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Gene Review

CDK5R1  -  cyclin-dependent kinase 5, regulatory...

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Disease relevance of CDK5R1

  • Three truncated forms of p35 including the one corresponding to the 25-kDa subunit of the kinase have been expressed in Escherichia coli and shown to activate a bacteria-expressed Cdk5 with equal efficacy [1].
  • Addition of supramitogenic doses of phytohemagglutinin (PHA) to short-term cultures of neoplastic or nonneoplastic lymphocytes infected with bovine leukemia virus increased the synthesis of the major core virion antigen (p25) by 5- to 10-fold [2].
  • A competitive radioimmunoassay was used to detect the major internal protein (p25) of bovine leukemia virus (BLV) in urine from infected cattle [3].
  • None of the sera from 15 M. paratuberculosis-free cows, 3 Mycobacterium bovis BCG-infected tuberculous cattle, or 3 cows artificially inoculated with multiple doses of viable M. paratuberculosis reacted with p35 [4].
  • The DNA fragment encoding the p35 gene hybridized only to DNA from Mycobacterium avium complex, but not to DNAs from other mycobacteria and nonmycobacterial organisms [4].

High impact information on CDK5R1


Chemical compound and disease context of CDK5R1


Biological context of CDK5R1

  • Tau protein kinase II (TPKII) is shown by immunoprecipitation to be a complex composed of two subunits, a catalytic subunit, cdk5, and regulatory subunit, p23 [11].
  • Chemical cross-linking of eIF-4F to cap-labeled mRNA, showed that phosphorylation increased the interaction of both the p25 and p220 subunits of eIF-4F with the 5' end of mRNA [12].
  • Its partial amino acid sequence was determined and found to be identical to that of a known brain-specific 25-kDa protein (p25) [13].
  • The present study describes a significant amino acid sequence homology between neuronal Cdk5 activator (nck5a) and an open reading frame of an unknown gene on the yeast S. cerevisiae chromosome III [14].
  • Late gestation Holstein cows with low titers of antibody to the p23 antigen of C. parvum were immunized three times with 300 microg affinity purified rC7 C. parvum recombinant protein (immune cows), or left nonimmunized (control cows) [15].

Anatomical context of CDK5R1

  • smg p25A/rab3A p25 is a member of the small GTP-binding protein superfamily which is implicated in intracellular vesicle transport. smg p25A has a cDNA-predicted C-terminal structure of Cys-Ala-Cys [16].
  • These results indicate that in bovine brain cytosol PA activates PKCalpha, which, in turn, phosphorylates p29, which may be identical with p25 [13].
  • Brain-specific p25 protein binds to tubulin and microtubules and induces aberrant microtubule assemblies at substoichiometric concentrations [17].
  • Identification and localization of gene expression of a low M(r) GTP-binding protein, ram p25 in pituitary gland [18].
  • In other parts of brain, no significant expression of ram-mRNA was detected, indicating that ram p25 may have an important role(s) in adenohypophysis [18].

Associations of CDK5R1 with chemical compounds

  • Activity for tyrosine and threonine phosphorylation of MAP kinase was present in two bands of approx. 48 and 46 kDa, which have sequence similarity to small GTP-binding protein p25 GDP dissociation inhibitor and protein kinases (PBS2, SPK1+, STE7, BYR1) respectively [19].
  • We absorbed a recombinant 23-kD sporozoite protein to polystyrene microspheres, and used flow cytometry to detect, titer, and determine the isotype of antibody to p23 that was shed in the feces of experimentally infected calves [20].
  • The zero-length crosslinking assay revealed that p35 formed a homodimer during Ca(2+)-dependent liposome aggregation [21].

Analytical, diagnostic and therapeutic context of CDK5R1

  • By sequence analysis of p23 cDNA, p23 was found to occupy a region from the 99th amino acid residue to the C-terminus of a novel protein with a molecular weight of 34,000 Da, suggesting that this 34 kDa protein is a precursor of p23 (pre-p23) [11].
  • 2. Its molecular weight, estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), was 23,000 (p23), and it gave a sedimentation value of 2.3s [5].
  • When bovine brain extract was analyzed by gel filtration PP1.I-2 and neuronal Cdc2-like protein kinase (NCLK), a heterodimer of Cdk5 and the regulatory p25 subunit, co-eluted as a approximately 450-kDa size species [6].
  • Circular dichroism data have revealed that, on one hand, the alpha-helix content of p25 is very low (4%) with respect to the predicted values (30-43%), and its binding to tubulin induces remarkable alteration in the secondary structure of the protein(s) [17].
  • As shown by turbidimetry, pelleting experiments, and electron microscopy, p25 binds to paclitaxel-stabilized microtubules and bundles them. p25 induces formation of unusual (mainly double-walled) microtubules from tubulin in the absence of paclitaxel [17].


