Rv2566 Family assigned · medium auto-curated

H37Rv Rv2566 · MTBC0 - · 1140 aa · 2886373–2889795 (+) · RefSeq NP_217082.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Contains Bact_transglu_N (PF08379.16), Transglut_core (PF01841.26), DUF2126 (PF09899.15) domain(s); putative function inferred from the domain architecture.

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 Q50732 TrEMBL · unreviewed · Evidence at protein level
UniProt nameLong conserved protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category E Amino acid transport and metabolism
eggNOG descriptiontransglutaminase
Orthologous groupCOG1305

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 0.898 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 10 synonymous, 24 missense, 1 nonsense, 3 frameshift
Disruption 4 distinct premature-stop/frameshift site(s); most common in 9.67% of strains (14039) · convergent

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
Bact_transglu_NPF08379.16 1.1e-2233–109 Bacterial transglutaminase-like N-terminal region
Transglut_corePF01841.26 8.2e-16166–284 Transglutaminase-like superfamily
DUF2126PF09899.15 0.0e+00314–1133 Putative amidoligase enzyme (DUF2126)

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

Closest characterised functional partner: Rv2565 (NTE family protein), high confidence from genomic context alone (score 773 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2567 hyp hypothetical protein 979 977 ctx neighborhood:892 cooccurence:767
Rv2411c hyp hypothetical protein 852 847 ctx neighborhood:526 cooccurence:660
Rv2568c hyp hypothetical protein 846 846 ctx neighborhood:544 cooccurence:675
Rv2565 NTE family protein 773 773 ctx neighborhood:770
Rv2410c hyp hypothetical protein 772 763 ctx neighborhood:526 cooccurence:501
Rv2409c hyp hypothetical protein 676 677 ctx cooccurence:629
Rv1673c hyp hypothetical protein 658 658 ctx cooccurence:610
Rv2560 hyp hypothetical protein 610 610 ctx neighborhood:609
Rv2559c hyp hypothetical protein 600 600 ctx neighborhood:599
Rv2572c aspS aspartate--tRNA ligase 544 544 ctx neighborhood:544
Rv2569c hyp hypothetical protein 504 505
Rv2564 glnQ glutamine ABC transporter ATP-binding protein 438 438 ctx neighborhood:437
Rv2563 glutamine ABC transporter permease 425 425 ctx neighborhood:423
Rv3163c hyp hypothetical protein 406 396
Rv2703 sigA RNA polymerase sigma factor SigA 459 71 textmining:442

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): Bact_transglu_N PF08379.16 (E=1e-22), Transglut_core PF01841.26 (E=8e-16), DUF2126 PF09899.15 (E=0e+00)
  • (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_217082.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Bact_transglu_N (PF08379.16), Transglut_core (PF01841.26), DUF2126 (PF09899.15)
  • 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 COG1305
  • Curated reference: UniProt Q50732 (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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 25 functional partner(s); context anchor Rv2565
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2566|
MPLRPTQVSGTGRTRCAGRSGVISSAAMSIKVALEHRTSYTFDRLVRVYPHIVRLRPAPHSRTSIEAYSLRIEPADHFINWQQDALGNFLARLVFPNPMRQLRITVGLIADLKVINPFDFFIEDWAEIWPCAGMAYPKALADDLRPYLRPVDEDGDGSGPGELTQAWVRNFTVPDGTRTIDFLVALNRAINADVGYCVRMEPGVQTPDFTLRTGVGSCRDSAWLLVSILRQFGLAARFVSGYLVQLASDIEALDGPSGPAADFTDLHAWAEAYIPGAGWIGLDPTSGLLAGEGHIPLAATPHPASAAPISGGTDVCDTVLEFSNTVTRVHEDPRVTLPYTDESWKTICEVGQRVDERLAAADVRLTVGGEPTFVSVDNQVAEEWRTAADGPHKRERASDLAARLKAVWAPQGLIHRGQGRWYPGEPLPRWQIALYWRTDGRPLWTNDALLADPWGAPPADPVDDDAAYRVLAGIADGLGLPISQVRPAYEDPLSRLAAAVRMPAGDPVESGDDLGCDTNPDTPTGRAALLARLDEAITSPAAYVLPLHRRDDGQGWASANWRLRRGRIVLLEGDSPAGLRLPLDSISWRPPRASFDADPVAVRSTLPAELHTDRAVVEDPETAPTTALVAEVRGGLVHIFLPPTDALEHFIDLVARVEAAATTANCPVVIEGYGPPPDPRLTSTTITPDPGVIEVNIAPTASFAEQRQQLETLYQQARLARLTTEAFDVDGTHGGTGGGNHITLGGVTPADSPLLRRPDLLVSLLTYWQRHPSLSYLFAGRFVGTTSQAPRVDEGRAEALYELEIAFAEILRLSPSSGGGRPQPWVTDRALRHLLTDITGNTHRAEFCIDKLYSPDSARGRLGLLELRGFEMPPHLHMAMVQSLLVRSLVAWFWDQPLRAPLIRHGANLHGRYLLPHFLIHDIADVAADLRAHGIAFETSWLDPFTEFRFPRIGTAVFDGIEIELRGAIEPWHTLGEEATAAGTARYVDSSVERIQVRIIGADRHRYVVTCNGYPMPLLATDNPDIHVGGVRFKAWQPPSALHPTITVDGPLRFELIDIATATSCGGCTYHVAHPGGRAYDEPPVNAVEAEARRARRFEATGFTPGKLDLSDIREKQARISTDIGAPGILDLRRVRTVQQ