Rv3524 Family assigned · medium auto-curated

H37Rv Rv3524 · MTBC0 mtbc0_003740 · 343 aa · 3984432–3985463 (+) · RefSeq NP_218041.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane protein
MTBC0 PGAP re-annotationNHL repeat-containing protein
Revised (this work)NHL repeat-containing protein. Pfam: NHL (PF01436.28).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt I6X7J6 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable conserved membrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionNHL repeat
Orthologous groupCOG3391

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 0.071 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 1 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
NHLPF01436.28 3.3e-06272–298 NHL repeat

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

Closest characterised functional partner: PE_PGRS23 (PE-PGRS family protein PE_PGRS23), medium confidence from genomic context alone (score 690 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1243c PE_PGRS23 PE-PGRS family protein PE_PGRS23 690 690 ctx cooccurence:649
Rv2383c mbtB phenyloxazoline synthase 668 668 coexpression:657
Rv2194 qcrC ubiquinol-cytochrome C reductase cytochrome subunit C 672 652 experimental:622
Rv3523 ltp3 lipid carrier protein 638 637 ctx neighborhood:636
Rv2853 PE_PGRS48 PE-PGRS family protein PE_PGRS48 612 612 ctx cooccurence:560
Rv0124 PE_PGRS2 PE-PGRS family protein PE_PGRS2 606 607 ctx cooccurence:554
Rv3522 ltp4 lipid transfer protein 601 601 ctx neighborhood:600
Rv3533c PPE62 PPE family protein PPE62 600 601 ctx cooccurence:598
Rv3521 hyp hypothetical protein 570 570 ctx neighborhood:570
Rv1135c PPE16 PPE family protein PPE16 559 560 ctx cooccurence:557
Rv3558 PPE64 PPE family protein PPE64 556 556 ctx cooccurence:554
Rv0755c PPE12 PPE family protein PPE12 540 540 ctx cooccurence:539
Rv3159c PPE53 PPE family protein PPE53 524 524 ctx cooccurence:523
Rv1157c hyp hypothetical protein 523 524 coexpression:421
Rv1918c PPE35 PPE family protein PPE35 521 522 ctx cooccurence:520

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

  • Legacy H37Rv annotation: membrane protein
  • MTBC0 PGAP product: NHL repeat-containing protein
  • Pfam (hmmscan --cut_ga): NHL PF01436.28 (E=3e-06)
  • (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_218041.1)
  • Domains: Pfam-A via hmmscan --cut_ga — NHL (PF01436.28)
  • 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 COG3391
  • Curated reference: UniProt I6X7J6 (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 — 40 functional partner(s); context anchor PE_PGRS23
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003740|Rv3524|
MVKFTPDSQTSVLRAGKCSGTLSPSRSRLQRGSWPVDSERRRYGWPRNRRTLAITGAAVVVVVTLAAIGYLIFEPKISGSSTSRQAASPTTPSPPSQVVVPIDLWNPDGVTVDLADAVYVADSGHKRLLKLPAGSNTPTTLPFTDTIGPGGVAVNSNRDVYVIDEDSHHVLKLAAGIEPPVELPFGSLGDAHGLAVDRSDSVYVVDYDNAKVLKLPPGADTPTELPFVGLDHPYDVAVDGAGTVYVTDSGHNRVVALTAGSATPVHLPFADLSFPAGVTVDRDDSVYVADLNNNRVLKLAAGSNAQSQLPFTGLFSPTDVAVDNDGAVYVIDFYNRMLKLPTA