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UniProtKB/Swiss-Prot entry P49327


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

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Entry information
Entry name FAS_HUMAN
Primary accession number P49327
Secondary accession numbers Q13479 Q16702 Q6P4U5 Q6SS02 Q969R1 Q96C68 Q96IT0
Integrated into Swiss-Prot on February 1, 1996
Sequence was last modified on June 7, 2005 (Sequence version 2)
Annotations were last modified on    October 14, 2008 (Entry version 97)
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
Synonyms: FAS
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Brain;
PubMed=7567999 [NCBI, ExPASy, EBI, Israel, Japan]
Jayakumar A., Tai M.-H., Huang W.-Y., Al-Feel W., Hsu M., Abu-Elheiga L., Chirala S.S., Wakil S.J.;
"Human fatty acid synthase: properties and molecular cloning.";
Proc. Natl. Acad. Sci. U.S.A. 92:8695-8699(1995).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
Hennigar R.A., Jenner K.H., Heine H.S., Kayler A.E., Wood F.D., Kuhajda F.P., Pasternack G.R.;
"Molecular cloning of tumor-associated human fatty acid synthase.";
Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [MRNA].
Mao J., Wakil S.J.;
"Recharacterization of the human fatty acid synthase (FAS) gene.";
Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Eye;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
PROTEIN SEQUENCE OF 1-12; 647-666; 791-802; 1242-1255; 1338-1349 AND 2126-2138, ACETYLATION AT MET-1, AND MASS SPECTROMETRY.
TISSUE=B-cell lymphoma;
Bienvenut W.V.;
Submitted (JUL-2005) to UniProtKB.
[6]
PROTEIN SEQUENCE OF 753-758 AND 1285-1297.
PubMed=8022791 [NCBI, ExPASy, EBI, Israel, Japan]
Kuhajda F.P., Jenner K., Wood F.D., Hennigar R.A., Jacobs L.B., Dick J.D., Pasternack G.R.;
"Fatty acid synthesis: a potential selective target for antineoplastic therapy.";
Proc. Natl. Acad. Sci. U.S.A. 91:6379-6383(1994).
[7]
NUCLEOTIDE SEQUENCE [MRNA] OF 2047-2511, AND TISSUE SPECIFICITY.
PubMed=7595075 [NCBI, ExPASy, EBI, Israel, Japan]
Semenkovich C.F., Coleman T., Fiedorek F.T. Jr.;
"Human fatty acid synthase mRNA: tissue distribution, genetic mapping, and kinetics of decay after glucose deprivation.";
J. Lipid Res. 36:1507-1521(1995).
[8]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-2204, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1073/pnas.0404720101; PubMed=15302935 [NCBI, ExPASy, EBI, Israel, Japan]
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
"Large-scale characterization of HeLa cell nuclear phosphoproteins.";
Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
[9]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-2204, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1016/j.cell.2006.09.026; PubMed=17081983 [NCBI, ExPASy, EBI, Israel, Japan]
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.";
Cell 127:635-648(2006).
[10]
SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
DOI=10.1021/pr060363j; PubMed=17081065 [NCBI, ExPASy, EBI, Israel, Japan]
Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.;
"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes.";
J. Proteome Res. 5:3135-3144(2006).
[11]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-2204, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1038/nbt1240; PubMed=16964243 [NCBI, ExPASy, EBI, Israel, Japan]
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
"A probability-based approach for high-throughput protein phosphorylation analysis and site localization.";
Nat. Biotechnol. 24:1285-1292(2006).
[12]
3D-STRUCTURE MODELING, AND ELECTRON CRYOMICROSCOPY.
DOI=10.1073/pnas.012589499; PubMed=11756679 [NCBI, ExPASy, EBI, Israel, Japan]
Brink J., Ludtke S.J., Yang C.Y., Gu Z.-W., Wakil S.J., Chiu W.;
"Quaternary structure of human fatty acid synthase by electron cryomicroscopy.";
Proc. Natl. Acad. Sci. U.S.A. 99:138-143(2002).
[13]
X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 2218-2502.
DOI=10.1073/pnas.0406901101; PubMed=15507492 [NCBI, ExPASy, EBI, Israel, Japan]
Chakravarty B., Gu Z., Chirala S.S., Wakil S.J., Quiocho F.A.;
"Human fatty acid synthase: structure and substrate selectivity of the thioesterase domain.";
Proc. Natl. Acad. Sci. U.S.A. 101:15567-15572(2004).
