zmp1 Resolved · high auto-curated

H37Rv Rv0198c · MTBC0 mtbc0_000212 · 663 aa · 234868–236859 (-) · RefSeq NP_214712.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)zinc metalloprotease
MTBC0 PGAP re-annotationzinc metalloprotease Zmp1
Revised (this work)Zinc metalloprotease Zmp1. Pfam: Peptidase_M13_N (PF05649.19), Peptidase_M13 (PF01431.28).

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

Curated reference (UniProt)

UniProt I6X8R2 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable zinc metalloprotease Zmp1

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
Preferred namepepO
eggNOG descriptionpeptidase
Orthologous groupCOG3590
EC number EC 3.4.24.11, EC 3.4.24.71
KEGG orthology K01389, K01415, K07386
KEGG pathways map04614, map04640, map04974, map05010

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 0.179 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 30 synonymous, 17 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_M13_NPF05649.19 5.7e-12120–400 Peptidase family M13
Peptidase_M13PF01431.28 2.3e-80452–659 Peptidase family M13

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

Closest characterised functional partner: Rv0199 (membrane protein), high confidence from genomic context alone (score 784 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0199 membrane protein 795 784 ctx neighborhood:759
Rv0200 transmembrane protein 795 784 ctx neighborhood:758
Rv1629 polA DNA polymerase I 595 529 coexpression:424
Rv2592c ruvB Holliday junction ATP-dependent DNA helicase RuvB 527 527 coexpression:527
Rv3633 hyp hypothetical protein 525 526 database:521
Rv1501 hyp hypothetical protein 523 524 database:521
Rv1436 gap glyceraldehyde 3-phosphate dehydrogenase 623 498 coexpression:498
Rv0457c peptidase 669 486 ctx cooccurence:444
Rv3794 embA arabinosyltransferase A 451 452 coexpression:405
Rv3795 embB arabinosyltransferase B 449 449 coexpression:402
Rv3793 embC arabinosyltransferase C 447 448 coexpression:400
Rv0632c echA3 enoyl-CoA hydratase EchA3 441 441 coexpression:441
Rv3864 espE ESX-1 secretion-associated protein EspE 425 425 coexpression:414
Rv1887 hyp hypothetical protein 425 425 coexpression:414
Rv1782 eccB5 ESX-5 type VII secretion system protein EccB5 415 416 coexpression:405

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: zinc metalloprotease
  • MTBC0 PGAP product: zinc metalloprotease Zmp1
  • Pfam (hmmscan --cut_ga): Peptidase_M13_N PF05649.19 (E=6e-121), Peptidase_M13 PF01431.28 (E=2e-80)
  • (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_214712.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Peptidase_M13_N (PF05649.19), Peptidase_M13 (PF01431.28)
  • 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 COG3590
  • Curated reference: UniProt I6X8R2 (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 — 74 functional partner(s); context anchor Rv0199
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000212|Rv0198c|zmp1
MTLAIPSGIDLSHIDADARPQDDLFGHVNGRWLAEHEIPADRATDGAFRSLFDRAETQVRDLIIQASQAGAAVGTDAQRIGDLYASFLDEEAVERAGVQPLHDELATIDSAADATELAAALGTLQRAGVGGGIGVYVDTDSKDSTRYLVHFTQSGIGLPDESYYRDEQHAAVLAAYPGHIARMFGLVYGGESRDHAKTADRIVALETKLADAHWDVVKRRDADLGYNLRTFAQLQTEGAGFDWVSWVTALGSAPDAMTELVVRQPDYLVTFASLWASVNVEDWKCWARWRLIRARAPWLTRALVAEDFEFYGRTLTGAQQLRDRWKRGVSLVENLMGDAVGKLYVQRHFPPDAKSRIDTLVDNLQEAYRISISELDWMTPQTRQRALAKLNKFTAKVGYPIKWRDYSKLAIDRDDLYGNVQRGYAVNHDRELAKLFGPVDRDEWFMTPQTVNAYYNPGMNEIVFPAAILQPPFFDPQADEAANYGGIGAVIGHEIGHGFDDQGAKYDGDGNLVDWWTDDDRTEFAARTKALIEQYHAYTPRDLVDHPGPPHVQGAFTIGENIGDLGGLSIALLAYQLSLNGNPAPVIDGLTGMQRVFFGWAQIWRTKSRAAEAIRRLAVDPHSPPEFRCNGVVRNVDAFYQAFDVTEDDALFLDPQRRVRIWN