Rv2474c Family assigned · low
H37Rv Rv2474c · MTBC0 mtbc0_002636 ·
217 aa · 2800564–2801217 (-) ·
RefSeq NP_216990.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | DnaN/beta-sliding-clamp-like fold; distinct from the genuine DNA polymerase III beta clamp dnaN/Rv0002 (fold-paralogue safeguard). Function of this paralogue undetermined. |
Curated reference (UniProt)
| UniProt |
I6X4D6
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein |
UniProt still lists this protein as Uncharacterized protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2DQ1M |
|---|
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 | 0.756 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 4 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 |
|---|---|---|---|---|
DUF8010 | PF26035.1 | 4.2e-36 | 1–100 | Domain of unknown function (DUF8010) |
DUF8185 | PF26572.1 | 3.0e-30 | 103–210 | Domain of unknown function (DUF8185) |
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 92.6 (very high). A confident model makes the fold comparison meaningful.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
6fvl-assembly1_B |
1.00 | 0.57 | 9.2e-07 sig | 6fvl-assembly1_B DNA polymerase sliding clamp from Escherichia coli with bound P7 peptide |
8dt6-assembly1_B |
1.00 | 0.58 | 1.2e-06 sig | 8dt6-assembly1_B Crystal Structure of DNA Polymerase III beta subunit from Elizabethkingia anophelis |
3t0p-assembly1_B |
1.00 | 0.57 | 1.2e-06 sig | 3t0p-assembly1_B Crystal structure of a Putative DNA polymerase III beta subunit (EUBREC_0002; ERE_29750) from Eubacterium rectale ATCC 33656 at 2.26 A resolution |
6fvl-assembly2_D |
1.00 | 0.55 | 6.9e-07 sig | 6fvl-assembly2_D DNA polymerase sliding clamp from Escherichia coli with bound P7 peptide |
3t0p-assembly1_A |
1.00 | 0.57 | 1.9e-06 sig | 3t0p-assembly1_A Crystal structure of a Putative DNA polymerase III beta subunit (EUBREC_0002; ERE_29750) from Eubacterium rectale ATCC 33656 at 2.26 A resolution |
4n95-assembly1_B |
1.00 | 0.53 | 4.6e-07 sig | 4n95-assembly1_B E. coli sliding clamp in complex with 5-chloroindoline-2,3-dione |
6fvm-assembly1_B |
1.00 | 0.56 | 1.1e-06 sig | 6fvm-assembly1_B Mutant DNA polymerase sliding clamp from Escherichia coli with bound P7 peptide |
6jir-assembly1_A-2 |
1.00 | 0.52 | 2.9e-07 sig | 6jir-assembly1_A-2 Crystal structure of C. crescentus beta sliding clamp with PEG bound to putative beta-motif tethering region |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gdh (NAD-dependent glutamate dehydrogenase), high confidence from genomic context alone (score 889 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) |
|---|---|---|---|---|
Rv2475c hyp |
hypothetical protein | 904 | 904 ctx | neighborhood:882 |
Rv2476c gdh |
NAD-dependent glutamate dehydrogenase | 889 | 889 ctx | neighborhood:881 |
Rv2477c ettA |
macrolide ABC transporter ATP-binding protein | 773 | 773 ctx | neighborhood:771 |
Rv3438 hyp |
hypothetical protein | 757 | 757 ctx | cooccurence:757 |
Rv2446c |
integral membrane protein | 752 | 753 ctx | cooccurence:746 |
Rv0358 hyp |
hypothetical protein | 752 | 752 ctx | cooccurence:752 |
Rv0556 |
transmembrane protein | 751 | 752 ctx | cooccurence:744 |
Rv0210 hyp |
hypothetical protein | 750 | 750 ctx | cooccurence:750 |
Rv0863 hyp |
hypothetical protein | 748 | 748 ctx | cooccurence:747 |
Rv3205c hyp |
hypothetical protein | 747 | 748 ctx | cooccurence:744 |
Rv1638A hyp |
hypothetical protein | 733 | 734 ctx | cooccurence:732 |
Rv1209 hyp |
hypothetical protein | 715 | 716 ctx | cooccurence:713 |
Rv3311 hyp |
hypothetical protein | 714 | 715 ctx | cooccurence:714 |
Rv3850 hyp |
hypothetical protein | 713 | 714 ctx | cooccurence:713 |
Rv3450c eccB4 |
ESX-4 secretion system protein EccB4 | 711 | 712 ctx | cooccurence:710 |
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
- Foldseek vs AFDB-SwissProt: beta sliding clamp, TM 0.54, E 1e-5 (dnaN = Rv0002, not this locus)
- Structural homology vs AlphaFold-Swiss-Prot (Foldseek; 542k curated SwissProt structures), project 'Still unknown gene function' phase13, 2026-06-10. Fold/family-level, not a demonstrated function.
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_216990.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF8010 (PF26035.1), DUF8185 (PF26572.1)
- 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
2DQ1M - Curated reference: UniProt I6X4D6 (TrEMBL, unreviewed; 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)
- Model confidence: ESMFold per-residue pLDDT (mean 92.6, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
82 functional partner(s); context anchor
gdh - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002636|Rv2474c| MVERGLWLPDPAHRADLATFVDHALRLDDAAVIRIRARSTGLLSAWVATGFDVLASRVVAGKVRPDDLSVAARSLAHGLATTDASGYVDPGYSMDSAWRGGLPPESGFTYLDDVPARVMLDLAHRGARLAKEHGSSAGPPVSLLDQEVIQVSSADVVVGLPMRCVFALTAMGFLPQSAETISADELIRVRISPAWLRLDARFGSVYRHRGHAALVLR