moaA2 Resolved · high auto-curated
H37Rv Rv0869c · MTBC0 mtbc0_000924 ·
360 aa · 969468–970550 (-) ·
RefSeq NP_215384.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | molybdenum cofactor biosynthesis protein MoaA |
|---|---|
| MTBC0 PGAP re-annotation | GTP 3'%2C8-cyclase MoaA |
| Revised (this work) | GTP 3'%2C8-cyclase MoaA. 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.
Curated reference (UniProt)
| UniProt |
P9WJS1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | GTP 3',8-cyclase 2 |
| EC (curated) |
EC 4.1.99.22
|
| Curated function | Catalyzes 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 name | moaA |
| eggNOG description | Catalyzes the cyclization of GTP to (8S)-3',8-cyclo-7,8- dihydroguanosine 5'-triphosphate |
| Orthologous group | COG2896 |
| EC number |
EC 4.1.99.22
|
| KEGG orthology |
K03639
|
| KEGG pathways |
map00790, map01100, map04122
|
| Gene Ontology (6) |
GO:0005575, GO:0005618, GO:0005623, GO:0030312, 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 | 2.285 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 6 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 |
|---|---|---|---|---|
Radical_SAM | PF04055.28 | 2.1e-31 | 43–206 | Radical SAM superfamily |
Mob_synth_C | PF06463.19 | 8.6e-35 | 211–342 | Molybdenum Cofactor Synthesis C |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: moaC2 (cyclic pyranopterin monophosphate synthase accessory protein), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0864 moaC2 |
cyclic pyranopterin monophosphate synthase accessory protein | 999 | 999 ctx | fusion:900 cooccurence:773 coexpression:647 database:900 textmining:929 |
Rv3324c moaC3 |
cyclic pyranopterin monophosphate synthase accessory protein | 999 | 999 ctx | fusion:899 cooccurence:773 coexpression:645 database:900 textmining:483 |
Rv3111 moaC1 |
cyclic pyranopterin monophosphate synthase accessory protein | 999 | 999 ctx | fusion:900 cooccurence:773 coexpression:645 database:900 textmining:738 |
Rv0868c moaD2 |
cyclic pyranopterin monophosphate synthase | 970 | 962 ctx | neighborhood:882 coexpression:404 database:500 |
Rv3109 moaA1 |
cyclic pyranopterin monophosphate synthase | 933 | 918 | database:900 |
Rv0866 moaE2 |
molybdopterin synthase catalytic subunit 2 | 995 | 907 ctx | cooccurence:641 coexpression:408 database:500 textmining:949 |
Rv3609c folE |
GTP cyclohydrolase I | 906 | 907 | database:900 |
Rv1415 ribA2 |
bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase | 907 | 904 | database:900 |
Rv1940 ribA1 |
riboflavin biosynthesis protein RibA | 906 | 903 | database:900 |
Rv0870c |
integral membrane protein | 883 | 883 ctx | neighborhood:882 |
Rv0438c moeA2 |
molybdopterin molybdenumtransferase | 903 | 864 ctx | cooccurence:767 |
Rv3119 moaE1 |
molybdopterin synthase catalytic subunit 1 | 870 | 862 ctx | cooccurence:559 coexpression:402 database:500 |
Rv3323c moaX |
MoaD-MoaE fusion protein MoaX | 889 | 852 ctx | cooccurence:547 coexpression:646 |
Rv0865 mog |
molybdopterin biosynthesis protein | 982 | 851 ctx | cooccurence:756 textmining:885 |
Rv0994 moeA1 |
molybdopterin molybdenumtransferase 1 | 849 | 830 ctx | cooccurence:745 |
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: molybdenum cofactor biosynthesis protein MoaA
- MTBC0 PGAP product: GTP 3'%2C8-cyclase MoaA
- Pfam (hmmscan --cut_ga): Radical_SAM PF04055.28 (E=2e-31), Mob_synth_C PF06463.19 (E=9e-35)
- (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_215384.1)
- 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 P9WJS1 (SwissProt, reviewed; 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 —
41 functional partner(s); context anchor
moaC2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000924|Rv0869c|moaA2 MTLTALGMPALRSRTNGIADPRVVPTTGPLVDTFGRVANDLRVSLTDRCNLRCSYCMPERGLRWLPGEQLLRPDELARLIHIAVTRLGVTSVRFTGGEPLLAHHLDEVVAATARLRPRPEISLTTNGVGLARRAGALAEAGLDRVNVSLDSIDRAHFAAITRRDRLAHVLAGLAAAKAAGLTPVKVNAVLDPTTGREDVVDLLRFCLERGYQLRVIEQMPLDAGHSWRRNIALSADDVLAALRPHFRLRPDPAPRGSAPAELWLVDAGPNTPRGRFGVIASVSHAFCSTCDRTRLTADGQIRSCLFSTEETDLRRLLRGGADDDAIEAAWRAAMWSKPAGHGINAPDFIQPDRPMSAIGG