cut4 Resolved · high auto-curated

H37Rv Rv3452 · MTBC0 mtbc0_003671 · 226 aa · 3899337–3900017 (+) · RefSeq NP_217969.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cutinase
MTBC0 PGAP re-annotationcutinase Cut4
Revised (this work)Cutinase Cut4. 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 O06319 SwissProt · reviewed · Evidence at protein level
UniProt namePhospholipase Culp4
EC (curated) EC 3.1.1.-
Curated functionA2-type phospholipase, which is probably involved in the degradation of macrophage membrane. Hydrolyzes dipalmitoylphosphatidylcholine. Also shows moderate esterase activity and hydrolyzes the p-nitrophenol-linked aliphatic ester pNP-butyrate (C4). Does not exhibit cutinase activity.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namecut4
eggNOG descriptionCatalyzes the hydrolysis of cutin, a polyester that forms the structure of plant cuticle
Orthologous group2A1QU
EC number EC 3.1.1.74
KEGG orthology K08095
Gene Ontology (2) GO:0005575, GO:0005576

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, 2 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.38% of strains (556) · 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
CutinasePF01083.29 2.2e-5147–225 Cutinase

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

Closest characterised functional partner: cut3 (cutinase), medium confidence from genomic context alone (score 690 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3451 cut3 cutinase 706 690 ctx neighborhood:671
Rv1592c hyp hypothetical protein 572 572 ctx cooccurence:571
Rv0290 eccD3 ESX-3 secretion system protein EccD 503 503 ctx cooccurence:503
Rv3450c eccB4 ESX-4 secretion system protein EccB4 473 473 ctx neighborhood:472
Rv0283 eccB3 ESX-3 secretion system protein EccB3 469 470 ctx cooccurence:469
Rv0888 spmT hyp hypothetical protein 463 463 ctx cooccurence:463
Rv0185 hyp hypothetical protein 460 460 ctx cooccurence:460
Rv3453 Rv3453, (MTCY13E12.06), len: 110 aa. Possible conserved transmembrane protein, showing weak similarity with other proteins e.g. Q9F6C3 putat 420 420 ctx neighborhood:418
Rv0282 eccA3 ESX-3 secretion system protein EccA 404 404 ctx cooccurence:404
Rv1270c lprA lipoprotein LprA 612 279 textmining:484
Rv2223c caeB carboxylesterase B 719 229 textmining:651
Rv3802c membrane protein 890 193 textmining:870
Rv2913c D-amino acid aminohydrolase 552 44 textmining:551
Rv1400c lipI lipase 803 41 textmining:803
Rv1399c nlhH carboxylesterase NlhH 750 41 textmining:750

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 Cut4
  • Pfam (hmmscan --cut_ga): Cutinase PF01083.29 (E=2e-51)
  • (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_217969.1)
  • 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 2A1QU
  • Curated reference: UniProt O06319 (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 — 18 functional partner(s); context anchor cut3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003671|Rv3452|cut4
MIPRPQPHSGRWRAGAARRLTSLVAAAFAAATLLLTPALAPPASAGCPDAEVVFARGTGEPPGLGRVGQAFVSSLRQQTNKSIGTYGVNYPANGDFLAAADGANDASDHIQQMASACRATRLVLGGYSQGAAVIDIVTAAPLPGLGFTQPLPPAADDHIAAIALFGNPSGRAGGLMSALTPQFGSKTINLCNNGDPICSDGNRWRAHLGYVPGMTNQAARFVASRI