ID FAS_RAT Reviewed; 2505 AA.
AC P12785; O09187; O09190; Q63577; Q64717;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 3.
DT 27-NOV-2024, entry version 215.
DE RecName: Full=Fatty acid synthase;
DE EC=2.3.1.85 {ECO:0000269|PubMed:15715522, ECO:0000269|PubMed:8250834, ECO:0000269|PubMed:8756713};
DE AltName: Full=Type I FAS {ECO:0000303|PubMed:18096506};
DE Includes:
DE RecName: Full=[Acyl-carrier-protein] S-acetyltransferase;
DE EC=2.3.1.38 {ECO:0000269|PubMed:18096506, ECO:0000269|PubMed:8250834, ECO:0000269|PubMed:8756713};
DE Includes:
DE RecName: Full=[Acyl-carrier-protein] S-malonyltransferase;
DE EC=2.3.1.39 {ECO:0000269|PubMed:8250834};
DE Includes:
DE RecName: Full=3-oxoacyl-[acyl-carrier-protein] synthase;
DE EC=2.3.1.41 {ECO:0000269|PubMed:15715522, ECO:0000269|PubMed:8250834, ECO:0000269|PubMed:8756713};
DE Includes:
DE RecName: Full=3-oxoacyl-[acyl-carrier-protein] reductase;
DE EC=1.1.1.100 {ECO:0000305|PubMed:15715522, ECO:0000305|PubMed:8250834, ECO:0000305|PubMed:8756713};
DE Includes:
DE RecName: Full=3-hydroxyacyl-[acyl-carrier-protein] dehydratase;
DE EC=4.2.1.59 {ECO:0000269|PubMed:18096506, ECO:0000269|PubMed:8250834};
DE Includes:
DE RecName: Full=Enoyl-[acyl-carrier-protein] reductase;
DE EC=1.3.1.39 {ECO:0000305|PubMed:15715522, ECO:0000305|PubMed:8250834, ECO:0000305|PubMed:8756713};
DE Includes:
DE RecName: Full=Acyl-[acyl-carrier-protein] hydrolase;
DE EC=3.1.2.14;
GN Name=Fasn;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2717611; DOI=10.1073/pnas.86.9.3114;
RA Amy C.M., Witkowski A., Naggert J., Williams B., Randhawa Z., Smith S.;
RT "Molecular cloning and sequencing of cDNAs encoding the entire rat fatty
RT acid synthase.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:3114-3118(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Liver;
RX PubMed=1339331; DOI=10.3109/10425179209020817;
RA Beck K.F., Schreglmann R., Stathopulos I., Klein H., Hoch J., Schweizer M.;
RT "The fatty acid synthase (FAS) gene and its promoter in Rattus
RT norvegicus.";
RL DNA Seq. 2:359-386(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1736293; DOI=10.1073/pnas.89.3.1105;
RA Amy C.M., Williams-Ahlf B., Naggert J., Smith S.;
RT "Intron-exon organization of the gene for the multifunctional animal fatty
RT acid synthase.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:1105-1108(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 75-2505.
RC STRAIN=Sprague-Dawley; TISSUE=Mammary gland;
RX PubMed=2915923; DOI=10.1093/nar/17.2.567;
RA Schweizer M., Takabeyashi K., Beck K.F., Schreglmann R.;
RT "Rat mammary gland fatty acid synthase: localization of the constituent
RT domains and two functional polyadenylation/termination signals in the
RT cDNA.";
RL Nucleic Acids Res. 17:567-586(1989).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1921-2324.
RC TISSUE=Mammary gland;
RX PubMed=3109907; DOI=10.1111/j.1432-1033.1987.tb11482.x;
RA Witlowski A., Naggert J., Mikkelsen J., Smith S.;
RT "Molecular cloning and sequencing of a cDNA encoding the acyl carrier
RT protein and its flanking domains in the mammalian fatty acid synthetase.";
RL Eur. J. Biochem. 165:601-606(1987).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 2085-2505.
RC TISSUE=Mammary gland;
RX PubMed=2891707; DOI=10.1016/s0021-9258(19)57278-7;
RA Naggert J., Witkowski A., Mikkelsen J., Smith S.;
RT "Molecular cloning and sequencing of a cDNA encoding the thioesterase
RT domain of the rat fatty acid synthetase.";
RL J. Biol. Chem. 263:1146-1150(1988).
RN [7]
RP NUCLEOTIDE SEQUENCE OF 2377-2413, AND INDUCTION.
RX PubMed=2313386; DOI=10.1093/jn/120.2.218;
RA Clarke S.D., Armstrong M.K., Jump D.B.;
RT "Nutritional control of rat liver fatty acid synthase and S14 mRNA
RT abundance.";
RL J. Nutr. 120:218-224(1990).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=8250834; DOI=10.1042/bj2960143;
RA Joshi A.K., Smith S.;
RT "Construction of a cDNA encoding the multifunctional animal fatty acid
RT synthase and expression in Spodoptera frugiperda cells using baculoviral
RT vectors.";
RL Biochem. J. 296:143-149(1993).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=8756713; DOI=10.1021/bi960910m;
RA Witkowski A., Joshi A., Smith S.;
RT "Fatty acid synthase: in vitro complementation of inactive mutants.";
RL Biochemistry 35:10569-10575(1996).
RN [10]
RP FUNCTION.
RX PubMed=9405069; DOI=10.1021/bi972242q;
RA Witkowski A., Joshi A.K., Smith S.;
RT "Characterization of the interthiol acyltransferase reaction catalyzed by
RT the beta-ketoacyl synthase domain of the animal fatty acid synthase.";
RL Biochemistry 36:16338-16344(1997).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=15715522; DOI=10.1042/bj20041963;
RA Rendina A.R., Cheng D.;
RT "Characterization of the inactivation of rat fatty acid synthase by C75:
RT inhibition of partial reactions and protection by substrates.";
RL Biochem. J. 388:895-903(2005).
