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P12785 (FAS_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Fatty acid synthase
EC=2.3.1.85

Including the following 7 domains:

  1. [Acyl-carrier-protein] S-acetyltransferase
    EC=2.3.1.38
  2. [Acyl-carrier-protein] S-malonyltransferase
    EC=2.3.1.39
  3. 3-oxoacyl-[acyl-carrier-protein] synthase
    EC=2.3.1.41
  4. 3-oxoacyl-[acyl-carrier-protein] reductase
    EC=1.1.1.100
  5. 3-hydroxyacyl-[acyl-carrier-protein] dehydratase
    EC=4.2.1.59
  6. Enoyl-[acyl-carrier-protein] reductase
    EC=1.3.1.10
  7. Oleoyl-[acyl-carrier-protein] hydrolase
    EC=3.1.2.14
Gene names
Name:Fasn
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length2505 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (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+.

Acetyl-CoA + [acyl-carrier-protein] = CoA + acetyl-[acyl-carrier-protein].

Malonyl-CoA + [acyl-carrier-protein] = CoA + malonyl-[acyl-carrier-protein].

Acyl-[acyl-carrier-protein] + malonyl-[acyl-carrier-protein] = 3-oxoacyl-[acyl-carrier-protein] + CO2 + [acyl-carrier-protein].

(3R)-3-hydroxyacyl-[acyl-carrier-protein] + NADP+ = 3-oxoacyl-[acyl-carrier-protein] + NADPH.

A (3R)-3-hydroxyacyl-[acyl-carrier protein] = a trans-2-enoyl-[acyl-carrier protein] + H2O.

Acyl-[acyl-carrier-protein] + NADP+ = trans-2,3-dehydroacyl-[acyl-carrier-protein] + NADPH.

Oleoyl-[acyl-carrier-protein] + H2O = [acyl-carrier-protein] + oleate.

Subunit structure

Homodimer which is arranged in a head to tail fashion.

Subcellular location

Cytoplasm By similarity. Melanosome By similarity.

Induction

Up-regulated in livers of rats fed on a high carbohydrate diet. Ref.7

Sequence similarities

Contains 1 acyl carrier domain.

Ontologies

Keywords
   Biological processFatty acid biosynthesis
Fatty acid metabolism
Lipid biosynthesis
Lipid metabolism
   Cellular componentCytoplasm
   LigandNAD
NADP
Phosphopantetheine
Pyridoxal phosphate
   Molecular functionHydrolase
Lyase
Oxidoreductase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processacetyl-CoA metabolic process

Inferred from direct assay PubMed 18062843. Source: RGD

fatty acid biosynthetic process

Inferred from mutant phenotype PubMed 15715522. Source: RGD

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Compara

glycogen granule

Inferred from electronic annotation. Source: Compara

melanosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from electronic annotation. Source: Compara

plasma membrane

Inferred from electronic annotation. Source: Compara

   Molecular_function3-hydroxyoctanoyl-[acyl-carrier-protein] dehydratase activity

Inferred from electronic annotation. Source: EC

3-hydroxypalmitoyl-[acyl-carrier-protein] dehydratase activity

Inferred from electronic annotation. Source: InterPro

3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity

Inferred from electronic annotation. Source: EC

3-oxoacyl-[acyl-carrier-protein] synthase activity

Inferred from electronic annotation. Source: EC

NADPH binding

Inferred from direct assay PubMed 15715522. Source: RGD

[acyl-carrier-protein] S-acetyltransferase activity

Inferred from electronic annotation. Source: EC

[acyl-carrier-protein] S-malonyltransferase activity

Inferred from electronic annotation. Source: EC

drug binding

Inferred from direct assay PubMed 15715522. Source: RGD

enoyl-[acyl-carrier-protein] reductase (NADPH, B-specific) activity

Inferred from electronic annotation. Source: EC

fatty acid synthase activity

Inferred from direct assay PubMed 18062843. Source: RGD

myristoyl-[acyl-carrier-protein] hydrolase activity

Inferred from electronic annotation. Source: EC

oleoyl-[acyl-carrier-protein] hydrolase activity

Inferred from electronic annotation. Source: EC

palmitoyl-[acyl-carrier-protein] hydrolase activity

Inferred from electronic annotation. Source: EC

protein homodimerization activity

Inferred from direct assay PubMed 19151726. Source: RGD

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself8EBI-493558,EBI-493558

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 25052505Fatty acid synthase
PRO_0000180279

