Function
Catalytic entry subunit that binds FMN and accepts a hydride from NADH before passing electrons into the iron-sulfur relay.
Reusable bacterial module for the conserved 14-subunit respiratory complex I, also called NDH-1 or NADH:quinone oxidoreductase. The peripheral arm oxidizes NADH, transfers electrons through FMN and iron-sulfur centers, and reduces the quinone pool. The membrane arm couples this redox chemistry to proton translocation. The module separates the NADH-input, quinone-reduction, membrane-interface, and antiporter-like proton-pumping parts so that fused subunits such as NuoC/D can be represented without collapsing the enzyme to a single step. It excludes the non-homologous, non-proton-pumping type-II NADH dehydrogenase (Ndh/NDH-2).
The 14-subunit NDH-1 core is conserved across proteobacteria and other bacterial phyla, so the module is written at the family level and grounded with two experimentally anchored gammaproteobacterial exemplar sets: the Escherichia coli K-12 NuoA-N complex, the best-characterized bacterial complex I genetically and biochemically, and the single-copy Pseudomonas putida KT2440 PP_4119-PP_4131 nuo locus. In both exemplars NuoC and NuoD are fused into one polypeptide (E. coli P33599, P. putida Q88FH5), so 13 proteins supply the 14 conserved subunit roles; in lineages with separate C and D subunits (for example Thermus thermophilus Nqo5 and Nqo4) the fused annoton is satisfied by the two polypeptides together. The fused-annoton grounding, PANTHER:PTHR11993, is the NuoD/49-kDa family; a separate NuoC/30-kDa polypeptide belongs to a different family that is not grounded here. Thermus Nqo subunits, which provided the first complete complex I structures, were not added as a third exemplar set because they would add 14 more members without adding a module role. PANTHER groundings were adopted from the module-wide grounding pass and checked against the PANTHER 19.0 member index: each exemplar falls in the cited family, except that PANTHER's own classification file places E. coli NuoF in PTHR11780:SF10 (with mitochondrial NDUFV1) while UniProt and InterPro place E. coli and P. putida NuoF in PTHR43578:SF3. The tree placement is adopted for E. coli NuoF (recorded in interpro/panther/panther-members-overrides.tsv), while P. putida NuoF, which PANTHER's files do not classify, stays in PTHR43578 by its UniProt cross-reference; the NuoF annoton is therefore grounded to both families, and the PTHR43578 and PTHR11780 reviews describe the split. NuoG is grounded at subfamily PTHR43105:SF10 rather than the family, because PTHR43105 is dominated by molybdopterin oxidoreductase catalytic subunits (nitrate reductases, formate dehydrogenases) for which a family-wide electron-transfer-subunit claim does not hold. Mitochondrial complex I, with its eukaryotic supernumerary NDUF subunits, is modelled separately (mitochondrial_complex_i_core); absence of those subunits here is not a pathway hole. GO:0050136 denotes non-electrogenic NADH:quinone activity and is incompatible with the defining proton-translocating chemistry of NDH-1; its automated propagation to Nuo subunits is removed in the exemplar gene reviews rather than used to model this module. The two terms are siblings, not parent and child: in GO, GO:0008137 NADH dehydrogenase (ubiquinone) activity (RHEA:29091, EC 7.1.1.2, with 4 H+ translocated per NADH) and GO:0050136 (RHEA:46160, EC 1.6.5.9) are each is_a GO:0003954 NADH dehydrogenase activity, and GO:0008137 is not an is_a descendant of GO:0050136 (checked against the GO release in the local OAK database, 2026-11-02).
All recommended fields populated.
✗ none found
No MODULE:bacterial_respiratory_complex_i deep-research report alongside the module YAML.
✓ every leaf node grounds to a representative protein.
✓ every declared conforms_to bundle matches its template motif.
12 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (21 comparison(s))
Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.