RN [12]
RP INTERACTION WITH CEACAM1.
RX PubMed=16054098; DOI=10.1016/j.cmet.2005.06.001;
RA Najjar S.M., Yang Y., Fernstroem M.A., Lee S.J., Deangelis A.M.,
RA Rjaily G.A., Al-Share Q.Y., Dai T., Miller T.A., Ratnam S., Ruch R.J.,
RA Smith S., Lin S.H., Beauchemin N., Oyarce A.M.;
RT "Insulin acutely decreases hepatic fatty acid synthase activity.";
RL Cell Metab. 2:43-53(2005).
RN [13]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=16969344; DOI=10.1038/sj.bjc.6603350;
RA Zhao W., Kridel S., Thorburn A., Kooshki M., Little J., Hebbar S.,
RA Robbins M.;
RT "Fatty acid synthase: a novel target for antiglioma therapy.";
RL Br. J. Cancer 95:869-878(2006).
RN [14]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=18096506; DOI=10.1016/j.chembiol.2007.11.007;
RA Pasta S., Witkowski A., Joshi A.K., Smith S.;
RT "Catalytic residues are shared between two pseudosubunits of the
RT dehydratase domain of the animal fatty acid synthase.";
RL Chem. Biol. 14:1377-1385(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-725; SER-1578; SER-2151 AND
RP SER-2191, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [16]
RP STRUCTURE BY NMR OF 2114-2202.
RX PubMed=12926246; DOI=10.1039/b208941f;
RA Reed M.A.C., Schweizer M., Szafranska A.E., Arthur C., Nicholson T.P.,
RA Cox R.J., Crosby J., Crump M.P., Simpson T.J.;
RT "The type I rat fatty acid synthase ACP shows structural homology and
RT analogous biochemical properties to type II ACPs.";
RL Org. Biomol. Chem. 1:463-471(2003).
CC -!- FUNCTION: Fatty acid synthetase is a multifunctional enzyme that
CC catalyzes the de novo biosynthesis of long-chain saturated fatty acids
CC starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This
CC multifunctional protein contains 7 catalytic activities and a site for
CC the binding of the prosthetic group 4'-phosphopantetheine of the acyl
CC carrier protein ([ACP]) domain. {ECO:0000269|PubMed:15715522,
CC ECO:0000269|PubMed:18096506, ECO:0000269|PubMed:8250834,
CC ECO:0000269|PubMed:8756713, ECO:0000305|PubMed:9405069}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + n malonyl-CoA + 2n NADPH + 2n H(+) = a long-chain
CC fatty acid + (n+1) CoA + n CO2 + 2n NADP(+).; EC=2.3.1.85;
CC Evidence={ECO:0000269|PubMed:15715522, ECO:0000269|PubMed:8250834,
CC ECO:0000269|PubMed:8756713};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=holo-[ACP] + acetyl-CoA = acetyl-[ACP] + CoA;
CC Xref=Rhea:RHEA:41788, Rhea:RHEA-COMP:9621, Rhea:RHEA-COMP:9685,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78446; EC=2.3.1.38;
CC Evidence={ECO:0000269|PubMed:18096506, ECO:0000269|PubMed:8250834,
CC ECO:0000269|PubMed:8756713};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41789;
CC Evidence={ECO:0000269|PubMed:18096506, ECO:0000269|PubMed:8250834,
CC ECO:0000269|PubMed:8756713};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=holo-[ACP] + malonyl-CoA = malonyl-[ACP] + CoA;
CC Xref=Rhea:RHEA:41792, Rhea:RHEA-COMP:9623, Rhea:RHEA-COMP:9685,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78449; EC=2.3.1.39;
CC Evidence={ECO:0000269|PubMed:8250834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41793;
CC Evidence={ECO:0000269|PubMed:8250834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a fatty acyl-[ACP] + malonyl-[ACP] + H(+) = a 3-oxoacyl-[ACP]
CC + holo-[ACP] + CO2; Xref=Rhea:RHEA:22836, Rhea:RHEA-COMP:9623,
CC Rhea:RHEA-COMP:9685, Rhea:RHEA-COMP:9916, Rhea:RHEA-COMP:14125,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78449, ChEBI:CHEBI:78776, ChEBI:CHEBI:138651;
CC EC=2.3.1.41; Evidence={ECO:0000269|PubMed:15715522,
CC ECO:0000269|PubMed:8250834, ECO:0000269|PubMed:8756713};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22837;
CC Evidence={ECO:0000269|PubMed:15715522, ECO:0000269|PubMed:8250834,
CC ECO:0000269|PubMed:8756713};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + NADPH
CC + H(+); Xref=Rhea:RHEA:17397, Rhea:RHEA-COMP:9916, Rhea:RHEA-
CC COMP:9945, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78776, ChEBI:CHEBI:78827; EC=1.1.1.100;
CC Evidence={ECO:0000305|PubMed:15715522, ECO:0000305|PubMed:8250834,
CC ECO:0000305|PubMed:8756713};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17399;
CC Evidence={ECO:0000305|PubMed:15715522, ECO:0000305|PubMed:8250834,
CC ECO:0000305|PubMed:8756713};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a (3R)-hydroxyacyl-[ACP] = a (2E)-enoyl-[ACP] + H2O;
CC Xref=Rhea:RHEA:13097, Rhea:RHEA-COMP:9925, Rhea:RHEA-COMP:9945,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:78784, ChEBI:CHEBI:78827; EC=4.2.1.59;
CC Evidence={ECO:0000269|PubMed:18096506, ECO:0000269|PubMed:8250834,
CC ECO:0000305|PubMed:8756713};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13098;
CC Evidence={ECO:0000269|PubMed:18096506, ECO:0000269|PubMed:8250834,
CC ECO:0000305|PubMed:8756713};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2,3-saturated acyl-[ACP] + NADP(+) = a (2E)-enoyl-[ACP] +
CC NADPH + H(+); Xref=Rhea:RHEA:22564, Rhea:RHEA-COMP:9925, Rhea:RHEA-
CC COMP:9926, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78784, ChEBI:CHEBI:78785; EC=1.3.1.39;
CC Evidence={ECO:0000305|PubMed:15715522, ECO:0000305|PubMed:8250834,
CC ECO:0000305|PubMed:8756713};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22566;
