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Q00535 (CDK5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 159. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cyclin-dependent kinase 5

EC=2.7.11.22
Alternative name(s):
Cell division protein kinase 5
Serine/threonine-protein kinase PSSALRE
Tau protein kinase II catalytic subunit
Short name=TPKII catalytic subunit
Gene names
Name:CDK5
Synonyms:CDKN5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length292 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.3 Ref.9 Ref.11 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.24 Ref.28 Ref.29 Ref.32 Ref.33 Ref.35 Ref.36 Ref.37 Ref.41 Ref.46

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Inhibited by 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine), 1-isopropyl-4-aminobenzyl-6-ether-linked benzimidazoles, resveratrol, AT-7519 and olomoucine. Activated by CDK5R1 (p35) and CDK5R2 (p39) during the development of the nervous system; degradation of CDK5R1 (p35) and CDK5R2 (p39) by proteasome result in down regulation of kinase activity, during this process, CDK5 phosphorylates p35 and induces its ubiquitination and subsequent degradation. Kinase activity is mainly determined by the amount of p35 available and subcellular location; reversible association to plasma membrane inhibits activity. Long-term inactivation as well as CDK5R1 (p25)-mediated hyperactivation of CDK5 triggers cell death. The pro-death activity of hyperactivated CDK5 is suppressed by membrane association of CDK5, via myristoylation of p35. Brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor (NGF), retinoic acid, laminin and neuregulin promote activity. Neurotoxicity enhances nuclear activity, thus leading to MEF2 phosphorylation and inhibition prior to apoptosis of cortical neurons. Repression by GSTP1 via p25/p35 translocation prevents neurodegeneration. Ref.8 Ref.13 Ref.14 Ref.19 Ref.34

Subunit structure

Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) and macromolecular complex composed of at least CDK5, CDK5R1 (p35) and CDK5RAP1 or CDK5RAP2 or CDK5RAP3. Only the heterodimer shows kinase activity. Under neurotoxic stress and neuronal injury conditions, p35 is cleaved by calpain to generate p25 that hyperactivates CDK5, that becomes functionally disabled and often toxic. Found in a trimolecular complex with CABLES1 and ABL1. Interacts with CABLES1 and CABLES2 By similarity. Interacts with AATK and GSTP1. Binds to HDAC1 when in complex with p25. Interaction with myristoylation p35 promotes CDK5 association with membranes. Both isoforms 1 and 2 interacts with beta-catenin/CTNNB1. Interacts with delta-catenin/CTNND2 and APEX1. Interacts with P53/TP53 in neurons. Interacts with EPHA4; may mediate the activation of NGEF by EPHA4. Interacts with PTK2/FAK1 By similarity. The complex p35/CDK5 interacts with CLOCK. Ref.3 Ref.12 Ref.16 Ref.17 Ref.20 Ref.34 Ref.46

Subcellular location

Isoform 1: Cytoplasm. Cell membrane; Peripheral membrane protein. Perikaryon. Cell projectionlamellipodium By similarity. Cell projectiongrowth cone By similarity. Cell junctionsynapsepostsynaptic cell membranepostsynaptic density By similarity. Note: In axonal growth cone with extension to the peripheral lamellipodia By similarity. Under neurotoxic stress and neuronal injury conditions, CDK5R (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. Ref.3 Ref.13 Ref.14 Ref.16 Ref.17 Ref.20 Ref.22 Ref.33

Isoform 2: Nucleus Ref.3 Ref.13 Ref.14 Ref.16 Ref.17 Ref.20 Ref.22 Ref.33.

Tissue specificity

Isoform 1 is ubiquitously expressed. Accumulates in cortical neurons (at protein level). Isoform 2 has only been detected in testis, skeletal muscle, colon, bone marrow and ovary. Ref.3 Ref.16

Post-translational modification

Phosphorylation on Tyr-15 by ABL1 and FYN, and on Ser-159 by casein kinase 1 promotes kinase activity. By contrast, phosphorylation at Thr-14 inhibits activity.

