Rv3649 Resolved · high auto-curated

H37Rv Rv3649 · MTBC0 mtbc0_000791 · 81 aa · 839409–839653 (+) · RefSeq NP_218166.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)helicase
MTBC0 PGAP re-annotationZn-binding domain-containing protein
Revised (this work)DEAD/DEAH box helicase. Pfam: DEAD (PF00270.36), Helicase_C (PF00271.38), WHD_HRQ1 (PF22982.4), MZB (PF09369.16).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt O06359 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable helicase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category L Replication, recombination and repair
eggNOG descriptionATP-dependent DNA helicase (RecQ)
Orthologous groupCOG0514
EC number EC 3.6.4.12
KEGG orthology K03654, K03657, K06877
KEGG pathways map03018, map03420, map03430

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 0.306 · purifying
Polymorphic sites (≥ 0.1% of strains) 11 synonymous, 9 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.17% of strains (243) · clonal

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)

PfamAccessioni-EvalueResiduesDescription
DEADPF00270.36 6.8e-2661–232 DEAD/DEAH box helicase
Helicase_CPF00271.38 8.4e-11294–402 Helicase conserved C-terminal domain
WHD_HRQ1PF22982.4 3.4e-08437–504 ATP-dependent helicase HRQ1, winged helix domain
MZBPF09369.16 3.4e-22660–738 MrfA Zn-binding domain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: cspA (cold shock protein A), medium confidence from genomic context alone (score 519 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3648c cspA cold shock protein A 825 519 ctx neighborhood:518 textmining:653
Rv3650 PE33 PE family protein PE33 503 503 ctx neighborhood:503
Rv2908c hyp hypothetical protein 897 242 textmining:870
Rv3920c hyp hypothetical protein 891 201 textmining:870
Rv0871 cspB cold shock-like protein CspB 812 74 textmining:806
Rv1253 deaD ATP-dependent RNA helicase DeaD 874 73 textmining:871
Rv1340 rphA ribonuclease PH 808 44 textmining:808
Rv2752c rnj ribonuclease J 803 44 textmining:803

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: helicase
  • MTBC0 PGAP product: DEAD/DEAH box helicase
  • Pfam (hmmscan --cut_ga): DEAD PF00270.36 (E=7e-26), Helicase_C PF00271.38 (E=8e-11), WHD_HRQ1 PF22982.4 (E=3e-08), MZB PF09369.16 (E=3e-22)
  • (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_218166.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DEAD (PF00270.36), Helicase_C (PF00271.38), WHD_HRQ1 (PF22982.4), MZB (PF09369.16)
  • 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 COG0514
  • Curated reference: UniProt O06359 (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 — 8 functional partner(s); context anchor cspA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000791|Rv3649|
MPTTAVIHTVTAEALGRIGIDAPRIPGSLDVAAHAAIGLLPLVAGCDRRHRRPVRGARAGRAAQVSLCMTAIRVEPVSSNA