CC Evidence={ECO:0000305|PubMed:15715522, ECO:0000305|PubMed:8250834,
CC ECO:0000305|PubMed:8756713};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoyl-[ACP] + H2O = hexadecanoate + holo-[ACP] + H(+);
CC Xref=Rhea:RHEA:41932, Rhea:RHEA-COMP:9652, Rhea:RHEA-COMP:9685,
CC ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:64479, ChEBI:CHEBI:78483; EC=3.1.2.14;
CC Evidence={ECO:0000305|PubMed:15715522, ECO:0000305|PubMed:8250834,
CC ECO:0000305|PubMed:8756713};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41933;
CC Evidence={ECO:0000305|PubMed:15715522, ECO:0000305|PubMed:8250834,
CC ECO:0000305|PubMed:8756713};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-[ACP] + malonyl-[ACP] + H(+) = 3-oxobutanoyl-[ACP] +
CC holo-[ACP] + CO2; Xref=Rhea:RHEA:41800, Rhea:RHEA-COMP:9621,
CC Rhea:RHEA-COMP:9623, Rhea:RHEA-COMP:9625, Rhea:RHEA-COMP:9685,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78446, ChEBI:CHEBI:78449, ChEBI:CHEBI:78450;
CC Evidence={ECO:0000269|PubMed:8250834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41801;
CC Evidence={ECO:0000269|PubMed:8250834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxobutanoyl-[ACP] + NADPH + H(+) = (3R)-hydroxybutanoyl-
CC [ACP] + NADP(+); Xref=Rhea:RHEA:41804, Rhea:RHEA-COMP:9625,
CC Rhea:RHEA-COMP:9626, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78450, ChEBI:CHEBI:78451;
CC Evidence={ECO:0000305|PubMed:8250834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41805;
CC Evidence={ECO:0000305|PubMed:8250834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxybutanoyl-[ACP] = (2E)-butenoyl-[ACP] + H2O;
CC Xref=Rhea:RHEA:41808, Rhea:RHEA-COMP:9626, Rhea:RHEA-COMP:9627,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:78451, ChEBI:CHEBI:78453;
CC Evidence={ECO:0000269|PubMed:18096506, ECO:0000305|PubMed:8250834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41809;
CC Evidence={ECO:0000269|PubMed:18096506, ECO:0000305|PubMed:8250834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-butenoyl-[ACP] + NADPH + H(+) = butanoyl-[ACP] + NADP(+);
CC Xref=Rhea:RHEA:41812, Rhea:RHEA-COMP:9627, Rhea:RHEA-COMP:9628,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78453, ChEBI:CHEBI:78454;
CC Evidence={ECO:0000305|PubMed:8250834};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41813;
CC Evidence={ECO:0000305|PubMed:8250834};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=butanoyl-[ACP] + malonyl-[ACP] + H(+) = 3-oxohexanoyl-[ACP] +
CC holo-[ACP] + CO2; Xref=Rhea:RHEA:41820, Rhea:RHEA-COMP:9623,
CC Rhea:RHEA-COMP:9628, Rhea:RHEA-COMP:9629, Rhea:RHEA-COMP:9685,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78449, ChEBI:CHEBI:78454, ChEBI:CHEBI:78456;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41821;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxohexanoyl-[ACP] + NADPH + H(+) = (3R)-hydroxyhexanoyl-
CC [ACP] + NADP(+); Xref=Rhea:RHEA:41824, Rhea:RHEA-COMP:9629,
CC Rhea:RHEA-COMP:9630, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78456, ChEBI:CHEBI:78457;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41825;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxyhexanoyl-[ACP] = (2E)-hexenoyl-[ACP] + H2O;
CC Xref=Rhea:RHEA:41828, Rhea:RHEA-COMP:9630, Rhea:RHEA-COMP:9631,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:78457, ChEBI:CHEBI:78458;
CC Evidence={ECO:0000269|PubMed:18096506};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41829;
CC Evidence={ECO:0000269|PubMed:18096506};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-hexenoyl-[ACP] + NADPH + H(+) = hexanoyl-[ACP] + NADP(+);
CC Xref=Rhea:RHEA:41832, Rhea:RHEA-COMP:9631, Rhea:RHEA-COMP:9632,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78458, ChEBI:CHEBI:78459;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41833;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexanoyl-[ACP] + malonyl-[ACP] + H(+) = 3-oxooctanoyl-[ACP] +
CC holo-[ACP] + CO2; Xref=Rhea:RHEA:41836, Rhea:RHEA-COMP:9623,
CC Rhea:RHEA-COMP:9632, Rhea:RHEA-COMP:9633, Rhea:RHEA-COMP:9685,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78449, ChEBI:CHEBI:78459, ChEBI:CHEBI:78460;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41837;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxooctanoyl-[ACP] + NADPH + H(+) = (3R)-hydroxyoctanoyl-
CC [ACP] + NADP(+); Xref=Rhea:RHEA:41840, Rhea:RHEA-COMP:9633,
CC Rhea:RHEA-COMP:9634, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78460, ChEBI:CHEBI:78461;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41841;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxyoctanoyl-[ACP] = (2E)-octenoyl-[ACP] + H2O;
CC Xref=Rhea:RHEA:41844, Rhea:RHEA-COMP:9634, Rhea:RHEA-COMP:9635,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:78461, ChEBI:CHEBI:78462;
CC Evidence={ECO:0000269|PubMed:18096506};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41845;
CC Evidence={ECO:0000269|PubMed:18096506};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-octenoyl-[ACP] + NADPH + H(+) = octanoyl-[ACP] + NADP(+);
CC Xref=Rhea:RHEA:41848, Rhea:RHEA-COMP:9635, Rhea:RHEA-COMP:9636,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78462, ChEBI:CHEBI:78463;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41849;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=octanoyl-[ACP] + malonyl-[ACP] + H(+) = 3-oxodecanoyl-[ACP] +
