Rv1021 Resolved · high auto-curated
H37Rv Rv1021 · MTBC0 mtbc0_001097 ·
325 aa · 1150008–1150985 (+) ·
RefSeq NP_215537.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | nucleoside triphosphate pyrophosphohydrolase |
|---|---|
| MTBC0 PGAP re-annotation | nucleoside triphosphate pyrophosphohydrolase |
| Revised (this work) | Nucleoside triphosphate pyrophosphohydrolase. Pfam: MazG_N (PF27510.1), MazG (PF03819.23). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P96379
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Nucleoside triphosphate pyrophosphohydrolase |
| EC (curated) |
EC 3.6.1.8
|
| Curated function | Required to maintain the full capacity of the mycobacterium to respond to oxidative stress via the degradation of oxidation-induced damaged nucleotides. Hydrolyzes all canonical (d)NTPs, as well as mutagenic dUTP and 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP). Also involved in the transcriptional activation of RelA in response to oxidative stress. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | mazG |
| eggNOG description | pyrophosphohydrolase |
| Orthologous group | COG1694 |
| EC number |
EC 3.6.1.66
|
| KEGG orthology |
K02428, K02499
|
| KEGG pathways |
map00230
|
| Gene Ontology (139) |
GO:0000287, GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0006139, GO:0006163, GO:0006195, GO:0006203, GO:0006213 +127 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 | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 1 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 |
|---|---|---|---|---|
MazG_N | PF27510.1 | 3.1e-26 | 1–76 | MazG N-terminal domain |
MazG | PF03819.23 | 5.6e-25 | 107–181 | MazG nucleotide pyrophosphohydrolase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mfd (transcription-repair coupling factor), high confidence from genomic context alone (score 887 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3624c hpt |
hypoxanthine-guanine phosphoribosyltransferase | 923 | 923 | database:900 |
Rv1341 rdgB |
non-canonical purine NTP pyrophosphatase | 916 | 916 | database:900 |
Rv3411c guaB2 |
inosine-5'-monophosphate dehydrogenase | 907 | 904 | database:900 |
Rv3396c guaA |
GMP synthase | 903 | 904 | database:900 |
Rv1843c guaB1 |
inosine-5'-monophosphate dehydrogenase | 906 | 901 | database:900 |
Rv3410c guaB3 |
oxidoreductase | 901 | 901 | database:900 |
Rv2445c ndkA |
nucleoside diphosphate kinase | 900 | 901 | database:900 |
Rv1020 mfd |
transcription-repair coupling factor | 958 | 887 ctx | neighborhood:881 textmining:645 |
Rv1025 hyp |
hypothetical protein | 686 | 687 ctx | neighborhood:682 |
Rv1026 ppx2 hyp |
hypothetical protein | 686 | 687 ctx | neighborhood:682 |
Rv1019 |
transcriptional regulator | 956 | 680 ctx | neighborhood:678 textmining:870 |
Rv1022 lpqU |
lipoprotein LpqU | 662 | 662 ctx | neighborhood:657 |
Rv1023 eno |
enolase | 569 | 553 ctx | neighborhood:552 |
Rv1024 |
membrane protein | 512 | 512 ctx | neighborhood:507 |
Rv1274 lprB |
lipoprotein LprB | 498 | 498 | coexpression:457 |
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: nucleoside triphosphate pyrophosphohydrolase
- MTBC0 PGAP product: nucleoside triphosphate pyrophosphohydrolase
- Pfam (hmmscan --cut_ga): MazG_N PF27510.1 (E=3e-26), MazG PF03819.23 (E=6e-25)
- (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_215537.1)
- Domains: Pfam-A via hmmscan --cut_ga — MazG_N (PF27510.1), MazG (PF03819.23)
- 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
COG1694 - Curated reference: UniProt P96379 (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 —
42 functional partner(s); context anchor
mfd - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001097|Rv1021| MIVVLVDPRRPTLVPVEAIEFLRGEVQYTEEMPVAVPWSLPAARSAHAGNDAPVLLSSDPNHPAVITRLAAGARLISAPDSQRGERLVDAVAMMDKLRTAGPWESEQTHDSLRRYLLEETYELLDAVRSGSVDQLREELGDLLLQVLFHARIAEDASQSPFTIDDVADTLMRKLGNRAPGVLAGESISLEDQLAQWEAAKASEKARKSVADDVHTGQPALALAQKVIQRAQKAGLPAHLIPDEITSVSVSADVDAENTLRTAVLDFIDRLRCAERAIAVARRGSNVAEQLDVTPLGVITEQEWLAHWPTAVNDSRGGSKKRKGMR