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UniProtKB/Swiss-Prot entry P12785


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name FAS_RAT
Primary accession number P12785
Secondary accession numbers O09187 O09190 Q63577 Q64717
Integrated into Swiss-Prot on October 1, 1989
Sequence was last modified on November 1, 1997 (Sequence version 3)
Annotations were last modified on    July 22, 2008 (Entry version 92)
Name and origin of the protein
Protein name Fatty acid synthase
Synonym EC 2.3.1.85
Includes [Acyl-carrier-protein] S-acetyltransferase
     (EC 2.3.1.38)
[Acyl-carrier-protein] S-malonyltransferase
     (EC 2.3.1.39)
3-oxoacyl-[acyl-carrier-protein] synthase
     (EC 2.3.1.41)
3-oxoacyl-[acyl-carrier-protein] reductase
     (EC 1.1.1.100)
3-hydroxypalmitoyl-[acyl-carrier-protein] dehydratase
     (EC 4.2.1.61)
Enoyl-[acyl-carrier-protein] reductase
     (EC 1.3.1.10)
Oleoyl-[acyl-carrier-protein] hydrolase
     (EC 3.1.2.14)
Gene name
Name: Fasn
From
Rattus norvegicus (Rat) [TaxID: 10116] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; Muroidea; Muridae; Murinae; Rattus.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE.
PubMed=2717611 [NCBI, ExPASy, EBI, Israel, Japan]
Amy C.M., Witkowski A., Naggert J., Williams B., Randhawa Z., Smith S.;
"Molecular cloning and sequencing of cDNAs encoding the entire rat fatty acid synthase.";
Proc. Natl. Acad. Sci. U.S.A. 86:3114-3118(1989).
[2]
NUCLEOTIDE SEQUENCE.
STRAIN=Sprague-Dawley;
TISSUE=Liver;
PubMed=1339331 [NCBI, ExPASy, EBI, Israel, Japan]
Beck K.F., Schreglmann R., Stathopulos I., Klein H., Hoch J., Schweizer M.;
"The fatty acid synthase (FAS) gene and its promoter in Rattus norvegicus.";
DNA Seq. 2:359-386(1992).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=1736293 [NCBI, ExPASy, EBI, Israel, Japan]
Amy C.M., Williams-Ahlf B., Naggert J., Smith S.;
"Intron-exon organization of the gene for the multifunctional animal fatty acid synthase.";
Proc. Natl. Acad. Sci. U.S.A. 89:1105-1108(1992).
[4]
NUCLEOTIDE SEQUENCE [MRNA] OF 75-2505.
STRAIN=Sprague-Dawley;
TISSUE=Mammary gland;
DOI=10.1093/nar/17.2.567; PubMed=2915923 [NCBI, ExPASy, EBI, Israel, Japan]
Schweizer M., Takabeyashi K., Beck K.F., Schreglmann R.;
"Rat mammary gland fatty acid synthase: localization of the constituent domains and two functional polyadenylation/termination signals in the cDNA.";
Nucleic Acids Res. 17:567-586(1989).
[5]
NUCLEOTIDE SEQUENCE [MRNA] OF 2085-2505.
TISSUE=Mammary gland;
PubMed=2891707 [NCBI, ExPASy, EBI, Israel, Japan]
Naggert J., Witkowski A., Mikkelsen J., Smith S.;
"Molecular cloning and sequencing of a cDNA encoding the thioesterase domain of the rat fatty acid synthetase.";
J. Biol. Chem. 263:1146-1150(1988).
[6]
NUCLEOTIDE SEQUENCE OF 1921-2324.
TISSUE=Mammary gland;
PubMed=3109907 [NCBI, ExPASy, EBI, Israel, Japan]
Witlowski A., Naggert J., Mikkelsen J., Smith S.;
"Molecular cloning and sequencing of a cDNA encoding the acyl carrier protein and its flanking domains in the mammalian fatty acid synthetase.";
Eur. J. Biochem. 165:601-606(1987).
[7]
NUCLEOTIDE SEQUENCE OF 2377-2413, AND INDUCTION.
PubMed=2313386 [NCBI, ExPASy, EBI, Israel, Japan]
Clarke S.D., Armstrong M.K., Jump D.B.;
