MTBC Gene Atlas

Rv3454 Family assigned · low auto-curated · to review

H37Rv Rv3454 · MTBC0 · 422 aa · 3874822–3876090 H37Rv (+) · RefSeq

Genomic neighbourhood (genome browser)

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+ strand − strand Rv3453 (Rv3453) — family_assigned: Possible conserved transmembrane protein Rv3454 (Rv3454) — family_assigned: Probable conserved integral membrane protein Rv3454 truA (Rv3455c) — requalified: tRNA pseudouridine synthase A infA (Rv3462c) — requalified: translation initiation factor IF-1 Rv3466 (Rv3466) — family_assigned: hypothetical protein Rv3467 (Rv3467) — family_assigned: hypothetical protein Rv3467 Rv3468c (Rv3468c) — requalified: dTDP-glucose 4,6-dehydratase Rv3468c 3 864 kb 3 868 kb 3 872 kb 3 876 kb 3 880 kb 3 884 kb

This gene (outlined) in its genomic context; arrows are neighbouring genes coloured by verdict. Click any gene to navigate. Pan and zoom in the full browser.

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)Probable conserved integral membrane protein
MTBC0 PGAP re-annotation—
Revised (this work)Probable conserved integral membrane protein
Functional category (TubercuList)cell wall and cell processes

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 functionUnknown

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 Mycobrowser is no longer maintained; its EC numbers predate recent nomenclature revisions, so a class change usually reflects re-numbering, not a conflict.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 O06321 TrEMBL · unreviewed
UniProt nameProbable conserved integral membrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category F Nucleotide transport and metabolism
eggNOG descriptionPermease for cytosine purines, uracil, thiamine, allantoin
Orthologous groupCOG1457

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 1.679 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 19 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.99% of strains (1433) · 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.

Essentiality (transposon mutagenesis)

DeJesus 2017 callNE · non-essential
What the call meansnon-essential
TA sites (Himar1) 28 in the ORF — 0 in the essential state, 0 growth-defect, 28 non-essential, 0 growth-advantage. Saturation 1.000, mean read count 115. A region of the protein devoid of TA sites is invisible to this assay: nothing can be inferred about it, in either direction.

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.

Predicted localisation (DeepTMHMM + lipobox) signal peptide

Predictionpredicted membrane protein with signal peptide (9 TM helixes)
DeepTMHMM classSP+TM
TM helices (DeepTMHMM)9

Transmembrane topology and signal peptide from DeepTMHMM (deep-learning reference predictor); lipoproteins from a (myco)bacterial lipobox motif. A sequence-based prediction of subcellular context.

Physico-chemical properties (computed, ProtParam)

Length422 aa
Molecular weight45.8 kDa
Theoretical pI8.51
GRAVY0.525 (hydrophobic)
Aliphatic index109.6
Aromaticity0.109
Instability index40.0 (unstable)

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).

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

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Rv3454 (family_assigned) — Probable conserved integral membrane protein Rv3454 Rv3453 (family_assigned) — Possible conserved transmembrane protein Rv3453 phoR (requalified) — sensory box histidine kinase PhoR phoR pyrB (family_assigned) — aspartate carbamoyltransferase catalytic subunit pyrB carB (family_assigned) — carbamoyl-phosphate synthase large subunit carB carA (family_assigned) — glutamine-hydrolyzing carbamoyl-phosphate synthase carA thiD (requalified) — hydroxymethylpyrimidine/phosphomethylpyrimidine ki thiD Rv1382 (requalified) — transporter Rv1382 Rv0543c (family_assigned) — DUF3349 domain-containing protein Rv0543c upp (requalified) — uracil phosphoribosyltransferase upp Rv3046c (family_assigned) — DUF3349 domain-containing protein Rv3046c

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.

Closest characterised functional partner: Rv3453 (Rv3453, (MTCY13E12.06), len: 110 aa. Possible conserved transmembrane protein, showing weak similarity with other proteins e.g. Q9F6C3 putat), high confidence from genomic context alone (score 997 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3453 Rv3453, (MTCY13E12.06), len: 110 aa. Possible conserved transmembrane protein, showing weak similarity with other proteins e.g. Q9F6C3 putat 996 997 ctx neighborhood:545 fusion:900 cooccurence:774 coexpression:729
Rv0758 phoR two component system response sensor kinase PhoR 836 836 ctx fusion:836
Rv1380 pyrB aspartate carbamoyltransferase 584 585 coexpression:580
Rv1384 carB carbamoyl-phosphate synthase large subunit 497 498 coexpression:492
Rv1383 carA carbamoyl-phosphate synthase small subunit 482 483 coexpression:477
Rv0422c thiD hydroxymethylpyrimidine/phosphomethylpyrimidine kinase 479 437 coexpression:405
Rv1382 hyp hypothetical protein 437 437 coexpression:437
Rv0543c hyp hypothetical protein 435 436 ctx cooccurence:432
Rv3309c upp uracil phosphoribosyltransferase 468 415 coexpression:414
Rv3046c hyp hypothetical protein 406 406 ctx cooccurence:406
Rv0414c thiE thiamine-phosphate synthase 425 399
Rv3659c conjugal transfer protein 416 52 textmining:410

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 COG1457
  • Curated reference: UniProt O06321 (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 88.5)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 12 functional partner(s); context anchor Rv3453
  • 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
  • Predicted localisation: DeepTMHMM (Hallgren et al. 2022, doi:10.1101/2022.04.08.487609) for transmembrane topology and signal peptide
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>|Rv3454|Rv3454
MAQGLKLGLHIPLWAGYACSTLIIFPLVVYGMKVLSQLQLWTTPLWLILMAAPFGYLVVSHPDSIGQFFSYAGKDGHGGLSFGSVLLAAGVCLSLIAQIAEQIDYLRFMPPRTPENANRWWTWTLLAGPGWVAFGATKQIIGLFLAVYLMANIPGSSTIANQPVHQFMQIYRTFVPGWLALTLAVILVVLSQIKINVTNAYSGSLAWTNSFTRLTKHYPGRVVFLGVNLAIALILMEANMFDFLNTILGCYANCGMAWVVAVASDIGFNKYLLGLSPKTPEFRRGMLYAINPVGFGSLLLAAGLSIVTFFGGLGAALQPYSPLVAIVTALVMPPILAAATKGKYYLRRTHDGIDLPMYDEHGNPSAAVLTCHVCHQDFERPDMLACQTHGAHVCSLCLSTDKQAEHVLPGLARAHIPGDQVP