Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
| MTBC0 PGAP re-annotation | DUF6542 domain-containing protein |
| Revised (this work) | Polytopic integral membrane protein with 4 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 |
O86351
TrEMBL · unreviewed
· Evidence at protein level
|
| UniProt name | DUF6542 domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
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 |
0.536 · relaxed/neutral
|
| Polymorphic sites (≥ 0.1% of strains) |
4 synonymous, 6 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 |
DUF6542 | PF20177.4 |
1.3e-32 | 23–141 |
Domain of unknown function (DUF6542) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner:
ychF (GTP-binding protein),
high confidence from genomic context alone
(score 787 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) |
Rv1112 ychF |
GTP-binding protein |
786 |
787 ctx |
neighborhood:786 |
Rv1109c hyp |
hypothetical protein |
769 |
770 ctx |
cooccurence:767 |
Rv3835 hyp |
hypothetical protein |
766 |
766 ctx |
cooccurence:756 |
Rv3909 hyp |
hypothetical protein |
760 |
761 ctx |
cooccurence:757 |
Rv0996 |
transmembrane protein |
751 |
752 ctx |
cooccurence:750 |
Rv3212 hyp |
hypothetical protein |
747 |
748 ctx |
cooccurence:745 |
Rv2732c |
transmembrane protein |
747 |
747 ctx |
cooccurence:741 |
Rv3415c hyp |
hypothetical protein |
743 |
743 ctx |
cooccurence:743 |
Rv0556 |
transmembrane protein |
732 |
733 ctx |
cooccurence:731 |
Rv0475 hbhA |
heparin binding hemagglutinin HbhA |
731 |
732 ctx |
cooccurence:730 |
Rv1083 hyp |
hypothetical protein |
726 |
726 ctx |
cooccurence:726 |
Rv2164c hyp |
hypothetical protein |
724 |
725 ctx |
cooccurence:722 |
Rv1222 rseA |
anti-sigma E factor RseA |
724 |
724 ctx |
cooccurence:724 |
Rv2418c octT hyp |
hypothetical protein |
719 |
720 ctx |
cooccurence:713 |
Rv0358 hyp |
hypothetical protein |
719 |
719 ctx |
cooccurence:718 |
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: 4 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_215627.2)
- Domains: Pfam-A via hmmscan --cut_ga — DUF6542 (PF20177.4)
- 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
2FH0D
- Curated reference: UniProt
O86351
(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 82.5, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
168 functional partner(s); context anchor
ychF
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001193|Rv1111c|
MSAQRARSAVQASHRSIHPHIPGVPWWAAILIAVTATAIGYAIDAGSGHKALTLVFTGCYIAGCVGAVLAVRQSDLFTALVQPPLILFCAVPGAYWLFHGGTIGKFKDLLINCGYSLIERFPLMLGTAAGVLLIGLVRWYLGTALFDSIARKLSSLMTGDSDDDGGRRSAQRPARTRSRHARPPSEDNREPIAERRSRRRPRPQNDPHPRRNAHERPAPRSSRFDSYRSYQPSEPSGPAEPVNRYERRGARYQPYARYEPTYEPQRRRARPSEPTNPTHHPISQVRYRGSATRDARRDNYREEQRFDRRDRSRAPRRPPAESWEYDV
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