"Nutritional control of rat liver fatty acid synthase and S14 mRNA abundance.";
J. Nutr. 120:218-224(1990).
[8]
STRUCTURE BY NMR OF 2114-2202.
DOI=10.1039/b208941f; PubMed=12926246 [NCBI, ExPASy, EBI, Israel, Japan]
Reed M.A.C., Schweizer M., Szafranska A.E., Arthur C., Nicholson T.P., Cox R.J., Crosby J., Crump M.P., Simpson T.J.;
"The type I rat fatty acid synthase ACP shows structural homology and analogous biochemical properties to type II ACPs.";
Org. Biomol. Chem. 1:463-471(2003).
Comments
  • FUNCTION: Fatty acid synthetase catalyzes the formation of long-chain fatty acids from acetyl-CoA, malonyl-CoA and NADPH. This multifunctional protein has 7 catalytic activities and an acyl carrier protein.
  • CATALYTIC ACTIVITY: Acetyl-CoA + n malonyl-CoA + 2n NADPH = a long-chain fatty acid + (n+1) CoA + n CO2 + 2n NADP+.
  • CATALYTIC ACTIVITY: Acetyl-CoA + [acyl-carrier-protein] = CoA + acetyl-[acyl-carrier-protein].
  • CATALYTIC ACTIVITY: Malonyl-CoA + [acyl-carrier-protein] = CoA + malonyl-[acyl-carrier-protein].
  • CATALYTIC ACTIVITY: Acyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = 3-oxoacyl-[acyl-carrier-protein] + CO2 + [acyl-carrier-protein].
  • CATALYTIC ACTIVITY: (3R)-3-hydroxyacyl-[acyl-carrier-protein] + NADP+ = 3-oxoacyl-[acyl-carrier-protein] + NADPH.
  • CATALYTIC ACTIVITY: (3R)-3-hydroxypalmitoyl-[acyl-carrier-protein] = hexadec-2-enoyl-[acyl-carrier-protein] + H2O.
  • CATALYTIC ACTIVITY: Acyl-[acyl-carrier-protein] + NADP+ = trans-2,3-dehydroacyl-[acyl-carrier-protein] + NADPH.
  • CATALYTIC ACTIVITY: Oleoyl-[acyl-carrier-protein] + H2O = [acyl-carrier-protein] + oleate.
  • SUBUNIT: Homodimer which is arranged in a head to tail fashion.
  • INTERACTION:
    Self; NbExp=2; IntAct=EBI-493558, EBI-493558;
  • SUBCELLULAR LOCATION: Cytoplasm (By similarity). Melanosome (By similarity).
  • INDUCTION: Up-regulated in livers of rats fed on a high carbohydrate diet.
  • SIMILARITY: Contains 1 acyl carrier domain.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M76767; AAA57219.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X62888; CAA44679.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X62889; CAA44680.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M84761; AAA41145.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X13415; CAA31780.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
X13527; CAA31882.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
J03514; AAA41144.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A30313; XYRTFA.
RefSeq NP_059028.1; -.
UniGene Rn.9486
3D structure databases
PDB
1N8L; NMR; -; A=2114-2202.[ExPASy / RCSB / EBI]
2PNG; NMR; -; A=2114-2202.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1N8L; -.
2PNG; -.
SMR P12785; 2211-2496.
ModBase P12785.
Protein-protein interaction databases
IntAct P12785; -.
Organism-specific databases
RGD 620665; Fasn.
Ontologies
GO
GO:0042802; Molecular function: identical protein binding (inferred from physical interaction from IntAct).
QuickGo view.
Family and domain databases
InterPro IPR001227; Ac_transferase_reg.
IPR009081; ACP_like.
IPR014043; Acyl_transferase.
IPR013149; AlcDHase_Zn-bd.
IPR002198; DHase_sc/Rdtase_SDR.
IPR000794; Ketoacyl_synth.
IPR014031; Ketoacyl_synth_C.
IPR014030; Ketoacyl_synth_N.
