Rv3235 Still unknown · low auto-curated

H37Rv Rv3235 · MTBC0 - · 213 aa · 3611300–3611941 (+) · RefSeq NP_217752.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF6459. Function unknown. Foldseek best (non-significant) hit: 8j07-assembly1_k1 96nm repeat of human respiratory doublet microtubule (prob 0.01, TM 0.10).

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

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 O05880 TrEMBL · unreviewed · Predicted
UniProt nameHypothetical alanine arginine proline rich protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2DPN9

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 0.767 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 2 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
DUF6459PF20060.5 1.3e-11105–213 Family of unknown function (DUF6459)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 87.3 (confident). 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
8j07-assembly1_k1 0.01 0.10 1.9e+00 8j07-assembly1_k1 96nm repeat of human respiratory doublet microtubule and associated axonemal complexes
8j07-assembly1_m2 0.01 0.10 3.0e+00 8j07-assembly1_m2 96nm repeat of human respiratory doublet microtubule and associated axonemal complexes

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

Closest characterised functional partner: Rv3233c (Rv3233c, (MTCY20B11.08c), len: 196 aa. Possible triacylglycerol synthase (See Daniel et al., 2004), similar to C-terminus of Q9RIU8|SCM11.13), medium confidence from genomic context alone (score 598 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3231c hyp hypothetical protein 613 614 ctx neighborhood:595
Rv3233c Rv3233c, (MTCY20B11.08c), len: 196 aa. Possible triacylglycerol synthase (See Daniel et al., 2004), similar to C-terminus of Q9RIU8|SCM11.13 597 598 ctx neighborhood:594
Rv3234c tgs3 diacyglycerol O-acyltransferase 597 598 ctx neighborhood:594
Rv3232c ppk2 polyphosphate kinase 501 501 ctx neighborhood:498
Rv3230c stearoyl-CoA 9-desaturase electron transfer protein 406 406

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
  • Pfam (hmmscan --cut_ga): DUF6459 PF20060.5 (E=1e-11)
  • Foldseek best: 8j07-assembly1_k1 96nm repeat of human respiratory doublet microtubule and assoc (prob 0.01, E=2e+00, TM=0.10)
  • (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_217752.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF6459 (PF20060.5)
  • 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 2DPN9
  • Curated reference: UniProt O05880 (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 87.3, confident)
  • 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 Rv3233c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3235|
MMASNQTAAQHSSATLQQAPRSIDDAGGCPLTISPIANSPGDTFAVTPVVEYEPPPRNIPPCGQSSHAARRPHTPQLARRQPIRPSGRAPAAVTSTAKSPRLRQAGTFADAALRRVLEVIDRRRPVGQLRPLLAPGLVDSVLAVSRTAAGHQQGAAMLRRIRLTPAGPDTADTAAEVFGTYSRGDRIHAIACRVEQRPAGNETRWLMVALHIG