Rv0004 Resolved · high
H37Rv Rv0004 · MTBC0 mtbc0_000004 ·
187 aa · 4434–4997 (+) ·
RefSeq NP_214518.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | DNA replication protein DciA |
| Revised (this work) | DciA, DNA replication protein. Directly binds DNA and the replicative helicase DnaB and regulates the DnaB-DnaA interaction; functional analogue of the DnaC/DnaI helicase loaders that mycobacteria lack. Essential for viability; its depletion blocks cell-cycle progression. |
Curated reference (UniProt)
| UniProt |
P9WFL1
SwissProt · reviewed
· Inferred from homology
|
|---|---|
| UniProt name | UPF0232 protein Rv0004 |
UniProt still lists this protein as UPF0232 protein Rv0004; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Belongs to the UPF0232 family |
| Orthologous group | COG5512 |
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 | 2.598 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 7 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.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DciA | PF05258.18 | 4.5e-24 | 75–162 | Dna[CI] antecedent, DciA |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: recF (DNA replication/repair protein RecF), high confidence from genomic context alone (score 903 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0003 recF |
DNA replication/repair protein RecF | 931 | 903 ctx | neighborhood:881 |
Rv0002 dnaN |
DNA polymerase III subunit beta | 910 | 874 ctx | neighborhood:855 |
Rv0005 gyrB |
DNA gyrase subunit B | 797 | 785 ctx | neighborhood:727 |
Rv0007 |
membrane protein | 704 | 704 ctx | neighborhood:635 |
Rv2256c hyp |
hypothetical protein | 686 | 686 ctx | cooccurence:685 |
Rv2050 rbpA |
RNA polymerase-binding protein RbpA | 653 | 653 ctx | cooccurence:652 |
Rv2708c hyp |
hypothetical protein | 630 | 630 ctx | cooccurence:630 |
Rv2413c hyp |
hypothetical protein | 811 | 618 ctx | cooccurence:605 textmining:528 |
Rv1830 |
HTH-type transcriptional regulator | 618 | 618 ctx | cooccurence:616 |
Rv0807 hyp |
hypothetical protein | 607 | 608 ctx | cooccurence:604 |
Rv1002c pmt |
dolichyl-phosphate-mannose--protein mannosyltransferase | 592 | 592 ctx | cooccurence:592 |
Rv2146c |
transmembrane protein | 586 | 587 ctx | cooccurence:584 |
Rv2699c hyp |
hypothetical protein | 583 | 584 ctx | cooccurence:582 |
Rv0006 gyrA |
DNA gyrase subunit A | 553 | 534 ctx | neighborhood:528 |
Rv1321 nucS |
endonuclease NucS | 650 | 525 ctx | cooccurence:521 |
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: 'DNA replication protein DciA' (was 'hypothetical protein' in the legacy H37Rv/Mycobrowser annotation)
- ESM SAE top features describe N-terminal basic RNA/DNA-binding patches and charged low-complexity segments, consistent with a nucleic-acid-binding protein
- Primary literature: Rv0004 is essential and binds DnaB, modulating DnaB-DnaA complex formation
ESM Atlas signal (exploratory)
Ancestral protein hash adfddfac6808f01e0815b66dcb7890c3 ·
10 ESM-space neighbours (max similarity 0.921).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|---|---|---|
| 1 | 8624 |
0.85 | Presequence-to-core transition helix |
| 2 | 4008 |
0.75 | N-terminal basic RNA-binding patches |
| 3 | 14994 |
0.71 | Charged low-complexity disordered tails |
| 4 | 1968 |
0.66 | Basic low-complexity N-termini |
| 5 | 14146 |
0.62 | Edge beta-hairpin interaction loops |
| 6 | 15621 |
0.59 | Short basic Zn-binding helices |
| 7 | 507 |
0.55 | Short cytosolic amphipathic helices |
| 8 | 5321 |
0.55 | N-terminal leader/capping segments |
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_214518.1)
- Domains: Pfam-A via hmmscan --cut_ga — DciA (PF05258.18)
- 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
COG5512 - Curated reference: UniProt P9WFL1 (SwissProt, reviewed; Inferred from homology)
- 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 —
36 functional partner(s); context anchor
recF - Primary literature: Mann KM, Huang DL, Hooppaw AJ, et al. (2017). Rv0004 is a new essential member of the mycobacterial DNA replication machinery PLoS Genetics. doi:10.1371/journal.pgen.1007115 PMID:29176877
- Primary literature: Brézellec P, et al. (2022). DciA helicase operators exhibit diversity across bacterial phyla Journal of Bacteriology. doi:10.1128/jb.00163-22
Ancestral MTBC0 protein sequence
>mtbc0_000004|Rv0004| MTGSVDRPDQNRGERSMKSPGLDLVRRTLDEARAAARARGQDAGRGRVASVASGRVAGRRRSWSGPGPDIRDPQPLGKAARELAKKRGWSVRVAEGMVLGQWSAVVGHQIAEHARPTALNDGVLSVIAESTAWATQLRIMQAQLLAKIAAAVGNDVVRSLKITGPAAPSWRKGPRHIAGRGPRDTYG