gpdA1 Resolved · high auto-curated

H37Rv Rv0564c · MTBC0 mtbc0_000593 · 341 aa · 658475–659500 (-) · RefSeq NP_215078.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)glycerol-3-phosphate dehydrogenase
MTBC0 PGAP re-annotationNAD(P)H-dependent glycerol-3-phosphate dehydrogenase
Revised (this work)NAD(P)H-dependent glycerol-3-phosphate dehydrogenase. Pfam: NAD_Gly3P_dh_N (PF01210.30), F420_oxidored (PF03807.24), NAD_Gly3P_dh_C (PF07479.20), GPD_NAD_C_bact (PF20618.4).

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

Curated reference (UniProt)

UniProt P9WN75 SwissProt · reviewed · Evidence at protein level
UniProt nameGlycerol-3-phosphate dehydrogenase [NAD(P)+] 1
EC (curated) EC 1.1.1.94
Curated functionCatalyzes the reduction of the glycolytic intermediate dihydroxyacetone phosphate (DHAP) to sn-glycerol 3-phosphate (G3P), the key precursor for phospholipid synthesis.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namegpsA
eggNOG descriptionGlycerol-3-phosphate dehydrogenase
Orthologous groupCOG0240
EC number EC 1.1.1.94
KEGG orthology K00057
KEGG pathways map00564, map01110

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 1.029 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 6 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
NAD_Gly3P_dh_NPF01210.30 1.5e-489–164 NAD-dependent glycerol-3-phosphate dehydrogenase N-terminus
F420_oxidoredPF03807.24 2.6e-049–111 NADP oxidoreductase coenzyme F420-dependent
NAD_Gly3P_dh_CPF07479.20 7.0e-50184–323 NAD-dependent glycerol-3-phosphate dehydrogenase C-terminus
GPD_NAD_C_bactPF20618.4 4.7e-20244–310 Bacterial GPD, NAD-dependent C-terminal

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

Closest characterised functional partner: Rv0565c (monooxygenase), high confidence from genomic context alone (score 807 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2249c glpD1 glycerol-3-phosphate dehydrogenase 960 916 database:900 textmining:554
Rv3302c glpD2 glycerol-3-phosphate dehydrogenase 945 916 database:900
Rv2982c gpdA2 glycerol-3-phosphate dehydrogenase 922 913 database:900
Rv1551 plsB1 acyltransferase PlsB 940 904 database:900 textmining:409
Rv2482c plsB2 glycerol-3-phosphate acyltransferase 927 904 database:900
Rv2182c 1-acylglycerol-3-phosphate O-acyltransferase 878 852 database:800
Rv0565c monooxygenase 812 807 ctx neighborhood:802
Rv2252 dagK diacylglycerol kinase 808 802 database:800
Rv1713 engA GTPase Der 812 788 coexpression:704
Rv0566c hyp hypothetical protein 735 735 ctx neighborhood:734
Rv1614 lgt prolipoprotein diacylglyceryl transferase 541 524 coexpression:497
Rv1329c dinG ATP-dependent helicase DinG 518 519 coexpression:502
Rv2043c pncA pyrazinamidase/nicotinamidase PncA 522 504 coexpression:411
Rv3068c pgmA phosphoglucomutase PgmA 507 476 coexpression:412
Rv3433c nnr bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase 467 468

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: glycerol-3-phosphate dehydrogenase
  • MTBC0 PGAP product: NAD(P)H-dependent glycerol-3-phosphate dehydrogenase
  • Pfam (hmmscan --cut_ga): NAD_Gly3P_dh_N PF01210.30 (E=1e-48), F420_oxidored PF03807.24 (E=3e-04), NAD_Gly3P_dh_C PF07479.20 (E=7e-50), GPD_NAD_C_bact PF20618.4 (E=5e-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_215078.1)
  • Domains: Pfam-A via hmmscan --cut_ga — NAD_Gly3P_dh_N (PF01210.30), F420_oxidored (PF03807.24), NAD_Gly3P_dh_C (PF07479.20), GPD_NAD_C_bact (PF20618.4)
  • 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 COG0240
  • Curated reference: UniProt P9WN75 (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 — 46 functional partner(s); context anchor Rv0565c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000593|Rv0564c|gpdA1
MAANKREPKVVVLGGGSWGTTVASICARRGPTLQWVRSAVTAQDINDNHRNSRYLGNDVVLSDTLRATTDFTEAANCADVVVMGVPSHGFRGVLVELSKELRPWVPVVSLVKGLEQGTNMRMSQIIEEVLPGHPAGILAGPNIAREVAEGYAAAAVLAMPDQHLATRLSAMFRTRRFRVYTTDDVVGVETAGALKNVFAIAVGMGYSLGIGENTRALVIARALREMTKLGVAMGGKSETFPGLAGLGDLIVTCTSQRSRNRHVGEQLGAGKPIDEIIASMSQVAEGVKAAGVVMEFANEFGLNMPIAREVDAVINHGSTVEQAYRGLIAEVPGHEVHGSGF