CC holo-[ACP] + CO2; Xref=Rhea:RHEA:41852, Rhea:RHEA-COMP:9623,
CC Rhea:RHEA-COMP:9636, Rhea:RHEA-COMP:9637, Rhea:RHEA-COMP:9685,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78449, ChEBI:CHEBI:78463, ChEBI:CHEBI:78464;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41853;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxodecanoyl-[ACP] + NADPH + H(+) = (3R)-hydroxydecanoyl-
CC [ACP] + NADP(+); Xref=Rhea:RHEA:41856, Rhea:RHEA-COMP:9637,
CC Rhea:RHEA-COMP:9638, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78464, ChEBI:CHEBI:78466;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41857;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxydecanoyl-[ACP] = (2E)-decenoyl-[ACP] + H2O;
CC Xref=Rhea:RHEA:41860, Rhea:RHEA-COMP:9638, Rhea:RHEA-COMP:9639,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:78466, ChEBI:CHEBI:78467;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41861;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-decenoyl-[ACP] + NADPH + H(+) = decanoyl-[ACP] + NADP(+);
CC Xref=Rhea:RHEA:41864, Rhea:RHEA-COMP:9639, Rhea:RHEA-COMP:9640,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78467, ChEBI:CHEBI:78468;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41865;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=decanoyl-[ACP] + malonyl-[ACP] + H(+) = 3-oxododecanoyl-[ACP]
CC + holo-[ACP] + CO2; Xref=Rhea:RHEA:41868, Rhea:RHEA-COMP:9623,
CC Rhea:RHEA-COMP:9640, Rhea:RHEA-COMP:9641, Rhea:RHEA-COMP:9685,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78449, ChEBI:CHEBI:78468, ChEBI:CHEBI:78469;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41869;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxododecanoyl-[ACP] + NADPH + H(+) = (3R)-hydroxydodecanoyl-
CC [ACP] + NADP(+); Xref=Rhea:RHEA:41872, Rhea:RHEA-COMP:9641,
CC Rhea:RHEA-COMP:9642, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78469, ChEBI:CHEBI:78470;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41873;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxydodecanoyl-[ACP] = (2E)-dodecenoyl-[ACP] + H2O;
CC Xref=Rhea:RHEA:41876, Rhea:RHEA-COMP:9642, Rhea:RHEA-COMP:9643,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:78470, ChEBI:CHEBI:78472;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41877;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-dodecenoyl-[ACP] + NADPH + H(+) = dodecanoyl-[ACP] +
CC NADP(+); Xref=Rhea:RHEA:41880, Rhea:RHEA-COMP:9643, Rhea:RHEA-
CC COMP:9644, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:65264, ChEBI:CHEBI:78472;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41881;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoyl-[ACP] + malonyl-[ACP] + H(+) = 3-oxotetradecanoyl-
CC [ACP] + holo-[ACP] + CO2; Xref=Rhea:RHEA:41884, Rhea:RHEA-COMP:9623,
CC Rhea:RHEA-COMP:9644, Rhea:RHEA-COMP:9645, Rhea:RHEA-COMP:9685,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:65264, ChEBI:CHEBI:78449, ChEBI:CHEBI:78473;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41885;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxotetradecanoyl-[ACP] + NADPH + H(+) = (3R)-
CC hydroxytetradecanoyl-[ACP] + NADP(+); Xref=Rhea:RHEA:41888,
CC Rhea:RHEA-COMP:9645, Rhea:RHEA-COMP:9646, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:78473,
CC ChEBI:CHEBI:78474; Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41889;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxytetradecanoyl-[ACP] = (2E)-tetradecenoyl-[ACP] +
CC H2O; Xref=Rhea:RHEA:41892, Rhea:RHEA-COMP:9646, Rhea:RHEA-COMP:9647,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:78474, ChEBI:CHEBI:78475;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41893;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-tetradecenoyl-[ACP] + NADPH + H(+) = tetradecanoyl-[ACP]
CC + NADP(+); Xref=Rhea:RHEA:41896, Rhea:RHEA-COMP:9647, Rhea:RHEA-
CC COMP:9648, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78475, ChEBI:CHEBI:78477;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41897;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=tetradecanoyl-[ACP] + malonyl-[ACP] + H(+) = 3-
CC oxohexadecanoyl-[ACP] + holo-[ACP] + CO2; Xref=Rhea:RHEA:41900,
CC Rhea:RHEA-COMP:9623, Rhea:RHEA-COMP:9648, Rhea:RHEA-COMP:9649,
CC Rhea:RHEA-COMP:9685, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:64479, ChEBI:CHEBI:78449, ChEBI:CHEBI:78477,
CC ChEBI:CHEBI:78478; Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41901;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxohexadecanoyl-[ACP] + NADPH + H(+) = (3R)-
CC hydroxyhexadecanoyl-[ACP] + NADP(+); Xref=Rhea:RHEA:41904, Rhea:RHEA-
CC COMP:9649, Rhea:RHEA-COMP:9650, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78478, ChEBI:CHEBI:78480;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41905;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxyhexadecanoyl-[ACP] = (2E)-hexadecenoyl-[ACP] +
CC H2O; Xref=Rhea:RHEA:41908, Rhea:RHEA-COMP:9650, Rhea:RHEA-COMP:9651,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:78480, ChEBI:CHEBI:78481;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41909;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-hexadecenoyl-[ACP] + NADPH + H(+) = hexadecanoyl-[ACP] +
