Rv1119c Family assigned · low

H37Rv Rv1119c · MTBC0 - · 49 aa · 1242864–1243013 H37Rv (-) · RefSeq NP_215635.1

Genomic neighbourhood (genome browser)

Open in full genome browser →

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 protein
MTBC0 PGAP re-annotation—
Revised (this work)Class III adenylyl/guanylyl cyclase domain (eggNOG COG2114, nucleotide-cyclase; COG category T) - one of the many M. tuberculosis class-III cyclases. Short ORF (partial-domain match); regulatory role undetermined.
Functional category (TubercuList)conserved hypotheticals

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

In the literature (TB corpus sweep) named only in full text

No publication in PubMed mentions this gene in its title or abstract — not under its H37Rv locus tag, nor under any of its ortholog identifiers (M. bovis, M. marinum, M. smegmatis, M. leprae, M. abscessus). The atlas annotation rests on sequence/structure evidence, not on a primary study of this gene.

Named in the body of 3 paper(s) in Europe PMC full text, though in no title or abstract. Matched under Rv1119c (3).

A hit does NOT mean functional characterisation -- it may be a mention in a genome-wide table or screen (e.g. a differential-expression supplementary table), exactly the mechanism that revealed the Rv3222c/Sarkar2021 co-induction. Restricted to hits CORROBORATED by the H37Rv tag itself, the gene name, or a substantial/multi-alias hit count -- single-low-count-ortholog-only hits were excluded pending individual review (cf. Rv0027/Mb0028, a confirmed collision unrelated to Mycobacterium). Coverage limit (P52.4, measured 2026-09-30): the body-text part of this search only sees articles whose full text Europe PMC holds, about 8-13 % of the TB literature published before 2005, 21 % for 2005-2009, 40 % for 2010-2014 and 66 % since 2020, so the absence of a hit says little about older mentions.

Full-text-only mention found (Europe PMC), not visible to the title/abstract sweep above.

Enrichment pass (not a full re-read): the wave-1/2 triage already recorded this claim as identity_claim=yes with reasoning that shares specific technical vocabulary with this atlas's own function assignment (Class III adenylyl/guanylyl cyclase domain (eggNOG COG2114, ). Treated as corroborating, not as new evidence changing the verdict.

CORROBORATES existing atlas assignment (lexical cross-check, wave1/2 enrichment pass, not independently re-read in full).

Lighter-weight than the dark-gene deep-dive protocol (phase141-151): no tbmonitor/fullTextXML re-read performed here, only a lexical consistency check against the pre-existing triage reasoning. Sufficient for an already-functional gene (enrichment), not for resolving a hypothetical.

Europe PMC full-text sweep (P16.2a-septies, phase138, vagues 1/2), passe d'enrichissement en masse (phase152, 2026-08-18) : corroboration etablie par chevauchement LEXICAL entre le raisonnement du triage initial et la fonction deja assignee dans l'atlas -- PAS une relecture integrale du papier (protocole delibere plus leger que le deep-dive dark, proportionne a une tache d'enrichissement de gene deja fonctionnel, pas de resolution d'un hypothetical).

Scope of the sweep: What was actually swept: the H37Rv locus tag and the ortholog locus tags (M. bovis Mb…, M. marinum MMAR_…, M. smegmatis MSMEG_…, M. leprae ML…, M. abscessus MAB_…), plus the gene name where one exists. NOT swept: protein and enzyme names, including family shorthands such as Ldt(Mt4) or VapC28, and their orthographic variants. An absent locus-tag mention is therefore evidence about the TAG, and only indirect evidence about the protein (P18.14).

A verified absence of literature is itself information: it flags an annotation with no primary study behind it. This distinguishes a gene that is dark because nobody has looked from one that is dark despite having been studied. Source: PubMed (whole), MULTI-ALIAS sweep: H37Rv locus tag AND every ortholog identifier (M. bovis Mb…, M. marinum MMAR_…, M. smegmatis MSMEG_…, M. leprae ML…, M. abscessus MAB_…), each hit VERIFIED against the abstract text (word-boundary regex). phase73/phase75, 2026-07-13.

