fadB Resolved · high auto-curated

H37Rv Rv0860 · MTBC0 mtbc0_000915 · 720 aa · 959443–961605 (+) · RefSeq NP_215375.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)fatty oxidation protein FadB
MTBC0 PGAP re-annotationfatty oxidation protein FadB
Revised (this work)Fatty oxidation protein FadB. Pfam: ECH_1 (PF00378.26), ECH_2 (PF16113.11), 3HCDH_N (PF02737.25), 3HCDH (PF00725.28).

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

Curated reference (UniProt)

UniProt O53872 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable fatty oxidation protein FadB

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred namefadB
eggNOG description3-hydroxyacyl-CoA dehydrogenase
Orthologous groupCOG1024
EC number EC 1.1.1.35, EC 4.2.1.17, EC 5.1.2.3
KEGG orthology K01782
KEGG pathways map00071, map00280, map00281, map00310, map00362, map00380, map00410, map00640, map00650, map00903, map00930, map01040, map01100, map01110, map01120, map01130, map01200, map01212
KEGG modules M00032, M00087

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 0.238 · purifying
Polymorphic sites (≥ 0.1% of strains) 7 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
ECH_1PF00378.26 1.1e-3113–213 Enoyl-CoA hydratase/isomerase
ECH_2PF16113.11 6.1e-2018–193 Enoyl-CoA hydratase/isomerase
3HCDH_NPF02737.25 5.5e-63328–505 3-hydroxyacyl-CoA dehydrogenase, NAD binding domain
3HCDHPF00725.28 3.5e-19508–607 3-hydroxyacyl-CoA dehydrogenase, C-terminal domain

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

Closest characterised functional partner: fadA (acyltransferase), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0859 fadA acyltransferase 999 1000 ctx neighborhood:882 cooccurence:730 coexpression:955 experimental:980 database:942 textmining:949
Rv0243 fadA2 acetyl-CoA acetyltransferase FadA 998 998 coexpression:697 experimental:804 database:942
Rv1323 fadA4 acetyl-CoA acetyltransferase 998 996 coexpression:698 experimental:804 database:942 textmining:580
Rv3556c fadA6 acetyl-CoA acetyltransferase FadA 997 996 coexpression:697 experimental:804 database:942
Rv1867 hyp hypothetical protein 996 996 coexpression:697 experimental:804 database:942
Rv3523 ltp3 lipid carrier protein 996 996 coexpression:696 experimental:804 database:942
Rv2790c ltp1 lipid-transfer protein 996 996 coexpression:696 experimental:804 database:942
Rv1074c fadA3 beta-ketoacyl CoA thiolase FadA 996 996 coexpression:697 experimental:804 database:942
Rv3546 fadA5 acetyl-CoA acetyltransferase FadA 996 996 coexpression:697 experimental:804 database:942
Rv0914c lipid carrier protein or keto acyl-CoA thiolase 996 996 coexpression:697 experimental:804 database:942
Rv1627c nonspecific lipid-transfer protein 970 966 coexpression:699 experimental:804 database:447
Rv1135A Rv1135A, len: 80 aa. Possible acetyl-CoA acetyltransferase (possible gene fragment), highly similar to other acetyl-CoA acetyltransferases e 970 966 coexpression:695 experimental:804 database:447
Rv3540c ltp2 lipid transfer protein 969 966 coexpression:697 experimental:804 database:447
Rv3522 ltp4 lipid transfer protein 967 966 coexpression:697 experimental:804 database:447
Rv2503c scoB succinyl-CoA:3-ketoacid-CoA transferase subunit B 946 939 database:900

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: fatty oxidation protein FadB
  • MTBC0 PGAP product: fatty oxidation protein FadB
  • Pfam (hmmscan --cut_ga): ECH_1 PF00378.26 (E=1e-31), ECH_2 PF16113.11 (E=6e-20), 3HCDH_N PF02737.25 (E=6e-63), 3HCDH PF00725.28 (E=4e-19)
  • (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_215375.1)
  • Domains: Pfam-A via hmmscan --cut_ga — ECH_1 (PF00378.26), ECH_2 (PF16113.11), 3HCDH_N (PF02737.25), 3HCDH (PF00725.28)
  • 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 COG1024
  • Curated reference: UniProt O53872 (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 — 272 functional partner(s); context anchor fadA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000915|Rv0860|fadB
MPDNTIQWDKDADGIVTLTMDDPSGSTNVMNEAYIESMGKAVDRLVAEKDSITGVVVASAKKTFFAGGDVKTMIQARPEDAGDVFNTVETIKRQLRTLETLGKPVVAAINGAALGGGLEIALACHHRIAADVKGSQLGLPEVTLGLLPGGGGVTRTVRMFGIQNAFVSVLAQGTRFKPAKAKEIGLVDELVATVEELVPAAKAWIKEELKANPDGAGVQPWDKKGYKMPGGTPSSPGLAAILPSFPSNLRKQLKGAPMPAPRAILAAAVEGAQVDFDTASRIESRYFASLVTGQVAKNMMQAFFFDLQAINAGGSRPEGIGKTPIKRIGVLGAGMMGAGIAYVSAKAGYEVVLKDVSLEAAAKGKGYSEKLEAKALERGRTTQERSDALLARITPTADAADFKGVDFVIEAVFENQELKHKVFGEIEDIVEPNAILGSNTSTLPITGLATGVKRQEDFIGIHFFSPVDKMPLVEIIKGEKTSDEALARVFDYTLAIGKTPIVVNDSRGFFTSRVIGTFVNEALAMLGEGVEPASIEQAGSQAGYPAPPLQLSDELNLELMHKIAVATRKGVEDAGGTYQPHPAEAVVEKMIELGRSGRLKGAGFYEYADGKRSGLWPGLRETFKSGSSQPPLQDMIDRMLFAEALETQKCLDEGVLTSTADANIGSIMGIGFPPWTGGSAQFIVGYSGPAGTGKAAFVARARELAAAYGDRFLPPESLLS