garA Resolved · high auto-curated

H37Rv Rv1827 · MTBC0 mtbc0_001941 · 162 aa · 2090684–2091172 (+) · RefSeq NP_216343.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)glycogen accumulation regulator GarA
MTBC0 PGAP re-annotationglycogen accumulation regulator GarA
Revised (this work)Glycogen accumulation regulator GarA. Pfam: Yop-YscD_cpl (PF16697.11), FHA (PF00498.32).

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

Curated reference (UniProt)

UniProt P9WJA9 SwissProt · reviewed · Evidence at protein level
UniProt nameGlycogen accumulation regulator GarA
Curated functionInvolved in regulation of glutamate metabolism. Acts as a phosphorylation-dependent molecular switch that modulates the activities of Kgd, Gdh and GltB.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category T Signal transduction mechanisms
Preferred namegarA
eggNOG descriptionFha domain
Orthologous groupCOG1716
Gene Ontology (90) GO:0003674, GO:0005488, GO:0005515, GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0005886, GO:0006109, GO:0006110, GO:0006140, GO:0006464 +78 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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.28% of strains (404) · clonal

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
Yop-YscD_cplPF16697.11 1.2e-1562–146 Inner membrane component of T3SS, cytoplasmic domain
FHAPF00498.32 3.1e-2078–140 FHA domain

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

Closest characterised functional partner: pknB (serine/threonine-protein kinase PknB), high confidence from genomic context alone (score 982 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1248c kgd multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase 999 999 experimental:999 textmining:920
Rv0014c pknB serine/threonine-protein kinase PknB 999 982 ctx cooccurence:471 experimental:964 textmining:949
Rv1828 HTH-type transcriptional regulator 918 912 ctx neighborhood:882
Rv2476c gdh NAD-dependent glutamate dehydrogenase 945 906 experimental:905 textmining:446
Rv0410c pknG serine/threonine-protein kinase PknG 995 902 experimental:899 textmining:959
Rv1829 hyp hypothetical protein 777 766 ctx neighborhood:763
Rv1826 gcvH glycine cleavage system protein H 734 735 ctx neighborhood:727
Rv2199c ctaF cytochrome c oxidase polypeptide 4 729 729 coexpression:729
Rv0015c pknA serine/threonine-protein kinase PknA 960 701 ctx cooccurence:467 experimental:443 textmining:873
Rv1824 hyp hypothetical protein 696 696 ctx neighborhood:692
Rv1364c sigma factor regulatory protein 687 686 coexpression:646
Rv2176 pknL serine/threonine-protein kinase PknL 791 667 ctx cooccurence:415 experimental:443
Rv1825 hyp hypothetical protein 658 658 ctx neighborhood:653
Rv1823 hyp hypothetical protein 657 656 ctx neighborhood:653
Rv1822 pgsA2 CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase 642 643 ctx neighborhood:626

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: glycogen accumulation regulator GarA
  • MTBC0 PGAP product: glycogen accumulation regulator GarA
  • Pfam (hmmscan --cut_ga): Yop-YscD_cpl PF16697.11 (E=1e-15), FHA PF00498.32 (E=3e-20)
  • (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_216343.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Yop-YscD_cpl (PF16697.11), FHA (PF00498.32)
  • 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 COG1716
  • Curated reference: UniProt P9WJA9 (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 — 78 functional partner(s); context anchor pknB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001941|Rv1827|garA
MTDMNPDIEKDQTSDEVTVETTSVFRADFLSELDAPAQAGTESAVSGVEGLPPGSALLVVKRGPNAGSRFLLDQAITSAGRHPDSDIFLDDVTVSRRHAEFRLENNEFNVVDVGSLNGTYVNREPVDSAVLANGDEVQIGKFRLVFLTGPKQGEDDGSTGGP