Rv3705c Family assigned · medium auto-curated
H37Rv Rv3705c · MTBC0 mtbc0_003927 ·
214 aa · 4172266–4172910 (-) ·
RefSeq NP_218222.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | sensor domain-containing protein |
| Revised (this work) | Sensor domain-containing protein. Pfam: PknH_C (PF14032.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6XI06
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved protein |
UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | PknH-like extracellular domain |
| Orthologous group | 2C8AX |
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 | 0.573 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 5 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 |
|---|---|---|---|---|
PknH_C | PF14032.13 | 2.6e-48 | 29–211 | PknH-like extracellular domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gshA (glutamate--cysteine ligase), medium confidence from genomic context alone (score 576 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) |
|---|---|---|---|---|
Rv3704c gshA |
glutamate--cysteine ligase | 576 | 576 ctx | neighborhood:556 |
Rv3702c egtC |
amidohydrolase EgtC | 575 | 575 ctx | neighborhood:555 |
Rv3701c egtD |
histidine-specific methyltransferase EtgD | 561 | 561 ctx | neighborhood:555 |
Rv3700c egtE |
pyridoxal-phosphate-dependent protein EgtE | 560 | 560 ctx | neighborhood:553 |
Rv3703c etgB |
iron(II)-dependent oxidoreductase EgtB | 557 | 557 ctx | neighborhood:543 |
Rv3705A hyp |
hypothetical protein | 536 | 536 ctx | neighborhood:531 |
Rv3706c hyp |
hypothetical protein | 434 | 433 ctx | neighborhood:430 |
Rv2253 hyp |
hypothetical protein | 871 | 53 | textmining:870 |
Rv0835 lpqQ |
lipoprotein LpqQ | 810 | 47 | textmining:809 |
Rv1352 hyp |
hypothetical protein | 808 | 47 | textmining:807 |
Rv1810 hyp |
hypothetical protein | 518 | 47 | textmining:515 |
Rv0063 |
oxidoreductase | 870 | 44 | textmining:870 |
Rv1418 lprH |
lipoprotein LprH | 870 | 44 | textmining:870 |
Rv3576 lppH |
lipoprotein LppH | 680 | 44 | textmining:679 |
Rv3016 lpqA |
lipoprotein LpqA | 870 | 42 | textmining:870 |
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: sensor domain-containing protein
- Pfam (hmmscan --cut_ga): PknH_C PF14032.13 (E=3e-48)
- (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_218222.1)
- Domains: Pfam-A via hmmscan --cut_ga — PknH_C (PF14032.13)
- 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
2C8AX - Curated reference: UniProt I6XI06 (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 —
16 functional partner(s); context anchor
gshA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003927|Rv3705c| MRIAAAVVSIGLAVIAGFAVPVADAHPSEPGVVSYAVLGKGSVGNIVGAPMGWEAVFTRPFQAFWVELPACNNWVDIGLPEVYDDPDLASFNGATTQTSATDQTHLVKQAVGVFASNDAADRAFHRVVDRTVGCSGQTTAIHLDDGTTQVWSFAGGPSTGTDEAWTKQEAGTDRRCFVQTRLRENVLLQAKVCQSGNAGPAVNVLAGAMQNTLG