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 03-APR-2013, entry version 133.
DE RecName: Full=Fatty acid synthase;
DE EC=2.3.1.85;
DE Includes:
DE RecName: Full=[Acyl-carrier-protein] S-acetyltransferase;
DE EC=2.3.1.38;
DE Includes:
DE RecName: Full=[Acyl-carrier-protein] S-malonyltransferase;
DE EC=2.3.1.39;
DE Includes:
DE RecName: Full=3-oxoacyl-[acyl-carrier-protein] synthase;
DE EC=2.3.1.41;
DE Includes:
DE RecName: Full=3-oxoacyl-[acyl-carrier-protein] reductase;
DE EC=1.1.1.100;
DE Includes:
DE RecName: Full=3-hydroxyacyl-[acyl-carrier-protein] dehydratase;
DE EC=4.2.1.59;
DE Includes:
DE RecName: Full=Enoyl-[acyl-carrier-protein] reductase;
DE EC=1.3.1.10;
DE Includes:
DE RecName: Full=Oleoyl-[acyl-carrier-protein] hydrolase;
DE EC=3.1.2.14;
GN Name=Fasn;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC Muroidea; Muridae; 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.,
RA Smith S.;
RT "Molecular cloning and sequencing of cDNAs encoding the entire rat
RT fatty 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;
RA Beck K.F., Schreglmann R., Stathopulos I., Klein H., Hoch J.,
RA 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
RT fatty 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
RT constituent domains and two functional polyadenylation/termination
RT signals in the 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
RT 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;
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;
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 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 catalyzes the formation of long-
CC chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This
CC multifunctional protein has 7 catalytic activities and an acyl
CC carrier protein.
CC -!- CATALYTIC ACTIVITY: Acetyl-CoA + n malonyl-CoA + 2n NADPH = a
CC long-chain fatty acid + (n+1) CoA + n CO(2) + 2n NADP(+).
CC -!- CATALYTIC ACTIVITY: Acetyl-CoA + [acyl-carrier-protein] = CoA +
CC acetyl-[acyl-carrier-protein].
CC -!- CATALYTIC ACTIVITY: Malonyl-CoA + [acyl-carrier-protein] = CoA +
CC malonyl-[acyl-carrier-protein].
CC -!- CATALYTIC ACTIVITY: Acyl-[acyl-carrier-protein] + malonyl-[acyl-
CC carrier-protein] = 3-oxoacyl-[acyl-carrier-protein] + CO(2) +
CC [acyl-carrier-protein].
CC -!- CATALYTIC ACTIVITY: (3R)-3-hydroxyacyl-[acyl-carrier-protein] +
CC NADP(+) = 3-oxoacyl-[acyl-carrier-protein] + NADPH.
CC -!- CATALYTIC ACTIVITY: A (3R)-3-hydroxyacyl-[acyl-carrier protein] =
CC a trans-2-enoyl-[acyl-carrier protein] + H(2)O.
CC -!- CATALYTIC ACTIVITY: Acyl-[acyl-carrier-protein] + NADP(+) = trans-
CC 2,3-dehydroacyl-[acyl-carrier-protein] + NADPH.
CC -!- CATALYTIC ACTIVITY: Oleoyl-[acyl-carrier-protein] + H(2)O = [acyl-
CC carrier-protein] + oleate.
CC -!- SUBUNIT: Homodimer which is arranged in a head to tail fashion.
CC -!- INTERACTION:
CC Self; NbExp=8; IntAct=EBI-493558, EBI-493558;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Melanosome (By
CC similarity).
CC -!- INDUCTION: Up-regulated in livers of rats fed on a high
CC carbohydrate diet.
CC -!- SIMILARITY: Contains 1 acyl carrier domain.
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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 IPI; IPI00200661; -.
DR PIR; A30313; XYRTFA.
DR RefSeq; NP_059028.1; NM_017332.1.
DR UniGene; Rn.9486; -.
DR PDB; 2PNG; NMR; -; A=2114-2202.
DR PDBsum; 2PNG; -.
DR ProteinModelPortal; P12785; -.
DR SMR; P12785; 423-819, 2114-2202, 2216-2501.
DR DIP; DIP-33893N; -.
DR PRIDE; P12785; -.
DR Ensembl; ENSRNOT00000073321; ENSRNOP00000064445; ENSRNOG00000045636.
DR GeneID; 50671; -.
DR KEGG; rno:50671; -.
DR CTD; 2194; -.
DR RGD; 620665; Fasn.
DR GeneTree; ENSGT00530000063309; -.
DR HOVERGEN; HBG005640; -.
DR KO; K00665; -.
DR SABIO-RK; P12785; -.
DR BindingDB; P12785; -.
DR ChEMBL; CHEMBL3783; -.
DR EvolutionaryTrace; P12785; -.
DR NextBio; 610498; -.
DR Genevestigator; P12785; -.
DR GO; GO:0042587; C:glycogen granule; IEA:Compara.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Compara.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:Compara.
DR GO; GO:0005886; C:plasma membrane; IEA:Compara.
DR GO; GO:0047451; F:3-hydroxyoctanoyl-[acyl-carrier-protein] dehydratase activity; IEA:EC.
DR GO; GO:0004317; F:3-hydroxypalmitoyl-[acyl-carrier-protein] dehydratase activity; IEA:InterPro.
DR GO; GO:0004316; F:3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; IEA:EC.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:EC.
DR GO; GO:0004313; F:[acyl-carrier-protein] S-acetyltransferase activity; IEA:EC.
