CDK5

Functionⁱ

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.21 Publications

Miscellaneous

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

Catalytic activityⁱ

ATP + a protein = ADP + a phosphoprotein.

Activity regulationⁱ

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.5 Publications

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Binding siteⁱ	33	ATPPROSITE-ProRule annotation		1
Active siteⁱ	126	Proton acceptorPROSITE-ProRule annotation		1

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Nucleotide bindingⁱ	10 – 18	ATPPROSITE-ProRule annotation		9

GO - Molecular functionⁱ

acetylcholine receptor activator activity Source: UniProtKB
ATP binding Source: UniProtKB-KW
cyclin-dependent protein serine/threonine kinase activity
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
cytoskeletal protein binding Source: Ensembl
ephrin receptor binding Source: Ensembl
ErbB-2 class receptor binding Source: UniProtKB
ErbB-3 class receptor binding Source: UniProtKB
Hsp90 protein binding Source: Ensembl
kinase activity Source: UniProtKB
p53 binding Source: Ensembl
protein kinase activity
Source: ProtInc
Traceable author statementⁱ
- 1639063
- 7834371
protein kinase binding Source: Ensembl
protein serine/threonine kinase activity
Source: UniProtKB
Inferred from direct assayⁱ
- 21145489
tau-protein kinase activity Source: UniProtKB
voltage-gated calcium channel activity involved in positive regulation of presynaptic cytosolic calcium levels Source: Ensembl

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

axon extension
Source: UniProtKB
Traceable author statementⁱ
- 21473899
axonogenesis
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
behavioral response to cocaine Source: Ensembl
calcium ion import Source: Ensembl
cell cycle Source: UniProtKB-KW
cell division Source: UniProtKB-KW
cell-matrix adhesion Source: Ensembl
cell proliferation
Source: ProtInc
Traceable author statementⁱ
- 8090221
cellular response to amyloid-beta Source: ARUK-UCL
central nervous system neuron development Source: Ensembl
cerebellar cortex formation Source: Ensembl
chemical synaptic transmission
Source: UniProtKB
Traceable author statementⁱ
- 21473899
corpus callosum development Source: Ensembl
cortical actin cytoskeleton organization Source: Ensembl
dendrite morphogenesis Source: Ensembl
excitatory postsynaptic potential Source: Ensembl
hippocampus development Source: Ensembl
intracellular protein transport Source: Ensembl
layer formation in cerebral cortex Source: Ensembl
microtubule cytoskeleton organization
Source: ARUK-UCL
Traceable author statementⁱ
- 17491008
mitochondrion organization Source: Ensembl
motor neuron axon guidance Source: Ensembl
negative regulation of axon extension Source: Ensembl
negative regulation of cell cycle Source: Ensembl
negative regulation of neuron death
Source: ParkinsonsUK-UCL
Inferred from direct assayⁱ
- 24548080
negative regulation of protein export from nucleus Source: Ensembl
negative regulation of protein ubiquitination Source: Ensembl
negative regulation of proteolysis
Source: ParkinsonsUK-UCL
Inferred from mutant phenotypeⁱ
- 24548080
negative regulation of synaptic plasticity Source: Ensembl
negative regulation of transcription, DNA-templated
Source: DFLAT
Inferred from mutant phenotypeⁱ
- 20357208
neuron apoptotic process
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
neuron differentiation Source: UniProtKB
neuron migration
Source: UniProtKB
Traceable author statementⁱ
- 21473899
neuron projection development Source: UniProtKB
nucleocytoplasmic transport Source: Ensembl
oligodendrocyte differentiation
Source: UniProtKB
Inferred from direct assayⁱ
- 18042622
peptidyl-serine phosphorylation
Source: UniProtKB
Inferred from direct assayⁱ
- 21145489
peptidyl-threonine phosphorylation Source: ARUK-UCL
phosphorylation
Source: DFLAT
Inferred from direct assayⁱ
- 20357208
positive regulation of actin cytoskeleton reorganization
Source: UniProtKB
Traceable author statementⁱ
- 21473899
positive regulation of glial cell apoptotic process Source: Ensembl
positive regulation of neuron apoptotic process Source: UniProtKB
positive regulation of protein binding Source: Ensembl
positive regulation of protein kinase activity Source: Ensembl
positive regulation of protein targeting to membrane Source: Ensembl
protein autophosphorylation Source: Ensembl
protein localization to synapse Source: Ensembl
protein phosphorylation
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
receptor catabolic process Source: Ensembl
receptor clustering Source: Ensembl
regulation of apoptotic process
Source: UniProtKB
Traceable author statementⁱ
- 21473899
regulation of cell cycle arrest
Source: UniProtKB
Traceable author statementⁱ
- 21473899
regulation of cell migration Source: Ensembl
regulation of dendritic spine morphogenesis Source: UniProtKB
regulation of macroautophagy
Source: ParkinsonsUK-UCL
Traceable author statementⁱ
- 21499257
regulation of protein localization to plasma membrane Source: ARUK-UCL
regulation of synaptic plasticity Source: UniProtKB
regulation of synaptic transmission, glutamatergic Source: ARUK-UCL
regulation of synaptic vesicle recycling
Source: ParkinsonsUK-UCL
Non-traceable author statementⁱ
- 22745285
response to wounding Source: Ensembl
rhythmic process Source: UniProtKB-KW
Schwann cell development Source: Ensembl
sensory perception of pain Source: Ensembl
serine phosphorylation of STAT protein Source: Ensembl
skeletal muscle tissue development Source: Ensembl
synapse assembly
Source: UniProtKB
Traceable author statementⁱ
- 21473899
synapse pruning Source: Ensembl
synaptic transmission, dopaminergic Source: Ensembl
synaptic transmission, glutamatergic Source: Ensembl
synaptic vesicle endocytosis
Source: UniProtKB
Traceable author statementⁱ
- 21473899
synaptic vesicle exocytosis
Source: UniProtKB
Traceable author statementⁱ
- 21473899
synaptic vesicle transport
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
visual learning Source: Ensembl

