Rv2228c Resolved · high auto-curated
H37Rv Rv2228c · MTBC0 - ·
364 aa · 2501644–2502738 (-) ·
RefSeq NP_216744.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | multifunctional RNASE H/alpha-ribazole phosphatase/acid phosphatase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Multifunctional RNASE H/alpha-ribazole phosphatase/acid phosphatase. Pfam: RNase_H (PF00075.31), RVT_3 (PF13456.13), His_Phos_1 (PF00300.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WLH5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Bifunctional protein Rv2228c [Includes: Ribonuclease H |
| EC (curated) |
EC 3.1.26.4, EC 3.1.3.73
|
| Curated function | Endonuclease that displays both RNase H activity with a hybrid RNA/DNA substrate as well as double-stranded RNase activity. As the only authenticated RNase HI in M.tuberculosis, probably plays an important role in the physiology of this organism, being likely involved in bacterial replication..; FUNCTION: Catalyzes the hydrolysis of the phospho group from alpha-ribazole 5'-phosphate to form alpha-ribazole. May also catalyze the conversion of adenosylcobalamin 5'-phosphate to adenosylcobalamin (vitamin B12) (By similarity). Has a possible role in B12 recycling, but the primary role of the C-ter. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
G Carbohydrate transport and metabolismL Replication, recombination and repair
|
|---|---|
| Preferred name | rnhA |
| eggNOG description | Ribonuclease |
| Orthologous group | COG0328 |
| EC number |
EC 3.1.26.4, EC 3.1.3.73
|
| KEGG orthology |
K02226, K22316
|
| KEGG pathways |
map00860, map01100, map03030
|
| KEGG modules |
M00122
|
| Gene Ontology (76) |
GO:0003674, GO:0003676, GO:0003824, GO:0004518, GO:0004519, GO:0004521, GO:0004523, GO:0004540, GO:0005488, GO:0006139, GO:0006401, GO:0006725 +64 more
|
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 | 0.274 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 3 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 |
|---|---|---|---|---|
RNase_H | PF00075.31 | 1.3e-08 | 3–129 | RNase H |
RVT_3 | PF13456.13 | 2.7e-23 | 7–129 | Reverse transcriptase-like |
His_Phos_1 | PF00300.28 | 6.3e-54 | 167–359 | Histidine phosphatase superfamily (branch 1) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2230c (GTP cyclohydrolase), high confidence from genomic context alone (score 919 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2229c hyp |
hypothetical protein | 996 | 968 ctx | neighborhood:882 coexpression:742 textmining:886 |
Rv2208 cobS |
adenosylcobinamide-GDP ribazoletransferase | 962 | 944 | database:900 |
Rv2207 cobT |
nicotinate-nucleotide-dimethylbenzimidazol phosphoribosyltransferase | 938 | 935 | database:900 |
Rv2230c |
GTP cyclohydrolase | 990 | 919 ctx | neighborhood:892 textmining:882 |
Rv2231c cobC |
aminotransferase | 959 | 890 ctx | neighborhood:882 textmining:646 |
Rv0054 ssb |
single-strand DNA-binding protein | 839 | 823 | experimental:775 |
Rv2478c hyp |
hypothetical protein | 816 | 797 | experimental:775 |
Rv2902c rnhB |
ribonuclease HII | 954 | 767 | experimental:741 textmining:813 |
Rv2234 ptpA |
protein-tyrosine-phosphatase | 815 | 755 ctx | neighborhood:746 |
Rv2235 |
transmembrane protein | 750 | 751 ctx | neighborhood:746 |
Rv2232 ptkA |
protein tyrosine kinase transcriptional regulator PtkA | 756 | 746 ctx | neighborhood:746 |
Rv2231A vapC16 |
ribonuclease VapC16 | 658 | 658 ctx | neighborhood:658 |
Rv1409 ribG |
bifunctional riboflavin biosynthesis diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino) uracil reductas | 597 | 598 ctx | neighborhood:479 |
Rv1747 |
ABC transporter ATP-binding protein/permease | 583 | 566 ctx | neighborhood:438 |
Rv1629 polA |
DNA polymerase I | 857 | 562 ctx | neighborhood:479 textmining:689 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): multifunctional RNASE H/alpha-ribazole phosphatase/acid phosphatase
- Pfam (hmmscan --cut_ga): RNase_H PF00075.31 (E=1e-08), RVT_3 PF13456.13 (E=3e-23), His_Phos_1 PF00300.28 (E=6e-54)
- (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_216744.1)
- Domains: Pfam-A via hmmscan --cut_ga — RNase_H (PF00075.31), RVT_3 (PF13456.13), His_Phos_1 (PF00300.28)
- 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
COG0328 - Curated reference: UniProt P9WLH5 (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 —
63 functional partner(s); context anchor
Rv2230c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2228c| MKVVIEADGGSRGNPGPAGYGAVVWTADHSTVLAESKQAIGRATNNVAEYRGLIAGLDDAVKLGATEAAVLMDSKLVVEQMSGRWKVKHPDLLKLYVQAQALASQFRRINYEWVPRARNTYADRLANDAMDAAAQSAAADADPAKIVATESPTSPGWTGARGTPTRLLLLRHGQTELSEQRRYSGRGNPGLNEVGWRQVGAAAGYLARRGGIAAVVSSPLQRAYDTAVTAARALALDVVVDDDLVETDFGAWEGLTFAEAAERDPELHRRWLQDTSITPPGGESFDDVLRRVRRGRDRIIVGYEGATVLVVSHVTPIKMLLRLALDAGSGVLYRLHLDLASLSIAEFYADGASSVRLVNQTGYL