 days.
• The same deletion has no effect on growth with fumarate, Fe(III) citrate or Fe(III)
  oxide PMID:19461962,
  and no effect on biofilm formation when fumarate is the acceptor. So the phenotype is
  specific to electrodes and is not a general growth defect.
• Purified OmcZS reduces Fe(III) citrate, U(VI), Cr(VI), Au(III), Mn(IV) oxide and
  AQDS in vitro, but not Fe(III) oxide PMID:20400562.
  This is single-turnover electron delivery by the reduced cytochrome, not shown to be
  catalytic; together with the lack of an Fe(III)-citrate growth phenotype I treat it as
  evidence of electron transfer activity and not as a metal reductase activity.
  Gu 2023 report that OmcZ nanowires do reduce Fe(III) oxide, but more slowly than OmcS,
  and that OmcZ is not essential for Fe(III) oxide reduction.
• Immunogold labelling puts OmcZ in the extracellular matrix, and concentrated at the
  biofilm-electrode interface in electrode-grown biofilms
  PMID:23761253.
  The omcZ promoter is active uniformly through the biofilm (PMID:22577044), so this
  localization is not explained by where the gene is expressed.
• The matrix that anchors OmcZ is polysaccharide-dependent: a xap (GSU1501) mutant's
  sheared matrix is "nearly devoid of c-type cytochromes such as OmcZ" (PMID:21169487).
• Secretion of OmcZ needs the PilA-N/PilA-C pilus. In ΔpilA-N cells OmcZ stays in the
  periplasm (PMID:34471289), so a ΔpilA-N current phenotype can be explained by OmcZ
  and OmcS never reaching the outside of the cell.
• Ye et al. 2022 (PMID:35164556): OmcZ contributes both structurally (to the biofilm)
  and conductively, as opposed to pili (structural only) and OmcS (conductive only).
• Jiang et al. 2023 (PMID:37881251): ΔomcZ was impaired in ferrihydrite and anode
  reduction and in co-culture with G. metallireducens; in a ΔhybL background, omcZ
  deletion alone abolished DIET-based co-culture. The ferrihydrite result conflicts
  with Nevin 2009 and with Gu 2023's statement that OmcZ is not essential for Fe(III)
  oxide reduction; both papers come from the same field, so I record the conflict
  rather than resolving it.
• Tang et al. 2019 (PMID:31088920): in strain ACLHF (no H2 uptake), omcZ deletion
  prevented growth on Fe(0), and complementation restored it. This is electron uptake
  through OmcZ; in wild-type backgrounds the earlier finding was the opposite (deletion
  did not inhibit uptake).

Conductivity claims and the controversy

• Yalcin et al. 2020 (PMID:32807967): an electric field applied to biofilms stimulates
  production of OmcZ nanowires with about 30 S/cm conductivity, roughly 1000-fold more
  than OmcS.
• Guberman-Pfeffer 2023 (PMID:37552847) computed that redox conductivity among OmcE,
  OmcS and OmcZ should differ by less than 10^3-fold, with redox currents of at most
  about 3 fA at a 0.1 V bias. Guberman-Pfeffer 2024 (PMID:38633696) argues that the
  reported metallic-like conductivities are artefacts.
• The Lovley group continues to argue that the electrically conductive filaments are
  e-pili (PilA) rather than cytochromes (debate summarised in PMID:38633696 and
  PMID:40740311).
• Curation consequence: the mechanism (redox hopping versus band-like conduction)
  and the absolute conductivity are disputed. That OmcZ transfers electrons is not
  disputed: it has eight redox-active hemes and delivers electrons to acceptors in vitro,
  and the genetic phenotype on electrodes is reproducible. The MF annotation is therefore
  GO:0009055 electron transfer activity, with no claim about the conduction mechanism.

Wissink et al. 2026 (supplied paper) — what it adds for G. sulfurreducens OmcZ

The paper is mainly about the archaeal homologue OmcZ2 of "Ca. Methanoperedens
vercellensis", solved at 3.3 Å from electrode-grown, near-axenic cultures at pH 7.25.
For the Geobacter protein (called OmcZGs in the paper) it adds:
- A structural alignment with an archaeal OmcZ that shares only about 30% sequence
identity. The fold and heme architecture are conserved across domains, with a
"core quadrangle" of four conserved short sequence regions around hemes V and VIII,
and three conserved His-His motifs that link heme pairs.
- Bacterial OmcZ forms its own phylogenetic group, Group VI; Groups I-V are archaeal
(ANME and Borg elements). Archaeal clusters co-occur with serine peptidases,
consistent with an OzpA-type maturation step.
- OmcZGs has only three N-glycosylation motifs and no detectable glycan density,
whereas the archaeal protein is extensively modified.
- In OmcZGs hemes I, III and VI are largely solvent exposed and the nanowires aggregate
into dense networks, while the archaeal filaments are straighter and their hemes more
buried.
- Archaea assemble OmcZ nanowires without a prolyl isomerase in the cluster. This makes
it questionable whether the Geobacter isomerase GSU2074 is needed for OmcZ folding,
as Gu 2023 proposed; it may instead be a lineage-specific requirement.
- The OmcZ phenotype in G. sulfurreducens is not re-tested here; the paper relies on the
earlier literature (its refs 27, 30, 33 = PMID:36732469, PMID:32807967, PMID:33837010).

Annotation decisions (summary)

All rows are NEW, because GOA has nothing for this protein.
- MF GO:0009055 electron transfer activity — IDA (PMID:20400562) — core.
- MF GO:0020037 heme binding — IDA (cryo-EM, PMID:36732469; heme counting, PMID:20400562).
- CC GO:0097311 bacterial biofilm matrix — IDA (immunogold, PMID:23761253) — core location.
- BP GO:0019645 anaerobic electron transport chain — IMP (PMID:19461962). OmcZ is
itself an electron carrier at the end of the chain, so it does part of the work; this
matches the term used for OmcA (SHEON), ImcH and CbcL (GEOSL) in this repository.
- BP GO:0051258 protein polymerization — IDA (in vitro self-assembly after OzpA
cleavage, PMID:36732469).
- Not added:
- GO:0016722 oxidoreductase activity, acting on metal ions — single-turnover in vitro
metal reduction with no growth phenotype on Fe(III) citrate.
- GO:0042710 biofilm formation — the defect is conditional on current-harvesting mode
and absent on fumarate, so it is probably secondary to failed respiration.
- GO:0009986 cell surface — the filaments are extracellular and matrix-embedded; there
is no evidence of an anchoring mechanism.
- Ontology gap: GO has no cellular-component term for an extracellular cytochrome
filament ("nanowire"), so one is proposed (see proposed_new_terms).