Rv1276c Family assigned · medium auto-curated
H37Rv Rv1276c · MTBC0 - ·
158 aa · 1425438–1425914 (-) ·
RefSeq NP_215792.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Contains His_Phos_1 (PF00300.28) domain(s); putative function inferred from the domain architecture. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WGF9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv1276c |
| EC (curated) |
EC 3.1.3.-
|
UniProt still lists this protein as Uncharacterized protein Rv1276c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| Preferred name | sixA |
| eggNOG description | Phosphohistidine phosphatase SixA |
| Orthologous group | COG2062 |
| KEGG orthology |
K08296
|
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 | 0.387 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 3 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 |
|---|---|---|---|---|
His_Phos_1 | PF00300.28 | 3.6e-06 | 1–71 | Histidine phosphatase superfamily (branch 1) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gltB (glutamate synthase large subunit), medium confidence from genomic context alone (score 544 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) |
|---|---|---|---|---|
Rv1278 hyp |
hypothetical protein | 743 | 743 ctx | neighborhood:740 |
Rv1277 hyp |
hypothetical protein | 742 | 742 ctx | neighborhood:740 |
Rv3859c gltB |
glutamate synthase large subunit | 544 | 544 ctx | neighborhood:544 |
Rv3232c ppk2 |
polyphosphate kinase | 489 | 490 | |
Rv1279 |
GMC-type oxidoreductase | 485 | 485 ctx | neighborhood:482 |
Rv3433c nnr |
bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase | 471 | 472 | |
Rv3279c birA |
bifunctional biotin operon repressor/biotin--[acetyl-CoA-carboxylase | 497 | 44 | textmining:496 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
- Pfam (hmmscan --cut_ga): His_Phos_1 PF00300.28 (E=4e-06)
- (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_215792.1)
- Domains: Pfam-A via hmmscan --cut_ga — His_Phos_1 (PF00300.28)
- 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
COG2062 - Curated reference: UniProt P9WGF9 (SwissProt, reviewed; 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 —
7 functional partner(s); context anchor
gltB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv1276c| MRHAKSAYPDGIADHDRPLAPRGIREAGLAGGWLRANLPAVDAVLCSTATRARQTLAHTGIDAPARYAERLYGAAPGTVIEEINRVGDNVTTLLVVGHEPTTSALAIVLASISGTDAAVAERISEKFPTSGIAVLRVAGHWADVEPGCAALVGFHVPR