Rv1362c Family assigned · low

H37Rv Rv1362c · MTBC0 mtbc0_001464 · 220 aa · 1544650–1545312 (-) · RefSeq NP_215878.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)IcmL/VirB8-like membrane-protein fold. RefSeq leaves it 'membrane protein'. The AlphaFold model superposes on an IcmL-like type-IV-secretion protein (PDB 5cnl; Foldseek prob 1.0, E 1e-4, TM 0.75); its neighbour Rv1363c shares a VirB8-periplasmic-domain fold (7q1v) and the two are mutual STRING partners. A membrane-associated secretion-system-like fold; no classical T4SS is annotated in M. tuberculosis.

Curated reference (UniProt)

UniProt P9WM01 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv1362c

UniProt still lists this protein as Uncharacterized protein Rv1362c; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
eggNOG descriptionHeat shock 70 kDa protein
Orthologous groupCOG0443
KEGG orthology K18481
KEGG modules M00670
Gene Ontology (6) GO:0005575, GO:0005623, GO:0005886, GO:0016020, 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)

pN/pS 0.223 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 4 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: Rv1363c (membrane protein), high confidence from genomic context alone (score 987 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1363c membrane protein 986 987 ctx neighborhood:800 cooccurence:773 coexpression:732
Rv0594 mce2F Mce family protein Mce2F 774 774 ctx cooccurence:765
Rv0172 mce1D Mce family protein Mce1D 772 773 ctx cooccurence:763
Rv0169 mce1A Mce family protein Mce1A 771 771 ctx cooccurence:761
Rv0174 mce1F Mce family protein Mce1F 770 770 ctx cooccurence:761
Rv3499c mce4A Mce family protein Mce4A 765 765 ctx cooccurence:754
Rv3495c lprN Mce family lipoprotein LprN 764 764 ctx cooccurence:753
Rv0591 mce2C Mce family protein Mce2C 762 763 ctx cooccurence:754
Rv0589 mce2A Mce family protein Mce2A 762 762 ctx cooccurence:753
Rv0592 mce2D Mce family protein Mce2D 762 762 ctx cooccurence:753
Rv0173 lprK Mce family lipoprotein LprK 759 759 ctx cooccurence:749
Rv3496c mce4D Mce family protein Mce4D 755 756 ctx cooccurence:744
Rv1972 Mce associated membrane protein 752 753 ctx cooccurence:719
Rv0593 lprL Mce family lipoprotein LprL 749 749 ctx cooccurence:740
Rv3497c mce4C Mce family protein Mce4C 746 747 ctx cooccurence:728

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

  • Foldseek -> IcmL-like T4SS protein (5cnl), prob 1.0, E 1e-4, TM 0.75
  • Paired with Rv1363c (VirB8-like, 7q1v); mutual STRING partners
  • Structural homology: AlphaFold DB model + Foldseek vs PDB (project 'Still unknown gene function', phase5-7, 2026-06-10). A fold-level family assignment, not a demonstrated activity.

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_215878.1)
  • 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 COG0443
  • Curated reference: UniProt P9WM01 (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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 303 functional partner(s); context anchor Rv1363c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001464|Rv1362c|
MTDDVRDVNTETTDATEVAEIDSAAGEAGDSATEAFDTDSATESTAQKGQRHRDLWRMQVTLKPVPVILILLMLISGGATGWLYLEQYRPDQQTDSGAARAAVAAASDGTIALLSYSPDTLDQDFATARSHLAGDFLSYYDQFTQQIVAPAAKQKSLKTTAKVVRAAVSELHPDSAVVLVFVDQSTTSKDSPNPSMAASSVMVTLAKVDGNWLITKFTPV