Rv3732 Still unknown · low auto-curated

H37Rv Rv3732 · MTBC0 mtbc0_003957 · 352 aa · 4207055–4208113 (+) · RefSeq NP_218249.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF2330 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF2330. Function unknown. Foldseek best (non-significant) hit: 6oiu-assembly3_C X-ray crystal structure of the ectodomain of the Toxo (prob 0.14, TM 0.24).

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

Curated reference (UniProt)

UniProt O69699 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionUncharacterized protein conserved in bacteria (DUF2330)
Orthologous groupCOG4402

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) pseudogene candidate

pN/pS 0.741 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 4 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 1.08% of strains (1574) · 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
DUF2330PF10092.15 1.6e-8029–298 Uncharacterized protein conserved in bacteria (DUF2330)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 87.0 (confident). A confident model makes the fold comparison meaningful.

Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.

TargetProbTME-valueDescription
6oiu-assembly3_C 0.14 0.24 1.3e-01 6oiu-assembly3_C X-ray crystal structure of the ectodomain of the Toxoplasma gondii ME49 Aminopeptidase N (TGME49_224350)
6oiu-assembly2_B 0.12 0.24 8.9e-02 6oiu-assembly2_B X-ray crystal structure of the ectodomain of the Toxoplasma gondii ME49 Aminopeptidase N (TGME49_224350)
6oiu-assembly4_D 0.11 0.24 1.3e-01 6oiu-assembly4_D X-ray crystal structure of the ectodomain of the Toxoplasma gondii ME49 Aminopeptidase N (TGME49_224350)
6fpy-assembly1_A 0.10 0.28 3.4e-01 6fpy-assembly1_A Inter-alpha-inhibitor heavy chain 1, wild type
8agb-assembly1_E 0.08 0.28 5.9e-01 8agb-assembly1_E Structure of yeast oligosaccharylransferase complex with lipid-linked oligosaccharide bound
6oiu-assembly1_A 0.07 0.22 4.0e-01 6oiu-assembly1_A X-ray crystal structure of the ectodomain of the Toxoplasma gondii ME49 Aminopeptidase N (TGME49_224350)
5dll-assembly1_A 0.06 0.23 4.5e-01 5dll-assembly1_A Aminopeptidase N (pepN) from Francisella tularensis subsp. tularensis SCHU S4
4qir-assembly1_A 0.06 0.27 1.3e+00 4qir-assembly1_A Crystal structure of Aminopeptidase N in complex with the phosphinic dipeptide analogue LL-(R,S)-2-(pyridin-3-yl)ethylGlyP[CH2]Phe

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

Closest characterised functional partner: Rv0538 (membrane protein), high confidence from genomic context alone (score 716 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0538 membrane protein 715 716 ctx cooccurence:714
Rv1267c embR transcriptional regulator EmbR 688 689 ctx cooccurence:686
Rv2113 integral membrane protein 679 680 ctx cooccurence:678
Rv3254 hyp hypothetical protein 598 599 ctx cooccurence:595
Rv1775 hyp hypothetical protein 591 592 ctx cooccurence:589
Rv3407 vapB47 antitoxin VapB47 588 588 ctx cooccurence:588
Rv1963c mce3R transcriptional repressor Mce3R 582 582 ctx cooccurence:580
Rv1853 ureD urease accessory protein UreD 556 556 ctx cooccurence:550
Rv3788 hyp hypothetical protein 553 553 ctx cooccurence:552
Rv3731 ligC DNA ligase C 544 544 ctx neighborhood:542
Rv1937 oxygenase 544 544 ctx cooccurence:543
Rv0339c iniR transcriptional regulator 541 541 ctx cooccurence:539
Rv2939 papA5 phthiocerol/phthiodiolone dimycocerosyl transferase 493 494 ctx cooccurence:491
Rv2560 hyp hypothetical protein 488 489 ctx cooccurence:487
Rv3903c cpnT hyp hypothetical protein 486 487 ctx cooccurence:484

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: DUF2330 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF2330 PF10092.15 (E=2e-80)
  • Foldseek best: 6oiu-assembly3_C X-ray crystal structure of the ectodomain of the Toxoplasma gon (prob 0.14, E=1e-01, TM=0.24)
  • (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_218249.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF2330 (PF10092.15)
  • 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 COG4402
  • Curated reference: UniProt O69699 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 87.0, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 38 functional partner(s); context anchor Rv0538
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003957|Rv3732|
MAVLPACRLGLVVCVATAVITATMVLATPSYACACGAAVTAHGSQATLNHEVALLHWDGTTETIVMQLAMNADTDNVALVVPTPTPAIVTTADQSTFGELDTLSAPLIEHQRHWSLRRGVGASGPQEAAARAPHVLNQVRLGPLEATTLTGGDLSGLQTWLSDNGYAIRPAVSAALDPYVRDGWAFVAIRLTSTDLIVGGLDPVRMTFRSSRLVYPMRLSVAAQEPQHVTIFTLSDHRQQRTDADAATQTTHVRFAGDMSTAVRDPLLRELIGNHGSYLTKVEVDIYQTSRISSDFTFGNAPNDDPYRQVVTVYDDVALPPLLLVVVSAIAVGAAGGAVVVVLRRRRRAHTG