Fatty acid synthase (FASN)

The protein contains 2511 amino acids for an estimated molecular weight of 273427 Da.

 

Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain. (updated: Aug. 12, 2020)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 100%
Model score: 79

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VariantDescription
dbSNP:rs2228305
dbSNP:rs561903908
dbSNP:rs2228307
dbSNP:rs113931914

The reference OMIM entry for this protein is 600212

Fatty acid synthase; fasn

DESCRIPTION

Fatty acid synthase (EC 2.3.1.85) catalyzes the conversion of acetyl-CoA and malonyl-CoA, in the presence of NADPH, into long-chain saturated fatty acids (Wakil, 1989). In prokaryotes and plants, FASN consists of an acyl carrier protein and 7 structurally independent monofunctional enzymes. In animals, however, all of the component enzymatic activities of FASN and acyl carrier protein are organized in one large polypeptide chain.

CLONING

Jayakumar et al. (1994) isolated and sequenced cDNA clones representing the 2 ends of the human FASN gene and also isolated overlapping genomic clones from human YAC libraries. Jayakumar et al. (1995) purified fatty acid synthase to near homogeneity from a human hepatoma cell line, HepG2. The specific activity of the enzyme was found to be half that of chicken liver enzyme. They also cloned the human brain FASN cDNA. The cDNA sequence had an open reading frame of 7,512 bp that encoded a 2504-amino acid protein with relative mass of 272,516. The amino acid sequence of the human enzyme had 79% and 63% identity, respectively, with the sequences of the rat and chicken enzymes. Northern analysis revealed that human FASN mRNA is about 9.3 kb in size and that its level varies among human tissues, with brain, lung, and liver tissues showing prominent expression. Sequence variants of unknown origin and significance were found in the enzyme derived from HepG2.

GENE FUNCTION

Ye et al. (2000) investigated the expression of ESR1 in prostate cancer cell lines and unexpectedly found a FASN/ESR1 fusion transcript. Using semi-nested RT-PCR analysis of ESR1 and its variants, Ye et al. (2000) found that the N-terminal coding region of FASN containing domain 1 was fused to the C-terminal coding region of the ESR1 ligand binding domain. Nested RT-PCR also detected the fusion transcript in breast, cervical, and bladder cancer cell lines. Loftus et al. (2000) identified a link between anabolic energy metabolism and appetite control. Both systemic and intracerebroventricular treatment of mice with fatty acid synthase inhibitors (cerulenin and C75, a synthetic compound) led to inhibition of feeding and dramatic weight loss. C75 inhibited expression of the prophagic signal neuropeptide Y (162640) in the hypothalamus and acted in a leptin (164160)-independent manner that appears to be mediated by malonyl-CoA. Loftus et al. (2000) suggested that FASN may represent an important link in feeding regulation and may be a potential therapeutic target for obesity. Camassei et al. (2003) found that FAS activation increased with increased retinoblastoma (180200) aggressiveness and postulated that FAS inhibition could represent an alternative treatment strategy in advanced and resistant retinoblastomas. Menendez et al. (2004) identified a molecular link between FASN and the HER2 oncogene (164870), a marker for poor prognosis that is overexpressed in 30% of breast and ovarian cancers. Pharmacologic FASN inhibitors were found to suppress p185(HER2) oncoprotein expression and tyrosine kinase activity in breast and ovarian cancers overexpressing HER2. Similar suppression was observed when FASN gene expression was silenced by using the highly sequence-specific mechanism of RNA interference (RNAi). Using a focused RNAi analysis, followed by validation with pharmacologic inhibitors, Heaton et al. (2010) identified 3 cellular pathways required for dengue virus (DENV; see 614371) replication: autophagy, a ... More on the omim web site

Subscribe to this protein entry history

Aug. 24, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

April 12, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600212 was added.