DR GO; GO:0004314; F:[acyl-carrier-protein] S-malonyltransferase activity; IEA:EC.
DR GO; GO:0008144; F:drug binding; IDA:RGD.
DR GO; GO:0004319; F:enoyl-[acyl-carrier-protein] reductase (NADPH, B-specific) activity; IEA:EC.
DR GO; GO:0004312; F:fatty acid synthase activity; IDA:RGD.
DR GO; GO:0016295; F:myristoyl-[acyl-carrier-protein] hydrolase activity; IEA:EC.
DR GO; GO:0070402; F:NADPH binding; IDA:RGD.
DR GO; GO:0004320; F:oleoyl-[acyl-carrier-protein] hydrolase activity; IEA:EC.
DR GO; GO:0016296; F:palmitoyl-[acyl-carrier-protein] hydrolase activity; IEA:EC.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:RGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006084; P:acetyl-CoA metabolic process; IDA:RGD.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IMP:RGD.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 1.10.1470.20; -; 1.
DR Gene3D; 3.40.366.10; -; 2.
DR Gene3D; 3.40.47.10; -; 2.
DR Gene3D; 3.40.50.720; -; 2.
DR InterPro; IPR001227; Ac_transferase_dom.
DR InterPro; IPR009081; Acyl_carrier_prot-like.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR013149; ADH_C.
DR InterPro; IPR023102; Fatty_acid_synthase_dom_2.
DR InterPro; IPR011032; GroES-like.
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; IPR016040; NAD(P)-bd_dom.
DR InterPro; IPR020842; PKS/FAS_KR.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR006162; PPantetheine_attach_site.
DR InterPro; IPR001031; Thioesterase.
DR InterPro; IPR016039; Thiolase-like.
DR InterPro; IPR016038; Thiolase-like_subgr.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00107; ADH_zinc_N; 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; PF00550; PP-binding; 1.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00822; PKS_KR; 1.
DR SUPFAM; SSF47336; ACP_like; 1.
DR SUPFAM; SSF52151; Acyl_Trfase/lysoPlipase; 1.
DR SUPFAM; SSF50129; GroES_like; 1.
DR SUPFAM; SSF55048; Malonyl_transacylase_ACP-bd; 1.
DR SUPFAM; SSF53901; Thiolase-like; 1.
DR PROSITE; PS50075; ACP_DOMAIN; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Fatty acid biosynthesis; Fatty acid metabolism; Hydrolase;
KW Lipid biosynthesis; Lipid metabolism; Lyase; Multifunctional enzyme;
KW NAD; NADP; Oxidoreductase; Phosphopantetheine; Phosphoprotein;
KW Pyridoxal phosphate; Reference proteome; Transferase.
FT CHAIN 1 2505 Fatty acid synthase.
FT /FTId=PRO_0000180279.
FT DOMAIN 2118 2174 Acyl carrier.
FT NP_BIND 1665 1682 NADP (ER).
FT NP_BIND 1765 1780 NADP (KR).
FT REGION 1 413 Beta-ketoacyl synthase.
FT REGION 429 817 Acyl and malonyl transferases.
FT REGION 1629 1857 Enoyl reductase.
FT REGION 1858 2113 Beta-ketoacyl reductase.
FT REGION 2202 2505 Thioesterase.
FT ACT_SITE 161 161 For beta-ketoacyl synthase activity (By
FT similarity).
FT ACT_SITE 581 581 For malonyltransferase activity (By
FT similarity).
FT ACT_SITE 878 878 For beta-hydroxyacyl dehydratase activity
FT (By similarity).
FT ACT_SITE 2302 2302 For thioesterase activity (By
FT similarity).
FT ACT_SITE 2475 2475 For thioesterase activity (By
FT similarity).
FT MOD_RES 1 1 N-acetylmethionine (By similarity).
FT MOD_RES 70 70 N6-acetyllysine (By similarity).
FT MOD_RES 207 207 Phosphoserine (By similarity).
FT MOD_RES 298 298 N6-acetyllysine (By similarity).
FT MOD_RES 528 528 N6-acetyllysine (By similarity).
FT MOD_RES 673 673 N6-acetyllysine (By similarity).
FT MOD_RES 1698 1698 N6-(pyridoxal phosphate)lysine (By
FT similarity).
FT MOD_RES 1698 1698 N6-acetyllysine (By similarity).
FT MOD_RES 1765 1765 N6-acetyllysine (By similarity).
FT MOD_RES 1841 1841 N6-acetyllysine (By similarity).
FT MOD_RES 1989 1989 N6-acetyllysine (By similarity).
FT MOD_RES 2151 2151 O-(pantetheine 4'-phosphoryl)serine (By
FT similarity).
FT MOD_RES 2230 2230 Phosphoserine (By similarity).
FT CONFLICT 184 184 I -> T (in Ref. 3; AAA41145).
FT CONFLICT 871 871 S -> P (in Ref. 4; CAA31780).
FT CONFLICT 2085 2085 C -> P (in Ref. 6; AAA41144).
FT CONFLICT 2106 2106 A -> V (in Ref. 1; AAA57219, 3; AAA41145
FT and 5; CAA31882).
FT CONFLICT 2296 2296 Y -> H (in Ref. 1; AAA57219 and 5;
FT CAA31882).
FT HELIX 2122 2124
FT HELIX 2126 2130
FT STRAND 2140 2142
FT HELIX 2144 2147
FT HELIX 2152 2164
FT HELIX 2171 2174
FT HELIX 2180 2184
FT STRAND 2188 2190
FT STRAND 2192 2194
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
//
