phoH2 Family assigned · medium auto-curated
H37Rv Rv1095 · MTBC0 mtbc0_001178 ·
433 aa · 1231437–1232738 (+) ·
RefSeq NP_215611.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | phosphate starvation-inducible protein PsiH |
|---|---|
| MTBC0 PGAP re-annotation | PhoH family protein |
| Revised (this work) | PhoH family protein. Pfam: PIN_4 (PF13638.13), PhoH (PF02562.23). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53443
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Protein PhoH2 |
| EC (curated) |
EC 3.1.-.-, EC 5.6.2.5
|
| Curated function | Toxic component of a type II toxin-antitoxin (TA) system. The cognate antitoxin is PhoAT; expression in M.smegmatis (strain mc(2)155) requires the cognate M.tuberculosis antitoxin gene. Expression in M.smegmatis strain mc(2)155 of the toxin alone slows growth and reduces cell viability, effects which are abrogated when cognate antitoxin PhoAT is coexpressed. Unwinds and/or cleaves 5'-tailed RNA in vitro that starts with 5'-AC, the reaction requires hydrolyzable ATP; double-stranded (ds)RNA and dsDNA are not unwound or cleaved. Can be expressed in the absence of its antitoxin gene in E.coli. In. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | phoH2 |
| eggNOG description | ATPase related to phosphate starvation-inducible protein PhoH |
| Orthologous group | COG1875 |
| KEGG orthology |
K07175
|
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 | 2.149 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 6 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.65% of strains (948) · 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 |
|---|---|---|---|---|
PIN_4 | PF13638.13 | 2.7e-26 | 7–145 | PIN domain |
PhoH | PF02562.23 | 1.4e-47 | 222–425 | PhoH-like protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv1096 (glycosyl hydrolase), medium confidence from genomic context alone (score 621 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2444c rne |
ribonuclease E | 765 | 765 | coexpression:703 |
Rv1096 |
glycosyl hydrolase | 621 | 621 ctx | neighborhood:601 |
Rv1094 desA2 |
acyl-ACP desaturase DesA | 732 | 506 ctx | neighborhood:474 textmining:479 |
Rv0513 |
transmembrane protein | 474 | 474 | coexpression:474 |
Rv0528 |
transmembrane protein | 446 | 446 ctx | cooccurence:420 |
Rv0430 hyp |
hypothetical protein | 405 | 405 | |
Rv0823c dusB |
tRNA-dihydrouridine synthase | 644 | 342 | textmining:481 |
Rv3303c lpdA |
NAD(P)H quinone reductase LpdA | 457 | 172 | |
Rv3051c nrdE |
ribonucleoside-diphosphate reductase subunit alpha | 574 | 133 | textmining:529 |
Rv0824c desA1 |
acyl-ACP desaturase DesA | 504 | 105 | textmining:469 |
Rv0400c fadE7 |
acyl-CoA dehydrogenase FadE7 | 536 | 87 | textmining:513 |
Rv3048c nrdF2 |
ribonucleoside-diphosphate reductase subunit beta NrdF2 | 579 | 82 | textmining:561 |
Rv3610c ftsH |
zinc metalloprotease FtsH | 469 | 82 | textmining:446 |
Rv1933c fadE18 |
acyl-CoA dehydrogenase FadE18 | 500 | 80 | textmining:479 |
Rv3053c nrdH |
glutaredoxin electron transport protein NrdH | 532 | 70 | textmining:518 |
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: phosphate starvation-inducible protein PsiH
- MTBC0 PGAP product: PhoH family protein
- Pfam (hmmscan --cut_ga): PIN_4 PF13638.13 (E=3e-26), PhoH PF02562.23 (E=1e-47)
- (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_215611.1)
- Domains: Pfam-A via hmmscan --cut_ga — PIN_4 (PF13638.13), PhoH (PF02562.23)
- 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
COG1875 - Curated reference: UniProt O53443 (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 —
23 functional partner(s); context anchor
Rv1096 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001178|Rv1095|phoH2 MTDTRTYVLDTSVLLSDPWACSRFAEHDVVVPLVVISELEAKRHHHELGWFARQALRLFDDLRLEHGRLDQPIPVGTQGGTLHVELNHTDPAVLPAGFRTDSNDSRILSCAANLAAEGKRVTLVSKDIPLRVKAAAVGLAADEYHAQDVVVSGWSGMHELETASADIDALFADGEIDLVEARDLPCHTGIRLLGGGSHALGRVNAHKRVQLVRGDREAFGLRGRSAEQRVALDLLLDESVGIVSLGGKAGTGKSALALCAGLEAVLERRTHRKVVVFRPLYAVGGQELGYLPGSESEKMGPWAQAVFDTLEGLASPAVLEEVLSRGMLEVLPLTHIRGRSLHDSFVIVDEAQSLERNVLLTVLSRLGTGSRVVLTHDIAQRDNLRVGRHDGVAAVIEKLKGHPLFAHITLLRSERSPIAALVTEMLEEITGPR