ATP-citrate synthase

Function

Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate in multiple biochemical reactions in protein, carbohydrate and lipid metabolism.

Classification

Family (Pfam)

PF16114 Citrate_bind, PF00285 Citrate_synt, PF24948 Citrate_synth_N, PF02629 CoA_binding, PF00549 Ligase_CoA

InterPro

ATP-citrate_synthase, Cit_synth/succinyl-CoA_lig_AS, Citrate-bd, Citrate_synth-like_sm_a-sub, Citrate_synth_N, Citrate_synthase, Citrate_synthase_sf, Citrt_syn/SCS-alpha_CS, CoA-bd, NAD(P)-bd_dom_sf, Succ-CoA_synthase_bsu_CS, SUCC_ACL_C, Succinyl-CoA_synth-like

Functional cluster

Oxidoreductases, Catalases & Peroxidases

Experimental structures · PDB · 35

• 3MWD X-ray 2.10A
• 3MWE X-ray 2.20A
• 3PFF X-ray 2.30A
• 5TDE X-ray 1.70A
• 5TDF X-ray 1.80A
• 5TDM X-ray 2.10A
• 5TDZ X-ray 2.00A
• 5TE1 X-ray 2.25A
• 5TEQ X-ray 2.30A
• 5TES X-ray 2.40A
• 5TET X-ray 2.20A
• 6HXH X-ray 3.30A
• … and 23 more

A predicted model is available from AlphaFold.

Gene Ontology · 17

• GO:0035578 azurophil granule lumen
• GO:0005829 cytosol
• GO:0070062 extracellular exosome
• GO:0005576 extracellular region
• GO:1904813 ficolin-1-rich granule lumen
• GO:0016020 membrane
• GO:0005524 ATP binding
• GO:0003878 ATP citrate synthase activity
• GO:0046872 metal ion binding
• GO:0006085 acetyl-CoA biosynthetic process
• GO:0006695 cholesterol biosynthetic process
• GO:0006101 citrate metabolic process
• GO:0015936 coenzyme A metabolic process
• GO:0006633 fatty acid biosynthetic process
• GO:0008610 lipid biosynthetic process
• GO:0110076 negative regulation of ferroptosis
• GO:0006107 oxaloacetate metabolic process

Drugs targeting this protein · 1

• BEMPEDOIC ACID inhibitor

Related proteins · sequence + function similarity

• ATP-citrate synthase 1.00
• ATP-citrate synthase 1.00
• ATP-citrate synthase 0.99
• ATP-citrate synthase 0.99
• Probable ATP-citrate synthase 0.93
• Probable ATP-citrate synthase subunit 1 0.79
• ATP-citrate synthase subunit 1 0.79
• ATP-citrate synthase beta chain protein 1 0.76
• Probable ATP-citrate synthase subunit 2 0.75
• ATP-citrate synthase beta chain protein 2 0.75
• Probable ATP-citrate synthase subunit 1 0.74
• ATP-citrate synthase beta chain protein 1 0.73

Co-cited proteins · studied together in the literature

• ATP-citrate synthase 2 shared papers
• Kelch-like protein 25 2 shared papers
• Tricarboxylate transport protein, mitochondrial 1 shared papers
• Ferroptosis suppressor protein 1 1 shared papers
• Kelch-like protein 25 1 shared papers
• Peptidyl-prolyl cis-trans isomerase F, mitochondrial 1 shared papers
• ATP-citrate synthase 2 shared papers
• Protein phosphatase Mn(2+)-dependent 1K 1 shared papers
• Branched-chain alpha-ketoacid dehydrogenase kinase 1 shared papers
• NAD-dependent protein deacetylase sirtuin-3, mitochondrial 1 shared papers
• 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial 1 shared papers
• E3 ubiquitin-protein ligase UBR4 1 shared papers

Literature · 30 cited papers

• SLC25A1 and ACLY maintain cytosolic acetyl-CoA and regulate ferroptosis susceptibility via FSP1 acetylation. EMBO J. · 2025
• SIRT3 differentially regulates lysine benzoylation from SIRT2 in mammalian cells. IScience · 2024
• ACLY ubiquitination by CUL3-KLHL25 induces the reprogramming of fatty acid metabolism to facilitate iTreg differentiation. Elife · 2021
• The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase. Cell Metab. · 2018
• Cullin3-KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit lipid synthesis and tumor progression. Genes Dev. · 2016
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol. Cell · 2013
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• ADP-Mg2+ bound to the ATP-grasp domain of ATP-citrate lyase. Acta Crystallogr. F · 2011
• System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• Identification of the citrate-binding site of human ATP-citrate lyase using X-ray crystallography. J. Biol. Chem. · 2010
• … and 18 more in the literature graph