IPR013217; Methyltransf_12.
IPR016040; NAD(P)-bd.
IPR006163; Phsphopanteth_bd.
IPR006162; Ppantne_S.
IPR001031; Thioesterase.
IPR016038; Thiolase-like_subgr.
Graphical view of domain structure.
Gene3D G3DSA:3.40.366.10; Ac_transferase_reg; 1.
G3DSA:1.10.1200.10; ACP_like; 1.
G3DSA:3.40.50.720; NAD(P)-bd; 2.
G3DSA:3.40.47.10; Thiolase-like_subgr; 2.
PANTHER PTHR11712; Ketoacyl_synth; 1.
Pfam PF00698; Acyl_transf_1; 1.
PF00106; adh_short; 1.
PF00107; ADH_zinc_N; 1.
PF00109; ketoacyl-synt; 1.
PF02801; Ketoacyl-synt_C; 1.
PF08242; Methyltransf_12; 1.
PF00550; PP-binding; 1.
PF00975; Thioesterase; 1.
Pfam graphical view of domain structure.
PROSITE PS50075; ACP_DOMAIN; 1.
PS00606; B_KETOACYL_SYNTHASE; 1.
PS00012; PHOSPHOPANTETHEINE; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS P12785.
Genome annotation databases
GeneID 50671; -.
KEGG rno:50671; -.
Phylogenomic databases
HOVERGEN P12785; -.
Other
ProtoNet P12785.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Acetylation; Cytoplasm; Fatty acid biosynthesis; Hydrolase; Lipid synthesis; Lyase; Multifunctional enzyme; NAD; NADP; Oxidoreductase; Phosphopantetheine; Pyridoxal phosphate; Transferase.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom    To Length Description FTId
CHAIN   1   2505  2505     Fatty acid synthase. PRO_0000180279
DOMAIN   2118   2174  57     Acyl carrier. 
NP_BIND   1665   1682  18     NADP (ER). 
NP_BIND   1765   1780  16     NADP (KR). 
REGION   1    413  413     Beta-ketoacyl synthase. 
REGION   429    817  389     Acyl and malonyl transferases. 
REGION   1629   1857  229     Enoyl reductase. 
REGION   1858   2113  256     Beta-ketoacyl reductase. 
REGION   2202   2505  304     Thioesterase. 
ACT_SITE   161    161        For beta-ketoacyl synthase activity (By similarity). 
ACT_SITE   581    581        For malonyltransferase activity (By similarity). 
ACT_SITE   878    878        For beta-hydroxyacyl dehydratase activity (By similarity). 
ACT_SITE   2302   2302        For thioesterase activity (By similarity). 
ACT_SITE   2475   2475        For thioesterase activity (By similarity). 
BINDING   1698   1698        Pyridoxal phosphate (covalent) (By similarity). 
BINDING   2151   2151        Phosphopantetheine (covalent) (By similarity). 
MOD_RES   1      1        N-acetylmethionine (By similarity). 
CONFLICT   184    184        I -> T (in Ref. 3; AAA41145). 
CONFLICT   871    871        S -> P (in Ref. 4; CAA31780). 
CONFLICT   1967   1968        MV -> IL (in Ref. 6). 
CONFLICT   2085   2085        C -> P (in Ref. 5; AAA41144). 
CONFLICT   2106   2106        A -> V (in Ref. 1, 3 and 6). 
CONFLICT   2296   2296        Y -> H (in Ref. 1 and 6). 
HELIX   2122   2124  3      
HELIX   2126   2130  5      
STRAND   2140   2142  3      
HELIX   2144   2147  4      
HELIX   2152   2164  13      
HELIX   2171   2174  4      
HELIX   2180   2184  5      
STRAND   2188   2190  3      
STRAND   2192   2194  3      
Sequence information
Length: 2505 AA [This is the length of the unprocessed precursor] Molecular weight: 272650 Da [This is the MW of the unprocessed precursor] CRC64: 5810EC13D37F3114 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MEEVVIAGMS GKLPESENLQ EFWANLIGGV DMVTDDDRRW KAGLYGLPKR SGKLKDLSKF 

