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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

CDK5 Gene

protein-coding GIFtS: 74
GCID: GC07M150750

Cyclin-Dependent Kinase 5

Alzheimer's & Parkinson's Diseases Congress

57 related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
About This Section

Aliases
Cyclin-Dependent Kinase 5¹ ²		EC 2.7.11.22³ ⁸
Cell Division Protein Kinase 5² ³		PSSALRE²
Serine/Threonine-Protein Kinase PSSALRE² ³		Protein Kinase CDK5 Splicing²
Tau Protein Kinase II Catalytic Subunit² ³		CDKN5³
TPKII Catalytic Subunit² ³		EC 2.7.11⁸

External Ids:	HGNC: 1774¹	Entrez Gene: 1020²	Ensembl: ENSG00000164885⁷	OMIM: 123831⁵	UniProtKB: Q00535³

Export aliases for CDK5 gene to outside databases

Previous GC identifers: GC07M148997 GC07M150065 GC07M150142 GC07M150188 GC07M150381 GC07M144563

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

GeneCards Summary for CDK5 Gene:

CDK5 (cyclin-dependent kinase 5) is a protein-coding gene. Diseases associated with CDK5 include aneurysmal bone cysts, and tauopathy, and among its related super-pathways are Development Slit-Robo signaling and Parkinson's disease. GO annotations related to this gene include protein serine/threonine kinase activity and p53 binding. An important paralog of this gene is CDK18.

UniProtKB/Swiss-Prot: CDK5_HUMAN, Q00535

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

summary for CDK5 Gene:

Cdks (cyclin-dependent kinases) are heteromeric serine/threonine kinases that control progression through

the cell cycle in concert with their regulatory subunits, the cyclins. Although there are 12 different cdk

genes, only 5 have been shown to directly drive the cell cycle (Cdk1, -2, -3, -4, and -6). Following

extracellular mitogenic stimuli, cyclin D gene expression is upregulated. Cdk4 forms a complex with cyclin D

and phosphorylates Rb protein, leading to liberation of the transcription factor E2F. E2F induces

transcription of genes including cyclins A and E, DNA polymerase and thymidine kinase. Cdk4-cyclin E

complexes form and initiate G1/S transition. Subsequently, Cdk1-cyclin B complexes form and induce G2/M

phase transition. Cdk1-cyclin B activation induces the breakdown of the nuclear envelope and the initiation

of mitosis. Cdks are constitutively expressed and are regulated by several kinases and phosphastases,

including Wee1, CDK-activating kinase and Cdc25 phosphatase. In addition, cyclin expression is induced by

molecular signals at specific points of the cell cycle, leading to activation of Cdks. Tight control of Cdks

is essential as misregulation can induce unscheduled proliferation, and genomic and chromosomal instability.

Cdk4 has been shown to be mutated in some types of cancer, whilst a chromosomal rearrangement can lead to

Cdk6 overexpression in lymphoma, leukemia and melanoma. Cdks are currently under investigation as potential

targets for antineoplastic therapy, but as Cdks are essential for driving each cell cycle phase, therapeutic

strategies that block Cdk activity are unlikely to selectively target tumor cells.

Gene Wiki entry for CDK5 (Cyclin-dependent kinase 5) Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000007.13 NC_018918.2 NT_007914.15 NT_079596.2

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the CDK5 gene promoter:
p53 p300 C/EBPalpha PPAR-gamma1 E2F-1 E2F HOXA5 PPAR-gamma2 RSRFC4
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): CDK5 promoter sequence

Search SABiosciences Chromatin IP Primers for CDK5

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat CDK5

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 7q36 Ensembl cytogenetic band: 7q36.1 HGNC cytogenetic band: 7q36

CDK5 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CDK5 gene location

GeneLoc information about chromosome 7 GeneLoc Exon Structure

GeneLoc location for GC07M150750: view genomic region (about GC identifiers)

Start:	150,750,899 bp from pter	End:	150,755,617 bp from pter
Size:	4,719 bases	Orientation:	minus strand

1 alternative location:

Chr7-,CRA_TCAG 150,080,438-150,084,591

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MAXQB RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

UniProtKB/Swiss-Prot: CDK5_HUMAN, Q00535 (See protein sequence)

Recommended Name: Cyclin-dependent kinase 5

Size: 292 amino acids; 33304 Da

Subunit: 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)

Subcellular location: Isoform 1: Cytoplasm. Cell membrane; Peripheral membrane protein. Perikaryon. Cell

projection, lamellipodium (By similarity). Cell projection, growth cone (By similarity). Cell junction, synapse,

postsynaptic cell membrane, postsynaptic 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.

