Rv2633c Resolved · high auto-curated
H37Rv Rv2633c · MTBC0 mtbc0_002802 ·
161 aa · 2982896–2983381 (-) ·
RefSeq NP_217149.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | non-heme di-iron catalase |
| Revised (this work) | Non-heme di-iron catalase. Pfam: Hemerythrin (PF01814.29). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WL59
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv2633c |
UniProt still lists this protein as Uncharacterized protein Rv2633c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Hemerythrin HHE cation binding domain |
| Orthologous group | COG5592 |
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 | 1.259 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 4 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 |
|---|---|---|---|---|
Hemerythrin | PF01814.29 | 1.2e-15 | 3–116 | Hemerythrin HHE cation binding domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0955 (integral membrane protein), high confidence from genomic context alone (score 724 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) |
|---|---|---|---|---|
Rv2632c hyp |
hypothetical protein | 956 | 786 ctx | neighborhood:512 coexpression:580 textmining:803 |
Rv3896c hyp |
hypothetical protein | 757 | 757 ctx | cooccurence:756 |
Rv0955 |
integral membrane protein | 723 | 724 ctx | cooccurence:721 |
Rv1978 hyp |
hypothetical protein | 723 | 724 ctx | cooccurence:722 |
Rv0688 |
ferredoxin reductase | 730 | 714 | coexpression:500 experimental:434 |
Rv1869c |
reductase | 730 | 714 | coexpression:500 experimental:434 |
Rv0252 nirB |
nitrite reductase large subunit NirB | 730 | 713 | coexpression:498 experimental:434 |
Rv0804 hyp |
hypothetical protein | 698 | 699 ctx | cooccurence:698 |
Rv2847c cysG |
multifunctional uroporphyrin-III C-methyltransferase/precorrin-2 oxidase/ferrochelatase | 773 | 690 | coexpression:647 |
Rv3604c |
transmembrane protein | 679 | 680 ctx | cooccurence:679 |
Rv3074 hyp |
hypothetical protein | 672 | 673 ctx | cooccurence:670 |
Rv1378c hyp |
hypothetical protein | 665 | 666 ctx | cooccurence:663 |
Rv0511 hemD |
uroporphyrin-III C-methyltransferase | 706 | 663 | coexpression:617 |
Rv1057 hyp |
hypothetical protein | 653 | 653 ctx | cooccurence:653 |
Rv1158c hyp |
hypothetical protein | 639 | 640 ctx | cooccurence:635 |
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: non-heme di-iron catalase
- Pfam (hmmscan --cut_ga): Hemerythrin PF01814.29 (E=1e-15)
- (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_217149.1)
- Domains: Pfam-A via hmmscan --cut_ga — Hemerythrin (PF01814.29)
- 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
COG5592 - Curated reference: UniProt P9WL59 (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 —
58 functional partner(s); context anchor
Rv0955 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002802|Rv2633c| MNAYDVLKRHHTVLKGLGRKVGEAPVNSEERHVLFDEMLIELDIHFRIEDDLYYPALSAAGKPITGTHAEHRQVVDQLATLLRTPQRAPGYEEEWNVFRTVLEAHADVEERDMIPAPTPVHITDAELEELGDKMAARIEQLRGSPLYTLRTKGKADLLKAI