tatA Family assigned · medium auto-curated
H37Rv Rv2094c · MTBC0 mtbc0_002228 ·
83 aa ·
2381670–2381921 MTBC0
(-) ·
RefSeq NP_216610.1
Genomic neighbourhood (genome browser)
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Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | Sec-independent protein translocase membrane-bound protein TatA |
|---|---|
| MTBC0 PGAP re-annotation | Sec-independent protein translocase subunit TatA |
| Revised (this work) | Sec-independent protein translocase subunit TatA. Pfam: TatA_B_E (PF02416.22). |
| Functional category (TubercuList) | cell wall and cell processes |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
In the literature (TB corpus sweep) 21 publications
21 TB publications mention this gene. 21 publication(s) discuss this gene (21 in a M. tuberculosis context, 7 in other mycobacteria — M. smegmatis (6), M. leprae (1), M. marinum (1)).
| Publication | Date |
|---|---|
| Establishment of minimum protein standards for Mycobacterium tuberculosis-derived extracellular vesicles through comparison of EV enrichment methods. doi:10.1186/s44350-025-00003-8 | 2025 |
| The Differentially Expressed Genes Responsible for the Development of T Helper 9 Cells From T Helper 2 Cells in Various Disease States: Immuno-Interactomics Study. doi:10.2196/42421 | 2023 |
| Selecting accurate post-elimination monitoring tools to prevent reemergence of urogenital schistosomiasis in Morocco: a pilot study. doi:10.1186/s40249-017-0289-z | 2017 |
| The PPE2 protein of Mycobacterium tuberculosis translocates to host nucleus and inhibits nitric oxide production. doi:10.1038/srep39706 | 2017 |
| Identification of novel loci associated with mycobacterial isoniazid resistance. doi:10.1016/j.tube.2015.09.008 | 2016 |
This layer CITES the literature and adds context; it does not change the verdict or the function stated elsewhere in this fiche. This distinguishes a gene that is dark because nobody has looked from one that is dark despite having been studied. Source: PubMed (whole): H37Rv locus tag + GENE NAME + ortholog identifiers (Mb…, MMAR_…, MSMEG_…, ML…, MAB_…), under a mycobacterial context filter; hits verified against the abstract text. Species-context counts distinguish M. tuberculosis literature from literature on other mycobacteria. phase76/phase77, 2026-07-13.
Intrinsic disorder (sequence + structure) highly disordered
| Predicted disorder | 42% of residues (metapredict) · mean AlphaFold pLDDT 75.6 |
|---|---|
| Disordered regions | 1 IDR(s), longest 34 aa [49-83] |
sequence-based disorder is high but AlphaFold folds it confidently (pLDDT>=70): treat the disorder call with caution (possible metapredict over-call)
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).
CRISPRi vulnerability
Vulnerability index -9.30 (95% CI -10.39 to -8.31). 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, pebble.rockefeller.edu).
Legacy record & comparison (Mycobrowser)
| Mycobrowser function | Involved in protein export: required for correct localization of precursor proteins bearing signal peptides with the twin arginine conserved motif S/T-R-R-X-F-L-K. This sec-independent pathway is termed tat for twin-arginine translocation system. This system mainly transports proteins with bound cofactors that require folding prior to export. |
|---|
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.
Orthologues (reciprocal best hits across mycobacteria)
| M. bovis |
Mb2121c
· 100.0% identity |
|---|---|
| M. leprae |
ML1331
· 69.3% identity |
| M. marinum |
MMAR_3080
· 83.0% identity |
| M. smegmatis |
MSMEG_3887
· 60.0% identity |
| M. orygis |
RJtmp_002164
· 100.0% identity |
| M. abscessus |
MAB_2187
· 62.0% 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 |
P9WGA1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Sec-independent protein translocase protein TatA |
| Curated function | Part of the twin-arginine translocation (Tat) system that transports large folded proteins containing a characteristic twin-arginine motif in their signal peptide across membranes. TatA could form the protein-conducting channel of the Tat system. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
U Intracellular trafficking, secretion and vesicular transport
|
|---|---|
| Preferred name | tatA |
| eggNOG description | Part of the twin-arginine translocation (Tat) system that transports large folded proteins containing a characteristic twin-arginine motif in their signal peptide across membranes. TatA could form the protein-conducting channel of the Tat system |
| Orthologous group | COG1826 |
| KEGG orthology |
K03116
|
| KEGG pathways |
map03060, map03070
|
| KEGG modules |
M00336
|
| Gene Ontology (2) |
GO:0008150, GO:0040007
|
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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 0 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.