Intrinsic disorder (sequence + structure) partially disordered

Predicted disorder18% of residues (metapredict) · mean AlphaFold pLDDT 74.2

carries a substantial disordered region (0/49 residues); disorder is a property, not a function

A property (biophysics), not a function. No LLPS/condensate claim is made from disorder alone. Verdict unchanged. Source: metapredict v3 (Emenecker/Holehouse) per-residue disorder + AlphaFold mean pLDDT (annotation_mtbc P16.13).

Genomic-neighbour overlap (structural caveat) co-directional · 3 % of gene

NeighbourRv1120c (Rv1120c, - strand)
Overlap4 bp, 3 % of this gene's length

co-directional overlap: ordinary (e.g. shared stop/start codons in an operon), not the Rv2438A-type artefact P20.1, derived from GFF3 gene coordinates, 2026-08-03.

Conditional expression context (iModulons)

Member of 1 independently-modulated gene set(s): SG_7.

iModulon membership (independently-modulated gene sets from a 647-sample RNA-seq compendium): the conditional co-expression context. Co-expression is a regulatory context, NOT a molecular function. Source: iModulonDB / modulome_mtb (Yoo 2022).

CRISPRi vulnerability

Vulnerability index 1.02 (95% CI -0.83 to 3.81). A more negative index = more vulnerable to knockdown (better drug-target quality); indicative threshold VI ≤ -6 = highly vulnerable.

Quantitative CRISPRi knockdown, graded (finer than binary Tn-seq essentiality). Source: CRISPRi vulnerability index (Bosch 2021, supplementary Table S2 'mmc3.xlsx', bulk import via Europe PMC -- supersedes the per-gene pebble.rockefeller.edu scrape of phase46_crispri_vulnerability.py).

Caveat on this estimate. Bosch et al. flag this gene's vulnerability estimate as NOT certain, and here that call has a mechanical cause visible in the library itself: every guide targeting this gene is >=21 nt (str_span=0.100 on a 0-1 scale, near the genome floor), and guide repression strength saturates from 21 nt on -- so the library never sampled a partial knockdown for this gene, only the near-maximal repression plateau. The dose-response fit (and this VI) is therefore essentially unconstrained by data, not merely uncertain -- a limitation of the CRISPRi library design for the non-essential class (Bosch et al. 2021), not a defect in this specific measurement. n_guides=3 is descriptive only and does not predict this. Do not cite this VI as a standalone vulnerability claim.

Legacy record & comparison (Mycobrowser) ahead of Mycobrowser

Mycobrowser classes this locus among conserved hypotheticals; the atlas now assigns a functional handle (COG category). Mycobrowser is no longer maintained, so its EC numbers predate recent nomenclature revisions (e.g. the 2018 EC 7 "translocase" class) — most EC differences are re-numberings of the same enzyme, not conflicts.

Orthologues (reciprocal best hits across mycobacteria)

M. bovis Mb1150c · 100.0% identity

Reciprocal-best-hit orthologues (DIAMOND) against the Mycobrowser reference proteomes. A missing species is informative: e.g. a gene absent from M. leprae was likely lost in its reductive genome evolution. Locus tags link to Mycobrowser.

Curated reference (UniProt)

UniProt O06571 TrEMBL · unreviewed · Predicted
UniProt nameUncharacterized protein

As checked on 2026-09-23, UniProt listed this protein as Uncharacterized protein; the revised annotation above goes beyond that record. UniProt may have been recurated since: check the live entry.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category T Signal transduction mechanisms
eggNOG descriptionPFAM Adenylyl cyclase class-3 4 guanylyl cyclase
Orthologous groupCOG2114

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.

Outgroup conservation (beyond the MTBC) Mycobacterium

M. canettii dN/dS (deep-divergence selection) undefined (dS = 0) · 8 consensus substitution(s) · 1 canettii-fixed disruption
substitutions present but dS=0 (dN/dS undefined); carries 1 M. canettii-clade-fixed disruptive substitution(s) (candidate lineage-specific pseudogenisation — cross-check the intra-MTBC pseudogene layer)
Limitation: dN/dS mixes fixed canettii-H37Rv divergence with intra-canettii polymorphism, and is not polarised (the per-gene repolarisation is not viable: 79 % of the consensus SPDI lie outside the polarised table).
Genus-wide presence (~53 non-MTBC Mycobacterium) present in 43/53 (81%) · mean identity 52.0% · 4/4 closest MTBAP relatives
conserved across the genus (present in 43/53 non-MTBC Mycobacterium genomes, incl. distant relatives) — an ancient core gene predating the genus radiation
Phylostratum (deepest detected homolog) MTBC-specific → Mycobacterium → Mycobacteriaceae → Corynebacteriales → Actinomycetia → Bacteria

short ORF (49 aa) a shallow stratum may reflect homology-detection failure, not true youth
present across the genus Mycobacterium (NTM) but not detected in any non-Mycobacterium genome — a Mycobacterium-genus gene

