ptbB Resolved · high auto-curated
H37Rv Rv0153c · MTBC0 mtbc0_000164 ·
276 aa · 181501–182331 (-) ·
RefSeq NP_214667.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | phosphotyrosine protein phosphatase |
|---|---|
| MTBC0 PGAP re-annotation | tyrosine-protein phosphatase PtbB |
| Revised (this work) | Tyrosine-protein phosphatase PtbB. Pfam: Y_phosphatase3 (PF13350.12). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6WXK4
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Triple specificity protein phosphatase PtpB |
| EC (curated) |
EC 3.1.3.-, EC 3.1.3.16, EC 3.1.3.48
|
| Curated function | Essential virulence factor that promotes mycobacterial survival within host macrophages. Acts as a phosphatase that possesses triple substrate specificity toward phosphotyrosine, phosphoserine/threonine and phosphoinositides. Supports mycobacteria survival during infection by modulating the normal host signaling pathways, attenuating the bactericidal immune responses and promoting the host cell survival. Inhibits host pyroptosis by disrupting the membrane localization of host gasdermin-D (GSDMD): acts by catalyzing dephosphorylation of phosphatidylinositol (4,5)-bisphosphate and phosphatidylin. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | ptpB |
| eggNOG description | COG2365 Protein tyrosine serine phosphatase |
| Orthologous group | COG2365 |
| EC number |
EC 3.1.3.48
|
| KEGG orthology |
K01104
|
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 | 0.186 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 14 synonymous, 7 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 |
|---|---|---|---|---|
Y_phosphatase3 | PF13350.12 | 3.5e-60 | 5–275 | Tyrosine phosphatase family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fadE2 (acyl-CoA dehydrogenase FadE2), high confidence from genomic context alone (score 920 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3157 nuoM |
NADH-quinone oxidoreductase subunit M | 942 | 928 | experimental:928 |
Rv0154c fadE2 |
acyl-CoA dehydrogenase FadE2 | 920 | 920 ctx | neighborhood:882 |
Rv2234 ptpA |
protein-tyrosine-phosphatase | 987 | 901 | database:900 textmining:881 |
Rv3146 nuoB |
NADH-quinone oxidoreductase subunit B | 799 | 799 | experimental:798 |
Rv3152 nuoH |
NADH-quinone oxidoreductase subunit H | 798 | 798 | experimental:798 |
Rv3145 nuoA |
NADH-quinone oxidoreductase subunit A | 798 | 798 | experimental:798 |
Rv3148 nuoD |
NADH-quinone oxidoreductase subunit D | 794 | 794 | experimental:793 |
Rv3153 nuoI |
NADH-quinone oxidoreductase subunit I | 793 | 794 | experimental:793 |
Rv3147 nuoC |
NADH-quinone oxidoreductase subunit C | 783 | 783 | experimental:782 |
Rv3158 nuoN |
NADH-quinone oxidoreductase subunit N | 773 | 773 | experimental:773 |
Rv3273 |
transmembrane carbonic anhydrase | 760 | 761 | experimental:749 |
Rv1707 |
transmembrane protein | 753 | 754 | experimental:749 |
Rv1739c |
sulfate ABC transporter permease | 753 | 754 | experimental:749 |
Rv1937 |
oxygenase | 711 | 701 | experimental:697 |
Rv2301 cut2 |
cutinase | 694 | 682 | experimental:629 |
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: phosphotyrosine protein phosphatase
- MTBC0 PGAP product: tyrosine-protein phosphatase PtbB
- Pfam (hmmscan --cut_ga): Y_phosphatase3 PF13350.12 (E=3e-60)
- (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_214667.1)
- Domains: Pfam-A via hmmscan --cut_ga — Y_phosphatase3 (PF13350.12)
- 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
COG2365 - Curated reference: UniProt I6WXK4 (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 —
43 functional partner(s); context anchor
fadE2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000164|Rv0153c|ptbB MAVRELPGAWNFRDVADTATALRPGRLFRSSELSRLDDAGRATLRRLGITDVADLRSSREVARRGPGRVPDGIDVHLLPFPDLADDDADDSAPHETAFKRLLTNDGSNGESGESSQSINDAATRYMTDEYRQFPTRNGAQRALHRVVTLLAAGRPVLTHCFAGKDRTGFVVALVLEAVGLDRDVIVADYLRSNDSVPQLRARISEMIQQRFDTELAPEVVTFTKARLSDGVLGVRAEYLAAARQTIDETYGSLGGYLRDAGISQATVNRMRGVLLG