Learn and talk about Cyclin-dependent kinase 5, Cell cycle, Human proteins, Proteins

Cyclin-dependent kinase 5

PDB rendering based on 1h41.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1H4L, 1UNG, 1UNH, 1UNL, 3O0G, 4AU8

Identifiers

Symbols

CDK5; PSSALRE

External IDs

OMIM: 123831 MGI: 101765 HomoloGene: 3623 ChEMBL: 4036 GeneCards: CDK5 Gene

EC number

2.7.11.22

Gene Ontology
Molecular function	• p53 binding • protein kinase activity • protein serine/threonine kinase activity • cyclin-dependent protein serine/threonine kinase activity • ErbB-2 class receptor binding • protein binding • ATP binding • kinase activity • acetylcholine receptor activator activity • ErbB-3 class receptor binding • ephrin receptor binding • tau-protein kinase activity
Cellular component	• nucleus • cytoplasm • cytosol • plasma membrane • postsynaptic density • membrane • cyclin-dependent protein kinase 5 holoenzyme complex • lamellipodium • cell junction • filopodium • axon • dendrite • growth cone • neuromuscular junction • neuronal cell body • perikaryon • postsynaptic membrane
Biological process	• neuron migration • synaptic transmission, dopaminergic • intracellular protein transport • nucleocytoplasmic transport • cell-matrix adhesion • synaptic transmission • axon guidance • synapse assembly • skeletal muscle tissue development • blood coagulation • motor neuron axon guidance • cell proliferation • visual learning • embryo development • Schwann cell development • synaptic vesicle exocytosis • phosphorylation • peptidyl-serine phosphorylation • peptidyl-threonine phosphorylation • sensory perception of pain • cerebellar cortex formation • hippocampus development • layer formation in cerebral cortex • central nervous system neuron development • corpus callosum development • neuron differentiation • regulation of cell migration • cortical actin cytoskeleton organization • neuron projection development • negative regulation of protein ubiquitination • negative regulation of synaptic plasticity • positive regulation of protein binding • receptor catabolic process • serine phosphorylation of STAT3 protein • synaptic transmission, glutamatergic • protein localization to synapse • regulation of apoptotic process • receptor clustering • positive regulation of neuron apoptotic process • regulated secretory pathway • negative regulation of cell cycle • positive regulation of protein kinase activity • negative regulation of transcription, DNA-dependent • positive regulation of calcium ion-dependent exocytosis • protein autophosphorylation • negative regulation of protein export from nucleus • behavioral response to cocaine • regulation of synaptic plasticity • synaptic vesicle endocytosis • axon extension • oligodendrocyte differentiation • dendrite morphogenesis • cell division • neuron apoptotic process • regulation of excitatory postsynaptic membrane potential • regulation of dendritic spine morphogenesis • calcium ion import • regulation of cell cycle arrest • positive regulation of protein targeting to membrane • positive regulation of actin cytoskeleton reorganization
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 7:
150.75 – 150.76 Mb

Chr 5:
24.42 – 24.42 Mb

PubMed search

[1]

[2]

Cell division protein kinase 5 is an enzyme that in humans is encoded by the CDK5 gene.^[1]^[1]^[2]^[2] The protein encoded by this gene is part of the cyclin-dependent kinase family.

1 Physiological Role
2 Role in Disease
3 History
4 Interactive pathway map
5 Interactions
6 References
7 Further reading
8 External links

Physiological Role [edit]

Recently Cdk5 has emerged as an essential kinase in sensory pathways. Recent reports of Pareek et al. from NIH suggest its necessity in pain signaling. CDK5 is required for proper development of the brain and to be activated, CDK5 must associate with CDK5R1 or CDK5R2.^[3]^[4] Unlike other cyclin dependent kinases, CDK5 does not also require phosphorylation on the T loop so that binding with the activator is sufficient to activate the kinase.^[5]

Cdk5 is involved in the processes of neuronal maturation^[6] and migration, phosphorylating the key intracellular adaptor of the reelin signaling chain.^[7]

Experiments performed on mice lacking p35, a necessary activator of cdk5 in early brain development, showed that the normal layering of neurons was reversed in the cortex. This disrupted lamination again implicated cdk5 in neuronal migration and plasticity.^[8]

Cdk5 is also involved in the regulation of synaptic vesicle exocytosis via phosphorylation of munc-18.^[9]

