UniProt Accession

 FAS_HUMAN; P49327; Q13479; Q16702; Q4LE83; Q6P4U5; Q6SS02; Q969R1; Q96C68; Q96IT0 

Genbank Protein ID

 U26644; U29344; AY451392; AB209988; AC135056; BC007267; BC007909; BC014634; BC063242; S80437 

Genbank Nucleotide ID

 AAC50259.1; AAA73576.1; AAS09886.1; BAE06070.1; AAH07267.1; AAH07909.1; AAH14634.2; AAH63242.1; AAB35516.1 

Protein Name

 Fatty acid synthase 

Protein Synonyms/Alias

 [Acyl-carrier-protein] S-acetyltransferase; [Acyl-carrier-protein] S-malonyltransferase; 3-oxoacyl-[acyl-carrier-protein] synthase; 3-oxoacyl-[acyl-carrier-protein] reductase; 3-hydroxyacyl-[acyl-carrier-protein] dehydratase; Enoyl-[acyl-carrier-protein] reductase; Oleoyl-[acyl-carrier-protein] hydrolase 

Gene Name

 FASN 

Gene Synonyms/Alias

 FAS 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
41	TDDDRRWKAGLYGLP	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8, 9, 10]
70	SFFGVHPKQAHTMDP	acetylation	[10, 11, 12]
70	SFFGVHPKQAHTMDP	ubiquitination	[1, 2, 3, 5, 6, 7, 8, 9, 10]
213	LSPEGTCKAFDTAGN	ubiquitination	[2, 3, 4, 5, 7, 10]
235	VVAVLLTKKSLARRV	ubiquitination	[1, 2, 3, 5, 8, 9]
236	VAVLLTKKSLARRVY	ubiquitination	[7]
257	GTNTDGFKEQGVTFP	ubiquitination	[2, 3, 7, 8, 10]
298	EAHGTGTKVGDPQEL	acetylation	[11, 12]
298	EAHGTGTKVGDPQEL	ubiquitination	[2, 3, 4, 5, 7, 8, 10]
326	PLLIGSTKSNMGHPE	ubiquitination	[1, 2, 3, 4, 5, 7, 8, 9, 10]
436	RTPEAVQKLLEQGLR	acetylation	[10, 11, 12, 13]
436	RTPEAVQKLLEQGLR	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8, 9, 14]
528	LRSDEAVKPFGLKVS	acetylation	[10, 11, 12]
528	LRSDEAVKPFGLKVS	ubiquitination	[1, 2, 3, 6, 7, 8, 9, 10]
611	YWRGQCIKEAHLPPG	ubiquitination	[7]
631	GLSWEECKQRCPPGV	ubiquitination	[3, 7]
646	VPACHNSKDTVTISG	ubiquitination	[3, 7]
667	EFVEQLRKEGVFAKE	ubiquitination	[2, 8]
673	RKEGVFAKEVRTGGM	acetylation	[10, 11, 12, 13, 15]
673	RKEGVFAKEVRTGGM	ubiquitination	[2, 5, 7, 8, 10]
699	PPLLQELKKVIREPK	ubiquitination	[8]
776	AVLKRGLKPSCTIIP	ubiquitination	[3, 7]
786	CTIIPLMKKDHRDNL	acetylation	[12]
786	CTIIPLMKKDHRDNL	ubiquitination	[7]
787	TIIPLMKKDHRDNLE	ubiquitination	[7]
957	GNLVVSGKVYQWDDP	ubiquitination	[8]
992	LAQAEVYKELRLRGY	ubiquitination	[1, 2, 3, 4, 7, 8, 9, 10]
1065	DPATHRQKLYTLQDK	ubiquitination	[2, 7]
1072	KLYTLQDKAQVADVV	acetylation	[12]
1072	KLYTLQDKAQVADVV	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 14]
1116	QQVPILEKFCFTPHT	ubiquitination	[3, 7, 10]
1142	QEELQLCKGLVQALQ	ubiquitination	[1, 5, 6, 7, 8, 9, 10, 14]
1151	LVQALQTKVTQQGLK	ubiquitination	[1, 5, 6, 7, 8, 9, 10, 14]
1158	KVTQQGLKMVVPGLD	ubiquitination	[1, 6, 7, 8, 9, 10, 16]
1208	VLAQERPKLPEDPLL	ubiquitination	[8]
1239	VENMPSLKMKVVEVL	acetylation	[12]
1239	VENMPSLKMKVVEVL	ubiquitination	[3, 5, 7, 10]
1241	NMPSLKMKVVEVLAG	ubiquitination	[3, 7, 8, 10]
1392	SLRLVGLKKSFYGST	ubiquitination	[2]
1393	LRLVGLKKSFYGSTL	ubiquitination	[1, 3, 6, 9]
1429	FRWVESLKGILADED	acetylation	[12]
1429	FRWVESLKGILADED	ubiquitination	[1, 2, 3, 4, 7, 8, 9, 10]
1495	PGSAELQKVLQGDLV	ubiquitination	[3]
1523	HFLLEEDKPEEPTAH	acetylation	[12]
1523	HFLLEEDKPEEPTAH	ubiquitination	[2, 7, 14]
1582	DIMLATGKLSPDAIP	acetylation	[10, 12]
1582	DIMLATGKLSPDAIP	ubiquitination	[2, 3, 6, 7, 8, 10]
1591	SPDAIPGKWTSQDSL	acetylation	[12]
1591	SPDAIPGKWTSQDSL	ubiquitination	[1, 2, 7, 8, 9]
1704	TTVGSAEKRAYLQAR	acetylation	[10, 11, 12]
1704	TTVGSAEKRAYLQAR	ubiquitination	[2, 3, 4, 5, 7, 8]
1739	VLWHTGGKGVDLVLN	ubiquitination	[2, 3, 8]
1752	LNSLAEEKLQASVRC	acetylation	[11, 12, 17]
1752	LNSLAEEKLQASVRC	ubiquitination	[2, 7, 8]
1771	GRFLEIGKFDLSQNH	acetylation	[11, 12, 13]
1771	GRFLEIGKFDLSQNH	ubiquitination	[8]
1827	DGVVRPLKCTVFHGA	ubiquitination	[3, 7]
1847	FRYMAQGKHIGKVVV	acetylation	[11, 12, 13]
1847	FRYMAQGKHIGKVVV	ubiquitination	[2, 7, 8, 10]
1851	AQGKHIGKVVVQVLA	ubiquitination	[2, 7, 8]
1866	EEPEAVLKGAKPKLM	ubiquitination	[1, 2, 3, 6, 7, 8, 9, 10]
1869	EAVLKGAKPKLMSAI	ubiquitination	[2, 3, 7, 8]
1871	VLKGAKPKLMSAISK	ubiquitination	[7]
1878	KLMSAISKTFCPAHK	ubiquitination	[1, 3, 6, 7, 9]
1911	LIQRGVQKLVLTSRS	ubiquitination	[1, 2, 3, 6, 7, 8, 9]
1927	IRTGYQAKQVRRWRR	ubiquitination	[2, 7, 8]
1993	EFFQDVCKPKYSGTL	ubiquitination	[2, 3, 5, 7, 10]
1995	FQDVCKPKYSGTLNL	acetylation	[11, 12]
1995	FQDVCKPKYSGTLNL	ubiquitination	[3, 7, 10]
2047	AMERICEKRRHEGLP	ubiquitination	[2]
2186	VRQLTLRKLQELSSK	ubiquitination	[2, 14]
2193	KLQELSSKADEASEL	ubiquitination	[3]
2206	ELACPTPKEDGLAQQ	ubiquitination	[3, 14]
2391	LEALLPLKGLEERVA	acetylation	[12]
2391	LEALLPLKGLEERVA	ubiquitination	[1, 2, 5, 6, 7, 8, 9, 10]
2406	AAVDLIIKSHQGLDR	ubiquitination	[7]
2426	AARSFYYKLRAAEQY	ubiquitination	[3, 7]
2436	AAEQYTPKAKYHGNV	acetylation	[10]
2436	AAEQYTPKAKYHGNV	ubiquitination	[2, 7]
2438	EQYTPKAKYHGNVML	ubiquitination	[6, 7]
2449	NVMLLRAKTGGAYGE	ubiquitination	[1, 2, 3, 6, 7, 8, 9, 10, 14]
2471	LSQVCDGKVSVHVIE	ubiquitination	[7]

