MTBC Gene Atlas

Rv3611 Still unknown · low auto-curated · to review

H37Rv Rv3611 · MTBC0 · 217 aa · 4052950–4053603 H37Rv (+) · RefSeq

Genomic neighbourhood (genome browser)

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+ strand − strand Rv3599c (Rv3599c) — dark: Hypothetical short protein folB (Rv3607c) — requalified: dihydroneopterin aldolase folP1 (Rv3608c) — requalified: dihydropteroate synthase folP1 Rv3611 (Rv3611) — dark: Hypothetical arginine and proline rich protein esxV (Rv3619c) — requalified: ESAT-6 like protein EsxV PPE65 (Rv3621c) — family_assigned: PPE family protein PPE65 PPE65 PE32 (Rv3622c) — family_assigned: PE family protein PE32 4 044 kb 4 048 kb 4 052 kb 4 056 kb 4 060 kb 4 064 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)Hypothetical arginine and proline rich protein
MTBC0 PGAP re-annotation—
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 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 Mycobrowser is no longer maintained; its EC numbers predate recent nomenclature revisions, so a class change usually reflects re-numbering, not a conflict.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 O06272 TrEMBL · unreviewed
UniProt nameHypothetical arginine and proline rich protein

Conservation & selection (intra-MTBC, 145 209 strains)

pN/pS 2.641 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 8 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) 2 in the ORF — 0 in the essential state, 0 growth-defect, 2 non-essential, 0 growth-advantage. Saturation 1.000, mean read count 104.5. A region of the protein devoid of TA sites is invisible to this assay: nothing can be inferred about it, in either direction.
CaveatStatistically thin call: only 2 TA (Himar1) sites in the whole ORF (atlas median 13; genes under 300 nt typically have very few). A DeJesus 2017 call built on so few independent observations is less robust than the same call on a longer gene, in either direction. Cross-check against the CRISPRi vulnerability index (independent of TA-site density) and, if this gene overlaps a neighbour (see Genomic-neighbour overlap section below), verify how many of its TA sites actually fall inside its own ORF. (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)

Length217 aa
Molecular weight23.8 kDa
Theoretical pI11.93
GRAVY-1.585 (hydrophilic)
Aliphatic index29.4
Aromaticity0.028
Instability index51.1 (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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Rv3611 (dark) — Hypothetical arginine and proline rich protein Rv3611 ftsH (requalified) — ATP-dependent zinc metalloprotease FtsH ftsH folK (requalified) — 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine folK folB (requalified) — dihydroneopterin aldolase folB folE (requalified) — GTP cyclohydrolase I FolE folE folP1 (requalified) — dihydropteroate synthase folP1 Rv3605c (family_assigned) — DUF3180 domain-containing protein Rv3605c Rv3108 (dark) — hypothetical protein Rv3108 pepE (family_assigned) — Xaa-Pro peptidase family protein pepE Rv1084 (family_assigned) — thioredoxin domain-containing protein Rv1084 chiZ (requalified) — cell wall hydrolase ChiZ chiZ

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: ftsH (zinc metalloprotease FtsH), medium confidence from genomic context alone (score 566 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3610c ftsH zinc metalloprotease FtsH 565 566 ctx neighborhood:566
Rv3606c folK 2-amino-4-hydroxy-6-hydroxymethyldihydropteridinepyrophosphokinase 546 546 ctx neighborhood:544
Rv3607c folB dihydroneopterin aldolase 545 545 ctx neighborhood:544
Rv3609c folE GTP cyclohydrolase I 543 544 ctx neighborhood:544
Rv3608c folP1 dihydropteroate synthase 543 544 ctx neighborhood:544
Rv3605c hyp hypothetical protein 543 544 ctx neighborhood:544
Rv3108 hyp hypothetical protein 632 47 textmining:630
Rv2089c pepE dipeptidase PepE 549 44 textmining:548
Rv1084 hyp hypothetical protein 643 43 textmining:643
Rv2719c chiZ membrane protein 444 42 textmining:444
Rv1066 hyp hypothetical protein 657 41 textmining:657
Rv3201c adnB ATP-dependent DNA helicase 548 41 textmining:548
Rv1187 rocA pyrroline-5-carboxylate dehydrogenase RocA 511 41 textmining:511
Rv0106 hyp hypothetical protein 511 41 textmining:511
Rv3143 response regulator 511 41 textmining:511

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
  • Curated reference: UniProt O06272 (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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 16 functional partner(s); context anchor ftsH
  • 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

>|Rv3611|Rv3611
VAIANPAEPGAAGRHHQPRGDRKPRAWRQCGPQNGPRRSQAITPEPGAAGRHHQPRGDRKPRAWRQCGPQNGPRRSQAITPEPGAAGRHHQPRGDRKPRAWRQCGPQNGPRRSQAITPEPGAAGRHHQPRGDRKPRAWRQCGPQNGPRRSQAITPEPGAAGRHHQPRGDRKPRAWRQCGPQNGPRRSQAITPEPGAAGRHWLDQRPVVPDGVGKSDS