Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
| MTBC0 PGAP re-annotation | DUF2752 domain-containing protein |
| Revised (this work) | Polytopic integral membrane protein with 3 predicted transmembrane helices (DeepTMHMM). RefSeq leaves it 'hypothetical protein'. A topological feature consistent with a membrane transporter/permease or membrane-embedded enzyme; the transported substrate and molecular function are undetermined. |
Curated reference (UniProt)
| UniProt |
O06133
TrEMBL · unreviewed
· Predicted
|
| UniProt name | Conserved membrane protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
| eggNOG description | Protein of unknown function (DUF2752) |
| Orthologous group | 2EGD2 |
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 |
1.095 · 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 |
DUF2752 | PF10825.14 |
9.9e-19 | 41–88 |
Protein of unknown function (DUF2752) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner:
Rv1615 (membrane protein),
high confidence from genomic context alone
(score 882 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) |
Rv1615 |
membrane protein |
882 |
882 ctx |
neighborhood:882 |
Rv1618 tesB1 |
acyl-CoA thioesterase II |
770 |
770 ctx |
neighborhood:768 |
Rv1617 pykA |
pyruvate kinase |
766 |
766 ctx |
neighborhood:765 |
Rv1619 hyp |
hypothetical protein |
587 |
586 ctx |
neighborhood:524 |
Rv3689 |
transmembrane protein |
689 |
561 ctx |
cooccurence:557 |
Rv1611 trpC |
indole-3-glycerol phosphate synthase |
552 |
548 ctx |
neighborhood:544 |
Rv1612 trpB |
tryptophan synthase subunit beta |
547 |
548 ctx |
neighborhood:544 |
Rv1613 trpA |
tryptophan synthase subunit alpha |
547 |
548 ctx |
neighborhood:544 |
Rv3859c gltB |
glutamate synthase large subunit |
546 |
547 ctx |
neighborhood:544 |
Rv1610 |
membrane protein |
597 |
424 ctx |
neighborhood:415 |
Rv0260c |
transcriptional regulator |
452 |
227 |
|
Rv2571c |
transmembrane protein |
407 |
160 |
|
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
- DeepTMHMM: 3 transmembrane helices (type TM)
- Integral membrane topology (localisation feature, not a function)
- DeepTMHMM topology prediction (project 'Still unknown gene function', phase8, 2026-06-10). A topological feature, not a demonstrated molecular function.
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_216132.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF2752 (PF10825.14)
- 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
2EGD2
- Curated reference: UniProt
O06133
(TrEMBL, unreviewed; Predicted)
- 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 93.1, very high)
- 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
Rv1615
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001723|Rv1616|
MEASGRQRRYAAAGSVVLLAGALGYIGLVDPHNSNSLYPPCLFKLLTGWNCPACGGLRMIHDLLHGELAASINDNVFLLVGVPVLASWVLLRRRHGDLALPIPVMIAVAVAVIAWTVLRNLPGFPLVPTISG
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