Rv3856c Family assigned · medium auto-curated
H37Rv Rv3856c · MTBC0 mtbc0_004089 ·
335 aa · 4352511–4353518 (-) ·
RefSeq NP_218373.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | PHP domain-containing protein |
| Revised (this work) | PHP domain-containing protein. Pfam: HHH_8 (PF14716.14), PHP (PF02811.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P96221
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Polymerase/histidinol phosphatase N-terminal domain-containing protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | polX |
| eggNOG description | PHP domain |
| Orthologous group | COG1387 |
| KEGG orthology |
K04477
|
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 | 0.336 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 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 |
|---|---|---|---|---|
HHH_8 | PF14716.14 | 5.3e-09 | 4–68 | Helix-hairpin-helix domain |
PHP | PF02811.27 | 9.9e-13 | 99–265 | PHP domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3857c (membrane protein), high confidence from genomic context alone (score 888 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) |
|---|---|---|---|---|
Rv3857c |
membrane protein | 888 | 888 ctx | neighborhood:882 |
Rv2367c ybeY |
endoribonuclease | 754 | 754 | coexpression:754 |
Rv3859c gltB |
glutamate synthase large subunit | 563 | 564 ctx | neighborhood:530 |
Rv3731 ligC |
DNA ligase C | 568 | 543 ctx | cooccurence:538 |
Rv1606 hisI |
phosphoribosyl-AMP cyclohydrolase | 563 | 482 | coexpression:439 |
Rv1601 hisB |
imidazole glycerol-phosphate dehydratase | 557 | 469 | coexpression:425 |
Rv0490 senX3 |
two component sensor histidine kinase SenX3 | 463 | 461 | coexpression:458 |
Rv1602 hisH |
imidazole glycerol phosphate synthase subunit HisH | 457 | 418 | |
Rv2964 purU |
formyltetrahydrofolate deformylase | 403 | 404 | coexpression:402 |
Rv1599 hisD |
histidinol dehydrogenase | 461 | 358 | |
Rv1605 hisF |
imidazole glycerol phosphate synthase subunit HisF | 447 | 312 | |
Rv0938 ligD |
multifunctional non-homologous end joining DNA repair protein/ATP dependent DNA ligase LigD | 427 | 248 | |
Rv1316c ogt |
methylated-DNA--protein-cysteine methyltransferase | 569 | 118 | textmining:532 |
Rv0670 end |
endonuclease IV | 826 | 68 | textmining:821 |
Rv0429c def |
polypeptide deformylase | 772 | 56 | textmining:769 |
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: PHP domain-containing protein
- Pfam (hmmscan --cut_ga): HHH_8 PF14716.14 (E=5e-09), PHP PF02811.27 (E=1e-12)
- (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_218373.1)
- Domains: Pfam-A via hmmscan --cut_ga — HHH_8 (PF14716.14), PHP (PF02811.27)
- 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
COG1387 - Curated reference: UniProt P96221 (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 —
15 functional partner(s); context anchor
Rv3857c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_004089|Rv3856c| MDPVTALRQIAYYKDRNRHDPRRVMAYRNAADIIEGLDDAARQRHGQANSWQSLAGIGPKTAKVIAQAWSGREPDLLAELRADAEDLGGGAIRAALRGDLHLHSNWSDGSAPIEEMMATAAALGHQYCALTDHSPRLTIANGLSPDRLRKQLDVIDELREKFAPLRILTGIEVDILEDGSLDQEPEMLDRLDIVVASVHSKLSMDSAAMTRRMVRAVANGHTDVLGHCTGRLIAGNRGIRPESKFDAEAVFTACREHGTAVEINSRPERRDPPTRLLHLARDIGCVFSIDTDAHAPGQLDFLGYGAQRALDAEVPADRIVNTWPADTLLAWTGSH