Two orthogonal outgroup signals. M. canettii (the immediate outgroup) gives a deep-divergence dN/dS (a low value confirms a constrained, real gene; shown as confident only at ≥8 substitutions, else flagged low-power). Genus-wide presence/absence (tblastn vs assembled non-MTBC genomes) places the gene on the ancient-core ↔ MTBC-specific axis: a gene absent even from the closest MTBAP relatives is a candidate MTBC-specific innovation (possible host-adaptation factor, to confirm by synteny). The phylostratum extends that axis outside the genus (tblastn vs 13 reference genomes spanning Mycobacteriaceae → Corynebacteriales → Actinomycetia → outside the phylum): it is the deepest clade in which a homolog is still detected, i.e. a proxy for gene age. Read it with the null model in mind: a shallow (young) stratum can also reflect homology-detection failure for short or fast-evolving ORFs, so it is a descriptive axis, not a proof of novelty.

Essentiality (transposon mutagenesis)

DeJesus 2017 callUncertain · uncertain
What the call meansuncertain (short or TA-poor ORF): no call possible
TA sites (Himar1) 3 in the ORF — 0 in the essential state, 0 growth-defect, 3 non-essential, 0 growth-advantage. Saturation 0.667, mean read count 44.5. A region of the protein devoid of TA sites is invisible to this assay: nothing can be inferred about it, in either direction.
All 3 sites lie in this ORF alone (no overlapping CDS shares any), so the call is attributable to this gene.
CaveatStatistically thin call: only 3 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, and this atlas can say which bias dominates, because it measured it on its own 482 undetected proteins. Size is the main factor: undetected proteins have a median length of 145 aa against 295 aa for detected ones, and 25.3 % of them are shorter than 100 aa against 6.0 %. Predicted localisation matters far less than usually assumed: detection rates are 89.3 % for globular, 84.9 % for transmembrane, 88.0 % for lipoproteins and 77.8 % for signal-peptide proteins — so a short protein is under-sampled whatever its predicted compartment, and hydrophobicity alone is a weak excuse. Condition-specific expression and few tryptic peptides (PE/PPE repeats) add to this.

Predicted localisation (DeepTMHMM + lipobox) no export signal, no TM helix

Predictionno signal peptide, no TM helix (DeepTMHMM class GLOB)
DeepTMHMM classGLOB

A verified absence of signals, which is not a compartment. No Sec/Tat signal peptide, no transmembrane helix and no lipobox were found on this sequence. The predictor reports topology and export signals; it does not measure where the protein ends up, so this page draws no cytoplasmic conclusion from it. In M. tuberculosis that reservation is not theoretical: the 12 Esx paralogues of this atlas — EsxA/ESAT-6 and EsxB/CFP-10 among them, the best-established secreted proteins of the species — carry this very call, because substrates of the type VII (ESX) secretion system leave no recognisable signal. « Secreted » and « no signal peptide » are true together here.

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)

Length49 aa
Molecular weight5.1 kDa
Theoretical pI4.39
GRAVY0.163 (hydrophobic)
Aliphatic index91.6
Aromaticity0.061
Instability index15.7 (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 (hmmscan --cut_ga scan completed).

3D structure (interactive — Mol*/pdbe-molstar)

No experimental structure is deposited for this gene: showing the AlphaFold DB predicted model (mean pLDDT 74.2, confident), coloured by per-residue confidence (dark blue = very high, orange/red = low — treat low-confidence regions as unreliable, especially termini and loops). Drag to rotate, scroll to zoom.

Genomic context (neighbours & predicted operon) operon of 3

Upstream (5' on genome)Rv1118c (- strand, 32 bp gap)
Downstream (3' on genome)Rv1120c (- strand, -4 bp gap)
Predicted operon Rv1118c · Rv1119c · Rv1120c

Neighbours from the H37Rv annotation (- strand). The operon is predicted by co-directional intergenic distance (same strand, gaps ≤50 bp) — a transcription-unit hypothesis, not a mapped TSS. For a "hypothetical", co-transcription with a characterised operon is a concrete functional lead (complements the STRING neighborhood channel below).

