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cyclin-dependent kinase-5 (CDK5), PSSALRE or tau protein kinase 2 catalytic subunit

Function: - role in control of the cell cycle (putative) - interacts with D1 & D3-type G1 cyclins & with a novel regulatory subunit, p35 - can phosphorylate histone H1, tau, MAP2 & NF-H & NF-M - also interacts with p35 which activates the kinase - heterodimer of a catalytic subunit & a regulatory subunit (p35) - CDK5/p35 functions in neuronal development - found in a trimolecular complex with CABLES1 & ABL1 - interacts with CABLES1 (putative) - interacts with AATK - substrates include: a) microtubule-associated protein tau b) focal adhesion kinase 1, phosphorylation of FAK1 on Ser-732 is important for microtubule organization, nuclear movement & neuronal migration [3] Structure: - belongs to the protein kinase superfamily, CMGC Ser/Thr protein kinase family, CDC2/CDKX subfamily - contains 1 protein kinase domain Compartment: - cytoplasm (putative), cell projection, - lamellipodium (putative) - cell projection, growth cone - in axonal growth cone with extension to the peripheral lamellipodia (putative) Pathology: - CDK5 hyperphosphorylates microtubule-associated protein tau to a form capable of aggregating into paired-helical filaments, [2] after oxidation of Cys to form intermolecular disulfides (see paired-helical filament tau)

General

cyclin-dependent kinase (CDK)

Properties

SIZE: entity length = 292 aa MW = 33 kD COMPARTMENT: cytoplasm STATE: active state MOTIF: kinase domain SITE: 4-286 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 10-18 Thr phosphorylation site {T14} Tyr phosphorylation site {Y15} ATP-binding site NAME: ATP-binding site SITE: 33-33 aspartate residue {D126} Ser-phosphate {S159}

Database Correlations

OMIM 123831 UniProt Q00535 Pfam PF00069 Entrez Gene 1020 Kegg hsa:1020 ENZYME 2.7.11.22

References

  1. Solomon MJ. The function(s) of CAK, the p34cdc2-activating kinase. Trends Biochem Sci. 1994 Nov;19(11):496-500. PMID: 7855894
  2. Noble W, Olm V, Takata K, Casey E, Mary O, Meyerson J et al Cdk5 is a key factor in tau aggregation and tangle formation in vivo. Neuron. 2003 May 22;38(4):555-65. PMID: 12765608
  3. Xie Z, Sanada K, Samuels BA, Shih H, Tsai LH. Serine 732 phosphorylation of FAK by Cdk5 is important for microtubule organization, nuclear movement, and neuronal migration. Cell. 2003 Aug 22;114(4):469-82. PMID: 12941275
  4. UniProt :accession Q00535

Component-of

molecular complex