hadC Family assigned · medium auto-curated

H37Rv Rv0637 · MTBC0 mtbc0_000674 · 166 aa · 736378–736878 (+) · RefSeq NP_215151.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)(3R)-hydroxyacyl-ACP dehydratase subunit HadC
MTBC0 PGAP re-annotation(3R)-hydroxyacyl-ACP dehydratase subunit HadC
Revised (this work)(3R)-hydroxyacyl-ACP dehydratase subunit HadC. Pfam: FAS1_DH_region (PF13452.12).

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

Curated reference (UniProt)

UniProt P9WFJ9 SwissProt · reviewed · Evidence at protein level
UniProt nameUPF0336 protein Rv0637

UniProt still lists this protein as UPF0336 protein Rv0637; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namehadA
eggNOG descriptionBelongs to the UPF0336 family
Orthologous groupCOG2030
Gene Ontology (41) GO:0001676, GO:0003674, GO:0003824, GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0006082, GO:0006629, GO:0006631, GO:0006633, GO:0008150 +29 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 0.097 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 1 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
FAS1_DH_regionPF13452.12 5.1e-2515–137 FAS1-like, dehydratase domain region

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

Closest characterised functional partner: hadB ((3R)-hydroxyacyl-ACP dehydratase subunit HadB), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0636 hadB (3R)-hydroxyacyl-ACP dehydratase subunit HadB 999 1000 ctx neighborhood:882 cooccurence:756 coexpression:855 experimental:999 textmining:934
Rv0635 hadA (3R)-hydroxyacyl-ACP dehydratase subunit HadA 934 934 ctx neighborhood:882 coexpression:431
Rv0718 rpsH 30S ribosomal protein S8 806 805 coexpression:805
Rv0704 rplB 50S ribosomal protein L2 786 787 coexpression:761
Rv0634B rpmG2 50S ribosomal protein L33 844 779 ctx neighborhood:768
Rv0719 rplF 50S ribosomal protein L6 770 770 coexpression:770
Rv1630 rpsA 30S ribosomal protein S1 857 758 coexpression:757 textmining:437
Rv0715 rplX 50S ribosomal protein L24 744 744 coexpression:744
Rv0733 adk adenylate kinase 747 738 coexpression:736
Rv0723 rplO 50S ribosomal protein L15 687 687 coexpression:687
Rv0721 rpsE 30S ribosomal protein S5 646 646 coexpression:415 database:420
Rv3339c icd1 isocitrate dehydrogenase 649 634 database:476
Rv0632c echA3 enoyl-CoA hydratase EchA3 623 622
Rv0639 nusG transcription termination/antitermination protein NusG 611 612 ctx neighborhood:544
Rv2242 hyp hypothetical protein 600 600 ctx cooccurence:599

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: (3R)-hydroxyacyl-ACP dehydratase subunit HadC
  • MTBC0 PGAP product: (3R)-hydroxyacyl-ACP dehydratase subunit HadC
  • Pfam (hmmscan --cut_ga): FAS1_DH_region PF13452.12 (E=5e-25)
  • (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_215151.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FAS1_DH_region (PF13452.12)
  • 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 COG2030
  • Curated reference: UniProt P9WFJ9 (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 — 162 functional partner(s); context anchor hadB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000674|Rv0637|hadC
MALKTDIRGMIWRYPDYFIVGREQCREFARAVKCDHPAFFSEEAAADLGYDALVAPLTFVTILAKYVQLDFFRHVDVGMETMQIVQVDQRFVFHKPVLAGDKLWARMDIHSVDERFGADIVVTRNLCTNDDGELVMEAYTTLMGQQGDGSARLKWDKESGQVIRTA