mycP1 Resolved · high auto-curated

H37Rv Rv3883c · MTBC0 mtbc0_004117 · 446 aa · 4387663–4389003 (-) · RefSeq NP_218400.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane-anchored mycosin
MTBC0 PGAP re-annotationtype VII secretion system ESX-1 serine protease mycosin MycP1
Revised (this work)Type VII secretion system ESX-1 serine protease mycosin MycP1. 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 O05461 SwissProt · reviewed · Evidence at protein level
UniProt nameMycosin-1
EC (curated) EC 3.4.21.-
Curated functionMay play a dual role in regulation of ESX-1 secretion and virulence. Acts as a protease that cleaves EspB. Essential for ESX-1 function, required for early replication in macrophages and full virulence in mice.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
Preferred namemycP
eggNOG descriptionPeptidase S8
Orthologous groupCOG1404
KEGG orthology K14743
Gene Ontology (34) GO:0003674, GO:0003824, GO:0004175, GO:0004252, GO:0005575, GO:0005623, GO:0005886, GO:0006508, GO:0006807, GO:0008150, GO:0008152, GO:0008233 +22 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 0.832 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 13 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 7.1e-3581–379 Subtilase family

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

Closest characterised functional partner: eccE1 (ESX-1 secretion system protein EccE1), high confidence from genomic context alone (score 987 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3882c eccE1 ESX-1 secretion system protein EccE1 996 987 ctx neighborhood:882 cooccurence:503 coexpression:802 textmining:697
Rv3881c espB ESX-1 secretion-associated protein EspB 950 745 ctx neighborhood:731 textmining:812
Rv3884c eccA2 ESX-2 secretion system protein EccA 912 742 ctx neighborhood:728 textmining:673
Rv3869 eccB1 ESX-1 secretion system protein EccB 842 717 ctx cooccurence:654 textmining:466
Rv3880c espL ESX-1 secretion-associated protein EspL 824 653 ctx neighborhood:648 textmining:514
Rv3877 eccD1 ESX-1 secretion system protein EccD1 695 609 ctx cooccurence:583
Rv3870 eccCa1 ESX-1 secretion system protein EccCa 681 556 ctx cooccurence:538
Rv3871 eccCb1 ESX-1 secretion system protein EccCb 663 506 ctx cooccurence:485
Rv2189c hyp hypothetical protein 530 502
Rv2235 transmembrane protein 498 499 experimental:412
Rv3876 espI ESX-1 secretion-associated protein EspI 596 474 ctx cooccurence:461
Rv3886c mycP2 membrane-anchored mycosin 517 473 ctx neighborhood:419
Rv0425c ctpH metal cation transporting ATPase H 491 469
Rv0107c ctpI cation-transporter ATPase I 491 469
Rv1997 ctpF cation transporter ATPase F 491 469

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
  • MTBC0 PGAP product: type VII secretion system ESX-1 serine protease mycosin MycP1
  • Pfam (hmmscan --cut_ga): Peptidase_S8 PF00082.28 (E=7e-35)
  • (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_218400.1)
  • 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 O05461 (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 — 67 functional partner(s); context anchor eccE1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004117|Rv3883c|mycP1
MHRIFLITVALALLTASPASAITPPPIDPGALPPDVTGPDQPTEQRVLCASPTTLPGSGFHDPPWSNTYLGVADAHKFATGAGVTVAVIDTGVDASPRVPAEPGGDFVDQAGNGLSDCDAHGTLTASIIAGRPAPTDGFVGVAPDARLLSLRQTSEAFEPVGSQANPNDPNATPAAGSIRSLARAVVHAANLGVGVINISEAACYKVSRPIDETSLGASIDYAVNVKGVVVVVAAGNTGGDCVQNPAPDPSTPGDPRGWNNVQTVVTPAWYAPLVLSVGGIGQTGMPSSFSMHGPWVDVAAPAENIVALGDTGEPVNALQGREGPVPIAGTSFAAAYVSGLAALLRQRFPDLTPAQIIHRITATARHPGGGVDDLVGAGVIDAVAALTWDIPPGPASAPYNVRRLPPPVVEPGPDRRPITAVALVAVGLTLALGLGALARRALSRR