Rv2275 Resolved · high auto-curated
H37Rv Rv2275 · MTBC0 - ·
289 aa · 2546883–2547752 (+) ·
RefSeq NP_216791.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cyclo(L-tyrosyl-L-tyrosyl) synthase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Cyclo(L-tyrosyl-L-tyrosyl) synthase. Pfam: CDPS (PF16715.12). |
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 |
P9WPF9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Cyclo(L-tyrosyl-L-tyrosyl) synthase |
| EC (curated) |
EC 2.3.2.21
|
| Curated function | Involved in the biosynthesis of mycocyclosin. It uses activated amino acids in the form of aminoacyl-tRNAs (aa-tRNAs) as substrates to catalyze the ATP-independent formation of cyclodipeptides which are intermediates in diketopiperazine (DKP) biosynthetic pathways. Catalyzes the formation of cyclo(L-Tyr-L-Tyr) (cYY) from L-tyrosyl-tRNA(Tyr). Can incorporate various nonpolar residues, such as L-phenylalanine, L-leucine, L-tyrosine and L-methionine, and to a much lesser extent L-alanine, into cyclodipeptides. Cyclodipeptides synthesized by Rv2275 always contain L-tyrosine. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Cyclodipeptide synthase |
| Orthologous group | 2EW5R |
| EC number |
EC 2.3.2.20, EC 2.3.2.21
|
| KEGG orthology |
K17484, K21382
|
| Gene Ontology (8) |
GO:0003674, GO:0003824, GO:0016740, GO:0016746, GO:0016755, GO:0016874, GO:0016875, GO:0140096
|
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) pseudogene candidate
| pN/pS | n/a |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 0 synonymous, 5 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 17.46% of strains (25352) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
CDPS | PF16715.12 | 9.6e-91 | 64–283 | Cyclodipeptide synthase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cyp121 (cytochrome P450 Cyp121), high confidence from genomic context alone (score 991 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2276 cyp121 |
cytochrome P450 Cyp121 | 996 | 991 ctx | neighborhood:881 coexpression:820 database:500 textmining:648 |
Rv1452c PE_PGRS28 |
PE-PGRS family protein PE_PGRS28 | 737 | 737 ctx | cooccurence:737 |
Rv2490c PE_PGRS43 |
PE-PGRS family protein PE_PGRS43 | 731 | 731 ctx | cooccurence:731 |
Rv0355c PPE8 |
PPE family protein PPE8 | 730 | 730 ctx | cooccurence:730 |
Rv3350c PPE56 |
PPE family protein PPE56 | 728 | 729 ctx | cooccurence:728 |
Rv3347c PPE55 |
PPE family protein PPE55 | 725 | 726 ctx | cooccurence:725 |
Rv1004c |
membrane protein | 721 | 721 ctx | cooccurence:721 |
Rv1917c PPE34 |
PPE family protein PPE34 | 720 | 720 ctx | cooccurence:719 |
Rv0304c PPE5 |
PPE family protein PPE5 | 709 | 710 ctx | cooccurence:709 |
Rv2209 |
integral membrane protein | 709 | 709 ctx | cooccurence:708 |
Rv3343c PPE54 |
PPE family protein PPE54 | 700 | 700 ctx | cooccurence:696 |
Rv1651c PE_PGRS30 |
PE-PGRS family protein PE_PGRS30 | 695 | 695 ctx | cooccurence:695 |
Rv2819c csm5 |
CRISPR type III-associated RAMP protein Csm5 | 690 | 691 ctx | cooccurence:690 |
Rv0872c PE_PGRS15 |
PE-PGRS family protein PE_PGRS15 | 689 | 689 ctx | cooccurence:689 |
Rv2082 hyp |
hypothetical protein | 684 | 685 ctx | cooccurence:683 |
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): cyclo(L-tyrosyl-L-tyrosyl) synthase
- Pfam (hmmscan --cut_ga): CDPS PF16715.12 (E=1e-90)
- (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_216791.1)
- Domains: Pfam-A via hmmscan --cut_ga — CDPS (PF16715.12)
- 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
2EW5R - Curated reference: UniProt P9WPF9 (SwissProt, reviewed; 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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
94 functional partner(s); context anchor
cyp121 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2275| MSYVAAEPGVLISPTDDLQSPRSAPAAHDENADGITGGTRDDSAPNSRFQLGRRIPEATAQEGFLVRPFTQQCQIIHTEGDHAVIGVSPGNSYFSRQRLRDLGLWGLTNFDRVDFVYTDVHVAESYEALGDSAIEARRKAVKNIRGVRAKITTTVNELDPAGARLCVRPMSEFQSNEAYRELHADLLTRLKDDEDLRAVCQDLVRRFLSTKVGPRQGATATQEQVCMDYICAEAPLFLDTPAILGVPSSLNCYHQSLPLAEMLYARGSGLRASRNQGHAIVTPDGSPAE