Rv1748 Still unknown · low auto-curated

H37Rv Rv1748 · MTBC0 - · 243 aa · 1976600–1977331 (+) · RefSeq NP_216264.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 6rf0-assembly1_C Crystal structure of the light-driven sodium pump KR2 (prob 0.20, TM 0.32).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt P72005 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 group2ERCX

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 0.119 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 1 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)

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 89.3 (confident). 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
6rf0-assembly1_C 0.20 0.32 1.4e+00 6rf0-assembly1_C Crystal structure of the light-driven sodium pump KR2 in the pentameric "dry" form
6rf4-assembly1_B 0.14 0.32 2.8e+00 6rf4-assembly1_B Crystal structure of the potassium-pumping S254A mutant of the light-driven sodium pump KR2 in the pentameric form, pH 8.0
4xtn-assembly2_G 0.13 0.32 3.1e+00 4xtn-assembly2_G Crystal structure of the light-driven sodium pump KR2 in the pentameric red form, pH 4.9
6rf0-assembly1_A 0.13 0.32 2.9e+00 6rf0-assembly1_A Crystal structure of the light-driven sodium pump KR2 in the pentameric "dry" form
6rf4-assembly1_D 0.13 0.32 2.9e+00 6rf4-assembly1_D Crystal structure of the potassium-pumping S254A mutant of the light-driven sodium pump KR2 in the pentameric form, pH 8.0
6xyt-assembly1_C 0.13 0.32 3.1e+00 6xyt-assembly1_C Crystal structure of the O-state of the light-driven sodium pump KR2 in the pentameric form, pH 8.0
6rf3-assembly1_B 0.12 0.32 3.4e+00 6rf3-assembly1_B Crystal structure of the potassium-pumping G263F mutant of the light-driven sodium pump KR2 in the pentameric form, pH 8.0
6yc2-assembly1_B 0.11 0.32 3.5e+00 6yc2-assembly1_B Crystal structure of the light-driven sodium pump KR2 in the pentameric form at room temperature, pH 8.0

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

Closest characterised functional partner: Rv0180c (transmembrane protein), medium confidence from genomic context alone (score 661 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1006 hyp hypothetical protein 685 685 ctx cooccurence:685
Rv1868 hyp hypothetical protein 662 663 ctx cooccurence:661
Rv0180c transmembrane protein 661 661 ctx cooccurence:659
Rv1364c sigma factor regulatory protein 599 600 ctx cooccurence:594
Rv1435c hyp hypothetical protein 595 595 ctx cooccurence:594
Rv0219 transmembrane protein 579 580 ctx cooccurence:576
Rv0541c integral membrane protein 569 569 ctx cooccurence:569
Rv3886c mycP2 membrane-anchored mycosin 563 564 ctx cooccurence:562
Rv2114 hyp hypothetical protein 552 552 ctx cooccurence:552
Rv1126c hyp hypothetical protein 538 539 ctx cooccurence:532
Rv2047c hyp hypothetical protein 538 538 ctx cooccurence:537
Rv1796 mycP5 membrane-anchored mycosin MycP 511 511 ctx cooccurence:511
Rv2938 drrC daunorubicin ABC transporter permease DrrC 484 484 ctx cooccurence:484
Rv3033 hyp hypothetical protein 483 483 ctx cooccurence:480
Rv1816 HTH-type transcriptional regulator 482 482 ctx cooccurence:482

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
  • Foldseek best: 6rf0-assembly1_C Crystal structure of the light-driven sodium pump KR2 in the pe (prob 0.20, E=1e+00, TM=0.32)
  • (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_216264.1)
  • 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 2ERCX
  • Curated reference: UniProt P72005 (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 89.3, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 24 functional partner(s); context anchor Rv0180c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1748|
MPGGVCSGRPWGRPWWHPGLVGLLIRLAELLVVMLPLIGVLYVGIKALSSFTRRLGEASGDLASDSPAMPRPTTVENDAARWRAITRAVEAHERTDARWLEYELDAAKLLDFPVMTDMRDPLTTAFHKAKLQADFHKPLRAEDLLDDPDAAGHYLDAVRDYVTAFDTAEAEAMRRRRTGFSREEQQRLARAQSLLRVASDAGATAQERERAYRLARTELDGLIVLPDRTRAGIERGIAGELDD