mmsA Resolved · high auto-curated
H37Rv Rv0753c · MTBC0 mtbc0_000800 ·
510 aa · 848846–850378 (-) ·
RefSeq NP_215267.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | methylmalonate-semialdehyde dehydrogenase |
|---|---|
| MTBC0 PGAP re-annotation | CoA-acylating methylmalonate-semialdehyde dehydrogenase |
| Revised (this work) | CoA-acylating methylmalonate-semialdehyde dehydrogenase. Pfam: Aldedh (PF00171.28), LuxC (PF05893.20). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53816
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | methylmalonate-semialdehyde dehydrogenase |
| EC (curated) |
EC 1.2.1.27
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| Preferred name | mmsA |
| eggNOG description | Dehydrogenase |
| Orthologous group | COG1012 |
| EC number |
EC 1.2.1.18, EC 1.2.1.27
|
| KEGG orthology |
K00140
|
| KEGG pathways |
map00280, map00410, map00562, map00640, map01100, map01200
|
| KEGG modules |
M00013
|
| Gene Ontology (54) |
GO:0000166, GO:0003674, GO:0003824, GO:0004029, GO:0004030, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005739, GO:0005759 +42 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 | 0.374 · 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 |
|---|---|---|---|---|
Aldedh | PF00171.28 | 7.8e-138 | 17–490 | Aldehyde dehydrogenase family |
LuxC | PF05893.20 | 1.8e-06 | 134–270 | Acyl-CoA reductase (LuxC) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mmsB (3-hydroxyisobutyrate dehydrogenase), high confidence from genomic context alone (score 998 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0751c mmsB |
3-hydroxyisobutyrate dehydrogenase | 998 | 998 ctx | neighborhood:875 cooccurence:426 coexpression:753 database:900 |
Rv0752c fadE9 |
acyl-CoA dehydrogenase FadE9 | 987 | 987 ctx | neighborhood:882 coexpression:875 |
Rv3667 acs |
acetyl-CoAsynthetase | 950 | 947 | coexpression:419 database:900 |
Rv2589 gabT |
4-aminobutyrate aminotransferase | 937 | 932 | database:900 |
Rv0768 aldA |
aldehyde dehydrogenase AldA | 929 | 927 | database:900 |
Rv0223c |
aldehyde dehydrogenase | 925 | 923 | database:900 |
Rv0147 |
aldehyde dehydrogenase | 936 | 922 | database:900 |
Rv0860 fadB |
fatty oxidation protein FadB | 926 | 922 | database:900 |
Rv0408 pta |
phosphate acetyltransferase | 926 | 915 | database:900 |
Rv0914c |
lipid carrier protein or keto acyl-CoA thiolase | 915 | 911 | database:900 |
Rv0859 fadA |
acyltransferase | 914 | 911 | database:900 |
Rv1867 hyp |
hypothetical protein | 914 | 911 | database:900 |
Rv1323 fadA4 |
acetyl-CoA acetyltransferase | 914 | 911 | database:900 |
Rv3546 fadA5 |
acetyl-CoA acetyltransferase FadA | 928 | 910 | database:900 |
Rv3523 ltp3 |
lipid carrier protein | 914 | 910 | database:900 |
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: methylmalonate-semialdehyde dehydrogenase
- MTBC0 PGAP product: CoA-acylating methylmalonate-semialdehyde dehydrogenase
- Pfam (hmmscan --cut_ga): Aldedh PF00171.28 (E=8e-138), LuxC PF05893.20 (E=2e-06)
- (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_215267.1)
- Domains: Pfam-A via hmmscan --cut_ga — Aldedh (PF00171.28), LuxC (PF05893.20)
- 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
COG1012 - Curated reference: UniProt O53816 (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 —
78 functional partner(s); context anchor
mmsB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000800|Rv0753c|mmsA MTTQISHFIDGQRTAGQSTRSADVFDPNTGQIQAKVPMAGKSDIDAAVASAVEAQKGWAAWNPQRRARVLMRFIELVNDTIDELAELLSREHGKTLADARGDVQRGIEVIEFCLGIPHLLKGEYTEGAGPGIDVYSLRQPLGVVAGITPFNFPAMIPLWKAGPALACGNAFVLKPSERDPSVPVRLAELFIEAGLPAGVFQVVHGDKEAVDAILHHPDIKAVGFVGSSDIAQYIYAGAAATGKRAQCFGGAKNHMIVMPDADLDQAVDALIGAGYGSAGERCMAISVAVPVGDQTAERLRARLIERINNLRVGHSLDPKADYGPLVTGAALARVRDYIGQGVAAGAELVVDGRDRASDDLTFGLPEGDANLEGGFFIGPTLFDHVAAHMSIYTDEIFGPVLCMVRARDYEEALRLPSEHEYGNGVAIFTRDGDAARDFVSRVQVGMVGVNVPIPVPVAYHTFGGWKRSGFGDLNQHGPAAIQFYTKVKTVTSRWPSGIKDGAEFVIPTMS