Rv0030 Still unknown · low

H37Rv Rv0030 · MTBC0 mtbc0_000036 · 109 aa · 33210–33539 (+) · RefSeq NP_214544.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF2710 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF2710 domain-containing. Function unknown. Foldseek yields only weak, near-threshold matches to uncharacterised proteins (e.g. H. pylori HP0035), with no functional assignment.

Curated reference (UniProt)

UniProt P9WM95 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv0030

UniProt still lists this protein as Uncharacterized protein Rv0030; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein of unknown function (DUF2710)
Orthologous group2AVE0

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 1.176 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 7 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)

PfamAccessioni-EvalueResiduesDescription
DUF2710PF10921.15 2.8e-516–106 Protein of unknown function (DUF2710)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 64.7 (low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.

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
3f42-assembly1_B-2 1.00 0.70 4.0e-03 sig 3f42-assembly1_B-2 Crystal structure of uncharacterized protein HP0035 from Helicobacter pylori
7ane-assembly1_an 1.00 0.67 3.5e-03 sig 7ane-assembly1_an Leishmania Major mitochondrial ribosome
3f42-assembly1_A-2 1.00 0.65 4.5e-03 sig 3f42-assembly1_A-2 Crystal structure of uncharacterized protein HP0035 from Helicobacter pylori
1pug-assembly2_D 1.00 0.76 3.8e-02 1pug-assembly2_D Structure of E. coli Ybab
1pug-assembly1_A 1.00 0.73 5.6e-02 1pug-assembly1_A Structure of E. coli Ybab
7pua-assembly1_DK 1.00 0.76 6.7e-02 7pua-assembly1_DK Middle assembly intermediate of the Trypanosoma brucei mitoribosomal small subunit
1j8b-assembly1_A-2 1.00 0.52 1.1e-02 1j8b-assembly1_A-2 Structure of YbaB from Haemophilus influenzae (HI0442), a protein of unknown function
1pug-assembly2_C 1.00 0.67 3.8e-02 1pug-assembly2_C Structure of E. coli Ybab

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

Closest characterised functional partner: Rv0031 (Rv0031, (MTCY10H4.31), len: 70 aa. Possible remnant of a transposase, showing partial similarity to mycobacterial transposases in a short ov), medium confidence from genomic context alone (score 693 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0029 hyp hypothetical protein 798 798 ctx neighborhood:792
Rv0031 Rv0031, (MTCY10H4.31), len: 70 aa. Possible remnant of a transposase, showing partial similarity to mycobacterial transposases in a short ov 693 693 ctx neighborhood:678
Rv3894c eccC2 ESX-2 type VII secretion system protein EccC 550 551 ctx neighborhood:544
Rv0028 hyp hypothetical protein 443 443 ctx neighborhood:439
Rv0027 hyp hypothetical protein 436 436 ctx neighborhood:432

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

  • MTBC0 PGAP product: 'DUF2710 domain-containing protein'
  • Pfam: DUF2710 PF10921 (E=2.8e-51) -- a domain of unknown function
  • Foldseek on the ESMFold model: only weak, near-threshold hits to uncharacterised proteins (HP0035, prob 1.0 but E~4e-3, TM 0.70); inconclusive

ESM Atlas signal (exploratory)

Ancestral protein hash c01c0c8f293e2bde8e36ce6f95f91491 · 1 ESM-space neighbours (max similarity 0.646). SAE features are orienting indices, not validated domains.

#IndexActivationInterpretation
116353 0.61 Acidic catalytic motifs and coiled-coils
214146 0.50 Edge beta-hairpin interaction loops
38624 0.47 Presequence-to-core transition helix
47936 0.47 Cofactor-binding beta-loop patches
514653 0.47 Charged coiled-coil stalk helices
613240 0.46 Amphipathic core helices
7407 0.46 Disordered pre-sequences and tails
812593 0.46 Disordered low-complexity regulatory tails

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_214544.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF2710 (PF10921.15)
  • 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 2AVE0
  • Curated reference: UniProt P9WM95 (SwissProt, reviewed; 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 64.7, low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 5 functional partner(s); context anchor Rv0031
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000036|Rv0030|
MVSGSDSRSEPSQLSDRDLVESVLRDLSEAADKWEALVTQAETVTYSVDLGDVRAVANSDGRLLELTLHPGVMTGYAHGELADRVNLAITALRDEVEAENRARYGGRLQ