moaA1 Resolved · high auto-curated

H37Rv Rv3109 · MTBC0 - · 359 aa · 3477649–3478728 (+) · RefSeq YP_177925.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cyclic pyranopterin monophosphate synthase
MTBC0 PGAP re-annotation
Revised (this work)Cyclic pyranopterin monophosphate synthase. Pfam: Radical_SAM (PF04055.28), Mob_synth_C (PF06463.19).

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 P9WJS3 SwissProt · reviewed · Evidence at transcript level
UniProt nameGTP 3',8-cyclase 1
EC (curated) EC 4.1.99.22
Curated functionCatalyzes the cyclization of GTP to (8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namemoaA
eggNOG descriptionCatalyzes the cyclization of GTP to (8S)-3',8-cyclo-7,8- dihydroguanosine 5'-triphosphate
Orthologous groupCOG2896
EC number EC 4.1.99.22
KEGG orthology K03639
KEGG pathways map00790, map01100, map04122
Gene Ontology (8) GO:0005575, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0040007, GO:0044464, GO:0071944

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 0.645 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 8 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
Radical_SAMPF04055.28 1.0e-3332–197 Radical SAM superfamily
Mob_synth_CPF06463.19 1.0e-34203–326 Molybdenum Cofactor Synthesis C

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

Closest characterised functional partner: moaC1 (cyclic pyranopterin monophosphate synthase accessory protein), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3111 moaC1 cyclic pyranopterin monophosphate synthase accessory protein 999 1000 ctx neighborhood:634 fusion:592 cooccurence:772 coexpression:948 database:900 textmining:863
Rv0864 moaC2 cyclic pyranopterin monophosphate synthase accessory protein 999 999 ctx fusion:900 cooccurence:772 coexpression:647 database:900 textmining:901
Rv3324c moaC3 cyclic pyranopterin monophosphate synthase accessory protein 999 996 ctx fusion:579 cooccurence:772 coexpression:649 database:900 textmining:901
Rv3112 moaD1 molybdenum cofactor biosynthesis protein MoaD 991 958 ctx neighborhood:592 coexpression:901 textmining:815
Rv3110 moaB1 pterin-4-alpha-carbinolamine dehydratase 988 944 ctx neighborhood:613 coexpression:860 textmining:806
Rv0869c moaA2 molybdenum cofactor biosynthesis protein MoaA 933 918 database:900
Rv3113 phosphatase 913 914 ctx neighborhood:408 coexpression:860
Rv3119 moaE1 molybdopterin synthase catalytic subunit 1 970 913 ctx cooccurence:667 coexpression:402 database:500 textmining:671
Rv3114 hyp hypothetical protein 913 913 coexpression:868
Rv0866 moaE2 molybdopterin synthase catalytic subunit 2 991 910 ctx cooccurence:688 coexpression:402 database:500 textmining:909
Rv1940 ribA1 riboflavin biosynthesis protein RibA 909 906 database:900
Rv3609c folE GTP cyclohydrolase I 906 906 database:900
Rv1415 ribA2 bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase 907 904 database:900
Rv3323c moaX MoaD-MoaE fusion protein MoaX 969 895 ctx cooccurence:677 coexpression:648 textmining:720
Rv0438c moeA2 molybdopterin molybdenumtransferase 853 835 ctx cooccurence:766

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): cyclic pyranopterin monophosphate synthase
  • Pfam (hmmscan --cut_ga): Radical_SAM PF04055.28 (E=1e-33), Mob_synth_C PF06463.19 (E=1e-34)
  • (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_177925.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Radical_SAM (PF04055.28), Mob_synth_C (PF06463.19)
  • 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 COG2896
  • Curated reference: UniProt P9WJS3 (SwissProt, reviewed; Evidence at transcript 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 — 50 functional partner(s); context anchor moaC1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3109|moaA1
MSTPTLPDMVAPSPRVRVKDRCRRMMGDLRLSVIDQCNLRCRYCMPEEHYTWLPRQDLLSVKEISAIVDVFLSVGVSKVRITGGEPLIRPDLPEIVRTLSAKVGEDSGLRDLAITTNGVLLADRVDGLKAAGMKRITVSLDTLQPERFKAISQRNSHDKVIAGIKAVAAAGFTDTKIDTTVMRGANHDELADLIEFARTVNAEVRFIEYMDVGGATHWAWEKVFTKANMLESLEKRYGRIEPLPKHDTAPANRYALPDGTTFGIIASTTEPFCATCDRSRLTADGLWLHCLYAISGINLREPLRAGATHDDLVETVTTGWRRRTDRGAEQRLAQRERGVFLPLSTLKADPHLEMHTRGG