MTBC Gene Atlas

Rv2561 Family assigned · low auto-curated · to review

H37Rv Rv2561 · MTBC0 · 97 aa · 2881409–2881702 H37Rv (+) · RefSeq

Genomic neighbourhood (genome browser)

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+ strand − strand Rv2548A (Rv2548A) — dark: hypothetical protein Rv2557 (Rv2557) — family_assigned: hypothetical protein Rv2558 (Rv2558) — family_assigned: hypothetical protein Rv2561 (Rv2561) — family_assigned: Conserved hypothetical protein Rv2562 (Rv2562) — family_assigned: Conserved hypothetical protein Rv2566 (Rv2566) — family_assigned: hypothetical protein Rv2566 2 872 kb 2 876 kb 2 880 kb 2 884 kb 2 888 kb 2 892 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)Conserved hypothetical protein
MTBC0 PGAP re-annotation—
Revised (this work)Pfam Adenylate and Guanylate cyclase catalytic domain
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 Mycobrowser is no longer maintained; its EC numbers predate recent nomenclature revisions, so a class change usually reflects re-numbering, not a conflict.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 Q50737 TrEMBL · unreviewed

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category T Signal transduction mechanisms
eggNOG descriptionPfam Adenylate and Guanylate cyclase catalytic domain
Orthologous groupCOG2114
EC number EC 4.6.1.1
KEGG orthology ko:K01768
KEGG pathways ko00230, ko02025, ko04113, ko04213, map00230, map02025, map04113, map04213
KEGG modules M00695

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 2.201 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 7 missense, 0 nonsense, 5 frameshift
Disruption 5 distinct premature-stop/frameshift site(s); most common in 97.41% of strains (141442) · reference-fixed

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) 4 in the ORF — 0 in the essential state, 0 growth-defect, 4 non-essential, 0 growth-advantage. Saturation 1.000, mean read count 278.25. 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 4 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) detected

MS detectiondetected in 2 of 16 independent MS datasets
Integrated abundance5.52 ppm · rank 2905/3519 (17.5th percentile)

Detection by mass spectrometry is direct, experimental evidence that the protein product exists — orthogonal to sequence conservation and to Tn-seq essentiality, and especially decisive for a "hypothetical" locus. Reproducible detection across several independent datasets (PaxDb) makes the existence claim robust; the integrated abundance places the protein in the proteome's dynamic range.

Physico-chemical properties (computed, ProtParam)

Length97 aa
Molecular weight10.6 kDa
Theoretical pI9.36
GRAVY-0.267 (hydrophilic)
Aliphatic index81.8
Aromaticity0.072
Instability index37.9 (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).

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

Explore full network →
Rv2561 (family_assigned) — Conserved hypothetical protein Rv2561 Rv2562 (family_assigned) — Conserved hypothetical protein Rv2562 Rv3899c (family_assigned) — hypothetical protein Rv3899c glnQ (family_assigned) — ATP-binding cassette domain-containing protein glnQ eccD2 (family_assigned) — type VII secretion system ESX-2 subunit EccD2 eccD2 Rv0452 (family_assigned) — TetR family transcriptional regulator Rv0452 Rv3768 (family_assigned) — nuclear transport factor 2 family protein Rv3768 Rv2423 (requalified) — class I SAM-dependent methyltransferase Rv2423 Rv2565 (family_assigned) — patatin-like phospholipase family protein Rv2565 Rv0386 (family_assigned) — LuxR family transcriptional regulator Rv0386 Rv2488c (family_assigned) — LuxR family transcriptional regulator Rv2488c

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: Rv2562 (Rv2562, (MTCY9C4.06c), len: 129 aa. Conserved hypothetical protein, highly similar, but shorter 83 aa, to downstream ORF AAK46951|RV2561|MT2), high confidence from genomic context alone (score 948 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2562 Rv2562, (MTCY9C4.06c), len: 129 aa. Conserved hypothetical protein, highly similar, but shorter 83 aa, to downstream ORF AAK46951|RV2561|MT2 992 948 ctx neighborhood:601 fusion:867 textmining:870
Rv3899c hyp hypothetical protein 694 694 ctx cooccurence:694
Rv2564 glnQ glutamine ABC transporter ATP-binding protein 639 626 ctx neighborhood:408
Rv3887c eccD2 ESX-2 secretion system protein EccD 596 596 ctx cooccurence:596
Rv0452 transcriptional regulator 557 558 ctx cooccurence:557
Rv3768 hyp hypothetical protein 552 552 ctx cooccurence:551
Rv2423 hyp hypothetical protein 543 543 ctx cooccurence:542
Rv2565 NTE family protein 553 536
Rv0386 transcriptional regulator 534 535 ctx cooccurence:471
Rv2488c LuxR family transcriptional regulator 520 520 ctx cooccurence:458
Rv2067c hyp hypothetical protein 490 490 ctx cooccurence:486
Rv0256c PPE2 PPE family protein PPE2 483 483 ctx cooccurence:480
Rv0891c hyp hypothetical protein 464 464 ctx cooccurence:464
Rv2912c TetR family HTH-type transcriptional regulator 446 446 ctx cooccurence:445
Rv1358 transcriptional regulator 437 438

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 COG2114
  • Curated reference: UniProt Q50737 (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 — 40 functional partner(s); context anchor Rv2562
  • Essentiality: genome-wide transposon mutagenesis in H37Rv — DeJesus et al. 2017 (mBio, doi:10.1128/mBio.02133-16, CC BY)
  • Proteomics: integrated mass-spectrometry abundance from PaxDb 5.0 (Huang et al. 2023, doi:10.1016/j.mcpro.2023.100640), taxon 83332 — weighted average of 16 datasets, incl. Schubert et al. 2013 (doi:10.1016/j.chom.2013.04.008) and Albrethsen et al. 2013 (doi:10.1074/mcp.M112.018846)
  • 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

>|Rv2561|Rv2561
MGIQRAVLLIADIGGYTNYMHWNRKHLAHAQWTVAQLLESVIDAAKGMKLAKLEGDAAFFWAPGGQHQCPGMRPAPADAPEVPHAARADQKRPSLRL