Version 5.4
Bos taurus Protein: CDK5
Summary
InnateDB Protein IDBP-689545.2
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol CDK5
Protein Name Cyclin-dependent kinase 5
Synonyms
Species Bos taurus
Ensembl Protein ENSBTAP00000010212
InnateDB Gene IDBG-637527 (CDK5)
Protein Structure
UniProt Annotation
Function Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3- type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1, huntingtin/HTT, ATM, MAP2, NEFH and NEFM. Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission, by phosphorylating key proteins. Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39), especially in post-mitotic neurons, and promotes CDK5R1 (p35) expression in an autostimulation loop. Phosphorylates many downstream substrates such as Rho and Ras family small GTPases (e.g. PAK1, RAC1, RHOA, CDC42) or microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B), and modulates actin dynamics to regulate neurite growth and/or spine morphogenesis. Phosphorylates also exocytosis associated proteins such as MCAM/MUC18, SEPT5, SYN1, and CDK16/PCTAIRE1 as well as endocytosis associated proteins such as DNM1, AMPH and SYNJ1 at synaptic terminals. In the mature central nervous system (CNS), regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity; synaptic vesicle exocytosis, vesicles fusion with the presynaptic membrane, and endocytosis. Promotes cell survival by activating anti-apoptotic proteins BCL2 and STAT3, and negatively regulating of JNK3/MAPK10 activity. Phosphorylation of p53/TP53 in response to genotoxic and oxidative stresses enhances its stabilization by preventing ubiquitin ligase-mediated proteasomal degradation, and induces transactivation of p53/TP53 target genes, thus regulating apoptosis. Phosphorylation of p35/CDK5R1 enhances its stabilization by preventing calpain-mediated proteolysis producing p25/CDK5R1 and avoiding ubiquitin ligase-mediated proteasomal degradation. During aberrant cell-cycle activity and DNA damage, p25/CDK5 activity elicits cell-cycle activity and double-strand DNA breaks that precedes neuronal death by deregulating HDAC1. DNA damage triggered phosphorylation of huntingtin/HTT in nuclei of neurons protects neurons against polyglutamine expansion as well as DNA damage mediated toxicity. Phosphorylation of PXN reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation. Negative regulator of Wnt/beta-catenin signaling pathway. Activator of the GAIT (IFN-gamma-activated inhibitor of translation) pathway, which suppresses expression of a post-transcriptional regulon of proinflammatory genes in myeloid cells; phosphorylates the linker domain of glutamyl-prolyl tRNA synthetase (EPRS) in a IFN-gamma- dependent manner, the initial event in assembly of the GAIT complex. Phosphorylation of SH3GLB1 is required for autophagy induction in starved neurons. Phosphorylation of TONEBP/NFAT5 in response to osmotic stress mediates its rapid nuclear localization. MEF2 is inactivated by phosphorylation in nucleus in response to neurotoxin, thus leading to neuronal apoptosis. APEX1 AP-endodeoxyribonuclease is repressed by phosphorylation, resulting in accumulation of DNA damage and contributing to neuronal death. NOS3 phosphorylation down regulates NOS3-derived nitrite (NO) levels. SRC phosphorylation mediates its ubiquitin- dependent degradation and thus leads to cytoskeletal reorganization. May regulate endothelial cell migration and angiogenesis via the modulation of lamellipodia formation. Involved in dendritic spine morphogenesis by mediating the EFNA1- EPHA4 signaling. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer in association with altered stability and subcellular distribution (By similarity). {ECO:0000250}.
Subcellular Localization Cytoplasm {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Perikaryon {ECO:0000250}. Cell projection, lamellipodium {ECO:0000250}. Cell projection, growth cone {ECO:0000250}. Nucleus {ECO:0000250}. Cell junction, synapse, postsynaptic cell membrane, postsynaptic density {ECO:0000250}. Note=In axonal growth cone with extension to the peripheral lamellipodia (By similarity). Under neurotoxic stress and neuronal injury conditions, CDK5R1 (p35) is cleaved by calpain to generate CDK5R1 (p25) in response to increased intracellular calcium. The elevated level of p25, when in complex with CDK5, leads to its subcellular misallocation as well as its hyperactivation. Colocalizes with CTNND2 in the cell body of neuronal cells, and with CTNNB1 in the cell-cell contacts and plasma membrane of undifferentiated and differentiated neuroblastoma cells. Reversibly attached to the plasma membrane in an inactive form when complexed to dephosphorylated p35 or CDK5R2 (p39), p35 phosphorylation releases this attachment and activates CDK5 (By similarity). {ECO:0000250}.
Disease Associations
Tissue Specificity
Comments
