Rv2728c Family assigned · low auto-curated · to review
H37Rv Rv2728c · MTBC0 mtbc0_002902 ·
231 aa · 3063181–3063876 (-) ·
RefSeq NP_217244.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | No Pfam domain above threshold; Foldseek indicates a fold similar to 5hee-assembly1_B Crystal structure of the TK2203 protein (prob 1.00, TM 0.73). Structure-based, putative. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).
Curated reference (UniProt)
| UniProt |
I6X579
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved alanine rich protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | ferrous iron binding |
| Orthologous group | COG3885 |
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 | 0.193 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 2 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 95.6 (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 |
|---|---|---|---|---|
5hee-assembly1_B |
1.00 | 0.73 | 1.3e-10 sig | 5hee-assembly1_B Crystal structure of the TK2203 protein |
8ihg-assembly1_D |
1.00 | 0.72 | 7.5e-08 sig | 8ihg-assembly1_D Crystal structure of aminophenol dioxygenase from Pseudomonas species AP-3 |
7txy-assembly2_E |
1.00 | 0.68 | 5.5e-08 sig | 7txy-assembly2_E Crystal structure of the 2-Aminophenol 1,6-dioxygenase from the ARO bacterial microcompartment of Micromonospora rosaria |
3vsj-assembly1_C |
1.00 | 0.68 | 1.4e-07 sig | 3vsj-assembly1_C Crystal structure of 1,6-APD (2-ANIMOPHENOL-1,6-DIOXYGENASE) complexed with intermediate products |
3vsg-assembly1_D |
1.00 | 0.69 | 1.7e-05 sig | 3vsg-assembly1_D Crystal structure of iron free 1,6-APD, 2-Animophenol-1,6-Dioxygenase |
8ihg-assembly1_C |
1.00 | 0.65 | 2.1e-05 sig | 8ihg-assembly1_C Crystal structure of aminophenol dioxygenase from Pseudomonas species AP-3 |
8in2-assembly2_B |
1.00 | 0.62 | 1.5e-05 sig | 8in2-assembly2_B 4,5-DOPA-extradiol-dioxygenase from Beta vulgaris |
3wrc-assembly1_A |
1.00 | 0.61 | 2.7e-05 sig | 3wrc-assembly1_A Crystal structure of the anaerobic DesB-Protocatechuate (PCA) complex |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: miaA (tRNA delta(2)-isopentenylpyrophosphate transferase), high confidence from genomic context alone (score 889 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) |
|---|---|---|---|---|
Rv2727c miaA |
tRNA delta(2)-isopentenylpyrophosphate transferase | 889 | 889 ctx | neighborhood:882 |
Rv2726c dapF |
diaminopimelate epimerase | 850 | 850 ctx | neighborhood:849 |
Rv2725c hflX |
GTP-binding protein HflX | 733 | 734 ctx | neighborhood:733 |
Rv1486c hyp |
hypothetical protein | 641 | 641 ctx | cooccurence:640 |
Rv2844 hyp |
hypothetical protein | 619 | 619 ctx | cooccurence:618 |
Rv1836c hyp |
hypothetical protein | 606 | 606 ctx | cooccurence:606 |
Rv2729c |
integral membrane protein | 570 | 570 ctx | neighborhood:558 |
Rv0817c lmeA hyp |
hypothetical protein | 538 | 539 ctx | cooccurence:537 |
Rv2180c |
integral membrane protein | 513 | 514 ctx | cooccurence:509 |
Rv3839 hyp |
hypothetical protein | 511 | 511 ctx | cooccurence:511 |
Rv2731 hyp |
hypothetical protein | 509 | 509 ctx | neighborhood:504 |
Rv1275 lprC |
lipoprotein LprC | 503 | 503 ctx | cooccurence:503 |
Rv0479c |
membrane protein | 503 | 503 ctx | cooccurence:503 |
Rv0227c |
membrane protein | 503 | 503 ctx | cooccurence:503 |
Rv1166 lpqW |
monoacyl phosphatidylinositol tetramannoside-binding protein LpqW | 501 | 501 ctx | cooccurence:501 |
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: 5hee-assembly1_B Crystal structure of the TK2203 protein (prob 1.00, E=1e-10, TM=0.73)
- (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_217244.1)
- 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
COG3885 - Curated reference: UniProt I6X579 (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 95.6, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
44 functional partner(s); context anchor
miaA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002902|Rv2728c| MLSAIGIVPSAPVLVPELAGAAAAELADLGAAVIAAASLLPKSWIAVGTGRADDVVRPTDVGTFAGFGADVRVGLAPQDGDGVAVPVELPLCALLTAWVRGQARPEARAQVHVYASDHGSDAAVARGRQLRADIDREPDPIGVLVVADGLNTLTPRAPGGYDPDGAGMQRALDDALASGDLAVLTRLPAQVLGRVAFQVLAGLAEPGPRSAKEFYRGAPHGVGYFAGVWQP