Rv1616 Family assigned · low

H37Rv Rv1616 · MTBC0 mtbc0_001723 · 132 aa · 1827647–1828045 (+) · RefSeq NP_216132.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF2752 domain-containing protein
Revised (this work)Polytopic integral membrane protein with 3 predicted transmembrane helices (DeepTMHMM). RefSeq leaves it 'hypothetical protein'. A topological feature consistent with a membrane transporter/permease or membrane-embedded enzyme; the transported substrate and molecular function are undetermined.

Curated reference (UniProt)

UniProt O06133 TrEMBL · unreviewed · Predicted
UniProt nameConserved membrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein of unknown function (DUF2752)
Orthologous group2EGD2

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 1.095 · 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)

PfamAccessioni-EvalueResiduesDescription
DUF2752PF10825.14 9.9e-1941–88 Protein of unknown function (DUF2752)

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

Closest characterised functional partner: Rv1615 (membrane protein), high confidence from genomic context alone (score 882 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv1615 membrane protein 882 882 ctx neighborhood:882
Rv1618 tesB1 acyl-CoA thioesterase II 770 770 ctx neighborhood:768
Rv1617 pykA pyruvate kinase 766 766 ctx neighborhood:765
Rv1619 hyp hypothetical protein 587 586 ctx neighborhood:524
Rv3689 transmembrane protein 689 561 ctx cooccurence:557
Rv1611 trpC indole-3-glycerol phosphate synthase 552 548 ctx neighborhood:544
Rv1612 trpB tryptophan synthase subunit beta 547 548 ctx neighborhood:544
Rv1613 trpA tryptophan synthase subunit alpha 547 548 ctx neighborhood:544
Rv3859c gltB glutamate synthase large subunit 546 547 ctx neighborhood:544
Rv1610 membrane protein 597 424 ctx neighborhood:415
Rv0260c transcriptional regulator 452 227
Rv2571c transmembrane protein 407 160

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

  • DeepTMHMM: 3 transmembrane helices (type TM)
  • Integral membrane topology (localisation feature, not a function)
  • DeepTMHMM topology prediction (project 'Still unknown gene function', phase8, 2026-06-10). A topological feature, not a demonstrated molecular function.

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_216132.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF2752 (PF10825.14)
  • 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 2EGD2
  • Curated reference: UniProt O06133 (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 93.1, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 12 functional partner(s); context anchor Rv1615
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001723|Rv1616|
MEASGRQRRYAAAGSVVLLAGALGYIGLVDPHNSNSLYPPCLFKLLTGWNCPACGGLRMIHDLLHGELAASINDNVFLLVGVPVLASWVLLRRRHGDLALPIPVMIAVAVAVIAWTVLRNLPGFPLVPTISG