dlaT Resolved · high auto-curated
H37Rv Rv2215 · MTBC0 mtbc0_002351 ·
553 aa · 2508122–2509783 (+) ·
RefSeq NP_216731.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | 2-oxoglutarate dehydrogenase%2C E2 component%2C dihydrolipoamide succinyltransferase |
| Revised (this work) | 2-oxoglutarate dehydrogenase%2C E2 component%2C dihydrolipoamide succinyltransferase. Pfam: Biotin_lipoyl (PF00364.29), E3_binding (PF02817.23), 2-oxoacid_dh (PF00198.29). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIS7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex |
| EC (curated) |
EC 2.3.1.12
|
| Curated function | Component of the pyruvate dehydrogenase (PDH) complex, that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2).; FUNCTION: Together with AhpC, AhpD and Lpd, constitutes an NADH-dependent peroxidase active against hydrogen and alkyl peroxides as well as serving as a peroxynitrite reductase, thus protecting the bacterium against reactive nitrogen intermediates and oxidative stress generated by the host immune system.; FUNCTION: Appears to be essential for Mtb pathogenesis. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | sucB |
| eggNOG description | Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex |
| Orthologous group | COG0508 |
| EC number |
EC 2.3.1.61
|
| KEGG orthology |
K00658
|
| KEGG pathways |
map00020, map00310, map01100, map01110, map01120, map01130, map01200
|
| KEGG modules |
M00009, M00011, M00032
|
| Gene Ontology (55) |
GO:0003674, GO:0003824, GO:0004148, GO:0005488, GO:0005504, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886 +43 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 | 0.643 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 9 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 |
|---|---|---|---|---|
Biotin_lipoyl | PF00364.29 | 3.3e-21 | 5–76 | Biotin-requiring enzyme |
E3_binding | PF02817.23 | 9.2e-15 | 243–277 | e3 binding domain |
2-oxoacid_dh | PF00198.29 | 3.4e-72 | 317–544 | 2-oxoacid dehydrogenases acyltransferase (catalytic domain) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lpdC (dihydrolipoamide dehydrogenase), high confidence from genomic context alone (score 995 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0462 lpdC |
dihydrolipoamide dehydrogenase | 999 | 995 ctx | cooccurence:546 coexpression:476 experimental:443 database:955 textmining:827 |
Rv1248c kgd |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 996 | 994 | coexpression:674 experimental:770 database:891 textmining:532 |
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta | 993 | 993 ctx | cooccurence:753 coexpression:671 experimental:773 database:627 |
Rv2241 aceE |
pyruvate dehydrogenase E1 component | 997 | 986 | coexpression:682 experimental:439 database:900 textmining:842 |
Rv0951 sucC |
succinyl-CoA ligase subunit beta | 989 | 978 | coexpression:744 database:900 textmining:568 |
Rv2497c bkdA |
3-methyl-2-oxobutanoate dehydrogenase subunit alpha | 981 | 974 ctx | cooccurence:746 coexpression:603 experimental:415 database:591 |
Rv0843 |
dehydrogenase | 981 | 974 ctx | cooccurence:740 coexpression:597 experimental:415 database:591 |
Rv0952 sucD |
succinyl-CoA ligase subunit alpha | 980 | 970 | coexpression:662 database:900 |
Rv3303c lpdA |
NAD(P)H quinone reductase LpdA | 965 | 924 ctx | cooccurence:468 coexpression:464 experimental:443 database:565 textmining:570 |
Rv2216 |
epimerase family protein | 936 | 923 ctx | neighborhood:881 |
Rv2218 lipA |
lipoyl synthase | 949 | 921 ctx | neighborhood:808 cooccurence:591 |
Rv2217 lipB |
octanoyltransferase | 943 | 916 ctx | neighborhood:808 cooccurence:505 |
Rv0400c fadE7 |
acyl-CoA dehydrogenase FadE7 | 917 | 915 | database:900 |
Rv2855 mtr |
mycothione reductase | 933 | 908 | coexpression:454 experimental:443 database:565 |
Rv2713 sthA |
pyridine nucleotide transhydrogenase | 943 | 907 | coexpression:454 experimental:443 database:565 textmining:416 |
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: pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase
- MTBC0 PGAP product: 2-oxoglutarate dehydrogenase%2C E2 component%2C dihydrolipoamide succinyltransferase
- Pfam (hmmscan --cut_ga): Biotin_lipoyl PF00364.29 (E=3e-21), E3_binding PF02817.23 (E=9e-15), 2-oxoacid_dh PF00198.29 (E=3e-72)
- (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_216731.1)
- Domains: Pfam-A via hmmscan --cut_ga — Biotin_lipoyl (PF00364.29), E3_binding (PF02817.23), 2-oxoacid_dh (PF00198.29)
- 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
COG0508 - Curated reference: UniProt P9WIS7 (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 —
135 functional partner(s); context anchor
lpdC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002351|Rv2215|dlaT MAFSVQMPALGESVTEGTVTRWLKQEGDTVELDEPLVEVSTDKVDTEIPSPAAGVLTKIIAQEDDTVEVGGELAVIGDAKDAGEAAAPAPEKVPAAQPESKPAPEPPPVQPTSGAPAGGDAKPVLMPELGESVTEGTVIRWLKKIGDSVQVDEPLVEVSTDKVDTEIPSPVAGVLVSISADEDATVPVGGELARIGVAADIGAAPAPKPAPKPVPEPAPTPKAEPAPSPPAAQPAGAAEGAPYVTPLVRKLASENNIDLAGVTGTGVGGRIRKQDVLAAAEQKKRAKAPAPAAQAAAAPAPKAPPAPAPALAHLRGTTQKASRIRQITANKTRESLQATAQLTQTHEVDMTKIVGLRARAKAAFAEREGVNLTFLPFFAKAVIDALKIHPNINASYNEDTKEITYYDAEHLGFAVDTEQGLLSPVIHDAGDLSLAGLARAIADIAARARSGNLKPDELSGGTFTITNIGSQGALFDTPILVPPQAAMLGTGAIVKRPRVVVDASGNESIGVRSVCYLPLTYDHRLIDGADAGRFLTTIKHRLEEGAFEADLGL