Rv0724A Family assigned · low auto-curated · to review

H37Rv Rv0724A · MTBC0 · 111 aa · 817531–817866 H37Rv (-) · RefSeq

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Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)Conserved hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Exhibits S-adenosyl-L-methionine-dependent methyltransferase activity
Functional category (TubercuList)conserved hypotheticals

Curation note: Added P16.5d: Mycobrowser-annotated gene absent from RefSeq NC_000962.3 (the atlas' original 3906-CDS reference). Foundation record from the Mycobrowser release + translated H37Rv sequence; heavy enrichment layers (structure, orthology, conservation, interaction) pending.

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).

In the literature (TB corpus sweep)

This distinguishes a gene that is dark because nobody has looked from one that is dark despite having been studied. Source: .

Legacy record & comparison (Mycobrowser)

Mycobrowser functionFunction unknown

The legacy Mycobrowser record is shown for verification. Mycobrowser is no longer maintained; its EC numbers predate recent nomenclature revisions, so a class change usually reflects re-numbering, not a conflict.

Curated reference (UniProt)

UniProt Q79FX1 TrEMBL · unreviewed
UniProt nameSAM-dependent methyltransferase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
eggNOG descriptionExhibits S-adenosyl-L-methionine-dependent methyltransferase activity
Orthologous groupCOG3315
Gene Ontology (8) GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0016020, GO:0030312, GO:0044464, GO:0071944

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 0.474 · purifying
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.

Essentiality (transposon mutagenesis)

DeJesus 2017 callNE · non-essential
What the call meansnon-essential
TA sites (Himar1) 6 in the ORF — 0 in the essential state, 0 growth-defect, 6 non-essential, 0 growth-advantage. Saturation 0.833, mean read count 83. A region of the protein devoid of TA sites is invisible to this assay: nothing can be inferred about it, in either direction.
CaveatRead with some caution: only 6 TA (Himar1) sites in the whole ORF (atlas median 13). The DeJesus 2017 call rests on fewer independent observations than for a longer gene. If this gene overlaps a neighbour (see Genomic-neighbour overlap section below), some of these 6 sites may fall inside the neighbour's ORF rather than its own, leaving even fewer truly informative sites than the raw count suggests. (P20.3)

Genome-wide Himar1 transposon essentiality in H37Rv (DeJesus 2017). An essential call (ES/ESD/GD) is strong, independent evidence that a "hypothetical" locus encodes a functional, selectively required gene — orthogonal to intra-species conservation.

Proteomics (mass spectrometry) not detected

Not detected in the mass-spectrometry datasets integrated by PaxDb. This is not evidence of absence: low-abundance, condition-specific, or MS-refractory proteins (e.g. small, highly hydrophobic, or repetitive PE/PPE families with few tryptic peptides) are systematically under-sampled.

Physico-chemical properties (computed, ProtParam)

Length111 aa
Molecular weight12.2 kDa
Theoretical pI4.76
GRAVY-0.286 (hydrophilic)
Aliphatic index87.7
Aromaticity0.072
Instability index33.3 (stable)

Computed from the ancestral MTBC0 sequence with the ExPASy ProtParam method (Biopython). Descriptive biophysical context: a positive GRAVY flags a hydrophobic (often membrane) protein, a high instability index (>40) predicts a short in-vitro half-life, an extreme pI hints at compartment or binding partner.

Domains (Pfam, hmmscan --cut_ga)

No Pfam-A domain above the gathering threshold (or not yet scanned).

Structural search (AlphaFold DB model, Foldseek vs PDB — genome-wide) pLDDT 90.7

PDB hitprobTM-scoreE-valueDescription
6id6-assembly1_A 1.00 0.90 1.9e-11 sig 6id6-assembly1_A Crystal structure of Rv0731c from Mycobacterium tuberculosis at 1.63 Angstroms.
2ckd-assembly2_B 1.00 0.74 1.9e-05 sig 2ckd-assembly2_B Crystal structure of ML2640 from Mycobacterium leprae
2uyq-assembly1_A 1.00 0.71 3.3e-05 sig 2uyq-assembly1_A Crystal structure of ML2640c from Mycobacterium leprae in complex with S-adenosylmethionine
2uyo-assembly1_A 1.00 0.70 4.1e-05 sig 2uyo-assembly1_A Crystal structure of ML2640c from Mycobacterium leprae in an hexagonal crystal form

Foldseek search of the AlphaFold DB model (mean pLDDT 90.7, gated at 70) against the PDB — a genome-wide extension of the ESMFold dark-gene search that also covers proteins beyond the single-sequence length limit. Confident structural neighbours (E < 0.01) shown.

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

Explore full network →

Node colour = verdict, dashed = hypothetical; edge colour = evidence (green experimental, orange genomic-context, grey co-expression), width ∝ score. Click a partner to open its page; "Explore full network" to walk the graph.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2765 hydrolase 661 54 textmining:657
Rv2051c ppm1 polyprenol-monophosphomannose synthase 517 47 textmining:514
Rv3680 anion transporter ATPase 804 46 textmining:803
Rv1781c malQ 4-alpha-glucanotransferase 654 44 textmining:653
Rv3366 spoU tRNA/rRNA methylase SpoU 803 41 textmining:803
Rv3812 PE_PGRS62 PE-PGRS family protein PE_PGRS62 434 41 textmining:434
Rv0557 mgtA GDP-mannose-dependent alpha-mannosyltransferase 434 41 textmining:434

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 exp badge marks an experimentally-supported partner (measured interaction, experimental/database channel ≥400) as opposed to a purely predicted one — but note that the M. tuberculosis experimental interactome is dominated by a noisy bacterial-two-hybrid screen, so a strong measured link that contradicts the operon/localisation context is likely a false positive. 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.

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 )
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 COG3315
  • Curated reference: UniProt Q79FX1 (TrEMBL, unreviewed)
  • Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
  • Genome-wide structure: AlphaFold DB model (Jumper et al. 2021, doi:10.1038/s41586-021-03819-2; Varadi et al. 2024, doi:10.1093/nar/gkad1011) searched vs PDB with Foldseek (mean pLDDT 90.7)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 7 functional partner(s)
  • Essentiality: genome-wide transposon mutagenesis in H37Rv — DeJesus et al. 2017 (mBio, doi:10.1128/mBio.02133-16, CC BY)
  • Functional category: TubercuList scheme (Cole et al. 1998, doi:10.1038/31159), via Mycobrowser (Kapopoulou et al. 2011, doi:10.1016/j.tube.2010.09.006)
  • Physico-chemical properties: ExPASy ProtParam method via Biopython (Gasteiger et al. 2005), computed from the MTBC0 sequence
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>|Rv0724A|Rv0724A
SQDRLFDNSTELSVAGSTIATELVPGIVDFDAGRVREMADSFRKHGVDIDMASLVYSGERSHVVDYLRAKGWDVEGTVRTDLFRRNGLPVPAPHDDDPLGEIIFISGRLNG