Acly ATP citrate lyase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Aclyprovided by MGI
Official Full Name: ATP citrate lyaseprovided by MGI
Primary source: MGI:MGI:103251
See related: Ensembl:ENSMUSG00000020917 AllianceGenome:MGI:103251
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: A730098H14Rik
Summary: Enables ATP citrate synthase activity. Predicted to be involved in acetyl-CoA biosynthetic process and carboxylic acid metabolic process. Predicted to act upstream of or within lipid metabolic process. Located in mitochondrion. Is expressed in several structures, including alimentary system; genitourinary system; nervous system; respiratory system; and sensory organ. Orthologous to human ACLY (ATP citrate lyase). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in subcutaneous fat pad adult (RPKM 333.0), mammary gland adult (RPKM 298.7) and 24 other tissues See more
Orthologs: human all
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Genomic context

Location:: 11 D; 11 63.47 cM

Exon count:: 30

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	11	NC_000077.7 (100367178..100418826, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	11	NC_000077.6 (100476352..100528000, complement)

Chromosome 11 - NC_000077.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Cytoplasmic Endonuclease G promotes nonalcoholic fatty liver disease via mTORC2-AKT-ACLY and endoplasmic reticulum stress.
Title: Cytoplasmic Endonuclease G promotes nonalcoholic fatty liver disease via mTORC2-AKT-ACLY and endoplasmic reticulum stress.
BCKDHA contributes to melanoma progression by promoting the expressions of lipogenic enzymes FASN and ACLY.
Title: BCKDHA contributes to melanoma progression by promoting the expressions of lipogenic enzymes FASN and ACLY.
PP2Cdelta Controls the Differentiation and Function of Dendritic Cells Through Regulating the NSD2/mTORC2/ACLY Pathway.
Title: PP2Cδ Controls the Differentiation and Function of Dendritic Cells Through Regulating the NSD2/mTORC2/ACLY Pathway.
Myeloid ATP Citrate Lyase Regulates Macrophage Inflammatory Responses In Vitro Without Altering Inflammatory Disease Outcomes.
Title: Myeloid ATP Citrate Lyase Regulates Macrophage Inflammatory Responses In Vitro Without Altering Inflammatory Disease Outcomes.
FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes.
Title: FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes.
Hrd1-mediated ACLY ubiquitination alleviate NAFLD in db/db mice.
Title: Hrd1-mediated ACLY ubiquitination alleviate NAFLD in db/db mice.
ACLY-3K acetylation also promotes ACLY protein stability in AML12 cells, a mouse hepatocyte cell line, and found that the deacetylase sirtuin 2 (SIRT2) deacetylates ACLY-3K and destabilizes ACLY in these cells. Mimicking ACLY-3K acetylation by replacing the three lysines with three glutamines (ACLY-3KQ variant) promoted lipid accumulation both in high glucose-treated AML12 cells and in the livers of high-fat diet.
Title: Enhanced acetylation of ATP-citrate lyase promotes the progression of nonalcoholic fatty liver disease.
Study revealed increased kidney expression of RIPK3 in mouse models of progressive kidney fibrosis and in human chronic kidney disease kidney and demonstrate a pathway by which RIPK3 promotes fibrogenesis through the AKT-dependent activation of ATP citrate lyase independently of mixed-lineage kinase domain-like protein-dependent necroptosis.
Title: RIPK3 promotes kidney fibrosis via AKT-dependent ATP citrate lyase.
ACL regulates the net amount of acetyl groups available, leading to alterations in acetylation of H3(K9/14) and H3(K27) at the MYOD locus, thus increasing MYOD expression.
Title: ATP Citrate Lyase Regulates Myofiber Differentiation and Increases Regeneration by Altering Histone Acetylation.
We propose that D2-HG promotes cardiac dysfunction by impairing alpha-ketoglutarate dehydrogenase and induces histone modifications in an ACL-dependent manner
Title: Oncometabolite d-2-hydroxyglutarate impairs α-ketoglutarate dehydrogenase and contractile function in rodent heart.

Submit: New GeneRIF Correction See all GeneRIFs (21)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Transgenic (1)
Gene trapped (2) 1 citation
Targeted (4) 1 citation
Endonuclease-mediated (5)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Acly (e-PCR), detects polymorphism
- UniSTS:506701

AW538652 (e-PCR)
- UniSTS:180319

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
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	ISO Inferred from Sequence Orthology more info
enables acyltransferase activity, acyl groups converted into alkyl on transfer	IEA Inferred from Electronic Annotation more info
enables catalytic activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transferase activity	IEA Inferred from Electronic Annotation more info

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	ISO Inferred from Sequence Orthology more info
involved_in acetyl-CoA metabolic process	ISO Inferred from Sequence Orthology more info
involved_in citrate metabolic process	ISO Inferred from Sequence Orthology more info
involved_in fatty acid biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in fatty acid biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in lipid biosynthetic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within lipid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in oxaloacetate metabolic process	ISO Inferred from Sequence Orthology more info
involved_in tricarboxylic acid cycle	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in mitochondrion	HDA more info	PubMed
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: ATP-citrate synthase

Names: ATP-citrate (pro-S-)-lyase; citrate cleavage enzyme

NP_001186225.1

EC 2.3.3.8

NP_598798.1

EC 2.3.3.8

XP_036012093.1

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.

mRNA and Protein(s)

NM_001199296.1 → NP_001186225.1 ATP-citrate synthase isoform 1

See identical proteins and their annotated locations for NP_001186225.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and it encodes the longer protein (isoform 1).

Source sequence(s)

AK132755, BE623317, BX842667

Consensus CDS

CCDS56807.1

UniProtKB/TrEMBL

Q3TED3, Q3V117

Related

ENSMUSP00000103012.2, ENSMUST00000107389.8

Conserved Domains (2) summary

cl25712
Location:1 → 419

SucC; Succinyl-CoA synthetase, beta subunit [Energy production and conversion]

cl26126
Location:489 → 1094

Ligase_CoA; CoA-ligase
NM_134037.3 → NP_598798.1 ATP-citrate synthase isoform 2

See identical proteins and their annotated locations for NP_598798.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an alternate, in-frame, exon in the middle of the coding region, compared to variant 1. The resulting protein (isoform 2) is shorter when it is compared to isoform 1.

Source sequence(s)

BC056378, BE623317, BX842667

Consensus CDS

CCDS25425.1

UniProtKB/Swiss-Prot

Q91V92

UniProtKB/TrEMBL

Q3TED3

Related

ENSMUSP00000007131.10, ENSMUST00000007131.16

Conserved Domains (2) summary

cl25712
Location:1 → 419

SucC; Succinyl-CoA synthetase, beta subunit [Energy production and conversion]

cl26126
Location:479 → 1084

Ligase_CoA; CoA-ligase

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000077.7 Reference GRCm39 C57BL/6J

Range

100367178..100418826 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036156200.1 → XP_036012093.1 ATP-citrate synthase isoform X1

Conserved Domains (1) summary

PLN02522
Location:1 → 591

PLN02522; ATP citrate (pro-S)-lyase