CC NADP(+); Xref=Rhea:RHEA:41912, Rhea:RHEA-COMP:9651, Rhea:RHEA-
CC COMP:9652, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78481, ChEBI:CHEBI:78483;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41913;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoyl-[ACP] + malonyl-[ACP] + H(+) = 3-oxooctadecanoyl-
CC [ACP] + holo-[ACP] + CO2; Xref=Rhea:RHEA:41916, Rhea:RHEA-COMP:9623,
CC Rhea:RHEA-COMP:9652, Rhea:RHEA-COMP:9653, Rhea:RHEA-COMP:9685,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:64479,
CC ChEBI:CHEBI:78449, ChEBI:CHEBI:78483, ChEBI:CHEBI:78487;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41917;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-oxooctadecanoyl-[ACP] + NADPH + H(+) = (3R)-
CC hydroxyoctadecanoyl-[ACP] + NADP(+); Xref=Rhea:RHEA:41920, Rhea:RHEA-
CC COMP:9653, Rhea:RHEA-COMP:9654, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:78487, ChEBI:CHEBI:78488;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41921;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(3R)-hydroxyoctadecanoyl-[ACP] = (2E)-octadecenoyl-[ACP] +
CC H2O; Xref=Rhea:RHEA:41924, Rhea:RHEA-COMP:9654, Rhea:RHEA-COMP:9655,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:78488, ChEBI:CHEBI:78489;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41925;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-octadecenoyl-[ACP] + NADPH + H(+) = octadecanoyl-[ACP] +
CC NADP(+); Xref=Rhea:RHEA:41928, Rhea:RHEA-COMP:9655, Rhea:RHEA-
CC COMP:9656, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:78489, ChEBI:CHEBI:78495;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41929;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=tetradecanoyl-[ACP] + H2O = tetradecanoate + holo-[ACP] +
CC H(+); Xref=Rhea:RHEA:30123, Rhea:RHEA-COMP:9648, Rhea:RHEA-COMP:9685,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30807,
CC ChEBI:CHEBI:64479, ChEBI:CHEBI:78477; EC=3.1.2.14;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:30124;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=octadecanoyl-[ACP] + H2O = octadecanoate + holo-[ACP] + H(+);
CC Xref=Rhea:RHEA:63204, Rhea:RHEA-COMP:9656, Rhea:RHEA-COMP:9685,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:25629,
CC ChEBI:CHEBI:64479, ChEBI:CHEBI:78495;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63205;
CC Evidence={ECO:0000250|UniProtKB:P49327};
CC -!- ACTIVITY REGULATION: Cerulenin, a potent non-competitive
CC pharmacological inhibitor of FAS, binds covalently to the active site
CC of the condensing enzyme region, inactivating a key enzyme step in
CC fatty acid synthesis (PubMed:16969344). Another inhibitor, though less
CC efficient, is C75, a member of the alpha-methylene-gamma-butyrolactone
CC chemical class, also proposed as an antitumour and anti-obesity agent
CC (PubMed:15715522). {ECO:0000269|PubMed:15715522,
CC ECO:0000269|PubMed:16969344}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=300 nmol/min/mg enzyme for the overall fatty acid synthase
CC reaction {ECO:0000269|PubMed:15715522};
CC Vmax=900 nmol/min/mg enzyme for the beta-ketoacyl reductase reaction
CC of acetoacetyl-CoA {ECO:0000269|PubMed:15715522};
CC Vmax=25 nmol/min/mg enzyme for the enoyl reductase reaction
CC {ECO:0000269|PubMed:15715522};
CC Vmax=25 nmol/min/mg enzyme for the thioesterase reaction
CC {ECO:0000269|PubMed:15715522};
CC Vmax=3 nmol/min/mg enzyme for the beta-ketoacyl synthase reaction
CC {ECO:0000269|PubMed:15715522, ECO:0000269|PubMed:8250834};
CC Vmax=16 nmol/min/ug enzyme for the transferase reaction using
CC malonyl-CoA as donor {ECO:0000269|PubMed:8250834};
CC Vmax=1.6 nmol/min/ug enzyme for the beta-ketoacyl reductase reaction
CC of acetoacetyl-CoA {ECO:0000269|PubMed:8250834};
CC Vmax=2.5 nmol/min/ug enzyme for the fatty acid synthase reaction
CC {ECO:0000269|PubMed:8250834};
CC Vmax=0.72 nmol/min/ug enzyme for the thioesterase reaction
CC {ECO:0000269|PubMed:8250834};
CC Vmax=1.9 nmol/min/ug enzyme for the enoyl reductase reaction
CC {ECO:0000269|PubMed:8250834};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis.
CC {ECO:0000269|PubMed:15715522, ECO:0000269|PubMed:8250834,
CC ECO:0000269|PubMed:8756713}.
CC -!- SUBUNIT: Homodimer which is arranged in a head to tail fashion (By
CC similarity). Interacts with CEACAM1; this interaction is insulin and
CC phosphorylation-dependent; reduces fatty-acid synthase activity
CC (PubMed:16054098). {ECO:0000250|UniProtKB:P49327,
CC ECO:0000269|PubMed:16054098}.
CC -!- INTERACTION:
CC P12785; P12785: Fasn; NbExp=9; IntAct=EBI-493558, EBI-493558;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Melanosome
CC {ECO:0000250}.
CC -!- INDUCTION: Up-regulated in livers of rats fed on a high carbohydrate
CC diet. {ECO:0000269|PubMed:2313386}.
CC -!- PTM: S-nitrosylation of Fatty acid synthase at cysteine residues Cys-
CC 1464 or Cys-2085 is important for the enzyme dimerization. In
CC adipocytes, S-nitrosylation of Fatty acid synthase occurs under
CC physiological conditions and gradually increases during adipogenesis.
CC {ECO:0000250|UniProtKB:P49327}.
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DR EMBL; M76767; AAA57219.1; -; mRNA.
DR EMBL; X62888; CAA44679.1; -; mRNA.
