Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | membrane protein |
|---|
| MTBC0 PGAP re-annotation | DUF58 domain-containing protein |
|---|
| Revised (this work) | Sec-translocon-associated membrane protein (translocon-associated protein TRAP-beta-like fold). RefSeq leaves it 'hypothetical protein'. |
|---|
Curated reference (UniProt)
| UniProt |
O69661
TrEMBL · unreviewed
· Evidence at protein level
|
|---|
| UniProt name | Possible conserved membrane protein |
|---|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|
| eggNOG description | conserved protein (some members contain a von Willebrand factor type A (vWA) domain) |
|---|
| Orthologous group | COG1721 |
|---|
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 |
0.589 · 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 |
|---|
DUF58 | PF01882.26 |
5.5e-19 | 193–382 |
Protein of unknown function DUF58 |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner:
Rv3690 (membrane protein),
high confidence from genomic context alone
(score 947 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|
Rv3691 hyp |
hypothetical protein |
978 |
977 ctx |
neighborhood:756 cooccurence:774 coexpression:621 |
Rv3690 |
membrane protein |
949 |
947 ctx |
neighborhood:684 cooccurence:772 |
Rv3692 moxR2 |
methanol dehydrogenase transcriptional regulator MoxR |
926 |
923 ctx |
neighborhood:756 cooccurence:622 |
Rv3689 |
transmembrane protein |
911 |
911 ctx |
neighborhood:671 cooccurence:733 |
Rv3694c |
transmembrane protein |
838 |
807 ctx |
cooccurence:774 |
Rv3695 |
membrane protein |
796 |
797 ctx |
cooccurence:774 |
Rv0421c hyp |
hypothetical protein |
744 |
744 |
coexpression:744 |
Rv3688c hyp |
hypothetical protein |
646 |
646 ctx |
neighborhood:645 |
Rv3164c moxR3 |
methanol dehydrogenase transcriptional regulator MoxR |
451 |
424 |
|
Rv3701c egtD |
histidine-specific methyltransferase EtgD |
747 |
52 |
textmining:745 |
Rv0772 purD |
phosphoribosylamine--glycine ligase |
747 |
51 |
textmining:745 |
Rv2498c citE |
citrate (pro-3S)-lyase subunit beta |
675 |
50 |
textmining:672 |
Rv3680 |
anion transporter ATPase |
646 |
49 |
textmining:644 |
Rv0913c |
dioxygenase |
511 |
47 |
textmining:508 |
Rv2421c nadD |
nicotinate-nucleotide adenylyltransferase |
437 |
47 |
textmining:434 |
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
- Foldseek vs AFDB-SwissProt: translocon-associated protein subunit beta, TM 0.55, E 5e-6
- Structural homology vs AlphaFold-Swiss-Prot (Foldseek; 542k curated SwissProt structures), project 'Still unknown gene function' phase13, 2026-06-10. Fold/family-level, not a demonstrated 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_218210.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF58 (PF01882.26)
- 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
COG1721
- Curated reference: UniProt
O69661
(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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
17 functional partner(s); context anchor
Rv3690
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003914|Rv3693|
MILTGRTGLLALICVLPIALSPWPARAFVMLLVALAVAVTVDTLLAASTRKLRFTRSPYTSARLGQPVDASLLLCNGGRRRFRGQVRDAWPPSARAQPHTHDVDVAAGQRQQVHTALRPVRRGDQRAAMVTARSIGPLGLAGRQSSQSVPGLVRVLPPFLSRKHLPSRLAKLREIDGLLPTLIRGQGTEFDSLREYVVGDDVRSIDWRASARRADVMVRTWRPERDRRVVIVLDTGRMAAGRVGVDPTAADPAGWPRLDWSMDAALLLAALASRAGDHVDFLAHDRISRAGVFGASRSELLAQLVDAMAPLRPALIESDWHAMIATILRRTRRRSLVVLLTDLNATALDEGLLPVLPQLSARHHVLVAAVADPRVDQLAAGRSDAAAVYDAAAAERARNDRRAIASQLRRGGVDVIDAPPAEIAPGLADRYLAMKATGRL
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