Phosphorylation at Ser-159 is essential for maximal catalytic activity.

Miscellaneous

Dysregulation of CDK5 is associated with neurodegenerative disorders such as Alzheimer, Parkinson, and Niemann-Pick type C diseases, ischemia, and amyotrophic lateral sclerosis.

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Cell cycle
Cell division
Neurogenesis
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Membrane
Nucleus
Postsynaptic cell membrane
Synapse
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseNeurodegeneration
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processSchwann cell development

Inferred from electronic annotation. Source: Ensembl

axon extension

Traceable author statement Ref.45. Source: UniProtKB

axon guidance

Traceable author statement. Source: Reactome

behavioral response to cocaine

Inferred from electronic annotation. Source: Ensembl

blood coagulation

Traceable author statement. Source: Reactome

calcium ion import

Inferred from electronic annotation. Source: Ensembl

cell division

Inferred from electronic annotation. Source: UniProtKB-KW

cell proliferation

Traceable author statement PubMed 8090221. Source: ProtInc

cell-matrix adhesion

Inferred from electronic annotation. Source: Ensembl

central nervous system neuron development

Inferred from electronic annotation. Source: Ensembl

cerebellar cortex formation

Inferred from electronic annotation. Source: Ensembl

corpus callosum development

Inferred from electronic annotation. Source: Ensembl

cortical actin cytoskeleton organization

Inferred from electronic annotation. Source: Ensembl

dendrite morphogenesis

Inferred from electronic annotation. Source: Ensembl

embryo development

Inferred from sequence or structural similarity. Source: UniProtKB

hippocampus development

Inferred from electronic annotation. Source: Ensembl

intracellular protein transport

Inferred from electronic annotation. Source: Ensembl

layer formation in cerebral cortex

Inferred from electronic annotation. Source: Ensembl

motor neuron axon guidance

Inferred from electronic annotation. Source: Ensembl

negative regulation of axon extension

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell cycle

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein export from nucleus

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein ubiquitination

Inferred from electronic annotation. Source: Ensembl

negative regulation of synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 20357208. Source: DFLAT

neuron apoptotic process

Traceable author statement Ref.45. Source: UniProtKB

neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

neuron migration

Traceable author statement Ref.45. Source: UniProtKB

neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

nucleocytoplasmic transport

Inferred from electronic annotation. Source: Ensembl

oligodendrocyte differentiation

Inferred from direct assay Ref.18. Source: UniProtKB

peptidyl-serine phosphorylation

Inferred from direct assay PubMed 21145489. Source: UniProtKB

peptidyl-threonine phosphorylation

Inferred from electronic annotation. Source: Ensembl

phosphorylation

Inferred from direct assay PubMed 20357208. Source: DFLAT

positive regulation of actin cytoskeleton reorganization

Traceable author statement Ref.45. Source: UniProtKB

positive regulation of calcium ion-dependent exocytosis

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein binding

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein kinase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein targeting to membrane

Inferred from electronic annotation. Source: Ensembl

positive regulation of receptor activity

Inferred from sequence or structural similarity. Source: GOC

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

protein localization to synapse

Inferred from electronic annotation. Source: Ensembl

receptor catabolic process

Inferred from electronic annotation. Source: Ensembl

receptor clustering

Inferred from electronic annotation. Source: Ensembl

regulated secretory pathway

Inferred from electronic annotation. Source: Ensembl

regulation of apoptotic process

Traceable author statement Ref.45. Source: UniProtKB

regulation of cell cycle arrest

Traceable author statement Ref.45. Source: UniProtKB

regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

regulation of dendritic spine morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of excitatory postsynaptic membrane potential

