Rv3672c Resolved · high auto-curated

H37Rv Rv3672c · MTBC0 mtbc0_003891 · 273 aa · 4137351–4138172 (-) · RefSeq NP_218189.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationCoA pyrophosphatase
Revised (this work)CoA pyrophosphatase. Pfam: NUDIX (PF00293.35).

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

Curated reference (UniProt)

UniProt I6XHX8 TrEMBL · unreviewed · Evidence at protein level
UniProt nameNudix hydrolase domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
Preferred namenudL
eggNOG descriptionNudix hydrolase
Orthologous groupCOG0494
KEGG orthology K18568
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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 0 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.48% of strains (699) · 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
NUDIXPF00293.35 6.4e-1397–200 NUDIX domain

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

Closest characterised functional partner: marP (serine protease), high confidence from genomic context alone (score 929 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3433c nnr bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase 941 933 experimental:787 database:643
Rv3671c marP serine protease 930 929 ctx neighborhood:816 database:530
Rv3673c membrane-anchored thioredoxin-like protein 921 919 ctx neighborhood:591 coexpression:771
Rv3211 rhlE ATP-dependent RNA helicase RhlE 787 774 experimental:403 database:615
Rv1253 deaD ATP-dependent RNA helicase DeaD 781 768 experimental:403 database:615
Rv2888c amiC amidase AmiC 761 762 coexpression:735
Rv1677 dsbF lipoprotein DsbF 734 724 coexpression:649
Rv2878c mpt53 soluble secreted antigen Mpt53 733 724 coexpression:648
Rv2524c fas fatty acid synthase 676 665 database:406
Rv1340 rphA ribonuclease PH 689 658 database:636
Rv0118c oxcA oxalyl-CoA decarboxylase OxcA 602 601 database:520
Rv3674c nth endonuclease III 617 597 ctx neighborhood:591
Rv3339c icd1 isocitrate dehydrogenase 594 595 database:581
Rv1391 dfp bifunctional phosphopantothenoylcysteine decarboxylase/phosphopantothenate--cysteine ligase 588 589 database:556
Rv1043c hyp hypothetical protein 594 584 database:530

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: CoA pyrophosphatase
  • Pfam (hmmscan --cut_ga): NUDIX PF00293.35 (E=6e-13)
  • (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_218189.1)
  • Domains: Pfam-A via hmmscan --cut_ga — NUDIX (PF00293.35)
  • 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 COG0494
  • Curated reference: UniProt I6XHX8 (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 — 103 functional partner(s); context anchor marP
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003891|Rv3672c|
MSAGGTPLQAGATPTGSRGTVALRPDAGPSWLRPLVDNVGQIPDAYRRRLPADVLAMVTAAGAVSAMTSSRRDHREAAVLVLFSGPEAGPGDGGVPDDADLLLTVRASTLRHHAGQAAFPGGVVDPADDGPVATALREANEETGIDPSRLHPLATMERTFIAPSRFHVVPVLAYSPDPGPVAVVNEAETAIVARVPVRAFINPANRLMVYRRPHTRRWAGPAFLLNQMLVWGFTGQVISAVLDVAGWAQPWDTGDIRELDAAMVLIDDESDPR