| Annoton | Participant | Function | Assessment |
|---|---|---|---|
| nuof_nadh_input | nuoF (PSEPK) UniProtKB:Q88FH3 Family Representative |
NADH dehydrogenase activity GO:0003954 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| nuof_nadh_input | nuoF (ECOLI) UniProtKB:P31979 Family Representative |
NADH dehydrogenase activity GO:0003954 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| nuoe_entry_fes | nuoE (PSEPK) UniProtKB:Q88FH4 Family Representative |
electron transfer activity GO:0009055 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| nuoe_entry_fes | nuoE (ECOLI) UniProtKB:P0AFD1 Family Representative |
electron transfer activity GO:0009055 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| nuog_fes_relay | nuoG (PSEPK) UniProtKB:Q88FH2 Family Representative |
electron transfer activity GO:0009055 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| nuog_fes_relay | nuoG (ECOLI) UniProtKB:P33602 Family Representative |
electron transfer activity GO:0009055 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| nuob_terminal_fes | nuoB (PSEPK) UniProtKB:Q88FH6 Family Representative |
electron transfer activity GO:0009055 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| nuob_terminal_fes | nuoB (ECOLI) UniProtKB:P0AFC7 Family Representative |
electron transfer activity GO:0009055 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| nuocd_quinone_site | nuoC (PSEPK) UniProtKB:Q88FH5 Family Representative |
quinone binding GO:0048038 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| nuocd_quinone_site | nuoC (ECOLI) UniProtKB:P33599 Family Representative |
quinone binding GO:0048038 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| nuoi_fes_relay | nuoI (PSEPK) UniProtKB:Q88FH0 Family Representative |
electron transfer activity GO:0009055 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| nuoi_fes_relay | nuoI (ECOLI) UniProtKB:P0AFD6 Family Representative |
electron transfer activity GO:0009055 |
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass). |
| nuoahjk_interface_subunits | PROTEIN_COMPLEX Gene |
proton transmembrane transporter activity GO:0015078 |
Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews. |
| nuolmn_proton_pump | PROTEIN_COMPLEX Gene |
proton transmembrane transporter activity GO:0015078 |
Participant Unchecked
No direct UniProt participant to compare. Abstract selectors and complex-wide activities cannot be inferred from donor or subunit gene reviews. |
| nuof_nadh_input | NuoF/Nqo1/NDUFV1 family PANTHER:PTHR43578 Family |
NADH dehydrogenase activity GO:0003954 |
Family Supported
Family review supports GO:0003954 FAMILY_WIDE. NADH oxidation at the FMN of the 51 kDa-type flavin module is shared by the complex I NuoF members (experimentally in E. coli NuoF) and by the NAD+-reducing hydrogenase and formate-dehydrogenase flavoprotein subunits, which catalyse the same NADH/NAD+ exchange (GO:0003954 is defined without direction-specific acceptor). The nuo locus itself was found with probes from the conserved NAD(H)-binding subunit shared by complex I and the NAD+-reducing hydrogenase. Two members are recorded as exceptions: the truncated ferredoxin P07324, and HndC, whose NADP specificity would put it outside this NADH-specific term. |
| nuof_nadh_input | NuoF/Nqo1/NDUFV1 family PANTHER:PTHR11780 Family |
NADH dehydrogenase activity GO:0003954 |
Family Supported
Family review supports GO:0003954 FAMILY_WIDE. The subunit's own chemistry, with the acceptor left unspecified: NADH docks on the glycine-rich loop (UniProt binding site 87-96 of P49821, GRGGAGFPTG, conserved in bacteria, plants, fungi and animals) and transfers a hydride to the bound FMN. This is true of every member, respiratory compartment and quinone identity aside, and it is the term a PAINT curator should place at the family root. PAINT currently asserts it only at the bacterial node PTN000207323, which is why human NDUFV1 - and every other eukaryotic member - receives no molecular-function IBA at all despite this being the single best-characterised function in the family. |
| nuoe_entry_fes | NuoE/Nqo2/NDUFV2 family PANTHER:PTHR10371 Family |
electron transfer activity GO:0009055 |
Family Supported
Family review supports GO:0009055 FAMILY_WIDE. The subunit's own molecular function: redox exchange through its [2Fe-2S] cluster N1a with the reduced FMN of the 51 kDa subunit. The four cysteine ligands and the cluster domain (NCBIfam TIGR01958, PIRSF000216, PROSITE PS01099) are conserved across the reviewed members, and rapid NADH-driven reduction of N1a is measured in E. coli complex I. The cluster is on a side path rather than the main wire, so the term asserts electron exchange, not a position on the FMN-to-quinone pathway. Applies equally to the S. pombe homologue, which keeps the cluster domain even without a complex I. |
| nuog_fes_relay | NuoG/Nqo3/NDUFS1 family PANTHER:PTHR43105:SF10 Family |
electron transfer activity GO:0009055 |
Family Supported
