gabD2 Resolved · high auto-curated

H37Rv Rv1731 · MTBC0 mtbc0_001843 · 518 aa · 1969749–1971305 (+) · RefSeq NP_214748.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)succinate-semialdehyde dehydrogenase
MTBC0 PGAP re-annotationsuccinic semialdehyde dehydrogenase
Revised (this work)Succinic 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 P9WNX7 SwissProt · reviewed · Evidence at protein level
UniProt namePutative succinate-semialdehyde dehydrogenase [NADP(+)] 2
EC (curated) EC 1.2.1.79
Curated functionCatalyzes the NADP(+)-dependent oxidation of succinate semialdehyde to succinate. Although it has succinate semialdehyde dehydrogenase activity, is likely to act physiologically on a different aldehyde(s). NAD(+) can substitute for NADP(+), but enzymatic activity is three times reduced.

UniProt still lists this protein as Putative succinate-semialdehyde dehydrogenase [NADP(+)] 2; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namegabD2
eggNOG descriptionBelongs to the aldehyde dehydrogenase family
Orthologous groupCOG1012
EC number EC 1.2.1.16, EC 1.2.1.20, EC 1.2.1.79
KEGG orthology K00135
KEGG pathways map00250, map00310, map00350, map00650, map00760, map01100, map01120
KEGG modules M00027
Gene Ontology (32) GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006091, GO:0006099, GO:0006101, GO:0008150, GO:0008152, GO:0009013 +20 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 0.393 · purifying
Polymorphic sites (≥ 0.1% of strains) 7 synonymous, 8 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 3.1e-13629–481 Aldehyde dehydrogenase family

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv2589 gabT 4-aminobutyrate aminotransferase 937 932 database:900
Rv3318 sdhA succinate dehydrogenase flavoprotein subunit 934 931 database:900
Rv0248c succinate dehydrogenase flavoprotein subunit 933 930 database:900
Rv0234c gabD1 succinate-semialdehyde dehydrogenase 925 925 database:900
Rv3319 sdhB succinate dehydrogenase iron-sulphur protein subunit 917 912 database:900
Rv0247c succinate dehydrogenase iron-sulfur subunit 915 912 database:900
Rv3316 sdhC succinate dehydrogenase cytochrome B-556 subunit 911 910 database:900
Rv3317 sdhD succinate dehydrogenase hydrophobic membrane anchor subunit 912 907 database:900
Rv0889c citA citrate synthase 2 894 890 database:800
Rv1131 prpC methylcitrate synthase PrpC 896 889 database:800
Rv0896 gltA2 citrate synthase 1 895 889 database:800
Rv2852c mqo malate:quinone oxidoreductase 850 842 database:800
Rv2455c korA 2-oxoglutarate oxidoreductase subunit KorA 869 829 database:800
Rv1240 mdh malate dehydrogenase 839 829 database:800
Rv1098c fum fumarate hydratase 838 829 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: succinate-semialdehyde dehydrogenase
  • MTBC0 PGAP product: succinic semialdehyde dehydrogenase
  • Pfam (hmmscan --cut_ga): Aldedh PF00171.28 (E=3e-136)
  • (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_214748.2)
  • 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 P9WNX7 (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 — 79 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001843|Rv1731|gabD2
MPAPSAEVFDRLRNLAAIKDVAARPTRTIDEVFTGKPLTTIPVGTAADVEAAFAEARAAQTDWAKRPVIERAAVIRRYRDLVIENREFLMDLLQAEAGKARWAAQEEIVDLIANANYYARVCVDLLKPRKAQPLLPGIGKTTVCYQPKGVVGVISPWNYPMTLTVSDSVPALVAGNAVVLKPDSQTPYCALACAELLYRAGLPRALYAIVPGPGSVVGTAITDNCDYLMFTGSSATGSRLAEHAGRRLIGFSAELGGKNPMIVARGANLDKVAKAATRACFSNAGQLCISIERIYVEKDIAEEFTRKFGDAVRNMKLGTAYDFSVDMGSLISEAQLKTVSGHVDDATAKGAKVIAGGKARPDIGPLFYEPTVLTNVAPEMECAANETFGPVVSIYPVADVDEAVEKANDTDYGLNASVWAGSTAEGQRIAARLRSGTVNVDEGYAFAWGSLSAPMGGMGLSGVGRRHGPEGLLKYTESQTIATARVFNLDPPFGIPATVWQKSLLPIVRTVMKLPGRR