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Kinase, Serine/threonine-protein kinase, Transferase
Biological process	Apoptosis, Biological rhythms, Cell cycle, Cell division, Neurogenesis
Ligand	ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAⁱ	2.7.11.22 2681
Reactomeⁱ	R-HSA-180024 DARPP-32 events R-HSA-399956 CRMPs in Sema3A signaling R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models R-HSA-9032845 Activated NTRK2 signals through CDK5 R-HSA-983231 Factors involved in megakaryocyte development and platelet production
SignaLinkⁱ	Q00535
SIGNORⁱ	Q00535

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Cyclin-dependent-like kinase 5 (EC:2.7.11.1) 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 namesⁱ	Name:CDK5 Synonyms:CDKN5
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 7

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000164885.12
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:1774 CDK5
MIMⁱ	123831 gene
neXtProtⁱ	NX_Q00535

Keywords - Cellular componentⁱ

Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane, Nucleus, Postsynaptic cell membrane, Synapse

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Lissencephaly 7, with cerebellar hypoplasia (LIS7)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA form of lissencephaly, a disorder of cortical development characterized by agyria or pachygyria and disorganization of the clear neuronal lamination of normal six-layered cortex. LIS7 patients manifest lack of psychomotor development, facial dysmorphism, arthrogryposis, and early-onset intractable seizures resulting in death in infancy.

Mutagenesis

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Mutagenesisⁱ	159	S → A: No phenotype. 1 Publication		1
Mutagenesisⁱ	159	S → T: Impaired p35/p25 (CDK5R1) binding. 1 Publication		1

Keywords - Diseaseⁱ

Lissencephaly, Neurodegeneration

Organism-specific databases

DisGeNET More...DisGeNETⁱ	1020
MalaCards human disease database More...MalaCardsⁱ	CDK5
MIMⁱ	616342 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000164885
PharmGKBⁱ	PA26310

Chemistry databases

ChEMBLⁱ	CHEMBL4036
Drug and drug target database More...DrugBankⁱ	DB04014 Alsterpaullone DB03496 Flavopiridol DB02950 Hymenialdisine DB02052 Indirubin-3'-Monoxime DB02116 Olomoucine DB03428 SU9516
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	1977

Polymorphism and mutation databases

BioMutaⁱ	CDK5
DMDMⁱ	4033704

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000085784	1 – 292	Cyclin-dependent-like kinase 5Add BLAST		292