Role in Disease [edit]

Dysregulation of this enzyme has been implicated in several neurodegenerative diseases^[10] including Alzheimer's.^[11]^[12]

It is involved in invasive cancers, apparently by reducing the activity of the actin regulatory protein caldesmon.^[13]

History [edit]

CDK5 was originally named NCLK for Neuronal CDC2-Like Kinase due to its similar phosphorylation motif. CDK5 in combination with an activator was also referred to as Tau Protein Kinase II.^[14] Furthermore, Cdk5 has been reported to be involved in T cell activation and play an important role in development of autoimmune disorders, such as multiple sclerosis.^[15]

Interactive pathway map [edit]

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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Nicotine Activity on Dopaminergic Neurons edit

^ The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602".

Interactions [edit]

Cyclin-dependent kinase 5 has been shown to interact with LMTK2,^[16] NDEL1,^[17] CDK5R1,^[5]^[18] Nestin^[19] and PAK1.^[20]

References [edit]

^ ^a ^b Demetrick DJ, Zhang H, Beach DH (February 1994). "Chromosomal mapping of human CDK2, CDK4, and CDK5 cell cycle kinase genes". Cytogenet Cell Genet 66 (1): 72–4. doi:10.1159/000133669. PMID 8275715.
^ ^a ^b Meyerson M, Enders GH, Wu CL, Su LK, Gorka C, Nelson C, Harlow E, Tsai LH (August 1992). "A family of human cdc2-related protein kinases". EMBO J 11 (8): 2909–17. PMC 556772. PMID 1639063.
^ Patrick GN, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai LH (1999). "Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration". Nature 402 (6762): 615–22. doi:10.1038/45159. PMID 10604467.
^ Paglini G, Cáceres A (2001). "The role of the Cdk5--p35 kinase in neuronal development". Eur. J. Biochem. 268 (6): 1528–33. doi:10.1046/j.1432-1327.2001.02023.x. PMID 11248669.
^ ^a ^b Tarricone C, Dhavan R, Peng J, Areces LB, Tsai LH, Musacchio A (September 2001). "Structure and regulation of the CDK5-p25(nck5a) complex". Mol. Cell 8 (3): 657–69. doi:10.1016/S1097-2765(01)00343-4. PMID 11583627.
^ Jessberger S, Aigner S, Clemenson GD, et al. (November 2008). "Cdk5 Regulates Accurate Maturation of Newborn Granule Cells in the Adult Hippocampus". In Danzer, Steve. PLoS Biol. 6 (11): e272. doi:10.1371/journal.pbio.0060272. PMC 2581629. PMID 18998770.
^ Ohshima T, Suzuki H, Morimura T, Ogawa M, Mikoshiba K (April 2007). "Modulation of Reelin signaling by Cyclin-dependent kinase 5". Brain Res. 1140: 84–95. doi:10.1016/j.brainres.2006.01.121. PMID 16529723.
^ Rakic S, Yanagawa Y, Obata K, Faux C, Parnavelas J, Nikolic M (November 2008). "Cortical Interneurons Require p35/Cdk5 for their Migration and Laminar Organization". Cerebral Cortex 19 (8): 1857–69. doi:10.1093/cercor/bhn213. PMC 2705696. PMID 19037081.
^ Fletcher AI, Shuang R, Giovannucci DR, Zhang L, Bittner MA, Stuenkel EL (February 1999). "Regulation of exocytosis by cyclin-dependent kinase 5 via phosphorylation of Munc18". J Biol Chem 274 (7): 4027–35. doi:10.1074/jbc.274.7.4027. PMID 9933594.
^ Dhavan R, Tsai LH (2001). "A decade of CDK5". Nat. Rev. Mol. Cell Biol. 2 (10): 749–59. doi:10.1038/35096019. PMID 11584302.
^ Monaco EA (2004). "Recent evidence regarding a role for Cdk5 dysregulation in Alzheimer's disease". Curr Alzheimer Res 1 (1): 33–8. doi:10.2174/1567205043480519. PMID 15975083.
^ Qu J; Nakamura, T.; Cao, G.; Holland, E. A.; McKercher, S. R.; Lipton, S. A. (2011). "S-Nitrosylation activates Cdk5 and contributes to synaptic spine loss induced by β-amyloid peptide". PNAS 108 (34): 14330–5. doi:10.1073/pnas.1105172108. PMC 3161554. PMID 21844361.
