Reviewed, UniProtKB/Swiss-Prot P12785 (FAS_RAT)

Names and origin

Protein names

Recommended name:
    Fatty acid synthase
    EC=2.3.1.85
Including the following 7 domains:
    1- Recommended name:
            [Acyl-carrier-protein] S-acetyltransferase
              EC=2.3.1.38
    2- Recommended name:
            [Acyl-carrier-protein] S-malonyltransferase
              EC=2.3.1.39
    3- Recommended name:
            3-oxoacyl-[acyl-carrier-protein] synthase
              EC=2.3.1.41
    4- Recommended name:
            3-oxoacyl-[acyl-carrier-protein] reductase
              EC=1.1.1.100
    5- Recommended name:
            3-hydroxypalmitoyl-[acyl-carrier-protein] dehydratase
              EC=4.2.1.61
    6- Recommended name:
            Enoyl-[acyl-carrier-protein] reductase
              EC=1.3.1.10
    7- Recommended name:
            Oleoyl-[acyl-carrier-protein] hydrolase
              EC=3.1.2.14

Gene names

Name:

Fasn

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	2505 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 CO(2) + 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] + CO(2) + [acyl-carrier-protein]. (3R)-3-hydroxyacyl-[acyl-carrier-protein] + NADP(+) = 3-oxoacyl-[acyl-carrier-protein] + NADPH. (3R)-3-hydroxypalmitoyl-[acyl-carrier-protein] = hexadec-2-enoyl-[acyl-carrier-protein] + H(2)O. Acyl-[acyl-carrier-protein] + NADP(+) = trans-2,3-dehydroacyl-[acyl-carrier-protein] + NADPH. Oleoyl-[acyl-carrier-protein] + H(2)O = [acyl-carrier-protein] + oleate.
Subunit structure	Homodimer which is arranged in a head to tail fashion.
Subcellular location	CytoplasmBy similarity. MelanosomeBy similarity.
Induction	Up-regulated in livers of rats fed on a high carbohydrate diet.
Sequence similarities	Contains 1 acyl carrier domain.

Ontologies

Keywords
Biological process	Fatty acid biosynthesis Lipid synthesis
Cellular component	Cytoplasm
Ligand	NAD NADP Phosphopantetheine Pyridoxal phosphate
Molecular function	Hydrolase Lyase Oxidoreductase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Multifunctional enzyme
Gene Ontology (GO)
Biological process	fatty acid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW oxidation reduction Inferred from electronic annotation. Source: InterPro
Cellular component	melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	3-hydroxypalmitoyl-[acyl-carrier-protein] dehydratase activity Inferred from electronic annotation. Source: EC 3-oxoacyl-[acyl-carrier-protein] reductase activity Inferred from electronic annotation. Source: EC 3-oxoacyl-[acyl-carrier-protein] synthase activity Inferred from electronic annotation. Source: EC [acyl-carrier-protein] S-acetyltransferase activity Inferred from electronic annotation. Source: EC [acyl-carrier-protein] S-malonyltransferase activity Inferred from electronic annotation. Source: EC acyl carrier activity Inferred from electronic annotation. Source: InterPro cofactor binding Inferred from electronic annotation. Source: InterPro enoyl-[acyl-carrier-protein] reductase (NADPH, B-specific) activity Inferred from electronic annotation. Source: EC identical protein binding Inferred from physical interaction. Source: IntAct oleoyl-[acyl-carrier-protein] hydrolase activity Inferred from electronic annotation. Source: EC phosphopantetheine binding Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-493558,EBI-493558

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 2505

2505

Fatty acid synthase

PRO_0000180279

Regions

Domain

2118 – 2174

57

Acyl carrier

Nucleotide binding

1665 – 1682

18

NADP (ER)

