CHKA explained

Choline kinase alpha is an enzyme that in humans is encoded by the CHKA gene.^{[1] [2] [3]}

The major pathway for the biosynthesis of phosphatidylcholine occurs via the CDP-choline pathway. The protein encoded by this gene is the initial enzyme in the sequence and may play a regulatory role. The encoded protein also catalyzes the phosphorylation of ethanolamine. Two transcript variants encoding different isoforms have been found for this gene.^[3]

In melanocytic cells CHKA gene expression may be regulated by MITF.^[4]

Clinical significance

Mutations of the CHKA gene cause a neurodevelopmental disorder with epilepsy and microcephaly.^[5]

Further reading

• Spanner S, Ansell GB . Choline kinase and ethanolamine kinase activity in the cytosol of nerve endings from rat forebrain . Biochem. J. . 178 . 3 . 753–60 . 1979 . 36885 . 10.1042/bj1780753. 1186576 .
• Book: Spanner S, Ansell GB . Choline and Ethanolamine Kinase Activity in the Cytoplasm of Nerve Endings from Rat Forebrain . Enzymes of Lipid Metabolism . Advances in Experimental Medicine and Biology . 101 . 237–45 . 1978 . 208357 . 10.1007/978-1-4615-9071-2_23. 978-1-4615-9073-6 .
• Kaplan O, Cohen JS . Lymphocyte activation-31P magnetic resonance studies of energy metabolism and phospholipid pathways . ImmunoMethods . 4 . 2 . 139–47 . 1994 . 8069533 . 10.1006/immu.1994.1015 .
• Price DJ, Rivnay B, Fu Y . Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes . J. Biol. Chem. . 272 . 9 . 5915–20 . 1997 . 9038210 . 10.1074/jbc.272.9.5915 . etal. free .
• Ross BM, Moszczynska A, Blusztajn JK . Phospholipid biosynthetic enzymes in human brain . Lipids . 32 . 4 . 351–8 . 1997 . 9113621 . 10.1007/s11745-997-0044-x . 4003647 . etal.
• Nakagami K, Uchida T, Ohwada S . Increased choline kinase activity and elevated phosphocholine levels in human colon cancer . Jpn. J. Cancer Res. . 90 . 4 . 419–24 . 1999 . 10363580 . 10.1111/j.1349-7006.1999.tb00764.x. etal. 5926083 .
• Ramírez de Molina A, Penalva V, Lucas L, Lacal JC . Regulation of choline kinase activity by Ras proteins involves Ral-GDS and PI3K . Oncogene . 21 . 6 . 937–46 . 2002 . 11840339 . 10.1038/sj.onc.1205144 . free .
• Dubois T, Howell S, Zemlickova E, Aitken A . Identification of casein kinase Ialpha interacting protein partners . FEBS Lett. . 517 . 1–3 . 167–71 . 2002 . 12062430 . 10.1016/S0014-5793(02)02614-5 . 84792445 . free . 2002FEBSL.517..167D .
• Ramírez de Molina A, Gutiérrez R, Ramos MA . Increased choline kinase activity in human breast carcinomas: clinical evidence for a potential novel antitumor strategy . Oncogene . 21 . 27 . 4317–22 . 2002 . 12082619 . 10.1038/sj.onc.1205556 . etal. free .
• Ramírez de Molina A, Rodríguez-González A, Gutiérrez R . Overexpression of choline kinase is a frequent feature in human tumor-derived cell lines and in lung, prostate, and colorectal human cancers . Biochem. Biophys. Res. Commun. . 296 . 3 . 580–3 . 2002 . 12176020 . 10.1016/S0006-291X(02)00920-8 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Gallego-Ortega D, Ramirez De Molina A, Gutierrez R . Generation and characterization of monoclonal antibodies against choline kinase alpha and their potential use as diagnostic tools in cancer . Int. J. Oncol. . 29 . 2 . 335–40 . 2006 . 16820874 . 10.3892/ijo.29.2.335. etal. free .
• Enaw JO, Zhu H, Yang W . CHKA and PCYT1A gene polymorphisms, choline intake and spina bifida risk in a California population . BMC Medicine . 4. 36 . 2007 . 17184542 . 10.1186/1741-7015-4-36 . 1770928 . etal . free .

Notes and References

1. Hosaka K, Tanaka S, Nikawa J, Yamashita S . Cloning of a human choline kinase cDNA by complementation of the yeast cki mutation . FEBS Lett . 304 . 2–3 . 229–32 . Aug 1992 . 1618328 . 10.1016/0014-5793(92)80625-Q . 25275208 . free . 1992FEBSL.304..229H .
2. Aoyama C, Liao H, Ishidate K . Structure and function of choline kinase isoforms in mammalian cells . Prog Lipid Res . 43 . 3 . 266–81 . Mar 2004 . 15003397 . 10.1016/j.plipres.2003.12.001 .
3. Web site: Entrez Gene: CHKA choline kinase alpha.
4. Hoek KS, Schlegel NC, Eichhoff OM . Novel MITF targets identified using a two-step DNA microarray strategy . Pigment Cell Melanoma Res. . 21 . 6 . 665–76 . 2008 . 19067971 . 10.1111/j.1755-148X.2008.00505.x . 24698373 . etal. free .
5. Klöckner C, Fernández-Murray JP, Tavasoli M, Sticht H, Stoltenburg-Didinger G, Scholle LM, Bakhtiari S, Kruer MC, Darvish H, Firouzabadi SG, Pagnozzi A, Shukla A, Girisha KM, Narayanan DL, Kaur P, Maroofian R, Zaki MS, Noureldeen MM, Merkenschlager A, Gburek-Augustat J, Cali E, Banu S, Nahar K, Efthymiou S, Houlden H, Jamra RA, Williams J, McMaster CR, Platzer K . Bi-allelic variants in CHKA cause a neurodevelopmental disorder with epilepsy and microcephaly . Brain: A Journal of Neurology . 145 . 6 . 1916–1923 . June 2022 . 35202461 . 10.1093/brain/awac074 . 9630884 .