Rv1333 Family assigned · medium auto-curated

H37Rv Rv1333 · MTBC0 mtbc0_001430 · 344 aa · 1512301–1513335 (+) · RefSeq NP_215849.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hydrolase
MTBC0 PGAP re-annotationP1 family peptidase
Revised (this work)P1 family peptidase. Pfam: Peptidase_S58 (PF03576.20).

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

Curated reference (UniProt)

UniProt P9WM23 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized aminopeptidase Rv1333
EC (curated) EC 3.4.11.-
Curated functionAminopeptidase.

UniProt still lists this protein as Uncharacterized aminopeptidase Rv1333; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namedmpA
eggNOG descriptionpeptidase S58, DmpA
Orthologous groupCOG3191
KEGG orthology K18572
KEGG pathways map00332, map01130

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 0.232 · purifying
Polymorphic sites (≥ 0.1% of strains) 10 synonymous, 6 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.11% of strains (156) · 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
Peptidase_S58PF03576.20 1.3e-652–331 Peptidase family S58

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

Closest characterised functional partner: clpS (ATP-dependent Clp protease adapter protein ClpS), high confidence from genomic context alone (score 890 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1331 clpS ATP-dependent Clp protease adapter protein ClpS 895 890 ctx neighborhood:861
Rv1334 mec [CysO 887 886 ctx neighborhood:881
Rv1332 transcriptional regulator 891 875 ctx neighborhood:861
Rv1335 cysO sulfur carrier protein CysO 856 856 ctx neighborhood:851
Rv1337 integral membrane protein 874 855 ctx neighborhood:847
Rv1338 murI glutamate racemase 854 854 ctx neighborhood:847
Rv1336 cysM O-phosphoserine sulfhydrylase 854 854 ctx neighborhood:847
Rv1339 hyp hypothetical protein 815 816 ctx neighborhood:813
Rv1340 rphA ribonuclease PH 803 803 ctx neighborhood:797
Rv1330c pncB1 nicotinic acid phosphoribosyltransferase PncB1 764 764 ctx neighborhood:763
Rv1341 rdgB non-canonical purine NTP pyrophosphatase 761 762 ctx neighborhood:758
Rv1329c dinG ATP-dependent helicase DinG 613 612 ctx neighborhood:609
Rv2075c hyp hypothetical protein 585 60 textmining:577
Rv2479c Probable transposase; Rv2479c, (MTV008.35c), len: 328 aa. Probable transposase for IS6110. Identical to many other M. tuberculosis IS6110 tr 439 50 textmining:434
Rv1521 fadD25 fatty-acid--CoA ligase FadD25 513 47 textmining:510

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: hydrolase
  • MTBC0 PGAP product: P1 family peptidase
  • Pfam (hmmscan --cut_ga): Peptidase_S58 PF03576.20 (E=1e-65)
  • (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_215849.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Peptidase_S58 (PF03576.20)
  • 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 COG3191
  • Curated reference: UniProt P9WM23 (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 — 17 functional partner(s); context anchor clpS
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001430|Rv1333|
MNSITDVGGIRVGHYQRLDPDASLGAGWACGVTVVLPPPGTVGAVDCRGGAPGTRETDLLDPANSVRFVDALLLAGGSAYGLAAADGVMRWLEEHRRGVAMDSGVVPIVPGAVIFDLPVGGWNCRPTADFGYSACAAAGVDVAVGTVGVGVGARAGALKGGVGTASATLQSGVTVGVLAVVNAAGNVVDPATGLPWMADLVGEFALRAPPAEQIAALAQLSSPLGAFNTPFNTTIGVIACDAALSPAACRRIAIAAHDGLARTIRPAHTPLDGDTVFALATGAVAVPPEAGVPAALSPETQLVTAVGAAAADCLARAVLAGVLNAQPVAGIPTYRDMFPGAFGS