Rv2390c Family assigned · low auto-curated · to review

H37Rv Rv2390c · MTBC0 mtbc0_002543 · 185 aa · 2707902–2708459 (-) · RefSeq NP_216906.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)No Pfam domain above threshold; Foldseek indicates a fold similar to 8rta-assembly1_G Arches-protomer complex full-length structure (TrwJ/VirB8) from (prob 1.00, TM 0.65). Structure-based, putative.

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).

Curated reference (UniProt)

UniProt P71754 TrEMBL · unreviewed · Predicted
UniProt nameMce associated membrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2E5H4
KEGG orthology K18481
KEGG modules M00670

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 0.491 · purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 2 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 1.05% of strains (1526) · 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 94.8 (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
8rta-assembly1_G 1.00 0.65 1.2e-04 sig 8rta-assembly1_G Arches-protomer complex full-length structure (TrwJ/VirB8) from the fully-assembled R388 type IV secretion system determined by cryo-EM.
7q1v-assembly1_D 1.00 0.64 1.9e-04 sig 7q1v-assembly1_D Arches protomer (trimer of TrwG/VirB8peri) structure from the fully-assembled R388 type IV secretion system determined by cryo-EM.
4l8p-assembly1_A 1.00 0.65 2.3e-04 sig 4l8p-assembly1_A Crystal structure of a bile-acid 7-alpha dehydratase (CLOHIR_00079) from Clostridium hiranonis DSM 13275 at 1.60 A resolution
7o41-assembly1_E-5 1.00 0.50 3.8e-05 sig 7o41-assembly1_E-5 Hexameric composite model of the Inner Membrane Complex (IMC) with the Arches from the fully-assembled R388 type IV secretion system determined by cryo-EM.
3b8l-assembly2_F 1.00 0.66 9.4e-04 sig 3b8l-assembly2_F CRYSTAL STRUCTURE OF A PUTATIVE AROMATIC RING HYDROXYLASE (SARO_3538) FROM NOVOSPHINGOBIUM AROMATICIVORANS DSM AT 1.75 A RESOLUTION
8rtd-assembly1_S 1.00 0.48 9.2e-05 sig 8rtd-assembly1_S Stalk-Arches-IMC structure from the fully-assembled R388 type IV secretion system determined by cryo-EM.
4akz-assembly1_A 1.00 0.70 2.2e-03 sig 4akz-assembly1_A CRYSTAL STRUCTURE OF VIRB8 FROM BRUCELLA SUIS
6of8-assembly1_B-2 1.00 0.64 4.1e-04 sig 6of8-assembly1_B-2 Structure of Thr354Asn, Glu355Gln, Thr412Asn, Ile414Met, Ile464His, and Phe467Met mutant human CamKII-alpha hub domain

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

Closest characterised functional partner: rpfD (resuscitation-promoting factor RpfD), high confidence from genomic context alone (score 895 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2389c rpfD resuscitation-promoting factor RpfD 922 895 ctx neighborhood:882
Rv3492c Mce associated protein 753 754 ctx cooccurence:752
Rv1527c pks5 polyketide synthase 763 735 experimental:470 database:508
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 763 735 experimental:470 database:508
Rv2048c pks12 polyketide synthase 762 735 experimental:470 database:508
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 762 734 experimental:470 database:508
Rv2940c mas multifunctional mycocerosic acid synthase 762 734 experimental:470 database:508
Rv1691 hyp hypothetical protein 742 731 experimental:417 database:540
Rv2267c stf3 hyp hypothetical protein 740 730 experimental:417 database:540
Rv3529c hyp hypothetical protein 740 729 experimental:417 database:540
Rv1663 pks17 polyketide synthase 739 729 experimental:458 database:508
Rv1334 mec [CysO 729 719 experimental:404 database:546
Rv1277 hyp hypothetical protein 704 705 experimental:438 database:493
Rv3696c glpK glycerol kinase 708 695 database:502
Rv1389 gmk guanylate kinase 701 689 experimental:411 database:491

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: hypothetical protein
  • MTBC0 PGAP product: hypothetical protein
  • Foldseek best: 8rta-assembly1_G Arches-protomer complex full-length structure (TrwJ/VirB8) from (prob 1.00, E=1e-04, TM=0.65)
  • (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_216906.1)
  • 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 2E5H4
  • Curated reference: UniProt P71754 (TrEMBL, unreviewed; Predicted)
  • 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 94.8, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 278 functional partner(s); context anchor rpfD
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002543|Rv2390c|
MAIFGRGHGASEPGGTGEPAETPGRGRLTRSVIGWVGAVAVVVSLAGSGWCGWVLFEKHQTDVAAGQALQAARSYVVKLATMDCERIDHNMRDILEGSTGEFKDKYGKSSAHLRQLLADNRVATHGTVVAASVKSATTNKVVVLMFIDQSVSNRNSPTPQIDRSRIKVIMDKVNGRWLASKVELL