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:
    Q92597:NDRG1; NbExp=1; IntAct=EBI-356658, EBI-716486;
  • SUBCELLULAR LOCATION: Cytoplasm. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
  • TISSUE SPECIFICITY: Ubiquitous. Prominent expression in brain, lung, and liver.
  • MISCELLANEOUS: The relatively low beta-ketoacyl synthase activity may be attributable to the low 4'-phosphopantetheine content of the protein.
  • SIMILARITY: Contains 1 acyl carrier domain.
  • SEQUENCE CAUTION:
    • Sequence=AAC50259.1; Type=Miscellaneous discrepancy; Note=Several sequencing errors
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
U26644; AAC50259.1; ALT_SEQ; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U29344; AAA73576.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY451392; AAS09886.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC007267; AAH07267.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC007909; AAH07909.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC014634; AAH14634.2; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC063242; AAH63242.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
S80437; AAB35516.1; ALT_INIT; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A57788; A57788.
G01880; G01880.
RefSeq NP_004095.4; -.
UniGene Hs.83190
3D structure databases
PDB
1XKT; X-ray; 2.60 A; A/B=2218-2502.[ExPASy / RCSB / EBI]
2CG5; X-ray; 2.70 A; B=2119-2207.[ExPASy / RCSB / EBI]
2JFD; X-ray; 2.81 A; A/B/C/D=422-823.[ExPASy / RCSB / EBI]
2JFK; X-ray; 2.40 A; A/B/C/D=422-831.[ExPASy / RCSB / EBI]
2PX6; X-ray; 2.30 A; A/B=2200-2511.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1XKT; -.
2CG5; -.
2JFD; -.
2JFK; -.
2PX6; -.
ModBase P49327.
Protein-protein interaction databases
IntAct P49327; -.
PTM databases
PhosphoSite P49327; -.
Enzyme and pathway databases
BioCyc MetaCyc:ENSG00000169710-MON; -.
Reactome REACT_11127; Metabolism of vitamins and cofactors.
REACT_1505; Integration of energy metabolism.
REACT_602; Lipid and lipoprotein metabolism.
Organism-specific databases
H-InvDB HIX0014269; -.
HGNC HGNC:3594; FASN.
GenAtlas FASN.
HPA CAB005192; -.
HPA006461; -.
MIM 600212; gene. [NCBI / EBI]
PharmGKB PA28006; -.
GeneCards P49327.
Gene expression databases
ArrayExpress P49327; -.
CleanEx HS_FAS; -.
HS_FASN; -.
GermOnline ENSG00000169710; Homo sapiens.
Ontologies
GO
GO:0005829; Cellular component: cytosol (inferred from experiment from Reactome).
GO:0019171; Molecular function: 3-hydroxyacyl-[acyl-carrier-protein] dehydratase activity (inferred from experiment from Reactome).
GO:0004316; Molecular function: 3-oxoacyl-[acyl-carrier-protein] reductase activity (inferred from experiment from Reactome).
GO:0004315; Molecular function: 3-oxoacyl-[acyl-carrier-protein] synthase activity (inferred from experiment from Reactome).
GO:0004313; Molecular function: [acyl-carrier-protein] S-acetyltransferase activity (inferred from experiment from Reactome).
GO:0004314; Molecular function: [acyl-carrier-protein] S-malonyltransferase activity (inferred from experiment from Reactome).
GO:0004319; Molecular function: enoyl-[acyl-carrier-protein] reductase (NADPH, B-specific) activity (inferred from experiment from Reactome).
GO:0004320; Molecular function: oleoyl-[acyl-carrier-protein] hydrolase activity (inferred from experiment from Reactome).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0006631; Biological process: fatty acid metabolic process (traceable author statement from ProtInc).
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 P49327.
Genome annotation databases
Ensembl ENSG00000169710; Homo sapiens. [Contig view]
GeneID 2194; -.
KEGG hsa:2194; -.
Phylogenomic databases
HOVERGEN P49327; -.
Other
DrugBank DB01034; Cerulenin.
DB01083; Orlistat.
DB00339; Pyrazinamide.
SOURCE FASN; Homo sapiens.
