Rv3668c Resolved · medium auto-curated

H37Rv Rv3668c · MTBC0 mtbc0_003887 · 232 aa · 4133613–4134311 (-) · RefSeq NP_218185.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)protease
MTBC0 PGAP re-annotationprotease
Revised (this work)Protease.

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

Curated reference (UniProt)

UniProt I6YGW2 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible protease

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
eggNOG descriptionendopeptidase activity
Orthologous groupCOG5640

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 0.172 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 1 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

Closest characterised functional partner: Rv3802c (membrane protein), high confidence from genomic context alone (score 779 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3802c membrane protein 778 779 ctx cooccurence:769
Rv1275 lprC lipoprotein LprC 774 775 ctx cooccurence:773
Rv1274 lprB lipoprotein LprB 773 774 ctx cooccurence:771
Rv3244c lpqB lipoprotein LpqB 768 768 ctx cooccurence:762
Rv0531 membrane protein 765 765 ctx cooccurence:764
Rv2673 aftC alpha-(1->3)-arabinofuranosyltransferase 763 764 ctx cooccurence:763
Rv3035 hyp hypothetical protein 763 763 ctx cooccurence:761
Rv1476 membrane protein 759 759 ctx cooccurence:759
Rv0227c membrane protein 756 756 ctx cooccurence:756
Rv2525c hyp hypothetical protein 769 755 ctx cooccurence:752
Rv3805c aftB terminal beta-(1->2)-arabinofuranosyltransferase 754 755 ctx cooccurence:754
Rv1754c hyp hypothetical protein 769 754 ctx cooccurence:601
Rv3669 transmembrane protein 733 733 ctx neighborhood:693
Rv1100 hyp hypothetical protein 731 731 ctx cooccurence:731
Rv0466 hyp hypothetical protein 725 725 ctx cooccurence:724

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: protease
  • MTBC0 PGAP product: protease
  • (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_218185.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 COG5640
  • Curated reference: UniProt I6YGW2 (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 — 115 functional partner(s); context anchor Rv3802c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003887|Rv3668c|
MQTAHRRFAAAFAAVLLAVVCLPANTAAADDKLPLGGGAGIVVNGDTMCTLTTIGHDKNGDLIGFTSAHCGGPGAQIAAEGAENAGPVGIMVAGNDGLDYAVIKFDPAKVTPVAVFNGFAINGIGPDPSFGQIACKQGRTTGNSCGVTWGPGESPGTLVMQVCGGPGDSGAPVTVDNLLVGMIHGAFSDNLPSCITKYIPLHTPAVVMSINADLADINAKNRPGAGFVPVPA