Rv1867 Resolved · high auto-curated

H37Rv Rv1867 · MTBC0 mtbc0_001980 · 494 aa · 2133803–2135287 (+) · RefSeq NP_216383.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationacetyl-CoA acetyltransferase
Revised (this work)Acetyl-CoA acetyltransferase. Pfam: TLP1_add_C (PF18313.8).

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

Curated reference (UniProt)

UniProt P95148 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
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 0.411 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 7 missense, 0 nonsense, 3 frameshift
Disruption 3 distinct premature-stop/frameshift site(s); most common in 2.56% of strains (3714) · 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
TLP1_add_CPF18313.8 2.5e-26409–490 Thiolase-like protein type 1 additional C-terminal domain

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv0860 fadB fatty oxidation protein FadB 996 996 coexpression:697 experimental:804 database:942
Rv1715 fadB3 3-hydroxybutyryl-CoA dehydrogenase FadB 965 964 coexpression:427 experimental:412 database:900
Rv0468 fadB2 3-hydroxybutyryl-CoA dehydrogenase 965 964 coexpression:424 experimental:412 database:900
Rv3667 acs acetyl-CoAsynthetase 944 941 coexpression:418 database:900
Rv1837c glcB malate synthase 927 923 database:900
Rv3710 leuA 2-isopropylmalate synthase 925 923 database:900
Rv2503c scoB succinyl-CoA:3-ketoacid-CoA transferase subunit B 924 921 database:900
Rv2504c scoA succinyl-CoA:3-ketoacid-CoA transferase subunit A 923 920 database:900
Rv0914c lipid carrier protein or keto acyl-CoA thiolase 917 918 database:900
Rv2790c ltp1 lipid-transfer protein 915 915 database:900
Rv0753c mmsA methylmalonate-semialdehyde dehydrogenase 914 911 database:900
Rv0408 pta phosphate acetyltransferase 918 907 database:900
Rv2495c bkdC branched-chain keto acid dehydrogenase E2 component 909 906 database:900
Rv2455c korA 2-oxoglutarate oxidoreductase subunit KorA 915 904 database:900
Rv3546 fadA5 acetyl-CoA acetyltransferase FadA 933 901 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: hypothetical protein
  • MTBC0 PGAP product: acetyl-CoA acetyltransferase
  • Pfam (hmmscan --cut_ga): TLP1_add_C PF18313.8 (E=3e-26)
  • (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_216383.1)
  • Domains: Pfam-A via hmmscan --cut_ga — TLP1_add_C (PF18313.8)
  • 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 P95148 (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 — 146 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001980|Rv1867|
MPVDPRTPVLIGYGQVNHRGDIDAEKQSIEPVDLMAAAARKAADSTVLEAVDSIRVVHMLSAHYRNPGQLLGERIKARTFTTGYSGVGGNMPQSLVNRACLDIQRGRAGVVLLAGAETWRTRTGLRAKGSKLEWTVQDESVPLPDMAGDDVPMAGAAELRINLDRPAYVYPIFEQALRIAYGESIENHRKRIGELWARFSAVAADNPHAWIRNPVTADEIWQPGPQNRMVSWPYTKLMNSNNMVDQGAALLLTSVERATRLRIPAERWVYPQAGTDAHDTPAVADRHRLHRSTAIRIAGARALELAGLGLDDIEYVDLYSCFPSAVQVAAIELGLDTDDPARPLTVTGGLTFAGGPWSNYVTHSIATMAELLAANPGRRGLITANGGYLTKHSFGVYGTEPPSEFRWEDMQPAVDREPTGDGLVEWEGIGTVEAWTTPVNRDGQPEKAFLAVRTPDGSRSLAVITDPASVQATVREDIAGVKVAVAPDGTATLR