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	15	Phosphotyrosine; by ABL1, EPHA4 and FYN2 Publications	1
Modified residueⁱ	17	PhosphothreonineCombined sources	1
Modified residueⁱ	56	N6-acetyllysineCombined sources	1
Modified residueⁱ	72	PhosphoserineCombined sources	1
Modified residueⁱ	159	Phosphoserine1 Publication	1

Post-translational modificationⁱ

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.3 Publications

Phosphorylation at Ser-159 is essential for maximal catalytic activity.1 Publication

Keywords - PTMⁱ

Acetylation, Phosphoprotein

Proteomic databases

EPDⁱ	Q00535
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q00535
PaxDbⁱ	Q00535
PeptideAtlas More...PeptideAtlasⁱ	Q00535
PRIDEⁱ	Q00535
ProteomicsDBⁱ	57852 57853 [Q00535-2]

PTM databases

iPTMnetⁱ	Q00535
PhosphoSitePlusⁱ	Q00535
SwissPalmⁱ	Q00535

Expressionⁱ

Tissue specificityⁱ

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.2 Publications

Gene expression databases

Bgeeⁱ	ENSG00000164885 Expressed in 182 organ(s), highest expression level in frontal cortex
CleanExⁱ	HS_CDK5
ExpressionAtlasⁱ	Q00535 baseline and differential
Genevisibleⁱ	Q00535 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB008909 HPA064535

HPAⁱ

CAB008909
HPA064535

Interactionⁱ

Subunit structureⁱ

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. Interacts with HTR6 (By similarity).By similarity9 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct
CABLES1	Q8TDN4	5	EBI-1041567,EBI-604615
CCNC	P24863	2	EBI-1041567,EBI-395261
CCND2	P30279	13	EBI-1041567,EBI-748789
CCND3	P30281	4	EBI-1041567,EBI-375013
CDK5R1	Q15078	11	EBI-1041567,EBI-746189
CDKN1A	P38936	4	EBI-1041567,EBI-375077
CDKN1B	P46527	7	EBI-1041567,EBI-519280
PPARG	P37231-2	2	EBI-1041567,EBI-781416

GO - Molecular functionⁱ

cytoskeletal protein binding Source: Ensembl
ephrin receptor binding Source: Ensembl
ErbB-2 class receptor binding Source: UniProtKB
ErbB-3 class receptor binding Source: UniProtKB
Hsp90 protein binding Source: Ensembl
p53 binding Source: Ensembl
protein kinase binding Source: Ensembl

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	107455, 110 interactors
ComplexPortalⁱ	CPX-2201 Cyclin-dependent protein kinase 5 holoenzyme complex, p35 variant CPX-3141 Cyclin-dependent protein kinase 5 holoenzyme complex, p39 variant CPX-3142 Cyclin-dependent protein kinase 5 holoenzyme complex, p25 variant
CORUMⁱ	Q00535
Database of interacting proteins More...DIPⁱ	DIP-24221N
ELMⁱ	Q00535
IntActⁱ	Q00535, 53 interactors
Molecular INTeraction database More...MINTⁱ	Q00535
STRINGⁱ	9606.ENSP00000419782

Chemistry databases

BindingDBⁱ

Q00535

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	4 – 12	Combined sources	9
Beta strandⁱ	14 – 23	Combined sources	10
Turnⁱ	24 – 26	Combined sources	3
Beta strandⁱ	29 – 36	Combined sources	8
Beta strandⁱ	40 – 42	Combined sources	3
Helixⁱ	46 – 55	Combined sources	10
Beta strandⁱ	66 – 70	Combined sources	5
Beta strandⁱ	76 – 81	Combined sources	6
Beta strandⁱ	84 – 86	Combined sources	3
Helixⁱ	87 – 94	Combined sources	8
Helixⁱ	100 – 119	Combined sources	20
Helixⁱ	129 – 131	Combined sources	3
Beta strandⁱ	132 – 134	Combined sources	3
Beta strandⁱ	140 – 142	Combined sources	3
Helixⁱ	145 – 147	Combined sources	3
Helixⁱ	165 – 167	Combined sources	3
Helixⁱ	170 – 173	Combined sources	4
Helixⁱ	182 – 196	Combined sources	15
Turnⁱ	197 – 199	Combined sources	3
Helixⁱ	208 – 219	Combined sources	12
Turnⁱ	224 – 226	Combined sources	3
Helixⁱ	228 – 232	Combined sources	5
Helixⁱ	248 – 250	Combined sources	3
Helixⁱ	257 – 266	Combined sources	10
Helixⁱ	271 – 273	Combined sources	3
Helixⁱ	277 – 281	Combined sources	5
Helixⁱ	284 – 286	Combined sources	3

