Rv1138c Resolved · high auto-curated

H37Rv Rv1138c · MTBC0 mtbc0_001223 · 338 aa · 1273912–1274928 (-) · RefSeq NP_215654.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)oxidoreductase
MTBC0 PGAP re-annotationNAD(P)/FAD-dependent oxidoreductase
Revised (this work)NAD(P)/FAD-dependent oxidoreductase. Pfam: FAD_binding_3 (PF01494.26), FAD_binding_2 (PF00890.31).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt O06538 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible oxidoreductase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namesrsC
eggNOG descriptionFAD dependent oxidoreductase
Orthologous groupCOG0644

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 1.138 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.81% of strains (1176) · clonal

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)

PfamAccessioni-EvalueResiduesDescription
FAD_binding_3PF01494.26 1.8e-115–169 FAD binding domain
FAD_binding_2PF00890.31 9.5e-057–38 FAD binding domain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: Rv1137c (Hypothetical protein; Rv1137c, (MTCI65.04c), len: 122 aa. Hypothetical unknown protein.), high confidence from genomic context alone (score 945 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1139c hyp hypothetical protein 988 979 ctx neighborhood:881 cooccurence:767 textmining:489
Rv1137c Hypothetical protein; Rv1137c, (MTCI65.04c), len: 122 aa. Hypothetical unknown protein. 945 945 ctx neighborhood:737 coexpression:801
Rv1660 pks10 chalcone synthase 905 867 ctx cooccurence:764
Rv1665 pks11 chalcone synthase 847 786 ctx cooccurence:762
Rv0736 rslA anti-sigma-L factor RslA 791 767 coexpression:767
Rv3029c fixA electron transfer flavoprotein subunit beta 781 752 experimental:652
Rv1372 pks18 alpha-pyrone synthesis polyketide synthase-like protein 753 654 ctx cooccurence:613
Rv3028c fixB electron transfer flavoprotein subunit alpha 634 586 experimental:446
Rv0735 sigL ECF RNA polymerase sigma factor SigL 514 514 coexpression:514
Rv2062c cobN cobalamin biosynthesis protein CobN 517 454 coexpression:436
Rv2850c magnesium chelatase 589 434 coexpression:416
Rv2638 hyp hypothetical protein 404 404
Rv1140 integral membrane protein 401 401
Rv3806c ubiA decaprenyl-phosphate phosphoribosyltransferase 438 363
Rv0958 magnesium chelatase 409 353

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: oxidoreductase
  • MTBC0 PGAP product: NAD(P)/FAD-dependent oxidoreductase
  • Pfam (hmmscan --cut_ga): FAD_binding_3 PF01494.26 (E=2e-11), FAD_binding_2 PF00890.31 (E=1e-04)
  • (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_215654.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_3 (PF01494.26), FAD_binding_2 (PF00890.31)
  • 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 COG0644
  • Curated reference: UniProt O06538 (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 — 17 functional partner(s); context anchor Rv1137c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001223|Rv1138c|
MTSYDTDLLVVGGGPGGLATALHARARGLSVIVAEPRENPIDKACGEGLMPGGLAELTSLGVDPVGLPFHGIAYVGEHRRVQARFRTGPGRGVRRTTLHAALAARAKEQDTEWIRSRVATIQQDAHGVTAAGVRAKWLVAADGLHSAVRRAVGIKATAGTPRRYGVRWHYRLPVWSDFVEVHWSRWGEAYVTPVEPDLVGVAILSRQRPELAWFPSLAHHLQDASRGHARGCGPLRQVVSRRVAGRVLLVGDAAGYEDALTGEGISLAVKQAAAAVSAIVDDTPASYEAAWHRITRDYRLVTRGLVLASTPRAARRAIVPLCALLPTAFRYGVNILAY