guaB3 Family assigned · medium auto-curated

H37Rv Rv3410c · MTBC0 mtbc0_003624 · 375 aa · 3854222–3855349 (-) · RefSeq NP_217927.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)oxidoreductase
MTBC0 PGAP re-annotationGuaB3 family IMP dehydrogenase-related protein
Revised (this work)GuaB3 family IMP dehydrogenase-related protein. Pfam: IMPDH (PF00478.32), FMN_dh (PF01070.25).

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

Curated reference (UniProt)

UniProt P9WKI5 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized oxidoreductase Rv3410c
EC (curated) EC 1.-.-.-
Curated functionHas no inosine-5'-monophosphate dehydrogenase activity.

UniProt still lists this protein as Uncharacterized oxidoreductase Rv3410c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
Preferred nameguaB3
eggNOG descriptionIMP dehydrogenase
Orthologous groupCOG0516
EC number EC 1.1.1.205
KEGG orthology K00088
KEGG pathways map00230, map00983, map01100, map01110
KEGG modules M00050
Gene Ontology (77) GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0006139, GO:0006163, GO:0006164, GO:0006183, GO:0006725, GO:0006753, GO:0006793 +65 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 0.562 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 3 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
IMPDHPF00478.32 5.6e-3117–302 IMP dehydrogenase / GMP reductase domain
FMN_dhPF01070.25 1.2e-07181–301 FMN-dependent dehydrogenase

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

Closest characterised functional partner: guaB2 (inosine-5'-monophosphate dehydrogenase), high confidence from genomic context alone (score 982 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3396c guaA GMP synthase 998 997 coexpression:952 database:900 textmining:497
Rv3411c guaB2 inosine-5'-monophosphate dehydrogenase 989 982 ctx neighborhood:789 database:900 textmining:417
Rv0357c purA adenylosuccinate synthetase 977 971 coexpression:646 database:900
Rv0957 purH bifunctional phosphoribosylaminoimidazolecarboxamide formyltransferase/inosinemonophosphate cyclohydrolase 947 942 coexpression:422 database:900
Rv1341 rdgB non-canonical purine NTP pyrophosphatase 926 919 database:900
Rv1843c guaB1 inosine-5'-monophosphate dehydrogenase 988 910 database:900 textmining:877
Rv3624c hpt hypoxanthine-guanine phosphoribosyltransferase 920 904 database:900
Rv1021 mazG nucleoside triphosphate pyrophosphohydrolase 901 901 database:900
Rv3412 hyp hypothetical protein 746 746 ctx neighborhood:744
Rv1390 rpoZ DNA-directed RNA polymerase subunit omega 720 709 ctx cooccurence:651
Rv1650 pheT phenylalanine--tRNA ligase subunit beta 767 696 coexpression:695
Rv3409c choD cholesterol oxidase 720 685 ctx neighborhood:682
Rv0667 rpoB DNA-directed RNA polymerase subunit beta 676 646 coexpression:646
Rv0734 mapA methionine aminopeptidase 661 641 database:478
Rv2861c mapB methionine aminopeptidase 660 640 database:478

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: GuaB3 family IMP dehydrogenase-related protein
  • Pfam (hmmscan --cut_ga): IMPDH PF00478.32 (E=6e-31), FMN_dh PF01070.25 (E=1e-07)
  • (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_217927.1)
  • Domains: Pfam-A via hmmscan --cut_ga — IMPDH (PF00478.32), FMN_dh (PF01070.25)
  • 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 COG0516
  • Curated reference: UniProt P9WKI5 (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 — 108 functional partner(s); context anchor guaB2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003624|Rv3410c|guaB3
MVEIGMGRTARRTYELSEISIVPSRRTRSSKDVSTAWQLDAYRFEIPVVAHPTDALVSPEFAIELGRLGGLGVLNGEGLIGRHLDVEAKIAQLLEAAAADPEPSTAIRLLQELHAAPLNPDLLGAAVARIREAGVTTAVRVSPQNAQWLTPVLVAAGIDLLVIQGTIVSAERVASDGEPLNLKTFISELDIPVVAGGVLDHRTALHLMRTGAAGVIVGYGSTQGVTTTDEVLGISVPMATAIADAAAARRDYLDETGGRYVHVLADGDIHTSGELAKAIACGADAVVLGTPLAESAEALGEGWFWPAAAAHPSLPRGALLQIAVGERPPLARVLGGPSDDPFGGLNLVGGLRRSMAKAGYCDLKEFQKVGLTVGG