mycP3 Resolved · high auto-curated

H37Rv Rv0291 · MTBC0 mtbc0_000310 · 461 aa · 357792–359177 (+) · RefSeq NP_214805.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane-anchored mycosin MycP
MTBC0 PGAP re-annotationtype VII secretion system ESX-3 serine protease mycosin MycP3
Revised (this work)Type VII secretion system ESX-3 serine protease mycosin MycP3. Pfam: Peptidase_S8 (PF00082.28).

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

Curated reference (UniProt)

UniProt O53695 SwissProt · reviewed · Evidence at protein level
UniProt nameMycosin-3
EC (curated) EC 3.4.21.-

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
Preferred namemycP3
eggNOG descriptionPeptidase S8
Orthologous groupCOG1404
KEGG orthology K14743
Gene Ontology (17) GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0005886, GO:0005887, GO:0008150, GO:0016020, GO:0016021, GO:0030312, GO:0031224, GO:0031226 +5 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 0.952 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 5 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
Peptidase_S8PF00082.28 4.0e-3486–389 Subtilase family

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

Closest characterised functional partner: eccD3 (ESX-3 secretion system protein EccD), high confidence from genomic context alone (score 987 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0290 eccD3 ESX-3 secretion system protein EccD 995 987 ctx neighborhood:882 coexpression:860 textmining:645
Rv0292 eccE3 ESX-3 secretion system protein EccE 991 983 ctx neighborhood:882 coexpression:860 textmining:541
Rv0289 espG3 ESX-3 secretion-associated protein EspG3 989 970 ctx neighborhood:815 coexpression:845 textmining:667
Rv0283 eccB3 ESX-3 secretion system protein EccB3 985 955 ctx neighborhood:535 cooccurence:474 coexpression:803 textmining:684
Rv0284 eccC3 ESX-3 secretion system protein EccC3 974 933 ctx neighborhood:581 coexpression:769 textmining:633
Rv0286 PPE4 PPE family protein PPE4 904 904 ctx neighborhood:469 coexpression:827
Rv0282 eccA3 ESX-3 secretion system protein EccA 926 832 ctx neighborhood:581 coexpression:515 textmining:578
Rv0288 esxH ESAT-6-like protein EsxH 737 721 ctx neighborhood:658
Rv0287 esxG ESAT-6 like protein EsxG 726 687 ctx neighborhood:592
Rv1997 ctpF cation transporter ATPase F 553 534
Rv0285 PE5 PE family protein PE5 547 526 ctx neighborhood:526
Rv2301 cut2 cutinase 534 516
Rv3724B cut5b Rv3724B, (MTV025.072), len: 187 aa. Probable cut5b,truncated cutinase, similar to C-terminal end of others e.g. Q9XB09|RVD2-RV1758 protein ( 533 515
Rv2189c hyp hypothetical protein 538 511
Rv3451 cut3 cutinase 518 499

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: membrane-anchored mycosin MycP
  • MTBC0 PGAP product: type VII secretion system ESX-3 serine protease mycosin MycP3
  • Pfam (hmmscan --cut_ga): Peptidase_S8 PF00082.28 (E=4e-34)
  • (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_214805.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Peptidase_S8 (PF00082.28)
  • 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 COG1404
  • Curated reference: UniProt O53695 (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 — 58 functional partner(s); context anchor eccD3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000310|Rv0291|mycP3
MIRAAFACLAATVVVAGWWTPPAWAIGPPVVDAAAQPPSGDPGPVAPMEQRGACSVSGVIPGTDPGVPTPSQTMLNLPAAWQFSRGEGQLVAIIDTGVQPGPRLPNVDAGGDFVESTDGLTDCDGHGTLVAGIVAGQPGNDGFSGVAPAARLLSIRAMSTKFSPRTSGGDPQLAQATLDVAVLAGAIVHAADLGAKVINVSTITCLPADRMVDQAALGAAIRYAAVDKDAVIVAAAGNTGASGSVSASCDSNPLTDLSRPDDPRNWAGVTSVSIPSWWQPYVLSVASLTSAGQPSKFSMPGPWVGIAAPGENIASVSNSGDGALANGLPDAHQKLVALSGTSYAAGYVSGVAALVRSRYPGLNATEVVRRLTATAHRGARESSNIVGAGNLDAVAALTWQLPAEPGGGAAPAKPVADPPVPAPKDTTPRNVAFAGAAALSVLVGLTAATVAIARRRREPTE