Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
| MTBC0 PGAP re-annotation | NfeD family protein |
| Revised (this work) | NfeD family protein. Pfam: NfeD (PF01957.26). |
Auto-curated: this verdict and function were generated by rules from
PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P71767
TrEMBL · unreviewed
· Evidence at protein level
|
| UniProt name | Conserved membrane protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
U Intracellular trafficking, secretion and vesicular transport
|
| eggNOG description | Membrane protein implicated in regulation of membrane protease activity |
| Orthologous group | COG1585 |
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 |
0.186 · strong purifying
|
| Polymorphic sites (≥ 0.1% of strains) |
2 synonymous, 1 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 |
NfeD | PF01957.26 |
8.8e-14 | 84–140 |
NfeD-like C-terminal, partner-binding domain |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
Rv1488 hyp |
hypothetical protein |
973 |
971 ctx |
neighborhood:851 cooccurence:750 |
Rv1489 hyp |
hypothetical protein |
853 |
854 ctx |
neighborhood:847 |
Rv2066 cobIJ |
bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase |
756 |
757 |
coexpression:726 |
Rv2208 cobS |
adenosylcobinamide-GDP ribazoletransferase |
749 |
750 |
coexpression:749 |
Rv0870c |
integral membrane protein |
733 |
734 |
coexpression:733 |
Rv1486c hyp |
hypothetical protein |
833 |
692 ctx |
neighborhood:644 textmining:479 |
Rv1489A hyp |
hypothetical protein |
665 |
665 ctx |
neighborhood:608 |
Rv2070c cobK |
precorrin-6A reductase |
441 |
441 |
coexpression:423 |
Rv2881c cdsA |
phosphatidate cytidylyltransferase |
436 |
436 |
coexpression:436 |
Rv0255c cobQ1 |
cobyric acid synthase |
436 |
436 |
coexpression:436 |
Rv2065 cobH |
precorrin-8X methylmutase |
418 |
419 |
coexpression:402 |
Rv2030c hyp |
hypothetical protein |
402 |
403 |
coexpression:403 |
Rv2071c cobM |
precorrin-4 C(11)-methyltransferase |
472 |
266 |
|
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: NfeD family protein
- Pfam (hmmscan --cut_ga): NfeD PF01957.26 (E=9e-14)
- (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_216003.1)
- Domains: Pfam-A via hmmscan --cut_ga — NfeD (PF01957.26)
- 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
COG1585
- Curated reference: UniProt
P71767
(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 —
13 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001590|Rv1487|
MPVALIWLIAALVLVGAEALTGDMFLLMLGGGALAASVSSWLLAWPMWADGAVFLLVSVLLLVLVRPAVRRRLTQTKGVQLGIEALEGKKAVVLGRVARDGGQVKLDGQVWTARPLNDGDVFEPGDSVTVVQIDGATAVVFKDV
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