omcS (GSU2504, UniProt Q74A86) — Geobacter sulfurreducens PCA

Starting point

• Q74A86 is a reviewed (Swiss-Prot) entry, integrated 2017, named "C-type cytochrome
  OmcS" with AltName "Outer membrane cytochrome S". 432 aa, signal peptide 1-25, mature
  chain 26-432. No transmembrane feature, no lipid-anchor feature, no lipobox.
• Six CXXCH heme motifs, at precursor positions 34, 72, 165, 264, 353 and 425, matching
  the curated "Binds 6 low-spin heme groups per subunit".
• Two cryo-EM filament structures: PDB 6EF8 (3.70 Å, seven chains, 26-432) and
  6NEF (3.42 Å, 26-432).
• GOA carries 10 annotations (omcS-goa.tsv, fetched 2026-11-09): two IBA, and four
  cellular-component terms each asserted once by IEA and three times by EXP.
• Classification is worth noting because the resources disagree in an informative way:
• CDD cd21555 is called "OmcS-like" — a dedicated conserved domain.
• TCDB 5.B.3.1.1 places it in "the geobacter nanowire electron transfer (g-net)
  family" — again dedicated.
• PANTHER puts it in PTHR30333:SF1 "CYTOCHROME C-TYPE PROTEIN NAPC", and InterPro
  gives it only IPR036280 (multiheme cytochrome superfamily) plus IPR051174, which
  is just InterPro's integration of that same PANTHER family.
• So two resources recognise OmcS as its own thing, and PANTHER files it with the
  NapC/NirT quinol dehydrogenases. See interpro/panther/PTHR30333/PTHR30333-review.yaml,
  where this is recorded as the family's heterogeneity: OmcS matches neither PF03264 nor
  IPR005126, the NapC/NirT N-terminal domain that every genuine member of that family has.
• No provider deep-research file exists for this gene; the literature below was assembled
  by hand from the Swiss-Prot reference list plus the OmcZ-review search.

Biology, with provenance

What it is

• Purified OmcS is 47015 Da with six low-spin bis-histidinyl hexacoordinated hemes and a
  midpoint potential of -212 mV
  PMID:21236241.
• It is loosely bound, not membrane-integrated
  PMID:21236241,
  and was originally found among proteins "easily sheared from the outer surfaces of intact
  cells" PMID:16332857.
• Secondary structure is mostly disordered: about 10% alpha-helix (PMID:21236241).

What it does

• Dithionite-reduced OmcS passes electrons to insoluble Fe(III) oxide, Mn(IV) oxide and
  humic substances
  PMID:21236241.
  Stopped-flow rates: 25.2 s⁻¹ with AQDS, 2.9 s⁻¹ with Fe(III) citrate, with hyperbolic
  dependence on substrate concentration. This is oxidation of the pre-reduced protein,
  i.e. stoichiometric electron delivery, not demonstrated catalytic turnover — the
  distinction matters for whether a metal-reductase term is warranted (see below).
• Deleting omcS abolishes Fe(III) oxide reduction while leaving soluble acceptors intact
  PMID:16332857,
  and expressing omcS in trans restores it. OmcT cannot substitute: Fe(III) oxide is not
  reduced when omcT is expressed but OmcS is absent (PMID:16332857).
• OmcS is essential for direct interspecies electron transfer, and is massively induced in
  DIET cocultures
  PMID:23377933.

Where it is, and why the answer changed

• 2010: immunogold puts OmcS along the pili
  PMID:20400557.
  The authors read the spacing as OmcS handing electrons from pili to Fe(III) oxide
  rather than conducting along them (PMID:20400557).
• 2019: cryo-EM shows the conductive filaments are not pili at all but polymers of OmcS
  PMID:30951668,
  with inter-subunit heme stacking and heme axial coordination by histidines from the
  neighbouring subunit. WT OmcS filaments are 100-fold more conductive than filaments from
  a ΔomcS strain PMID:30951668. The paper states plainly that
  "the conductive extracellular appendages of wild-type G. sulfurreducens strain are primarily OmcS filaments"
  PMID:30951668.
• 2021: OmcS reaches the extracellular fraction only via the PilA-N/PilA-C filament; in
  ΔpilA-N cells it stays in the periplasm
  PMID:34471289.

Consequence for the CC annotations. The mature, functional OmcS is a polymerised
extracellular filament attached to the cell surface. It has no transmembrane segment and no
lipid anchor, and it shears off easily. GO:0009986 cell surface fits exactly — its GO
definition covers products "attached (integrated or loosely bound) to the plasma membrane
or cell wall". GO:0009279 cell outer membrane asserts residence in the outer lipid
bilayer, which nothing shows. That term traces to the protein's 2005 name and to
outer-surface shear fractions, and predates the structure. It is marked over-annotated, not
removed: OmcS genuinely sits at the outer-membrane surface, so the term is imprecise rather
than false.

Conductivity and the wider dispute

• Ye et al. 2022 separate the roles: OmcS filaments are conductive but not structural,
  pili structural but not conductive
  PMID:35164556.
• Jiang et al. 2023 find ΔomcS impaired for ferrihydrite and for coculture, but able to
  regain anode reduction PMID:37881251.
• As with OmcZ, the absolute conductivity values and the conduction mechanism are disputed
  (PMID:37552847, PMID:38633696). That OmcS carries electrons is not in dispute: six
  redox-active hemes, direct in vitro transfer to several acceptors, and a clean genetic
  phenotype. The MF annotation therefore stays at GO:0009055 and makes no mechanistic claim.

Annotation decisions

Existing (10 rows):
- GO:0009055 electron transfer activity, IBA → ACCEPT. The node PTN001251186 was
assessed SOUND in the PTHR30333 family review; OmcS also has direct evidence of its own.
- GO:0019645 anaerobic electron transport chain, IBA → ACCEPT, same node.
- GO:0009986 cell surface, IEA + 3 × EXP → ACCEPT (all four rows).
- GO:0009279 cell outer membrane, IEA + 3 × EXP → MARK_AS_OVER_ANNOTATED (all four
rows, kept consistent). Recorded as a source_defects entry against UniProt
(OUTDATED_STATEMENT, CHECK) rather than a demand to delete.

New (2 rows):
- GO:0020037 heme binding — six hemes, curated COFACTOR, two structures.
- GO:0051258 protein polymerization — OmcS is itself the polymer; the filament is a
homopolymer whose inter-subunit contacts include heme stacking and cross-subunit axial
histidine coordination.

Not added, and why:
- GO:0016722 oxidoreductase activity, acting on metal ions. Declined, as for OmcZ. What
was measured is the rate at which pre-reduced OmcS is oxidised by a substrate, not
catalytic turnover; no kcat/Km for a catalysed reaction is reported. The repo does use
this term for Shewanella OmcA, but there the evidence is different — a measured kcat of
10.2 s⁻¹ and Km of 41 µM for Cr(VI) reduction.
- GO:0005576 extracellular region. Its GO comment says it is for products not attached
to the cell surface; OmcS filaments are cell-attached, so GO:0009986 is the correct term.
- A DIET term. GO has nothing for direct interspecies electron transfer (checked via OLS),
and the role is a property of the partnership rather than of a step OmcS performs alone.
Recorded as a question instead.
- A pilus term. OmcS is secreted through the PilA-N/PilA-C filament and was once seen
along pili, but it is not a pilus component.

Ontology gap: GO still has no cellular-component term for an extracellular cytochrome
filament. The same proposal was made in the OmcZ review; it is repeated here deliberately,
because two independent genes needing the term is the strongest argument for creating it.