ltp3 Family assigned · medium auto-curated

H37Rv Rv3523 · MTBC0 mtbc0_003739 · 394 aa · 3983206–3984390 (+) · RefSeq NP_218040.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)lipid carrier protein
MTBC0 PGAP re-annotationthiolase domain-containing protein
Revised (this work)Thiolase domain-containing protein. Pfam: Thiolase_C_1 (PF22691.3).

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

Curated reference (UniProt)

UniProt I6YGD8 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable lipid carrier protein or keto acyl-CoA thiolase Ltp3

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Preferred nameltp3
eggNOG descriptionCatalyzes the synthesis of acetoacetyl coenzyme A from two molecules of acetyl coenzyme A. It can also act as a thiolase, catalyzing the reverse reaction and generating two-carbon units from the four-carbon product of fatty acid oxidation
Orthologous groupCOG0183
EC number EC 2.3.1.9
KEGG orthology K00626
KEGG pathways map00071, map00072, map00280, map00310, map00362, map00380, map00620, map00630, map00640, map00650, map00720, map00900, map01100, map01110, map01120, map01130, map01200, map01212, map02020
KEGG modules M00088, M00095, M00373, M00374, M00375

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) pseudogene candidate

pN/pS n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 4 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 7.00% of strains (10170) · clonal

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
Thiolase_C_1PF22691.3 2.5e-29253–377 Thiolase C-terminal domain-like

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

Closest characterised functional partner: ltp4 (lipid transfer protein), high confidence from genomic context alone (score 917 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0860 fadB fatty oxidation protein FadB 996 996 coexpression:696 experimental:804 database:942
Rv3521 hyp hypothetical protein 996 986 ctx neighborhood:844 cooccurence:763 coexpression:428 experimental:415 textmining:787
Rv1715 fadB3 3-hydroxybutyryl-CoA dehydrogenase FadB 966 965 coexpression:428 experimental:412 database:900
Rv0468 fadB2 3-hydroxybutyryl-CoA dehydrogenase 966 964 coexpression:424 experimental:412 database:900
Rv3667 acs acetyl-CoAsynthetase 943 941 coexpression:411 database:900
Rv0914c lipid carrier protein or keto acyl-CoA thiolase 928 928 database:900
Rv2790c ltp1 lipid-transfer protein 929 927 database:900
Rv3542c chsH2 hyp hypothetical protein 953 924 ctx cooccurence:740 coexpression:434 experimental:508 textmining:416
Rv1837c glcB malate synthase 927 924 database:900
Rv3710 leuA 2-isopropylmalate synthase 926 923 database:900
Rv2503c scoB succinyl-CoA:3-ketoacid-CoA transferase subunit B 926 921 database:900
Rv2504c scoA succinyl-CoA:3-ketoacid-CoA transferase subunit A 924 920 database:900
Rv3522 ltp4 lipid transfer protein 966 917 ctx neighborhood:861 textmining:618
Rv3546 fadA5 acetyl-CoA acetyltransferase FadA 972 913 database:900 textmining:691
Rv0753c mmsA methylmalonate-semialdehyde dehydrogenase 914 910 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: lipid carrier protein
  • MTBC0 PGAP product: thiolase domain-containing protein
  • Pfam (hmmscan --cut_ga): Thiolase_C_1 PF22691.3 (E=2e-29)
  • (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_218040.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Thiolase_C_1 (PF22691.3)
  • 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 COG0183
  • Curated reference: UniProt I6YGD8 (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 — 164 functional partner(s); context anchor ltp4
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003739|Rv3523|ltp3
MAGKLAAVLGTGQTKYVAKRQDVSMNGLVREAIDRALADSGSTFDDIDAVVVGKAPDFFEGVMMPELFMADAMGATGKPLIRVHTAGSVGGSTGVVAASLVQSGKYRRVLALAWEKQSESNAMWALSIPVPFTKPVGAGAGGYFAPHVRAYIRRSGAPAHIGAMVAVKDRLNGSRNPLAHLQQPDITLEKVMASQMLWDPIRFDETCPSSDGACAVVVGDEEIADARLAQGHPVAWIHGTALRTEPLAFAGRDQVNPQAGRDAAAALWKAAGITSPIDEIDAAEIYVPFSWFEPMWLENLGFAREGEGWKLTEAGETAIGGRLPVNPSGGVLSANPIGASGLIRFAEAAIQVMGKAEARQVPGARKALGHAYGGGSQYFSMWVVGCEKPKQAAA