^ Quintavalle, M.; Elia, L.; Price, J. H.; Heynen-Genel, S.; Courtneidge, S. A. (2011). "A Cell-Based High-Content Screening Assay Reveals Activators and Inhibitors of Cancer Cell Invasion". Science Signaling 4 (183): ra49. doi:10.1126/scisignal.2002032. PMC 3291516. PMID 21791703.
^ Kobayashi S, Ishiguro K, Omori A, Takamatsu M, Arioka M, Imahori K, Uchida T. (1993). "A cdc2-related kinase PSSALRE/cdk5 is homologous with the 30 kDa subunit of tau protein kinase II, a proline-directed protein kinase associated with microtubule". FEBS Letters 335 (2): 171–175. doi:10.1016/0014-5793(93)80723-8. PMID 8253190.
^ Pareek TK, Lam E, Zheng X, Askew D, Kulkarni AB, Chance MR, Huang AY, Cooke KR, Letterio JJ (October 2010). "Cyclin-dependent kinase 5 activity is required for T cell activation and induction of experimental autoimmune encephalomyelitis". J. Exp. Med. 207 (11): 2507–19. doi:10.1084/jem.20100876. PMC 2964575. PMID 20937706.
^ Kesavapany, Sashi; Lau Kwok-Fai, Ackerley Steven, Banner Steven J, Shemilt Stephen J A, Cooper Jonathan D, Leigh P Nigel, Shaw Christopher E, McLoughlin Declan M, Miller Christopher C J (June 2003). "Identification of a novel, membrane-associated neuronal kinase, cyclin-dependent kinase 5/p35-regulated kinase". J. Neurosci. (United States) 23 (12): 4975–83. PMID 12832520.
^ Niethammer, M; Smith D S, Ayala R, Peng J, Ko J, Lee M S, Morabito M, Tsai L H (December 2000). "NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein". Neuron (United States) 28 (3): 697–711. doi:10.1016/S0896-6273(00)00147-1. ISSN 0896-6273. PMID 11163260.
^ Chen, F; Studzinski G P (June 2001). "Expression of the neuronal cyclin-dependent kinase 5 activator p35Nck5a in human monocytic cells is associated with differentiation". Blood (United States) 97 (12): 3763–7. doi:10.1182/blood.V97.12.3763. ISSN 0006-4971. PMID 11389014.
^ Sahlgren, Cecilia M; Mikhailov Andrey, Vaittinen Samuli, Pallari Hanna-Mari, Kalimo Hannu, Pant Harish C, Eriksson John E (July 2003). "Cdk5 Regulates the Organization of Nestin and Its Association with p35". Mol. Cell. Biol. (United States) 23 (14): 5090–106. doi:10.1128/MCB.23.14.5090-5106.2003. ISSN 0270-7306. PMC 162223. PMID 12832492.
^ Rashid, T; Banerjee M, Nikolic M (December 2001). "Phosphorylation of Pak1 by the p35/Cdk5 kinase affects neuronal morphology". J. Biol. Chem. (United States) 276 (52): 49043–52. doi:10.1074/jbc.M105599200. ISSN 0021-9258. PMID 11604394.

External links [edit]

Cyclin-Dependent Kinase 5 at the US National Library of Medicine Medical Subject Headings (MeSH)
CDK5 human gene location in the UCSC Genome Browser.
CDK5 human gene details in the UCSC Genome Browser.

Cell cycle proteins

Cyclin

A (A1, A2)
B (B1, B2, B3)
D (D1, D2, D3)
E (E1, E2)

CDK

1
2
3
4
5
6
7
8
9
10
CDK-activating kinase

CDK inhibitor

INK4a/ARF (p14arf/p16, p15, p18, p19)
cip/kip (p21, p27, p57)

P53 p63 p73 family

Phases and
checkpoints

Interphase	G₁ phase S phase G₂ phase

M phase	Mitosis (Preprophase Prophase Prometaphase Metaphase Anaphase Telophase) Cytokinesis

Cell cycle checkpoints	Restriction point Spindle checkpoint Postreplication checkpoint

Other cellular phases	Apoptosis G₀ phase Meiosis

B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)

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Cyclin-dependent kinase 5

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