Rv3231c Still unknown · low auto-curated

H37Rv Rv3231c · MTBC0 mtbc0_003440 · 169 aa · 3630506–3631015 (-) · RefSeq NP_217748.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF6912. Function unknown. Foldseek best (non-significant) hit: 8zm3-assembly1_C Cryo-EM strcuture of Cas5-HNH Cascade,apo-Conf2 (prob 0.03, TM 0.35).

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

Curated reference (UniProt)

UniProt O05876 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2DRWJ

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 0 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
DUF6912PF21853.2 2.2e-583–166 Family of unknown function (DUF6912)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 82.5 (confident). A confident model makes the fold comparison meaningful.

Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.

TargetProbTME-valueDescription
8zm3-assembly1_C 0.03 0.35 7.1e+00 8zm3-assembly1_C Cryo-EM strcuture of Cas5-HNH Cascade,apo-Conf2
2rgi-assembly1_B 0.02 0.31 6.2e+00 2rgi-assembly1_B Crystal structure of Ca2+-free S100A2 at 1.6 A resolution
6bnl-assembly2_E 0.02 0.28 3.3e+00 6bnl-assembly2_E Crystal structure of TCR-MHC-like molecule
6ihv-assembly1_A 0.02 0.16 8.9e-01 6ihv-assembly1_A Crystal structure of bacterial serine phosphatase bearing R161E mutation
7rno-assembly1_A 0.01 0.22 5.1e+00 7rno-assembly1_A Model of the Ac-6-FP/hpMR1/bB2m/TAPBPR complex from integrated docking, NMR and restrained MD
3gmq-assembly1_A 0.01 0.20 5.8e+00 3gmq-assembly1_A Structure of mouse CD1d expressed in SF9 cells, no ligand added
3tvm-assembly2_E 0.01 0.19 5.1e+00 3tvm-assembly2_E Structure of the mouse CD1d-SMC124-iNKT TCR complex
4pj8-assembly1_A 0.01 0.23 7.6e+00 4pj8-assembly1_A Structure of human MR1-5-OP-RU in complex with human MAIT TRBV20 TCR

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

Closest characterised functional partner: ppk2 (polyphosphate kinase), high confidence from genomic context alone (score 882 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3232c ppk2 polyphosphate kinase 975 882 ctx neighborhood:881 textmining:803
Rv2170 GCN5-like N-acetyltransferase 770 771 ctx cooccurence:770
Rv3230c stearoyl-CoA 9-desaturase electron transfer protein 952 769 ctx neighborhood:768 textmining:803
Rv3233c Rv3233c, (MTCY20B11.08c), len: 196 aa. Possible triacylglycerol synthase (See Daniel et al., 2004), similar to C-terminus of Q9RIU8|SCM11.13 908 744 ctx neighborhood:740 textmining:658
Rv3234c tgs3 diacyglycerol O-acyltransferase 906 742 ctx neighborhood:740 textmining:652
Rv0948c chorismate mutase 730 730 ctx cooccurence:722
Rv3311 hyp hypothetical protein 722 723 ctx cooccurence:721
Rv3412 hyp hypothetical protein 717 717 ctx cooccurence:716
Rv1332 transcriptional regulator 711 711 ctx cooccurence:707
Rv3229c desA3 stearoyl-CoA 9-desaturase 710 710 ctx neighborhood:709
Rv3657c membrane protein 699 699 ctx cooccurence:691
Rv3605c hyp hypothetical protein 669 669 ctx cooccurence:669
Rv2179c 3'-5' exoribonuclease 664 664 ctx cooccurence:664
Rv3259 hyp hypothetical protein 651 651 ctx cooccurence:650
Rv2744c 35kd_ag hyp hypothetical protein 640 640 ctx cooccurence:637

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: hypothetical protein
  • MTBC0 PGAP product: hypothetical protein
  • Pfam (hmmscan --cut_ga): DUF6912 PF21853.2 (E=2e-58)
  • Foldseek best: 8zm3-assembly1_C Cryo-EM strcuture of Cas5-HNH Cascade,apo-Conf2 (prob 0.03, E=7e+00, TM=0.35)
  • (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_217748.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF6912 (PF21853.2)
  • 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 2DRWJ
  • Curated reference: UniProt O05876 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 82.5, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 73 functional partner(s); context anchor ppk2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003440|Rv3231c|
MTQVYIPATLAMLQRLVADGALWPVNGTAFAVTPTLRESYAEGDDEELAEVALREAALASLRLLAADIGATADALPPRRAVLAAEVDDATYRPDLDDAVVRLAGPITIDQVVAAYVDNAGAEPAVMAAIAVIDAADLGDEDAELVVGDAQDHDLAWYANQELPFLLDLL