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ACLY ATP citrate lyase [ Homo sapiens (human) ]

Gene ID: 47, updated on 7-Apr-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
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Genomic context

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Location:
17q21.2
Exon count:
30
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (41866917..41930545, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (42723421..42775531, complement)
105.20220307 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
  • 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. ACLY-induced reprogramming of glycolytic metabolism plays an important role in the progression of breast cancer. Lu Y, et al. Acta Biochim Biophys Sin (Shanghai), 2023 Apr 28. PMID 37140234, Free PMC Article
  2. 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
  3. Targeting ACLY efficiently inhibits SARS-CoV-2 replication. Yuen TT, et al. Int J Biol Sci, 2022. PMID 35874959, Free PMC Article
  4. Deletion of ACLY Disrupts Histone Acetylation and IL-10 Secretion in Trophoblasts, Which Inhibits M2 Polarization of Macrophages: A Possible Role in Recurrent Spontaneous Abortion. Chen X, et al. Oxid Med Cell Longev, 2022. PMID 35602106, 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 (235) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. [Expression and Clinical Significance of ATP Citrate Lyase in Hepatocellular Carcinoma].
    Title: [Expression and Clinical Significance of ATP Citrate Lyase in Hepatocellular Carcinoma].
  4. 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.
  5. 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.
  6. 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.
  7. Activation of ACLY by SEC63 deploys metabolic reprogramming to facilitate hepatocellular carcinoma metastasis upon endoplasmic reticulum stress.
    Title: Activation of ACLY by SEC63 deploys metabolic reprogramming to facilitate hepatocellular carcinoma metastasis upon endoplasmic reticulum stress.
  8. Allosteric role of the citrate synthase homology domain of ATP citrate lyase.
    Title: Allosteric role of the citrate synthase homology domain of ATP citrate lyase.
  9. Selective autophagic degradation of ACLY (ATP citrate lyase) maintains citrate homeostasis and promotes oocyte maturation.
    Title: Selective autophagic degradation of ACLY (ATP citrate lyase) maintains citrate homeostasis and promotes oocyte maturation.
  10. ARHGEF3 regulates the stability of ACLY to promote the proliferation of lung cancer.
    Title: ARHGEF3 regulates the stability of ACLY to promote the proliferation of lung cancer.
Submit: New GeneRIF Correction See all GeneRIFs (68)

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 
involved_in tricarboxylic acid cycle IEA
Inferred from Electronic Annotation
more info
  
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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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_2023_10

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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