Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
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| MTBC0 PGAP re-annotation | dormancy-associated translation inhibitor |
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| Revised (this work) | DATIN (Dormancy-Associated Translation Inhibitor), a DosR-regulon protein. Pfam Ribosom_S30AE_C (PF16321) places it in the ribosome-associated / hibernation-factor family; it is proposed to bind the 30S/70S ribosomal subunits and inhibit or stabilise translation during dormancy. The activity remains a (well-argued) prediction. |
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Curated reference (UniProt)
| UniProt |
P9WMA9
SwissProt · reviewed
· Evidence at protein level
|
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| UniProt name | Dormancy associated translation inhibitor |
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| Curated function | Involved in translation regulation. Inhibits protein synthesis and decreases bacterial growth when expressed in E.coli. Can also stimulate macrophages and peripheral blood mononuclear cells (PBMC) to secrete important cytokines that may be significant in granuloma formation and its maintenance. Increases secretion of IFN-gamma, TNF, IL-1 beta and IL-8 through human Toll-like receptor 2 (TLR2) signaling pathway. |
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Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
J Translation, ribosomal structure and biogenesis
|
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| eggNOG description | Sigma 54 modulation/S30EA ribosomal protein C terminus |
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| Orthologous group | COG1544 |
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| Gene Ontology (69) |
GO:0003674, GO:0005488, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005840, GO:0005886, GO:0006417, GO:0006448 +57 more
|
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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 |
0.578 · relaxed/neutral
|
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| Polymorphic sites (≥ 0.1% of strains) |
2 synonymous, 3 missense, 0 nonsense, 0 frameshift
|
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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.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|
Ribosom_S30AE_C | PF16321.11 |
3.2e-11 | 132–181 |
Sigma 54 modulation/S30EA ribosomal protein C terminus |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv0080 hyp |
hypothetical protein |
989 |
983 ctx |
neighborhood:882 coexpression:860 textmining:435 |
Rv2785c rpsO |
30S ribosomal protein S15 |
925 |
922 |
experimental:829 database:540 |
Rv3442c rpsI |
30S ribosomal protein S9 |
928 |
921 |
experimental:829 database:540 |
Rv0721 rpsE |
30S ribosomal protein S5 |
925 |
919 |
experimental:829 database:540 |
Rv3459c rpsK |
30S ribosomal protein S11 |
918 |
919 |
experimental:829 database:540 |
Rv0705 rpsS |
30S ribosomal protein S19 |
921 |
918 |
experimental:829 database:540 |
Rv0710 rpsQ |
30S ribosomal protein S17 |
921 |
918 |
experimental:829 database:540 |
Rv0683 rpsG |
30S ribosomal protein S7 |
920 |
918 |
experimental:829 database:540 |
Rv0707 rpsC |
30S ribosomal protein S3 |
919 |
918 |
experimental:829 database:540 |
Rv2890c rpsB |
30S ribosomal protein S2 |
918 |
918 |
experimental:829 database:540 |
Rv0718 rpsH |
30S ribosomal protein S8 |
918 |
918 |
experimental:829 database:540 |
Rv1630 rpsA |
30S ribosomal protein S1 |
913 |
909 |
experimental:806 database:540 |
Rv1996 |
universal stress protein |
927 |
903 |
coexpression:903 |
Rv0055 rpsR1 |
30S ribosomal protein S18 |
891 |
892 |
experimental:773 database:540 |
Rv2055c rpsR2 |
30S ribosomal protein S18 |
891 |
891 |
experimental:773 database:540 |
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.
Evidence
- MTBC0 PGAP product: 'dormancy-associated translation inhibitor'
- Pfam: Ribosom_S30AE_C PF16321 (E=3.2e-11) -- ribosome-associated / hibernation-factor C-terminal domain
- Member of the DosR dormancy regulon
ESM Atlas signal (exploratory)
Ancestral protein hash 8541bcd1d8970c9fd3afccd98f2db90c ·
10 ESM-space neighbours (max similarity 0.870).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|
| 1 | 10679 |
0.75 |
Charged N-terminal subdomain activation |
| 2 | 7305 |
0.69 |
Polyanion-binding beta-sheet surfaces |
| 3 | 3221 |
0.50 |
N-terminal basic interaction tails |
| 4 | 8334 |
0.48 |
Terminal interface-proximal polar segments |
| 5 | 7365 |
0.48 |
Basic aromatic nucleotide-contacting surfaces |
| 6 | 128 |
0.47 |
Ordered amphipathic interface segments |
| 7 | 12878 |
0.46 |
Loop-to-helix interface motifs |
| 8 | 7998 |
0.46 |
Intrinsic disorder/low-complexity detector |
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_214593.1)
- Domains: Pfam-A via hmmscan --cut_ga — Ribosom_S30AE_C (PF16321.11)
- 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
COG1544
- Curated reference: UniProt
P9WMA9
(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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
104 functional partner(s)
- Primary literature: (2012). Mycobacterium tuberculosis DosR Regulon Gene Rv0079 Encodes a Putative, 'Dormancy Associated Translation Inhibitor (DATIN)' PLoS ONE.
doi:10.1371/journal.pone.0038709 PMID:22701698
Ancestral MTBC0 protein sequence
>mtbc0_000089|Rv0079|
MEPKRSRLVVCAPEPSHAREFPDVAVFSGGRANASQAERLARAVGRVLADRGVTGGARVRLTMANCADGPTLVQINLQVGDTPLRAQAATAGIDDLRPALIRLDRQIVRASAQWCPRPWPDRPRRRLTTPAEALVTRRKPVVLRRATPLQAIAAMDAMDYDVHLFTDAETGEDAVVYRAGPSGLRLARQHHVFPPGWSRCRAPAGPPVPLIVNSRPTPVLTEAAAVDRAREHGLPFLFFTDQATGRGQLLYSRYDGNLGLITPTGDGVADGLA
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