dapA Resolved · high auto-curated

H37Rv Rv2753c · MTBC0 mtbc0_002930 · 300 aa · 3088637–3089539 (-) · RefSeq NP_217269.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)4-hydroxy-tetrahydrodipicolinate synthase
MTBC0 PGAP re-annotation4-hydroxy-tetrahydrodipicolinate synthase
Revised (this work)4-hydroxy-tetrahydrodipicolinate synthase. Pfam: DHDPS (PF00701.29).

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

Curated reference (UniProt)

UniProt P9WP25 SwissProt · reviewed · Evidence at protein level
UniProt name4-hydroxy-tetrahydrodipicolinate synthase
EC (curated) EC 4.3.3.7
Curated functionCatalyzes the condensation of (S)-aspartate-beta-semialdehyde [(S)-ASA] and pyruvate to 4-hydroxy-tetrahydrodipicolinate (HTPA).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Preferred namedapA
eggNOG descriptionCatalyzes the condensation of (S)-aspartate-beta- semialdehyde (S)-ASA and pyruvate to 4-hydroxy- tetrahydrodipicolinate (HTPA)
Orthologous groupCOG0329
EC number EC 4.3.3.7
KEGG orthology K01714
KEGG pathways map00261, map00300, map01100, map01110, map01120, map01130, map01230
KEGG modules M00016, M00525, M00526, M00527
Gene Ontology (43) GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006082, GO:0006520, GO:0006553, GO:0006807, GO:0008150, GO:0008152, GO:0008652 +31 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 0.376 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 4 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
DHDPSPF00701.29 3.6e-7713–295 Dihydrodipicolinate synthetase family

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

Closest characterised functional partner: dapB (4-hydroxy-tetrahydrodipicolinate reductase), high confidence from genomic context alone (score 990 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2773c dapB 4-hydroxy-tetrahydrodipicolinate reductase 997 990 ctx cooccurence:772 coexpression:479 database:900 textmining:778
Rv3708c asd aspartate-semialdehyde dehydrogenase 996 972 ctx cooccurence:497 coexpression:450 database:900 textmining:877
Rv1294 thrA homoserine dehydrogenase 962 939 database:900 textmining:409
Rv2752c rnj ribonuclease J 934 885 ctx neighborhood:839 textmining:449
Rv2754c thyX thymidylate synthase ThyX 861 822 ctx neighborhood:795
Rv1293 lysA diaminopimelate decarboxylase 961 817 ctx cooccurence:752 textmining:800
Rv2726c dapF diaminopimelate epimerase 965 730 ctx cooccurence:697 textmining:877
Rv3709c ask aspartokinase 959 722 ctx cooccurence:523 textmining:862
Rv3012c gatC glutamyl-tRNA(GLN) amidotransferase subunit C 736 721 coexpression:698
Rv2785c rpsO 30S ribosomal protein S15 699 699 coexpression:653
Rv2756c hsdM type I restriction/modification system DNA methylase HsdM 681 682 ctx neighborhood:677
Rv0948c chorismate mutase 688 669 coexpression:650
Rv1885c chorismate mutase 687 669 coexpression:650
Rv0706 rplV 50S ribosomal protein L22 662 662 coexpression:654
Rv2762c hyp hypothetical protein 755 655 ctx neighborhood:643

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: 4-hydroxy-tetrahydrodipicolinate synthase
  • MTBC0 PGAP product: 4-hydroxy-tetrahydrodipicolinate synthase
  • Pfam (hmmscan --cut_ga): DHDPS PF00701.29 (E=4e-77)
  • (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_217269.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DHDPS (PF00701.29)
  • 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 COG0329
  • Curated reference: UniProt P9WP25 (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 — 71 functional partner(s); context anchor dapB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002930|Rv2753c|dapA
MTTVGFDVAARLGTLLTAMVTPFSGDGSLDTATAARLANHLVDQGCDGLVVSGTTGESPTTTDGEKIELLRAVLEAVGDRARVIAGAGTYDTAHSIRLAKACAAEGAHGLLVVTPYYSKPPQRGLQAHFTAVADATELPMLLYDIPGRSAVPIEPDTIRALASHPNIVGVKDAKADLHSGAQIMADTGLAYYSGDDALNLPWLAMGATGFISVIAHLAAGQLRELLSAFGSGDIATARKINIAVAPLCNAMSRLGGVTLSKAGLRLQGIDVGDPRLPQVAATPEQIDALAADMRAASVLR