DR EMBL; X62889; CAA44680.1; -; Genomic_DNA.
DR EMBL; M84761; AAA41145.1; -; Genomic_DNA.
DR EMBL; X13415; CAA31780.1; -; mRNA.
DR EMBL; X13527; CAA31882.1; -; mRNA.
DR EMBL; J03514; AAA41144.1; -; mRNA.
DR PIR; A30313; XYRTFA.
DR RefSeq; NP_059028.1; NM_017332.1.
DR PDB; 2PNG; NMR; -; A=2114-2202.
DR PDBsum; 2PNG; -.
DR AlphaFoldDB; P12785; -.
DR BMRB; P12785; -.
DR SMR; P12785; -.
DR BioGRID; 248415; 5.
DR DIP; DIP-33893N; -.
DR IntAct; P12785; 2.
DR MINT; P12785; -.
DR STRING; 10116.ENSRNOP00000064445; -.
DR BindingDB; P12785; -.
DR ChEMBL; CHEMBL3783; -.
DR SwissLipids; SLP:000001864; -.
DR ESTHER; ratno-fas; Thioesterase.
DR CarbonylDB; P12785; -.
DR GlyGen; P12785; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P12785; -.
DR PhosphoSitePlus; P12785; -.
DR jPOST; P12785; -.
DR PaxDb; 10116-ENSRNOP00000064445; -.
DR Ensembl; ENSRNOT00000073321.3; ENSRNOP00000064445.1; ENSRNOG00000045636.3.
DR Ensembl; ENSRNOT00055056294; ENSRNOP00055046446; ENSRNOG00055032554.
DR Ensembl; ENSRNOT00060015551; ENSRNOP00060012144; ENSRNOG00060009215.
DR Ensembl; ENSRNOT00065007006; ENSRNOP00065004819; ENSRNOG00065004831.
DR GeneID; 50671; -.
DR KEGG; rno:50671; -.
DR AGR; RGD:620665; -.
DR CTD; 2194; -.
DR RGD; 620665; Fasn.
DR eggNOG; KOG1202; Eukaryota.
DR GeneTree; ENSGT00940000157276; -.
DR HOGENOM; CLU_000022_31_7_1; -.
DR InParanoid; P12785; -.
DR OrthoDB; 3378513at2759; -.
DR PhylomeDB; P12785; -.
DR Reactome; R-RNO-199220; Vitamin B5 (pantothenate) metabolism.
DR Reactome; R-RNO-75105; Fatty acyl-CoA biosynthesis.
DR SABIO-RK; P12785; -.
DR UniPathway; UPA00094; -.
DR EvolutionaryTrace; P12785; -.
DR PRO; PR:P12785; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000045636; Expressed in liver and 19 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0042587; C:glycogen granule; ISO:RGD.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0019171; F:(3R)-hydroxyacyl-[acyl-carrier-protein] dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0004316; F:3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0004313; F:[acyl-carrier-protein] S-acetyltransferase activity; ISO:RGD.
DR GO; GO:0004314; F:[acyl-carrier-protein] S-malonyltransferase activity; IMP:UniProtKB.
DR GO; GO:0141148; F:enoyl-[acyl-carrier-protein] reductase (NADPH) activity; IEA:UniProtKB-EC.
DR GO; GO:0004312; F:fatty acid synthase activity; IDA:CACAO.
DR GO; GO:0016297; F:fatty acyl-[ACP] hydrolase activity; IEA:UniProtKB-EC.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006084; P:acetyl-CoA metabolic process; IDA:RGD.
DR GO; GO:0071353; P:cellular response to interleukin-4; ISO:RGD.
DR GO; GO:0090557; P:establishment of endothelial intestinal barrier; ISO:RGD.
DR GO; GO:0008611; P:ether lipid biosynthetic process; ISO:RGD.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IDA:RGD.
DR GO; GO:0002068; P:glandular epithelial cell development; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR GO; GO:0008610; P:lipid biosynthetic process; ISO:RGD.
DR GO; GO:0030879; P:mammary gland development; ISO:RGD.
DR GO; GO:0030224; P:monocyte differentiation; ISO:RGD.
DR GO; GO:0030223; P:neutrophil differentiation; ISO:RGD.
DR GO; GO:0007584; P:response to nutrient; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0009888; P:tissue development; ISO:RGD.
DR CDD; cd05195; enoyl_red; 1.
DR CDD; cd08954; KR_1_FAS_SDR_x; 2.
DR CDD; cd00833; PKS; 1.
DR FunFam; 1.10.1200.10:FF:000013; Fatty acid synthase; 1.
DR FunFam; 3.10.129.110:FF:000002; Fatty acid synthase; 1.
DR FunFam; 3.40.366.10:FF:000005; Fatty acid synthase; 1.
DR FunFam; 3.40.47.10:FF:000033; Fatty acid synthase; 1.
DR FunFam; 3.40.50.150:FF:000186; Fatty acid synthase; 1.
DR FunFam; 3.40.50.1820:FF:000059; Fatty acid synthase; 1.
DR FunFam; 3.40.50.1820:FF:000105; Fatty acid synthase; 1.
DR FunFam; 3.40.50.720:FF:000249; Fatty acid synthase; 1.
DR FunFam; 3.90.180.10:FF:000015; Fatty acid synthase; 1.
DR FunFam; 3.40.50.720:FF:000209; Polyketide synthase Pks12; 1.
DR Gene3D; 3.30.70.3290; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 1.10.1200.10; ACP-like; 1.
DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 2.
DR Gene3D; 3.40.366.10; Malonyl-Coenzyme A Acyl Carrier Protein, domain 2; 1.
DR Gene3D; 3.90.180.10; Medium-chain alcohol dehydrogenases, catalytic domain; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR Gene3D; 3.10.129.110; Polyketide synthase dehydratase; 1.
DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR InterPro; IPR029058; AB_hydrolase_fold.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase_dom.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR049391; FAS_pseudo-KR.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020807; PKS_DH.
