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    ACLY ATP citrate lyase [ Homo sapiens (human) ]

    Gene ID: 47, updated on 5-Nov-2024

    Summary

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    Official Symbol
    ACLYprovided by HGNC
    Official Full Name
    ATP citrate lyaseprovided by HGNC
    Primary source
    HGNC:HGNC:115
    See related
    Ensembl:ENSG00000131473 MIM:108728; AllianceGenome:HGNC:115
    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. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Dec 2014]
    Expression
    Ubiquitous expression in prostate (RPKM 37.3), kidney (RPKM 29.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ACLY in Genome Data Viewer
    Location:
    17q21.2
    Exon count:
    30
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (41866917..41930545, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (42723421..42775531, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (40023170..40075275, complement)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8501 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8502 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12174 Neighboring gene 5'-nucleotidase, cytosolic IIIB Neighboring gene kelch like family member 10 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:40019607-40020116 Neighboring gene kelch like family member 11 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8503 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:40021860-40022360 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:40022361-40022861 Neighboring gene uncharacterized LOC124904005 Neighboring gene MPRA-validated peak2844 silencer Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr17:40066298-40067497 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8504 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8505 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:40085993-40086896 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12176 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:40091696-40092276 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:40102816-40102967 Neighboring gene outer dynein arm docking complex subunit 4 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:40110957-40111564 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:40111565-40112170 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:40112171-40112776 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:40112777-40113382 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8506 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12177 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8507 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8508 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:40119287-40119844 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:40119845-40120402 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:40120403-40120960 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12178 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12179 Neighboring gene 2',3'-cyclic nucleotide 3' phosphodiesterase Neighboring gene DnaJ heat shock protein family (Hsp40) member C7

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. ATP-Citrate Lyase Epigenetically Potentiates Oxidative Phosphorylation to Promote Melanoma Growth and Adaptive Resistance to MAPK Inhibition. Guo W, et al. Clin Cancer Res, 2020 Jun 1. PMID 32034077
    2. Molecular basis for acetyl-CoA production by ATP-citrate lyase. Wei X, et al. Nat Struct Mol Biol, 2020 Jan. PMID 31873304, Free PMC Article
    3. Allosteric role of the citrate synthase homology domain of ATP citrate lyase. Wei X, et al. Nat Commun, 2023 Apr 19. PMID 37076498, Free PMC Article
    4. Mendelian Randomization Study of ACLY and Cardiovascular Disease. Ference BA, et al. N Engl J Med, 2019 Mar 14. PMID 30865797, Free PMC Article
    5. Selective autophagic degradation of ACLY (ATP citrate lyase) maintains citrate homeostasis and promotes oocyte maturation. He H, et al. Autophagy, 2023 Jan. PMID 35404187, Free PMC Article

    See all (273) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The pathological significance and potential mechanism of ACLY in cholangiocarcinoma.
      Title: The pathological significance and potential mechanism of ACLY in cholangiocarcinoma.
    2. Human umbilical cord mesenchymal stem cell-derived exosomal miR-214-3p regulates the progression of gallbladder cancer by regulating ACLY/GLUT1.
      Title: Human umbilical cord mesenchymal stem cell-derived exosomal miR-214-3p regulates the progression of gallbladder cancer by regulating ACLY/GLUT1.
    3. Enhanced lipid biosynthesis in oral squamous cell carcinoma cancer-associated fibroblasts contributes to tumor progression: Role of IL8/AKT/p-ACLY axis.
      Title: Enhanced lipid biosynthesis in oral squamous cell carcinoma cancer-associated fibroblasts contributes to tumor progression: Role of IL8/AKT/p-ACLY axis.
    4. CILP2 promotes hypertrophic scar through Snail acetylation by interaction with ACLY.
      Title: CILP2 promotes hypertrophic scar through Snail acetylation by interaction with ACLY.
    5. ATP citrate lyase (ACLY)-dependent immunometabolism in mucosal T cells drives experimental colitis in vivo.
      Title: ATP citrate lyase (ACLY)-dependent immunometabolism in mucosal T cells drives experimental colitis in vivo.
    6. Cutting Edge: STING Induces ACLY Activation and Metabolic Adaptations in Human Macrophages through TBK1.
      Title: Cutting Edge: STING Induces ACLY Activation and Metabolic Adaptations in Human Macrophages through TBK1.
    7. [Expression and Clinical Significance of ATP Citrate Lyase in Hepatocellular Carcinoma].
      Title: [Expression and Clinical Significance of ATP Citrate Lyase in Hepatocellular Carcinoma].
    8. BCAT2 promotes melanoma progression by activating lipogenesis via the epigenetic regulation of FASN and ACLY expressions.
      Title: BCAT2 promotes melanoma progression by activating lipogenesis via the epigenetic regulation of FASN and ACLY expressions.
    9. ACLY as a modulator of liver cell functions and its role in Metabolic Dysfunction-Associated Steatohepatitis.
      Title: ACLY as a modulator of liver cell functions and its role in Metabolic Dysfunction-Associated Steatohepatitis.
    10. ACLY-induced reprogramming of glycolytic metabolism plays an important role in the progression of breast cancer.
      Title: ACLY-induced reprogramming of glycolytic metabolism plays an important role in the progression of breast cancer.
    Submit: New GeneRIF Correction See all GeneRIFs (72)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Tandem affinity purification and mass spectrometry analysis identify ATP citrate lyase (ACLY), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Gag-Pol gag-pol Tandem affinity purification and mass spectrometry analysis identify ATP citrate lyase (ACLY), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Nef nef Tandem affinity purification and mass spectrometry analysis identify ATP citrate lyase (ACLY), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Pr55(Gag) gag Tandem affinity purification and mass spectrometry analysis identify ATP citrate lyase (ACLY), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ25350, FLJ44061

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables ATP citrate synthase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ATP citrate synthase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ATP citrate synthase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in acetyl-CoA biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in acetyl-CoA biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cholesterol biosynthetic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in citrate metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in coenzyme A metabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in fatty acid biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in fatty acid biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in lipid biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in oxaloacetate metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in azurophil granule lumen TAS
    Traceable Author Statement
    more info
    		  
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
    		  
    located_in ficolin-1-rich granule lumen TAS
    Traceable Author Statement
    more info
    		  
    located_in membrane HDA PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    ATP-citrate synthase
    Names
    ATP-citrate (pro-S-)-lyase
    citrate cleavage enzyme
    NP_001087.2
    NP_001290203.1
    NP_001290204.1
    NP_942127.1
    XP_005257452.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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.

    Genomic

    1. NG_047031.1 RefSeqGene

      Range
      16592..68625
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001096.3 → NP_001087.2  ATP-citrate synthase isoform 1

      See identical proteins and their annotated locations for NP_001087.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) has an alternate splice site, which results in translation initiation at a downstream AUG start codon, compared to variant 3. The resulting isoform (1) is shorter at the N-terminus, compared to isoform 3.
      Source sequence(s)
      AC125257, BC006195, BG037168
      Consensus CDS
      CCDS11412.1
      UniProtKB/Swiss-Prot
      B4DIM0, B4E3P0, P53396, Q13037, Q9BRL0
      UniProtKB/TrEMBL
      Q4LE36
      Related
      ENSP00000253792.2, ENST00000352035.7
      Conserved Domains (2) summary
      PLN02522
      Location:491 → 1094
      PLN02522; ATP citrate (pro-S)-lyase
      cl29684
      Location:1 → 419
      Citrate_bind; ATP citrate lyase citrate-binding

    2. NM_001303274.1 → NP_001290203.1  ATP-citrate synthase isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) encodes the longest isoform (3).
      Source sequence(s)
      AB210035, AK304802, DB072009
      UniProtKB/TrEMBL
      Q4LE36
      Conserved Domains (7) summary
      cd06100
      Location:910 → 1147
      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:55 → 473
      PLN02235; ATP citrate (pro-S)-lyase
      PLN02522
      Location:545 → 1148
      PLN02522; ATP citrate (pro-S)-lyase
      smart00881
      Location:546 → 655
      CoA_binding; CoA binding domain
      pfam16114
      Location:301 → 475
      Citrate_bind; ATP citrate lyase citrate-binding
      cl17255
      Location:60 → 261
      ATP-grasp_4; ATP-grasp domain
      cl22543
      Location:714 → 839
      Ligase_CoA; CoA-ligase

    3. NM_001303275.1 → NP_001290204.1  ATP-citrate synthase isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an in-frame coding exon, compared to variant 3. The resulting isoform (4) lacks an internal segment, compared to isoform 3.
      Source sequence(s)
      AB210035, AK295675, BC006195
      UniProtKB/TrEMBL
      Q4LE36
      Conserved Domains (7) summary
      cd06100
      Location:900 → 1137
      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:55 → 473
      PLN02235; ATP citrate (pro-S)-lyase
      PLN02522
      Location:535 → 1138
      PLN02522; ATP citrate (pro-S)-lyase
      smart00881
      Location:536 → 645
      CoA_binding; CoA binding domain
      pfam16114
      Location:301 → 475
      Citrate_bind; ATP citrate lyase citrate-binding
      cl17255
      Location:60 → 261
      ATP-grasp_4; ATP-grasp domain
      cl22543
      Location:704 → 829
      Ligase_CoA; CoA-ligase

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

      See identical proteins and their annotated locations for NP_942127.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has an alternate splice site, which results in translation initiation at a downstream AUG start codon, and lacks an in-frame coding exon, compared to variant 3. The resulting isoform (2) is shorter at the N-terminus and lacks an internal segment, compared to isoform 3.
      Source sequence(s)
      AC125257, BC006195, BG037168
      Consensus CDS
      CCDS11413.1
      UniProtKB/TrEMBL
      Q4LE36
      Related
      ENSP00000345398.1, ENST00000353196.5
      Conserved Domains (7) summary
      cd06100
      Location:846 → 1083
      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
      PLN02235; ATP citrate (pro-S)-lyase
      PLN02522
      Location:481 → 1084
      PLN02522; ATP citrate (pro-S)-lyase
      smart00881
      Location:482 → 591
      CoA_binding; CoA binding domain
      pfam16114
      Location:247 → 421
      Citrate_bind; ATP citrate lyase citrate-binding
      cl17255
      Location:6 → 207
      ATP-grasp_4; ATP-grasp domain
      cl22543
      Location:650 → 775
      Ligase_CoA; CoA-ligase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

      Range
      41866917..41930545 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005257395.2 → XP_005257452.1  ATP-citrate synthase isoform X1

      See identical proteins and their annotated locations for XP_005257452.1

      UniProtKB/Swiss-Prot
      B4DIM0, B4E3P0, P53396, Q13037, Q9BRL0
      UniProtKB/TrEMBL
      Q4LE36
      Conserved Domains (2) summary
      PLN02522
      Location:491 → 1094
      PLN02522; ATP citrate (pro-S)-lyase
      cl29684
      Location:1 → 419
      Citrate_bind; ATP citrate lyase citrate-binding

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      42723421..42775531 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P53396.3 GenPept UniProtKB/Swiss-Prot:P53396

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