Nucleotide binding

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

Sites

Active site

161

1

For beta-ketoacyl synthase activity By similarity

Active site

581

1

For malonyltransferase activity By similarity

Active site

878

1

For beta-hydroxyacyl dehydratase activity By similarity

Active site

2302

1

For thioesterase activity By similarity

Active site

2475

1

For thioesterase activity By similarity

Binding site

1698

1

Pyridoxal phosphate (covalent) By similarity

Binding site

2151

1

Phosphopantetheine (covalent) By similarity

Amino acid modifications

Modified residue

1

1

N-acetylmethionine By similarity

Modified residue

207

1

Phosphoserine By similarity

Modified residue

2230

1

Phosphoserine By similarity

Experimental info

Sequence conflict

184

1

I → T in AAA41145. Ref.3

Sequence conflict

871

1

S → P in CAA31780. Ref.4

Sequence conflict

1967 – 1968

2

MV → IL Ref.6

Sequence conflict

2085

1

C → P in AAA41144. Ref.5

Sequence conflict

2106

1

A → V Ref.1 Ref.3 Ref.6

Sequence conflict

2296

1

Y → H Ref.1 Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

2505

Helix Strand Turn

Details...

Helix

2122 – 2124

3

Helix

2126 – 2130

5

Beta strand

2140 – 2142

3

Helix

2144 – 2147

4

Helix

2152 – 2164

13

Helix

2171 – 2174

4

Helix

2180 – 2184

5

Beta strand

2188 – 2190

3

Beta strand

2192 – 2194

3

Sequences

	Sequence		Length	Mass (Da)
	P12785-1 [UniParc]. Last modified November 1, 1997. Version 3. Checksum: 5810EC13D37F3114	FASTA	2,505	272,650
	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

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: 2717611] [Abstract] Cited for: NUCLEOTIDE SEQUENCE.
[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: 1339331] [Abstract] Cited for: NUCLEOTIDE SEQUENCE. 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: 1736293] [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: 2915923] [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 thioesterase domain of the rat fatty acid synthetase." Naggert J., Witkowski A., Mikkelsen J., Smith S. J. Biol. Chem. 263:1146-1150(1988) [PubMed: 2891707] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2085-2505. Tissue: Mammary gland.
[6]	"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: 3109907] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1921-2324. 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: 2313386] [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: 12926246] [Abstract] Cited for: STRUCTURE BY NMR OF 2114-2202.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

PIR

XYRTFA. A30313.

RefSeq

NP_059028.1.

UniGene

Rn.9486

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1N8L	NMR	-	A	2114-2202	[»]
2PNG	NMR	-	A	2114-2202	[»]

SMR

P12785. Positions 2211-2496.

ModBase

Search...

Protein-protein interaction databases

IntAct

P12785.

Genome annotation databases

GeneID

50671.

KEGG

rno:50671.

Organism-specific databases

RGD

620665. Fasn.

Phylogenomic databases

HOVERGEN

P12785.

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]

Gene3D

G3DSA:3.40.366.10. Ac_transferase_reg. 1 hit.
G3DSA:1.10.1200.10. ACP_like. 1 hit.
G3DSA:3.40.50.720. NAD(P)-bd. 2 hits.
G3DSA:3.40.47.10. Thiolase-like_subgr. 2 hits.

PANTHER

PTHR11712. Ketoacyl_synth. 1 hit.

Pfam

PF00698. Acyl_transf_1. 1 hit.
PF00106. adh_short. 1 hit.
PF00107. ADH_zinc_N. 1 hit.
PF00109. ketoacyl-synt. 1 hit.
PF02801. Ketoacyl-synt_C. 1 hit.
PF08242. Methyltransf_12. 1 hit.
PF00550. PP-binding. 1 hit.
PF00975. Thioesterase. 1 hit.
[Graphical view]

PROSITE

PS50075. ACP_DOMAIN. 1 hit.
PS00606. B_KETOACYL_SYNTHASE. 1 hit.
PS00012. PHOSPHOPANTETHEINE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

610498.

Entry information

Entry name

FAS_RAT

Accession

Primary (citable) accession number: P12785
Secondary accession number(s): O09187 , O09190, Q63577, Q64717

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	November 1, 1997
Last modified:	November 25, 2008
This is version 94 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)