Outgroup conservation (beyond the MTBC) Bacteria
| M. canettii dN/dS (deep-divergence selection) |
0.0 (low power)
· 1 consensus substitution(s) low power (1 canettii-consensus substitution(s)); present in M. canettii but dN/dS not reliable |
|---|---|
| Genus-wide presence (~53 non-MTBC Mycobacterium) |
present in 53/53 (100%) · mean identity 74.7%
· 4/4 closest MTBAP relatives conserved across the genus (present in 53/53 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 detected in 10/13 non-Mycobacterium reference genomes (down to Bacteria) · mean identity 49.7% detected down to outside the phylum (Proteobacteria/Firmicutes controls) — a universally conserved, ancient bacterial 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 call | Uncertain · uncertain |
|---|---|
| What the call means | uncertain (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 0.333, mean read count 135. A region of the protein devoid of TA sites is invisible to this assay: nothing can be inferred about it, in either direction. |
| Caveat | Statistically 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) detected
| MS detection | detected in 13 of 16 independent MS datasets |
|---|---|
| Integrated abundance | 699.0 ppm · rank 314/3519 (91.1th 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.
Predicted localisation (DeepTMHMM + lipobox)
| Prediction | predicted membrane protein (1 TM helix) |
|---|---|
| DeepTMHMM class | TM |
| TM helices (DeepTMHMM) | 1 |
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)
| Length | 83 aa |
|---|---|
| Molecular weight | 8.9 kDa |
| Theoretical pI | 8.16 |
| GRAVY | -0.235 (hydrophilic) |
| Aliphatic index | 89.4 |
| Aromaticity | 0.048 |
| Instability index | 57.4 (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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
TatA_B_E | PF02416.22 | 1.6e-17 | 4–49 | mttA/Hcf106 family |
Genomic context (neighbours & predicted operon) operon of 4
| Upstream (5' on genome) | tatC (- strand, 16 bp gap) |
|---|---|
| Downstream (3' on genome) | pafC (- strand, 67 bp gap) |
| Predicted operon |
Rv2091c · helY · tatC · tatA
|
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).
Functional interaction network (STRING v12, guilt-by-association)
Explore full network →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: tatC (Sec-independent protein translocase transmembrane protein TatC), high confidence from genomic context alone (score 983 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2093c tatC exp |
Sec-independent protein translocase transmembrane protein TatC | 994 | 983 ctx | neighborhood:787 coexpression:706 experimental:629 textmining:668 |
Rv3396c guaA |
GMP synthase | 935 | 933 | coexpression:921 |
Rv2097c pafA |
proteasome accessory factor PafA | 824 | 801 ctx | neighborhood:796 |
Rv2096c pafB |
proteasome accessory factor B | 809 | 799 ctx | neighborhood:796 |
Rv2095c pafC |
proteasome accessory factor C | 807 | 797 ctx | neighborhood:796 |
Rv2092c helY |
ATP-dependent DNA helicase HelY | 674 | 675 ctx | neighborhood:673 |
Rv2091c |
membrane protein | 533 | 533 ctx | neighborhood:508 |
Rv1337 exp |
integral membrane protein | 542 | 475 | experimental:467 |
Rv2098c PE_PGRS36 |
PE-PGRS family protein PE_PGRS36; Rv2098c, (MTCY49.38c), len: 434 aa. PE_PGRS36,Member of the Mycobacterium tuberculosis PE family, PGRS sub | 500 | 474 ctx | neighborhood:471 |
Rv2099c PE21 |
Rv2099c, (MTCY49.39c), len: 58 aa. PE21, Member of the Mycobacterium tuberculosis PE family (see Brennan and Delogu, 2002); 5'-end of Rv2098 | 497 | 471 ctx | neighborhood:471 |
Rv0110 exp |
integral membrane protein | 575 | 469 | experimental:467 |
Rv2146c |
transmembrane protein | 467 | 468 ctx | cooccurence:429 |
Rv2122c hisE |
phosphoribosyl-ATP pyrophosphatase | 463 | 463 | |
Rv0846c mmcO exp |
oxidase | 556 | 433 | experimental:415 |
Rv0799c hyp |
hypothetical protein | 495 | 433 | coexpression:401 |
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.
Evidence
- Legacy H37Rv annotation: Sec-independent protein translocase membrane-bound protein TatA
- MTBC0 PGAP product: Sec-independent protein translocase subunit TatA
- Pfam (hmmscan --cut_ga): TatA_B_E PF02416.22 (E=2e-17)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
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_216610.1)
- Domains: Pfam-A via hmmscan --cut_ga — TatA_B_E (PF02416.22)
- 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
COG1826 - Curated reference: UniProt P9WGA1 (SwissProt, reviewed; Evidence at protein level)
- 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 75.6)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
35 functional partner(s); context anchor
tatC - 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)
- 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
>mtbc0_002228|Rv2094c|tatA MGSLSPWHWAILAVVVIVLFGAKKLPDAARSLGKSLRIFKSEVRELQNENKAEASIETPTPVQSQRVDPSAASGQDSTEARPA
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