Rv3489 Still unknown · low auto-curated
H37Rv Rv3489 · MTBC0 mtbc0_003704 ·
54 aa · 3932654–3932818 (+) ·
RefSeq NP_218006.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 3daq-assembly2_D Crystal structure of dihydrodipicolinate synthase fro (prob 0.06, TM 0.44). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YC91
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein |
UniProt still lists this protein as Uncharacterized protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2FG3C |
|---|
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 | 0.313 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 1 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 60.9 (low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.
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 |
|---|---|---|---|---|
3daq-assembly2_D |
0.06 | 0.44 | 7.8e+00 | 3daq-assembly2_D Crystal structure of dihydrodipicolinate synthase from methicillin-resistant Staphylococcus aureus |
3si9-assembly1_C |
0.06 | 0.40 | 7.3e+00 | 3si9-assembly1_C Crystal structure of Dihydrodipicolinate Synthase from Bartonella Henselae |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: otsA (trehalose-phosphate synthase), high confidence from genomic context alone (score 887 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) |
|---|---|---|---|---|
Rv3490 otsA |
trehalose-phosphate synthase | 887 | 887 ctx | neighborhood:882 |
Rv3488 hyp |
hypothetical protein | 610 | 610 ctx | neighborhood:608 |
Rv3491 hyp |
hypothetical protein | 523 | 523 ctx | neighborhood:511 |
Rv2779c |
Lrp/AsnC family transcriptional regulator | 555 | 52 | textmining:550 |
Rv1220c |
methyltransferase | 758 | 50 | textmining:756 |
Rv1219c raaS |
transcriptional regulator | 804 | 47 | textmining:803 |
Rv2938 drrC |
daunorubicin ABC transporter permease DrrC | 544 | 47 | textmining:542 |
Rv0880 |
HTH-type transcriptional regulator | 513 | 45 | textmining:511 |
Rv1218c |
tetronasin ABC transporter ATP-binding protein | 651 | 44 | textmining:650 |
Rv1217c |
tetronasin ABC transporter integral membrane protein | 658 | 43 | textmining:658 |
Rv1216c |
integral membrane protein | 724 | 42 | textmining:724 |
Rv1215c hyp |
hypothetical protein | 870 | 41 | textmining:870 |
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: hypothetical protein
- MTBC0 PGAP product: hypothetical protein
- Foldseek best: 3daq-assembly2_D Crystal structure of dihydrodipicolinate synthase from methicil (prob 0.06, E=8e+00, TM=0.44)
- (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_218006.1)
- 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
2FG3C - Curated reference: UniProt I6YC91 (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 60.9, low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
12 functional partner(s); context anchor
otsA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003704|Rv3489| MSTKSDHGEIGDVEPLADSTASQARRVVAAYANDADECRIFLSMLGIGPAKLES