Rv3818 Resolved · high auto-curated
H37Rv Rv3818 · MTBC0 mtbc0_004047 ·
516 aa · 4306559–4308109 (+) ·
RefSeq NP_218335.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | MBL fold metallo-hydrolase |
| Revised (this work) | MBL fold metallo-hydrolase. Pfam: Lactamase_B_3 (PF13483.13), SCP2_Rv3818 (PF25451.2), Rieske (PF00355.33). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WH21
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative Rieske 2Fe-2S iron-sulfur protein Rv3818 |
| EC (curated) |
EC 1.-.-.-
|
UniProt still lists this protein as Putative Rieske 2Fe-2S iron-sulfur protein Rv3818; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
P Inorganic ion transport and metabolism
|
|---|---|
| eggNOG description | Rieske 2Fe-2S |
| Orthologous group | COG2146 |
| KEGG orthology |
K14952
|
| KEGG pathways |
map05152
|
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 | 0.315 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 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 |
|---|---|---|---|---|
Lactamase_B_3 | PF13483.13 | 2.1e-06 | 2–73 | Beta-lactamase superfamily domain |
SCP2_Rv3818 | PF25451.2 | 1.4e-46 | 332–450 | Rv3818-like, SCP2-like domain |
Rieske | PF00355.33 | 2.5e-08 | 466–507 | Rieske [2Fe-2S] domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv3817 (phosphotransferase), medium confidence from genomic context alone (score 671 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) |
|---|---|---|---|---|
Rv3819 hyp |
hypothetical protein | 970 | 970 ctx | neighborhood:881 coexpression:761 |
Rv0688 |
ferredoxin reductase | 730 | 714 | coexpression:500 experimental:434 |
Rv0252 nirB |
nitrite reductase large subunit NirB | 730 | 713 | coexpression:498 experimental:434 |
Rv1869c |
reductase | 730 | 713 | coexpression:498 experimental:434 |
Rv0511 hemD |
uroporphyrin-III C-methyltransferase | 747 | 710 | coexpression:617 |
Rv2847c cysG |
multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | 785 | 707 | coexpression:647 |
Rv3817 |
phosphotransferase | 671 | 671 ctx | neighborhood:671 |
Rv0495c hyp |
hypothetical protein | 644 | 644 ctx | cooccurence:643 |
Rv1125 hyp |
hypothetical protein | 630 | 611 ctx | cooccurence:596 |
Rv2876 |
transmembrane protein | 598 | 599 ctx | cooccurence:539 |
Rv3035 hyp |
hypothetical protein | 574 | 575 ctx | cooccurence:568 |
Rv0331 |
dehydrogenase/reductase | 595 | 570 | experimental:484 |
Rv3813c hyp |
hypothetical protein | 581 | 566 ctx | neighborhood:565 |
Rv3647c hyp |
hypothetical protein | 562 | 562 ctx | cooccurence:562 |
Rv3816c |
acyltransferase | 568 | 559 ctx | neighborhood:559 |
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: MBL fold metallo-hydrolase
- Pfam (hmmscan --cut_ga): Lactamase_B_3 PF13483.13 (E=2e-06), SCP2_Rv3818 PF25451.2 (E=1e-46), Rieske PF00355.33 (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_218335.1)
- Domains: Pfam-A via hmmscan --cut_ga — Lactamase_B_3 (PF13483.13), SCP2_Rv3818 (PF25451.2), Rieske (PF00355.33)
- 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
COG2146 - Curated reference: UniProt P9WH21 (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 —
65 functional partner(s); context anchor
Rv3817 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_004047|Rv3818| MQVTSVGHAGFLIQTQAGSILCDPWVNPAYFASWFPFPDNSGLDWGALGECDYLYVSHLHKDHFDAENLRAHVNKDAVVLLPDFPVPDLRNELQKLGFHRFFETTDSVKHRLRGPNGDLDVMIIALRAPADGPIGDSALVVADGETTAFNMNDARPVDLDVLASEFGHIDVHMLQYSGAIWYPMVYDMPARAKDAFGAQKRQRQMDRARQYIAQVGATWVVPSAGPPCFLAPELRHLNDDGSDPANIFPDQMVFLDQMRAHGQDGGLLMIPGSTADFTGTTLNSLRHPLPAEQVEAIFTTDKAAYIADYADRMAPVLAAQKAGWAAAAGEPLLQPLRTLFEPIMLQSNEICDGIGYPVELAIGPETIVLDFPKRAVREPIPDERFRYGFAIAPELVRTVLRDNEPDWVNTIFLSTRFRAWRVGGYNEYLYTFFKCLTDERIAYADGWFAEAHDDSSSITLNGWEIQRRCPHLKADLSKFGVVEGNTLTCNLHGWQWRLDDGRCLTARGHQLRSSRP