rocA Resolved · high auto-curated

H37Rv Rv1187 · MTBC0 mtbc0_001275 · 543 aa · 1337832–1339463 (+) · RefSeq NP_215703.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)pyrroline-5-carboxylate dehydrogenase RocA
MTBC0 PGAP re-annotationL-glutamate gamma-semialdehyde dehydrogenase
Revised (this work)L-glutamate gamma-semialdehyde dehydrogenase. Pfam: Aldedh (PF00171.28).

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

Curated reference (UniProt)

UniProt O50443 TrEMBL · unreviewed · Evidence at protein level
UniProt nameL-glutamate gamma-semialdehyde dehydrogenase
EC (curated) EC 1.2.1.88

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namepruA
eggNOG descriptionDehydrogenase
Orthologous groupCOG1012
EC number EC 1.2.1.88
KEGG orthology K00294
KEGG pathways map00250, map00330, map01100

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 0.432 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 5 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
AldedhPF00171.28 3.5e-9153–522 Aldehyde dehydrogenase family

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

Closest characterised functional partner: Rv1188 (proline dehydrogenase), high confidence from genomic context alone (score 999 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1188 proline dehydrogenase 999 999 ctx neighborhood:882 cooccurence:650 coexpression:830 database:900 textmining:649
Rv2322c rocD1 Rv2322c, (MTCY3G12.12), len: 221 aa. Probable rocD1,ornithine aminotransferase, highly similar to N-terminal region of other ornithine amino 941 939 database:900
Rv3859c gltB glutamate synthase large subunit 940 917 database:900
Rv3432c gadB glutamate decarboxylase GadB 921 917 database:900
Rv3858c gltD glutamate synthase small subunit 915 911 database:900
Rv2476c gdh NAD-dependent glutamate dehydrogenase 909 907 database:900
Rv2220 glnA1 glutamine synthetase 910 906 database:900
Rv2860c glnA4 glutamine synthetase 909 906 database:900
Rv1878 glnA3 glutamine synthetase GlnA 909 906 database:900
Rv0500 proC pyrroline-5-carboxylate reductase 957 905 database:900 textmining:570
Rv2222c glnA2 glutamine synthetase 910 905 database:900
Rv2439c proB glutamate 5-kinase protein 914 902 database:900
Rv2427c proA gamma-glutamyl phosphate reductase 907 901 database:900
Rv0788 purQ phosphoribosylformylglycinamidine synthase 901 901 database:900
Rv2211c gcvT aminomethyltransferase 865 840 database:800

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: pyrroline-5-carboxylate dehydrogenase RocA
  • MTBC0 PGAP product: L-glutamate gamma-semialdehyde dehydrogenase
  • Pfam (hmmscan --cut_ga): Aldedh PF00171.28 (E=3e-91)
  • (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_215703.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Aldedh (PF00171.28)
  • 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 COG1012
  • Curated reference: UniProt O50443 (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 — 82 functional partner(s); context anchor Rv1188
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001275|Rv1187|rocA
MDAITQVPVPANEPVHDYAPKSPERTRLRTELASLADHPIDLPHVIGGRHRMGDGERIDVVQPHRHAARLGTLTNATHADAAAAVEAAMSAKSDWAALPFDERAAVFLRAADLLAGPWREKIAAATMLGQSKSVYQAEIDAVCELIDFWRFNVAFARQILEQQPISGPGEWNRIDYRPLDGFVYAITPFNFTSIAGNLPTAPALMGNTVIWKPSITQTLAAYLTMQLLEAAGLPPGVINLVTGDGFAVSDVALADPRLAGIHFTGSTATFGHLWQWVGTNIGRYHSYPRLVGETGGKDFVVAHASARPDVLRTALIRGAFDYQGQKCSAVSRAFIAHSVWQRMGDELLAKAAELRYGDITDLSNYGGALIDQRAFVKNVDAIERAKGAAAVTVAVGGEYDDSEGYFVRPTVLLSDDPTDESFVIEYFGPLLSVHVYPDERYEQILDVIDTGSRYALTGAVIADDRQAVLTALDRLRFAAGNFYVNDKPTGAVVGRQPFGGARGSGTNDKAGSPLNLLRWTSARSIKETFVAATDHIYPHMAVD