ptkA Family assigned · medium auto-curated
H37Rv Rv2232 · MTBC0 - ·
291 aa · 2506278–2507153 (+) ·
RefSeq NP_216748.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | protein tyrosine kinase transcriptional regulator PtkA |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Protein tyrosine kinase transcriptional regulator PtkA. Pfam: Hydrolase (PF00702.33), HAD_2 (PF13419.13), HAD (PF12710.14), Hydrolase_like (PF13242.13). |
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 |
P9WPI9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Tyrosine-protein kinase PtkA |
| EC (curated) |
EC 2.7.10.-
|
| Curated function | Required for growth within macrophages. Catalyzes the phosphorylation of PtpA on the tyrosine residues at positions 128 and 129, thereby increasing PtpA phosphatase activity and promoting pathogenicity. Also phosphorylates the thioredoxin reductase TrxB. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | nt5e |
| eggNOG description | IA, variant 1 |
| Orthologous group | COG0546 |
| EC number |
EC 3.1.3.18
|
| KEGG orthology |
K01091
|
| KEGG pathways |
map00630, map01100, map01110, map01130
|
| Gene Ontology (40) |
GO:0003674, GO:0003824, GO:0004672, GO:0004713, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006464, GO:0006468, GO:0006793 +28 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 | 1.117 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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 |
|---|---|---|---|---|
Hydrolase | PF00702.33 | 5.3e-24 | 80–252 | haloacid dehalogenase-like hydrolase |
HAD_2 | PF13419.13 | 2.4e-32 | 82–258 | Haloacid dehalogenase-like hydrolase |
HAD | PF12710.14 | 3.1e-12 | 82–246 | haloacid dehalogenase-like hydrolase |
Hydrolase_like | PF13242.13 | 2.8e-08 | 221–278 | HAD-hyrolase-like |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ptpA (protein-tyrosine-phosphatase), high confidence from genomic context alone (score 884 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2234 ptpA |
protein-tyrosine-phosphatase | 959 | 884 ctx | neighborhood:882 textmining:660 |
Rv2235 |
transmembrane protein | 883 | 883 ctx | neighborhood:882 |
Rv2231c cobC |
aminotransferase | 952 | 763 ctx | neighborhood:746 textmining:808 |
Rv2230c |
GTP cyclohydrolase | 747 | 748 ctx | neighborhood:746 |
Rv2229c hyp |
hypothetical protein | 747 | 748 ctx | neighborhood:746 |
Rv2228c |
multifunctional RNASE H/alpha-ribazole phosphatase/acid phosphatase | 756 | 746 ctx | neighborhood:746 |
Rv2231A vapC16 |
ribonuclease VapC16 | 538 | 538 ctx | neighborhood:538 |
Rv1307 atpH |
ATP synthase subunit b/delta | 467 | 450 | coexpression:418 |
Rv1408 rpe |
ribulose-phosphate 3-epimerase | 503 | 437 | coexpression:405 |
Rv3197 |
ABC transporter ATP-binding protein | 411 | 411 | coexpression:401 |
Rv0647c hyp |
hypothetical protein | 408 | 408 | |
Rv0408 pta |
phosphate acetyltransferase | 441 | 356 | |
Rv0015c pknA |
serine/threonine-protein kinase PknA | 439 | 178 | |
Rv0018c pstP |
phosphoserine/threonine phosphatase PstP | 551 | 48 | textmining:548 |
Rv3297 nei |
endonuclease VIII | 408 | 46 | textmining:405 |
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): protein tyrosine kinase transcriptional regulator PtkA
- Pfam (hmmscan --cut_ga): Hydrolase PF00702.33 (E=5e-24), HAD_2 PF13419.13 (E=2e-32), HAD PF12710.14 (E=3e-12), Hydrolase_like PF13242.13 (E=3e-08)
- (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_216748.2)
- Domains: Pfam-A via hmmscan --cut_ga — Hydrolase (PF00702.33), HAD_2 (PF13419.13), HAD (PF12710.14), Hydrolase_like (PF13242.13)
- 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
COG0546 - Curated reference: UniProt P9WPI9 (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 —
19 functional partner(s); context anchor
ptpA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2232|ptkA MSSPRERRPASQAPRLSRRPPAHQTSRSSPDTTAPTGSGLSNRFVNDNGIVTDTTASGTNCPPPPRAAARRASSPGESPQLVIFDLDGTLTDSARGIVSSFRHALNHIGAPVPEGDLATHIVGPPMHETLRAMGLGESAEEAIVAYRADYSARGWAMNSLFDGIGPLLADLRTAGVRLAVATSKAEPTARRILRHFGIEQHFEVIAGASTDGSRGSKVDVLAHALAQLRPLPERLVMVGDRSHDVDGAAAHGIDTVVVGWGYGRADFIDKTSTTVVTHAATIDELREALGV