ExplorEnz: EC 2.7.10.4

Your query returned 1 entry. Printable version

2.7.10.4

Accepted name:

[Src-family] C-terminal protein kinase

Reaction:

ATP + [a protein]-(L-tyrosine) = ADP + [a protein]-(L-tyrosine)-phosphate. The optimal peptide substrate contains the sequence (relative to the phosphorylated tyrosine): Glu-Glu-Asp/Glu-Ile-Tyr-Phe-Phe-Phe-Phe [1]. Physiological substrates are C-terminal tail of Src-family protein kinases [1].

Other name(s):

C-terminal Src kinase; CSK (human gene name); Tyrosine-protein kinase CSK

Systematic name:

ATP:[protein]-L-tyrosine O-phosphotransferase (Src-specific)

Comments:

Requires Mg²⁺. Specifically phosphorylates a C-terminal tyrosine in Src family of non-receptor protein kinases (Tyr 527 chicken c-Src numbering, Tyr 530 human c-Src numbering) [1,2]. The enzyme engages in particular binding mode with its substrate proteins to present the C-terminal sequence in the active site. A shortened activation loop disrupts the conventional substrate peptide docking observed in most tyrosine kinases [1]. It can be activated by docking of the SH2 and linking regions to the kinase domain [3]. Removal of the SH3/SH2 domain decreases kinase activity by 100-fold [4]. Phosphorylation of Ser³⁶⁴ by cAMP-dependent protein kinase (EC 2.7.11.1) activates the enzyme in the presence of the Csk SH3 domain [5]. The SH3 domain lacks a tyrosine for autophosphorylation in its activation loop and requires a specific binding mode to its substrate proteins for catalysis [6].

Links to other databases:

BRENDA, EXPASY, KEGG, MetaCyc

References:

1.	Sondhi, D., Xu, W., Songyang, Z., Eck, M.J. and Cole, P.A. Peptide and protein phosphorylation by protein tyrosine kinase Csk: insights into specificity and mechanism. Biochemistry 37 (1998) 165–172. [DOI] [PMID: 9425036]
2.	Nada, S., Okada, M., MacAuley, A., Cooper, J.A. and Nakagawa, H. Cloning of a complementary DNA for a protein-tyrosine kinase that specifically phosphorylates a negative regulatory site of p60c-src. Nature 351 (1991) 69–72. [DOI] [PMID: 1709258]
3.	Ogawa, A., Takayama, Y., Sakai, H., Chong, K.T., Takeuchi, S., Nakagawa, A., Nada, S., Okada, M. and Tsukihara, T. Structure of the carboxyl-terminal Src kinase, Csk. J. Biol. Chem. 277 (2002) 14351–14354. [DOI] [PMID: 11884384]
4.	Sondhi, D. and Cole, P.A. Domain interactions in protein tyrosine kinase Csk. Biochemistry 38 (1999) 11147–11155. [DOI] [PMID: 10460171]
5.	Yaqub, S., Abrahamsen, H., Zimmerman, B., Kholod, N., Torgersen, K.M., Mustelin, T., Herberg, F.W., Tasken, K. and Vang, T. Activation of C-terminal Src kinase (Csk) by phosphorylation at serine-364 depends on the Csk-Src homology 3 domain. Biochem. J. 372 (2003) 271–278. [DOI] [PMID: 12600271]
6.	Levinson, N.M., Seeliger, M.A., Cole, P.A. and Kuriyan, J. Structural basis for the recognition of c-Src by its inactivator Csk. Cell 134 (2008) 124–134. [DOI] [PMID: 18614016]

[EC 2.7.10.4 created 2025]