lhr Resolved · high auto-curated
H37Rv Rv3296 · MTBC0 mtbc0_003504 ·
1513 aa · 3698855–3703396 (+) ·
RefSeq NP_217813.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | ATP-dependent helicase |
|---|---|
| MTBC0 PGAP re-annotation | ATP-dependent helicase |
| Revised (this work) | ATP-dependent helicase. Pfam: DEAD (PF00270.36), ResIII (PF04851.22), Helicase_C (PF00271.38), WHD_Lhr (PF19306.6), DEAD_assoc (PF08494.17), WHD_2nd_Lhr (PF23236.2), WHD_3rd_Lhr (PF23235.2), WHD_4th_Lhr (PF23234.2). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P96901
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable ATP-dependent helicase Lhr |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
L Replication, recombination and repair
|
|---|---|
| Preferred name | lhr |
| eggNOG description | dead DEAH box helicase |
| Orthologous group | COG1201 |
| KEGG orthology |
K03724
|
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 | 0.51 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 15 synonymous, 20 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 |
|---|---|---|---|---|
DEAD | PF00270.36 | 9.5e-31 | 28–212 | DEAD/DEAH box helicase |
ResIII | PF04851.22 | 3.2e-05 | 34–211 | Type III restriction enzyme, res subunit |
Helicase_C | PF00271.38 | 4.2e-13 | 334–399 | Helicase conserved C-terminal domain |
WHD_Lhr | PF19306.6 | 1.3e-49 | 427–594 | Large helicase-related protein, winged helix domain |
DEAD_assoc | PF08494.17 | 6.7e-61 | 659–851 | DEAD/H associated |
WHD_2nd_Lhr | PF23236.2 | 8.4e-34 | 896–1000 | Large helicase-related protein, winged-helix domain |
WHD_3rd_Lhr | PF23235.2 | 7.0e-30 | 1091–1179 | Large helicase-related protein, winged-helix domain |
WHD_4th_Lhr | PF23234.2 | 2.9e-30 | 1301–1380 | Large helicase-related protein, winged-helix domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: nei (endonuclease VIII), high confidence from genomic context alone (score 985 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3297 nei |
endonuclease VIII | 996 | 985 ctx | neighborhood:881 coexpression:839 textmining:803 |
Rv3295 |
TetR family transcriptional regulator | 820 | 820 ctx | neighborhood:818 |
Rv3555c hyp |
hypothetical protein | 800 | 800 | coexpression:799 |
Rv3585 radA |
DNA repair protein RadA | 793 | 793 | coexpression:793 |
Rv2191 hyp |
hypothetical protein | 767 | 750 | coexpression:735 |
Rv3242c hyp |
hypothetical protein | 574 | 575 | coexpression:575 |
Rv3293 pcd |
piperideine-6-carboxylic acid dehydrogenase | 546 | 547 ctx | neighborhood:544 |
Rv3202c adnA |
ATP-dependent DNA helicase | 515 | 491 | coexpression:474 |
Rv3294c hyp |
hypothetical protein | 469 | 469 ctx | neighborhood:464 |
Rv3586 disA |
DNA integrity scanning protein DisA | 449 | 449 | coexpression:449 |
Rv3730c ligD hyp |