Published operon evidence (two independent sources)

Roback 2007 (logistic regression: distance + expression correlation, 474 microarrays) operon of 2: Rv1119c · Rv1120c — disagrees with the distance heuristic above
REMap 2016 (RNA-seq coverage continuity, CDC1551, tag MT1151) not expressed (exponential phase)
not expressed (stationary phase)

Two independent published operon maps, cited alongside the distance heuristic above: an association corroborating or contradicting the heuristic, never proof of shared function. REMap's RNA-seq coverage continuity is the most direct of the three signals; Roback's logistic regression and the intergenic-distance heuristic are statistical proxies.

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

Explore full network →

Node colour = verdict, dashed = still uncharacterised; 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: Rv1120c (hypothetical protein), high confidence (score 882, all STRING channels except text-mining; the partner is chosen on its genomic-context evidence).

All 14 partner(s) at medium confidence are shown. None rests on an interaction measured in M. tuberculosis itself.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1120c hypothetical protein 882 882 ctx neighborhood:882
Rv1118c hypothetical protein 744 744 ctx neighborhood:710
Rv1121 zwf1 glucose-6-phosphate 1-dehydrogenase 557 556 ctx neighborhood:552
Rv1122 gnd2 6-phosphogluconate dehydrogenase (decarboxylating) 520 521 ctx neighborhood:519
Rv2434c transmembrane protein 438 421
Rv0073 glutamine ABC transporter ATP-binding protein 431 409
Rv2564 glnQ glutamine ABC transporter ATP-binding protein 431 409
Rv2565 NTE family protein 430 408
Rv3728 membrane protein 430 408
Rv3239c transmembrane transport protein 430 408
Rv3676 crp cAMP receptor protein 418 400
Rv0104 hypothetical protein 417 399
Rv1675c cmr HTH-type transcriptional regulator Cmr 415 397
Rv0998 acetyltransferase Pat 415 397

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 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.

Where the experimental evidence comes from, and why it matters here. STRING's experimental channel fuses interactions measured in M. tuberculosis with interactions measured in another organism and transferred to this pair by orthology. The two are not equivalent for this atlas, whose standing rule is that better studied elsewhere is not a function established in M. tuberculosis. Measured on the served network: of the 38 229 partner pairs shown across the atlas, 13 483 partner rows carry a non-zero experimental channel, and only 106 pairs rest on an interaction measured in M. tuberculosis itself — 0.3 % of the network. Those 106 are long-established complexes (ESX-1/ESAT-6, RNA polymerase with CarD and RbpA, the Pup–Mpa proteasome, gyrase, Emb, GarA with PknB and PknG, the Rel modules); no still-uncharacterised gene is among them. The reason is not a gap in this atlas but in the literature: there is almost no experimental interactome of this bacterium, IntAct holding 134 curated protein pairs for a ~4 000-gene proteome. A exp (transferred) badge is therefore a lead, never a measurement, and an absence of badge is not evidence that the pair does not interact.

Evidence

  • eggNOG ortholog COG2114 (COG category T), e-value 6.92e-12
  • eggNOG-mapper orthology (COG/EC functional assignment, under-propagated by the auto-curation which keys on cog_cat only). Family/activity-level transfer from orthology, not a substrate demonstrated in M. tuberculosis.

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 NP_215635.1)
  • 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 O06571 (TrEMBL, unreviewed; Predicted)
  • Model confidence: ESMFold per-residue pLDDT (mean 67.0, low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 14 functional partner(s); context anchor Rv1120c
  • 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)
  • Orthologues: reciprocal best hits (DIAMOND, Buchfink et al. 2021, doi:10.1038/s41592-021-01101-x) against Mycobrowser release 5 reference proteomes
  • Genomic context / operon: H37Rv annotation; operon predicted by co-directional intergenic distance (Salgado et al. 2000, doi:10.1073/pnas.030539397)
  • 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

>H37Rv|Rv1119c|
MTARVAGQAVGGQILVGEPVHDAVSDCADIRFGSYRLFSLDAAPGPDLD