Rv3635 Family assigned · medium

H37Rv Rv3635 · MTBC0 mtbc0_003852 · 591 aa · 4097338–4099113 (+) · RefSeq NP_218152.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Apolipoprotein-N-acyltransferase-family membrane enzyme (eggNOG COG0815, cell-envelope COG category M): transfers a fatty-acyl group onto membrane lipoproteins (lipoprotein N-acylation / maturation). RefSeq leaves it a 'conserved transmembrane protein'. Family/activity-level; not asserted as the sole M. tuberculosis Lnt.

Curated reference (UniProt)

UniProt I6Y460 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable conserved transmembrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
eggNOG descriptionTransfers the fatty acyl group on membrane lipoproteins
Orthologous groupCOG0815

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 0.322 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 5 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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

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

Closest characterised functional partner: galE1 (UDP-glucose 4-epimerase), high confidence from genomic context alone (score 795 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3634c galE1 UDP-glucose 4-epimerase 796 795 ctx neighborhood:790
Rv0227c membrane protein 731 732 ctx cooccurence:715
Rv0226c transmembrane protein 730 730 ctx cooccurence:687
Rv1476 membrane protein 715 716 ctx cooccurence:715
Rv3035 hyp hypothetical protein 717 707 ctx cooccurence:704
Rv3346c transmembrane protein 704 705 ctx cooccurence:703
Rv2673 aftC alpha-(1->3)-arabinofuranosyltransferase 699 699 ctx cooccurence:695
Rv3802c membrane protein 686 686 ctx cooccurence:686
Rv3527 hyp hypothetical protein 668 668 ctx cooccurence:668
Rv1254 acyltransferase 655 640 ctx cooccurence:627
Rv3244c lpqB lipoprotein LpqB 626 626 ctx cooccurence:618
Rv0224c methyltransferase 613 614 ctx cooccurence:607
Rv0466 hyp hypothetical protein 594 594 ctx cooccurence:593
Rv1275 lprC lipoprotein LprC 593 594 ctx cooccurence:591
Rv0479c membrane protein 582 582 ctx cooccurence:582

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

  • eggNOG COG0815 = apolipoprotein N-acyltransferase (transfers fatty-acyl onto membrane lipoprotein)
  • Integral membrane (DeepTMHMM, phase8)
  • eggNOG-mapper orthology (COG functional assignment, under-propagated by the auto-curation). A family/activity-level assignment from orthology, not a substrate demonstrated in M. tuberculosis.

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_218152.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 COG0815
  • Curated reference: UniProt I6Y460 (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 — 56 functional partner(s); context anchor galE1
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003852|Rv3635|
MPAPRMPRVALVAVLLITVQLVVRVVLAFGGYFYWDDLILVGRAGTGGLLSPSYLFDDHDGHVMPGAFLVAGAIIRVAPLVWTGPAISLVVLQLLESLALLRALYVISSWRPVLLIPLTFALFTPLAVPGFAWWAAALNSLPMLAALAWVCADAILLVRTGNHRYAVTGVLVYLGGLLFFEKAAVIPFVSFAVAALQCHVRGDRSALATVWRAGVRLWTPSLALTVGWVALYLAVVDQRRWSSDLSMTWDLLCRSVTHGIVPALAGGPWDWARWAPASPWATPPAVVMVLGWLVLIAVLALSLVRKRRIGPVWLTAAGYAVACQVPIFLMRSSPFTALELAQTLRYFPDLVVVLALLAAVALQAPNRAGTRWLDASPARAVATVASAVLFLTSSLYSTATFLASWRDNPTEGYLKNAQASLAAAASGAPLLDQEVDPLVLQRVAWPENLASHMFALLRVRPEFATTTTQLRMFTSTGRLVDAKVTWVRTIIAGPVPQCGYFVQPDRPERLILDGPLLPGDWTVELNYLANSDGSMALALSDGPERKVPVHPGLNRVYARLPGAGDAITVRANTTALSLCIGAAPVGFLAPA