Rv1251c Family assigned · medium auto-curated
H37Rv Rv1251c · MTBC0 mtbc0_001340 ·
1139 aa · 1404265–1407684 (-) ·
RefSeq NP_215767.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | TM0106 family RecB-like putative nuclease |
| Revised (this work) | TM0106 family RecB-like putative nuclease. Pfam: PDDEXK_1 (PF12705.14), RNase_H_2 (PF13482.13), AAA_19 (PF13245.13), AAA_30 (PF13604.13), NAT10_TcmA_helicase (PF05127.22), AAA_12 (PF13087.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O50466
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)
| COG category |
L Replication, recombination and repair
|
|---|---|
| eggNOG description | nuclease |
| Orthologous group | COG1112 |
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) pseudogene candidate
| pN/pS | 0.307 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 20 synonymous, 16 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 6.00% of strains (8719) · 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 |
|---|---|---|---|---|
PDDEXK_1 | PF12705.14 | 9.3e-05 | 76–199 | PD-(D/E)XK nuclease superfamily |
RNase_H_2 | PF13482.13 | 6.0e-17 | 312–501 | RNase_H superfamily |
AAA_19 | PF13245.13 | 5.4e-08 | 752–906 | AAA domain |
AAA_30 | PF13604.13 | 1.2e-11 | 754–910 | AAA domain |
NAT10_TcmA_helicase | PF05127.22 | 8.2e-05 | 764–879 | RNA cytidine acetyltransferase NAT10/TcmA, helicase domain |
AAA_12 | PF13087.13 | 4.3e-24 | 932–1110 | AAA domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lprE (lipoprotein LprE), high confidence from genomic context alone (score 902 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) |
|---|---|---|---|---|
Rv1252c lprE |
lipoprotein LprE | 905 | 902 ctx | neighborhood:682 coexpression:703 |
Rv0111 |
acyltransferase | 752 | 752 | coexpression:751 |
Rv2756c hsdM |
type I restriction/modification system DNA methylase HsdM | 655 | 620 | coexpression:480 |
Rv1253 deaD |
ATP-dependent RNA helicase DeaD | 562 | 563 ctx | neighborhood:539 |
Rv1254 |
acyltransferase | 550 | 550 ctx | neighborhood:513 |
Rv2345 |
transmembrane protein | 486 | 486 ctx | cooccurence:475 |
Rv3433c nnr |
bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase | 483 | 484 | coexpression:403 |
Rv1419 hyp |
hypothetical protein | 422 | 423 | coexpression:423 |
Rv3054c hyp |
hypothetical protein | 422 | 423 | coexpression:403 |
Rv1482c hyp |
hypothetical protein | 419 | 419 |
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: hypothetical protein
- MTBC0 PGAP product: TM0106 family RecB-like putative nuclease
- Pfam (hmmscan --cut_ga): PDDEXK_1 PF12705.14 (E=9e-05), RNase_H_2 PF13482.13 (E=6e-17), AAA_19 PF13245.13 (E=5e-08), AAA_30 PF13604.13 (E=1e-11), NAT10_TcmA_helicase PF05127.22 (E=8e-05), AAA_12 PF13087.13 (E=4e-24)
- (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_215767.1)
- Domains: Pfam-A via hmmscan --cut_ga — PDDEXK_1 (PF12705.14), RNase_H_2 (PF13482.13), AAA_19 (PF13245.13), AAA_30 (PF13604.13), NAT10_TcmA_helicase (PF05127.22), AAA_12 (PF13087.13)
- 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
COG1112 - Curated reference: UniProt O50466 (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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
10 functional partner(s); context anchor
lprE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001340|Rv1251c| MFVTGDSIVYSASDLAAAARCQYALLREFDAKLGRGPAVAVDDELMARAAVLGSAHEGRRLDQLRHEFGDAVAIIGRPAYTPAGLAAAADATRRAIANHAPVVYQAAMFDGRFVGFADFLIRDGHRYRVADTKLARSPTVTALLQLAAYADALVHSGVPVAADAELELGDGTIVRYRVGELIPVYRSQRALLQRLLDGHYTAGTAVRWDDERVQACFRCPQCTERLRASDDLLLVGGMRVRQRDKLLEAGITTIAELADHTAPVPGLTTNALGKLTAQAKLQIRQRDTGAPQFEIVDPRPLTLLPEPNPGDLFFDFEGDPLWTADGKQWGLEYLFGVLEAGRAGVFRPLWAHDRTAERQALTDFLAIVARRRRRHPNMHIYHYAPYEKTALLRLVGRYGIGEDDVDDLLRNGVLVDLYPLVRKSIRVGTDSFSLKALEPLYLGTQPRSGDVTTAADSINSYARYCELRAAGRIDEAATVLKEIEGYNHYDCRSTRALRDWLLMRAWEAGVTPIGAQPVPDADPIDDGDSLASVLSKFTGDAAAGERTPEQTAVALLAAARGYHRREDKPFWWAHFDRLNYPVDEWSDSTDVFLASEASVTVDWHMPPRARKPQRRVRLTGELARGDLNGNVFALYEPPAPPGMTDNPDRRAAGPAAVVETDDPTVPTEVVIVERTGSDGNTFQQLPFALAPGPPVPTTALRESIESTAAAVASGSPQLPSTALMDVLLRRPPRTRSGAALPRSSDPVTDIAAAALDLDSSYLAVHGPPGTGKTYTAARVIAELVTEHAWRIGVVAQSHATVENLLEGVISAGLDPGQVAKKPHDHTAGRWQSIDGSQYTEFIRDTAGCVIGGTAWDFANGNRVPKASLDLLVIDEAGQFCLANTIAVAPAATNLLLLGDPQQLPQVSQGTHPEPVDTSALSWLVDGQHTLPDERGYFLDRSYRMHPAVCAAVSALSYEGRLCSHTERTAVRRLDGYPPGVHTRGVHHKGNSIESPEEAEAILAELRQLLGSPWTDEHGTRPLAASDVLVLAPYNAQVALVRRRLASAGLGGADGVRVGTVDKFQGGQAPVVFISMTASSADDVPRGISFLLNRNRLNVAVSRAQYAAVIVRSELLTQYLPATPDGLVDLGAFLGLTSTS