Rv2712c Still unknown · low auto-curated

H37Rv Rv2712c · MTBC0 mtbc0_002886 · 352 aa · 3046685–3047743 (-) · RefSeq NP_217228.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationDUF4192 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF4192. Function unknown. Foldseek best (non-significant) hit: 7ya9-assembly1_A-2 Fis1 (Mitochondrial fission 1 protein) (prob 0.99, TM 0.57).

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

Curated reference (UniProt)

UniProt I6YE70 TrEMBL · unreviewed · Predicted
UniProt nameDUF4192 domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionDomain of unknown function (DUF4192)
Orthologous group2AR9G

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 1.117 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 8 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.16% of strains (229) · clonal

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
DUF4192PF13830.12 1.6e-9313–321 Domain of unknown function (DUF4192)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 93.5 (very high). 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
7ya9-assembly1_A-2 0.99 0.57 1.6e-01 7ya9-assembly1_A-2 Fis1 (Mitochondrial fission 1 protein)
8xwx-assembly1_B 0.97 0.58 3.3e-01 8xwx-assembly1_B Crystal structure of FIS1-BAP31 complex from human
1nzn-assembly1_A 0.97 0.59 3.6e-01 1nzn-assembly1_A Cytosolic domain of the human mitchondrial fission protein Fis1 adopts a TPR fold
8u1z-assembly1_A 0.93 0.58 5.7e-01 8u1z-assembly1_A Crystal structure of the Fis1 cytosolic domain bound to a peptide inhibitor
4n3c-assembly1_A 0.75 0.59 1.4e+00 4n3c-assembly1_A Crystal Structure of human O-GlcNAc Transferase bound to a peptide from HCF-1 pro-repeat2(1-26) and UDP-GlcNAc
1pc2-assembly1_A 0.72 0.42 3.1e-01 1pc2-assembly1_A Solution structure of human mitochondria fission protein Fis1
3asd-assembly1_A 0.57 0.47 1.2e+00 3asd-assembly1_A MamA R50E mutant
4cgw-assembly1_A 0.54 0.52 1.6e+00 4cgw-assembly1_A Second TPR of Spaghetti (RPAP3) bound to HSP90 peptide SRMEEVD

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

Closest characterised functional partner: sthA (pyridine nucleotide transhydrogenase), high confidence from genomic context alone (score 779 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2713 sthA pyridine nucleotide transhydrogenase 779 779 ctx neighborhood:778
Rv1486c hyp hypothetical protein 712 712 ctx cooccurence:712
Rv1109c hyp hypothetical protein 685 685 ctx cooccurence:685
Rv1222 rseA anti-sigma E factor RseA 665 666 ctx cooccurence:661
Rv0817c lmeA hyp hypothetical protein 662 662 ctx cooccurence:662
Rv3244c lpqB lipoprotein LpqB 657 657 ctx cooccurence:656
Rv3212 hyp hypothetical protein 653 653 ctx cooccurence:651
Rv2672 protease 638 638 ctx cooccurence:638
Rv2743c hyp hypothetical protein 636 637 ctx cooccurence:635
Rv2138 lppL lipoprotein LppL 633 633 ctx cooccurence:631
Rv0479c membrane protein 620 621 ctx cooccurence:620
Rv2862c hyp hypothetical protein 617 618 ctx cooccurence:617
Rv1166 lpqW monoacyl phosphatidylinositol tetramannoside-binding protein LpqW 615 615 ctx cooccurence:613
Rv2360c hyp hypothetical protein 613 613 ctx cooccurence:611
Rv1312 hyp hypothetical protein 612 612 ctx cooccurence:612

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: DUF4192 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF4192 PF13830.12 (E=2e-93)
  • Foldseek best: 7ya9-assembly1_A-2 Fis1 (Mitochondrial fission 1 protein) (prob 0.99, E=2e-01, TM=0.57)
  • (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_217228.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF4192 (PF13830.12)
  • 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 2AR9G
  • Curated reference: UniProt I6YE70 (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)
  • Model confidence: ESMFold per-residue pLDDT (mean 93.5, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 105 functional partner(s); context anchor sthA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002886|Rv2712c|
MTKYRGQFELNRPATLIAALPAILGFVPEKSLVLVSLAAGELGSVMRADLCDELADRVGHLAELVAAANPAAAIAVIVDANGAQCPRCNEEYRQLCAALAAALSQRDIVLWAAHVVDRVAAGGRWHCVDGCGCSGVIDDPSASPLAMAAVLDGRQLYPRRSDLQAVIAVDDPVRSAELAVALGHQAADREIAHRADSVGCSRQDVENALAAAARVADGQSLSDTELARLGCALGDARVRDMLYALAVGENAGAAESLWALLARVLPEPWRVEALVLLAFSAYARGDGPLAGVSLQAALCCEPGHRMAGMLDTALQSGLRPEHIRDIAVTGYQRAEQLGIRLPPRRAFGQRAG