Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|
| MTBC0 PGAP re-annotation | DUF4190 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 |
O86316
TrEMBL · unreviewed
· Predicted
|
|---|
| UniProt name | Conserved hypothetical membrane protein |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|
| eggNOG description | Domain of unknown function (DUF4190) |
|---|
| Orthologous group | 2EGCD |
|---|
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)
pseudogene candidate
| pN/pS |
0.905 · relaxed/neutral
|
|---|
| Polymorphic sites (≥ 0.1% of strains) |
2 synonymous, 5 missense, 0 nonsense, 1 frameshift
|
|---|
| Disruption |
1 distinct premature-stop/frameshift site(s); most common in
1.27% of strains
(1848) · clonal
|
|---|
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 |
|---|
DUF4190 | PF13828.12 |
4.9e-18 | 132–192 |
Domain of unknown function (DUF4190) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner:
Rv1231c (membrane protein),
high confidence from genomic context alone
(score 802 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) |
|---|
Rv1232c hyp |
hypothetical protein |
804 |
804 ctx |
neighborhood:801 |
Rv1231c |
membrane protein |
802 |
802 ctx |
neighborhood:801 |
Rv1234 |
transmembrane protein |
538 |
538 ctx |
neighborhood:533 |
Rv1230c |
membrane protein |
513 |
513 ctx |
neighborhood:510 |
Rv1236 sugA |
sugar ABC transporter permease SugA |
510 |
511 ctx |
neighborhood:502 |
Rv1238 sugC |
sugar ABC transporter ATP-binding protein SugC |
510 |
510 ctx |
neighborhood:502 |
Rv1235 lpqY |
trehalose ABC transporter substrate-binding lipoprotein LpqY |
508 |
509 ctx |
neighborhood:502 |
Rv1237 sugB |
sugar ABC transporter permease SugB |
504 |
505 ctx |
neighborhood:502 |
Rv0538 |
membrane protein |
497 |
497 ctx |
cooccurence:494 |
Rv3533c PPE62 |
PPE family protein PPE62 |
488 |
488 ctx |
cooccurence:488 |
Rv2126c PE_PGRS37 |
PE-PGRS family protein PE_PGRS37 |
484 |
485 ctx |
cooccurence:472 |
Rv3903c cpnT hyp |
hypothetical protein |
497 |
478 ctx |
cooccurence:475 |
Rv2353c PPE39 |
PPE family protein PPE39 |
459 |
459 ctx |
cooccurence:459 |
Rv3864 espE |
ESX-1 secretion-associated protein EspE |
457 |
458 ctx |
cooccurence:441 |
Rv1753c PPE24 |
PPE family protein PPE24 |
445 |
445 ctx |
cooccurence:445 |
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_215749.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF4190 (PF13828.12)
- 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
2EGCD
- Curated reference: UniProt
O86316
(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 82.4, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
23 functional partner(s); context anchor
Rv1231c
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001322|Rv1233c|
MTAPSGSSGESAHDAAGGPPPVGERPPEQPIADAPWAPPASSPMANHPPPAYPPSGYPPAYQPGYPTGYPPPMPPGGYAPPGYPPPGTSSAGYGDIPYPPMPPPYGGSPGGYYPEPGYLDGYGPSQPGMNTMALVSLISALVGVLCCIGSIVGIVFGAIAINQIKQTREEGYGLAVAGIVIGIATLLVYMIAGIFAIP
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