ddlA Resolved · high auto-curated
H37Rv Rv2981c · MTBC0 mtbc0_003166 ·
373 aa · 3358105–3359226 (-) ·
RefSeq NP_217497.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | D-alanine--D-alanine ligase |
|---|---|
| MTBC0 PGAP re-annotation | D-alanine--D-alanine ligase DdlA |
| Revised (this work) | D-alanine--D-alanine ligase DdlA. Pfam: Dala_Dala_lig_N (PF01820.28), Dala_Dala_lig_C (PF07478.19), ATP-grasp (PF02222.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WP31
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | D-alanine--D-alanine ligase |
| EC (curated) |
EC 6.3.2.4
|
| Curated function | Catalyzes the ATP-driven ligation of two D-alanine molecules to form the D-alanyl-D-alanine dipeptide. This molecule is a key building block in peptidoglycan biosynthesis. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | ddl |
| eggNOG description | Belongs to the D-alanine--D-alanine ligase family |
| Orthologous group | COG1181 |
| EC number |
EC 6.3.2.4
|
| KEGG orthology |
K01921
|
| KEGG pathways |
map00473, map00550, map01100, map01502
|
| Gene Ontology (44) |
GO:0000270, GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006022, GO:0006023, GO:0006024, GO:0006807, GO:0008150, GO:0008152 +32 more
|
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 | 0.305 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 5 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Dala_Dala_lig_N | PF01820.28 | 5.8e-38 | 12–141 | D-ala D-ala ligase N-terminus |
Dala_Dala_lig_C | PF07478.19 | 1.7e-71 | 158–363 | D-ala D-ala ligase C-terminus |
ATP-grasp | PF02222.28 | 1.3e-08 | 159–332 | ATP-grasp domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: murF (UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase), high confidence from genomic context alone (score 989 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2157c murF |
UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase | 998 | 989 ctx | cooccurence:697 coexpression:426 database:900 textmining:910 |
Rv2152c murC |
UDP-N-acetylmuramate--alanine ligase | 993 | 973 ctx | fusion:887 cooccurence:470 coexpression:555 textmining:783 |
Rv3423c alr |
alanine racemase | 998 | 966 ctx | cooccurence:616 database:900 textmining:965 |
Rv2153c murG |
UDP-N-acetylglucosamine--N-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol-N-acetylglucosamine transferase | 964 | 822 ctx | cooccurence:427 coexpression:678 textmining:808 |
Rv2155c murD |
UDP-N-acetylmuramoylalanine--D-glutamate ligase | 959 | 765 | coexpression:639 textmining:834 |
Rv2154c ftsW |
lipid II flippase FtsW | 876 | 758 ctx | cooccurence:587 coexpression:406 textmining:510 |
Rv2151c ftsQ |
cell division protein FtsQ | 838 | 744 | coexpression:723 |
Rv2156c murX |
phospho-N-acetylmuramoyl-pentappeptidetransferase | 848 | 677 ctx | cooccurence:463 textmining:551 |
Rv3042c serB2 |
phosphoserine phosphatase SerB | 669 | 669 | coexpression:650 |
Rv2982c gpdA2 |
glycerol-3-phosphate dehydrogenase | 726 | 651 ctx | neighborhood:646 |
Rv2158c murE |
UDP-N-acetylmuramoylalanyl-D-glutamate--2,6-diaminopimelate ligase | 951 | 643 | coexpression:405 textmining:870 |
Rv0482 murB |
UDP-N-acetylenolpyruvoylglucosamine reductase | 872 | 595 | coexpression:441 textmining:699 |
Rv0017c rodA |
cell division protein RodA | 705 | 595 | coexpression:406 |
Rv2163c pbpB |
penicillin-binding membrane protein PbpB | 648 | 553 | |
Rv2150c ftsZ |
cell division protein FtsZ | 878 | 526 | textmining:755 |
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: D-alanine--D-alanine ligase
- MTBC0 PGAP product: D-alanine--D-alanine ligase DdlA
- Pfam (hmmscan --cut_ga): Dala_Dala_lig_N PF01820.28 (E=6e-38), Dala_Dala_lig_C PF07478.19 (E=2e-71), ATP-grasp PF02222.28 (E=1e-08)
- (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_217497.1)
- Domains: Pfam-A via hmmscan --cut_ga — Dala_Dala_lig_N (PF01820.28), Dala_Dala_lig_C (PF07478.19), ATP-grasp (PF02222.28)
- 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
COG1181 - Curated reference: UniProt P9WP31 (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 —
72 functional partner(s); context anchor
murF - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003166|Rv2981c|ddlA MSANDRRDRRVRVAVVFGGRSNEHAISCVSAGSILRNLDSRRFDVIAVGITPAGSWVLTDANPDALTITNRELPQVKSGSGTELALPADPRRGGQLVSLPPGAGEVLESVDVVFPVLHGPYGEDGTIQGLLELAGVPYVGAGVLASAVGMDKEFTKKLLAADGLPVGAYAVLRPPRSTLHRQECERLGLPVFVKPARGGSSIGVSRVSSWDQLPAAVARARRHDPKVIVEAAISGRELECGVLEMPDGTLEASTLGEIRVAGVRGREDSFYDFATKYLDDAAELDVPAKVDDQVAEAIRQLAIRAFAAIDCRGLARVDFFLTDDGPVINEINTMPGFTTISMYPRMWAASGVDYPTLLATMIETALARGVGLH