Regions

Domain2118 – 217457Acyl carrier
Nucleotide binding1665 – 168218NADP (ER)
Nucleotide binding1765 – 178016NADP (KR)
Region1 – 413413Beta-ketoacyl synthase
Region429 – 817389Acyl and malonyl transferases
Region1629 – 1857229Enoyl reductase
Region1858 – 2113256Beta-ketoacyl reductase
Region2202 – 2505304Thioesterase

Sites

Active site1611For beta-ketoacyl synthase activity By similarity
Active site5811For malonyltransferase activity By similarity
Active site8781For beta-hydroxyacyl dehydratase activity By similarity
Active site23021For thioesterase activity By similarity
Active site24751For thioesterase activity By similarity

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue701N6-acetyllysine By similarity
Modified residue2071Phosphoserine By similarity
Modified residue2981N6-acetyllysine By similarity
Modified residue5281N6-acetyllysine By similarity
Modified residue6731N6-acetyllysine By similarity
Modified residue16981N6-(pyridoxal phosphate)lysine By similarity
Modified residue16981N6-acetyllysine By similarity
Modified residue17651N6-acetyllysine By similarity
Modified residue18411N6-acetyllysine By similarity
Modified residue19891N6-acetyllysine By similarity
Modified residue21511O-(pantetheine 4'-phosphoryl)serine By similarity
Modified residue22301Phosphoserine By similarity

Experimental info

Sequence conflict1841I → T in AAA41145. Ref.3
Sequence conflict8711S → P in CAA31780. Ref.4
Sequence conflict20851C → P in AAA41144. Ref.6
Sequence conflict21061A → V in AAA57219. Ref.1
Sequence conflict21061A → V in AAA41145. Ref.3
Sequence conflict21061A → V in CAA31882. Ref.5
Sequence conflict22961Y → H in AAA57219. Ref.1
Sequence conflict22961Y → H in CAA31882. Ref.5

Secondary structure

1 ................... 2505
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P12785 [UniParc].

Last modified November 1, 1997. Version 3.
Checksum: 5810EC13D37F3114

FASTA2,505272,650
        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

« Hide

References

[1]"Molecular cloning and sequencing of cDNAs encoding the entire rat fatty acid synthase."
Amy C.M., Witkowski A., Naggert J., Williams B., Randhawa Z., Smith S.
Proc. Natl. Acad. Sci. U.S.A. 86:3114-3118(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The fatty acid synthase (FAS) gene and its promoter in Rattus norvegicus."
Beck K.F., Schreglmann R., Stathopulos I., Klein H., Hoch J., Schweizer M.
DNA Seq. 2:359-386(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
Strain: Sprague-Dawley.
Tissue: Liver.
[3]"Intron-exon organization of the gene for the multifunctional animal fatty acid synthase."
Amy C.M., Williams-Ahlf B., Naggert J., Smith S.
Proc. Natl. Acad. Sci. U.S.A. 89:1105-1108(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Rat mammary gland fatty acid synthase: localization of the constituent domains and two functional polyadenylation/termination signals in the cDNA."
Schweizer M., Takabeyashi K., Beck K.F., Schreglmann R.
Nucleic Acids Res. 17:567-586(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 75-2505.
Strain: Sprague-Dawley.
Tissue: Mammary gland.
[5]"Molecular cloning and sequencing of a cDNA encoding the acyl carrier protein and its flanking domains in the mammalian fatty acid synthetase."
Witlowski A., Naggert J., Mikkelsen J., Smith S.
Eur. J. Biochem. 165:601-606(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1921-2324.
Tissue: Mammary gland.
[6]"Molecular cloning and sequencing of a cDNA encoding the thioesterase domain of the rat fatty acid synthetase."
Naggert J., Witkowski A., Mikkelsen J., Smith S.
J. Biol. Chem. 263:1146-1150(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2085-2505.
Tissue: Mammary gland.
[7]"Nutritional control of rat liver fatty acid synthase and S14 mRNA abundance."
Clarke S.D., Armstrong M.K., Jump D.B.
J. Nutr. 120:218-224(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE OF 2377-2413, INDUCTION.
[8]"The type I rat fatty acid synthase ACP shows structural homology and analogous biochemical properties to type II ACPs."
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.
Org. Biomol. Chem. 1:463-471(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 2114-2202.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		M76767 mRNA. Translation: AAA57219.1.
X62888 mRNA. Translation: CAA44679.1.
X62889 Genomic DNA. Translation: CAA44680.1.
M84761 Genomic DNA. Translation: AAA41145.1.
X13415 mRNA. Translation: CAA31780.1.
X13527 mRNA. Translation: CAA31882.1.
J03514 mRNA. Translation: AAA41144.1.
IPIIPI00200661.
PIRXYRTFA. A30313.
RefSeqNP_059028.1. NM_017332.1.
UniGeneRn.9486.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2PNGNMR-A2114-2202[»]
ProteinModelPortalP12785.
SMRP12785. Positions 423-819, 2114-2202, 2216-2501.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-33893N.

