Rv2975c Still unknown · low auto-curated

H37Rv Rv2975c · MTBC0 - · 84 aa · 3331358–3331612 (-) · RefSeq NP_217491.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Conserved hypothetical protein; no recognised domain. Function unknown. Foldseek best (non-significant) hit: 6gj3-assembly1_F The baseplate complex from the type VI secretion syst (prob 0.18, TM 0.62).

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 P95120 TrEMBL · unreviewed · Predicted
UniProt nameDhaL domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
Preferred namedak3
eggNOG descriptionglycerone kinase activity
Orthologous groupCOG1461
EC number EC 2.7.1.28, EC 2.7.1.29, EC 4.6.1.15
KEGG orthology K00863, K07030
KEGG pathways map00051, map00561, map00680, map01100, map01120, map01200, map04622
KEGG modules M00344

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 0.344 · purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 1 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 61.67% of strains (89551) · reference-fixed

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)

No Pfam-A domain above the gathering threshold (or not yet scanned).

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 58.2 (low). Low-confidence model: the fold may be unreliable, so treat these structural hits with caution.

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
6gj3-assembly1_F 0.18 0.62 5.0e+00 6gj3-assembly1_F The baseplate complex from the type VI secretion system
6e3y-assembly1_R 0.18 0.62 5.3e+00 6e3y-assembly1_R Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor
9avg-assembly1_Q 0.18 0.46 1.9e+00 9avg-assembly1_Q Structure of human calcium-sensing receptor in complex with chimeric Gs (miniGis) protein in nanodiscs
9asb-assembly1_Q 0.15 0.48 2.7e+00 9asb-assembly1_Q Structure of human calcium-sensing receptor in complex with chimeric Gq (miniGisq) protein in nanodiscs
9ayf-assembly1_Q 0.13 0.45 2.9e+00 9ayf-assembly1_Q Structure of human calcium-sensing receptor in complex with Gi1 (miniGi1) protein in detergent
8wpu-assembly1_B 0.13 0.44 2.7e+00 8wpu-assembly1_B Human calcium-sensing receptor(CaSR) bound to cinacalcet in complex with Gq protein
9axf-assembly1_Q 0.11 0.45 4.2e+00 9axf-assembly1_Q Structure of human calcium-sensing receptor in complex with chimeric Gq (miniGisq) protein in detergent
4nqi-assembly1_A 0.08 0.41 5.0e+00 4nqi-assembly1_A Structure of the N-terminal I-BAR domain (1-259) of D.Discoideum IBARa

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

Closest characterised functional partner: recG (ATP-dependent DNA helicase RecG), high confidence from genomic context alone (score 801 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2974c hyp hypothetical protein 978 978 ctx neighborhood:773 fusion:875
Rv2973c recG ATP-dependent DNA helicase RecG 801 801 ctx neighborhood:800
Rv2972c hyp hypothetical protein 801 801 ctx neighborhood:800
Rv2417c DegV domain-containing protein 762 753 experimental:652
Rv1081c membrane protein 559 560 ctx cooccurence:558
Rv3205c hyp hypothetical protein 531 531 ctx cooccurence:512
Rv2927c sepIVA hyp hypothetical protein 511 512 ctx cooccurence:445
Rv0948c chorismate mutase 505 506 ctx cooccurence:504
Rv2698 transmembrane protein 497 498 ctx cooccurence:495
Rv0556 transmembrane protein 480 481 ctx cooccurence:479
Rv2171 lppM lipoprotein LppM 469 470 ctx cooccurence:468
Rv0358 hyp hypothetical protein 463 463 ctx cooccurence:463
Rv1474c transcriptional regulator 435 436 ctx cooccurence:434
Rv2732c transmembrane protein 431 432 ctx cooccurence:426
Rv3647c hyp hypothetical protein 429 430 ctx cooccurence:426

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
  • Foldseek best: 6gj3-assembly1_F The baseplate complex from the type VI secretion system (prob 0.18, E=5e+00, TM=0.62)
  • (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_217491.1)
  • Domains: Pfam-A via hmmscan --cut_ga — none above threshold
  • 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 COG1461
  • Curated reference: UniProt P95120 (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 58.2, low)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 20 functional partner(s); context anchor recG
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2975c|
MGTADRPLDASALRDWAHAVVSDLILHIDEINRLNVFPVADSDTGVNMLFTMRAAVVEADLHANSQADAEDVARVAAALAAGAR