ACLY ATP citrate lyase [Homo sapiens (human)] - Gene

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; 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

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_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
[Expression and Clinical Significance of ATP Citrate Lyase in Hepatocellular Carcinoma].
Title: [Expression and Clinical Significance of ATP Citrate Lyase in Hepatocellular Carcinoma].
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.
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.
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.
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.
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.
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.
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)

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

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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

GDB:392280 (e-PCR)
- UniSTS:157185

D17S1205 (e-PCR)
- UniSTS:69157

D17S2155 (e-PCR)
- UniSTS:5950

WI-20027 (e-PCR)
- UniSTS:69195

SHGC-132072 (e-PCR)
- UniSTS:170629

D17S1209 (e-PCR)
- UniSTS:52644

WI-19716 (e-PCR)
- UniSTS:30916

SHGC-11986 (e-PCR)
- UniSTS:3576

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 more info	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 more info	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

EC 2.3.3.8

NP_001290203.1

EC 2.3.3.8

NP_001290204.1

EC 2.3.3.8

NP_942127.1

EC 2.3.3.8

XP_005257452.1

EC 2.3.3.8

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

NG_047031.1 RefSeqGene

Range

16592..68625

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

41866917..41930545 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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