Rv2003c Family assigned · medium auto-curated
H37Rv Rv2003c · MTBC0 - ·
285 aa · 2248563–2249420 (-) ·
RefSeq NP_216519.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Contains Methyltransf_11 (PF08241.19), Methyltransf_25 (PF13649.13), Methyltransf_23 (PF13489.13) 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 |
P9WJZ5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv2003c |
UniProt still lists this protein as Uncharacterized protein Rv2003c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| eggNOG description | methyltransferase |
| Orthologous group | COG0500 |
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 | 1.116 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 6 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 |
|---|---|---|---|---|
Methyltransf_11 | PF08241.19 | 4.7e-11 | 102–187 | Methyltransferase domain |
Methyltransf_25 | PF13649.13 | 4.2e-08 | 102–183 | Methyltransferase domain |
Methyltransf_23 | PF13489.13 | 2.4e-08 | 102–234 | Methyltransferase domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2005c (universal stress protein), high confidence from genomic context alone (score 912 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) |
|---|---|---|---|---|
Rv2004c hyp |
hypothetical protein | 978 | 955 ctx | neighborhood:623 coexpression:860 textmining:537 |
Rv2005c |
universal stress protein | 911 | 912 ctx | neighborhood:572 coexpression:802 |
Rv2006 otsB1 |
trehalose-6-phosphate phosphatase OtsB | 897 | 898 ctx | neighborhood:420 coexpression:831 |
Rv2624c |
universal stress protein | 800 | 800 | coexpression:800 |
Rv1997 ctpF |
cation transporter ATPase F | 799 | 800 | coexpression:800 |
Rv0571c hyp |
hypothetical protein | 825 | 799 | coexpression:799 |
Rv0570 nrdZ |
vitamin B12-dependent ribonucleoside-diphosphate reductase | 798 | 799 | coexpression:797 |
Rv3132c devS |
two component sensor histidine kinase DevS | 738 | 739 | coexpression:738 |
Rv2028c |
universal stress protein | 734 | 734 | coexpression:734 |
Rv0573c pncB2 |
nicotinic acid phosphoribosyltransferase PncB2 | 553 | 549 | coexpression:474 |
Rv2954c hyp |
hypothetical protein | 454 | 450 | |
Rv2029c pfkB |
6-phosphofructokinase PfkB | 414 | 415 | coexpression:415 |
Rv2337c hyp |
hypothetical protein | 413 | 414 | |
Rv1525 wbbL2 |
rhamnosyl transferase WbbL | 406 | 406 | |
Rv2631 rtcB |
RNA-splicing ligase RtcB | 713 | 402 | textmining:540 |
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): Methyltransf_11 PF08241.19 (E=5e-11), Methyltransf_25 PF13649.13 (E=4e-08), Methyltransf_23 PF13489.13 (E=2e-08)
- (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_216519.1)
- Domains: Pfam-A via hmmscan --cut_ga — Methyltransf_11 (PF08241.19), Methyltransf_25 (PF13649.13), Methyltransf_23 (PF13489.13)
- 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
COG0500 - Curated reference: UniProt P9WJZ5 (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 —
29 functional partner(s); context anchor
Rv2005c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2003c| MVKRSRATRLSPSIWSGWESPQCRSIRARLLLPRGRSRPPNADCCWNQLAVTPDTRMPASSAAGRDAAAYDAWYDSPTGRPILATEVAALRPLIEVFAQPRLEIGVGTGRFADLLGVRFGLDPSRDALMFARRRGVLVANAVGEAVPFVSRHFGAVLMAFTLCFVTDPAAIFRETRRLLADGGGLVIGFLPRGTPWADLYALRAARGQPGYRDARFYTAAELEQLLADSGFRVIARRCTLHQPPGLARYDIEAAHDGIQAGAGFVAISAVDQAHEPKDDHPLESE