Inferred from electronic annotation. Source: Ensembl

regulation of synaptic plasticity

Inferred from sequence or structural similarity. Source: UniProtKB

sensory perception of pain

Inferred from electronic annotation. Source: Ensembl

serine phosphorylation of STAT3 protein

Inferred from electronic annotation. Source: Ensembl

skeletal muscle tissue development

Inferred from electronic annotation. Source: Ensembl

synapse assembly

Traceable author statement Ref.45. Source: UniProtKB

synaptic transmission

Traceable author statement Ref.45. Source: UniProtKB

synaptic transmission, dopaminergic

Inferred from electronic annotation. Source: Ensembl

synaptic transmission, glutamatergic

Inferred from electronic annotation. Source: Ensembl

synaptic vesicle endocytosis

Traceable author statement Ref.45. Source: UniProtKB

synaptic vesicle exocytosis

Traceable author statement Ref.45. Source: UniProtKB

visual learning

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentaxon

Inferred from sequence or structural similarity. Source: UniProtKB

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cyclin-dependent protein kinase 5 holoenzyme complex

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

dendrite

Inferred from sequence or structural similarity. Source: UniProtKB

filopodium

Inferred from electronic annotation. Source: Ensembl

growth cone

Inferred from sequence or structural similarity. Source: UniProtKB

lamellipodium

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane

Inferred from sequence or structural similarity. Source: UniProtKB

neuromuscular junction

Inferred from sequence or structural similarity. Source: UniProtKB

neuronal cell body

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

perikaryon

Inferred from electronic annotation. Source: UniProtKB-SubCell

postsynaptic density

Inferred from sequence or structural similarity. Source: UniProtKB

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

ErbB-2 class receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

ErbB-3 class receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

acetylcholine receptor activator activity

Inferred from sequence or structural similarity. Source: UniProtKB

cyclin-dependent protein serine/threonine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase activity

Traceable author statement Ref.1PubMed 7834371. Source: ProtInc

protein serine/threonine kinase activity

Inferred from direct assay PubMed 21145489. Source: UniProtKB

tau-protein kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q00535-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q00535-2)

Also known as: CDK5-SV;

The sequence of this isoform differs from the canonical sequence as follows:
     105-136: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 292292Cyclin-dependent kinase 5
PRO_0000085784

Regions

Domain4 – 286283Protein kinase
Nucleotide binding10 – 189ATP By similarity

Sites

Active site1261Proton acceptor By similarity
Binding site331ATP By similarity

Amino acid modifications

Modified residue151Phosphotyrosine; by ABL1, EPHA4 and FYN Ref.49
Modified residue561N6-acetyllysine Ref.27
Modified residue721Phosphoserine Ref.23 Ref.26
Modified residue1591Phosphoserine Ref.10

Natural variations

Alternative sequence105 – 13632Missing in isoform 2.
VSP_041948
Natural variant2251E → D. Ref.50
Corresponds to variant rs35186917 [ dbSNP | Ensembl ].
VAR_041977

Experimental info

Mutagenesis1591S → A: No phenotype. Ref.47
Mutagenesis1591S → T: Impaired p35/p25 (CDK5R1) binding. Ref.47

Secondary structure

................................................... 292
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 15, 1998. Version 3.
Checksum: 54D10495F017D527

FASTA29233,304
        10         20         30         40         50         60 
MQKYEKLEKI GEGTYGTVFK AKNRETHEIV ALKRVRLDDD DEGVPSSALR EICLLKELKH 

        70         80         90        100        110        120 
KNIVRLHDVL HSDKKLTLVF EFCDQDLKKY FDSCNGDLDP EIVKSFLFQL LKGLGFCHSR 

       130        140        150        160        170        180 
NVLHRDLKPQ NLLINRNGEL KLADFGLARA FGIPVRCYSA EVVTLWYRPP DVLFGAKLYS 

       190        200        210        220        230        240 
TSIDMWSAGC IFAELANAGR PLFPGNDVDD QLKRIFRLLG TPTEEQWPSM TKLPDYKPYP 

       250        260        270        280        290 
MYPATTSLVN VVPKLNATGR DLLQNLLKCN PVQRISAEEA LQHPYFSDFC PP 

« Hide

Isoform 2 (CDK5-SV) [UniParc].

