moaX Resolved · high auto-curated

H37Rv Rv3323c · MTBC0 - · 221 aa · 3709049–3709714 (-) · RefSeq YP_177959.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)MoaD-MoaE fusion protein MoaX
MTBC0 PGAP re-annotation
Revised (this work)MoaD-MoaE fusion protein MoaX. Pfam: ThiS (PF02597.27), MoaE (PF02391.23).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt Q6MWY3 TrEMBL · unreviewed · Evidence at protein level
UniProt nameMolybdopterin synthase catalytic subunit 1
EC (curated) EC 2.8.1.12
Curated functionConverts molybdopterin precursor Z into molybdopterin. This requires the incorporation of two sulfur atoms into precursor Z to generate a dithiolene group. The sulfur is provided by MoaD.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namemoaE
eggNOG descriptionMolybdopterin
Orthologous groupCOG0314
EC number EC 2.8.1.12
KEGG orthology K03635, K21142
KEGG pathways map00790, map01100, map04122

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 0.321 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 2 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)

PfamAccessioni-EvalueResiduesDescription
ThiSPF02597.27 3.5e-176–82 ThiS family
MoaEPF02391.23 1.3e-3689–200 MoaE protein

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

Closest characterised functional partner: moaC3 (cyclic pyranopterin monophosphate synthase accessory protein), high confidence from genomic context alone (score 999 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3324c moaC3 cyclic pyranopterin monophosphate synthase accessory protein 999 999 ctx neighborhood:801 cooccurence:471 coexpression:921 database:900 textmining:845
Rv3111 moaC1 cyclic pyranopterin monophosphate synthase accessory protein 998 996 ctx cooccurence:466 coexpression:920 database:900 textmining:730
Rv0864 moaC2 cyclic pyranopterin monophosphate synthase accessory protein 998 996 ctx cooccurence:486 coexpression:920 database:900 textmining:550
Rv0868c moaD2 cyclic pyranopterin monophosphate synthase 997 993 coexpression:498 experimental:868 database:900 textmining:600
Rv3116 moeB2 molybdenum cofactor biosynthesis protein MoeB 997 990 coexpression:447 experimental:473 database:934 textmining:735
Rv3206c moeB1 adenylyltransferase/sulfurtransferase MoeZ 996 989 coexpression:444 experimental:473 database:934 textmining:718
Rv0866 moaE2 molybdopterin synthase catalytic subunit 2 976 975 coexpression:492 experimental:463 database:900
Rv3112 moaD1 molybdenum cofactor biosynthesis protein MoaD 974 972 coexpression:494 experimental:463 database:900
Rv3119 moaE1 molybdopterin synthase catalytic subunit 1 973 972 coexpression:491 experimental:463 database:900
Rv1335 cysO sulfur carrier protein CysO 979 971 coexpression:491 experimental:463 database:900
Rv0438c moeA2 molybdopterin molybdenumtransferase 943 925 ctx cooccurence:581 coexpression:805
Rv0994 moeA1 molybdopterin molybdenumtransferase 1 931 908 ctx cooccurence:487 coexpression:805
Rv3109 moaA1 cyclic pyranopterin monophosphate synthase 969 895 ctx cooccurence:677 coexpression:648 textmining:720
Rv3322c methyltransferase 885 884 ctx neighborhood:882
Rv0869c moaA2 molybdenum cofactor biosynthesis protein MoaA 889 852 ctx cooccurence:547 coexpression:646

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): MoaD-MoaE fusion protein MoaX
  • Pfam (hmmscan --cut_ga): ThiS PF02597.27 (E=4e-17), MoaE PF02391.23 (E=1e-36)
  • (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 YP_177959.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ThiS (PF02597.27), MoaE (PF02391.23)
  • 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 COG0314
  • Curated reference: UniProt Q6MWY3 (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 — 67 functional partner(s); context anchor moaC3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3323c|moaX
MITVNVLYFGAVREACKVAHEKISLESGTTVDGLVDQLQIDYPPLADFRKRVRMAVNESIAPASTILDDGDTVAFIPQVAGGSDVYCRLTDEPLSVDEVLNAISGPSQGGAVIFVGTVRNNNNGHEVTKLYYEAYPAMVHRTLMDIIEECERQADGVRVAVAHRTGELRIGDAAVVIGASAPHRAAAFDAARMCIERLKQDVPIWKKEFALDGVEWVANRP