disA Resolved · high auto-curated
H37Rv Rv3586 · MTBC0 mtbc0_003805 ·
358 aa · 4051568–4052644 (+) ·
RefSeq NP_218103.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | DNA integrity scanning protein DisA |
|---|---|
| MTBC0 PGAP re-annotation | DNA integrity scanning diadenylate cyclase DisA |
| Revised (this work) | DNA integrity scanning diadenylate cyclase DisA. Pfam: DAC (PF02457.22), DisA-linker (PF10635.15). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WNW5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | DNA integrity scanning protein DisA |
| EC (curated) |
EC 2.7.7.85
|
| Curated function | Participates in a DNA-damage check-point. DisA forms globular foci that rapidly scan along the chromosomes searching for lesions..; FUNCTION: Also has diadenylate cyclase activity, catalyzing the condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP). c-di-AMP likely acts as a signaling molecule that may couple DNA integrity with a cellular process. To a lesser extent, can also use ADP as substrate to produce c-di-AMP. Does not convert GTP to c-di-GMP. Also exhibits residual ATPase and ADPase activities in vitro. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| Preferred name | disA |
| eggNOG description | Has also diadenylate cyclase activity, catalyzing the condensation of 2 ATP molecules into cyclic di-AMP (c-di-AMP). c- di-AMP likely acts as a signaling molecule that may couple DNA integrity with a cellular process |
| Orthologous group | COG1623 |
| EC number |
EC 2.7.7.85
|
| KEGG orthology |
K07067
|
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 | 0.441 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 5 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.86% of strains (1246) · 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.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DAC | PF02457.22 | 3.0e-26 | 24–137 | DisA bacterial checkpoint controller nucleotide-binding |
DisA-linker | PF10635.15 | 3.0e-47 | 141–284 | DisA bacterial checkpoint controller linker region |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: radA (DNA repair protein RadA), high confidence from genomic context alone (score 991 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3585 radA |
DNA repair protein RadA | 997 | 991 ctx | neighborhood:881 coexpression:929 textmining:758 |
Rv3584 lpqE |
lipoprotein LpqE | 809 | 797 ctx | neighborhood:796 |
Rv3202c adnA |
ATP-dependent DNA helicase | 751 | 751 | coexpression:751 |
Rv0606 |
Possible transposase (fragment); Rv0606, (MTCY19H5.16c), len: 247 aa. Possible truncated transposase for IS_1536 element, highly similar to | 730 | 730 | coexpression:730 |
Rv3714c hyp |
hypothetical protein | 730 | 730 | coexpression:730 |
Rv2375 hyp |
hypothetical protein | 717 | 718 ctx | cooccurence:717 |
Rv3582c ispD |
2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase | 691 | 692 ctx | neighborhood:491 coexpression:419 |
Rv3583c carD |
RNA polymerase-binding transcription factor CarD | 579 | 579 ctx | neighborhood:498 |
Rv3581c ispF |
2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase | 546 | 546 ctx | neighborhood:509 |
Rv3555c hyp |
hypothetical protein | 512 | 512 | coexpression:441 |
Rv2191 hyp |
hypothetical protein | 476 | 476 | coexpression:474 |
Rv3296 lhr |
ATP-dependent helicase | 449 | 449 | coexpression:449 |
Rv3579c rlmB |
23S rRNA (guanosine(2251)-2'-O)-methyltransferase RlmB | 443 | 443 ctx | neighborhood:410 |
Rv3580c cysS1 |
cysteine--tRNA ligase | 426 | 426 ctx | neighborhood:410 |
Rv0605 |
IS1536 family serine type transposase | 422 | 423 | coexpression:423 |
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
- Legacy H37Rv annotation: DNA integrity scanning protein DisA
- MTBC0 PGAP product: DNA integrity scanning diadenylate cyclase DisA
- Pfam (hmmscan --cut_ga): DAC PF02457.22 (E=3e-26), DisA-linker PF10635.15 (E=3e-47)
- (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_218103.1)
- Domains: Pfam-A via hmmscan --cut_ga — DAC (PF02457.22), DisA-linker (PF10635.15)
- 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
COG1623 - Curated reference: UniProt P9WNW5 (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 —
27 functional partner(s); context anchor
radA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003805|Rv3586|disA MHAVTRPTLREAVARLAPGTGLRDGLERILRGRTGALIVLGHDENVEAICDGGFSLDVRYAATRLRELCKMDGAVVLSTDGSRIVRANVQLVPDPSIPTDESGTRHRSAERAAIQTGYPVISVSHSMNIVTVYVRGERHVLTDSATILSRANQAIATLERYKTRLDEVSRQLSRAEIEDFVTLRDVMTVVQRLELVRRIGLVIDYDVVELGTDGRQLRLQLDELLGGNDTARELIVRDYHANPEPPSTGQINATLDELDALSDGDLLDFTALAKVFGYPTTTEAQDSALSPRGYRAMAGIPRLQFAHADLLVRAFGTLQGLLAASAGDLQSVDGIGAMWARHVREGLSQLAESTISDQ