Checksum: 808E46028B657622
Show »

FASTA26029,544

References

« Hide 'large scale' references
[1]"A family of human cdc2-related protein kinases."
Meyerson M., Enders G.H., Wu C.-L., Su L.-K., Gorka C., Nelson C., Harlow E., Tsai L.-H.
EMBO J. 11:2909-2917(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fetal brain.
[2]Meyerson M.
Submitted (FEB-1993) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"Characterization of a novel human CDK5 splicing variant that inhibits Wnt/beta-catenin signaling."
Li Q., Liu X., Zhang M., Ye G., Qiao Q., Ling Y., Wu Y., Zhang Y., Yu L.
Mol. Biol. Rep. 37:2415-2421(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH CTNNB1, FUNCTION IN WNT/B-CATENIN SIGNALING PATHWAY.
Tissue: Testis.
[4]Hu X., Xu Y., Zhang B., Peng X., Yuan J., Qiang B.
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lung.
[8]"Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5."
Meijer L., Borgne A., Mulner O., Chong J.P.J., Blow J.J., Inagaki N., Inagaki M., Delcros J.-G., Moulinoux J.-P.
Eur. J. Biochem. 243:527-536(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION BY ROSCOVITINE AND OLOMOUCINE.
[9]"Evidence for the participation of the neuron-specific CDK5 activator P35 during laminin-enhanced axonal growth."
Paglini G., Pigino G., Kunda P., Morfini G., Maccioni R., Quiroga S., Ferreira A., Caceres A.
J. Neurosci. 18:9858-9869(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN AXON GROWTH.
[10]"Regulation of cyclin-dependent kinase 5 catalytic activity by phosphorylation."
Sharma P., Sharma M., Amin N.D., Albers R.W., Pant H.C.
Proc. Natl. Acad. Sci. U.S.A. 96:11156-11160(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-159.
[11]"Influence of phosphorylation of p35, an activator of cyclin-dependent kinase 5 (cdk5), on the proteolysis of p35."
Kerokoski P., Suuronen T., Salminen A., Soininen H., Pirttilae T.
Brain Res. Mol. Brain Res. 106:50-56(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS P35/CDK5R1 KINASE.
[12]"Apoptosis-associated tyrosine kinase is a Cdk5 activator p35 binding protein."
Honma N., Asada A., Takeshita S., Enomoto M., Yamakawa E., Tsutsumi K., Saito T., Satoh T., Itoh H., Kaziro Y., Kishimoto T., Hisanaga S.
Biochem. Biophys. Res. Commun. 310:398-404(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AATK.
[13]"Cdk5-mediated inhibition of the protective effects of transcription factor MEF2 in neurotoxicity-induced apoptosis."
Gong X., Tang X., Wiedmann M., Wang X., Peng J., Zheng D., Blair L.A.C., Marshall J., Mao Z.
Neuron 38:33-46(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS MEF2A KINASE, ENZYME REGULATION, SUBCELLULAR LOCATION.
[14]"Activation of latent cyclin-dependent kinase 5 (Cdk5)-p35 complexes by membrane dissociation."
Zhu Y.-S., Saito T., Asada A., Maekawa S., Hisanaga S.
J. Neurochem. 94:1535-1545(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS P35 KINASE, SUBCELLULAR LOCATION, ENZYME REGULATION.
[15]"Suppression of calpain-dependent cleavage of the CDK5 activator p35 to p25 by site-specific phosphorylation."
Kamei H., Saito T., Ozawa M., Fujita Y., Asada A., Bibb J.A., Saido T.C., Sorimachi H., Hisanaga S.
J. Biol. Chem. 282:1687-1694(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS P35/CDK5R KINASE.
[16]"cdk5 modulates beta- and delta-catenin/Pin1 interactions in neuronal cells."
Munoz J.P., Huichalaf C.H., Orellana D., Maccioni R.B.
J. Cell. Biochem. 100:738-749(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS CTNNB1 AND CTNND2 KINASE, INTERACTION WITH CTNNB1 AND CTNND2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[17]"Stabilization and activation of p53 induced by Cdk5 contributes to neuronal cell death."
Lee J.-H., Kim H.-S., Lee S.-J., Kim K.-T.
J. Cell Sci. 120:2259-2271(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS P53/TP53 KINASE, INTERACTION WITH P53/TP53, SUBCELLULAR LOCATION.
[18]"Cdk5 regulates differentiation of oligodendrocyte precursor cells through the direct phosphorylation of paxillin."