Reference

 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [4] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [5] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [6] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [7] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [8] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [9] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [10] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [11] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [12] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [13] Monoclonal antibody cocktail as an enrichment tool for acetylome analysis.
 Shaw PG, Chaerkady R, Zhang Z, Davidson NE, Pandey A.
 Anal Chem. 2011 May 15;83(10):3623-6. [PMID: 21466224]
 [14] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931]
 [15] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [16] A data set of human endogenous protein ubiquitination sites.
 Shi Y, Chan DW, Jung SY, Malovannaya A, Wang Y, Qin J.
 Mol Cell Proteomics. 2011 May;10(5):M110.002089. [PMID: 20972266]
 [17] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 2123 2179 Acyl carrier.
 NP_BIND 1671 1688 NADP (ER) (By similarity).
 NP_BIND 1886 1901 NADP (KR) (By similarity).
 REGION 1 414 Beta-ketoacyl synthase (By similarity).
 REGION 429 817 Acyl and malonyl transferases (By
 REGION 1635 1863 Enoyl reductase (By similarity).
 REGION 1864 2118 Beta-ketoacyl reductase (By similarity).
 REGION 2207 2511 Thioesterase (By similarity).
 ACT_SITE 161 161 For beta-ketoacyl synthase activity (By
 ACT_SITE 581 581 For malonyltransferase activity (By
 ACT_SITE 878 878 For beta-hydroxyacyl dehydratase activity
 ACT_SITE 2308 2308 For thioesterase activity.
 ACT_SITE 2481 2481 For thioesterase activity (By
 MOD_RES 1 1 N-acetylmethionine.
 MOD_RES 70 70 N6-acetyllysine.
 MOD_RES 207 207 Phosphoserine.
 MOD_RES 298 298 N6-acetyllysine.
 MOD_RES 436 436 N6-acetyllysine.
 MOD_RES 528 528 N6-acetyllysine.
 MOD_RES 673 673 N6-acetyllysine.
 MOD_RES 1704 1704 N6-(pyridoxal phosphate)lysine; alternate
 MOD_RES 1704 1704 N6-acetyllysine; alternate.
 MOD_RES 1771 1771 N6-acetyllysine.
 MOD_RES 1847 1847 N6-acetyllysine.
 MOD_RES 1995 1995 N6-acetyllysine.
 MOD_RES 2156 2156 O-(pantetheine 4'-phosphoryl)serine (By
 MOD_RES 2198 2198 Phosphoserine.
 MOD_RES 2204 2204 Phosphothreonine.
 MOD_RES 2236 2236 Phosphoserine.  

