Rv0434 Family assigned · medium auto-curated

H37Rv Rv0434 · MTBC0 mtbc0_000456 · 217 aa · 524879–525532 (+) · RefSeq NP_214948.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationLON peptidase substrate-binding domain-containing protein
Revised (this work)LON peptidase substrate-binding domain-containing protein. Pfam: LON_substr_bdg (PF02190.23).

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

Curated reference (UniProt)

UniProt P96280 TrEMBL · unreviewed · Evidence at protein level
UniProt nameLon N-terminal domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionATP-dependent protease
Orthologous groupCOG2802
EC number EC 3.4.21.53
KEGG orthology K01338, K07157
KEGG pathways map04112

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 0.552 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 3 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
LON_substr_bdgPF02190.23 3.8e-338–204 ATP-dependent protease La (LON) substrate-binding domain

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

Closest characterised functional partner: Rv0433 (carboxylate-amine ligase), high confidence from genomic context alone (score 827 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0433 carboxylate-amine ligase 827 827 ctx neighborhood:801
Rv0432 sodC superoxide dismutase 804 804 ctx neighborhood:801
Rv0431 tuberculin-like peptide 760 760 ctx neighborhood:758
Rv0430 hyp hypothetical protein 740 741 ctx neighborhood:739
Rv1277 hyp hypothetical protein 699 683 database:637
Rv1278 hyp hypothetical protein 706 680 database:637
Rv1747 ABC transporter ATP-binding protein/permease 705 676 database:560
Rv0428c GCN5-like N-acetyltransferase 665 665 ctx neighborhood:609
Rv2337c hyp hypothetical protein 658 645 database:595
Rv3206c moeB1 adenylyltransferase/sulfurtransferase MoeZ 658 645 database:595
Rv2338c moeW molybdopterin biosynthesis protein MoeW 657 645 database:595
Rv0429c def polypeptide deformylase 646 645 ctx neighborhood:642
Rv3116 moeB2 molybdenum cofactor biosynthesis protein MoeB 657 644 database:595
Rv3196 hyp hypothetical protein 657 644 database:595
Rv1355c moeY molybdopterin biosynthesis protein MoeY 656 643 database:595

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: LON peptidase substrate-binding domain-containing protein
  • Pfam (hmmscan --cut_ga): LON_substr_bdg PF02190.23 (E=4e-33)
  • (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_214948.1)
  • Domains: Pfam-A via hmmscan --cut_ga — LON_substr_bdg (PF02190.23)
  • 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 COG2802
  • Curated reference: UniProt P96280 (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 — 41 functional partner(s); context anchor Rv0433
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000456|Rv0434|
MADFAPVELAMFPLESAPLPDEDLPLHIFEPRYAALVRDCMDTADPRFGVVLISRGREVGGGDTRCDVGTLARITECADAGSGRYMLRCRVGERIRVCDWLPDDPYPRAKVRFWPDQPGHPVTAAQLLEVEDRVVALFERIAAARGVRLPAREVVLGYPVVDPADTGQRLYALACRVPMGPADRYAVLAAPSAADRLVRLGDALDSVAAMVEFELST