Show more details

3D structure databases

ProteinModelPortalⁱ	Q00535
SMRⁱ	Q00535
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	Q00535

EvolutionaryTraceⁱ

Q00535

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	4 – 286	Protein kinasePROSITE-ProRule annotationAdd BLAST		283

Sequence similaritiesⁱ

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

Phylogenomic databases

eggNOGⁱ	KOG0594 Eukaryota ENOG410XPP3 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00910000144030
HOGENOMⁱ	HOG000233024
HOVERGENⁱ	HBG014652
InParanoidⁱ	Q00535
KEGG Orthology (KO) More...KOⁱ	K02090
OMAⁱ	TVRSFMY
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0CH0
PhylomeDBⁱ	Q00535
TreeFamⁱ	TF101023

Family and domain databases

InterProⁱ	View protein in InterPro IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR017441 Protein_kinase_ATP_BS IPR008271 Ser/Thr_kinase_AS
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00069 Pkinase, 1 hit
SMARTⁱ	View protein in SMART SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF56112 SSF56112, 1 hit
PROSITEⁱ	View protein in PROSITE PS00107 PROTEIN_KINASE_ATP, 1 hit PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2)ⁱ

Sequence statusⁱ: Complete.

This entry describes 2 isoformsⁱ produced by alternative splicing. Align Add to basket

Isoform 1 (identifier: Q00535-1) [UniParc]FASTA Add to basket

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.

« Hide

        10         20         30         40         50
MQKYEKLEKI GEGTYGTVFK AKNRETHEIV ALKRVRLDDD DEGVPSSALR 
        60         70         80         90        100
EICLLKELKH KNIVRLHDVL HSDKKLTLVF EFCDQDLKKY FDSCNGDLDP 
       110        120        130        140        150
EIVKSFLFQL LKGLGFCHSR NVLHRDLKPQ NLLINRNGEL KLADFGLARA 
       160        170        180        190        200
FGIPVRCYSA EVVTLWYRPP DVLFGAKLYS TSIDMWSAGC IFAELANAGR 
       210        220        230        240        250
PLFPGNDVDD QLKRIFRLLG TPTEEQWPSM TKLPDYKPYP MYPATTSLVN 
       260        270        280        290 
VVPKLNATGR DLLQNLLKCN PVQRISAEEA LQHPYFSDFC PP

Length:292

Mass (Da):33,304

Last modified:December 15, 1998 - v3

Checksum:ⁱ54D10495F017D527

GO

Isoform 2 (identifier: Q00535-2) [UniParc]FASTA Add to basket

Also known as: CDK5-SV

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

« Hide

        10         20         30         40         50
MQKYEKLEKI GEGTYGTVFK AKNRETHEIV ALKRVRLDDD DEGVPSSALR 
        60         70         80         90        100
EICLLKELKH KNIVRLHDVL HSDKKLTLVF EFCDQDLKKY FDSCNGDLDP 
       110        120        130        140        150
EIVKNGELKL ADFGLARAFG IPVRCYSAEV VTLWYRPPDV LFGAKLYSTS 
       160        170        180        190        200
IDMWSAGCIF AELANAGRPL FPGNDVDDQL KRIFRLLGTP TEEQWPSMTK 
       210        220        230        240        250
LPDYKPYPMY PATTSLVNVV PKLNATGRDL LQNLLKCNPV QRISAEEALQ 
       260
HPYFSDFCPP

Show »

Length:260

Mass (Da):29,544

Checksum:ⁱ808E46028B657622

GO

Natural variant

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_041977	225	E → D1 PublicationCorresponds to variant dbSNP:rs35186917Ensembl.		1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_041948	105 – 136	Missing in isoform 2. 1 PublicationAdd BLAST		32

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS47748.1 [Q00535-1] CCDS55184.1 [Q00535-2]
PIRⁱ	S23386
NCBI Reference Sequences More...RefSeqⁱ	NP_001157882.1, NM_001164410.2 [Q00535-2] NP_004926.1, NM_004935.3 [Q00535-1]
UniGeneⁱ	Hs.647078

