Rv1248c Family assigned · medium auto-curated
H37Rv Rv1248c · MTBC0 mtbc0_001337 ·
1231 aa · 1397801–1401496 (-) ·
RefSeq NP_215764.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase |
|---|---|
| MTBC0 PGAP re-annotation | multifunctional oxoglutarate decarboxylase/oxoglutarate dehydrogenase thiamine pyrophosphate-binding subunit/dihydrolipoyllysine-residue succinyltransferase subunit |
| Revised (this work) | Multifunctional oxoglutarate decarboxylase/oxoglutarate dehydrogenase thiamine pyrophosphate-binding subunit/dihydrolipoyllysine-residue succinyltransferase subunit. Pfam: 2-oxogl_dehyd_N (PF16078.11), 2-oxoacid_dh (PF00198.29), E1_dh (PF00676.26), Transket_pyr (PF02779.30), OxoGdeHyase_C (PF16870.11). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIS5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Multifunctional 2-oxoglutarate metabolism enzyme |
| EC (curated) |
EC 1.2.4.2, EC 2.2.1.5, EC 2.3.1.61, EC 4.1.1.71
|
| Curated function | Shows three enzymatic activities that share a first common step, the attack of thiamine-PP on 2-oxoglutarate (alpha-ketoglutarate, KG), leading to the formation of an enamine-thiamine-PP intermediate upon decarboxylation. Thus, displays KGD activity, catalyzing the decarboxylation from five-carbon 2-oxoglutarate to four-carbon succinate semialdehyde (SSA). Also catalyzes C-C bond formation between the activated aldehyde formed after decarboxylation of alpha-ketoglutarate and the carbonyl of glyoxylate (GLX), to yield 2-hydroxy-3-oxoadipate (HOA), which spontaneously decarboxylates to form 5-hy. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | kgd |
| eggNOG description | Shows three enzymatic activities that share a first common step, the attack of thiamine-PP on 2-oxoglutarate (alpha- ketoglutarate, KG), leading to the formation of an enamine- thiamine-PP intermediate upon decarboxylation. Thus, displays KGD activity, catalyzing the decarboxylation from five-carbon 2- oxoglutarate to four-carbon succinate semialdehyde (SSA). Also catalyzes C-C bond formation between the activated aldehyde formed after decarboxylation of alpha-ketoglutarate and the carbonyl of glyoxylate (GLX), to yield 2-hydroxy-3-oxoadipate (HOA), which spontaneously decarboxylates to form 5-hydroxylevulinate (HLA). And is also a component of the 2-oxoglutarate dehydrogenase (ODH) complex, that catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2). The KG decarboxylase and KG dehydrogenase reactions provide two alternative, tightly regulated, pathways connecting the oxidative and reductive branches of the TCA cycle |
| Orthologous group | COG0508 |
| EC number |
EC 1.2.4.2, EC 4.1.1.71
|
| KEGG orthology |
K00164, K01616
|
| KEGG pathways |
map00020, map00310, map00380, map01100, map01110, map01120, map01130, map01200
|
| KEGG modules |
M00009, M00011, M00032
|
| Gene Ontology (62) |
GO:0000287, GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0006082 +50 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 | 0.367 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 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 |
|---|---|---|---|---|
2-oxogl_dehyd_N | PF16078.11 | 7.7e-11 | 8–37 | 2-oxoglutarate dehydrogenase N-terminus |
2-oxoacid_dh | PF00198.29 | 4.1e-50 | 102–335 | 2-oxoacid dehydrogenases acyltransferase (catalytic domain) |
E1_dh | PF00676.26 | 8.9e-53 | 489–817 | Dehydrogenase E1 component |
Transket_pyr | PF02779.30 | 1.6e-40 | 879–1078 | Transketolase, pyrimidine binding domain |
OxoGdeHyase_C | PF16870.11 | 7.6e-40 | 1084–1230 | 2-oxoglutarate dehydrogenase C-terminal |
Functional interaction network (STRING v12, guilt-by-association)
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0462 lpdC |
