MTBC Gene Atlas

Rv3435c Family assigned · low

H37Rv Rv3435c · MTBC0 mtbc0_003654 · 284 aa · 3879825–3880679 (-) · RefSeq NP_217952.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationDUF4436 domain-containing protein
Revised (this work)Cell-wall-associated virulence protein, conserved in pathogenic but not non-pathogenic mycobacteria. RefSeq leaves it of unknown function. Heterologous expression shows Rv3435c is a cell-wall-related protein that alters colony morphology and fatty-acid levels, enhances stress resistance, inhibits inflammatory-cytokine secretion and host-cell apoptosis, and promotes intramacrophage/in-vivo survival (Zhao 2023, Liu 2025). Molecular function unfixed.

Curated reference (UniProt)

UniProt O06252 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable conserved transmembrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionDomain of unknown function (DUF4436)
Orthologous group2E1SP

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 0.733 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 6 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
DUF4436PF14494.12 7.2e-10524–275 Domain of unknown function (DUF4436)

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

Closest characterised functional partner: Rv3434c (transmembrane protein), high confidence from genomic context alone (score 884 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3434c transmembrane protein 903 884 ctx neighborhood:832
Rv3433c nnr bifunctional ADP-dependent (S)-NAD(P)H-hydrate dehydratase/NAD(P)H-hydrate epimerase 828 797 ctx neighborhood:796
Rv2423 hyp hypothetical protein 767 768 ctx cooccurence:767
Rv3166c hyp hypothetical protein 745 745 ctx cooccurence:745
Rv3843c transmembrane protein 743 744 ctx cooccurence:743
Rv2067c hyp hypothetical protein 740 741 ctx cooccurence:737
Rv3899c hyp hypothetical protein 727 728 ctx cooccurence:725
Rv2487c PE_PGRS42 PE-PGRS family protein PE_PGRS42 715 715 ctx cooccurence:715
Rv0048c membrane protein 715 715 ctx cooccurence:714
Rv2079 hyp hypothetical protein 677 677 ctx cooccurence:674
Rv2098c PE_PGRS36 PE-PGRS family protein PE_PGRS36; Rv2098c, (MTCY49.38c), len: 434 aa. PE_PGRS36,Member of the Mycobacterium tuberculosis PE family, PGRS sub 671 671 ctx cooccurence:671
Rv3446c hyp hypothetical protein 670 671 ctx cooccurence:669
Rv3432c gadB glutamate decarboxylase GadB 662 662 ctx neighborhood:661
Rv3099c hyp hypothetical protein 654 654 ctx cooccurence:652
Rv3773c hyp hypothetical protein 636 636 ctx cooccurence:634

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

  • Pathogen-specific cell-wall-associated virulence protein; modulates inflammation/apoptosis (Zhao 2023, PMID 37355194)
  • Curated from the literature crible (project 'Still unknown gene function', 2026-06-09)

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_217952.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF4436 (PF14494.12)
  • 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 2E1SP
  • Curated reference: UniProt O06252 (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 — 65 functional partner(s); context anchor Rv3434c
  • Primary literature: Zhao D, Song YH, Li D, Zhang R, Xu JB, Shi K, Li JM, Leng X, Zong Y, Zeng FL, Gong QL, Du R (2023). Mycobacterium tuberculosis Rv3435c regulates inflammatory cytokines and promotes the intracellular survival of recombinant Mycobacteria Acta Trop 246:106974. doi:10.1016/j.actatropica.2023.106974 PMID:37355194

Ancestral MTBC0 protein sequence

>mtbc0_003654|Rv3435c|
MGRILRVVVGLVLVIAAYVTVIALYHSTGLGRPHEVAHGRPTADGTTVTLHVEQLQTIKGVLVANLAVSPGTELLDSQTQGLKDDLTVTVTSVVTPTKRTWSSGSLPGVFPVPLTISGDPANWPFDHYRSGPITVQLYRGAAHAPERVSVTFVDRLPGWNVDISGVGDANVPAPYRVGLHRSPSSVAFGTVIVGVLIALAGVGLFVAVQTARGRRQFQPPMTTWYAAMLFAVIPLRNALPDAPPIGFWIDVTVVLWVVVALVTSMVLYILCWWWHLKPDVDETM