purM Resolved · high auto-curated

H37Rv Rv0809 · MTBC0 mtbc0_000858 · 364 aa · 906792–907886 (+) · RefSeq NP_215324.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)phosphoribosylformylglycinamidine cyclo-ligase PurM
MTBC0 PGAP re-annotationphosphoribosylformylglycinamidine cyclo-ligase
Revised (this work)Phosphoribosylformylglycinamidine cyclo-ligase. Pfam: AIRS (PF00586.30), AIRS_C (PF02769.28).

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

Curated reference (UniProt)

UniProt I6Y4V6 TrEMBL · unreviewed · Evidence at protein level
UniProt namePhosphoribosylformylglycinamidine cyclo-ligase
EC (curated) EC 6.3.3.1

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred namepurM
eggNOG descriptionPhosphoribosylformylglycinamidine cyclo-ligase
Orthologous groupCOG0150
EC number EC 6.3.3.1
KEGG orthology K01933
KEGG pathways map00230, map01100, map01110, map01130
KEGG modules M00048
Gene Ontology (14) GO:0003674, GO:0003824, GO:0004641, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0016874, GO:0016879, GO:0016882, GO:0044424 +2 more

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 0.059 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 1 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
AIRSPF00586.30 7.5e-2469–174 AIR synthase related protein, N-terminal domain
AIRS_CPF02769.28 5.2e-35186–352 AIR synthase related protein, C-terminal domain

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

Closest characterised functional partner: purF (amidophosphoribosyltransferase), high confidence from genomic context alone (score 998 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0808 purF amidophosphoribosyltransferase 998 998 ctx neighborhood:830 fusion:680 cooccurence:773 coexpression:859 textmining:409
Rv0788 purQ phosphoribosylformylglycinamidine synthase 998 998 ctx fusion:552 cooccurence:646 coexpression:857 database:900
Rv0956 purN phosphoribosylglycinamide formyltransferase PurN 998 997 ctx fusion:900 cooccurence:755 coexpression:857 textmining:606
Rv0772 purD phosphoribosylamine--glycine ligase 998 997 ctx fusion:900 cooccurence:774 coexpression:857 textmining:593
Rv0803 purL phosphoribosylformylglycinamidine synthase 2 996 993 ctx cooccurence:496 coexpression:857 database:900 textmining:519
Rv3276c purK 5-(carboxyamino)imidazole ribonucleotide synthase 995 992 ctx cooccurence:420 coexpression:857 database:900 textmining:449
Rv0787A purS hyp hypothetical protein 991 989 coexpression:857 database:900
Rv3275c purE 5-(carboxyamino)imidazole ribonucleotide mutase 976 970 ctx cooccurence:768 coexpression:858
Rv0957 purH bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/inosinemonophosphate cyclohydrolase 976 962 ctx cooccurence:705 coexpression:858 textmining:413
Rv1296 thrB homoserine kinase 909 899 ctx fusion:898
Rv0780 purC phosphoribosylaminoimidazole-succinocarboxamide synthase 936 892 coexpression:857 textmining:431
Rv0777 purB adenylosuccinate lyase PurB 903 868 coexpression:830
Rv0423c thiC phosphomethylpyrimidine synthase 814 803 database:800
Rv0389 purT phosphoribosylglycinamide formyltransferase PurT 909 750 coexpression:729 textmining:655
Rv1383 carA carbamoyl-phosphate synthase small subunit 702 674 coexpression:663

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: phosphoribosylformylglycinamidine cyclo-ligase PurM
  • MTBC0 PGAP product: phosphoribosylformylglycinamidine cyclo-ligase
  • Pfam (hmmscan --cut_ga): AIRS PF00586.30 (E=8e-24), AIRS_C PF02769.28 (E=5e-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_215324.1)
  • Domains: Pfam-A via hmmscan --cut_ga — AIRS (PF00586.30), AIRS_C (PF02769.28)
  • 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 COG0150
  • Curated reference: UniProt I6Y4V6 (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 — 58 functional partner(s); context anchor purF
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000858|Rv0809|purM
MTDLAKGPGKDPGSRGITYASAGVDIEAGDRAIDLFKPLASKATRPEVRGGLGGFAGLFTLRGDYREPVLAASSDGVGTKLAIAQAMDKHDTVGLDLVAMVVDDLVVCGAEPLFLLDYIAVGRIVPERLSAIVAGIADGCMRAGCALLGGETAEHPGLIEPDHYDISATGVGVVEADNVLGPDRVKPGDVIIAMGSSGLHSNGYSLVRKVLLEIDRMNLAGHVEEFGRTLGEELLEPTRIYAKDCLALAAETRVRTFCHVTGGGLAGNLQRVIPHGLIAEVDRGTWTPAPVFTMIAQRGRVRRTEMEKTFNMGVGMIAVVAPEDTTRALAVLTARHLDCWVLGTVCKGGKQGPRAKLVGQHPRF