Rv0633c Still unknown · low

H37Rv Rv0633c · MTBC0 mtbc0_000666 · 279 aa · 732880–733719 (-) · RefSeq NP_215147.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)Conserved hypothetical; Foldseek best hit (KirBac channel, TM 0.43, 4.1A) not conclusive. Function unknown.

Curated reference (UniProt)

UniProt P96923 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible exported protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2EM4J

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 0.246 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 3 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.14% of strains (210) · 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)

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 87.1 (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
6o9t-assembly1_A 1.00 0.43 3.5e-03 sig 6o9t-assembly1_A KirBac3.1 mutant at a resolution of 4.1 Angstroms
7n9k-assembly1_A 0.99 0.40 5.4e-03 sig 7n9k-assembly1_A KirBac3.1 L124M mutant
8fk7-assembly1_B 0.97 0.35 1.8e-02 8fk7-assembly1_B Structure of the Pyrobaculum calidifontis flagellar-like archaeal type IV pilus
2x6b-assembly1_A 0.97 0.38 7.2e-03 sig 2x6b-assembly1_A Potassium Channel from Magnetospirillum Magnetotacticum
3ly6-assembly3_C 0.44 0.33 1.2e-01 3ly6-assembly3_C Crystal structure of human transglutaminase 2 complex with adenosine 5' Triphosphate
8gi2-assembly1_A 0.25 0.26 1.4e-01 8gi2-assembly1_A Cryo-EM structure of Natrinema sp. J7-2 Type IV pilus
6a8p-assembly3_C 0.25 0.27 9.3e-02 6a8p-assembly3_C Transglutaminase 2 mutant G224V in complex with GTP
1qun-assembly10_O 0.23 0.34 5.3e-01 1qun-assembly10_O X-RAY STRUCTURE OF THE FIMC-FIMH CHAPERONE ADHESIN COMPLEX FROM UROPATHOGENIC E.COLI

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

Closest characterised functional partner: echA3 (enoyl-CoA hydratase EchA3), high confidence from genomic context alone (score 818 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0632c echA3 enoyl-CoA hydratase EchA3 817 818 ctx neighborhood:815
Rv0634c glyoxalase II 539 539 ctx neighborhood:535
Rv0634A hyp hypothetical protein 437 437 ctx neighborhood:430
Rv0760c hyp hypothetical protein 871 49 textmining:870
Rv2168c Rv2168c, (MTV021.01c), len: 108 aa. Putative transposase for IS6110 (fragment), identical to many other Mycobacterium tuberculosis IS6110 tr 870 47 textmining:870
Rv2286c hyp hypothetical protein 870 47 textmining:870
Rv0759c hyp hypothetical protein 844 47 textmining:844
Rv0840c pip proline iminopeptidase 653 42 textmining:653
Rv0795 Rv0795, (MTV042.05), len: 108 aa. Putative transposase for IS6110 (fragment), identical to Q50686 insertion element IS6110 (108 aa), FASTA s 627 42 textmining:627
Rv2169c transmembrane protein 806 41 textmining:806

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

  • MTBC0 PGAP product: hypothetical protein
  • Foldseek best: 6o9t-assembly1_A KirBac3.1 mutant at a resolution of 4.1 Angstroms (prob 1.00, E=3e-03, TM=0.43)
  • (structure-only promotion reviewed by hand, 2026-06-01)

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_215147.1)
  • 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 2EM4J
  • Curated reference: UniProt P96923 (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 87.1, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 10 functional partner(s); context anchor echA3
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000666|Rv0633c|
MVDSMGWVLSSWHEVTGVDSGTWLAWAAWAALGLGVVALVVTKRQIQRNRRLAAEQTRPYVAMFMEPHVADWHVIELVVRNFGRTAAYDVRFSFPNPPTVAQYENAANGYADVVELRLPQELPMLAPGQEWRMVWDSALDRAEIGRGIESRFPGTVTYYDRPEQPRRWRFWRRGRRPLETKVVLDWDALPPVARIELMTTHDLAKREKQKLELLRSLLTYFHYASKETRPDVFRSEIDRINRAAAETQDRWRARQVEVPTEVSQRSEGQGPQPTRIPAG