ProtoNet P49327.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Fatty acid biosynthesis; Hydrolase; Lipid synthesis; Lyase; Multifunctional enzyme; NAD; NADP; Oxidoreductase; Phosphopantetheine; Phosphoprotein; Pyridoxal phosphate; Transferase.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
</
KeyFrom    To Length Description FTId
CHAIN   1   2511  2511     Fatty acid synthase. PRO_0000180276
DOMAIN   2123   2179  57     Acyl carrier. 
NP_BIND   1671   1688  18     NADP (ER) (By similarity). 
NP_BIND   1886   1901  16     NADP (KR) (By similarity). 
REGION   1    414  414     Beta-ketoacyl synthase (By similarity). 
REGION   429    817  389     Acyl and malonyl transferases (By similarity). 
REGION   1635   1863  229     Enoyl reductase (By similarity). 
REGION   1864   2118  255     Beta-ketoacyl reductase (By similarity). 
REGION   2207   2511  305     Thioesterase (By similarity). 
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   2308   2308        For thioesterase activity (By similarity). 
ACT_SITE   2481   2481        For thioesterase activity (By similarity). 
BINDING   1704   1704        Pyridoxal phosphate (covalent) (By similarity). 
BINDING   2156   2156        Phosphopantetheine (covalent) (By similarity). 
MOD_RES   1      1        N-acetylmethionine. 
MOD_RES   2204   2204        Phosphothreonine. 
CONFLICT   459    462        AVPA -> LSPT (in Ref. 2; AAA73576). 
CONFLICT   528    529        KP -> NR (in Ref. 2; AAA73576). 
CONFLICT   637    637        G -> A (in Ref. 2; AAA73576). 
CONFLICT   801    801        G -> R (in Ref. 2; AAA73576). 
CONFLICT   902    902        A -> P (in Ref. 2; AAA73576). 
CONFLICT   958    958        V -> M (in Ref. 3; AAS09886). 
CONFLICT   1121   1121        P -> S (in Ref. 2 and 3). 
CONFLICT   1151   1151        T -> K (in Ref. 2 and 3). 
CONFLICT   1353   1356        LGDI -> SGH (in Ref. 2; AAA73576). 
CONFLICT   1386   1386        L -> V (in Ref. 2; AAA73576). 
CONFLICT   1467   1468        NR -> T (in Ref. 2; AAA73576). 
CONFLICT   1827   1827        K -> E (in Ref. 3; AAS09886). 
CONFLICT   1934   1934        R -> A (in Ref. 2; AAA73576). 
CONFLICT   2065   2065        D -> H (in Ref. 7). 
CONFLICT   2087   2087        R -> A (in Ref. 2; AAA73576). 
CONFLICT   2363   2363        A -> P (in Ref. 7). 
CONFLICT   2428   2428        R -> G (in Ref. 2; AAA73576). 
CONFLICT   2453   2453        A -> T (in Ref. 7). 
CONFLICT   2456   2456        E -> Q (in Ref. 7). 
STRAND   422    430  9      
HELIX   431    442  12      
TURN   443    446  4      
HELIX   448    457  10      
TURN   462    464  3      
STRAND   467    477  11      
STRAND   481    484  4      
STRAND   492    496  5      
TURN   504    508  5      
HELIX   509    512  4      
HELIX   514    526  13      
TURN   527    531  5      
HELIX   534    539  6      
HELIX   545    547  3      
HELIX   549    569  21      
STRAND   575    579  5      
HELIX   583    590  8      
HELIX   596    613  18      
STRAND   618    625  8      
HELIX   627    633  7      
STRAND   639    645  7      
STRAND   648    654  7      
HELIX   655    667  13      
STRAND   672    675  4      
STRAND   677    679  3      
HELIX   685    690  6      
HELIX   691    701  11      
STRAND   702    704  3      
STRAND   715    717  3      
HELIX   719    721  3      
HELIX   725    728  4      
HELIX   732    740  9      
HELIX   745    749  5      
STRAND   757    764  8      
HELIX   768    773  6      
STRAND   779    784  6      
HELIX   792    805  14      
HELIX   812    815  4      
HELIX   2127   2134  8      
TURN   2149   2153  5      
HELIX   2156   2170  15      
HELIX   2176   2180  5      
HELIX   2184   2192  9      
HELIX   2218   2220  3      
STRAND   2230   2234  5      
STRAND   2244   2247  4      
HELIX   2255   2257  3      
HELIX   2258   2263  6      
STRAND   2268   2271  4      
HELIX   2282   2293  12