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UniProtKB - Q00535 (CDK5_HUMAN)

Entry version 221 (17 Jun 2020)
Sequence version 3 (15 Dec 1998)
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Protein

Cyclin-dependent-like kinase 5

Gene

CDK5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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.

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>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 keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei33ATPPROSITE-ProRule annotation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei126Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi10 – 18ATPPROSITE-ProRule annotation9

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Biological rhythms, Cell cycle, Cell division, Neurogenesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...BRENDAi		2.7.11.22 2681

Reactome - a knowledgebase of biological pathways and processes

More...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

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		Q00535

SIGNOR Signaling Network Open Resource

More...SIGNORi		Q00535

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>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
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:CDK5
Synonyms:CDKN5
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 7

Organism-specific databases

Eukaryotic Pathogen Database Resources

More...EuPathDBi		HostDB:ENSG00000164885.12

Human Gene Nomenclature Database

More...HGNCi		HGNC:1774 CDK5

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		123831 gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_Q00535

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

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

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>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.
Related information in OMIM

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi159S → A: No phenotype. 1 Publication1
Mutagenesisi159S → T: Impaired p35/p25 (CDK5R1) binding. 1 Publication1

Keywords - Diseasei

Lissencephaly, Neurodegeneration

Organism-specific databases

DisGeNET

More...DisGeNETi		1020

MalaCards human disease database

More...MalaCardsi		CDK5
MIMi616342 phenotype

Open Targets

More...OpenTargetsi		ENSG00000164885

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA26310

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		Q00535 Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL4036

Drug and drug target database

More...DrugBanki		DB07364 6-PHENYL[5H]PYRROLO[2,3-B]PYRAZINE
DB04014 Alsterpaullone
DB03496 Alvocidib
DB02950 Hymenialdisine
DB02052 Indirubin-3'-monoxime
DB02116 Olomoucine
DB03428 SU9516

DrugCentral

More...DrugCentrali		Q00535

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		1977

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		CDK5

Domain mapping of disease mutations (DMDM)

More...DMDMi		4033704

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000857841 – 292Cyclin-dependent-like kinase 5Add BLAST292

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei15Phosphotyrosine; by ABL1, EPHA4 and FYN2 Publications1
Modified residuei17PhosphothreonineCombined sources1
Modified residuei56N6-acetyllysineCombined sources1
Modified residuei72PhosphoserineCombined sources1
Modified residuei159Phosphoserine1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>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

Encyclopedia of Proteome Dynamics

More...EPDi		Q00535

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		Q00535

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		Q00535

MaxQB - The MaxQuant DataBase

More...MaxQBi		Q00535

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		Q00535

PeptideAtlas

More...PeptideAtlasi		Q00535

PRoteomics IDEntifications database

More...PRIDEi		Q00535

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		57852 [Q00535-1]
57853 [Q00535-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		Q00535

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		Q00535

SwissPalm database of S-palmitoylation events

More...SwissPalmi		Q00535

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>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

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000164885 Expressed in frontal cortex and 181 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		Q00535 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		Q00535 HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000164885 Tissue enhanced (brain)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>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

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		107455, 126 interactors

ComplexPortal: manually curated resource of macromolecular complexes

More...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

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		Q00535

Database of interacting proteins

More...DIPi		DIP-24221N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...ELMi		Q00535

Protein interaction database and analysis system

More...IntActi		Q00535, 62 interactors

Molecular INTeraction database

More...MINTi		Q00535

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000419782

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		Q00535

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		Q00535 protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1292
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		Q00535

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		Q00535

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini4 – 286Protein kinasePROSITE-ProRule annotationAdd BLAST283

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

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

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG0594 Eukaryota
ENOG410XPP3 LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00940000160805

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_000288_181_1_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		Q00535

KEGG Orthology (KO)

More...KOi		K02090

Identification of Orthologs from Complete Genome Data

More...OMAi		KPNFHVY

Database for complete collections of gene phylogenies

More...PhylomeDBi		Q00535

TreeFam database of animal gene trees

More...TreeFami		TF101023

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...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

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00220 S_TKc, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF56112 SSF56112, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 2 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q00535-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i54D10495F017D527
GO
Isoform 2 (identifier: Q00535-2) [UniParc]FASTAAdd to basket
Also known as: CDK5-SV