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 1 experimentally validated interaction(s) in this database.
They are also associated with 53 interaction(s) predicted by orthology.
Experimentally validated
Total 1 [view]
Protein-Protein 1 [view]
Protein-DNA 0
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 53 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000166 nucleotide binding
GO:0002039 p53 binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0005176 ErbB-2 class receptor binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0030549 acetylcholine receptor activator activity
GO:0035173 histone kinase activity
GO:0043125 ErbB-3 class receptor binding
GO:0050321 tau-protein kinase activity
Biological Process
GO:0001764 neuron migration
GO:0001963 synaptic transmission, dopaminergic
GO:0006468 protein phosphorylation
GO:0006886 intracellular protein transport
GO:0006915 apoptotic process
GO:0007049 cell cycle
GO:0007160 cell-matrix adhesion
GO:0007399 nervous system development
GO:0007409 axonogenesis
GO:0007416 synapse assembly
GO:0007519 skeletal muscle tissue development
GO:0008045 motor neuron axon guidance
GO:0008219 cell death
GO:0008306 associative learning
GO:0008542 visual learning
GO:0009790 embryo development
GO:0014044 Schwann cell development
GO:0016310 phosphorylation
GO:0016477 cell migration
GO:0016572 histone phosphorylation
GO:0018105 peptidyl-serine phosphorylation
GO:0018107 peptidyl-threonine phosphorylation
GO:0019233 sensory perception of pain
GO:0021537 telencephalon development
GO:0021549 cerebellum development
GO:0021695 cerebellar cortex development
GO:0021697 cerebellar cortex formation
GO:0021766 hippocampus development
GO:0021819 layer formation in cerebral cortex
GO:0021954 central nervous system neuron development
GO:0021987 cerebral cortex development
GO:0022038 corpus callosum development
GO:0030182 neuron differentiation
GO:0030334 regulation of cell migration
GO:0030517 negative regulation of axon extension
GO:0030900 forebrain development
GO:0031175 neuron projection development
GO:0031397 negative regulation of protein ubiquitination
GO:0031914 negative regulation of synaptic plasticity
GO:0032092 positive regulation of protein binding
GO:0032801 receptor catabolic process
GO:0033136 serine phosphorylation of STAT3 protein
GO:0035249 synaptic transmission, glutamatergic
GO:0035418 protein localization to synapse
GO:0042220 response to cocaine
GO:0043113 receptor clustering
GO:0043525 positive regulation of neuron apoptotic process
GO:0045786 negative regulation of cell cycle
GO:0045860 positive regulation of protein kinase activity
GO:0045861 negative regulation of proteolysis
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045956 positive regulation of calcium ion-dependent exocytosis
GO:0046826 negative regulation of protein export from nucleus
GO:0048148 behavioral response to cocaine
GO:0048167 regulation of synaptic plasticity
GO:0048511 rhythmic process
GO:0048709 oligodendrocyte differentiation
GO:0048813 dendrite morphogenesis
GO:0051301 cell division
GO:0051402 neuron apoptotic process
GO:0060078 regulation of postsynaptic membrane potential
GO:0060079 regulation of excitatory postsynaptic membrane potential
GO:0061001 regulation of dendritic spine morphogenesis
GO:0070509 calcium ion import
GO:0090314 positive regulation of protein targeting to membrane
GO:1901215 negative regulation of neuron death
GO:2000273 positive regulation of receptor activity
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0014069 postsynaptic density
GO:0016020 membrane
GO:0030027 lamellipodium
GO:0030054 cell junction
GO:0030175 filopodium
GO:0030424 axon
GO:0030425 dendrite
GO:0030426 growth cone
GO:0031594 neuromuscular junction
GO:0042995 cell projection
GO:0043025 neuronal cell body
GO:0043204 perikaryon
GO:0045202 synapse
GO:0045211 postsynaptic membrane
Protein Structure and Domains
PDB ID
InterPro IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain
PFAM PF00069
PF07714
PRINTS PR00109
PIRSF
SMART SM00220
SM00219
TIGRFAMs
Post-translational Modifications
Modification
Cross-References
SwissProt Q02399
PhosphoSite PhosphoSite-Q02399
TrEMBL
UniProt Splice Variant
Entrez Gene 281066
UniGene
RefSeq NP_776442
HUGO
OMIM
CCDS
HPRD
IMGT
EMBL BC120083 L04798 X82440
GenPept AAA30606 AAI20084 CAA57821

If you use InnateDB for your research, please cite the following publication:

Breuer et al., InnateDB: systems biology of innate immunity and beyond - recent updates and continuing curation. Nucl. Acids Res. (2013) 41 (D1) 

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Funding is currently provided by Allergen and EMBL Australia. Previous funding has been provided by Genome Canada, the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative and by Teagasc. InnateDB curated interactions are licensed under the Design Science License. All other data is licensed under the terms of the originating database. Contact: innatedb-mail@sfu.ca