kasA Resolved · high auto-curated
H37Rv Rv2245 · MTBC0 mtbc0_002387 ·
416 aa · 2544273–2545523 (+) ·
RefSeq NP_216761.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 3-oxoacyl-ACP synthase 1 |
|---|---|
| MTBC0 PGAP re-annotation | 3-oxoacyl-ACP synthase KasA |
| Revised (this work) | 3-oxoacyl-ACP synthase KasA. Pfam: ketoacyl-synt (PF00109.33), Thiolase_N (PF00108.30), Ketoacyl-synt_C (PF02801.29). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WQD9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 3-oxoacyl-[acyl-carrier-protein] synthase 1 |
| EC (curated) |
EC 2.3.1.293
|
| Curated function | Part of the mycobacterial fatty acid elongation system FAS-II, which is involved in mycolic acid biosynthesis. Catalyzes the elongation of long chain acyl-ACP substrates by the addition of two carbons from malonyl-ACP to an acyl acceptor. Involved in the initial extension of the mycolate chain and forms monounsaturated fatty acids that averaged 40 carbons in length. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
I Lipid transport and metabolismQ Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | kasA |
| eggNOG description | Belongs to the beta-ketoacyl-ACP synthases family |
| Orthologous group | COG0304 |
| EC number |
EC 2.3.1.179
|
| KEGG orthology |
K09458, K11609
|
| KEGG pathways |
map00061, map00780, map01100, map01212
|
| KEGG modules |
M00083, M00572
|
| Gene Ontology (49) |
GO:0003674, GO:0003824, GO:0004312, GO:0004315, GO:0005488, GO:0005515, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0005829 +37 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 | 0.148 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 3 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 |
|---|---|---|---|---|
ketoacyl-synt | PF00109.33 | 1.1e-49 | 13–252 | Beta-ketoacyl synthase, N-terminal domain |
Thiolase_N | PF00108.30 | 9.8e-07 | 152–199 | Thiolase, N-terminal domain |
Ketoacyl-synt_C | PF02801.29 | 9.5e-32 | 262–374 | Beta-ketoacyl synthase, C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: fabD (malonyl CoA-acyl carrier protein transacylase), high confidence from genomic context alone (score 997 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2243 fabD |
malonyl CoA-acyl carrier protein transacylase | 999 | 997 ctx | neighborhood:788 cooccurence:769 coexpression:934 textmining:947 |
Rv2244 acpM |
meromycolate extension acyl carrier protein | 999 | 989 ctx | neighborhood:882 coexpression:810 experimental:408 textmining:946 |
Rv2246 kasB |
3-oxoacyl-ACP synthase 2 | 977 | 977 ctx | neighborhood:836 coexpression:860 |
Rv0904c accD3 |
acetyl-CoAcarboxylase carboxyl transferase subunit beta | 983 | 976 | coexpression:961 |
Rv2247 accD6 |
acetyl-/propionyl-CoA carboxylase subunit beta | 997 | 971 ctx | neighborhood:798 coexpression:860 textmining:914 |
Rv0533c fabH |
3-oxoacyl-ACP synthase III | 988 | 922 ctx | cooccurence:750 coexpression:678 textmining:860 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 929 | 899 | coexpression:485 experimental:785 |
Rv1527c pks5 |
polyketide synthase | 928 | 899 | coexpression:488 experimental:785 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 928 | 899 | coexpression:485 experimental:785 |
Rv2048c pks12 |
polyketide synthase | 926 | 899 | coexpression:488 experimental:785 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 926 | 899 | coexpression:490 experimental:785 |
Rv1663 pks17 |
polyketide synthase | 889 | 882 | coexpression:443 experimental:785 |
Rv1484 inhA |
NADH-dependent enoyl-[ACP | 994 | 836 ctx | cooccurence:466 coexpression:688 textmining:965 |
Rv3285 accA3 |
bifunctional protein acetyl-/propionyl-CoA carboxylase subunit alpha AccA | 854 | 808 ctx | cooccurence:654 coexpression:449 |
Rv1483 fabG1 |
3-oxoacyl-ACP reductase FabG | 947 | 792 ctx | cooccurence:655 textmining:759 |
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: 3-oxoacyl-ACP synthase 1
- MTBC0 PGAP product: 3-oxoacyl-ACP synthase KasA
- Pfam (hmmscan --cut_ga): ketoacyl-synt PF00109.33 (E=1e-49), Thiolase_N PF00108.30 (E=1e-06), Ketoacyl-synt_C PF02801.29 (E=9e-32)
- (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_216761.1)
- Domains: Pfam-A via hmmscan --cut_ga — ketoacyl-synt (PF00109.33), Thiolase_N (PF00108.30), Ketoacyl-synt_C (PF02801.29)
- 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
COG0304 - Curated reference: UniProt P9WQD9 (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 —
138 functional partner(s); context anchor
fabD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002387|Rv2245|kasA MSQPSTANGGFPSVVVTAVTATTSISPDIESTWKGLLAGESGIHALEDEFVTKWDLAVKIGGHLKDPVDSHMGRLDMRRMSYVQRMGKLLGGQLWESAGSPEVDPDRFAVVVGTGLGGAERIVESYDLMNAGGPRKVSPLAVQMIMPNGAAAVIGLQLGARAGVMTPVSACSSGSEAIAHAWRQIVMGDADVAVCGGVEGPIEALPIAAFSMMRAMSTRNDEPERASRPFDKDRDGFVFGEAGALMLIETEEHAKARGAKPLARLLGAGITSDAFHMVAPAADGVRAGRAMTRSLELAGLSPADIDHVNAHGTATPIGDAAEANAIRVAGCDQAAVYAPKSALGHSIGAVGALESVLTVLTLRDGVIPPTLNYETPDPEIDLDVVAGEPRYGDYRYAVNNSFGFGGHNVALAFGRY