ptpA Resolved · high auto-curated
H37Rv Rv2234 · MTBC0 mtbc0_002374 ·
163 aa · 2533304–2533795 (+) ·
RefSeq NP_216750.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | protein-tyrosine-phosphatase |
|---|---|
| MTBC0 PGAP re-annotation | protein-tyrosine-phosphatase |
| Revised (this work) | Protein-tyrosine-phosphatase. Pfam: LMWPc (PF01451.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIA1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Low molecular weight protein-tyrosine phosphatase A |
| EC (curated) |
EC 3.1.3.48
|
| Curated function | Key virulence factor required for mycobacterial survival within host macrophages. Exhibits protein tyrosine phosphatase activity. Shows no detectable activity towards substrates containing phosphoserine/threonine residues..; FUNCTION: Supports mycobacteria survival during infection by modulation of the phagosome maturation and modulation of the normal host signaling pathways, including host innate immune responses and cell apoptosis. Affects the phagocytosis process by preventing phagosome acidification and maturation in the macrophage. This inhibition depends on both PtpA phosphatase activity. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | ptpA |
| eggNOG description | Low molecular weight phosphotyrosine protein phosphatase |
| Orthologous group | COG0394 |
| EC number |
EC 3.1.3.48
|
| KEGG orthology |
K01104
|
| Gene Ontology (69) |
GO:0003674, GO:0003824, GO:0004721, GO:0004725, GO:0005575, GO:0005576, GO:0005623, GO:0005886, GO:0006464, GO:0006470, GO:0006793, GO:0006796 +57 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 | 0.344 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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 |
|---|---|---|---|---|
LMWPc | PF01451.28 | 1.4e-54 | 6–155 | Low molecular weight phosphotyrosine protein phosphatase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2235 (transmembrane protein), high confidence from genomic context alone (score 887 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0153c ptbB |
phosphotyrosine protein phosphatase | 987 | 901 | database:900 textmining:881 |
Rv2235 |
transmembrane protein | 887 | 887 ctx | neighborhood:882 |
Rv2232 ptkA |
protein tyrosine kinase transcriptional regulator PtkA | 959 | 884 ctx | neighborhood:882 textmining:660 |
Rv2230c |
GTP cyclohydrolase | 766 | 758 ctx | neighborhood:746 |
Rv2228c |
multifunctional RNASE H/alpha-ribazole phosphatase/acid phosphatase | 815 | 755 ctx | neighborhood:746 |
Rv2229c hyp |
hypothetical protein | 754 | 754 ctx | neighborhood:746 |
Rv2231c cobC |
aminotransferase | 748 | 748 ctx | neighborhood:746 |
Rv2231A vapC16 |
ribonuclease VapC16 | 539 | 539 ctx | neighborhood:539 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 558 | 510 | |
Rv1527c pks5 |
polyketide synthase | 557 | 509 | |
Rv2048c pks12 |
polyketide synthase | 557 | 509 | |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 556 | 508 | |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 555 | 506 | |
Rv3206c moeB1 |
adenylyltransferase/sulfurtransferase MoeZ | 503 | 485 | |
Rv3116 moeB2 |
molybdenum cofactor biosynthesis protein MoeB | 501 | 483 |
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: protein-tyrosine-phosphatase
- MTBC0 PGAP product: protein-tyrosine-phosphatase
- Pfam (hmmscan --cut_ga): LMWPc PF01451.28 (E=1e-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_216750.1)
- Domains: Pfam-A via hmmscan --cut_ga — LMWPc (PF01451.28)
- 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
COG0394 - Curated reference: UniProt P9WIA1 (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 —
56 functional partner(s); context anchor
Rv2235 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002374|Rv2234|ptpA MSDPLHVTFVCTGNICRSPMAEKMFAQQLRHRGLGDAVRVTSAGTGNWHVGSCADERAAGVLRAHGYPTDHRAAQVGTEHLAADLLVALDRNHARLLRQLGVEAARVRMLRSFDPRSGTHALDVEDPYYGDHSDFEEVFAVIESALPGLHDWVDERLARNGPS