Proteomic databases

PRIDEP12785.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000073321; ENSRNOP00000064445; ENSRNOG00000045636.
GeneID50671.
KEGGrno:50671.

Organism-specific databases

CTD2194.
RGD620665. Fasn.

Phylogenomic databases

GeneTreeENSGT00530000063309.
HOVERGENHBG005640.
KOK00665.

Enzyme and pathway databases

SABIO-RKP12785.

Gene expression databases

GenevestigatorP12785.

Family and domain databases

Gene3D1.10.1200.10. 1 hit.
1.10.1470.20. 1 hit.
3.40.366.10. 2 hits.
3.40.47.10. 2 hits.
3.40.50.720. 2 hits.
InterProIPR001227. Ac_transferase_dom.
IPR009081. Acyl_carrier_prot-like.
IPR014043. Acyl_transferase.
IPR016035. Acyl_Trfase/lysoPLipase.
IPR013149. ADH_C.
IPR023102. Fatty_acid_synthase_dom_2.
IPR011032. GroES-like.
IPR018201. Ketoacyl_synth_AS.
IPR014031. Ketoacyl_synth_C.
IPR014030. Ketoacyl_synth_N.
IPR016036. Malonyl_transacylase_ACP-bd.
IPR013217. Methyltransf_12.
IPR016040. NAD(P)-bd_dom.
IPR020842. PKS/FAS_KR.
IPR020843. PKS_ER.
IPR013968. PKS_KR.
IPR006162. PPantetheine_attach_site.
IPR001031. Thioesterase.
IPR016039. Thiolase-like.
IPR016038. Thiolase-like_subgr.
[Graphical view]
PfamPF00698. Acyl_transf_1. 1 hit.
PF00107. ADH_zinc_N. 1 hit.
PF00109. ketoacyl-synt. 1 hit.
PF02801. Ketoacyl-synt_C. 1 hit.
PF08659. KR. 1 hit.
PF08242. Methyltransf_12. 1 hit.
PF00550. PP-binding. 1 hit.
PF00975. Thioesterase. 1 hit.
[Graphical view]
SMARTSM00829. PKS_ER. 1 hit.
SM00822. PKS_KR. 1 hit.
[Graphical view]
SUPFAMSSF47336. ACP_like. 1 hit.
SSF52151. Acyl_Trfase/lysoPlipase. 1 hit.
SSF50129. GroES_like. 1 hit.
SSF55048. Malonyl_transacylase_ACP-bd. 1 hit.
SSF53901. Thiolase-like. 1 hit.
PROSITEPS50075. ACP_DOMAIN. 1 hit.
PS00606. B_KETOACYL_SYNTHASE. 1 hit.
PS00012. PHOSPHOPANTETHEINE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

BindingDBP12785.
ChEMBLCHEMBL3783.
EvolutionaryTraceP12785.
NextBio610498.

Entry information

Entry nameFAS_RAT
AccessionPrimary (citable) accession number: P12785
Secondary accession number(s): O09187 expand/collapse secondary AC list , O09190, Q63577, Q64717
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: November 1, 1997
Last modified: April 3, 2013
This is version 133 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

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