Rv0336 Still unknown · low auto-curated

H37Rv Rv0336 · MTBC0 - · 503 aa · 400192–401703 (+) · RefSeq NP_214850.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF222. Function unknown.

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 O33266 TrEMBL · unreviewed · Predicted
UniProt nameConserved 13E12 repeat family protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category V Defense mechanisms
eggNOG descriptionHNH endonuclease
Orthologous groupCOG1403

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 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)

PfamAccessioni-EvalueResiduesDescription
DUF222PF02720.23 1.9e-9935–339 Domain of unknown function (DUF222)

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

Closest characterised functional partner: eccD5 (ESX-5 type VII secretion system protein EccD), medium confidence from genomic context alone (score 603 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0515 hyp hypothetical protein 861 861 coexpression:860
Rv1765c hyp hypothetical protein 819 820 ctx cooccurence:765
Rv2015c hyp hypothetical protein 815 816 ctx cooccurence:766
Rv1702c hyp hypothetical protein 958 802 ctx cooccurence:747 textmining:801
Rv0606 Possible transposase (fragment); Rv0606, (MTCY19H5.16c), len: 247 aa. Possible truncated transposase for IS_1536 element, highly similar to 759 760 coexpression:729
Rv1148c hyp hypothetical protein 949 749 ctx cooccurence:734 textmining:808
Rv1128c hyp hypothetical protein 949 749 ctx cooccurence:747 textmining:808
Rv2791c tnpB transposase 748 748 coexpression:748
Rv1945 hyp hypothetical protein 948 744 ctx cooccurence:736 textmining:808
Rv0094c hyp hypothetical protein 742 742 ctx cooccurence:730
Rv3467 hyp hypothetical protein 741 742 ctx cooccurence:730
Rv2885c transposase 731 731 coexpression:731
Rv1587c hyp hypothetical protein 726 726 ctx cooccurence:719
Rv0756c hyp hypothetical protein 630 630 ctx cooccurence:626
Rv1795 eccD5 ESX-5 type VII secretion system protein EccD 602 603 ctx cooccurence:585

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): DUF222 PF02720.23 (E=2e-99)
  • (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_214850.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF222 (PF02720.23)
  • 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 COG1403
  • Curated reference: UniProt O33266 (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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 45 functional partner(s); context anchor eccD5
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0336|
MPSPEAIAHFDERFECHAPRTTRVSAAFIDRICSATRAENRAAAAQLVALGELFAYRWSRCGGREEWVMDTMAAVAAEVAAALRISQGLAASRLRYARAMRERLPKTAEVFSAGDIGYLMFATIVYRTDLIVDPDVLAAVDAQLAANVARWPSMTKARLAGQVDKIVARADADAVRRRKEYQAQRQFWVGESQDGVCQIGGSLLAVDAHALDARLSALAGTVCEHDPRSREQRRADALGALAGGADRLGCGCGRADCAAGKRPAAPPVVIHLIAEAATINGTGSAPASQMNADGLITAELVAELAKTATLVPLVHPGDAPPEPGYAPSKALADFVRCRDLTCRWPGCDEPATNCDLDHTIPYAAGGPTHASNLKCYCRTHHLVKTFWGWRDQQLPDGTLILTSPSGHTYVSTPGSALLFPSLCHFSGGIPAPEADPPYDHCDQRTAMMPKRRRTRAQDRAYRIATERRQNHAARQRAQVLTQTAAATDTHGPPPDPNDDPPPF