        70         80         90        100        110        120 
DASFFGVHPK QAHTMDPQLR LLLEVSYEAI VDGGINPASL RGTNTGVWVG VSGSEASEAL 

       130        140        150        160        170        180 
SRDPETLLGY SMVGCQRAMM ANRLSFFFDF KGPSIALDTA CSSSLLALQN AYQAIRSGEC 

       190        200        210        220        230        240 
PAAIVGGINL LLKPNTSVQF MKLGMLSPDG TCRSFDDSGN GYCRAEAVVA VLLTKKSLAR 

       250        260        270        280        290        300 
RVYATILNAG TNTDGCKEQG VTFPSGEAQE QLIRSLYQPG GVAPESLEYI EAHGTGTKVG 

       310        320        330        340        350        360 
DPQELNGITR SLCAFRQSPL LIGSTKSNMG HPEPASGLAA LTKVLLSLEN GVWAPNLHFH 

       370        380        390        400        410        420 
NPNPEIPALL DGRLQVVDRP LPVRGGIVGI NSFGFGGANV HVILQPNTQQ APAPAPHAAL 

       430        440        450        460        470        480 
PHLLHASGRT MEAVQGLLEQ GRQHSQDLAF VSMLNDIAAT PTAAMPFRGY TVLGVEGHVQ 

       490        500        510        520        530        540 
EVQQVPASQR PLWFICSGMG TQWRGMGLSL MRLDSFRESI LRSDEALKPL GVKVSDLLLS 

       550        560        570        580        590        600 
TDEHTFDDIV HSFVSLTAIQ IALIDLLTSM GLKPDGIIGH SLGEVACGYA DGCLSQREAV 

       610        620        630        640        650        660 
LAAYWRGQCI KDANLPAGSM AAVGLSWEEC KQRCPPGVVP ACHNSEDTVT ISGPQAAVNE 

       670        680        690        700        710        720 
FVEQLKQEGV FAKEVRTGGL AFHSYFMEGI APTLLQALKK VIREPRPRSA RWLSTSIPEA 

       730        740        750        760        770        780 
QWQSSLARTS SAEYNVNNLV SPVLFQEALW HVPEHAVVLE IAPHALLQAV LKRGVKPSCT 

       790        800        810        820        830        840 
IIPLMKRDHK DNLEFFLTNL GKVHLTGIDI NPNALFPPVE FPVPRGTPLI SPHIKWDHSQ 

       850        860        870        880        890        900 
TWDIPVAEDF PNGSSSSSAT VYNIDASSES SDHYLVDHCI DGRVLFPGTG YLYLVWKTLA 

       910        920        930        940        950        960 
RSLSLSLEET PVVFENVTFH QATILPRTGT VPLEVRLLEA SHAFEVSDSG NLIVSGKVYQ 

       970        980        990       1000       1010       1020 
WEDPDSKLFD HPEVPIPAES ESVSRLTQGE VYKELRLRGY DYGPHFQGVY EATLEGEQGK 

      1030       1040       1050       1060       1070       1080 
LLWKDNWVTF MDTMLQISIL GFSKQSLQLP TRVTAIYIDP ATHLQKVYML EGDTQVADVT 

      1090       1100       1110       1120       1130       1140 
TSRCLGVTVS GGVYISRLQT TATSRRQQEQ LVPTLEKFVF TPHVEPECLS ESAILQKELQ 

      1150       1160       1170       1180       1190       1200 
LCKGLAKALQ TKATQQGLKM TVPGLEDLPQ HGLPRLLAAA CQLQLNGNLQ LELGEVLARE 

      1210       1220       1230       1240       1250       1260 
RLLLPEDPLI SGLLNSQALK ACIDTALENL STLKMKVVEV LAGEGHLYSH ISALLNTQPM 

      1270       1280       1290       1300       1310       1320 
LQLEYTATDR HPQALKDVQT KLQQHDVAQG QWDPSGPAPT NLGALDLVVC NCALATLGDP 

