Rv2315c Family assigned · medium auto-curated
H37Rv Rv2315c · MTBC0 mtbc0_002463 ·
505 aa · 2612036–2613553 (-) ·
RefSeq NP_216831.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | TldD/PmbA family protein |
| Revised (this work) | TldD/PmbA family protein. Pfam: PmbA_TldD_1st (PF01523.22), PmbA_TldD_3rd (PF19289.5). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P71897
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved protein |
UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | tldD |
| eggNOG description | Modulator of DNA gyrase |
| Orthologous group | COG0312 |
| KEGG orthology |
K03568
|
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 | 1.137 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 9 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.45% of strains (657) · 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 |
|---|---|---|---|---|
PmbA_TldD_1st | PF01523.22 | 1.0e-11 | 35–98 | PmbA/TldA metallopeptidase domain 1 |
PmbA_TldD_3rd | PF19289.5 | 1.7e-28 | 251–496 | PmbA/TldA metallopeptidase C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: uspC (sugar ABC transporter substrate-binding lipoprotein UspC), high confidence from genomic context alone (score 791 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) |
|---|---|---|---|---|
Rv2314c hyp |
hypothetical protein | 973 | 974 ctx | neighborhood:882 cooccurence:774 |
Rv2313c hyp |
hypothetical protein | 879 | 880 ctx | neighborhood:879 |
Rv2318 uspC |
sugar ABC transporter substrate-binding lipoprotein UspC | 790 | 791 ctx | neighborhood:790 |
Rv2316 uspA |
sugar ABC transporter permease UspA | 790 | 791 ctx | neighborhood:790 |
Rv2317 uspB |
sugar ABC transporter permease UspB | 789 | 790 ctx | neighborhood:790 |
Rv1473A |
transcriptional regulator | 531 | 531 ctx | cooccurence:531 |
Rv1094 desA2 |
acyl-ACP desaturase DesA | 404 | 376 | |
Rv3703c etgB |
iron(II)-dependent oxidoreductase EgtB | 755 | 79 | textmining:745 |
Rv1385 pyrF |
orotidine 5'-phosphate decarboxylase | 750 | 62 | textmining:745 |
Rv3303c lpdA |
NAD(P)H quinone reductase LpdA | 748 | 55 | textmining:745 |
Rv0489 gpm1 |
2,3-bisphosphoglycerate-dependent phosphoglycerate mutase | 580 | 53 | textmining:575 |
Rv0670 end |
endonuclease IV | 747 | 50 | textmining:745 |
Rv2135c hyp |
hypothetical protein | 866 | 47 | textmining:866 |
Rv2323c hyp |
hypothetical protein | 746 | 47 | textmining:745 |
Rv2071c cobM |
precorrin-4 C(11)-methyltransferase | 746 | 45 | textmining:745 |
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: TldD/PmbA family protein
- Pfam (hmmscan --cut_ga): PmbA_TldD_1st PF01523.22 (E=1e-11), PmbA_TldD_3rd PF19289.5 (E=2e-28)
- (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_216831.1)
- Domains: Pfam-A via hmmscan --cut_ga — PmbA_TldD_1st (PF01523.22), PmbA_TldD_3rd (PF19289.5)
- 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
COG0312 - Curated reference: UniProt P71897 (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)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
15 functional partner(s); context anchor
uspC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002463|Rv2315c| MTPNRGIDEDFLDLPRQQLADAALSAAATAGASHADLRVHRISTEIIQLRDGELETAVISRELGLAVRVIVAGTWGFASHAELAPDVAAATARHAVHVATVLAALNTERVRLAPEPVYTDAEWVSNYRIDPFGVPASEKIAVLRDYSGRLLDADGIDHVSASLNAVKEQTFYADTFGSSITQQRVRLLPCLDAVAVDSAAGNFESMRTLAPPTARGWEVVAGDEIWNWTDELAQLPSLLAEKVRAPSVMPGPTDLVIDPTNLWLTIHESIGHATEYDRAIGYEAAYAGTSFATPDKLGTLRYGSPVMNVTADRTAEFGLATVGYDDEGVAAQSWDLVRDGVFVGYQLDRAFAPRLGEPRSNGCSYADSPHHVPIQRMANISLQPGIEDLSTADLIGRVDDGIYIVGDKSWSIDMQRYNFQFTGQRFFRIRGGQLYGQLRDVAYQSSTTDFWNAMEAVGGPSTWRMGGAINCGKAQPGQVAAVSHGCPSALFRGVNVLNTRTEGGR