Rv2475c Family assigned · medium auto-curated

H37Rv Rv2475c · MTBC0 mtbc0_002637 · 138 aa · 2801223–2801639 (-) · RefSeq NP_216991.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationthioesterase family protein
Revised (this work)Thioesterase family protein. Pfam: Acyl-ACP_TE_C (PF20791.4), 4HBT_2 (PF13279.13).

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

Curated reference (UniProt)

UniProt I6Y9E8 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 S Function unknown
eggNOG descriptionthioesterase
Orthologous groupCOG0824
KEGG orthology K07107

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 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
Acyl-ACP_TE_CPF20791.4 1.0e-047–34 Acyl-ACP thioesterase C-terminal domain
4HBT_2PF13279.13 3.0e-1311–129 Thioesterase-like superfamily

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

Closest characterised functional partner: gdh (NAD-dependent glutamate dehydrogenase), high confidence from genomic context alone (score 968 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2476c gdh NAD-dependent glutamate dehydrogenase 968 968 ctx neighborhood:881 coexpression:744
Rv2940c mas multifunctional mycocerosic acid synthase 932 913 coexpression:483 experimental:816
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 931 912 coexpression:477 experimental:816
Rv2048c pks12 polyketide synthase 931 912 coexpression:474 experimental:816
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 931 911 coexpression:473 experimental:816
Rv1527c pks5 polyketide synthase 931 911 coexpression:470 experimental:816
Rv2474c hyp hypothetical protein 904 904 ctx neighborhood:882
Rv2946c pks1 polyketide synthase 844 826 coexpression:652 experimental:454
Rv2932 ppsB phthiocerol synthesis polyketide synthase type I PpsB 834 820 coexpression:651 experimental:454
Rv2477c ettA macrolide ABC transporter ATP-binding protein 778 778 ctx neighborhood:771
Rv1661 pks7 polyketide synthase 748 722 coexpression:468 experimental:454
Rv1181 pks4 polyketide beta-ketoacyl synthase 748 721 coexpression:467 experimental:454
Rv2243 fabD malonyl CoA-acyl carrier protein transacylase 743 721 coexpression:406
Rv3800c pks13 polyketide synthase 740 704 coexpression:462 experimental:454
Rv2931 ppsA phthiocerol synthesis polyketide synthase type I PpsA 724 704 coexpression:463 experimental:454

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: thioesterase family protein
  • Pfam (hmmscan --cut_ga): Acyl-ACP_TE_C PF20791.4 (E=1e-04), 4HBT_2 PF13279.13 (E=3e-13)
  • (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_216991.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Acyl-ACP_TE_C (PF20791.4), 4HBT_2 (PF13279.13)
  • 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 COG0824
  • Curated reference: UniProt I6Y9E8 (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 — 55 functional partner(s); context anchor gdh
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002637|Rv2475c|
MSVGFVTPVGVRWSDIDMYQHVNHATMVTILEEARVPFLKDAFGADITSTGLLIADVRVTYKGQLRLSDSPLQVTIWTKRLRAVDFTLGYEVRSVNAEPDSRPAVIAESQLAAFHIEEQRLVRLSPHHREYLQRWFRG