Rv3205c Family assigned · low
H37Rv Rv3205c · MTBC0 - ·
292 aa · 3581627–3582505 (-) ·
RefSeq NP_217721.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Protein-kinase-like (APH/ePK) fold whose active site is NOT retained. RefSeq leaves it 'hypothetical protein'. The AlphaFold model superposes on an aminoglycoside 3',5"-phosphotransferase (PDB 1l8t = M-CSA entry 640, EC 2.7.1.95), but the M-CSA active-site check shows the 4 catalytic residues are all ALIGNED yet SUBSTITUTED (0/4 conserved) -> same fold, active site not retained. A worked negative control: the kinase fold is present but the gene is NOT an active aminoglycoside phosphotransferase. |
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 |
O05861
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved protein |
UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Aminoglycoside phosphotransferase |
| Orthologous group | COG2334 |
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 | 0.557 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 91.9 (very high). A confident model makes the fold comparison meaningful.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
2ppq-assembly1_A-2 |
1.00 | 0.58 | 5.2e-08 sig | 2ppq-assembly1_A-2 Crystal structure of the homoserine kinase from Agrobacterium tumefaciens |
3i0q-assembly1_A |
1.00 | 0.55 | 2.0e-05 sig | 3i0q-assembly1_A Crystal Structure of the AMP-bound complex of Spectinomycin Phosphotransferase, APH(9)-Ia |
1l8t-assembly1_A |
1.00 | 0.48 | 1.1e-05 sig | 1l8t-assembly1_A Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Kanamycin A Complex |
3i0o-assembly1_A |
1.00 | 0.53 | 4.9e-05 sig | 3i0o-assembly1_A Crystal Structure of Spectinomycin Phosphotransferase, APH(9)-Ia, in complex with ADP and Spectinomcyin |
2q83-assembly2_B |
1.00 | 0.48 | 4.2e-05 sig | 2q83-assembly2_B Crystal structure of ytaA (2635576) from Bacillus subtilis at 2.50 A resolution |
8i8h-assembly1_A |
1.00 | 0.53 | 3.8e-04 sig | 8i8h-assembly1_A Crystal structure of Cph001-D189N in complex with VIO and ATP |
4fex-assembly3_C |
1.00 | 0.51 | 5.6e-04 sig | 4fex-assembly3_C Crystal structure of the aminoglycoside phosphotransferase APH(3')-Ia, with substrate kanamycin and small molecule inhibitor tyrphostin AG1478 |
4few-assembly9_F |
1.00 | 0.49 | 6.3e-04 sig | 4few-assembly9_F Crystal structure of the aminoglycoside phosphotransferase APH(3')-Ia, with substrate kanamycin and small molecule inhibitor pyrazolopyrimidine PP2 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: moeB1 (adenylyltransferase/sulfurtransferase MoeZ), high confidence from genomic context alone (score 784 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3212 hyp |
hypothetical protein | 811 | 811 ctx | cooccurence:759 |
Rv3206c moeB1 |
adenylyltransferase/sulfurtransferase MoeZ | 785 | 784 ctx | neighborhood:739 |
Rv0358 hyp |
hypothetical protein | 781 | 781 ctx | cooccurence:773 |
Rv2732c |
transmembrane protein | 780 | 781 ctx | cooccurence:774 |
Rv3438 hyp |
hypothetical protein | 777 | 778 ctx | cooccurence:772 |
Rv2446c |
integral membrane protein | 776 | 776 ctx | cooccurence:773 |
Rv0556 |
transmembrane protein | 773 | 774 ctx | cooccurence:773 |
Rv3850 hyp |
hypothetical protein | 773 | 773 ctx | cooccurence:772 |
Rv1109c hyp |
hypothetical protein | 771 | 771 ctx | cooccurence:770 |
Rv0863 hyp |
hypothetical protein | 770 | 770 ctx | cooccurence:769 |
Rv0475 hbhA |
heparin binding hemagglutinin HbhA | 760 | 760 ctx | cooccurence:758 |
Rv1083 hyp |
hypothetical protein | 760 | 760 ctx | cooccurence:760 |
Rv3311 hyp |
hypothetical protein | 757 | 758 ctx | cooccurence:756 |
Rv2171 lppM |
lipoprotein LppM | 754 | 755 ctx | cooccurence:745 |
Rv3217c |
integral membrane protein | 753 | 754 ctx | cooccurence:746 |
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
- Foldseek -> aminoglycoside phosphotransferase (1l8t), prob 1.0, E 2e-5
- M-CSA 640 active-site check: 4/4 catalytic residues aligned, 0/4 identical -> FOLD-ONLY
- Fold present, activity not retained (do not requalify as enzyme)
- Structural homology: AlphaFold DB model + Foldseek vs PDB (project 'Still unknown gene function', phase5-7, 2026-06-10). A fold-level family assignment, not a demonstrated activity.
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_217721.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
COG2334 - Curated reference: UniProt O05861 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 91.9, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
123 functional partner(s); context anchor
moeB1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3205c| MGSTRLTGVNVEPPPEHVLVAFGLAGAQPILLGAGWEGGWRCGEVVLSMVADNARAAWSARVRETLFVDGVRLARPVRSTDGRYVVSGWRADTFVAGAPEPRHDEVVSAAVRLHEATGKLERPRFLTQGPAAPWAEIDVFVAADRAGWEERPLQSVPPGVPTAPPAADPQRSIDLINQLAGLRKPTKSPNQLVHGDLYGTVLFAGTAPPGITDITPYWRPASWAAGVAVVDALSWGAADDGLIERWNALPEWPQMLLRALMFRLAVYALHPRSTAEAFPGLAHTAALVRLVL