dihydrolipoamide dehydrogenase | 999 | 1000 | coexpression:756 experimental:970 database:954 textmining:776 |
Rv0794c |
oxidoreductase | 999 | 999 | coexpression:756 experimental:970 database:844 textmining:705 |
Rv1827 garA |
glycogen accumulation regulator GarA | 999 | 999 | experimental:999 textmining:920 |
Rv2713 sthA |
pyridine nucleotide transhydrogenase | 999 | 999 | coexpression:754 experimental:970 database:844 |
Rv2855 mtr |
mycothione reductase | 999 | 999 | coexpression:756 experimental:970 database:844 |
Rv3303c lpdA |
NAD(P)H quinone reductase LpdA | 999 | 999 | coexpression:755 experimental:970 database:844 textmining:553 |
Rv2496c bkdB |
3-methyl-2-oxobutanoate dehydrogenase subunit beta | 999 | 998 | coexpression:752 experimental:955 database:844 textmining:430 |
Rv0951 sucC |
succinyl-CoA ligase subunit beta | 998 | 998 | coexpression:988 database:540 textmining:430 |
Rv0952 sucD |
succinyl-CoA ligase subunit alpha | 998 | 996 | coexpression:982 database:540 textmining:479 |
Rv2215 dlaT |
pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase | 996 | 994 | coexpression:674 experimental:770 database:891 textmining:532 |
Rv1747 |
ABC transporter ATP-binding protein/permease | 989 | 985 | experimental:984 |
Rv0020c fhaA |
FHA domain-containing protein FhaA | 988 | 984 | experimental:984 |
Rv0019c fhaB |
FHA domain-containing protein FhaB | 985 | 984 | experimental:984 |
Rv3360 hyp |
hypothetical protein | 985 | 984 | experimental:984 |
Rv1017c prsA |
ribose-phosphate pyrophosphokinase | 987 | 980 | experimental:831 database:844 textmining:429 |
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: multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase
- MTBC0 PGAP product: multifunctional oxoglutarate decarboxylase/oxoglutarate dehydrogenase thiamine pyrophosphate-binding subunit/dihydrolipoyllysine-residue succinyltransferase subunit
- Pfam (hmmscan --cut_ga): 2-oxogl_dehyd_N PF16078.11 (E=8e-11), 2-oxoacid_dh PF00198.29 (E=4e-50), E1_dh PF00676.26 (E=9e-53), Transket_pyr PF02779.30 (E=2e-40), OxoGdeHyase_C PF16870.11 (E=8e-40)
- (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_215764.2)
- Domains: Pfam-A via hmmscan --cut_ga — 2-oxogl_dehyd_N (PF16078.11), 2-oxoacid_dh (PF00198.29), E1_dh (PF00676.26), Transket_pyr (PF02779.30), OxoGdeHyase_C (PF16870.11)
- 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 P9WIS5 (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 — 280 functional partner(s)
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001337|Rv1248c| MANISSPFGQNEWLVEEMYRKFRDDPSSVDPSWHEFLVDYSPEPTSQPAAEPTRVTSPLVAERAAAAAPQAPPKPADTAAAGNGVVAALAAKTAVPPPAEGDEVAVLRGAAAAVVKNMSASLEVPTATSVRAVPAKLLIDNRIVINNQLKRTRGGKISFTHLLGYALVQAVKKFPNMNRHYTEVDGKPTAVTPAHTNLGLAIDLQGKDGKRSLVVAGIKRCETMRFAQFVTAYEDIVRRARDGKLTTEDFAGVTISLTNPGTIGTVHSVPRLMPGQGAIIGVGAMEYPAEFQGASEERIAELGIGKLITLTSTYDHRIIQGAESGDFLRTIHELLLSDGFWDEVFRELSIPYLPVRWSTDNPDSIVDKNARVMNLIAAYRNRGHLMADTDPLRLDKARFRSHPDLEVLTHGLTLWDLDRVFKVDGFAGAQYKKLRDVLGLLRDAYCRHIGVEYAHILDPEQKEWLEQRVETKHVKPTVAQQKYILSKLNAAEAFETFLQTKYVGQKRFSLEGAESVIPMMDAAIDQCAEHGLDEVVIGMPHRGRLNVLANIVGKPYSQIFTEFEGNLNPSQAHGSGDVKYHLGATGLYLQMFGDNDIQVSLTANPSHLEAVDPVLEGLVRAKQDLLDHGSIDSDGQRAFSVVPLMLHGDAAFAGQGVVAETLNLANLPGYRVGGTIHIIVNNQIGFTTAPEYSRSSEYCTDVAKMIGAPIFHVNGDDPEACVWVARLAVDFRQRFKKDVVIDMLCYRRRGHNEGDDPSMTNPYMYDVVDTKRGARKSYTEALIGRGDISMKEAEDALRDYQGQLERVFNEVRELEKHGVQPSESVESDQMIPAGLATAVDKSLLARIGDAFLALPNGFTAHPRVQPVLEKRREMAYEGKIDWAFGELLALGSLVAEGKLVRLSGQDSRRGTFSQRHSVLIDRHTGEEFTPLQLLATNSDGSPTGGKFLVYDSPLSEYAAVGFEYGYTVGNPDAVVLWEAQFGDFVNGAQSIIDEFISSGEAKWGQLSNVVLLLPHGHEGQGPDHTSARIERFLQLWAEGSMTIAMPSTPSNYFHLLRRHALDGIQRPLIVFTPKSMLRHKAAVSEIKDFTEIKFRSVLEEPTYEDGIGDRNKVSRILLTSGKLYYELAARKAKDNRNDLAIVRLEQLAPLPRRRLRETLDRYENVKEFFWVQEEPANQGAWPRFGLELPELLPDKLAGIKRISRRAMSAPSSGSSKVHAVEQQEILDEAFG