Rv2618 Family assigned · low auto-curated · to review

H37Rv Rv2618 · MTBC0 - · 225 aa · 2946434–2947111 (+) · RefSeq NP_217134.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)No Pfam domain above threshold; Foldseek indicates a fold similar to 6cmv-assembly3_F Crystal structure of Archaeal Biofilm Regulator (AbfR2) from Su (prob 1.00, TM 0.57). 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).

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 O06195 TrEMBL · unreviewed · Evidence at protein level
UniProt nameTranscriptional regulator

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category K Transcription
eggNOG descriptiontranscriptional regulator
Orthologous groupCOG2345

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 1.104 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 3 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 91.7 (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
6cmv-assembly3_F 1.00 0.57 2.0e-04 sig 6cmv-assembly3_F Crystal structure of Archaeal Biofilm Regulator (AbfR2) from Sulfolobus acidocaldarius
1q1h-assembly1_A 1.00 0.80 1.8e-02 1q1h-assembly1_A An extended winged helix domain in general transcription factor E/IIE alpha
3r0a-assembly1_A 1.00 0.69 5.4e-03 sig 3r0a-assembly1_A Possible transcriptional regulator from Methanosarcina mazei Go1 (gi 21227196)
6pln-assembly2_B 1.00 0.63 3.4e-03 sig 6pln-assembly2_B X-ray crystal structure of Pyrococcus furiosus general transcription factor TFE-alpha
3f21-assembly1_A 1.00 0.72 1.8e-02 3f21-assembly1_A Crystal structure of Zalpha in complex with d(CACGTG)
1ku9-assembly1_B 1.00 0.49 1.5e-03 sig 1ku9-assembly1_B X-ray Structure of a Methanococcus jannaschii DNA-Binding Protein: Implications for Antibiotic Resistance in Staphylococcus aureus
6xjf-assembly3_C 1.00 0.69 2.0e-02 6xjf-assembly3_C X-ray crystal structure of Pyrococcus furiosus general transcription factor TFE-alpha (SeMet labeled protein)
2d1h-assembly1_B 1.00 0.65 3.3e-02 2d1h-assembly1_B Crystal structure of ST1889 protein from thermoacidophilic archaeon Sulfolobus tokodaii

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

Closest characterised functional partner: Rv2617c (transmembrane protein), high confidence from genomic context alone (score 873 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2617c transmembrane protein 873 873 ctx neighborhood:581 cooccurence:706
Rv2428 ahpC alkyl hydroperoxide reductase subunit AhpC 499 500 coexpression:481
Rv2359 zur zinc uptake regulation protein 457 458 coexpression:440
Rv1909c furA ferric uptake regulation protein FurA 456 457 coexpression:439
Rv3887c eccD2 ESX-2 secretion system protein EccD 448 448 ctx cooccurence:448
Rv1156 hyp hypothetical protein 442 442 ctx cooccurence:442
Rv3153 nuoI NADH-quinone oxidoreductase subunit I 438 438 experimental:431
Rv3191c transposase 434 41 textmining:434

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: 6cmv-assembly3_F Crystal structure of Archaeal Biofilm Regulator (AbfR2) from Su (prob 1.00, E=2e-04, TM=0.57)
  • (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_217134.1)
  • 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 COG2345
  • Curated reference: UniProt O06195 (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 91.7, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 8 functional partner(s); context anchor Rv2617c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2618|
MDPVRRQLYQFVCSQSMPVSRDQAADAVGIPRHQAKFHLDRLTAEGLLDTEYARLTGRSGPGAGRTAKLYRRAGRDIALSLPQREYELAGRLMAAAIVLSATTGEPTVEVLNRIAHDYGQAMGAAATTRPPADPAAALELTLDVLRKYGYEPRRPAGPGDDEVELVNCPFHALAREQTELACNMNHALITGVADALAPHSPAVRLAPGPARCCVVLKRCSAHDPE