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    ACLY ATP citrate lyase [ Homo sapiens ]

    Gene ID: 47, updated on 11-May-2012
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    Summary

    Official Symbol
    ACLYprovided by HGNC
    Official Full Name
    ATP citrate lyaseprovided by HGNC
    Primary source
    HGNC:115
    See related
    Ensembl:ENSG00000131473; HPRD:00155; MIM:108728; Vega:OTTHUMG00000133507
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    ACL; ATPCL; CLATP
    Summary
    ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. The enzyme is a tetramer (relative molecular weight approximately 440,000) of apparently identical subunits. It catalyzes the formation of acetyl-CoA and oxaloacetate from citrate and CoA with a concomitant hydrolysis of ATP to ADP and phosphate. The product, acetyl-CoA, serves several important biosynthetic pathways, including lipogenesis and cholesterogenesis. In nervous tissue, ATP citrate-lyase may be involved in the biosynthesis of acetylcholine. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    17q21.2
    Sequence :
    Chromosome: 17; NC_000017.10 (40023179..40075272, complement)
    See ACLY in Epigenomics, MapViewer

    Chromosome 17 - NC_000017.10Genomic Context describing neighboring genes Neighboring gene kelch-like 10 (Drosophila) Neighboring gene kelch-like 11 (Drosophila) Neighboring gene tetratricopeptide repeat domain 25 Neighboring gene putative uncharacterized protein encoded by NCRNA00269-like Neighboring gene 2',3'-cyclic nucleotide 3' phosphodiesterase

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. ADP-Mg2+ bound to the ATP-grasp domain of ATP-citrate lyase. Sun T, et al. Acta Crystallogr Sect F Struct Biol Cryst Commun, 2011 Oct 1. PMID 22102020.
    2. Systematic and quantitative assessment of the ubiquitin-modified proteome. Kim W, et al. Mol Cell, 2011 Oct 21. PMID 21906983.
    3. A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Wagner SA, et al. Mol Cell Proteomics, 2011 Oct. PMID 21890473.
    4. The lipogenesis pathway as a cancer target. Abramson HN. J Med Chem, 2011 Aug 25. PMID 21726077.
    5. Differences between human and rodent pancreatic islets: low pyruvate carboxylase, atp citrate lyase, and pyruvate carboxylation and high glucose-stimulated acetoacetate in human pancreatic islets. MacDonald MJ, et al. J Biol Chem, 2011 May 27. PMID 21454710.

    See all (43) citations in PubMed

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. crystals of ATP-citrate lyase diffracted to 2.3 A resolution
      Title: ADP-Mg2+ bound to the ATP-grasp domain of ATP-citrate lyase.
    2. three major enzymes of the pathway, FASN, ACC, and ACLY, are up-regulated in numerous tumor types.
      Title: The lipogenesis pathway as a cancer target.
    3. Differences between human and rodent pancreatic islets: low pyruvate carboxylase, atp citrate lyase, and pyruvate carboxylation and high glucose-stimulated acetoacetate in human pancreatic islets.
      Title: Differences between human and rodent pancreatic islets: low pyruvate carboxylase, atp citrate lyase, and pyruvate carboxylation and high glucose-stimulated acetoacetate in human pancreatic islets.
    4. Data suggest that ATP-citrate lyase (ACLY) expression and activity can be suppressed by exogenous lipids and demonstrate a critical role for ACLY in pancreatic beta cell survival.
      Title: ATP-citrate lyase reduction mediates palmitate-induced apoptosis in pancreatic beta cells.
    5. Data show that siRNA-mediated silencing of SREBP-1 and ATP citrate lyase significantly attenuated H(2)O(2)-induced senescence
      Title: Sterol regulatory element-binding protein (SREBP)-1-mediated lipogenesis is involved in cell senescence.
    6. Identification of the citrate-binding site of human ATP-citrate lyase using X-ray crystallography.
      Title: Identification of the citrate-binding site of human ATP-citrate lyase using X-ray crystallography.
    7. ACLY is a positive regulator of glycolysis in glioblastoma cells.
      Title: Identification of ATP citrate lyase as a positive regulator of glycolytic function in glioblastomas.
    8. The activities of ATP citrate lyase were decreased by 57% in pancreatic islets of patients with type 2 diabetes.
      Title: Decreased levels of metabolic enzymes in pancreatic islets of patients with type 2 diabetes.
    9. findings suggest that ATP-citrate lyase activity is required to link growth factor-induced increases in nutrient metabolism to the regulation of histone acetylation and gene expression
      Title: ATP-citrate lyase links cellular metabolism to histone acetylation.
    10. Atp citrate lyase is involved in lung cancer pathogenesis associated with metabolic abnormality and might offer a novel therapeutic target.
      Title: ATP citrate lyase: activation and therapeutic implications in non-small cell lung cancer.
    Submit: New GeneRIF Correction See all (13)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    P53396 P53396 ACLY    HPRD  PubMed  
    P53396 P49841 GSK3B    HPRD  PubMed  
    P53396 P17612 PRKACA    HPRD  PubMed  
    BioGRID:106563 BioGRID:107463 CDKN2A    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:106563 BioGRID:109187 GSK3B    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:106563 BioGRID:115331 HDAC5    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:106563 BioGRID:114593 HGS    BioGRID  PubMed Reconstituted Complex 
    BioGRID:106563 BioGRID:115000 IKBKE    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:106563 BioGRID:110895 NME2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:106563 BioGRID:111551 PRKAB1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:106563 BioGRID:112872 TERF1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:106563 BioGRID:112873 TERF2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:106563 BioGRID:112888 TFE3    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:106563 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:106563 BioGRID:1678002 UL27    BioGRID  PubMed Affinity Capture-MS 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • ChREBP activates metabolic gene expression, organism-specific biosystem (from REACTOME)
      ChREBP activates metabolic gene expression, organism-specific biosystemChREBP (Carbohydrate Response Element Binding Protein) is a large multidomain protein containing a nuclear localization signal near its amino terminus, polyproline domains, a basic helix-loop-helix-l...
    • Citrate cycle (TCA cycle), organism-specific biosystem (from KEGG)
      Citrate cycle (TCA cycle), organism-specific biosystemThe citrate cycle (TCA cycle, Krebs cycle) is an important aerobic pathway for the final steps of the oxidation of carbohydrates and fatty acids. The cycle starts with acetyl-CoA, the activated form ...
    • Citrate cycle (TCA cycle), conserved biosystem (from KEGG)
      Citrate cycle (TCA cycle), conserved biosystemThe citrate cycle (TCA cycle, Krebs cycle) is an important aerobic pathway for the final steps of the oxidation of carbohydrates and fatty acids. The cycle starts with acetyl-CoA, the activated form ...
    • Fatty Acid Biosynthesis, organism-specific biosystem (from WikiPathways)
      Fatty Acid Biosynthesis, organism-specific biosystem
      Fatty Acid Biosynthesis
    • Fatty Acyl-CoA Biosynthesis, organism-specific biosystem (from REACTOME)
      Fatty Acyl-CoA Biosynthesis, organism-specific biosystemFatty acyl-CoA biosynthesis involves following steps: -Palmitate synthesis catalyzed by Acetyl-CoA carboxylase and Fatty acid synthase-Conversion of palmitic acid to long chain fatty acids and-Conver...
    • Fatty acid, triacylglycerol, and ketone body metabolism, organism-specific biosystem (from REACTOME)
      Fatty acid, triacylglycerol, and ketone body metabolism, organism-specific biosystemThe reactions involved in the metabolism of fatty acids and of the triacylglycerols and ketone bodies derived from them form a closely interrelated, coordinately regulated module that plays a central...
    • Integration of energy metabolism, organism-specific biosystem (from REACTOME)
      Integration of energy metabolism, organism-specific biosystemMany hormones that affect individual physiological processes including the regulation of appetite, absorption, transport, and oxidation of foodstuffs influence energy metabolism pathways. While insul...
    • Metabolic pathways, organism-specific biosystem (from KEGG)
      Metabolic pathways, organism-specific biosystem
      Metabolic pathways
    • Metabolism, organism-specific biosystem (from REACTOME)
      Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
    • Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
      Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
    • Triglyceride Biosynthesis, organism-specific biosystem (from REACTOME)
      Triglyceride Biosynthesis, organism-specific biosystemThe overall process of triglyceride (triacylglycerol) biosynthesis consists of four biochemical pathways: fatty acyl-CoA biosynthesis, conversion of fatty acyl-CoA to phosphatidic acid, conversion of...
    • acetyl-CoA biosynthesis III (from citrate), organism-specific biosystem (from BIOCYC)
      acetyl-CoA biosynthesis III (from citrate), organism-specific biosystem
      acetyl-CoA biosynthesis III (from citrate)

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    ATP citrate synthase activity TAS
    Traceable Author Statement
    more info
    		  
    binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    ligase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    succinate-CoA ligase (ADP-forming) activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    transferase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    ATP catabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    cellular carbohydrate metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    cellular lipid metabolic process TAS
    Traceable Author Statement
    more info
    		  
    citrate metabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    coenzyme A metabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    energy reserve metabolic process TAS
    Traceable Author Statement
    more info
    		  
    lipid biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    long-chain fatty-acyl-CoA biosynthetic process TAS
    Traceable Author Statement
    more info
    		  
    positive regulation of cellular metabolic process TAS
    Traceable Author Statement
    more info
    		  
    small molecule metabolic process TAS
    Traceable Author Statement
    more info
    		  
    triglyceride biosynthetic process TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    citrate lyase complex TAS
    Traceable Author Statement
    more info
    		 PubMed 
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    mitochondrion IEA
    Inferred from Electronic Annotation
    more info
    		  
    NOT nucleolus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
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    General protein information

    Preferred Names
    ATP-citrate synthase
    Names
    ATP-citrate synthase
    ATP citrate synthase
    citrate cleavage enzyme
    ATP-citrate (pro-S-)-lyase
    NP_001087.2
    NP_942127.1
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001096.2 → NP_001087.2  ATP-citrate synthase isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript, and encodes the longer isoform (1).
      Source sequence(s)
      BC006195, BG037168
      Consensus CDS
      CCDS11412.1
      UniProtKB/Swiss-Prot
      P53396
      Related
      ENSP00000253792, OTTHUMP00000164772, ENST00000352035, OTTHUMT00000257465
      Conserved Domains (6) summary
      cd06100
      Location:856 – 1093
      Blast Score: 745
      CCL_ACL-C; Citryl-CoA lyase (CCL), the C-terminal portion of the single-subunit type ATP-citrate lyase (ACL) and the C-terminal portion of the large subunit of the two-subunit type ACL. CCL cleaves citryl-CoA (CiCoA) to acetyl-CoA (AcCoA) and oxaloacetate (OAA). ...
      PLN02235
      Location:1 – 419
      Blast Score: 1053
      PLN02235; ATP citrate (pro-S)-lyase
      PLN02522
      Location:491 – 1094
      Blast Score: 2396
      PLN02522; ATP citrate (pro-S)-lyase
      cl02894
      Location:660 – 785
      Blast Score: 220
      Ligase_CoA; CoA-ligase
      cl03087
      Location:55 – 207
      Blast Score: 92
      ATP-grasp_4; ATP-grasp domain
      cl09931
      Location:492 – 601
      Blast Score: 127
      NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

    2. NM_198830.1 → NP_942127.1  ATP-citrate synthase isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame segment of the coding region, compared to variant 1. This results in a shorter isoform (2), compared to isoform 1.
      Source sequence(s)
      BC006195, BG037168
      Consensus CDS
      CCDS11413.1
      UniProtKB/Swiss-Prot
      P53396
      Related
      ENSP00000345398, ENST00000353196
      Conserved Domains (6) summary
      cd06100
      Location:846 – 1083
      Blast Score: 744
      CCL_ACL-C; Citryl-CoA lyase (CCL), the C-terminal portion of the single-subunit type ATP-citrate lyase (ACL) and the C-terminal portion of the large subunit of the two-subunit type ACL. CCL cleaves citryl-CoA (CiCoA) to acetyl-CoA (AcCoA) and oxaloacetate (OAA). ...
      PLN02235
      Location:1 – 419
      Blast Score: 1053
      PLN02235; ATP citrate (pro-S)-lyase
      PLN02522
      Location:481 – 1084
      Blast Score: 2396
      PLN02522; ATP citrate (pro-S)-lyase
      cl02894
      Location:650 – 775
      Blast Score: 219
      Ligase_CoA; CoA-ligase
      cl03087
      Location:55 – 207
      Blast Score: 92
      ATP-grasp_4; ATP-grasp domain
      cl09931
      Location:482 – 591
      Blast Score: 127
      NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000017.10 Reference GRCh37.p5 Primary Assembly

      Range
      40023179..40075272, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh37.p5 PATCHES

    Genomic

    1. NW_003571052.1 Reference GRCh37.p5 PATCHES

      Range
      153568..205661, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000149.1 Alternate HuRef

      Range
      35785140..35836956, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC091172.11 (84159..136252) None
    genomic CH471152.1 EAW60777.1
      EAW60778.1
      EAW60779.1
      EAW60780.1
      EAW60781.1
    mRNA AB210035.1 BAE06117.1
    mRNA AK095084.1 BAC04484.1
    mRNA AK295675.1 BAG58532.1
    mRNA AK304802.1 BAG65552.1
    mRNA AK312315.1 None
    mRNA BC006195.2 AAH06195.1
    mRNA BG037168.1 None
    mRNA U18197.1 AAB60340.1
    mRNA X64330.1 CAA45614.1
    mRNA DQ575356.1 None
    other-genetic JF432308.1 ADZ15525.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P53396.3 GenPept UniProtKB/Swiss-Prot:P53396
    Q4LE36 GenPept UniProtKB/TrEMBL:Q4LE36
    Q8N9C4 GenPept UniProtKB/TrEMBL:Q8N9C4
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    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
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