Miyamoto Y., Yamauchi J., Chan J.R., Okada A., Tomooka Y., Hisanaga S., Tanoue A.
J. Cell Sci. 120:4355-4366(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS PXN KINASE.
[19]"Phosphorylation of huntingtin by cyclin-dependent kinase 5 is induced by DNA damage and regulates wild-type and mutant huntingtin toxicity in neurons."
Anne S.L., Saudou F., Humbert S.
J. Neurosci. 27:7318-7328(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS HUNTINGTIN KINASE, ENZYME REGULATION BY ROSCOVITINE.
[20]"Regulation of membrane association and kinase activity of Cdk5-p35 by phosphorylation of p35."
Sato K., Zhu Y.-S., Saito T., Yotsumoto K., Asada A., Hasegawa M., Hisanaga S.
J. Neurosci. Res. 85:3071-3078(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS P35/CDK5R KINASE, INTERACTION WITH P35/CDK5R, SUBCELLULAR LOCATION.
[21]"Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism."
Fu W.Y., Chen Y., Sahin M., Zhao X.S., Shi L., Bikoff J.B., Lai K.O., Yung W.H., Fu A.K., Greenberg M.E., Ip N.Y.
Nat. Neurosci. 10:67-76(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY EPHA4 AT TYR-15.
[22]"Myristoylation of p39 and p35 is a determinant of cytoplasmic or nuclear localization of active cyclin-dependent kinase 5 complexes."
Asada A., Yamamoto N., Gohda M., Saito T., Hayashi N., Hisanaga S.
J. Neurochem. 106:1325-1336(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[23]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[24]"Deregulation of HDAC1 by p25/Cdk5 in neurotoxicity."
Kim D., Frank C.L., Dobbin M.M., Tsunemoto R.K., Tu W., Peng P.L., Guan J.S., Lee B.H., Moy L.Y., Giusti P., Broodie N., Mazitschek R., Delalle I., Haggarty S.J., Neve R.L., Lu Y., Tsai L.H.
Neuron 60:803-817(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS HDAC REGULATOR.
[25]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[26]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[27]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-56, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]"Cyclin-dependent kinase 5 regulates endothelial cell migration and angiogenesis."
Liebl J., Weitensteiner S.B., Vereb G., Takacs L., Fuerst R., Vollmar A.M., Zahler S.
J. Biol. Chem. 285:35932-35943(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ANGIOGENESIS.
[29]"CDK5 phosphorylates eNOS at Ser-113 and regulates NO production."
Lee C.-H., Wei Y.-W., Huang Y.-T., Lin Y.-T., Lee Y.-C., Lee K.-H., Lu P.-J.
J. Cell. Biochem. 110:112-117(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS NOS3 KINASE.
[30]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[31]"Design, synthesis, and testing of an 6-O-linked series of benzimidazole based inhibitors of CDK5/p25."
Jain P., Flaherty P.T., Yi S., Chopra I., Bleasdell G., Lipay J., Ferandin Y., Meijer L., Madura J.D.
Bioorg. Med. Chem. 19:359-373(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INHIBITORS.
[32]"Cdk5 targets active Src for ubiquitin-dependent degradation by phosphorylating Src(S75)."
Pan Q., Qiao F., Gao C., Norman B., Optican L., Zelenka P.S.
Cell. Mol. Life Sci. 68:3425-3436(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS SRC KINASE.
[33]"Cdk5 mediates vimentin Ser56 phosphorylation during GTP-induced secretion by neutrophils."
Lee K.Y., Liu L., Jin Y., Fu S.B., Rosales J.L.
J. Cell. Physiol. 227:739-750(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS VIM KINASE, SUBCELLULAR LOCATION.
[34]"Glutathione-S-transferase P1 is a critical regulator of Cdk5 kinase activity."
Sun K.H., Chang K.H., Clawson S., Ghosh S., Mirzaei H., Regnier F., Shah K.
J. Neurochem. 118:902-914(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, INTERACTION WITH GSTP1.
[35]"High NaCl-induced activation of CDK5 increases phosphorylation of the osmoprotective transcription factor TonEBP/OREBP at threonine 135, which contributes to its rapid nuclear localization."
Gallazzini M., Heussler G.E., Kunin M., Izumi Y., Burg M.B., Ferraris J.D.
Mol. Biol. Cell 22:703-714(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS TONEBP/NFAT5 KINASE.