Genome annotation databases

Ensemblⁱ	ENST00000297518; ENSP00000297518; ENSG00000164885 [Q00535-2] ENST00000485972; ENSP00000419782; ENSG00000164885 [Q00535-1]
GeneIDⁱ	1020
KEGGⁱ	hsa:1020
UCSC genome browser More...UCSCⁱ	uc003wir.3 human [Q00535-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q00535	Cyclin-dependent kinase 5		HUMAN		292	UniRef100_Q00535
Cyclin dependent kinase 5		CALJA		292
CDK5 isoform 1		PANTR		292
Cyclin-dependent kinase 5 isoform 1		MACMU		292
CDK5 isoform 1		PONAB		292
+12
Q00535-2	CDK5 isoform 2		PANTR		260	UniRef100_K7C0V1
Cyclin-dependent kinase 5 isoform 2 (Fragment)		HUMAN		260
Uncharacterized protein		CALJA		260
Uncharacterized protein		COLAP		260
CDK5 isoform 2		PONAB		260
+1

Protein	Similar proteins		Species	Score	Length	Source
Q00535	Cyclin-dependent-like kinase 5		MOUSE		292	UniRef90_P49615
Cyclin-dependent-like kinase 5		BOVIN		292
Cyclin-dependent-like kinase 5		RAT		292
Cyclin-dependent-like kinase 5		XENLA		292
Cyclin-dependent kinase 5		SHEEP		292
+136
Q00535-2	Cyclin-dependent-like kinase 5		MOUSE		260	UniRef90_A0A0G2JDL3
Uncharacterized protein		FELCA		260
cyclin-dependent-like kinase 5 isoform X2		ODORO		260
cyclin-dependent-like kinase 5 isoform X2		ERIEU		260
cyclin-dependent-like kinase 5 isoform X2		Enhydra lutris kenyoni		260
+24

Protein	Similar proteins		Species	Score	Length	Source
Q00535	Cyclin-dependent-like kinase 5		MOUSE		292	UniRef50_P49615
Cyclin-dependent-like kinase 5		BOVIN		292
Cyclin-dependent-like kinase 5		RAT		292
Cyclin-dependent-like kinase 5		XENLA		292
Negative regulator of the PHO system		CANAX		326
+496
Q00535-2	Cyclin-dependent-like kinase 5		MOUSE		260	UniRef50_A0A0G2JDL3
Uncharacterized protein		FELCA		260
cyclin-dependent-like kinase 5 isoform X2		ODORO		260
cyclin-dependent-like kinase 5 isoform X2		ERIEU		260
cyclin-dependent-like kinase 5 isoform X2		Enhydra lutris kenyoni		260
+28

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	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
CCDSⁱ	CCDS47748.1 [Q00535-1] CCDS55184.1 [Q00535-2]
PIRⁱ	S23386
RefSeqⁱ	NP_001157882.1, NM_001164410.2 [Q00535-2] NP_004926.1, NM_004935.3 [Q00535-1]
UniGeneⁱ	Hs.647078

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	1H4L	X-ray	2.65	A/B	1-292	[»]
	1LFR	model	-	A	1-292	[»]
	1UNG	X-ray	2.30	A/B	1-292	[»]
	1UNH	X-ray	2.35	A/B	1-292	[»]
	1UNL	X-ray	2.20	A/B	1-292	[»]
	3O0G	X-ray	1.95	A/B	1-292	[»]
	4AU8	X-ray	1.90	A/B	2-292	[»]
ProteinModelPortalⁱ	Q00535
SMRⁱ	Q00535
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	107455, 110 interactors
ComplexPortalⁱ	CPX-2201 Cyclin-dependent protein kinase 5 holoenzyme complex, p35 variant CPX-3141 Cyclin-dependent protein kinase 5 holoenzyme complex, p39 variant CPX-3142 Cyclin-dependent protein kinase 5 holoenzyme complex, p25 variant
CORUMⁱ	Q00535
DIPⁱ	DIP-24221N
ELMⁱ	Q00535
IntActⁱ	Q00535, 53 interactors
MINTⁱ	Q00535
STRINGⁱ	9606.ENSP00000419782

