Rv1043c Resolved · high auto-curated

H37Rv Rv1043c · MTBC0 mtbc0_001120 · 341 aa · 1173119–1174144 (-) · RefSeq NP_215559.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationserine protease
Revised (this work)Serine protease. Pfam: Trypsin (PF00089.33), Trypsin_2 (PF13365.13).

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

Curated reference (UniProt)

UniProt P96358 TrEMBL · unreviewed · Predicted
UniProt nameSerine protease

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
eggNOG descriptionTrypsin
Orthologous groupCOG0265

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 0.538 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 8 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.43% of strains (619) · clonal

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
TrypsinPF00089.33 1.5e-08143–297 Trypsin
Trypsin_2PF13365.13 2.4e-17145–293 Trypsin-like peptidase domain

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

Closest characterised functional partner: PE_PGRS28 (PE-PGRS family protein PE_PGRS28), high confidence from genomic context alone (score 736 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2115c mpa proteasome-associated ATPase 824 813 experimental:551 database:594
Rv3696c glpK glycerol kinase 769 754 experimental:402 database:589
Rv1452c PE_PGRS28 PE-PGRS family protein PE_PGRS28 736 736 ctx cooccurence:728
Rv2490c PE_PGRS43 PE-PGRS family protein PE_PGRS43 736 736 ctx cooccurence:728
Rv1651c PE_PGRS30 PE-PGRS family protein PE_PGRS30 733 733 ctx cooccurence:725
Rv0872c PE_PGRS15 PE-PGRS family protein PE_PGRS15 729 729 ctx cooccurence:721
Rv1004c membrane protein 738 726 ctx cooccurence:702
Rv0355c PPE8 PPE family protein PPE8 721 722 ctx cooccurence:718
Rv3350c PPE56 PPE family protein PPE56 719 720 ctx cooccurence:716
Rv3347c PPE55 PPE family protein PPE55 718 718 ctx cooccurence:714
Rv2209 integral membrane protein 721 714 ctx cooccurence:712
Rv2082 hyp hypothetical protein 713 714 ctx cooccurence:712
Rv1334 mec [CysO 710 700 database:576
Rv1045 hyp hypothetical protein 697 697 ctx neighborhood:460 cooccurence:459
Rv0304c PPE5 PPE family protein PPE5 696 696 ctx cooccurence:692

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: hypothetical protein
  • MTBC0 PGAP product: serine protease
  • Pfam (hmmscan --cut_ga): Trypsin PF00089.33 (E=1e-08), Trypsin_2 PF13365.13 (E=2e-17)
  • (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_215559.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Trypsin (PF00089.33), Trypsin_2 (PF13365.13)
  • 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 COG0265
  • Curated reference: UniProt P96358 (TrEMBL, unreviewed; Predicted)
  • 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 — 284 functional partner(s); context anchor PE_PGRS28
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001120|Rv1043c|
MCAHQFFGLVHNPVVAAAIGKPEPPPVDSDIGLPTTVPFEPWSVADFSRYLSTLGLPAAGDAVTLHRILSSMERAGLLLPLGWDPRLPVMGQKYISQGAISKGQRGGNLWLSEVFGAELIIPSYNAVTVQLAGHDDAGNPVDSWGTGLVVDHNHVITNKHVVTGLAGTSAGLSVYPSSNHAEAELVNFSGTAHPHPTLDVAVIKFEMPEGKYIPRLGGMAFRDPDWADEVYVFGYPRVPMTAEMAITVQRGEVVNPAATTIPGRQKIFLYSAIARPGNSGGPIVAQDGRVIGLVVEDSAEAPSTGTGPNAAPFYRGIPSSEVIRALDELDFGGIVEMDTLP