MTBC Gene Atlas

Rv3521 Family assigned · medium auto-curated

H37Rv Rv3521 · MTBC0 - · 303 aa · 3957521–3958432 (+) · RefSeq NP_218038.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation—
Revised (this work)Contains OB_ChsH2_C (PF01796.24) 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 O53566 TrEMBL · unreviewed · Predicted
UniProt nameChsH2 C-terminal OB-fold domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionNucleic-acid-binding protein containing a Zn-ribbon
Orthologous groupCOG1545
KEGG orthology K07068

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 1.344 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 8 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
OB_ChsH2_CPF01796.24 1.6e-13207–271 ChsH2, C-terminal OB-fold domain

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

Closest characterised functional partner: ltp4 (lipid transfer protein), high confidence from genomic context alone (score 989 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3522 ltp4 lipid transfer protein 996 989 ctx neighborhood:863 cooccurence:774 coexpression:453 experimental:415 textmining:705
Rv3523 ltp3 lipid carrier protein 996 986 ctx neighborhood:844 cooccurence:763 coexpression:428 experimental:415 textmining:787
Rv3540c ltp2 lipid transfer protein 916 895 ctx cooccurence:706 coexpression:424 experimental:415
Rv3541c chsH1 hyp hypothetical protein 874 843 ctx cooccurence:774
Rv3520c coenzyme F420-dependent oxidoreductase 986 822 ctx neighborhood:771 textmining:928
Rv0940c oxidoreductase 799 792 ctx neighborhood:544 cooccurence:559
Rv3526 kshA 3-ketosteroid-9-alpha-monooxygenase oxygenase subunit 774 775 ctx cooccurence:760
Rv3542c chsH2 hyp hypothetical protein 784 774 ctx cooccurence:773
Rv3552 CoA-transferase subunit beta 773 774 ctx cooccurence:764
Rv3551 CoA-transferase subunit alpha 768 768 ctx cooccurence:759
Rv3574 kstR HTH-type transcriptional regulator KstR 771 765 ctx cooccurence:765
Rv3504 fadE26 acyl-CoA dehydrogenase FadE26 754 754 ctx cooccurence:745
Rv3543c fadE29 acyl-CoA dehydrogenase FadE29 793 753 ctx cooccurence:745
Rv3515c fadD19 acyl-CoA synthetase 878 745 ctx cooccurence:733 textmining:543
Rv3568c hsaC extradiol dioxygenase 737 736 ctx cooccurence:733

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): OB_ChsH2_C PF01796.24 (E=2e-13)
  • (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_218038.1)
  • Domains: Pfam-A via hmmscan --cut_ga — OB_ChsH2_C (PF01796.24)
  • 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 COG1545
  • Curated reference: UniProt O53566 (TrEMBL, unreviewed; Predicted)
  • 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 — 53 functional partner(s); context anchor ltp4
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3521|
MGPTLSRFFTALRARRIVGVRGSDGRVHVPPVEYDPVTYEPLSEMVPVSSVGTVASWTWQPEPLAGQPLDRPFAWALIKLDGADTLLMHAVDVGTAGPSAIHTGARVHAHWADQPVGAITDIACFALGETAEPVAAHKTEDARDPVTMIVTPIQLEIQHTASHEESAYLRAIAQGKLVGARTGKTGKVYFPPHGADPATGKPTSEFVELPDKGTVTTFAIVNIPFLGQRIKPPYVAAYVLLDGADIPFLHLVSDVDAHQVRMGMRVEAVWKPRERWGLGIDNIEYFRPTGEPDANYDTYKHHL