Choline kinase alpha

Function

Plays a key role in phospholipid biosynthesis by catalyzing the phosphorylation of free choline to phosphocholine, the first step in phosphatidylcholine biosynthesis. Also phosphorylates ethanolamine, thereby contributing to phosphatidylethanolamine biosynthesis. Has higher activity with choline. May contribute to tumor cell growth.

Classification

Family (Pfam)

PF01633 Choline_kinase

InterPro

Kinase-like_dom_sf

Functional cluster

Mixed Regulatory & Membrane Proteins

Experimental structures · PDB · 26

• 2CKO X-ray 2.15A
• 2CKP X-ray 3.10A
• 2CKQ X-ray 2.40A
• 2I7Q X-ray 1.90A
• 3F2R X-ray 2.35A
• 3G15 X-ray 1.70A
• 3ZM9 X-ray 1.90A
• 4BR3 X-ray 2.20A
• 4CG8 X-ray 1.75A
• 4CG9 X-ray 1.83A
• 4CGA X-ray 1.74A
• 4DA5 X-ray 2.40A
• … and 14 more

A predicted model is available from AlphaFold.

Gene Ontology · 15

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005811 lipid droplet
• GO:0005524 ATP binding
• GO:0004103 choline kinase activity
• GO:0004305 ethanolamine kinase activity
• GO:0042803 protein homodimerization activity
• GO:0004713 protein tyrosine kinase activity
• GO:0006657 CDP-choline pathway
• GO:0042149 cellular response to glucose starvation
• GO:1905691 lipid droplet disassembly
• GO:0006629 lipid metabolic process
• GO:0006869 lipid transport
• GO:0006656 phosphatidylcholine biosynthetic process
• GO:0006646 phosphatidylethanolamine biosynthetic process

Disease associations

• neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures MONDO:0859282

Drugs targeting this protein · 1

• RSM-932A inhibitor

Related proteins · sequence + function similarity

• Choline kinase alpha 0.97
• Choline kinase alpha 0.95
• Choline/ethanolamine kinase 0.76
• Choline/ethanolamine kinase 0.68
• Choline/ethanolamine kinase 0.68
• Glutaminase kidney isoform, mitochondrial 0.63
• Glutaminase kidney isoform, mitochondrial 0.62
• Glutaminase kidney isoform, mitochondrial 0.62
• CAAX prenyl protease 2 0.61
• CAAX prenyl protease 2 0.60
• RNA N(6)-adenosine-methyltransferase METTL16 0.60
• FHF complex subunit HOOK-interacting protein 1B 0.60

Co-cited proteins · studied together in the literature

• Choline/ethanolamine kinase 2 shared papers
• Phosphatidylinositol 4-kinase alpha 1 shared papers
• Genome polyprotein 1 shared papers
• Perilipin-2 1 shared papers
• Perilipin-3 1 shared papers
• 5'-AMP-activated protein kinase catalytic subunit alpha-1 1 shared papers
• 5'-AMP-activated protein kinase catalytic subunit alpha-2 1 shared papers
• 5'-AMP-activated protein kinase catalytic subunit alpha-2 1 shared papers
• 5'-AMP-activated protein kinase catalytic subunit alpha-1 1 shared papers
• Histone acetyltransferase KAT5 1 shared papers

Literature · 10 cited papers

• Bi-allelic variants in CHKA cause a neurodevelopmental disorder with epilepsy and microcephaly. Brain · 2022
• Choline kinase alpha 2 acts as a protein kinase to promote lipolysis of lipid droplets. Mol. Cell · 2021
• Hepatitis C Virus Subverts Human Choline Kinase-alpha To Bridge Phosphatidylinositol-4-Kinase IIIalpha (PI4KIIIalpha) and NS5A and Upregulates PI4KIIIalpha Activation, Thereby Promoting the Translocation of the Ternary Complex to the Endoplasmic Reticulum for Viral Replication. J. Virol. · 2017
• Kinetic and mechanistic characterisation of Choline Kinase-alpha. Biochim. Biophys. Acta · 2013
• Crystal structures of human choline kinase isoforms in complex with hemicholinium-3: single amino acid near the active site influences inhibitor sensitivity. J. Biol. Chem. · 2010
• Differential role of human choline kinase alpha and beta enzymes in lipid metabolism: implications in cancer onset and treatment. PLoS ONE · 2009
• Elucidation of human choline kinase crystal structures in complex with the products ADP or phosphocholine. J. Mol. Biol. · 2006
• Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Cloning of a human choline kinase cDNA by complementation of the yeast cki mutation. FEBS Lett. · 1992