fas Resolved · high auto-curated

H37Rv Rv2524c · MTBC0 mtbc0_002688 · 3069 aa · 2863013–2872222 (-) · RefSeq NP_217040.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)fatty acid synthase
MTBC0 PGAP re-annotationfatty acid synthase
Revised (this work)Fatty acid synthase. Pfam: SAT (PF16073.11), FAS_AT_central (PF22690.2), Fas1-AflB-like_hel (PF08354.16), SBS_FAS (PF18094.8), MaoC_dehydratas (PF01575.26), Acyl_transf_1 (PF00698.27), ketoacyl-synt (PF00109.33), 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 P95029 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable fatty acid synthase Fas

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category I Lipid transport and metabolism
Q Secondary metabolites biosynthesis, transport and catabolism
Preferred namefas
eggNOG descriptionsynthase
Orthologous groupCOG0304
KEGG orthology K11533
KEGG pathways map00061, map01100, map01212, map04931
KEGG modules M00082, M00083

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 0.29 · purifying
Polymorphic sites (≥ 0.1% of strains) 38 synonymous, 31 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)

PfamAccessioni-EvalueResiduesDescription
SATPF16073.11 4.3e-0737–254 Starter unit:ACP transacylase in aflatoxin biosynthesis
FAS_AT_centralPF22690.2 1.5e-34196–279 Fatty acid synthase central AT domain
Fas1-AflB-like_helPF08354.16 2.4e-111561–898 Fatty acid synthase subunit beta/Fas1-like, helical
SBS_FASPF18094.8 1.6e-25935–1037 Fatty acid synthase, SBS domain
MaoC_dehydratasPF01575.26 4.6e-311199–1318 MaoC like domain
Acyl_transf_1PF00698.27 1.3e-311333–1504 Acyl transferase domain
ketoacyl-syntPF00109.33 1.2e-262576–2805 Beta-ketoacyl synthase, N-terminal domain
Ketoacyl-synt_CPF02801.29 5.3e-192816–2941 Beta-ketoacyl synthase, C-terminal domain

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: pks7 (polyketide synthase), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1661 pks7 polyketide synthase 999 1000 ctx neighborhood:544 coexpression:810 experimental:999 database:549 textmining:736
Rv1663 pks17 polyketide synthase 999 1000 ctx neighborhood:544 coexpression:929 experimental:999 database:604 textmining:519
Rv3825c pks2 phthioceranic/hydroxyphthioceranic acid synthase 999 1000 ctx neighborhood:544 coexpression:974 experimental:999 database:604 textmining:745
Rv2940c mas multifunctional mycocerosic acid synthase 999 1000 ctx neighborhood:544 coexpression:974 experimental:999 database:604 textmining:766
Rv0904c accD3 acetyl-CoAcarboxylase carboxyl transferase subunit beta 999 1000 ctx neighborhood:544 coexpression:999 textmining:788
Rv0405 pks6 membrane bound polyketide synthase 999 1000 ctx neighborhood:511 coexpression:776 experimental:994 database:549 textmining:519
Rv2932 ppsB phthiocerol synthesis polyketide synthase type I PpsB 999 1000 ctx neighborhood:544 coexpression:846 experimental:994 database:549 textmining:699
Rv1181 pks4 polyketide beta-ketoacyl synthase 999 1000 ctx neighborhood:544 coexpression:812 experimental:999 database:549 textmining:736
Rv2933 ppsC phthiocerol synthesis polyketide synthase type I PpsC 999 1000 ctx neighborhood:544 coexpression:974 experimental:999 database:604 textmining:745
Rv2931 ppsA phthiocerol synthesis polyketide synthase type I PpsA 999 1000 ctx neighborhood:511 coexpression:777 experimental:994 database:549 textmining:519
Rv2946c pks1 polyketide synthase 999 1000 ctx neighborhood:544 coexpression:906 experimental:999 database:549 textmining:745
Rv3800c pks13 polyketide synthase 999 1000 ctx neighborhood:544 coexpression:840 experimental:994 database:549 textmining:767
Rv1527c pks5 polyketide synthase 999 1000 ctx neighborhood:544 coexpression:974 experimental:999 database:604 textmining:745
Rv2048c pks12 polyketide synthase 999 1000 ctx neighborhood:544 coexpression:974 experimental:999 database:604 textmining:745
Rv2380c mbtE peptide synthetase 996 990 ctx neighborhood:417 coexpression:689 experimental:895 database:549 textmining:658

