Reaction: (1) ATP + [protein]-L-serine = ADP + [protein]-O-phospho-L-serine
(2) ATP + [protein]-L-threonine = ADP + [protein]-O-phospho-L-threonine
Other name(s): CRIK; CIT; SGK21; Citron; Citron-K; Sticky/Citron Kinase; Citron Rho-Interacting Kinase
Comments: Requires Mg2+. Peptide array data show a preference for phosphorylation of Thr over Ser and a preference for basic residues in the -5 to -1 positions [1]. CRIK is an animal-specific protein kinase that phosphorylates myosin light chain (cf. EC 2.7.11.18, myosin-light-chain kinase) and is involved in cytokinesis in both mammals and Drosophila. Human CRIK phosphorylates myosin light chain, MYL9/MRLC1 on T19/S20 [2] and GLI2 on S149 [3]. Drosophila CRIK (sticky) interacts with the kinesins Nebbish and Pavarotti, and human CRIK interacts with their orthologs, KIF14 and KIF23/MKLP1 to promote midbody formation during cytokinesis [4]. In Drosophila, CRIK/Sticky catalytic activity was required for this function. Human CRIK is mostly highly expressed in brain, and mutations that alter splicing or kinase activity lead to microcephaly [5, 6], as do knockouts in mouse and rat, and mutations in its interacting partner, the kinesin KIF14 [6].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Johnson, J.L., Yaron, T.M., Huntsman, E.M., Kerelsky, A., Song, J., Regev, A., Lin, T.Y., Liberatore, K., Cizin, D.M., Cohen, B.M., Vasan, N., Ma, Y., Krismer, K., Robles, J.T., van de Kooij, B., van Vlimmeren, A.E., Andree-Busch, N., Kaufer, N.F., Dorovkov, M.V., Ryazanov, A.G., Takagi, Y., Kastenhuber, E.R., Goncalves, M.D., Hopkins, B.D., Elemento, O., Taatjes, D.J., Maucuer, A., Yamashita, A., Degterev, A., Uduman, M., Lu, J., Landry, S.D., Zhang, B., Cossentino, I., Linding, R., Blenis, J., Hornbeck, P.V., Turk, B.E., Yaffe, M.B. and Cantley, L.C. An atlas of substrate specificities for the human serine/threonine kinome. Nature 613 (2023) 759-766. [PMID: 36631611]
2. Yamashiro, S., Totsukawa, G., Yamakita, Y., Sasaki, Y., Madaule, P., Ishizaki, T., Narumiya, S. and Matsumura, F. Citron kinase, a Rho-dependent kinase, induces di-phosphorylation of regulatory light chain of myosin II. Mol. Biol. Cell 14 (2003) 1745-1756. [PMID: 12802051]
3. Xing, Z., Lin, A., Li, C., Liang, K., Wang, S., Liu, Y., Park, P.K., Qin, L., Wei, Y., Hawke, D.H., Hung, M.C., Lin, C. and Yang, L. lncRNA directs cooperative epigenetic regulation downstream of chemokine signals. Cell 159 (2014) 1110-1125. [PMID: 25416949]
4. Bassi, Z.I., Audusseau, M., Riparbelli, M.G., Callaini, G. and D'Avino, P.P. Citron kinase controls a molecular network required for midbody formation in cytokinesis. Proc. Natl. Acad. Sci. USA 110 (2013) 9782-9787. [PMID: 23716662]
5. Shaheen, R., Hashem, A., Abdel-Salam, G.M., Al-Fadhli, F., Ewida, N. and Alkuraya, F.S. Mutations in CIT, encoding citron rho-interacting serine/threonine kinase, cause severe primary microcephaly in humans. Hum Genet 135 (2016) 1191-1197. [PMID: 27503289]
6. Li, H., Bielas, S.L., Zaki, M.S., Ismail, S., Farfara, D., Um, K., Rosti, R.O., Scott, E.C., Tu, S., Chi, N.C., Gabriel, S., Erson-Omay, E.Z., Ercan-Sencicek, A.G., Yasuno, K., Caglayan, A.O., Kaymakcalan, H., Ekici, B., Bilguvar, K., Gunel, M. and Gleeson, J.G. Biallelic mutations in citron kinase link mitotic cytokinesis to human primary microcephaly. Am. J. Hum. Genet. 99 (2016) 501-510. [PMID: 27453578]