Chemistry databases

BindingDBⁱ	Q00535
ChEMBLⁱ	CHEMBL4036
DrugBankⁱ	DB04014 Alsterpaullone DB03496 Flavopiridol DB02950 Hymenialdisine DB02052 Indirubin-3'-Monoxime DB02116 Olomoucine DB03428 SU9516
GuidetoPHARMACOLOGYⁱ	1977

PTM databases

iPTMnetⁱ	Q00535
PhosphoSitePlusⁱ	Q00535
SwissPalmⁱ	Q00535

Polymorphism and mutation databases

BioMutaⁱ	CDK5
DMDMⁱ	4033704

Proteomic databases

EPDⁱ	Q00535
MaxQBⁱ	Q00535
PaxDbⁱ	Q00535
PeptideAtlasⁱ	Q00535
PRIDEⁱ	Q00535
ProteomicsDBⁱ	57852 57853 [Q00535-2]

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	1020
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000297518; ENSP00000297518; ENSG00000164885 [Q00535-2] ENST00000485972; ENSP00000419782; ENSG00000164885 [Q00535-1]
GeneIDⁱ	1020
KEGGⁱ	hsa:1020
UCSCⁱ	uc003wir.3 human [Q00535-1]

Organism-specific databases

CTDⁱ	1020
DisGeNETⁱ	1020
EuPathDBⁱ	HostDB:ENSG00000164885.12
GeneCardsⁱ	CDK5
HGNCⁱ	HGNC:1774 CDK5
HPAⁱ	CAB008909 HPA064535
MalaCardsⁱ	CDK5
MIMⁱ	123831 gene 616342 phenotype
neXtProtⁱ	NX_Q00535
OpenTargetsⁱ	ENSG00000164885
PharmGKBⁱ	PA26310
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG0594 Eukaryota ENOG410XPP3 LUCA
GeneTreeⁱ	ENSGT00910000144030
HOGENOMⁱ	HOG000233024
HOVERGENⁱ	HBG014652
InParanoidⁱ	Q00535
KOⁱ	K02090
OMAⁱ	TVRSFMY
OrthoDBⁱ	EOG091G0CH0
PhylomeDBⁱ	Q00535
TreeFamⁱ	TF101023

Enzyme and pathway databases

BRENDAⁱ	2.7.11.22 2681
Reactomeⁱ	R-HSA-180024 DARPP-32 events R-HSA-399956 CRMPs in Sema3A signaling R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models R-HSA-9032845 Activated NTRK2 signals through CDK5 R-HSA-983231 Factors involved in megakaryocyte development and platelet production
SignaLinkⁱ	Q00535
SIGNORⁱ	Q00535

Miscellaneous databases

ChiTaRSⁱ	CDK5 human
EvolutionaryTraceⁱ	Q00535
GeneWikiⁱ	Cyclin-dependent_kinase_5
GenomeRNAiⁱ	1020
Protein Ontology More...PROⁱ	PR:Q00535
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000164885 Expressed in 182 organ(s), highest expression level in frontal cortex
CleanExⁱ	HS_CDK5
ExpressionAtlasⁱ	Q00535 baseline and differential
Genevisibleⁱ	Q00535 HS

Family and domain databases

InterProⁱ	View protein in InterPro IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR017441 Protein_kinase_ATP_BS IPR008271 Ser/Thr_kinase_AS
Pfamⁱ	View protein in Pfam PF00069 Pkinase, 1 hit
SMARTⁱ	View protein in SMART SM00220 S_TKc, 1 hit
SUPFAMⁱ	SSF56112 SSF56112, 1 hit
PROSITEⁱ	View protein in PROSITE PS00107 PROTEIN_KINASE_ATP, 1 hit PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	CDK5_HUMAN
Accessionⁱ	Q00535Primary (citable) accession number: Q00535 Secondary accession number(s): A1XKG3
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
	Last sequence update:	December 15, 1998
	Last modified:	November 7, 2018
	This is version 207 of the entry and version 3 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

Documents

SIMILARITY comments
Index of protein domains and families
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM
Human and mouse protein kinases
Human and mouse protein kinases: classification and index

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UniProtKB - Q00535 (CDK5_HUMAN)

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Cyclin-dependent-like kinase 5

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Keywords - PTMi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