Rv1269c Family assigned · low

H37Rv Rv1269c · MTBC0 mtbc0_001359 · 124 aa · 1427562–1427936 (-) · RefSeq NP_215785.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF4189 domain-containing protein
Revised (this work)DUF4189; same fold as Rv1813c (PDB 7NHZ); secreted DUF4189-family protein.

Curated reference (UniProt)

UniProt P9WM45 SwissProt · reviewed · Evidence at protein level
UniProt nameProtein Rv1269c

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionDomain of unknown function (DUF4189)
Orthologous group2DE1B
Gene Ontology (7) GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0030312, GO:0044464, GO:0071944

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) pseudogene candidate

pN/pS n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 5 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 14.02% of strains (20353) · clonal

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
DUF4189PF13827.12 1.7e-1839–115 Domain of unknown function (DUF4189)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 94.4 (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
7nhz-assembly1_A 1.00 0.70 6.5e-08 sig 7nhz-assembly1_A NMR structure of Rv1813c from Mycobacterium tuberculosis
8wr4-assembly1_B 0.23 0.46 6.3e-01 8wr4-assembly1_B Structure of CbCas9-PcrIIC1 complex bound to 62-bp DNA substrate (non-targeting complex)
2le2-assembly1_A 0.03 0.42 9.6e+00 2le2-assembly1_A Novel dimeric structure of phage phi29-encoded protein p56: Insights into Uracil-DNA glycosylase inhibition
1wj4-assembly1_A 0.01 0.19 8.0e+00 1wj4-assembly1_A Solution structure of the UBX domain of KIAA0794 protein

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

Closest characterised functional partner: lprA (lipoprotein LprA), medium confidence from genomic context alone (score 669 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1270c lprA lipoprotein LprA 668 669 ctx neighborhood:669
Rv1268c hyp hypothetical protein 491 491 ctx neighborhood:491
Rv1747 ABC transporter ATP-binding protein/permease 457 385
Rv0450c mmpL4 transmembrane transport protein MmpL4 571 153 textmining:515
Rv3283 sseA thiosulfate sulfurtransferase SseA 811 51 textmining:809
Rv3005c hyp hypothetical protein 651 41 textmining:651

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: DUF4189 domain-containing protein
  • Pfam: DUF4189 PF13827.12
  • Foldseek best: 7nhz-assembly1_A NMR structure of Rv1813c from Mycobacterium tuberculosis (prob 1.00, E=6e-08, TM=0.70)
  • (structure-only promotion reviewed by hand, 2026-06-01)

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_215785.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF4189 (PF13827.12)
  • 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 2DE1B
  • Curated reference: UniProt P9WM45 (SwissProt, reviewed; 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 94.4, very high)
  • 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 lprA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001359|Rv1269c|
MTTMITLRRRFAVAVAGVATAAATTVTLAPAPANAADVYGAIAYSGNGSWGRSWDYPTRAAAEATAVKSCGYSDCKVLTSFTACGAVAANDRAYQGGVGPTLAAAMKDALTKLGGGYIDTWACN