Rv0421c Family assigned · medium auto-curated

H37Rv Rv0421c · MTBC0 mtbc0_000442 · 209 aa · 510497–511126 (-) · RefSeq NP_214935.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationalpha/beta family hydrolase
Revised (this work)Alpha/beta family hydrolase. Pfam: Abhydrolase_11 (PF20408.5).

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

Curated reference (UniProt)

UniProt P96267 TrEMBL · unreviewed · Evidence at protein level
UniProt nameKANL3/Tex30 alpha/beta hydrolase-like domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionhydrolase of the alpha beta-hydrolase fold
Orthologous groupCOG3571
KEGG orthology K07020

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 1.157 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 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
Abhydrolase_11PF20408.5 2.2e-3020–188 Alpha/beta hydrolase domain

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

Closest characterised functional partner: thiD (hydroxymethylpyrimidine/phosphomethylpyrimidine kinase), high confidence from genomic context alone (score 971 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0422c thiD hydroxymethylpyrimidine/phosphomethylpyrimidine kinase 970 971 ctx neighborhood:882 coexpression:761
Rv0423c thiC phosphomethylpyrimidine synthase 848 848 ctx neighborhood:846
Rv3693 membrane protein 744 744 coexpression:744
Rv0420c transmembrane protein 489 489 ctx neighborhood:486
Rv0424c hyp hypothetical protein 489 489 ctx neighborhood:466
Rv2828A hyp hypothetical protein 411 411
Rv2923c hyp hypothetical protein 886 159 textmining:870
Rv1841c hyp hypothetical protein 541 100 textmining:511
Rv3724B cut5b Rv3724B, (MTV025.072), len: 187 aa. Probable cut5b,truncated cutinase, similar to C-terminal end of others e.g. Q9XB09|RVD2-RV1758 protein ( 812 68 textmining:807
Rv0982 mprB two component histidine-protein kinase/phosphatase MprB 446 58 textmining:437
Rv2593c ruvA Holliday junction ATP-dependent DNA helicase RuvA 553 55 textmining:547
Rv2676c hemQ hyp hypothetical protein 420 53 textmining:413
Rv1907c hyp hypothetical protein 804 47 textmining:803
Rv2033c hyp hypothetical protein 416 47 textmining:413
Rv0360c hyp hypothetical protein 416 46 textmining:413

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: alpha/beta family hydrolase
  • Pfam (hmmscan --cut_ga): Abhydrolase_11 PF20408.5 (E=2e-30)
  • (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_214935.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Abhydrolase_11 (PF20408.5)
  • 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 COG3571
  • Curated reference: UniProt P96267 (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 — 20 functional partner(s); context anchor thiD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000442|Rv0421c|
MNLDQIAGVAHQPAGPPHGVVVLTHGAGGSRESTLLQQVCAEWTRRGWLAVRYNLPYRRRRPTGPPSGSGSGDRAGIVEAIQLCRGLAEGPLIAGGHSYGGRQTSMVVAAGQAPVDVLTLFSYPVHPPGKPERVRTEHLPGIAVPTVFTHGTADPFGTLAQVRSAAAMVSAPTEVVEITGARHDLGSKTLDVARLAVDAALRLSAGQIA