      1330       1340       1350       1360       1370       1380 
ALALDNMVAA LKDGGFLLMH TVLKGHALGE TLACLPSEVQ PGPSFLSQEE WESLFSRKAL 

      1390       1400       1410       1420       1430       1440 
HLVGLKKSFY GTALFLCRRL SPQDKPIFLP VEDTSFQWVD SLKSILATSS SQPVWLTAMN 

      1450       1460       1470       1480       1490       1500 
CPTSGVVGLV NCLRKEPGGH RIRCILLSNL SSTSHVPKLD PGSSELQKVL ESDLVMNVYR 

      1510       1520       1530       1540       1550       1560 
DGAWGAFRHF QLEQDKPEEQ TAHAFVNVLT RGDLASIRWV SSPLKHMQPP SSSGAQLCTV 

      1570       1580       1590       1600       1610       1620 
YYASLNFRDI MLATGKLSPD AIPGKWASRD CMLGMEFSGR DKCGRRVMGL VPAEGLATSV 

      1630       1640       1650       1660       1670       1680 
LLSPDFLWDV PSSWTLEEAA SVPVVYTTAY YSLVVRGRIQ HGETVLIHSG SGGVGQAAIS 

      1690       1700       1710       1720       1730       1740 
IALSLGCRVF TTVGSAEKRA YLQARFPQLD DTSFANSRDT SFEQHVLLHT GGKGVDLVLN 

      1750       1760       1770       1780       1790       1800 
SLAEEKLQAS VRCLAQHGRF LEIGKFDLSN NHPLGMAIFL KNVTFHGILL DALFEGANDS 

      1810       1820       1830       1840       1850       1860 
WREVAELLKA GIRDGVVKPL KCTVFPKAQV EDAFRYMAQG KHIGKVLVQV REEEPEAMLP 

      1870       1880       1890       1900       1910       1920 
GAQPTLISAI SKTFCPEHKS YIITGGLGGF GLELARWLVL RGAQRLVLTS RSGIRTGYQA 

      1930       1940       1950       1960       1970       1980 
KHVREWRRQG IHVLVSTSNV SSLEGARALI AEATKLGPVG GVFNLAMVLR DAMLENQTPE 

      1990       2000       2010       2020       2030       2040 
LFQDVNKPKY NGTLNLDRAT REACPELDYF VAFSSVSCGR GNAGQSNYGF ANSTMERICE 

      2050       2060       2070       2080       2090       2100 
QRRHDGLPGL AVQWGAIGDV GIILEAMGTN DTVVGGTLPQ RISSCMEVLD LFLNQPHAVL 

      2110       2120       2130       2140       2150       2160 
SSFVLAEKKA VAHGDGEAQR DLVKAVAHIL GIRDLAGINL DSSLADLGLD SLMGVEVRQI 

      2170       2180       2190       2200       2210       2220 
LEREHDLVLP IREVRQLTLR KLQEMSSKAG SDTELAAPKS KNDTSLKQAQ LNLSILLVNP 

      2230       2240       2250       2260       2270       2280 
EGPTLTRLNS VQSSERPLFL VHPIEGSITV FHSLAAKLSV PTYGLQCTQA APLDSIPNLA 

      2290       2300       2310       2320       2330       2340 
AYYIDCIKQV QPEGPYRVAG YSFGACVAFE MCSQLQAQQG PAPAHNNLFL FDGSHTYVLA 

      2350       2360       2370       2380       2390       2400 
YTQSYRAKLT PGCEAEAEAE AICFFIKQFV DAEHSKVLEA LLPLKSLEDR VAAAVDLITR 

      2410       2420       2430       2440       2450       2460 
SHQSLDRRDL SFAAVSFYYK LRAADQYKPK AKYHGNVILL RAKTGGTYGE DLGADYNLSQ 

      2470       2480       2490       2500 
VCDGKVSVHI IEGDHRTLLE GRGLESIINI IHSSLAEPRV SVREG 

P12785 in FASTA format

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