  1. Reconstitution of neuronal Cdc2-like kinase from bacteria-expressed Cdk5 and an active fragment of the brain-specific activator. Kinase activation in the absence of Cdk5 phosphorylation. Qi, Z., Huang, Q.Q., Lee, K.Y., Lew, J., Wang, J.H. J. Biol. Chem. (1995) [Pubmed]
  2. Phytohemagglutinin activation of the transcription of the bovine leukemia virus genome requires de novo protein synthesis. Chatterjee, R., Gupta, P., Kashmiri, S.V., Ferrer, J.F. J. Virol. (1985) [Pubmed]
  3. Detection of bovine leukemia virus antigen in urine from naturally infected cattle. Gupta, P., Ferrer, J.F. Int. J. Cancer (1980) [Pubmed]
  4. Characterization of a specific Mycobacterium paratuberculosis recombinant clone expressing 35,000-molecular-weight antigen and reactivity with sera from animals with clinical and subclinical Johne's disease. El-Zaatari, F.A., Naser, S.A., Graham, D.Y. J. Clin. Microbiol. (1997) [Pubmed]
  5. Properties of two isolated antigens associated with bovine leukemia virus infection. Onuma, M., Olson, C., Driscoll, D.M. J. Natl. Cancer Inst. (1976) [Pubmed]
  6. Neuronal Cdc2-like protein kinase (Cdk5/p25) is associated with protein phosphatase 1 and phosphorylates inhibitor-2. Agarwal-Mawal, A., Paudel, H.K. J. Biol. Chem. (2001) [Pubmed]
  7. GTP-dependent binding of ADP-ribosylation factor to coatomer in close proximity to the binding site for dilysine retrieval motifs and p23. Zhao, L., Helms, J.B., Brunner, J., Wieland, F.T. J. Biol. Chem. (1999) [Pubmed]
  8. Site-specific phosphorylation of synapsin I by mitogen-activated protein kinase and Cdk5 and its effects on physiological functions. Matsubara, M., Kusubata, M., Ishiguro, K., Uchida, T., Titani, K., Taniguchi, H. J. Biol. Chem. (1996) [Pubmed]
  9. Interaction of cyclin-dependent kinase 5 (Cdk5) and neuronal Cdk5 activator in bovine brain. Lee, K.Y., Rosales, J.L., Tang, D., Wang, J.H. J. Biol. Chem. (1996) [Pubmed]
  10. Comparison of various serological and direct methods for the diagnosis of BLV infection in cattle. Gupta, P., Ferrer, J.F. Int. J. Cancer (1981) [Pubmed]
  11. Precursor of cdk5 activator, the 23 kDa subunit of tau protein kinase II: its sequence and developmental change in brain. Uchida, T., Ishiguro, K., Ohnuma, J., Takamatsu, M., Yonekura, S., Imahori, K. FEBS Lett. (1994) [Pubmed]
  12. Phosphorylation of eIF-4F by protein kinase C or multipotential S6 kinase stimulates protein synthesis at initiation. Morley, S.J., Dever, T.E., Etchison, D., Traugh, J.A. J. Biol. Chem. (1991) [Pubmed]
  13. Phosphatidic acid-dependent phosphorylation of a 29-kDa protein by protein kinase Calpha in bovine brain cytosol. Yokozeki, T., Homma, K., Kuroda, S., Kikkawa, U., Ohno, S., Takahashi, M., Imahori, K., Kanaho, Y. J. Neurochem. (1998) [Pubmed]
  14. A novel yeast protein showing specific association with the cyclin-dependent kinase 5. Huang, Q.Q., Lee, K.Y., Wang, J.H. FEBS Lett. (1996) [Pubmed]
  15. Protection of calves against cryptosporidiosis with immune bovine colostrum induced by a Cryptosporidium parvum recombinant protein. Perryman, L.E., Kapil, S.J., Jones, M.L., Hunt, E.L. Vaccine (1999) [Pubmed]
  16. A novel prenyltransferase for a small GTP-binding protein having a C-terminal Cys-Ala-Cys structure. Horiuchi, H., Kawata, M., Katayama, M., Yoshida, Y., Musha, T., Ando, S., Takai, Y. J. Biol. Chem. (1991) [Pubmed]
  17. Brain-specific p25 protein binds to tubulin and microtubules and induces aberrant microtubule assemblies at substoichiometric concentrations. Hlavanda, E., Kovács, J., Oláh, J., Orosz, F., Medzihradszky, K.F., Ovádi, J. Biochemistry (2002) [Pubmed]
  18. Identification and localization of gene expression of a low M(r) GTP-binding protein, ram p25 in pituitary gland. Nagata, K., Sakagami, H., Kondo, H., Nozawa, Y. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  19. Renaturation and partial peptide sequencing of mitogen-activated protein kinase (MAP kinase) activator from rabbit skeletal muscle. Wu, J., Michel, H., Rossomando, A., Haystead, T., Shabanowitz, J., Hunt, D.F., Sturgill, T.W. Biochem. J. (1992) [Pubmed]
  20. Detection of mucosally delivered antibody to Cryptosporidium parvum p23 in infected calves. Wyatt, C.R., Perryman, L.E. Ann. N. Y. Acad. Sci. (2000) [Pubmed]
  21. Plant annexin form homodimer during Ca(2+)-dependent liposome aggregation. Hoshino, T., Mizutani, A., Chida, M., Hidaka, H., Mizutani, J. Biochem. Mol. Biol. Int. (1995) [Pubmed]
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