hsdM Resolved · high auto-curated
H37Rv Rv2756c · MTBC0 mtbc0_002933 ·
540 aa · 3090876–3092498 (-) ·
RefSeq NP_217272.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | type I restriction/modification system DNA methylase HsdM |
|---|---|
| MTBC0 PGAP re-annotation | class I SAM-dependent DNA methyltransferase |
| Revised (this work) | Class I SAM-dependent DNA methyltransferase. Pfam: HsdM_N (PF12161.15), N6_Mtase (PF02384.23). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O33298
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | site-specific DNA-methyltransferase |
| EC (curated) |
EC 2.1.1.72
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| Preferred name | hsdM |
| eggNOG description | DNA methylase |
| Orthologous group | COG0286 |
| EC number |
EC 2.1.1.72
|
| KEGG orthology |
K03427
|
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 | 0.716 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 19 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 |
|---|---|---|---|---|
HsdM_N | PF12161.15 | 6.9e-26 | 18–164 | HsdM N-terminal domain |
N6_Mtase | PF02384.23 | 5.4e-120 | 177–502 | N-6 DNA Methylase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: hsdS.1 (Rv2755c, (MTV002.20c), len: 91 aa. Possible hsdS.1,fragment of type I restriction/modification system specificity determinant (S protein), s), high confidence from genomic context alone (score 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2755c hsdS.1 |
Rv2755c, (MTV002.20c), len: 91 aa. Possible hsdS.1,fragment of type I restriction/modification system specificity determinant (S protein), s | 999 | 998 ctx | neighborhood:800 cooccurence:729 coexpression:786 experimental:828 textmining:919 |
Rv2761c hsdS |
type I restriction/modification system specificity determinant HsdS | 999 | 994 ctx | neighborhood:557 cooccurence:719 coexpression:740 experimental:828 textmining:883 |
Rv2757c vapC21 |
ribonuclease VapC21 | 890 | 888 ctx | neighborhood:598 coexpression:733 |
Rv2754c thyX |
thymidylate synthase ThyX | 763 | 763 ctx | neighborhood:727 |
Rv2762c hyp |
hypothetical protein | 745 | 745 ctx | neighborhood:741 |
Rv2753c dapA |
4-hydroxy-tetrahydrodipicolinate synthase | 681 | 682 ctx | neighborhood:677 |
Rv2752c rnj |
ribonuclease J | 650 | 650 ctx | neighborhood:644 |
Rv1251c hyp |
hypothetical protein | 655 | 620 | coexpression:480 |
Rv2758c vapB21 |
antitoxin VapB21 | 618 | 618 ctx | neighborhood:598 |
Rv2528c mrr |
restriction system protein | 643 | 589 | coexpression:423 |
Rv2759c vapC42 |
ribonuclease VapC42 | 553 | 552 ctx | neighborhood:532 |
Rv2760c vapB42 |
antitoxin VapB42 | 544 | 543 ctx | neighborhood:532 |
Rv2763c dfrA |
dihydrofolate reductase | 507 | 507 ctx | neighborhood:502 |
Rv1633 uvrB |
excinuclease ABC subunit UvrB | 502 | 473 | experimental:464 |
Rv2764c thyA |
thymidylate synthase ThyA | 420 | 420 ctx | neighborhood:416 |
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 DNA methylase HsdM
- MTBC0 PGAP product: class I SAM-dependent DNA methyltransferase
- Pfam (hmmscan --cut_ga): HsdM_N PF12161.15 (E=7e-26), N6_Mtase PF02384.23 (E=5e-120)
- (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_217272.1)
- Domains: Pfam-A via hmmscan --cut_ga — HsdM_N (PF12161.15), N6_Mtase (PF02384.23)
- 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
COG0286 - Curated reference: UniProt O33298 (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
hsdS.1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002933|Rv2756c|hsdM MPPRKKQAPQAPSTMKELKDTLWKAADKLRGSLSASQYKDVILGLVFLKYVSDAYDERREAIRAELAAEGMEESQIEDLIDDPEQYQGYGVFVVPVSARWKFLAENTKGKPAVGGEPAKNIGQLIDEAMDAVMKANPTLGGTLPRLYNKDNIDQRRLGELIDLFNSARFSRQGEHRARDLMGEVYEYFLGNFARAEGKRGGEFFTPPSVVKVIVEVLEPSSGRVYDPCCGSGGMFVQTEKFIYEHDGDPKDVSIYGQESIEETWRMAKMNLAIHGIDNKGLGARWSDTFARDQHPDVQMDYVMANPPFNIKDWARNEEDPRWRFGVPPANNANYAWIQHILYKLAPGGRAGVVMANGSMSSNSNGEGDIRAQIVEADLVSCMVALPTQLFRSTGIPVCLWFFAKDKAAGKQGSIDRCGQVLFIDARELGDLVDRAERALTNEEIVRIGDTFHAWRGSKSAAVKGIMYEDVPGFCKSATLAEIKATDYALTPGRYVGTPAVEDDGEPIDEKMARLSKALLEAFDESARLERVVREQLGRLR