FASN

Protein identityUniProt · HPA

UniProt accession

P49327

Gene

FASN

Ensembl

ENSG00000169710

Chromosome

17

Canonical length

2511 aa

Protein class

Cancer-related genes, Enzymes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Plasma membrane,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

The enzyme encoded by this gene is a multifunctional protein. Its main function is to catalyze the synthesis of palmitate from acetyl-CoA and malonyl-CoA, in the presence of NADPH, into long-chain saturated fatty acids. In some cancer cell lines, this protein has been found to be fused with estrogen receptor-alpha (ER-alpha), in which the N-terminus of FAS is fused in-frame with the C-terminus of ER-alpha. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

2511 residues, UniProt reviewed canonical sequence.

>P49327|FASN
     1  MEEVVIAGMS GKLPESENLQ EFWDNLIGGV DMVTDDDRRW KAGLYGLPRR SGKLKDLSRF
    61  DASFFGVHPK QAHTMDPQLR LLLEVTYEAI VDGGINPDSL RGTHTGVWVG VSGSETSEAL
   121  SRDPETLVGY SMVGCQRAMM ANRLSFFFDF RGPSIALDTA CSSSLMALQN AYQAIHSGQC
   181  PAAIVGGINV LLKPNTSVQF LRLGMLSPEG TCKAFDTAGN GYCRSEGVVA VLLTKKSLAR
   241  RVYATILNAG TNTDGFKEQG VTFPSGDIQE QLIRSLYQSA GVAPESFEYI EAHGTGTKVG
   301  DPQELNGITR ALCATRQEPL LIGSTKSNMG HPEPASGLAA LAKVLLSLEH GLWAPNLHFH
   361  SPNPEIPALL DGRLQVVDQP LPVRGGNVGI NSFGFGGSNV HIILRPNTQP PPAPAPHATL
   421  PRLLRASGRT PEAVQKLLEQ GLRHSQDLAF LSMLNDIAAV PATAMPFRGY AVLGGERGGP
   481  EVQQVPAGER PLWFICSGMG TQWRGMGLSL MRLDRFRDSI LRSDEAVKPF GLKVSQLLLS
   541  TDESTFDDIV HSFVSLTAIQ IGLIDLLSCM GLRPDGIVGH SLGEVACGYA DGCLSQEEAV
   601  LAAYWRGQCI KEAHLPPGAM AAVGLSWEEC KQRCPPGVVP ACHNSKDTVT ISGPQAPVFE
   661  FVEQLRKEGV FAKEVRTGGM AFHSYFMEAI APPLLQELKK VIREPKPRSA RWLSTSIPEA
   721  QWHSSLARTS SAEYNVNNLV SPVLFQEALW HVPEHAVVLE IAPHALLQAV LKRGLKPSCT
   781  IIPLMKKDHR DNLEFFLAGI GRLHLSGIDA NPNALFPPVE FPAPRGTPLI SPLIKWDHSL
   841  AWDVPAAEDF PNGSGSPSAA IYNIDTSSES PDHYLVDHTL DGRVLFPATG YLSIVWKTLA
   901  RALGLGVEQL PVVFEDVVLH QATILPKTGT VSLEVRLLEA SRAFEVSENG NLVVSGKVYQ
   961  WDDPDPRLFD HPESPTPNPT EPLFLAQAEV YKELRLRGYD YGPHFQGILE ASLEGDSGRL
  1021  LWKDNWVSFM DTMLQMSILG SAKHGLYLPT RVTAIHIDPA THRQKLYTLQ DKAQVADVVV
  1081  SRWLRVTVAG GVHISGLHTE SAPRRQQEQQ VPILEKFCFT PHTEEGCLSE RAALQEELQL
  1141  CKGLVQALQT KVTQQGLKMV VPGLDGAQIP RDPSQQELPR LLSAACRLQL NGNLQLELAQ
  1201  VLAQERPKLP EDPLLSGLLD SPALKACLDT AVENMPSLKM KVVEVLAGHG HLYSRIPGLL
  1261  SPHPLLQLSY TATDRHPQAL EAAQAELQQH DVAQGQWDPA DPAPSALGSA DLLVCNCAVA
  1321  ALGDPASALS NMVAALREGG FLLLHTLLRG HPLGDIVAFL TSTEPQYGQG ILSQDAWESL
  1381  FSRVSLRLVG LKKSFYGSTL FLCRRPTPQD SPIFLPVDDT SFRWVESLKG ILADEDSSRP
  1441  VWLKAINCAT SGVVGLVNCL RREPGGNRLR CVLLSNLSST SHVPEVDPGS AELQKVLQGD
  1501  LVMNVYRDGA WGAFRHFLLE EDKPEEPTAH AFVSTLTRGD LSSIRWVCSS LRHAQPTCPG
  1561  AQLCTVYYAS LNFRDIMLAT GKLSPDAIPG KWTSQDSLLG MEFSGRDASG KRVMGLVPAK
  1621  GLATSVLLSP DFLWDVPSNW TLEEAASVPV VYSTAYYALV VRGRVRPGET LLIHSGSGGV
  1681  GQAAIAIALS LGCRVFTTVG SAEKRAYLQA RFPQLDSTSF ANSRDTSFEQ HVLWHTGGKG
  1741  VDLVLNSLAE EKLQASVRCL ATHGRFLEIG KFDLSQNHPL GMAIFLKNVT FHGVLLDAFF
  1801  NESSADWREV WALVQAGIRD GVVRPLKCTV FHGAQVEDAF RYMAQGKHIG KVVVQVLAEE
  1861  PEAVLKGAKP KLMSAISKTF CPAHKSYIIA GGLGGFGLEL AQWLIQRGVQ KLVLTSRSGI
  1921  RTGYQAKQVR RWRRQGVQVQ VSTSNISSLE GARGLIAEAA QLGPVGGVFN LAVVLRDGLL
  1981  ENQTPEFFQD VCKPKYSGTL NLDRVTREAC PELDYFVVFS SVSCGRGNAG QSNYGFANSA
  2041  MERICEKRRH EGLPGLAVQW GAIGDVGILV ETMSTNDTIV SGTLPQRMAS CLEVLDLFLN
  2101  QPHMVLSSFV LAEKAAAYRD RDSQRDLVEA VAHILGIRDL AAVNLDSSLA DLGLDSLMSV
  2161  EVRQTLEREL NLVLSVREVR QLTLRKLQEL SSKADEASEL ACPTPKEDGL AQQQTQLNLR
  2221  SLLVNPEGPT LMRLNSVQSS ERPLFLVHPI EGSTTVFHSL ASRLSIPTYG LQCTRAAPLD
  2281  SIHSLAAYYI DCIRQVQPEG PYRVAGYSYG ACVAFEMCSQ LQAQQSPAPT HNSLFLFDGS
  2341  PTYVLAYTQS YRAKLTPGCE AEAETEAICF FVQQFTDMEH NRVLEALLPL KGLEERVAAA
  2401  VDLIIKSHQG LDRQELSFAA RSFYYKLRAA EQYTPKAKYH GNVMLLRAKT GGAYGEDLGA
  2461  DYNLSQVCDG KVSVHVIEGD HRTLLEGSGL ESIISIIHSS LAEPRVSVRE G

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FASN can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.22

Highest tissue expression

364 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FASN.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 2,517 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• FASN-associated disorder

Disease | ImmuneIEDB

Conditions an epitope on FASN was assayed in.

• carbamazepine allergy T cell

ReferencesPubMed · IEDB

Publications for FASN from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.16

gnomAD pLI

1

gnomAD missense Z

2.36

DepMap mean gene effect

-0.17

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• acetyl-CoA metabolic process
• cellular response to interleukin-4
• establishment of endothelial intestinal barrier
• ether lipid biosynthetic process
• fatty acid biosynthetic process
• fatty acid metabolic process
• fatty-acyl-CoA biosynthetic process
• host-mediated perturbation of viral process
• inflammatory response
• mammary gland development
• monocyte differentiation
• neutrophil differentiation
• osteoblast differentiation
• response to caloric restriction
• response to nutrient

Molecular functions

• (3R)-hydroxyacyl-[acyl-carrier-protein] dehydratase activity
• 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity
• 3-oxoacyl-[acyl-carrier-protein] synthase activity
• [acyl-carrier-protein] S-malonyltransferase activity
• cadherin binding
• enoyl-[acyl-carrier-protein] reductase (NADPH) activity
• fatty acyl-[ACP] hydrolase activity
• identical protein binding
• RNA binding
• [acyl-carrier-protein] S-acetyltransferase activity
• fatty acid synthase activity
• phosphopantetheine binding

Cellular components

• cytoplasm
• cytosol
• extracellular exosome
• glycogen granule
• Golgi apparatus
• melanosome
• membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Thioesterase
• Acyl transferase domain superfamily
• Phosphopantetheine attachment site
• Phosphopantetheine binding ACP domain
• GroES-like superfamily
• Alcohol dehydrogenase-like, C-terminal
• Methyltransferase type 12
• Beta-ketoacyl synthase-like, N-terminal domain
• Beta-ketoacyl synthase, C-terminal domain
• Acyl transferase domain
• Acyl transferase/acyl hydrolase/lysophospholipase
• Malonyl-CoA ACP transacylase, ACP-binding
• Thiolase-like
• Beta-ketoacyl synthase, active site
• Polyketide synthase, beta-ketoacyl synthase domain
• Enoylreductase domain
• Alpha/Beta hydrolase fold
• S-adenosyl-L-methionine-dependent methyltransferase superfamily
• NAD(P)-binding domain superfamily
• ACP-like superfamily
• Ketoreductase domain
• Zinc-binding dehydrogenase
• Beta-ketoacyl synthase, N-terminal domain
• Phosphopantetheine attachment site
• Acyl transferase domain
• Thioesterase domain
• Beta-ketoacyl synthase, C-terminal domain
• Methyltransferase domain
• Polyketide synthase-like, ketoreductase domain
• Polyketide synthase-like, phosphopantetheine-binding domain
• Polyketide/metazoan fatty acid synthase-like, dehydratase domain
• Polyketide synthase, C-terminal extension
• Polyketide synthase, dehydratase domain superfamily
• Fatty acid synthase, pseudo-KR domain
• Polyketide synthase, dehydratase domain, N-terminal
• Polyketide synthase, dehydratase domain
• Polyketide and Nonribosomal Peptide Biosynthesis Enzymes
• KR domain
• Ketoacyl-synthetase C-terminal extension
• Polyketide synthase dehydratase domain
• Fatty acid synthase, pseudo-KR domain

KeywordsUniProt

• Acetylation
• Cytoplasm
• Fatty acid biosynthesis
• Fatty acid metabolism
• Hydrolase
• Isopeptide bond
• Lipid biosynthesis
• Lipid metabolism
• Lyase
• Multifunctional enzyme
• NAD
• NADP
• Oxidoreductase
• Phosphopantetheine
• Phosphoprotein
• Pyridoxal phosphate
• S-nitrosylation
• Transferase
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of FASN in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CEACAM1
• CD5L
• LACC1
• AKT1
• HIF1A