hypothetical protein | 439 | 439 ctx | cooccurence:434 |
Rv0269c hyp |
hypothetical protein | 428 | 429 ctx | cooccurence:427 |
Rv2917 hyp |
hypothetical protein | 428 | 429 | |
Rv2737c recA |
recombinase A | 697 | 425 | textmining:495 |
Rv3201c adnB |
ATP-dependent DNA helicase | 615 | 209 | textmining:534 |
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: ATP-dependent helicase
- MTBC0 PGAP product: ATP-dependent helicase
- Pfam (hmmscan --cut_ga): DEAD PF00270.36 (E=1e-30), ResIII PF04851.22 (E=3e-05), Helicase_C PF00271.38 (E=4e-13), WHD_Lhr PF19306.6 (E=1e-49), DEAD_assoc PF08494.17 (E=7e-61), WHD_2nd_Lhr PF23236.2 (E=8e-34), WHD_3rd_Lhr PF23235.2 (E=7e-30), WHD_4th_Lhr PF23234.2 (E=3e-30)
- (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_217813.1)
- Domains: Pfam-A via hmmscan --cut_ga — DEAD (PF00270.36), ResIII (PF04851.22), Helicase_C (PF00271.38), WHD_Lhr (PF19306.6), DEAD_assoc (PF08494.17), WHD_2nd_Lhr (PF23236.2), WHD_3rd_Lhr (PF23235.2), WHD_4th_Lhr (PF23234.2)
- 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
COG1201 - Curated reference: UniProt P96901 (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 —
32 functional partner(s); context anchor
nei - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003504|Rv3296|lhr MRFAQPSALSRFSALTRDWFTSTFAAPTAAQASAWAAIADGDNTLVIAPTGSGKTLAAFLWALDSLAGSEPMSERPAATRVLYVSPLKALAVDVERNLRTPLAGLTRLAERQGLPAPQIRVGVRSGDTPPALRRQLVSQPPDVLITTPESLFLMLTSAARQTLTGVQTVIIDEIHAIAATKRGAHLALSLERLDDLSSRRRAQRIGLSATVRPPEELARFLSGQSPTTIVAPPAAKTVELSVQVPVPDMANLTDNTIWPDVEARLVDLIESHNSTIVFANSRRLAERLTARLNEIHAARCGIELAPDTNQQVAGGAPAHIMGSGQTFGAPPVLARAHHGSISKEQRAVVEEDLKRGQLKAVVATSSLELGIDMGAVDLVIQVQAPPSVASGLQRIGRAGHQVGEISRGVLFPKHRTDLLGCAVSVQRMLAGEIETMRVPANPLDILAQHTVAAAALEPLDADAWFDTVRRAAPFATLPRSLFEATLDLLSGKYPSTEFAELRPRLVYDRDTGTLTARPGAQRLAVTSGGAIPDRGLFAVYLATERPSRVGELDEEMVYESRPGDVISLGATSWRITEITHDRVLVIPAPGQPARLPFWRGDDAGRPAELGAALGALTGELAALDRTAFGTRCAGLGFDDYATDNLWRLLDDQRTATAVVPTDSTLLVERFRDELGDWRVILHSPYGLRVHGPLALAVGRRLRDRYGIDEKPTASDNGIVVRLPDTVSAGEDSPPGAELFVFDADEIDPIVTTEVAGSALFASRFRESAARALLLPRRHPGRRSPLWQQRQRAARLLEVARKYPDFPIVLETVRECLQDVYDVPILVELMARIAQRRVRVAEAETAKPSPFAASLLFGYVGAFMYEGDTPLAERRAAALALDGTLLAELLGRVELRELLDPDVIAATSRQLQHLAADRVARDAEGVADLLRLLGPLTEDEIAARAGAPEVSGWLDGLRAAKRALVVSFAGRSWWVAVEDMGRLRDGVGAAVPVGLPASFTEAVADPLGELLGRYARTHTPFTTAAAAARFGLGLRVTADVLGRLASDGRLVRGEFVAAAEGSAGGEQWCDAEVLRILRRRSLAALRAQAEPVSTAAYGRFLPAWQHVSAGNSGIDGLAAVIDQLAGVRIPASAIEPLVLAPRIRDYSPAMLDELLASGDVTWSGAGSISGSDGWIALHPADSAPMTLAEPAEIDFTDAHRAILASLGTGGAYFFRQLTHDGLTEAELKAALWELIWAGRVTGDTFAPVRAVLGGAGTRKRAAPAHGGHRPPRLSRYRLTHAQARNADPTVAGRWSALPLPEPDSTLRAHYQAELLLNRHGVLTKDAVAAEGVAGGFATLYKVLSAFEDAGRCQRGYFIESLGGAQFAVASTVDRLRSYLDGVDPEQPDYHAVVLAAADPANPYGAALPWPASSADGTARPGRKAGALVVLVDGELAWFLERGGRSLLTFTDDPEANHAAAIGLADLVTAGRVASILVERADGMPVLQPGGRASAALTALLAAGFVRTPRGLRRR