Co-localizes 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

Subcellular location: Isoform 2: Nucleus

Miscellaneous: Dysregulation of CDK5 is associated with neurodegenerative disorders such as Alzheimer, Parkinson,

and Niemann-Pick type C diseases, ischemia, and amyotrophic lateral sclerosis

6/7 PDB 3D structures from and Proteopedia for CDK5 (see all 7):

1H4L (3D)

1LFR (3D)

1UNG (3D)

1UNH (3D)

1UNL (3D)

3O0G (3D)

Secondary accessions: A1XKG3

Alternative splicing: 2 isoforms: Q00535-1 Q00535-2

Explore the universe of human proteins at neXtProt for CDK5: NX_Q00535

Explore proteomics data for CDK5 at MOPED

Post-translational modifications:

UniProtKB: 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

UniProtKB: Phosphorylation at Ser-159 is essential for maximal catalytic activity

View modification sites using PhosphoSitePlus

View neXtProt modification sites for NX_Q00535

4/20 DME Specific Peptides for CDK5 (Q00535) (see all 20)

WSAGCIF

LGTPTEE

VVTLWYR

LVFEFCD

CDK5 Protein expression data from MOPED¹, PaxDb² and MAXQB³ : About this image

REFSEQ proteins (2 alternative transcripts):

NP_001157882.1 NP_004926.1

ENSEMBL proteins:

ENSP00000419782 ENSP00000297518

Reactome Protein details: Q00535
Human Recombinant Protein Products for CDK5:

	EMD Millipore Purified and/or Recombinant CDK5 Protein
	Browse R&D Systems for human recombinant proteins
	Enzo Life Sciences proteins for CDK5
	OriGene Purified Protein for CDK5 OriGene Protein Over-expression Lysate for CDK5 OriGene MassSpec for CDK5 OriGene Custom Protein Services for CDK5
	GenScript Custom Purified and Recombinant Proteins Services for CDK5
	Novus Biologicals CDK5 Proteins Novus Biologicals CDK5 Lysates
	Sino Biological Recombinant Protein for CDK5 Browse Sino Biological Cell Lysates
	ProSpec Recombinant Protein for CDK5
	Cloud-Clone Corp. Proteins for CDK5

Gene Ontology (GO): 5/19 cellular component terms (GO ID links to tree view) (see all 19): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	ISS	--
GO:0005737	cytoplasm	ISS	--
GO:0005829	cytosol	TAS	--
GO:0005856	cytoskeleton	--	--
GO:0005886	plasma membrane	IEA	--

CDK5 for ontologies About GeneDecksing

CDK5 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of CDK5
	Browse R&D Systems for Antibodies
	Cell Signaling Technology (CST) Antibodies for CDK5
	OriGene Antibodies for CDK5 OriGene Custom Antibody Services for CDK5
	GenScript Superior Antibodies for CDK5
	Novus Biologicals CDK5 Antibodies
	Abcam antibodies for CDK5
	Cloud-Clone Corp. Antibodies for CDK5
	ThermoFisher Antibody for CDK5
	LSBio Antibodies in human, mouse, rat for CDK5

Assay Products for CDK5:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Assay Services for CDK5
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for CDK5
	Browse Enzo Life Sciences for kits & assays
	Cloud-Clone Corp. ELISAs for CDK5 Cloud-Clone Corp. CLIAs for CDK5

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

HGNC Gene Families:

CDK: Cyclin-dependent kinases

IUPHAR Guide to PHARMACOLOGY protein family classification: cyclin-dependent kinase 5

CDK5 subfamily

5 InterPro protein domains:

IPR017441 Protein_kinase_ATP_BS

IPR002290 Ser/Thr_dual-sp_kinase_dom

IPR011009 Kinase-like_dom

IPR008271 Ser/Thr_kinase_AS

IPR000719 Prot_kinase_cat_dom

Graphical View of Domain Structure for InterPro Entry Q00535

ProtoNet protein and cluster: Q00535

UniProtKB/Swiss-Prot: CDK5_HUMAN, Q00535

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

Similarity: Contains 1 protein kinase domain

CDK5 for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: CDK5_HUMAN, Q00535