Rv0210 Still unknown · low

H37Rv Rv0210 · MTBC0 mtbc0_000224 · 492 aa · 250472–251950 (+) · RefSeq NP_214724.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Conserved hypothetical protein; no Pfam domain above threshold. Foldseek gives only a low-TM (0.21) partial match to Mtb IniA, not conclusive. Uncharacterised.

Curated reference (UniProt)

UniProt P96392 TrEMBL · unreviewed · Predicted
UniProt nameTransmembrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionAn essential GTPase that binds both GDP and GTP, with rapid nucleotide exchange. Plays a role in 16S rRNA processing and 30S ribosomal subunit biogenesis and possibly also in cell cycle regulation and energy metabolism
Orthologous groupCOG1159

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 1.182 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 8 missense, 1 nonsense, 3 frameshift
Disruption 4 distinct premature-stop/frameshift site(s); most common in 0.45% of strains (658) · convergent

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 93.2 (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
6j73-assembly2_B 1.00 0.21 2.4e-08 sig 6j73-assembly2_B Crystal structure of IniA from Mycobacterium smegmatis
6j72-assembly1_A 1.00 0.20 2.7e-07 sig 6j72-assembly1_A Crystal structure of IniA from Mycobacterium smegmatis with GTP bound
6j73-assembly1_A 1.00 0.20 2.2e-07 sig 6j73-assembly1_A Crystal structure of IniA from Mycobacterium smegmatis
1mky-assembly1_A 1.00 0.46 4.4e-03 sig 1mky-assembly1_A Structural Analysis of the Domain Interactions in Der, a Switch Protein Containing Two GTPase Domains
4aur-assembly1_A 1.00 0.22 2.1e-05 sig 4aur-assembly1_A LeoA bacterial dynamin GTPase from ETEC
4dcu-assembly1_A 0.97 0.40 5.0e-02 4dcu-assembly1_A Crystal Structure of B. subtilis EngA in complex with GDP
4tql-assembly2_B 0.54 0.32 4.3e-01 4tql-assembly2_B Computationally designed three helix bundle
3zx6-assembly1_A 0.54 0.29 2.5e-01 3zx6-assembly1_A Structure of Hamp(AF1503)-Tsr fusion - Hamp (A291V) mutant

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

Closest characterised functional partner: trmB (tRNA (guanine-N(7)-)-methyltransferase), high confidence from genomic context alone (score 801 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0209 hyp hypothetical protein 976 976 ctx neighborhood:882 coexpression:806
Rv0208c trmB tRNA (guanine-N(7)-)-methyltransferase 801 801 ctx neighborhood:775
Rv0207c hyp hypothetical protein 775 775 ctx neighborhood:775
Rv2474c hyp hypothetical protein 750 750 ctx cooccurence:750
Rv3413c rsdA anti-sigma-D factor RsdA 746 746 ctx cooccurence:746
Rv2687c antibiotic ABC transporter permease 739 739 ctx cooccurence:739
Rv2686c antibiotic ABC transporter permease 734 735 ctx cooccurence:734
Rv1978 hyp hypothetical protein 732 733 ctx cooccurence:732
Rv0206c mmpL3 transmembrane transport protein MmpL3 722 722 ctx neighborhood:721
Rv1182 papA3 acyltransferase papA3 716 717 ctx cooccurence:715
Rv0479c membrane protein 703 704 ctx cooccurence:703
Rv3824c papA1 acyltransferase 686 686 ctx cooccurence:686
Rv2743c hyp hypothetical protein 673 674 ctx cooccurence:672
Rv3405c HTH-type transcriptional regulator 666 667 ctx cooccurence:663
Rv3527 hyp hypothetical protein 652 652 ctx cooccurence:652

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: 'hypothetical protein'
  • Pfam: none above threshold
  • Foldseek on the ESMFold model: only a partial, low-TM match -- inconclusive

ESM Atlas signal (exploratory)

Ancestral protein hash 2615589eb7f7c6d74965a0ad7a605c15 · 10 ESM-space neighbours (max similarity 0.923). SAE features are orienting indices, not validated domains.

#IndexActivationInterpretation
16012 1.42 Post-GTPase helical scaffolds
211893 1.33 Dynamin helical stalk/paddle
32174 1.29 P-loop GTPase coupling helix
48885 1.17 Coiled-coil machine head domains
511953 1.16 GTPase-flanking coiled-coil scaffolds
65138 1.16 Canonical P-loop GTPase G-domain
74409 1.13 G-domain Walker A P-loop
81965 1.09 Transmembrane helical hairpins and anchors

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_214724.1)
  • 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 COG1159
  • Curated reference: UniProt P96392 (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 93.2, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 80 functional partner(s); context anchor trmB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000224|Rv0210|
MIRAASDDPAGVDELVAAIAPGLAGLGLPVINRREVVLVTGPWLAGVSGVRAALAERLPQRRFVETAELGPGDAPVAVVFVVSAATALTESDCVLLDTAAEHTDAVVAVVSKIDVHRGWRDVLTSNRDRLAARASRYARVPWVGAAAAPELGEPYLDDLVAAIQKQLADPAVARRNMLRAWESRLLMVARRFDGDAQSAGRRARVDALRQQRRTVLRQGRQSKSEHTIALRAQIQHARVKLSYFARNRCSLLRVELQEHVAGLSRKDIARFAAYTRGRVQEVVAEVGEGAVAHLADVAQLLGVPVQPPVLENLPAVLPTVVAPPLTSRRLEIRLTTLLGAGFGLGIALTLSRLVAGLTPGLAASGMVAGVAIGLAVTAWVVNARALLHDRVVVDRWTGEVTASLRSVVEQLVATRVVAVETLLSTAISERDDAENARVADQVSIIDGELREHAVAAARAAALRDREMPAVRAALEAVRAELGEPGTPTTGLF