Rv1742 Family assigned · low

H37Rv Rv1742 · MTBC0 mtbc0_001855 · 245 aa · 1980245–1980982 (+) · RefSeq NP_216258.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)LolA-superfamily fold (lipoprotein / lipid carrier-like beta-barrel). RefSeq leaves it 'hypothetical protein'. The AlphaFold model superposes on a LolA-superfamily protein (PDB 3buu; Foldseek prob 1.0, E 3e-8, TM 0.57). STRING context: the toxin vapC34 (Rv1741). A carrier/periplasmic-binding fold; the cargo is undemonstrated.

Curated reference (UniProt)

UniProt O33271 TrEMBL · unreviewed · Evidence at protein level
UniProt nameUncharacterized protein

UniProt still lists this protein as Uncharacterized protein; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group28MQW

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) pseudogene candidate

pN/pS 0.345 · purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 2 missense, 1 nonsense, 1 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 11.98% of strains (17398) · 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 96.5 (very high). A confident model makes the fold comparison meaningful.

Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.

TargetProbTME-valueDescription
4z48-assembly2_B 1.00 0.53 1.3e-07 sig 4z48-assembly2_B Crystal structure of a DUF1329 family protein (DESPIG_00262) from Desulfovibrio piger ATCC 29098 at 1.75 A resolution
3m4w-assembly2_D 0.92 0.26 1.1e-03 sig 3m4w-assembly2_D Structural basis for the negative regulation of bacterial stress response by RseB
6n5x-assembly1_A 0.30 0.62 1.8e+00 6n5x-assembly1_A Crystal structure of the SNX5 PX domain in complex with the CI-MPR (space group P212121 - Form 1)
1xks-assembly1_A 0.30 0.19 1.1e-02 1xks-assembly1_A The crystal structure of the N-terminal domain of Nup133 reveals a beta-propeller fold common to several nucleoporins
6lk8-assembly1_J 0.23 0.20 1.8e-02 6lk8-assembly1_J Structure of Xenopus laevis Cytoplasmic Ring subunit.
2l33-assembly1_A 0.21 0.53 1.6e+00 2l33-assembly1_A Solution NMR Structure of DRBM 2 domain of Interleukin enhancer-binding factor 3 from Homo sapiens, Northeast Structural Genomics Consortium Target HR4527E
6lk8-assembly1_j 0.20 0.19 2.0e-02 6lk8-assembly1_j Structure of Xenopus laevis Cytoplasmic Ring subunit.
7wb4-assembly1_P 0.15 0.18 3.2e-02 7wb4-assembly1_P Cryo-EM structure of the NR subunit from X. laevis NPC

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

Closest characterised functional partner: vapC34 (ribonuclease VapC34), high confidence from genomic context alone (score 792 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1741 vapC34 ribonuclease VapC34 792 792 ctx neighborhood:785
Rv1740 vapB34 antitoxin VapB34 786 785 ctx neighborhood:780
Rv3879c espK ESX-1 secretion-associated protein EspK 609 609 ctx cooccurence:609
Rv3882c eccE1 ESX-1 secretion system protein EccE1 595 595 ctx cooccurence:595
Rv3877 eccD1 ESX-1 secretion system protein EccD1 577 578 ctx cooccurence:575
Rv1739c sulfate ABC transporter permease 575 575 ctx neighborhood:570
Rv1743 pknE serine/threonine-protein kinase PknE 540 539 ctx neighborhood:535
Rv2542 hyp hypothetical protein 491 491 ctx cooccurence:488
Rv0341 iniB isoniazid inducible protein IniB 457 457 ctx cooccurence:457
Rv0304c PPE5 PPE family protein PPE5 422 423 ctx cooccurence:421
Rv3869 eccB1 ESX-1 secretion system protein EccB 414 415 ctx cooccurence:414
Rv2317 uspB sugar ABC transporter permease UspB 657 54 textmining:653
Rv0994 moeA1 molybdopterin molybdenumtransferase 1 656 49 textmining:654
Rv2505c fadD35 fatty-acid--CoA ligase FadD35 655 47 textmining:653
Rv3393 iunH nucleoside hydrolase 652 47 textmining:650

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

  • Foldseek -> LolA-superfamily protein (3buu), prob 1.0, E 3e-8, TM 0.57
  • STRING neighbour vapC34/Rv1741
  • Structural homology: AlphaFold DB model + Foldseek vs PDB (project 'Still unknown gene function', phase5-7, 2026-06-10). A fold-level family assignment, not a demonstrated activity.

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_216258.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 28MQW
  • Curated reference: UniProt O33271 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 96.5, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 23 functional partner(s); context anchor vapC34
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001855|Rv1742|
MSALLDGVLDAHGGLQRWRAAETVHGRVRTGGLLLRTRVPGNRFADYRITVHVQQARTVLDPFPRDGYRGVFESGQVRIESHDGAVISSRAHPRAAFFGRSGLRRNIRWDPLDSVYFAGYAMWNYLTTPYLLTREGVAVEEGAPWQQEGETWRRLIVSFPPDIDTHSPRQTFYVDASGLLRRHDYVPEVVGHWARAAHYCADPVDVDGFVFPTCRWVHPIGPGNRSLPFPTLVSILLTDIRVETD