cut2 Family assigned · medium auto-curated

H37Rv Rv2301 · MTBC0 mtbc0_002441 · 230 aa · 2597764–2598456 (+) · RefSeq NP_216817.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cutinase
MTBC0 PGAP re-annotationcutinase family protein
Revised (this work)Cutinase family protein. Pfam: Cutinase (PF01083.29).

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

Curated reference (UniProt)

UniProt P9WP41 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable carboxylesterase Culp2
EC (curated) EC 3.1.1.-
Curated functionShows weak esterase activity with the p-nitrophenol-linked aliphatic ester pNP-butyrate. Does not exhibit cutinase activity..; FUNCTION: Induces interferon-gamma (IFN-gamma) release in animal models and in human TB patients. Also induces a strong delayed-type hypersensitivity (DTH) response in animal models.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namecut2
eggNOG descriptionCatalyzes the hydrolysis of cutin, a polyester that forms the structure of plant cuticle
Orthologous group2DVMQ
EC number EC 3.1.1.74
KEGG orthology K08095
Gene Ontology (27) GO:0005575, GO:0005576, GO:0008150, GO:0009605, GO:0009607, GO:0020012, GO:0030682, GO:0042783, GO:0043207, GO:0044403, GO:0044413, GO:0044415 +15 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 0.5 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 3 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
CutinasePF01083.29 2.5e-4844–229 Cutinase

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

Closest characterised functional partner: eccD3 (ESX-3 secretion system protein EccD), medium confidence from genomic context alone (score 674 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1278 hyp hypothetical protein 716 717 ctx cooccurence:401 database:544
Rv0153c ptbB phosphotyrosine protein phosphatase 694 682 experimental:629
Rv0290 eccD3 ESX-3 secretion system protein EccD 674 674 ctx cooccurence:673
Rv1747 ABC transporter ATP-binding protein/permease 661 648 database:530
Rv1277 hyp hypothetical protein 635 636 database:544
Rv3157 nuoM NADH-quinone oxidoreductase subunit M 648 630 experimental:629
Rv2302 hyp hypothetical protein 627 627 ctx neighborhood:560
Rv0434 hyp hypothetical protein 609 609 database:561
Rv3812 PE_PGRS62 PE-PGRS family protein PE_PGRS62 601 598 database:543
Rv2328 PE23 PE family protein PE23 601 598 database:543
Rv3036c TB22.2 hyp hypothetical protein 601 598 database:543
Rv0832 PE_PGRS12 PE-PGRS family protein PE_PGRS12 601 598 database:543
Rv1827 garA glycogen accumulation regulator GarA 596 596 database:530
Rv0020c fhaA FHA domain-containing protein FhaA 596 596 database:530
Rv3196 hyp hypothetical protein 608 594 database:464

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: cutinase
  • MTBC0 PGAP product: cutinase family protein
  • Pfam (hmmscan --cut_ga): Cutinase PF01083.29 (E=2e-48)
  • (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_216817.2)
  • Domains: Pfam-A via hmmscan --cut_ga — Cutinase (PF01083.29)
  • 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 2DVMQ
  • Curated reference: UniProt P9WP41 (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 — 90 functional partner(s); context anchor eccD3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002441|Rv2301|cut2
MNDLLTRRLLTMGAAAAMLAAVLLLTPITVPAGYPGAVAPATAACPDAEVVFARGRFEPPGIGTVGNAFVSALRSKVNKNVGVYAVKYPADNQIDVGANDMSAHIQSMANSCPNTRLVPGGYSLGAAVTDVVLAVPTQMWGFTNPLPPGSDEHIAAVALFGNGSQWVGPITNFSPAYNDRTIELCHGDDPVCHPADPNTWEANWPQHLAGAYVSSGMVNQAADFVAGKLQ