Rv3819 Still unknown · low auto-curated

H37Rv Rv3819 · MTBC0 mtbc0_004048 · 111 aa · 4308106–4308441 (+) · RefSeq NP_218336.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 3dcx-assembly1_A Crystal structure of a duf1696 family protein with a (prob 0.99, TM 0.50).

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

Curated reference (UniProt)

UniProt O07804 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 grouparCOG09609

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 0.171 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 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 65.1 (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
3dcx-assembly1_A 0.99 0.50 2.7e-03 sig 3dcx-assembly1_A Crystal structure of a duf1696 family protein with a pleckstrin-homology domain (shew_0819) from shewanella loihica pv-4 at 2.00 A resolution
3hsa-assembly1_B 0.96 0.50 2.3e-02 3hsa-assembly1_B Crystal structure of pleckstrin homology domain (YP_926556.1) from SHEWANELLA AMAZONENSIS SB2B at 1.99 A resolution
5yqr-assembly1_A 0.82 0.56 2.0e-01 5yqr-assembly1_A Crystal structure of the PH-like domain of Lam6
2cay-assembly1_A 0.63 0.51 2.3e-01 2cay-assembly1_A Vps36 N-terminal PH domain
2d4q-assembly1_B 0.51 0.48 3.0e-01 2d4q-assembly1_B Crystal structure of the Sec-PH domain of the human neurofibromatosis type 1 protein
8e20-assembly1_A 0.51 0.46 2.0e-01 8e20-assembly1_A Cryo-EM structure of the full-length human NF1 dimer
7pgu-assembly1_N 0.51 0.47 2.6e-01 7pgu-assembly1_N Autoinhibited structure of human neurofibromin isoform 2 stabilized by Zinc.
3p7z-assembly1_B 0.47 0.49 3.8e-01 3p7z-assembly1_B Crystal structure of the Neurofibromin Sec14-PH module containing the patient derived mutation I1584V

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

Closest characterised functional partner: Rv3817 (phosphotransferase), medium confidence from genomic context alone (score 671 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3818 hyp hypothetical protein 970 970 ctx neighborhood:881 coexpression:761
Rv3817 phosphotransferase 671 671 ctx neighborhood:671
Rv3815c acyltransferase 513 513 ctx neighborhood:513
Rv3816c acyltransferase 501 501 ctx neighborhood:501
Rv3814c acyltransferase 495 495 ctx neighborhood:495
Rv3813c hyp hypothetical protein 428 429 ctx neighborhood:425

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: 3dcx-assembly1_A Crystal structure of a duf1696 family protein with a pleckstrin (prob 0.99, E=3e-03, TM=0.50)
  • (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_218336.1)
  • 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 arCOG09609
  • Curated reference: UniProt O07804 (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 65.1, low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 6 functional partner(s); context anchor Rv3817
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_004048|Rv3819|
MMQFYDDGVVQLDRAALTLRRYHFPSGTAKVIPLDQIRGYQAESLGFLMARFNIWGRPDLRRWLPLDVYRPLKSTLVTLDVPGMRPKPACTPTRPKEFIALLDELLALHRT