[36]"Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson's disease."
Wong A.S., Lee R.H., Cheung A.Y., Yeung P.K., Chung S.K., Cheung Z.H., Ip N.Y.
Nat. Cell Biol. 13:568-579(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS SH3GLB1 KINASE.
[37]"Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational control."
Arif A., Jia J., Moodt R.A., DiCorleto P.E., Fox P.L.
Proc. Natl. Acad. Sci. U.S.A. 108:1415-1420(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS EPRS KINASE.
[38]"A decade of CDK5."
Dhavan R., Tsai L.H.
Nat. Rev. Mol. Cell Biol. 2:749-759(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[39]"Cell cycle, CDKs and cancer: a changing paradigm."
Malumbres M., Barbacid M.
Nat. Rev. Cancer 9:153-166(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON INHIBITORS, GENE FAMILY.
[40]"Making a neuron: Cdk5 in embryonic and adult neurogenesis."
Jessberger S., Gage F.H., Eisch A.J., Lagace D.C.
Trends Neurosci. 32:575-582(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON NEURONAL PHYSIOLOGY.
[41]"Cdk5, the multifunctional surveyor."
Lalioti V., Pulido D., Sandoval I.V.
Cell Cycle 9:284-311(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[42]"Regulation and role of cyclin-dependent kinase activity in neuronal survival and death."
Hisanaga S., Endo R.
J. Neurochem. 115:1309-1321(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON REGULATION.
[43]"Nucleocytoplasmic Cdk5 is involved in neuronal cell cycle and death in post-mitotic neurons."
Zhang J., Herrup K.
Cell Cycle 10:1208-1214(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON NEURON DEVELOPMENT.
[44]"Cdk5: Mediator of neuronal development, death and the response to DNA damage."
Zhu J., Li W., Mao Z.
Mech. Ageing Dev. 132:389-394(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON NEURON DEVELOPMENT.
[45]"Cdk5: multitasking between physiological and pathological conditions."
Lopes J.P., Agostinho P.
Prog. Neurobiol. 94:49-63(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON NEURONS.
[46]"Cyclin-dependent kinase 5 (Cdk5) regulates the function of CLOCK protein by direct phosphorylation."
Kwak Y., Jeong J., Lee S., Park Y.U., Lee S.A., Han D.H., Kim J.H., Ohshima T., Mikoshiba K., Suh Y.H., Cho S., Park S.K.
J. Biol. Chem. 288:36878-36889(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CLOCK.
[47]"Structure and regulation of the CDK5-p25(nck5a) complex."
Tarricone C., Dhavan R., Peng J., Areces L.B., Tsai L.-H., Musacchio A.
Mol. Cell 8:657-669(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) IN COMPLEX WITH P25, MUTAGENESIS OF SER-159.
[48]"Defining Cdk5 ligand chemical space with small molecule inhibitors of tau phosphorylation."
Ahn J.S., Radhakrishnan M.L., Mapelli M., Choi S., Tidor B., Cuny G.D., Musacchio A., Yeh L.A., Kosik K.S.
Chem. Biol. 12:811-823(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
[49]"Mechanism of CDK5/p25 binding by CDK inhibitors."
Mapelli M., Massimiliano L., Crovace C., Seeliger M.A., Tsai L.H., Meijer L., Musacchio A.
J. Med. Chem. 48:671-679(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH INHIBITORS AND P25, PHOSPHORYLATION AT TYR-15.
[50]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] ASP-225.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X66364 mRNA. Translation: CAA47007.1.
DQ411039 mRNA. Translation: ABD66016.1.
AY049778 mRNA. Translation: AAL15435.1.
BT006680 mRNA. Translation: AAP35326.1.
AC010973 Genomic DNA. No translation available.
BC005115 mRNA. Translation: AAH05115.1.
PIRS23386.
RefSeqNP_001157882.1. NM_001164410.1.
NP_004926.1. NM_004935.3.
UniGeneHs.647078.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1H4LX-ray2.65A/B1-292[»]
1LFRmodel-A1-292[»]
1UNGX-ray2.30A/B1-292[»]
1UNHX-ray2.35A/B1-292[»]
1UNLX-ray2.20A/B1-292[»]
3O0GX-ray1.95A/B1-292[»]
4AU8X-ray1.90A/B2-292[»]
ProteinModelPortalQ00535.
SMRQ00535. Positions 1-292.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107455. 155 interactions.
DIPDIP-24221N.
IntActQ00535. 42 interactions.
MINTMINT-1037488.
STRING9606.ENSP00000297518.

