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    ACLY ATP citrate lyase [ Homo sapiens (human) ]

    Gene ID: 47, updated on 15-Jun-2019

    Summary

    Official Symbol
    ACLYprovided by HGNC
    Official Full Name
    ATP citrate lyaseprovided by HGNC
    Primary source
    HGNC:HGNC:115
    See related
    Ensembl:ENSG00000131473 MIM:108728
    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

    Genomic context

    See ACLY in Genome Data Viewer
    Location:
    17q21.2
    Exon count:
    30
    Annotation release Status Assembly Chr Location
    109 current GRCh38.p12 (GCF_000001405.38) 17 NC_000017.11 (41866916..41930542, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (40023169..40086795, complement)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene 5'-nucleotidase, cytosolic IIIB Neighboring gene kelch like family member 10 Neighboring gene kelch like family member 11 Neighboring gene tetratricopeptide repeat domain 25 Neighboring gene 2',3'-cyclic nucleotide 3' phosphodiesterase Neighboring gene DnaJ heat shock protein family (Hsp40) member C7

    Genomic regions, transcripts, and products

    Expression

    • 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

    Related articles in PubMed

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    HIV-1 interactions

    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 BioSystems

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Clone Names

    • FLJ25350, FLJ44061

    Gene Ontology Provided by GOA

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

    General protein information

    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
    XP_016880177.1

    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.

    Genomic

    1. NG_047031.1 RefSeqGene

      Range
      16521..68626
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001096.3NP_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
      P53396
      UniProtKB/TrEMBL
      A0A024R1T9
      Related
      ENSP00000253792.2, ENST00000352035.7
      Conserved Domains (2) summary
      cl25712
      Location:1419
      SucC; Succinyl-CoA synthetase, beta subunit [Energy production and conversion]
      cl26126
      Location:4911094
      Ligase_CoA; CoA-ligase
    2. NM_001303274.1NP_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/Swiss-Prot
      P53396
      UniProtKB/TrEMBL
      Q4LE36
      Conserved Domains (7) summary
      cd06100
      Location:9101147
      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:55473
      PLN02235; ATP citrate (pro-S)-lyase
      PLN02522
      Location:5451148
      PLN02522; ATP citrate (pro-S)-lyase
      smart00881
      Location:546655
      CoA_binding; CoA binding domain
      pfam16114
      Location:301475
      Citrate_bind; ATP citrate lyase citrate-binding
      cl17255
      Location:60261
      ATP-grasp_4; ATP-grasp domain
      cl22543
      Location:714839
      Ligase_CoA; CoA-ligase
    3. NM_001303275.1NP_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/Swiss-Prot
      P53396
      UniProtKB/TrEMBL
      Q4LE36
      Conserved Domains (7) summary
      cd06100
      Location:9001137
      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:55473
      PLN02235; ATP citrate (pro-S)-lyase
      PLN02522
      Location:5351138
      PLN02522; ATP citrate (pro-S)-lyase
      smart00881
      Location:536645
      CoA_binding; CoA binding domain
      pfam16114
      Location:301475
      Citrate_bind; ATP citrate lyase citrate-binding
      cl17255
      Location:60261
      ATP-grasp_4; ATP-grasp domain
      cl22543
      Location:704829
      Ligase_CoA; CoA-ligase
    4. NM_198830.1NP_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)
      BC006195, BG037168
      Consensus CDS
      CCDS11413.1
      UniProtKB/Swiss-Prot
      P53396
      UniProtKB/TrEMBL
      A0A024R1Y2
      Related
      ENSP00000345398.1, ENST00000353196.5
      Conserved Domains (7) summary
      cd06100
      Location:8461083
      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:1419
      PLN02235; ATP citrate (pro-S)-lyase
      PLN02522
      Location:4811084
      PLN02522; ATP citrate (pro-S)-lyase
      smart00881
      Location:482591
      CoA_binding; CoA binding domain
      pfam16114
      Location:247421
      Citrate_bind; ATP citrate lyase citrate-binding
      cl17255
      Location:6207
      ATP-grasp_4; ATP-grasp domain
      cl22543
      Location:650775
      Ligase_CoA; CoA-ligase

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p13 Primary Assembly

      Range
      41866916..41930542 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017024688.1XP_016880177.1  ATP-citrate synthase isoform X2

      UniProtKB/TrEMBL
      A0A024R1Y2
      Conserved Domains (7) summary
      cd06100
      Location:8461083
      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:1419
      PLN02235; ATP citrate (pro-S)-lyase
      PLN02522
      Location:4811084
      PLN02522; ATP citrate (pro-S)-lyase
      smart00881
      Location:482591
      CoA_binding; CoA binding domain
      pfam16114
      Location:247421
      Citrate_bind; ATP citrate lyase citrate-binding
      cl17255
      Location:6207
      ATP-grasp_4; ATP-grasp domain
      cl22543
      Location:650775
      Ligase_CoA; CoA-ligase
    2. XM_005257395.1XP_005257452.1  ATP-citrate synthase isoform X1

      See identical proteins and their annotated locations for XP_005257452.1

      UniProtKB/Swiss-Prot
      P53396
      UniProtKB/TrEMBL
      A0A024R1T9
      Conserved Domains (2) summary
      cl25712
      Location:1419
      SucC; Succinyl-CoA synthetase, beta subunit [Energy production and conversion]
      cl26126
      Location:4911094
      Ligase_CoA; CoA-ligase
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