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

Show »
Length:260
Mass (Da):29,544
Checksum:i808E46028B657622
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_041977225E → D1 PublicationCorresponds to variant dbSNP:rs35186917Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_041948105 – 136Missing in isoform 2. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...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]

Protein sequence database of the Protein Information Resource

More...PIRi		S23386

NCBI Reference Sequences

More...RefSeqi		NP_001157882.1, NM_001164410.2 [Q00535-2]
NP_004926.1, NM_004935.3 [Q00535-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000297518; ENSP00000297518; ENSG00000164885 [Q00535-2]
ENST00000485972; ENSP00000419782; ENSG00000164885 [Q00535-1]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		1020

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:1020

UCSC genome browser

More...UCSCi		uc003wir.3 human [Q00535-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>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
CCDSiCCDS47748.1 [Q00535-1]
CCDS55184.1 [Q00535-2]
PIRiS23386
RefSeqiNP_001157882.1, NM_001164410.2 [Q00535-2]
NP_004926.1, NM_004935.3 [Q00535-1]

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 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[»]
SMRiQ00535
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi107455, 126 interactors
ComplexPortaliCPX-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
CORUMiQ00535
DIPiDIP-24221N
ELMiQ00535
IntActiQ00535, 62 interactors
MINTiQ00535
STRINGi9606.ENSP00000419782

Chemistry databases

BindingDBiQ00535
ChEMBLiCHEMBL4036
DrugBankiDB07364 6-PHENYL[5H]PYRROLO[2,3-B]PYRAZINE
DB04014 Alsterpaullone
DB03496 Alvocidib
DB02950 Hymenialdisine
DB02052 Indirubin-3'-monoxime
DB02116 Olomoucine
DB03428 SU9516
DrugCentraliQ00535
GuidetoPHARMACOLOGYi1977

PTM databases

iPTMnetiQ00535
PhosphoSitePlusiQ00535
SwissPalmiQ00535

Polymorphism and mutation databases

BioMutaiCDK5
DMDMi4033704

Proteomic databases

EPDiQ00535
jPOSTiQ00535
MassIVEiQ00535
MaxQBiQ00535
PaxDbiQ00535
PeptideAtlasiQ00535
PRIDEiQ00535
ProteomicsDBi57852 [Q00535-1]
57853 [Q00535-2]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		4556 967 antibodies

The DNASU plasmid repository

More...DNASUi		1020

Genome annotation databases

EnsembliENST00000297518; ENSP00000297518; ENSG00000164885 [Q00535-2]
ENST00000485972; ENSP00000419782; ENSG00000164885 [Q00535-1]
GeneIDi1020
KEGGihsa:1020
UCSCiuc003wir.3 human [Q00535-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		1020
DisGeNETi1020
EuPathDBiHostDB:ENSG00000164885.12

GeneCards: human genes, protein and diseases

More...GeneCardsi		CDK5
HGNCiHGNC:1774 CDK5
HPAiENSG00000164885 Tissue enhanced (brain)
MalaCardsiCDK5
MIMi123831 gene
616342 phenotype
neXtProtiNX_Q00535
OpenTargetsiENSG00000164885
PharmGKBiPA26310

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG0594 Eukaryota
ENOG410XPP3 LUCA
GeneTreeiENSGT00940000160805
HOGENOMiCLU_000288_181_1_1
InParanoidiQ00535
KOiK02090
OMAiKPNFHVY
PhylomeDBiQ00535
TreeFamiTF101023

Enzyme and pathway databases

BRENDAi2.7.11.22 2681
ReactomeiR-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
SignaLinkiQ00535
SIGNORiQ00535

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		1020 6 hits in 817 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		CDK5 human
EvolutionaryTraceiQ00535

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		Cyclin-dependent_kinase_5

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		1020
PharosiQ00535 Tchem

Protein Ontology

More...PROi		PR:Q00535
RNActiQ00535 protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000164885 Expressed in frontal cortex and 181 other tissues
ExpressionAtlasiQ00535 baseline and differential
GenevisibleiQ00535 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiCDK5_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q00535
Secondary accession number(s): A1XKG3
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: December 15, 1998
Last modified: June 17, 2020
This is version 221 of the entry and version 3 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

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