Chemistry

BindingDBQ00535.
ChEMBLCHEMBL1907600.
GuidetoPHARMACOLOGY1977.

PTM databases

PhosphoSiteQ00535.

Polymorphism databases

DMDM4033704.

Proteomic databases

PaxDbQ00535.
PRIDEQ00535.

Protocols and materials databases

DNASU1020.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000297518; ENSP00000297518; ENSG00000164885. [Q00535-2]
ENST00000485972; ENSP00000419782; ENSG00000164885. [Q00535-1]
GeneID1020.
KEGGhsa:1020.
UCSCuc003wir.2. human. [Q00535-1]
uc003wis.2. human. [Q00535-2]

Organism-specific databases

CTD1020.
GeneCardsGC07M150750.
HGNCHGNC:1774. CDK5.
HPACAB008909.
HPA018977.
MIM123831. gene.
neXtProtNX_Q00535.
PharmGKBPA26310.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233024.
HOVERGENHBG014652.
InParanoidQ00535.
KOK02090.
OMATVKSFMY.
OrthoDBEOG7966H8.
PhylomeDBQ00535.
TreeFamTF101023.

Enzyme and pathway databases

BRENDA2.7.11.22. 2681.
ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_604. Hemostasis.
SignaLinkQ00535.

Gene expression databases

BgeeQ00535.
CleanExHS_CDK5.
GenevestigatorQ00535.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ00535.
GeneWikiCyclin-dependent_kinase_5.
GenomeRNAi1020.
NextBio4287.
PROQ00535.
SOURCESearch...

Entry information

Entry nameCDK5_HUMAN
AccessionPrimary (citable) accession number: Q00535
Secondary accession number(s): A1XKG3
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: December 15, 1998
Last modified: April 16, 2014
This is version 159 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM