id: P49327
gene_symbol: FASN
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  FASN encodes fatty acid synthase, the cytosolic type I fatty acid synthase of mammals:
  a large multifunctional homodimeric "megasynthase" (~273 kDa per protomer) that carries
  out the complete cycle of de novo long-chain saturated fatty acid biosynthesis, producing
  mainly palmitate (C16:0) from acetyl-CoA and malonyl-CoA using NADPH as reductant. Each
  subunit contains seven catalytic activities and an acyl-carrier-protein (ACP) domain
  bearing a 4'-phosphopantetheine prosthetic group. Using an acetyl-CoA primer, the enzyme
  iteratively condenses malonyl-CoA-derived two-carbon units and reduces the growing chain
  through a repeating condensation/reduction/dehydration/reduction cycle, releasing palmitate
  via its C-terminal thioesterase. The catalytic components are: the bifunctional
  malonyl/acetyl transferase (MAT; [ACP] S-acetyltransferase and S-malonyltransferase), the
  beta-ketoacyl (condensing) synthase (KS), beta-ketoacyl reductase (KR), beta-hydroxyacyl
  dehydratase (DH), enoyl reductase (ER), and thioesterase (TE), organized into a condensing
  region and a modifying region joined by a flexible neck, with catalytically dead pseudo-KR
  and pseudo-methyltransferase domains. The tethered ACP shuttles intermediates between the
  active sites. FASN is the primary enzyme of de novo lipogenesis, supplying fatty acids for
  membrane phospholipids, energy storage, protein acylation (e.g. palmitoylation) and lipid
  signaling. It is expressed ubiquitously with prominent expression in liver, adipose tissue,
  brain, lung and mammary gland, is transcriptionally induced by SREBP and ChREBP in response
  to nutrients/insulin, and is frequently overexpressed in cancers.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:16210410
  title: Differential expression profiling of membrane proteins by quantitative proteomics
    in a human mesenchymal stem cell line undergoing osteoblast differentiation.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Quantitative proteomics of a membrane-enriched fraction during osteoblast
      differentiation; FASN is one of many differentially detected proteins. Supports a
      correlative/high-throughput association only, not a direct role of FASN in osteoblast
      differentiation or membrane localization.
- id: PMID:17081065
  title: Proteomic and bioinformatic characterization of the biogenesis and function
    of melanosomes.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Large-scale MS characterization of melanosome fractions; basis for the UniProt
      cytoplasm/melanosome subcellular location. FASN is a cytosolic enzyme, so the
      melanosome signal is a secondary/co-purifying localization.
- id: PMID:18022563
  title: Mechanism and substrate recognition of human holo ACP synthase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Structure of the FASN ACP domain (2119-2207) in complex with AASDHPPT (human holo-ACP
      synthase, Q9NRN7) and CoA; defines phosphopantetheinylation of the ACP. Basis of the
      IPI interaction with AASDHPPT and confirms the phosphopantetheine attachment site.
- id: PMID:18455495
  title: Differential activation of recombinant human acetyl-CoA carboxylases 1 and
    2 by citrate.
  findings: []
  reference_review:
    relevance: LOW
    correctness: MISCITED
    review_notes: >-
      Reactome-linked EXP citation for FASN fatty acid synthase activity (GO:0004312). The
      cached abstract is about acetyl-CoA carboxylase (ACACA/ACACB) activation by citrate,
      the enzyme immediately upstream of FASN, and does not itself demonstrate FASN activity.
      Retained (experimental annotation, not removed) but the core FASN activity is better
      supported by PMID:8962082 and PMID:26851298.
- id: PMID:19056867
  title: Large-scale proteomics and phosphoproteomics of urinary exosomes.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Detection of FASN in urinary exosome proteomics; supports the extracellular exosome
      HDA localization as a co-purifying/secondary observation only.
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Membrane-proteome survey detecting FASN; high-throughput membrane association of a
      soluble cytosolic enzyme, not a bona fide membrane localization.
- id: PMID:20458337
  title: MHC class II-associated proteins in B-cell exosomes and potential functional
    implications for exosome biogenesis.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Exosome proteomics detecting FASN; supports extracellular exosome HDA localization as
      a secondary observation.
- id: PMID:22658674
  title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      System-wide mRNA-interactome capture that lists FASN among RNA-crosslinked proteins.
      No evidence for a dedicated RNA-binding function; likely reflects the abundance of this
      metabolic enzyme.
- id: PMID:22681889
  title: The mRNA-bound proteome and its global occupancy profile on protein-coding
    transcripts.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Second mRNA-interactome capture dataset listing FASN; same caveat as PMID:22658674.
- id: PMID:23427160
  title: Hepatitis C virus replication is modulated by the interaction of nonstructural
    protein NS5B and fatty acid synthase.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Reports a physical interaction between HCV NS5B and human FASN modulating viral
      replication; basis of the IPI "protein binding" annotation to the HCV NS5B chain. A
      virus-host interaction, informative for the proviral role but not a core cellular
      function.
- id: PMID:23533145
  title: In-depth proteomic analyses of exosomes isolated from expressed prostatic
    secretions in urine.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Prostatic-secretion exosome proteomics detecting FASN; supports the extracellular
      exosome HDA localization as a secondary observation.
- id: PMID:25468996
  title: E-cadherin interactome complexity and robustness resolved by quantitative
    proteomics.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Proximity-biotinylation/quantitative proteomics of the E-cadherin interactome; FASN is
      one of hundreds of proximal proteins, the basis of the HDA "cadherin binding"
      annotation. Proximity/abundance association, not a specific adhesion function.
- id: PMID:25959826
  title: Quantitative interaction proteomics of neurodegenerative disease proteins.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Interaction proteomics of neurodegenerative-disease proteins; source of an IPI
      "protein binding" to HTT (P42858). Generic co-complex association.
- id: PMID:26851298
  title: S-nitrosylation of fatty acid synthase regulates its activity through dimerization.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Primary study on human FASN: directly assays FASN enzymatic activity and its partial
      activities, identifies FASN as a key lipogenic enzyme in adipocytes, and shows
      S-nitrosylation at Cys-1471/Cys-2091 activates the enzyme via dimerization. Basis of
      several EXP/IDA activity annotations. Abstract-only in cache.
- id: PMID:27478939
  title: C13orf31 (FAMIN) is a central regulator of immunometabolic function.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Shows FAMIN (LACC1, Q8IV20) forms a complex with FASN on peroxisomes and promotes de
      novo lipogenesis, linking FASN to immunometabolism. Basis of the IPI interaction with
      LACC1; a functional interaction but peripheral to the core catalytic function.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      High-throughput yeast two-hybrid binary interactome map; source of IPI "protein
      binding" to ADIPOQ (Q15848) and LNX1 (Q8TBB1). Generic binary interactions of unclear
      biological significance for FASN.
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Neurodegenerative-disease interactome map; a second source of an IPI "protein binding"
      to HTT (P42858). Generic association.
- id: PMID:34320401
  title: Inhibitors of VPS34 and fatty-acid metabolism suppress SARS-CoV-2 replication.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Shows FASN activity/de novo fatty acid synthesis is required for SARS-CoV-2
      replication (FASN knockout impairs replication, rescued by fatty-acid supplementation).
      Basis of the IDA GO:0044788 (host-mediated perturbation of viral process) and the
      UniProt microbial-infection FUNCTION line. A host-pathogen context role.
- id: PMID:36604718
  title: Targeting fatty acid synthase modulates sensitivity of hepatocellular carcinoma
    to sorafenib via ferroptosis.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Source of an IPI "protein binding" to GPX4 (Q16665) in a cancer/ferroptosis context.
      Disease-context interaction, not a core cellular function.
- id: PMID:37308485
  title: Atomic model for core modifying region of human fatty acid synthase in complex
    with Denifanstat.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      CryoEM of the human FASN modifying region (DH, ΨME, ΨKR, ER, KR) as a homodimer,
      defining the domain architecture and drug-binding pocket. Basis of the ComplexPortal
      cytosol IDA. Confirms FASN is a homodimeric cytosolic multienzyme.
- id: PMID:39979457
  title: Snapshots of acyl carrier protein shuttling in human fatty acid synthase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      CryoEM of full-length human FASN capturing the ACP shuttling mechanism; both human and
      mouse FASN form stable homodimers; interface mutations impair in vitro activity and
      cellular de novo lipogenesis (palmitate labeling). Basis of the ComplexPortal
      GO:0005835 (fatty acid synthase complex) IPI and GO:0046949 NAS annotations.
- id: PMID:7835891
  title: Isolation and chromosomal mapping of genomic clones encoding the human fatty
    acid synthase gene.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Genomic cloning and chromosomal mapping of human FASN; the TAS basis for the fatty
      acid metabolic process annotation. Establishes gene identity.
- id: PMID:8962082
  title: Cloning and expression of the multifunctional human fatty acid synthase and
    its subdomains in Escherichia coli.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Definitive functional study: recombinant full-length human FASN catalyzes palmitate
      synthesis from acetyl-CoA, malonyl-CoA and NADPH and exhibits all partial activities;
      dissected subdomains carry the acetyl/malonyl transacylase, dehydratase, enoyl and
      beta-ketoacyl reductase and thioesterase activities. Basis of multiple EXP/IDA
      activity annotations. Abstract-only in cache but abstract is fully dispositive.
- id: Reactome:R-HSA-163733
  title: Transcriptional activation of FASN monomer gene by ChREBP:MLX
  findings: []
- id: Reactome:R-HSA-163756
  title: Formation of fatty acid synthase (FAS) dimer
  findings: []
- id: Reactome:R-HSA-1655843
  title: Expression of Fatty Acid Synthase (FASN)
  findings: []
- id: Reactome:R-HSA-199202
  title: Phosphopantetheine conjugation of the ACP domain of FAS
  findings: []
- id: Reactome:R-HSA-75105
  title: Fatty acyl-CoA biosynthesis
  findings: []
- id: Reactome:R-HSA-75872
  title: Conversion of malonyl-CoA and acetyl-CoA to palmitate
  findings: []
- id: Reactome:R-HSA-9605063
  title: Expression of FASN regulated by NR1H2 or NR1H3
  findings: []
- id: Reactome:R-HSA-9948053
  title: NS3 binds FASN dimer
  findings: []
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      FASN is a cytosolic enzyme; the phylogenetic (IBA) inference that it is active in the
      cytoplasm is correct. Cytosol (GO:0005829) is the more precise term captured by
      experimental annotations, but cytoplasm is not wrong.
    action: ACCEPT
- term:
    id: GO:0004312
    label: fatty acid synthase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Core molecular function. FASN is the fatty acid synthase; the IBA inference across the
      family is correct and is directly confirmed experimentally in human FASN.
    action: ACCEPT
- term:
    id: GO:0006633
    label: fatty acid biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: >-
      Core biological process. FASN performs de novo fatty acid biosynthesis; the IBA
      inference is correct.
    action: ACCEPT
- term:
    id: GO:0004312
    label: fatty acid synthase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Core molecular function, IEA duplicate of the experimentally supported fatty acid
      synthase activity (EC 2.3.1.85). Correct; kept as core rather than flagged as a
      redundant IEA.
    action: ACCEPT
- term:
    id: GO:0004313
    label: '[acyl-carrier-protein] S-acetyltransferase activity'
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Genuine partial activity of the bifunctional MAT domain (EC 2.3.1.38), directly
      demonstrated experimentally in human FASN (also annotated EXP/IDA below). Correct.
    action: ACCEPT
- term:
    id: GO:0004314
    label: '[acyl-carrier-protein] S-malonyltransferase activity'
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Genuine partial activity of the bifunctional MAT domain (EC 2.3.1.39). UniProt lists
      EC 2.3.1.39 with ECO:0000269 experimental support from PubMed:7567999, 8962082 and
      9356448. Correct component activity.
    action: ACCEPT
- term:
    id: GO:0004315
    label: 3-oxoacyl-[acyl-carrier-protein] synthase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Genuine condensing (beta-ketoacyl synthase / KS) partial activity (EC 2.3.1.41),
      directly demonstrated in human FASN (also EXP below). Correct.
    action: ACCEPT
- term:
    id: GO:0004316
    label: 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Genuine beta-ketoacyl reductase (KR) partial activity (EC 1.1.1.100), directly
      demonstrated in human FASN (also IDA below). Correct.
    action: ACCEPT
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: >-
      Correct cytoplasmic localization (IEA duplicate). Cytosol (GO:0005829) is the more
      precise experimentally supported location.
    action: ACCEPT
- term:
    id: GO:0006631
    label: fatty acid metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Correct but a general parent of the more specific fatty acid biosynthetic process
      (GO:0006633) that is the core BP for FASN. Kept as accurate but non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0006633
    label: fatty acid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: >-
      Core biological process (IEA duplicate of the IBA annotation). Correct.
    action: ACCEPT
- term:
    id: GO:0008610
    label: lipid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      Correct but a broad parent of fatty acid biosynthetic process. Kept as accurate but
      non-core given the more specific term is annotated.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0016297
    label: fatty acyl-[ACP] hydrolase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Genuine thioesterase (TE) partial activity of FASN (EC 3.1.2.14) that releases the
      finished palmitate; directly demonstrated in human FASN (UniProt ECO:0000269 from
      PubMed:15507492, 7567999, 8962082, 9356448). Correct component activity.
    action: ACCEPT
- term:
    id: GO:0016491
    label: oxidoreductase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Root-level parent term covering the KR and ER reductase activities of FASN. Correct in
      the broadest sense but uninformative; the specific reductase terms (GO:0004316,
      GO:0141148) are the informative annotations.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0016740
    label: transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Very general parent (covers the MAT and KS acyltransferase activities). Uninformative;
      the specific transferase terms are already annotated.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0016746
    label: acyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      General parent of the MAT ([ACP] S-acetyl/S-malonyltransferase) and KS acyltransferase
      activities. Correct but subsumed by the more specific terms; over-annotated at this
      level.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0019171
    label: (3R)-hydroxyacyl-[acyl-carrier-protein] dehydratase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Genuine beta-hydroxyacyl dehydratase (DH) partial activity of FASN (EC 4.2.1.59),
      directly demonstrated in human FASN (also IDA/EXP below). Correct.
    action: ACCEPT
- term:
    id: GO:0031177
    label: phosphopantetheine binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      The ACP domain of FASN carries a covalently attached 4'-phosphopantetheine prosthetic
      group (attachment at Ser-2156/Ser-2156 region), so phosphopantetheine binding is a real
      cofactor-associated feature of the enzyme. Kept as a real but ancillary (non-core)
      molecular feature supporting the ACP carrier function.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0042470
    label: melanosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      FASN was detected by mass spectrometry in melanosome fractions (UniProt SUBCELLULAR
      LOCATION note; PMID:17081065), which is the basis of this SubCell-derived IEA. FASN is
      a cytosolic enzyme, so this is a secondary/co-purifying localization; kept non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0141148
    label: enoyl-[acyl-carrier-protein] reductase (NADPH) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Genuine enoyl reductase (ER) partial activity of FASN (EC 1.3.1.39), directly
      demonstrated in human FASN (also EXP below). Correct component activity.
    action: ACCEPT
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23427160
  qualifier: enables
  review:
    summary: >-
      IPI interaction with HCV nonstructural protein NS5B (Q99IB8 chain), modulating HCV
      replication. A real virus-host interaction but "protein binding" is uninformative as a
      molecular function. Kept per policy (experimental IPI) but flagged as over-annotated.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25959826
  qualifier: enables
  review:
    summary: >-
      IPI interaction with HTT (P42858) from interaction proteomics. Generic "protein
      binding"; uninformative as a molecular function. Kept (IPI) but over-annotated.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27478939
  qualifier: enables
  review:
    summary: >-
      IPI interaction with FAMIN/LACC1 (Q8IV20); FAMIN forms a complex with FASN on
      peroxisomes and promotes de novo lipogenesis. A biologically meaningful interaction, but
      the bare "protein binding" term is uninformative. Kept (IPI) but over-annotated.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      IPI interaction with ADIPOQ (Q15848) from a binary interactome map. Generic "protein
      binding"; uninformative. Kept (IPI) but over-annotated.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: >-
      IPI interaction with LNX1 (Q8TBB1) from a binary interactome map. Generic "protein
      binding"; uninformative. Kept (IPI) but over-annotated.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: >-
      IPI interaction with HTT (P42858) from a neurodegenerative-disease interactome map.
      Generic "protein binding"; uninformative. Kept (IPI) but over-annotated.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36604718
  qualifier: enables
  review:
    summary: >-
      IPI interaction with GPX4 (Q16665) in a hepatocellular-carcinoma ferroptosis context.
      Generic "protein binding"; uninformative as a molecular function. Kept (IPI) but
      over-annotated.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0006084
    label: acetyl-CoA metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      FASN consumes acetyl-CoA (primer) and malonyl-CoA (derived from acetyl-CoA via ACC) as
      substrates, so participation in acetyl-CoA metabolism is defensible. Orthology-based
      (Ensembl) transfer; kept as accurate but peripheral to the core biosynthetic role.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0007584
    label: response to nutrient
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      FASN expression/activity is strongly regulated by nutritional state (SREBP/ChREBP,
      insulin, feeding), consistent with a response-to-nutrient role by orthology transfer.
      Regulatory/physiological context; kept non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0031667
    label: response to nutrient levels
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      As with response to nutrient, FASN is induced by high-nutrient/lipogenic states. A
      regulatory/physiological context term; kept non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: >-
      FASN is an obligate homodimer arranged head-to-tail; identical protein binding
      (self-association) is a genuine molecular property confirmed structurally
      (PMID:37308485, PMID:39979457) and in the UniProt SUBUNIT record. Kept as accurate but
      non-core relative to the catalytic function.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0046949
    label: fatty-acyl-CoA biosynthetic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-75105
  qualifier: involved_in
  review:
    summary: >-
      Reactome pathway ("Fatty acyl-CoA biosynthesis") placing FASN in fatty acid/acyl-CoA
      biosynthesis. FASN produces free palmitate (released by its thioesterase), which is
      subsequently activated to acyl-CoA by other enzymes; the term is pathway-context
      accurate. Kept non-core (the direct product term is fatty acid biosynthetic process).
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0004312
    label: fatty acid synthase activity
  evidence_type: EXP
  original_reference_id: PMID:18455495
  qualifier: enables
  review:
    summary: >-
      Reactome-assigned EXP annotation of the core fatty acid synthase activity. The linked
      PMID cached abstract is about acetyl-CoA carboxylase activation by citrate (the enzyme
      upstream of FASN) and does not itself demonstrate FASN catalysis; the citation is a poor
      match. The activity itself is correct and strongly supported elsewhere (PMID:8962082,
      PMID:26851298), so per policy the experimental annotation is retained rather than
      removed, but its supporting reference is flagged (see reference_review for PMID:18455495).
    action: ACCEPT
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      Core localization. FASN is a soluble cytosolic enzyme; immunofluorescence (HPA IDA)
      correctly places it in the cytosol.
    action: ACCEPT
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      Immunofluorescence (HPA) plasma-membrane signal. FASN is a cytosolic soluble enzyme
      with no membrane-anchoring features; this likely reflects peripheral/cortical staining
      or a minor pool. Kept per policy (IDA) but treated as a non-core, secondary localization.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:37308485
  qualifier: located_in
  review:
    summary: >-
      Core localization, supported by ComplexPortal IDA from the cryoEM study of the human
      FASN modifying region. Correct.
    action: ACCEPT
- term:
    id: GO:0005835
    label: fatty acid synthase complex
  evidence_type: IPI
  original_reference_id: PMID:39979457
  qualifier: part_of
  review:
    summary: >-
      Core assembly. FASN is the sole component of the homodimeric fatty acid synthase
      complex (ComplexPortal CPX-26624); the cryoEM study confirms a stable homodimer. Correct
      cellular-component/complex annotation.
    action: ACCEPT
- term:
    id: GO:0046949
    label: fatty-acyl-CoA biosynthetic process
  evidence_type: NAS
  original_reference_id: PMID:39979457
  qualifier: involved_in
  review:
    summary: >-
      NAS annotation placing FASN in fatty-acyl-CoA/palmitate biosynthesis, consistent with
      its role as the primary de novo lipogenesis enzyme. Pathway-context accurate; kept
      non-core relative to fatty acid biosynthetic process (its direct product is free
      palmitate).
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0004316
    label: 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity
  evidence_type: IDA
  original_reference_id: PMID:26851298
  qualifier: enables
  review:
    summary: >-
      Directly assayed beta-ketoacyl reductase (KR) partial activity of human FASN. Genuine
      component activity of the megasynthase. Correct.
    action: ACCEPT
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:17081065
  qualifier: is_active_in
  review:
    summary: >-
      IDA (large-scale) that FASN is active in the cytoplasm; consistent with its cytosolic
      localization and function. Correct, though cytosol (GO:0005829) is more precise.
    action: ACCEPT
- term:
    id: GO:0006631
    label: fatty acid metabolic process
  evidence_type: IDA
  original_reference_id: PMID:26851298
  qualifier: involved_in
  review:
    summary: >-
      IDA that FASN participates in fatty acid metabolism, from the S-nitrosylation/activity
      study. Correct but a general parent of the core fatty acid biosynthetic process
      (GO:0006633). Kept as accurate but non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0019171
    label: (3R)-hydroxyacyl-[acyl-carrier-protein] dehydratase activity
  evidence_type: IDA
  original_reference_id: PMID:8962082
  qualifier: enables
  review:
    summary: >-
      Directly assayed beta-hydroxyacyl dehydratase (DH) partial activity in recombinant
      human FASN domain I. Genuine component activity. Correct.
    action: ACCEPT
- term:
    id: GO:0004312
    label: fatty acid synthase activity
  evidence_type: EXP
  original_reference_id: PMID:26851298
  qualifier: enables
  review:
    summary: >-
      Core molecular function, experimentally supported: this study directly measures human
      FASN enzymatic activity (and its regulation by S-nitrosylation). Correct.
    action: ACCEPT
- term:
    id: GO:0004313
    label: '[acyl-carrier-protein] S-acetyltransferase activity'
  evidence_type: EXP
  original_reference_id: PMID:26851298
  qualifier: enables
  review:
    summary: >-
      Experimentally supported [ACP] S-acetyltransferase (MAT) partial activity of human
      FASN. Genuine component activity. Correct.
    action: ACCEPT
- term:
    id: GO:0004315
    label: 3-oxoacyl-[acyl-carrier-protein] synthase activity
  evidence_type: EXP
  original_reference_id: PMID:26851298
  qualifier: enables
  review:
    summary: >-
      Experimentally supported condensing (KS / beta-ketoacyl synthase) partial activity of
      human FASN. Genuine component activity. Correct.
    action: ACCEPT
- term:
    id: GO:0019171
    label: (3R)-hydroxyacyl-[acyl-carrier-protein] dehydratase activity
  evidence_type: EXP
  original_reference_id: PMID:26851298
  qualifier: enables
  review:
    summary: >-
      Experimentally supported beta-hydroxyacyl dehydratase (DH) partial activity of human
      FASN (duplicate of the IDA from PMID:8962082). Genuine component activity. Correct.
    action: ACCEPT
- term:
    id: GO:0141148
    label: enoyl-[acyl-carrier-protein] reductase (NADPH) activity
  evidence_type: EXP
  original_reference_id: PMID:26851298
  qualifier: enables
  review:
    summary: >-
      Experimentally supported enoyl reductase (ER) partial activity of human FASN. Genuine
      component activity. Correct.
    action: ACCEPT
- term:
    id: GO:0004313
    label: '[acyl-carrier-protein] S-acetyltransferase activity'
  evidence_type: IDA
  original_reference_id: PMID:8962082
  qualifier: enables
  review:
    summary: >-
      Directly assayed [ACP] S-acetyltransferase (MAT) partial activity in recombinant human
      FASN domain I. Genuine component activity. Correct.
    action: ACCEPT
- term:
    id: GO:0044788
    label: host-mediated perturbation of viral process
  evidence_type: IDA
  original_reference_id: PMID:34320401
  qualifier: involved_in
  review:
    summary: >-
      FASN activity/de novo fatty acid synthesis is required for SARS-CoV-2 replication;
      FASN knockout impairs replication and is rescued by fatty acids. This is the UniProt
      "microbial infection" FUNCTION. A genuine host-pathogen context role but not a core
      cellular function of the enzyme; kept non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0045296
    label: cadherin binding
  evidence_type: HDA
  original_reference_id: PMID:25468996
  qualifier: enables
  review:
    summary: >-
      From a high-throughput E-cadherin proximity-interactome dataset in which FASN is one of
      hundreds of proximal proteins. Reflects proximity/abundance rather than a dedicated
      cadherin-binding molecular function. Over-annotation.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0001649
    label: osteoblast differentiation
  evidence_type: HDA
  original_reference_id: PMID:16210410
  qualifier: involved_in
  review:
    summary: >-
      Derived from a differential membrane-proteomics dataset during osteoblast
      differentiation; FASN abundance changes correlatively. No direct evidence that FASN
      functions in osteoblast differentiation. Correlative high-throughput association; kept
      non-core.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:16210410
  qualifier: located_in
  review:
    summary: >-
      Detection in a membrane-enriched proteomic fraction. FASN is a soluble cytosolic
      enzyme with no membrane-anchoring features; a high-throughput co-fractionation signal.
      Over-annotation.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-163733
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS placing FASN in the cytosol. Correct core localization.
    action: ACCEPT
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-163756
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS (FAS dimer formation) placing FASN in the cytosol. Correct core
      localization.
    action: ACCEPT
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-199202
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS (phosphopantetheine conjugation of the ACP domain) placing FASN in the
      cytosol. Correct core localization.
    action: ACCEPT
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-75872
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS (conversion of malonyl-CoA and acetyl-CoA to palmitate) placing FASN in
      the cytosol. Correct core localization.
    action: ACCEPT
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9948053
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS placing FASN in the cytosol. Correct core localization.
    action: ACCEPT
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1655843
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS (expression of FASN) placing FASN in the cytosol. Correct core
      localization.
    action: ACCEPT
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9605063
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS placing FASN in the cytosol. Correct core localization.
    action: ACCEPT
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:23533145
  qualifier: located_in
  review:
    summary: >-
      Detection of FASN in exosome proteomics. A high-throughput co-purifying signal for an
      abundant cytosolic enzyme; not a functional extracellular localization. Over-annotation.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: >-
      Detection in an NK-cell membrane-proteome survey. FASN is a soluble cytosolic enzyme;
      a high-throughput membrane co-fractionation signal. Over-annotation.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22658674
  qualifier: enables
  review:
    summary: >-
      From a system-wide mRNA-interactome capture study. There is no evidence for a dedicated
      RNA-binding function of FASN; the crosslink likely reflects the enzyme's abundance and
      nucleotide-cofactor (NADPH/acyl-CoA) chemistry. Over-annotation.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22681889
  qualifier: enables
  review:
    summary: >-
      Second mRNA-interactome capture dataset; same caveat as PMID:22658674. No evidence for
      a functional RNA-binding role. Over-annotation.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:19056867
  qualifier: located_in
  review:
    summary: >-
      Detection in urinary exosome proteomics; high-throughput co-purifying signal.
      Over-annotation of a cytosolic enzyme.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0070062
    label: extracellular exosome
  evidence_type: HDA
  original_reference_id: PMID:20458337
  qualifier: located_in
  review:
    summary: >-
      Detection in B-cell exosome proteomics; high-throughput co-purifying signal.
      Over-annotation of a cytosolic enzyme.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18022563
  qualifier: enables
  review:
    summary: >-
      IPI interaction with AASDHPPT (Q9NRN7), the human holo-ACP synthase / phosphopantetheinyl
      transferase that installs the 4'-phosphopantetheine on the FASN ACP domain (co-crystal
      structure). This is a functionally important, mechanistically specific interaction, but
      the bare "protein binding" term is uninformative. Kept (IPI) but flagged as over-annotated.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0006631
    label: fatty acid metabolic process
  evidence_type: TAS
  original_reference_id: PMID:7835891
  qualifier: involved_in
  review:
    summary: >-
      TAS from the human FASN genomic cloning paper. Correct but a general parent of the core
      fatty acid biosynthetic process (GO:0006633). Kept as accurate but non-core.
    action: KEEP_AS_NON_CORE
core_functions:
- description: >-
    Overall fatty acid synthase activity (EC 2.3.1.85): FASN is the mammalian type I fatty
    acid synthase that catalyzes de novo synthesis of long-chain saturated fatty acids
    (mainly palmitate, C16:0) from an acetyl-CoA primer, malonyl-CoA extender units and NADPH,
    iterating condensation/reduction/dehydration/reduction cycles until palmitate is released.
  molecular_function:
    id: GO:0004312
    label: fatty acid synthase activity
  supported_by:
  - reference_id: PMID:8962082
    supporting_text: >-
      catalyzed palmitate synthesis from acetyl-CoA, malonyl-CoA, and NADPH and
  - reference_id: PMID:39979457
    supporting_text: >-
      FASN is the primary enzyme in DNL that condenses cytosolic acetyl-CoA and malonyl-CoA into the 16-carbon saturated fatty acid palmitate
  - reference_id: file:human/FASN/FASN-uniprot.txt
    supporting_text: >-
      Fatty acid synthetase is a multifunctional enzyme that
  directly_involved_in:
  - id: GO:0006633
    label: fatty acid biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol
  in_complex:
    id: GO:0005835
    label: fatty acid synthase complex
- description: >-
    Malonyl/acetyl transferase (MAT) activity: the bifunctional MAT domain loads the ACP with
    acetyl and malonyl groups, transferring the acetyl primer ([ACP] S-acetyltransferase,
    EC 2.3.1.38) and malonyl extender ([ACP] S-malonyltransferase, EC 2.3.1.39) from CoA onto
    the phosphopantetheine of the acyl-carrier-protein domain.
  molecular_function:
    id: GO:0004313
    label: '[acyl-carrier-protein] S-acetyltransferase activity'
  supported_by:
  - reference_id: PMID:8962082
    supporting_text: >-
      exhibited the activities of the acetyl/malonyl
  - reference_id: file:human/FASN/FASN-uniprot.txt
    supporting_text: 'RecName: Full=[Acyl-carrier-protein] S-acetyltransferase;'
  directly_involved_in:
  - id: GO:0006633
    label: fatty acid biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol
- description: >-
    Malonyl transfer to ACP ([ACP] S-malonyltransferase, EC 2.3.1.39): the second activity of
    the bifunctional MAT domain, loading malonyl groups from malonyl-CoA onto the ACP
    phosphopantetheine to provide the two-carbon extender units for each condensation cycle.
  molecular_function:
    id: GO:0004314
    label: '[acyl-carrier-protein] S-malonyltransferase activity'
  supported_by:
  - reference_id: PMID:8962082
    supporting_text: >-
      exhibited the activities of the acetyl/malonyl
  - reference_id: file:human/FASN/FASN-uniprot.txt
    supporting_text: 'RecName: Full=[Acyl-carrier-protein] S-malonyltransferase;'
  directly_involved_in:
  - id: GO:0006633
    label: fatty acid biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol
- description: >-
    Condensing (beta-ketoacyl synthase, KS) activity (EC 2.3.1.41): the KS domain condenses
    the acyl-ACP with malonyl-ACP, decarboxylatively extending the growing chain by two carbons
    to form a 3-oxoacyl-ACP in each elongation cycle.
  molecular_function:
    id: GO:0004315
    label: 3-oxoacyl-[acyl-carrier-protein] synthase activity
  supported_by:
  - reference_id: PMID:8962082
    supporting_text: >-
      beta-ketoacyl synthase, acetyl-CoA and malonyl-CoA transacylases
  - reference_id: file:human/FASN/FASN-uniprot.txt
    supporting_text: 'RecName: Full=3-oxoacyl-[acyl-carrier-protein] synthase;'
  directly_involved_in:
  - id: GO:0006633
    label: fatty acid biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol
- description: >-
    Beta-ketoacyl reductase (KR) activity (EC 1.1.1.100): the KR domain uses NADPH to reduce
    the 3-oxoacyl-ACP to (3R)-hydroxyacyl-ACP in the first reductive step of each elongation
    cycle.
  molecular_function:
    id: GO:0004316
    label: 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity
  supported_by:
  - reference_id: PMID:8962082
    supporting_text: >-
      the enoyl and beta-ketoacyl reductases and the thioesterase
  - reference_id: file:human/FASN/FASN-uniprot.txt
    supporting_text: 'RecName: Full=3-oxoacyl-[acyl-carrier-protein] reductase;'
  directly_involved_in:
  - id: GO:0006633
    label: fatty acid biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol
- description: >-
    Beta-hydroxyacyl dehydratase (DH) activity (EC 4.2.1.59): the DH domain dehydrates the
    (3R)-hydroxyacyl-ACP to the (2E)-enoyl-ACP.
  molecular_function:
    id: GO:0019171
    label: (3R)-hydroxyacyl-[acyl-carrier-protein] dehydratase activity
  supported_by:
  - reference_id: PMID:8962082
    supporting_text: >-
      the beta-hydroxyacyl dehydratase
  - reference_id: file:human/FASN/FASN-uniprot.txt
    supporting_text: 'RecName: Full=3-hydroxyacyl-[acyl-carrier-protein] dehydratase;'
  directly_involved_in:
  - id: GO:0006633
    label: fatty acid biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol
- description: >-
    Enoyl reductase (ER) activity (EC 1.3.1.39): the ER domain uses NADPH to reduce the
    (2E)-enoyl-ACP to the saturated acyl-ACP, completing each two-carbon elongation cycle.
  molecular_function:
    id: GO:0141148
    label: enoyl-[acyl-carrier-protein] reductase (NADPH) activity
  supported_by:
  - reference_id: PMID:8962082
    supporting_text: >-
      the enoyl and beta-ketoacyl reductases and the thioesterase
  - reference_id: file:human/FASN/FASN-uniprot.txt
    supporting_text: 'RecName: Full=Enoyl-[acyl-carrier-protein] reductase;'
  directly_involved_in:
  - id: GO:0006633
    label: fatty acid biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol
- description: >-
    Thioesterase (TE) activity (EC 3.1.2.14): the C-terminal thioesterase domain hydrolyzes
    the finished palmitoyl-ACP thioester to release free palmitate (chain-length control),
    terminating fatty acid synthesis.
  molecular_function:
    id: GO:0016297
    label: fatty acyl-[ACP] hydrolase activity
  supported_by:
  - reference_id: PMID:8962082
    supporting_text: >-
      the enoyl and beta-ketoacyl reductases and the thioesterase
  - reference_id: file:human/FASN/FASN-uniprot.txt
    supporting_text: 'RecName: Full=Acyl-[acyl-carrier-protein] hydrolase;'
  directly_involved_in:
  - id: GO:0006633
    label: fatty acid biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol