ACLY

Protein identityUniProt · HPA

UniProt accession

P53396

Gene

ACLY

Ensembl

ENSG00000131473

Chromosome

17

Canonical length

1101 aa

Protein class

Cancer-related genes, Citric acid cycle related proteins, Enzymes, FDA approved drug targets, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Primary cilium transition zone,Basal body,Cytosol,Principal piece

Quaternary structure

Homotetramer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1101 residues, UniProt reviewed canonical sequence.

>P53396|ACLY
     1  MSAKAISEQT GKELLYKFIC TTSAIQNRFK YARVTPDTDW ARLLQDHPWL LSQNLVVKPD
    61  QLIKRRGKLG LVGVNLTLDG VKSWLKPRLG QEATVGKATG FLKNFLIEPF VPHSQAEEFY
   121  VCIYATREGD YVLFHHEGGV DVGDVDAKAQ KLLVGVDEKL NPEDIKKHLL VHAPEDKKEI
   181  LASFISGLFN FYEDLYFTYL EINPLVVTKD GVYVLDLAAK VDATADYICK VKWGDIEFPP
   241  PFGREAYPEE AYIADLDAKS GASLKLTLLN PKGRIWTMVA GGGASVVYSD TICDLGGVNE
   301  LANYGEYSGA PSEQQTYDYA KTILSLMTRE KHPDGKILII GGSIANFTNV AATFKGIVRA
   361  IRDYQGPLKE HEVTIFVRRG GPNYQEGLRV MGEVGKTTGI PIHVFGTETH MTAIVGMALG
   421  HRPIPNQPPT AAHTANFLLN ASGSTSTPAP SRTASFSESR ADEVAPAKKA KPAMPQDSVP
   481  SPRSLQGKST TLFSRHTKAI VWGMQTRAVQ GMLDFDYVCS RDEPSVAAMV YPFTGDHKQK
   541  FYWGHKEILI PVFKNMADAM RKHPEVDVLI NFASLRSAYD STMETMNYAQ IRTIAIIAEG
   601  IPEALTRKLI KKADQKGVTI IGPATVGGIK PGCFKIGNTG GMLDNILASK LYRPGSVAYV
   661  SRSGGMSNEL NNIISRTTDG VYEGVAIGGD RYPGSTFMDH VLRYQDTPGV KMIVVLGEIG
   721  GTEEYKICRG IKEGRLTKPI VCWCIGTCAT MFSSEVQFGH AGACANQASE TAVAKNQALK
   781  EAGVFVPRSF DELGEIIQSV YEDLVANGVI VPAQEVPPPT VPMDYSWARE LGLIRKPASF
   841  MTSICDERGQ ELIYAGMPIT EVFKEEMGIG GVLGLLWFQK RLPKYSCQFI EMCLMVTADH
   901  GPAVSGAHNT IICARAGKDL VSSLTSGLLT IGDRFGGALD AAAKMFSKAF DSGIIPMEFV
   961  NKMKKEGKLI MGIGHRVKSI NNPDMRVQIL KDYVRQHFPA TPLLDYALEV EKITTSKKPN
  1021  LILNVDGLIG VAFVDMLRNC GSFTREEADE YIDIGALNGI FVLGRSMGFI GHYLDQKRLK
  1081  QGLYRHPWDD ISYVLPEHMS M

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ACLY can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

65 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.38

gnomAD pLI

0.08

gnomAD missense Z

3.28

DepMap mean gene effect

-0.4

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• acetyl-CoA biosynthetic process
• cholesterol biosynthetic process
• citrate metabolic process
• coenzyme A metabolic process
• fatty acid biosynthetic process
• lipid biosynthetic process
• negative regulation of ferroptosis
• oxaloacetate metabolic process

Molecular functions

• ATP binding
• metal ion binding
• ATP citrate synthase activity

Cellular components

• azurophil granule lumen
• ciliary basal body
• ciliary transition zone
• cytosol
• extracellular exosome
• extracellular region
• ficolin-1-rich granule lumen
• membrane
• nucleoplasm
• sperm principal piece

Protein domainsUniProt · Pfam · InterPro

• Citrate synthase
• CoA-binding
• ATP-citrate synthase/succinyl-CoA ligase, C-terminal domain
• Succinyl-CoA synthetase-like
• Citrate synthase-like, small alpha subdomain
• ATP-citrate lyase/succinyl-CoA ligase, active site
• Succinyl-CoA synthetase, beta subunit, conserved site
• ATP-citrate lyase/succinyl-CoA ligase, conserved site
• NAD(P)-binding domain superfamily
• Citrate synthase superfamily
• Citrate synthase, C-terminal domain
• CoA-ligase
• CoA binding domain
• ATP-citrate synthase
• ATP-citrate synthase, citrate-binding domain
• ATP-citrate synthase, ATP-grasp domain
• ATP citrate lyase citrate-binding
• ATP-citrate synthase ATP-grasp domain

KeywordsUniProt

• Acetylation
• ATP-binding
• Cytoplasm
• Isopeptide bond
• Lipid biosynthesis
• Lipid metabolism
• Magnesium
• Metal-binding
• Nucleotide-binding
• Phosphoprotein
• Transferase
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of ACLY in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MORC2
• KLHL25