DR InterPro; IPR049552; PKS_DH_N.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR049900; PKS_mFAS_DH.
DR InterPro; IPR050091; PKS_NRPS_Biosynth_Enz.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR001031; Thioesterase.
DR InterPro; IPR016039; Thiolase-like.
DR PANTHER; PTHR43775; FATTY ACID SYNTHASE; 1.
DR PANTHER; PTHR43775:SF7; FATTY ACID SYNTHASE; 1.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF13602; ADH_zinc_N_2; 1.
DR Pfam; PF21149; FAS_pseudo-KR; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF21089; PKS_DH_N; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00822; PKS_KR; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; ACP-like; 1.
DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1.
DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 1.
DR SUPFAM; SSF50129; GroES-like; 1.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 2.
DR SUPFAM; SSF55048; Probable ACP-binding domain of malonyl-CoA ACP transacylase; 1.
DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR SUPFAM; SSF53901; Thiolase-like; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00606; KS3_1; 1.
DR PROSITE; PS52004; KS3_2; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
DR PROSITE; PS52019; PKS_MFAS_DH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Fatty acid biosynthesis;
KW Fatty acid metabolism; Hydrolase; Isopeptide bond; Lipid biosynthesis;
KW Lipid metabolism; Lyase; Multifunctional enzyme; NAD; NADP; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Pyridoxal phosphate;
KW Reference proteome; S-nitrosylation; Transferase; Ubl conjugation.
FT CHAIN 1..2505
FT /note="Fatty acid synthase"
FT /id="PRO_0000180279"
FT DOMAIN 1..406
FT /note="Ketosynthase family 3 (KS3)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT DOMAIN 844..1112
FT /note="PKS/mFAS DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT DOMAIN 2113..2193
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 429..817
FT /note="Acyl and malonyl transferases"
FT REGION 844..966
FT /note="N-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 983..1112
FT /note="C-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1629..1857
FT /note="Enoyl reductase"
FT REGION 1858..2113
FT /note="Beta-ketoacyl reductase"
FT REGION 2202..2505
FT /note="Thioesterase"
FT ACT_SITE 161
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 293
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 331
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 581
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 878
FT /note="Proton acceptor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT ACT_SITE 1032
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT ACT_SITE 2302
FT /note="For thioesterase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 2475
FT /note="For thioesterase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT BINDING 647..648
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P19096"
FT BINDING 671
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P19096"
FT BINDING 773
FT /ligand="an acyl-CoA"
FT /ligand_id="ChEBI:CHEBI:58342"
FT /evidence="ECO:0000250|UniProtKB:P19096"
FT BINDING 1665..1682
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="1"
FT /ligand_note="for enoyl reductase activity"
FT BINDING 1765..1780
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /ligand_label="2"
FT /ligand_note="for ketoreductase activity"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P49327"
FT MOD_RES 59
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P19096"
FT MOD_RES 63
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49327"
FT MOD_RES 70
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P49327"
FT MOD_RES 207
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49327"
FT MOD_RES 298
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P49327"
FT MOD_RES 528
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P49327"
FT MOD_RES 673
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P49327"
FT MOD_RES 725
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 790
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P19096"
FT MOD_RES 993
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P19096"
FT MOD_RES 1276
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P19096"
FT MOD_RES 1464
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P49327"
FT MOD_RES 1578
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1588
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19096"
FT MOD_RES 1698
FT /note="N6-(pyridoxal phosphate)lysine; alternate"
FT /evidence="ECO:0000250"
FT MOD_RES 1698
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P49327"
FT MOD_RES 1765
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P49327"
FT MOD_RES 1841
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P49327"
FT MOD_RES 1989
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P49327"
FT MOD_RES 2085
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:P49327"
FT MOD_RES 2151
FT /note="O-(pantetheine 4'-phosphoryl)serine; alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2151
FT /note="Phosphoserine; alternate"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 2191
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 2230
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49327"
FT MOD_RES 2385
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P19096"
FT CROSSLNK 2443
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P49327"
FT CONFLICT 184
FT /note="I -> T (in Ref. 3; AAA41145)"
FT /evidence="ECO:0000305"
FT CONFLICT 871
FT /note="S -> P (in Ref. 4; CAA31780)"
FT /evidence="ECO:0000305"
FT CONFLICT 2085
FT /note="C -> P (in Ref. 6; AAA41144)"
FT /evidence="ECO:0000305"
FT CONFLICT 2106
FT /note="A -> V (in Ref. 1; AAA57219, 3; AAA41145 and 5;
FT CAA31882)"
FT /evidence="ECO:0000305"
FT CONFLICT 2296
FT /note="Y -> H (in Ref. 1; AAA57219 and 5; CAA31882)"
FT /evidence="ECO:0000305"
FT HELIX 2122..2124
FT /evidence="ECO:0007829|PDB:2PNG"
FT HELIX 2126..2130
FT /evidence="ECO:0007829|PDB:2PNG"
FT STRAND 2140..2142
FT /evidence="ECO:0007829|PDB:2PNG"
FT HELIX 2144..2147
FT /evidence="ECO:0007829|PDB:2PNG"
FT HELIX 2152..2164
FT /evidence="ECO:0007829|PDB:2PNG"
FT HELIX 2171..2174
FT /evidence="ECO:0007829|PDB:2PNG"
FT HELIX 2180..2184
FT /evidence="ECO:0007829|PDB:2PNG"
FT STRAND 2188..2190
FT /evidence="ECO:0007829|PDB:2PNG"
FT STRAND 2192..2194
FT /evidence="ECO:0007829|PDB:2PNG"
SQ SEQUENCE 2505 AA; 272650 MW; 5810EC13D37F3114 CRC64;
MEEVVIAGMS GKLPESENLQ EFWANLIGGV DMVTDDDRRW KAGLYGLPKR SGKLKDLSKF
DASFFGVHPK QAHTMDPQLR LLLEVSYEAI VDGGINPASL RGTNTGVWVG VSGSEASEAL
SRDPETLLGY SMVGCQRAMM ANRLSFFFDF KGPSIALDTA CSSSLLALQN AYQAIRSGEC
PAAIVGGINL LLKPNTSVQF MKLGMLSPDG TCRSFDDSGN GYCRAEAVVA VLLTKKSLAR
RVYATILNAG TNTDGCKEQG VTFPSGEAQE QLIRSLYQPG GVAPESLEYI EAHGTGTKVG
DPQELNGITR SLCAFRQSPL LIGSTKSNMG HPEPASGLAA LTKVLLSLEN GVWAPNLHFH
NPNPEIPALL DGRLQVVDRP LPVRGGIVGI NSFGFGGANV HVILQPNTQQ APAPAPHAAL
PHLLHASGRT MEAVQGLLEQ GRQHSQDLAF VSMLNDIAAT PTAAMPFRGY TVLGVEGHVQ
EVQQVPASQR PLWFICSGMG TQWRGMGLSL MRLDSFRESI LRSDEALKPL GVKVSDLLLS
TDEHTFDDIV HSFVSLTAIQ IALIDLLTSM GLKPDGIIGH SLGEVACGYA DGCLSQREAV
LAAYWRGQCI KDANLPAGSM AAVGLSWEEC KQRCPPGVVP ACHNSEDTVT ISGPQAAVNE
FVEQLKQEGV FAKEVRTGGL AFHSYFMEGI APTLLQALKK VIREPRPRSA RWLSTSIPEA
QWQSSLARTS SAEYNVNNLV SPVLFQEALW HVPEHAVVLE IAPHALLQAV LKRGVKPSCT
IIPLMKRDHK DNLEFFLTNL GKVHLTGIDI NPNALFPPVE FPVPRGTPLI SPHIKWDHSQ
TWDIPVAEDF PNGSSSSSAT VYNIDASSES SDHYLVDHCI DGRVLFPGTG YLYLVWKTLA
RSLSLSLEET PVVFENVTFH QATILPRTGT VPLEVRLLEA SHAFEVSDSG NLIVSGKVYQ
WEDPDSKLFD HPEVPIPAES ESVSRLTQGE VYKELRLRGY DYGPHFQGVY EATLEGEQGK
LLWKDNWVTF MDTMLQISIL GFSKQSLQLP TRVTAIYIDP ATHLQKVYML EGDTQVADVT
TSRCLGVTVS GGVYISRLQT TATSRRQQEQ LVPTLEKFVF TPHVEPECLS ESAILQKELQ
LCKGLAKALQ TKATQQGLKM TVPGLEDLPQ HGLPRLLAAA CQLQLNGNLQ LELGEVLARE
RLLLPEDPLI SGLLNSQALK ACIDTALENL STLKMKVVEV LAGEGHLYSH ISALLNTQPM
LQLEYTATDR HPQALKDVQT KLQQHDVAQG QWDPSGPAPT NLGALDLVVC NCALATLGDP
ALALDNMVAA LKDGGFLLMH TVLKGHALGE TLACLPSEVQ PGPSFLSQEE WESLFSRKAL
HLVGLKKSFY GTALFLCRRL SPQDKPIFLP VEDTSFQWVD SLKSILATSS SQPVWLTAMN
CPTSGVVGLV NCLRKEPGGH RIRCILLSNL SSTSHVPKLD PGSSELQKVL ESDLVMNVYR
DGAWGAFRHF QLEQDKPEEQ TAHAFVNVLT RGDLASIRWV SSPLKHMQPP SSSGAQLCTV
YYASLNFRDI MLATGKLSPD AIPGKWASRD CMLGMEFSGR DKCGRRVMGL VPAEGLATSV
LLSPDFLWDV PSSWTLEEAA SVPVVYTTAY YSLVVRGRIQ HGETVLIHSG SGGVGQAAIS
IALSLGCRVF TTVGSAEKRA YLQARFPQLD DTSFANSRDT SFEQHVLLHT GGKGVDLVLN
SLAEEKLQAS VRCLAQHGRF LEIGKFDLSN NHPLGMAIFL KNVTFHGILL DALFEGANDS
WREVAELLKA GIRDGVVKPL KCTVFPKAQV EDAFRYMAQG KHIGKVLVQV REEEPEAMLP
GAQPTLISAI SKTFCPEHKS YIITGGLGGF GLELARWLVL RGAQRLVLTS RSGIRTGYQA
KHVREWRRQG IHVLVSTSNV SSLEGARALI AEATKLGPVG GVFNLAMVLR DAMLENQTPE
LFQDVNKPKY NGTLNLDRAT REACPELDYF VAFSSVSCGR GNAGQSNYGF ANSTMERICE
QRRHDGLPGL AVQWGAIGDV GIILEAMGTN DTVVGGTLPQ RISSCMEVLD LFLNQPHAVL
SSFVLAEKKA VAHGDGEAQR DLVKAVAHIL GIRDLAGINL DSSLADLGLD SLMGVEVRQI
LEREHDLVLP IREVRQLTLR KLQEMSSKAG SDTELAAPKS KNDTSLKQAQ LNLSILLVNP
EGPTLTRLNS VQSSERPLFL VHPIEGSITV FHSLAAKLSV PTYGLQCTQA APLDSIPNLA
AYYIDCIKQV QPEGPYRVAG YSFGACVAFE MCSQLQAQQG PAPAHNNLFL FDGSHTYVLA
YTQSYRAKLT PGCEAEAEAE AICFFIKQFV DAEHSKVLEA LLPLKSLEDR VAAAVDLITR
SHQSLDRRDL SFAAVSFYYK LRAADQYKPK AKYHGNVILL RAKTGGTYGE DLGADYNLSQ
VCDGKVSVHI IEGDHRTLLE GRGLESIINI IHSSLAEPRV SVREG
//
