MTBC Gene Atlas

Rv0590A Family assigned · low auto-curated · to review

H37Rv Rv0590A · MTBC0 · 84 aa · 688808–689062 H37Rv (+) · RefSeq

Genomic neighbourhood (genome browser)

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+ strand − strand mce2A (Rv0589) — family_assigned: Mce family protein Mce2A mce2A mce2B (Rv0590) — family_assigned: Mce-family protein Mce2B mce2B Rv0590A (Rv0590A) — family_assigned: Mce-family related protein lprL (Rv0593) — family_assigned: Mce family lipoprotein LprL lprL Rv0600c (Rv0600c) — requalified: two component sensor kinase HK1 Rv0601c (Rv0601c) — requalified: two component sensor kinase HK2 tcrA (Rv0602c) — family_assigned: two component DNA binding transcriptional regulator TcrA 680 kb 684 kb 688 kb 692 kb 696 kb 700 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)Mce-family related protein
MTBC0 PGAP re-annotation—
Revised (this work)Mce-family related protein
Functional category (TubercuList)virulence, detoxification, adaptation

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, but could be involved in host cell invasion.

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 Mycobrowser is no longer maintained; its EC numbers predate recent nomenclature revisions, so a class change usually reflects re-numbering, not a conflict.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 I6X9D2 TrEMBL · unreviewed
UniProt nameMce-family related protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category Q Secondary metabolites biosynthesis, transport and catabolism
eggNOG descriptionVirulence factor Mce family protein
Orthologous groupCOG1463
KEGG orthology ko:K02067
KEGG pathways ko02010, map02010
KEGG modules M00210, M00669, M00670

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 1 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.13% of strains (193) · 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) 7 in the ORF — 0 in the essential state, 0 growth-defect, 7 non-essential, 0 growth-advantage. Saturation 0.714, mean read count 78.6. 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 7 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 7 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)

Length84 aa
Molecular weight9.2 kDa
Theoretical pI6.29
GRAVY-0.01 (hydrophilic)
Aliphatic index101.0
Aromaticity0.095
Instability index28.3 (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).

Transcriptional regulation (signed TRN: ChIP-seq + TFOE)

Regulated by (3 TF) trcR (activates) · Rv2011c (represses) · Rv2250c (represses)

Regulatory edges from the ISB signed transcriptional regulatory network (TF ChIP-seq binding, Minch 2015 + TF-overexpression response, Rustad 2014). An edge is regulatory evidence (binding and/or expression change), not necessarily direct. For a "hypothetical", membership in a known regulon (e.g. DosR dormancy, PhoP virulence) is a strong physiological-context lead.

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

Explore full network →
Rv0590A (family_assigned) — Mce-family related protein Rv0590A Rv0588 (family_assigned) — ABC transporter permease Rv0588 yrbE2A (family_assigned) — ABC transporter permease yrbE2A mce2B (family_assigned) — Mce-family protein Mce2B mce2B mce2C (family_assigned) — virulence factor Mce family protein mce2C mce2D (family_assigned) — virulence factor Mce family protein mce2D mce2A (family_assigned) — Mce family protein Mce2A mce2A mce2R (family_assigned) — FadR family transcriptional regulator Mce2R mce2R mce2F (family_assigned) — MlaD family protein mce2F lprL (family_assigned) — Mce family lipoprotein LprL lprL Rv0585c (family_assigned) — lysylphosphatidylglycerol synthase transmembrane d Rv0585c

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: mce2B (Mce-family protein Mce2B; Rv0590, (MTCY19H5.32c), len: 275 aa. Mce2B; belongs to 24-membered Mycobacterium tuberculosis Mce protein family (), high confidence from genomic context alone (score 864 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0588 yrbE2B hyp hypothetical protein 884 880 ctx neighborhood:791
Rv0587 yrbE2A hyp hypothetical protein 881 877 ctx neighborhood:786
Rv0590 mce2B Mce-family protein Mce2B; Rv0590, (MTCY19H5.32c), len: 275 aa. Mce2B; belongs to 24-membered Mycobacterium tuberculosis Mce protein family ( 951 864 ctx neighborhood:773 fusion:408 textmining:653
Rv0591 mce2C Mce family protein Mce2C 818 801 ctx neighborhood:792
Rv0592 mce2D Mce family protein Mce2D 799 788 ctx neighborhood:781
Rv0589 mce2A Mce family protein Mce2A 812 787 ctx neighborhood:781
Rv0586 mce2R HTH-type transcriptional regulator Mce2R 787 786 ctx neighborhood:785
Rv0594 mce2F Mce family protein Mce2F 797 784 ctx neighborhood:781
Rv0593 lprL Mce family lipoprotein LprL 796 784 ctx neighborhood:781
Rv0585c integral membrane protein 545 544 ctx neighborhood:544
Rv0655 mkl exp ABC transporter ATP-binding protein 555 535 experimental:431
Rv1964 yrbE3A integral membrane protein 506 496
Rv0168 yrbE1B membrane protein 493 474
Rv1965 yrbE3B integral membrane protein 490 471
Rv0167 yrbE1A membrane protein 485 463

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 COG1463
  • Curated reference: UniProt I6X9D2 (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 84.8)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 27 functional partner(s); context anchor mce2B
  • 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)
  • Transcriptional regulation: ISB signed TRN — TF ChIP-seq (Minch et al. 2015, doi:10.1038/ncomms6829) + TF overexpression (Rustad et al. 2014, doi:10.1186/gb-2014-15-11-502)
  • 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

>|Rv0590A|Rv0590A
LLHSSFGHLEGIQQPLIDELAELDHVLGKLPDAYRIIGRAGGIYGDFFNFYLCDISLKVNGLQPGGPVRTVKLFGQPTGRCTPQ