hsdS Family assigned · medium auto-curated
H37Rv Rv2761c · MTBC0 mtbc0_002938 ·
364 aa · 3093961–3095055 (-) ·
RefSeq NP_217277.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | type I restriction/modification system specificity determinant HsdS |
|---|---|
| MTBC0 PGAP re-annotation | restriction endonuclease subunit S |
| Revised (this work) | Restriction endonuclease subunit S. Pfam: Methylase_S (PF01420.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
I6YEB1
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Possible type I restriction/modification system specificity determinant HsdS |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
V Defense mechanisms
|
|---|---|
| Preferred name | hsdS |
| eggNOG description | I restriction modification system specificity determinant |
| Orthologous group | COG0732 |
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 | 0.722 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 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 |
|---|---|---|---|---|
Methylase_S | PF01420.26 | 1.3e-07 | 5–160 | Type I restriction modification DNA specificity domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hsdM (type I restriction/modification system DNA methylase HsdM), high confidence from genomic context alone (score 994 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2756c hsdM |
type I restriction/modification system DNA methylase HsdM | 999 | 994 ctx | neighborhood:557 cooccurence:719 coexpression:740 experimental:828 textmining:883 |
Rv2762c hyp |
hypothetical protein | 947 | 947 ctx | neighborhood:800 coexpression:746 |
Rv2755c hsdS.1 |
Rv2755c, (MTV002.20c), len: 91 aa. Possible hsdS.1,fragment of type I restriction/modification system specificity determinant (S protein), s | 876 | 859 ctx | neighborhood:503 cooccurence:724 |
Rv2760c vapB42 |
antitoxin VapB42 | 811 | 811 ctx | neighborhood:801 |
Rv2759c vapC42 |
ribonuclease VapC42 | 811 | 810 ctx | neighborhood:801 |
Rv2757c vapC21 |
ribonuclease VapC21 | 741 | 741 ctx | neighborhood:731 |
Rv2758c vapB21 |
antitoxin VapB21 | 735 | 735 ctx | neighborhood:731 |
Rv0538 |
membrane protein | 755 | 722 ctx | cooccurence:721 |
Rv1775 hyp |
hypothetical protein | 714 | 714 ctx | cooccurence:711 |
Rv3903c cpnT hyp |
hypothetical protein | 713 | 714 ctx | cooccurence:710 |
Rv1937 |
oxygenase | 700 | 700 ctx | cooccurence:692 |
Rv2763c dfrA |
dihydrofolate reductase | 631 | 631 ctx | neighborhood:619 |
Rv2113 |
integral membrane protein | 620 | 620 ctx | cooccurence:618 |
Rv2164c hyp |
hypothetical protein | 541 | 541 ctx | cooccurence:536 |
Rv0493c hyp |
hypothetical protein | 522 | 522 ctx | cooccurence:522 |
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: type I restriction/modification system specificity determinant HsdS
- MTBC0 PGAP product: restriction endonuclease subunit S
- Pfam (hmmscan --cut_ga): Methylase_S PF01420.26 (E=1e-07)
- (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_217277.1)
- Domains: Pfam-A via hmmscan --cut_ga — Methylase_S (PF01420.26)
- 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
COG0732 - Curated reference: UniProt I6YEB1 (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 —
57 functional partner(s); context anchor
hsdM - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002938|Rv2761c|hsdS MSRVEKVEKVRLGDHLDFSNGHTSGHTSPASEPGGRYPVYGANGVIGYSAQHNARGPLIVVGRVGSYCGSLRYCDSDVWVTDNALACRAKKPEETRYWYYALLGFGLNRYRAGSGQPLLSQGVLRNVSVSAVAAPDRPRIGEILGAFDDKIAANDRVIEAAEALMLAIVGRLSAYVPLSSLASRSTACLDAQHFDSTVAHYSFAAFDGGAQPSRVGGRTIRSAKLVVSQPCVLFPKLNPRIPRIWNITSLPSEMALASTEFVVLRPVGVDTSALWAALRQPDVLAELRQLVGGMTGSRQRIQPTQLLRVWVRDVRRLTPGHAAAIANLGALCNERRIESARLASCRDALLPLLMSGIDGLPAGR