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: fatty acid synthase
  • MTBC0 PGAP product: fatty acid synthase
  • Pfam (hmmscan --cut_ga): SAT PF16073.11 (E=4e-07), FAS_AT_central PF22690.2 (E=1e-34), Fas1-AflB-like_hel PF08354.16 (E=2e-111), SBS_FAS PF18094.8 (E=2e-25), MaoC_dehydratas PF01575.26 (E=5e-31), Acyl_transf_1 PF00698.27 (E=1e-31), ketoacyl-synt PF00109.33 (E=1e-26), Ketoacyl-synt_C PF02801.29 (E=5e-19)
  • (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_217040.1)
  • Domains: Pfam-A via hmmscan --cut_ga — SAT (PF16073.11), FAS_AT_central (PF22690.2), Fas1-AflB-like_hel (PF08354.16), SBS_FAS (PF18094.8), MaoC_dehydratas (PF01575.26), Acyl_transf_1 (PF00698.27), ketoacyl-synt (PF00109.33), 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 P95029 (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 — 525 functional partner(s); context anchor pks7
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002688|Rv2524c|fas
MTIHEHDRVSADRGGDSPHTTHALVDRLMAGEPYAVAFGGQGSAWLETLEELVSATGIETELATLVGEAELLLDPVTDELIVVRPIGFEPLQWVRALAAEDPVPSDKHLTSAAVSVPGVLLTQIAATRALARQGMDLVATPPVAMAGHSQGVLAVEALKAGGARDVELFALAQLIGAAGTLVARRRGISVLGDRPPMVSVTNADPERIGRLLDEFAQDVRTVLPPVLSIRNGRRAVVITGTPEQLSRFELYCRQISEKEEADRKNKVRGGDVFSPVFEPVQVEVGFHTPRLSDGIDIVAGWAEKAGLDVALARELADAILIRKVDWVDEITRVHAAGARWILDLGPGDILTRLTAPVIRGLGIGIVPAATRGGQRNLFTVGATPEVARAWSSYAPTVVRLPDGRVKLSTKFTRLTGRSPILLAGMTPTTVDAKIVAAAANAGHWAELAGGGQVTEEIFGNRIEQMAGLLEPGRTYQFNALFLDPYLWKLQVGGKRLVQKARQSGAAIDGVVISAGIPDLDEAVELIDELGDIGISHVVFKPGTIEQIRSVIRIATEVPTKPVIMHVEGGRAGGHHSWEDLDDLLLATYSELRSRANITVCVGGGIGTPRRAAEYLSGRWAQAYGFPLMPIDGILVGTAAMATKESTTSPSVKRMLVDTQGTDQWISAGKAQGGMASSRSQLGADIHEIDNSASRCGRLLDEVAGDAEAVAERRDEIIAAMAKTAKPYFGDVADMTYLQWLRRYVELAIGEGNSTADTASVGSPWLADTWRDRFEQMLQRAEARLHPQDFGPIQTLFTDAGLLDNPQQAIAALLARYPDAETVQLHPADVPFFVTLCKTLGKPVNFVPVIDQDVRRWWRSDSLWQAHDARYDADAVCIIPGTASVAGITRMDEPVGELLDRFEQAAIDEVLGAGVEPKDVASRRLGRADVAGPLAVVLDAPDVRWAGRTVTNPVHRIADPAEWQVHDGPENPRATHSSTGARLQTHGDDVALSVPVSGTWVDIRFTLPANTVDGGTPVIATEDATSAMRTVLAIAAGVDSPEFLPAVANGTATLTVDWHPERVADHTGVTATFGEPLAPSLTNVPDALVGPCWPAVFAAIGSAVTDTGEPVVEGLLSLVHLDHAARVVGQLPTVPAQLTVTATAANATDTDMGRVVPVSVVVTGADGAVIATLEERFAILGRTGSAELADPARAGGAVSANATDTPRRRRRDVTITAPVDMRPFAVVSGDHNPIHTDRAAALLAGLESPIVHGMWLSAAAQHAVTATDGQARPPARLVGWTARFLGMVRPGDEVDFRVERVGIDQGAEIVDVAARVGSDLVMSASARLAAPKTVYAFPGQGIQHKGMGMEVRARSKAARKVWDTADKFTRDTLGFSVLHVVRDNPTSIIASGVHYHHPDGVLYLTQFTQVAMATVAAAQVAEMREQGAFVEGAIACGHSVGEYTALACVTGIYQLEALLEMVFHRGSKMHDIVPRDELGRSNYRLAAIRPSQIDLDDADVPAFVAGIAESTGEFLEIVNFNLRGSQYAIAGTVRGLEALEAEVERRRELTGGRRSFILVPGIDVPFHSRVLRVGVAEFRRSLDRVMPRDADPDLIIGRYIPNLVPRLFTLDRDFIQEIRDLVPAEPLDEILADYDTWLRERPREMARTVFIELLAWQFASPVRWIETQDLLFIEEAAGGLGVERFVEIGVKSSPTVAGLATNTLKLPEYAHSTVEVLNAERDAAVLFATDTDPEPEPEEDEPVAESPAPDVVSEAAPVAPAASSAGPRPDDLVFDAADATLALIALSAKMRIDQIEELDSIESITDGASSRRNQLLVDLGSELNLGAIDGAAESDLAGLRSQVTKLARTYKPYGPVLSDAINDQLRTVLGPSGKRPGAIAERVKKTWELGEGWAKHVTVEVALGTREGSSVRGGAMGHLHEGALADAASVDKVIDAAVASVAARQGVSVALPSAGSGGGATIDAAALSEFTDQITGREGVLASAARLVLGQLGLDDPVNALPAAPDSELIDLVTAELGADWPRLVAPVFDPKKAVVFDDRWASAREDLVKLWLTDEGDIDADWPRLAERFEGAGHVVATQATWWQGKSLAAGRQIHASLYGRIAAGAENPEPGRYGGEVAVVTGASKGSIAASVVARLLDGGATVIATTSKLDEERLAFYRTLYRDHARYGAALWLVAANMASYSDVDALVEWIGTEQTESLGPQSIHIKDAQTPTLLFPFAAPRVVGDLSEAGSRAEMEMKVLLWAVQRLIGGLSTIGAERDIASRLHVVLPGSPNRGMFGGDGAYGEAKSALDAVVSRWHAESSWAARVSLAHALIGWTRGTGLMGHNDAIVAAVEEAGVTTYSTDEMAALLLDLCDAESKVAAARSPIKADLTGGLAEANLDMAELAAKAREQMSAAAAVDEDAEAPGAIAALPSPPRGFTPAPPPQWDDLDVDPADLVVIVGGAEIGPYGSSRTRFEMEVENELSAAGVLELAWTTGLIRWEDDPQPGWYDTESGEMVDESELVQRYHDAVVQRVGIREFVDDGAIDPDHASPLLVSVFLEKDFAFVVSSEADARAFVEFDPEHTVIRPVPDSTDWQVIRKAGTEIRVPRKTKLSRVVGGQIPTGFDPTVWGISADMAGSIDRLAVWNMVATVDAFLSSGFSPAEVMRYVHPSLVANTQGTGMGGGTSMQTMYHGNLLGRNKPNDIFQEVLPNIIAAHVVQSYVGSYGAMIHPVAACATAAVSVEEGVDKIRLGKAQLVVAGGLDDLTLEGIIGFGDMAATADTSMMRGRGIHDSKFSRPNDRRRLGFVEAQGGGTILLARGDLALRMGLPVLAVVAFAQSFGDGVHTSIPAPGLGALGAGRGGKDSPLARALAKLGVAADDVAVISKHDTSTLANDPNETELHERLADALGRSEGAPLFVVSQKSLTGHAKGGAAVFQMMGLCQILRDGVIPPNRSLDCVDDELAGSAHFVWVRDTLRLGGKFPLKAGMLTSLGFGHVSGLVALVHPQAFIASLDPAQRADYQRRADARLLAGQRRLASAIAGGAPMYQRPGDRRFDHHAPERPQEASMLLNPAARLGDGEAYIG