Rv2305 Family assigned · medium
H37Rv Rv2305 · MTBC0 mtbc0_002445 ·
429 aa · 2600558–2601847 (+) ·
RefSeq NP_216821.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Condensation/epimerization-domain-like fold of the non-ribosomal peptide synthetase (NRPS) superfamily. RefSeq leaves it 'hypothetical protein'. The AlphaFold model superposes strongly on an NRPS epimerization domain (PDB 6ta8; Foldseek prob 1.0, E 3e-21, TM 0.67), and eggNOG places it near D-alanyl carrier / D-Ala-D-Ala chemistry (COG Q, secondary metabolism). Fold/family assignment; the catalysed step and substrate are undemonstrated. |
Curated reference (UniProt)
| UniProt |
P9WLD1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv2305 |
UniProt still lists this protein as Uncharacterized protein Rv2305; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| eggNOG description | D-alanine [D-alanyl carrier protein] ligase activity |
| Orthologous group | COG1020 |
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, GO:0044464, GO:0071944
|
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 | 0.442 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 6 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2306A (Rv2306A, len: 197 aa. Possible conserved membrane protein, similar to several hypothetical membrane proteins from Mycobacterium tuberculosis), high confidence from genomic context alone (score 774 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2082 hyp |
hypothetical protein | 818 | 818 ctx | cooccurence:718 |
Rv2306A |
Rv2306A, len: 197 aa. Possible conserved membrane protein, similar to several hypothetical membrane proteins from Mycobacterium tuberculosis | 774 | 774 ctx | neighborhood:770 |
Rv2490c PE_PGRS43 |
PE-PGRS family protein PE_PGRS43 | 772 | 772 ctx | cooccurence:772 |
Rv0341 iniB |
isoniazid inducible protein IniB | 768 | 769 ctx | cooccurence:768 |
Rv2098c PE_PGRS36 |
PE-PGRS family protein PE_PGRS36; Rv2098c, (MTCY49.38c), len: 434 aa. PE_PGRS36,Member of the Mycobacterium tuberculosis PE family, PGRS sub | 767 | 767 ctx | cooccurence:766 |
Rv2306B |
Rv2306B, len: 144 aa. Possible conserved membrane protein, similar to C-terminal part of several hypothetical membrane proteins from Mycobac | 766 | 766 ctx | neighborhood:763 |
Rv2487c PE_PGRS42 |
PE-PGRS family protein PE_PGRS42 | 765 | 765 ctx | cooccurence:765 |
Rv0355c PPE8 |
PPE family protein PPE8 | 759 | 759 ctx | cooccurence:758 |
Rv3347c PPE55 |
PPE family protein PPE55 | 758 | 759 ctx | cooccurence:757 |
Rv3350c PPE56 |
PPE family protein PPE56 | 758 | 758 ctx | cooccurence:756 |
Rv1452c PE_PGRS28 |
PE-PGRS family protein PE_PGRS28 | 758 | 758 ctx | cooccurence:758 |
Rv2209 |
integral membrane protein | 757 | 757 ctx | cooccurence:756 |
Rv1004c |
membrane protein | 756 | 757 ctx | cooccurence:755 |
Rv0304c PPE5 |
PPE family protein PPE5 | 751 | 752 ctx | cooccurence:751 |
Rv3800c pks13 |
polyketide synthase | 807 | 745 | coexpression:708 |
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
- Foldseek -> NRPS condensation/epimerization domain (6ta8), prob 1.0, E 3e-21, TM 0.67
- eggNOG COG Q (secondary metabolite); D-alanyl-carrier-related OG
- Structural homology: AlphaFold DB model + Foldseek vs PDB (project 'Still unknown gene function', phase5-7, 2026-06-10). A fold-level family assignment, not a demonstrated activity.
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_216821.1)
- 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
COG1020 - Curated reference: UniProt P9WLD1 (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 —
127 functional partner(s); context anchor
Rv2306A - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002445|Rv2305| MTQTLRLTALDEMFITDDIDIVPSVQIEARVSGRFDLDRLAAALRAAVAKHALARARLGRASLTARTLYWEVPDRADHLAVEITDEPVGEVRSRFYARAPELHRSPVFAVAVVRETVGDRLLLNFHHAAFDGMGGLRLLLSLARAYAGEPDEVGGPPIEEARNLKGVAGSRDLFDVLIRARGLAKPAIDRKRTTRVAPDGGSPDGPRFVFAPLTIESDEMATAVARRPEGATVNDLAMAALALTILQWNRTHDVPAADSVSVNMPVNFRPTAWSTEVISNFASYLAIVLRVDEVTDLEKATAIVAGITGPLKQSGAAGWVVDLLEGGKVLPAMLKRQLQLLLPLVEDRFVESVCLSNLGRVDVPAFGGEAGDTTEVWFSPTAAMSVMPIGVGLVGFGGTLRAMFRGDGRTIGGEALGRFAALYRDTLLT