Rv3225c Family assigned · medium auto-curated
H37Rv Rv3225c · MTBC0 mtbc0_003434 ·
474 aa · 3623158–3624582 (-) ·
RefSeq NP_217742.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | GCN5-like N-acetyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | bifunctional GNAT family N-acetyltransferase/aminoglycoside 3'-phosphotransferase/choline kinase family protein |
| Revised (this work) | Bifunctional GNAT family N-acetyltransferase/aminoglycoside 3'-phosphotransferase/choline kinase family protein. Pfam: Acetyltransf_3 (PF13302.14), Acetyltransf_1 (PF00583.32), APH (PF01636.30). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O05841
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Bifunctional AAC/APH |
| EC (curated) |
EC 2.7.1.190
|
| Curated function | Involved in resistance to gentamicin, tobramycin, and kanamycin. Tobramycin and kanamycin resistance is due to the ACC activity, specified by N-terminal region. The C-terminal region is a kinase that phosphorylates several 4,6-disubstituted aminoglycosides. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| eggNOG description | Phosphotransferase enzyme family |
| Orthologous group | COG1670 |
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 | 0.795 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 9 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.29% of strains (414) · 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 |
|---|---|---|---|---|
Acetyltransf_3 | PF13302.14 | 2.9e-19 | 15–152 | Acetyltransferase (GNAT) domain |
Acetyltransf_1 | PF00583.32 | 1.4e-09 | 51–152 | Acetyltransferase (GNAT) family |
APH | PF01636.30 | 9.9e-43 | 210–430 | Phosphotransferase enzyme family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: pks1 (polyketide synthase), medium confidence from genomic context alone (score 660 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2946c pks1 |
polyketide synthase | 703 | 660 ctx | neighborhood:543 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 753 | 653 ctx | neighborhood:544 |
Rv2048c pks12 |
polyketide synthase | 753 | 653 ctx | neighborhood:544 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 753 | 653 ctx | neighborhood:544 |
Rv1527c pks5 |
polyketide synthase | 751 | 650 ctx | neighborhood:544 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 750 | 649 ctx | neighborhood:544 |
Rv2925c rnc |
ribonuclease III | 556 | 557 | coexpression:542 |
Rv1832 gcvB |
glycine dehydrogenase | 548 | 549 ctx | neighborhood:544 |
Rv2636 |
O-phosphotransferase | 543 | 525 ctx | cooccurence:524 |
Rv3226c hyp |
hypothetical protein | 525 | 524 ctx | neighborhood:507 |
Rv2378c mbtG |
L-lysine N6-monooxygenase | 562 | 522 | coexpression:506 |
Rv0802c |
succinyl-CoA transferase | 512 | 512 | |
Rv3227 aroA |
3-phosphoshikimate 1-carboxyvinyltransferase | 462 | 462 ctx | neighborhood:449 |
Rv1004c |
membrane protein | 416 | 416 | |
Rv3228 rsgA hyp |
hypothetical protein | 417 | 415 ctx | neighborhood:412 |
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: GCN5-like N-acetyltransferase
- MTBC0 PGAP product: bifunctional GNAT family N-acetyltransferase/aminoglycoside 3'-phosphotransferase/choline kinase family protein
- Pfam (hmmscan --cut_ga): Acetyltransf_3 PF13302.14 (E=3e-19), Acetyltransf_1 PF00583.32 (E=1e-09), APH PF01636.30 (E=1e-42)
- (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_217742.1)
- Domains: Pfam-A via hmmscan --cut_ga — Acetyltransf_3 (PF13302.14), Acetyltransf_1 (PF00583.32), APH (PF01636.30)
- 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
COG1670 - Curated reference: UniProt O05841 (TrEMBL, unreviewed; 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 —
31 functional partner(s); context anchor
pks1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003434|Rv3225c| MRFAKLSDGLSDGIVTLSPLCLDDVDAHLAGGDERLVRWLSGMPSTRASVEAYIRHCREQWVTGGPLRSFGIRTVAETIVGTIDLRFDGEGLASGQVNVAYGLYPSWRGRGLATRAVDLVCQYAAEHGATEAVIKVEPENSASARVALRAGFAFVRRICEQDGTVFDRYERVLRAKMHADEVDIDEDLVRRLLRAQFPQWADLPIAPVRSAGTDNAMYRLGEDLAVRIPRIGWAIESLRTEQQWLPRIAAHLGVASPVPVGLGSPAEGFGWPWSVCRWVAGENPSAAEFVEPNRAVEDLADFITALRATDPMGGPPAKRGAPLGEQDAEVRAALAALDGIIDVHAATAAWESALRVPPYAGPPMWFHGDLSRFNILTAQGRLTGVIDFGLMGVGDPSVDLIIAWNLLSAPARAQFRVAVGAADDDWMRGRGRALAIALIALPYYQDTNPPLAASARYAIGEVLADFRYGARPGC