Family review supports GO:0009055 for PANTHER:PTHR43105:SF10. For the complex I 75 kDa subunits electron transfer through their iron-sulfur clusters is the subunit's own function (E. coli NuoG clusters N1b, N4, N5 on the main path). For the molybdoenzyme majority the defining function is substrate-specific catalysis at the Mo/W cofactor; their clusters do move electrons, so the term is not wrong there, but it does not describe the family's shared function and is asserted here only for the complex I subfamilies. SF10 is mixed (it also holds AioA, IdrA and assimilatory nitrate reductases, which are themselves Fe-S redox enzymes), so the grant is safe for all its members though informative mainly for NuoG. |
| nuob_terminal_fes | NuoB/Nqo6/NDUFS7 family PANTHER:PTHR11995 Family |
electron transfer activity GO:0009055 |
Family Supported
Family review supports GO:0009055 FAMILY_WIDE. Every characterised member is the terminal iron-sulfur subunit of a complex I-type enzyme (bacterial NDH-1 NuoB, mitochondrial NDUFS7, chloroplast NDH NdhK) and carries the conserved four-cysteine motif (Pfam Oxidored_q6, PROSITE COMPLEX1_20K) that ligates the [4Fe-4S] cluster N2, which passes electrons from the iron-sulfur chain to the bound quinone. The electron donor upstream differs (NADH versus ferredoxin) but the subunit's own electron-transfer role does not, so the term is safe family-wide, unlike the NADH-specific GO:0008137. The minor subfamilies SF33 (second NuoB copies) and SF22 (mitochondrial NDUFS7) retain the same motif family assignment; no member is known to have lost the cluster. |
| nuocd_quinone_site | NuoC-NuoD/Nqo5-Nqo4/NDUFS3-NDUFS2 families PANTHER:PTHR11993 Family |
quinone binding GO:0048038 |
Family Supported
Family review supports GO:0048038 FAMILY_WIDE. Every member of the family, respiratory and plastid alike, builds the chamber in which a quinone is reduced, and the His/Tyr pair that contacts the headgroup is invariant across animals, plants, plastids and bacteria (see the quinone_channel_his_tyr site). The term names the chemistry without naming the acceptor, which is precisely the granularity at which this family is coherent. This is also the term a future PAINT curator could safely place at the family root: no node in the current PTHR11993 PAINT slice asserts any quinone-binding term at all, although the quinone channel is the defining structural contribution of the subunit. |
| nuoi_fes_relay | NuoI/Nqo9/NDUFS8 family PANTHER:PTHR10849 Family |
electron transfer activity GO:0009055 |
Family Supported
Family review supports GO:0009055 FAMILY_WIDE. Every member has two cysteine-ligated 4Fe-4S ferredoxin-type domains and is the two-cluster relay segment of a complex-I-like electron path. In complex I the clusters bridge N5 and N2, and the homologous FHL, hydrogenase-4 and F420H2 dehydrogenase subunits occupy the equivalent relay position. Electron transfer through the subunit's own clusters is the shared activity, whatever the donor and acceptor of the parent complex. |
26 complete review(s) · 1 with deep research · 0 missing review · 25 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| nuoA P0AFC3 | ✓ | ✓ | ✗ |
| nuoA Q88FH7 | ✓ | ✓ | ✗ |
| nuoB P0AFC7 | ✓ | ✓ | ✗ |
| nuoB Q88FH6 | ✓ | ✓ | ✗ |
| nuoC P33599 | ✓ | ✓ | ✗ |
| nuoC Q88FH5 | ✓ | ✓ | ✗ |
| nuoE P0AFD1 | ✓ | ✓ | ✗ |
| nuoE Q88FH4 | ✓ | ✓ | ✗ |
| nuoF P31979 | ✓ | ✓ | ✗ |
| nuoF Q88FH3 | ✓ | ✓ | ✓ |
| nuoG P33602 | ✓ | ✓ | ✗ |
| nuoG Q88FH2 | ✓ | ✓ | ✗ |
| nuoH P0AFD4 | ✓ | ✓ | ✗ |
| nuoH Q88FH1 | ✓ | ✓ | ✗ |
| nuoI P0AFD6 | ✓ | ✓ | ✗ |
| nuoI Q88FH0 | ✓ | ✓ | ✗ |
| nuoJ P0AFE0 | ✓ | ✓ | ✗ |
| nuoJ Q88FG9 | ✓ | ✓ | ✗ |
| nuoK P0AFE4 | ✓ | ✓ | ✗ |
| nuoK Q88FG8 | ✓ | ✓ | ✗ |
| nuoL P33607 | ✓ | ✓ | ✗ |
| nuoL Q88FG7 | ✓ | ✓ | ✗ |
| nuoM P0AFE8 | ✓ | ✓ | ✗ |
| nuoM Q88FG6 | ✓ | ✓ | ✗ |
| nuoN P0AFF0 | ✓ | ✓ | ✗ |
| nuoN Q88FG5 | ✓ | ✓ | ✗ |
Soluble peripheral-arm segment in which NuoF oxidizes NADH at FMN and NuoE and NuoG relay electrons through iron-sulfur centers.
Catalytic entry subunit that binds FMN and accepts a hydride from NADH before passing electrons into the iron-sulfur relay.
Small iron-sulfur subunit at the NADH-input end of the peripheral arm.
Large peripheral-arm iron-sulfur protein that relays electrons away from the FMN-containing input site using one 2Fe-2S and three 4Fe-4S clusters in the exemplar subunits.
Peripheral-arm segment that completes the iron-sulfur wire and forms the quinone-reactive cavity at the membrane-arm junction.
Carries the terminal iron-sulfur center that supplies electrons to quinone at the Q-site.
Forms the quinone-cavity scaffold. In E. coli, P. putida and many other Gammaproteobacteria the C and D subunits are fused into one polypeptide; elsewhere they are separate subunits.
Iron-sulfur subunit in the distal portion of the relay leading toward the terminal quinone-reducing center.
Conserved small membrane subunits and NuoH form the proximal membrane arm around the quinone site and transmit redox-linked conformational changes into the proton-pumping arm.
Membrane-embedded coupling interface between quinone chemistry and the distal antiporter-like proton-translocation machinery.
Three homologous long membrane subunits form the distal membrane arm and are required for vectorial proton translocation by complex I.
Distal membrane-arm unit that converts redox-linked conformational changes into proton translocation.