mec Resolved · high auto-curated

H37Rv Rv1334 · MTBC0 mtbc0_001431 · 146 aa · 1513343–1513783 (+) · RefSeq NP_215850.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)[CysO
MTBC0 PGAP re-annotationCysO-cysteine peptidase
Revised (this work)CysO-cysteine peptidase. Pfam: Prok-JAB (PF14464.12).

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

Curated reference (UniProt)

UniProt P9WHS1 SwissProt · reviewed · Evidence at protein level
UniProt nameCysO-cysteine peptidase
EC (curated) EC 3.13.1.6
Curated functionProtease that hydrolyzes the covalent CysO-cysteine adduct synthesized by CysM to release L-cysteine and regenerate CysO.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namemec
eggNOG descriptionmetal-dependent protease of the Pad1 Jab1 superfamily
Orthologous groupCOG1310
EC number EC 3.13.1.6
KEGG orthology K21140
KEGG pathways map04122
Gene Ontology (59) GO:0000096, GO:0000097, GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006082, GO:0006508 +47 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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 4 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
Prok-JABPF14464.12 1.9e-2915–130 Prokaryotic homologs of the JAB domain

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

Closest characterised functional partner: cysM (O-phosphoserine sulfhydrylase), high confidence from genomic context alone (score 992 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2115c mpa proteasome-associated ATPase 994 993 coexpression:463 experimental:918 database:844
Rv1336 cysM O-phosphoserine sulfhydrylase 991 992 ctx neighborhood:847 cooccurence:439 coexpression:809 database:500
Rv1335 cysO sulfur carrier protein CysO 991 991 ctx neighborhood:851 cooccurence:715 coexpression:797
Rv3696c glpK glycerol kinase 988 986 experimental:908 database:844
Rv0707 rpsC 30S ribosomal protein S3 958 957 experimental:854 database:652
Rv0705 rpsS 30S ribosomal protein S19 956 957 experimental:868 database:652
Rv1329c dinG ATP-dependent helicase DinG 950 948 ctx neighborhood:750 database:774
Rv0683 rpsG 30S ribosomal protein S7 948 948 experimental:852 database:623
Rv0721 rpsE 30S ribosomal protein S5 946 947 experimental:834 database:644
Rv0710 rpsQ 30S ribosomal protein S17 946 947 experimental:838 database:652
Rv0700 rpsJ 30S ribosomal protein S10 943 944 experimental:839 database:644
Rv2785c rpsO 30S ribosomal protein S15 950 943 experimental:835 database:644
Rv2890c rpsB 30S ribosomal protein S2 945 942 experimental:827 database:605
Rv0718 rpsH 30S ribosomal protein S8 942 940 experimental:826 database:652
Rv0702 rplD 50S ribosomal protein L4 942 939 experimental:826 database:643

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: [CysO
  • MTBC0 PGAP product: CysO-cysteine peptidase
  • Pfam (hmmscan --cut_ga): Prok-JAB PF14464.12 (E=2e-29)
  • (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_215850.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Prok-JAB (PF14464.12)
  • 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 COG1310
  • Curated reference: UniProt P9WHS1 (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 — 171 functional partner(s); context anchor cysM
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001431|Rv1334|mec
MLLRKGTVYVLVIRADLVNAMVAHARRDHPDEACGVLAGPEGSDRPERHIPMTNAERSPTFYRLDSGEQLKVWRAMEDADEVPVVIYHSHTATEAYPSRTDVKLATEPDAHYVLVSTRDPHRHELRSYRIVDGAVTEEPVNVVEQY