Rv2974c Family assigned · medium auto-curated
H37Rv Rv2974c · MTBC0 - ·
470 aa · 3329949–3331361 (-) ·
RefSeq NP_217490.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Contains Dak2 (PF02734.23), FakA-like_M (PF21645.4), FakA-like_C (PF13684.12) 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 |
I6Y259
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved hypothetical alanine rich protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | dak3 |
| eggNOG description | Dihydroxyacetone kinase |
| Orthologous group | COG1461 |
| KEGG orthology |
K07030
|
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 | 1.363 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 7 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 |
|---|---|---|---|---|
Dak2 | PF02734.23 | 7.5e-17 | 1–131 | DAK2 domain |
FakA-like_M | PF21645.4 | 8.0e-15 | 162–232 | Fatty acid kinase subunit A-like, middle domain |
FakA-like_C | PF13684.12 | 1.9e-49 | 249–470 | Fatty acid kinase subunit A-like, C-terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: recG (ATP-dependent DNA helicase RecG), high confidence from genomic context alone (score 944 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) |
|---|---|---|---|---|
Rv2975c hyp |
hypothetical protein | 978 | 978 ctx | neighborhood:773 fusion:875 |
Rv2973c recG |
ATP-dependent DNA helicase RecG | 944 | 944 ctx | neighborhood:800 coexpression:732 |
Rv2417c |
DegV domain-containing protein | 930 | 928 ctx | cooccurence:774 experimental:652 |
Rv2972c hyp |
hypothetical protein | 809 | 809 ctx | neighborhood:800 |
Rv2185c TB16.3 hyp |
hypothetical protein | 521 | 521 ctx | cooccurence:521 |
Rv0854 hyp |
hypothetical protein | 515 | 515 ctx | cooccurence:515 |
Rv0857 hyp |
hypothetical protein | 499 | 499 ctx | cooccurence:496 |
Rv1696 recN |
DNA repair protein RecN | 440 | 440 | coexpression:440 |
Rv0474 |
HTH-type transcriptional regulator | 428 | 428 ctx | cooccurence:423 |
Rv1018c glmU |
bifunctional UDP-N-acetylglucosamine pyrophosphorylase/glucosamine-1-phosphate N-acetyltransferase | 410 | 410 | coexpression:410 |
Rv0024 |
NLP/P60 family protein | 419 | 188 | |
Rv2065 cobH |
precorrin-8X methylmutase | 667 | 79 | textmining:654 |
Rv2070c cobK |
precorrin-6A reductase | 529 | 78 | textmining:511 |
Rv0105c rpmB1 |
50S ribosomal protein L28 | 526 | 73 | textmining:510 |
Rv2277c |
glycerolphosphodiesterase | 658 | 47 | textmining:656 |
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): Dak2 PF02734.23 (E=7e-17), FakA-like_M PF21645.4 (E=8e-15), FakA-like_C PF13684.12 (E=2e-49)
- (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_217490.1)
- Domains: Pfam-A via hmmscan --cut_ga — Dak2 (PF02734.23), FakA-like_M (PF21645.4), FakA-like_C (PF13684.12)
- 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
COG1461 - Curated reference: UniProt I6Y259 (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 —
26 functional partner(s); context anchor
recG - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2974c| MNGARGNSGVILSQILRGIAEVTATAAAASGAVLRAVDANALGAALWRGVELVVASMGGVEVPGTIVSVLRAAAGAVDQCAHEGLAGAVTAAGDAAVIALEKTPEQLDVLADAGAVDAGGRGLLVLLDALRSTICGQAPARAVYEPSPRALPTDTATQRPAPQFEVMYLLAVCDAAAADQLRDRLKELGESVAIAAAPPDSYSVHVHTDDAGAAVEAGLAVGRVSRIVISALGSGTSGLPAGGWTRGRAVLAVVDGDGAAELFAGEGACVLRPGPDAVTPAADISAHQLVRAVVDTGAAHVMVLPNGYVAAEELVAGCTAAIGWGVDVVPVPTGSMVQGLAALAVHDAARQAVDDGYSMARAAGASRHGSVRIATQKALTWAGTCKPGDGLGIAGDEVLIVADDVAAAAIGLVDLLLASGGDLVTVLIGAGVTEDVAVVLERHVHDHHPGTELVSYRTGHRGDALLIGVE