Rv0338c Resolved · high auto-curated
H37Rv Rv0338c · MTBC0 mtbc0_000358 ·
882 aa · 406516–409164 (-) ·
RefSeq NP_214852.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | iron-sulfur-binding reductase |
|---|---|
| MTBC0 PGAP re-annotation | heterodisulfide reductase-related iron-sulfur binding cluster |
| Revised (this work) | Heterodisulfide reductase-related iron-sulfur binding cluster. Pfam: Fer4_10 (PF13237.12), Fer4_9 (PF13187.12), CCG (PF02754.22). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O33268
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable iron-sulfur-binding reductase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| eggNOG description | Fe-S oxidoreductase |
| Orthologous group | COG0247 |
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.185 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 25 synonymous, 14 missense, 0 nonsense, 0 frameshift |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Fer4_10 | PF13237.12 | 1.6e-07 | 290–403 | 4Fe-4S dicluster domain |
Fer4_9 | PF13187.12 | 1.1e-10 | 295–405 | 4Fe-4S dicluster domain |
CCG | PF02754.22 | 2.9e-19 | 607–693 | Cysteine-rich domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: aspC (aspartate aminotransferase), high confidence from genomic context alone (score 719 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3464 rmlB |
dTDP-glucose 4,6-dehydratase | 811 | 812 | coexpression:812 |
Rv1436 gap |
glyceraldehyde 3-phosphate dehydrogenase | 748 | 733 | coexpression:732 |
Rv0337c aspC |
aspartate aminotransferase | 719 | 719 ctx | neighborhood:695 |
Rv0632c echA3 |
enoyl-CoA hydratase EchA3 | 715 | 705 | coexpression:695 |
Rv3029c fixA |
electron transfer flavoprotein subunit beta | 837 | 585 | textmining:625 |
Rv3028c fixB |
electron transfer flavoprotein subunit alpha | 786 | 581 | textmining:512 |
Rv2841c nusA |
transcription termination/antitermination protein NusA | 554 | 555 | coexpression:497 |
Rv3859c gltB |
glutamate synthase large subunit | 602 | 552 ctx | neighborhood:544 |
Rv0339c iniR |
transcriptional regulator | 542 | 543 ctx | neighborhood:532 |
Rv2783c gpsI |
bifunctional guanosine pentaphosphate synthetase/polyribonucleotide nucleotidyltransferase | 527 | 508 | coexpression:446 |
Rv2538c aroB |
3-dehydroquinate synthase | 515 | 491 | coexpression:433 |
Rv0487 hyp |
hypothetical protein | 453 | 453 ctx | cooccurence:445 |
Rv1292 argS |
arginine--tRNA ligase | 479 | 446 | |
Rv3302c glpD2 |
glycerol-3-phosphate dehydrogenase | 497 | 440 | coexpression:407 |
Rv0244c fadE5 |
acyl-CoA dehydrogenase FadE5 | 460 | 439 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: iron-sulfur-binding reductase
- MTBC0 PGAP product: heterodisulfide reductase-related iron-sulfur binding cluster
- Pfam (hmmscan --cut_ga): Fer4_10 PF13237.12 (E=2e-07), Fer4_9 PF13187.12 (E=1e-10), CCG PF02754.22 (E=3e-19)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_214852.1)
- Domains: Pfam-A via hmmscan --cut_ga — Fer4_10 (PF13237.12), Fer4_9 (PF13187.12), CCG (PF02754.22)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG0247 - Curated reference: UniProt O33268 (TrEMBL, unreviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
44 functional partner(s); context anchor
aspC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000358|Rv0338c| MTTQTLIRLILGMSMTAVVGVFALRRVWWLYKLVMSGQPASGRTDNLGTRIWTQISEVLGQRRLLKWSIPGLAHFFTMWGFFILLTVYIEAYGLLFEERFHIPVIGRWDALGFLQDFFATAVFLGITTFAIIRILRNPREIGRSSRFYGSHNGGAWLVLLMIFNVIWTYVLVRGSAVNNGTLPYGNGAFLSQLFGAILRPLGQPANEIIETTALLLHIGVMLAFLILVLHSKHLHIFLAPINVTFKRLPDGLGPLLPLEADGKPIDFENPSEDAVFGRGKIEDFTWKGMLDFATCTECGRCQSQCPAWNTGKPLSPKLVIMDLRDHWMAKAPYILGQKDASAGGEAGHQEHHHVPESGFGRVPGHGPEQATRPLVGTEEQGGVIDPDVLWSCVTCGACVEQCPVDIEHVDHIVDMRRYQVMMESEFPSELSVLFKNLETKGNPWGQNASDRTNWIDEVDFDVPVYGQDVDSFDGYEYLFWVGCAGAYDDKAKKTTKAVAELLAVAGVKYLVLGAGETCNGDSARRSGNEFLFQQLAQQAVETLDGLFEGVETVDRKIVVTCPHCFNTIGKEYRQLGANYTVLHHTQLLNRLVRDKRLVPVTPVSQDITYHDPCYLGRHNKVYEAPRELIGAAGASLTEMPRHADRSFCCGAGGARMWMEEHIGKRINHERVDEALATDATAIATACPFCRVMVTDGVNDRQEEAGRSGVEVLDVAQVLLGSLDHDKAQLPAKGTAAKQAQERAPKAAPKAAAPVTPVEAPAEAPQAPAPAAPAAPVKGLGMAAGAKRPGAKKAAPTPAAPAAPAAPVKGLGIAAGAKRPGAKKTPPPAPGLAEPAAQPQPEAKPQPEPAAPPKPQTDGDPAAPAAPVKGLGIARGARPPGKR