Keyword

 3D-structure; Acetylation; Complete proteome; Cytoplasm; Direct protein sequencing; Fatty acid biosynthesis; Fatty acid metabolism; Hydrolase; Lipid biosynthesis; Lipid metabolism; Lyase; Multifunctional enzyme; NAD; NADP; Oxidoreductase; Phosphopantetheine; Phosphoprotein; Polymorphism; Pyridoxal phosphate; Reference proteome; Transferase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 2511 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0042587; C:glycogen granule; IEA:Compara.
 GO:0005794; C:Golgi apparatus; IDA:HPA.
 GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
 GO:0005739; C:mitochondrion; IEA:Compara.
 GO:0005886; C:plasma membrane; IDA:HPA.
 GO:0047451; F:3-hydroxyoctanoyl-[acyl-carrier-protein] dehydratase activity; IEA:EC.
 GO:0004317; F:3-hydroxypalmitoyl-[acyl-carrier-protein] dehydratase activity; IEA:InterPro.
 GO:0004316; F:3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; IEA:EC.
 GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:EC.
 GO:0004313; F:[acyl-carrier-protein] S-acetyltransferase activity; IEA:EC.
 GO:0004314; F:[acyl-carrier-protein] S-malonyltransferase activity; IEA:EC.
 GO:0008144; F:drug binding; IEA:Compara.
 GO:0004319; F:enoyl-[acyl-carrier-protein] reductase (NADPH, B-specific) activity; IEA:EC.
 GO:0004312; F:fatty acid synthase activity; TAS:Reactome.
 GO:0016295; F:myristoyl-[acyl-carrier-protein] hydrolase activity; IEA:EC.
 GO:0070402; F:NADPH binding; IEA:Compara.
 GO:0004320; F:oleoyl-[acyl-carrier-protein] hydrolase activity; IEA:EC.
 GO:0016296; F:palmitoyl-[acyl-carrier-protein] hydrolase activity; IEA:EC.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0006084; P:acetyl-CoA metabolic process; IEA:Compara.
 GO:0006112; P:energy reserve metabolic process; TAS:Reactome.
 GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
 GO:0006631; P:fatty acid metabolic process; TAS:ProtInc.
 GO:0035338; P:long-chain fatty-acyl-CoA biosynthetic process; TAS:Reactome.
 GO:0015939; P:pantothenate metabolic process; TAS:Reactome.
 GO:0031325; P:positive regulation of cellular metabolic process; TAS:Reactome.
 GO:0019432; P:triglyceride biosynthetic process; TAS:Reactome. 

Interpro

 IPR001227; Ac_transferase_dom.
 IPR009081; Acyl_carrier_prot-like.
 IPR014043; Acyl_transferase.
 IPR016035; Acyl_Trfase/lysoPLipase.
 IPR013149; ADH_C.
 IPR002198; DH_sc/Rdtase_SDR.
 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.
 IPR006162; PPantetheine_attach_site.
 IPR001031; Thioesterase.
 IPR016039; Thiolase-like.
 IPR016038; Thiolase-like_subgr. 

Pfam

 PF00698; Acyl_transf_1
 PF00106; adh_short
 PF00107; ADH_zinc_N
 PF00109; ketoacyl-synt
 PF02801; Ketoacyl-synt_C
 PF08242; Methyltransf_12
 PF00550; PP-binding
 PF00975; Thioesterase 

SMART

 SM00829; PKS_ER
 SM00822; PKS_KR 

PROSITE

 PS50075; ACP_DOMAIN
 PS00606; B_KETOACYL_SYNTHASE
 PS00012; PHOSPHOPANTETHEINE 

PRINTS