meaB Resolved · high auto-curated

H37Rv Rv1496 · MTBC0 mtbc0_001600 · 334 aa · 1696689–1697693 (+) · RefSeq NP_216012.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transport system kinase
MTBC0 PGAP re-annotationmethylmalonyl Co-A mutase-associated GTPase MeaB
Revised (this work)Methylmalonyl Co-A mutase-associated GTPase MeaB. Pfam: MeaB (PF03308.23), cobW (PF02492.26).

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

Curated reference (UniProt)

UniProt P9WPZ1 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable GTPase Rv1496
EC (curated) EC 3.6.-.-
Curated functionProbable GTPase. May also bind and hydrolyze ATP. May function as chaperone (Probable).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred nameargK
eggNOG descriptionLAO AO transport system ATPase
Orthologous groupCOG1703
KEGG orthology K07588

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 0.249 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 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
MeaBPF03308.23 1.0e-13026–298 Methylmalonyl Co-A mutase-associated GTPase MeaB
cobWPF02492.26 7.2e-0661–214 CobW/HypB/UreG, nucleotide-binding domain

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

Closest characterised functional partner: mutB (methylmalonyl-CoA mutase large subunit), high confidence from genomic context alone (score 994 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1493 mutB methylmalonyl-CoA mutase large subunit 996 994 ctx neighborhood:789 cooccurence:774 coexpression:857 textmining:432
Rv1492 mutA methylmalonyl-CoA mutase small subunit 982 981 ctx neighborhood:867 cooccurence:774 coexpression:404
Rv1322A hyp hypothetical protein 905 899 ctx fusion:588 cooccurence:743
Rv1494 mazE4 antitoxin MazE4 803 802 ctx neighborhood:801
Rv1495 mazF4 mRNA interferase MazF4 803 802 ctx neighborhood:801
Rv1491c TVP38/TMEM64 family membrane protein 754 754 ctx neighborhood:753
Rv1489A hyp hypothetical protein 751 727 coexpression:690
Rv1497 lipL esterase LipL 657 658 ctx neighborhood:654
Rv1864c hyp hypothetical protein 424 424 coexpression:405
Rv3280 accD5 propionyl-CoA carboxylase subunit beta 403 380
Rv1672c integral membrane transport protein 479 41 textmining:479

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: transport system kinase
  • MTBC0 PGAP product: methylmalonyl Co-A mutase-associated GTPase MeaB
  • Pfam (hmmscan --cut_ga): MeaB PF03308.23 (E=1e-130), cobW PF02492.26 (E=7e-06)
  • (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_216012.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MeaB (PF03308.23), cobW (PF02492.26)
  • 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 COG1703
  • Curated reference: UniProt P9WPZ1 (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 — 11 functional partner(s); context anchor mutB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001600|Rv1496|meaB
MMAASHDDDTVDGLATAVRGGDRAALPRAITLVESTRPDHREQAQQLLLRLLPDSGNAHRVGITGVPGVGKSTAIEALGMHLIERGHRVAVLAVDPSSTRTGGSILGDKTRMARLAVHPNAYIRPSPTSGTLGGVTRATRETVVLLEAAGFDVILIETVGVGQSEVAVANMVDTFVLLTLARTGDQLQGIKKGVLELADIVVVNKADGEHHKEARLAARELSAAIRLIYPREALWRPPVLTMSAVEGRGLAELWDTVERHRQVLTGAGEFDARRRDQQVDWTWQLVRDAVLDRVWSNPTVRKVRSELERRVRAGELTPALAAQQILEIANLTDR