Summary | |
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Symbol | CDK5 |
Name | cyclin-dependent kinase 5 |
Aliases | PSSALRE; LIS7; TPKII catalytic subunit; cell division protein kinase 5; protein kinase CDK5 splicing; serine ...... |
Chromosomal Location | 7q36 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway |
Subcellular Location | Isoform 1: Cytoplasm. Cell membrane; Peripheral membrane protein. Perikaryon. Cell projection, lamellipodium Cell projection, growth cone Cell junction, synapse, postsynaptic cell membrane, postsynaptic density Note=In axonal growth cone with extension to the peripheral lamellipodia (By similarity). Under neurotoxic stress and neuronal injury conditions, CDK5R (p35) is cleaved by calpain to generate CDK5R1 (p25) in response to increased intracellular calcium. The elevated level of p25, when in complex with CDK5, leads to its subcellular misallocation as well as its hyperactivation. Colocalizes with CTNND2 in the cell body of neuronal cells, and with CTNNB1 in the cell-cell contacts and plasma membrane of undifferentiated and differentiated neuroblastoma cells. Reversibly attached to the plasma membrane in an inactive form when complexed to dephosphorylated p35 or CDK5R2 (p39), p35 phosphorylation releases this attachment and activates CDK5. ; SUBCELLULAR LOCATION: Isoform 2: Nucleus. |
Domain |
PF00069 Protein kinase domain |
Function |
Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1, huntingtin/HTT, ATM, MAP2, NEFH and NEFM. Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission, by phosphorylating key proteins. Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39), especially in post-mitotic neurons, and promotes CDK5R1 (p35) expression in an autostimulation loop. Phosphorylates many downstream substrates such as Rho and Ras family small GTPases (e.g. PAK1, RAC1, RHOA, CDC42) or microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B), and modulates actin dynamics to regulate neurite growth and/or spine morphogenesis. Phosphorylates also exocytosis associated proteins such as MCAM/MUC18, SEPT5, SYN1, and CDK16/PCTAIRE1 as well as endocytosis associated proteins such as DNM1, AMPH and SYNJ1 at synaptic terminals. In the mature central nervous system (CNS), regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity; synaptic vesicle exocytosis, vesicles fusion with the presynaptic membrane, and endocytosis. Promotes cell survival by activating anti-apoptotic proteins BCL2 and STAT3, and negatively regulating of JNK3/MAPK10 activity. Phosphorylation of p53/TP53 in response to genotoxic and oxidative stresses enhances its stabilization by preventing ubiquitin ligase-mediated proteasomal degradation, and induces transactivation of p53/TP53 target genes, thus regulating apoptosis. Phosphorylation of p35/CDK5R1 enhances its stabilization by preventing calpain-mediated proteolysis producing p25/CDK5R1 and avoiding ubiquitin ligase-mediated proteasomal degradation. During aberrant cell-cycle activity and DNA damage, p25/CDK5 activity elicits cell-cycle activity and double-strand DNA breaks that precedes neuronal death by deregulating HDAC1. DNA damage triggered phosphorylation of huntingtin/HTT in nuclei of neurons protects neurons against polyglutamine expansion as well as DNA damage mediated toxicity. Phosphorylation of PXN reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation. Negative regulator of Wnt/beta-catenin signaling pathway. Activator of the GAIT (IFN-gamma-activated inhibitor of translation) pathway, which suppresses expression of a post-transcriptional regulon of proinflammatory genes in myeloid cells; phosphorylates the linker domain of glutamyl-prolyl tRNA synthetase (EPRS) in a IFN-gamma-dependent manner, the initial event in assembly of the GAIT complex. Phosphorylation of SH3GLB1 is required for autophagy induction in starved neurons. Phosphorylation of TONEBP/NFAT5 in response to osmotic stress mediates its rapid nuclear localization. MEF2 is inactivated by phosphorylation in nucleus in response to neurotoxin, thus leading to neuronal apoptosis. APEX1 AP-endodeoxyribonuclease is repressed by phosphorylation, resulting in accumulation of DNA damage and contributing to neuronal death. NOS3 phosphorylation down regulates NOS3-derived nitrite (NO) levels. SRC phosphorylation mediates its ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. May regulate endothelial cell migration and angiogenesis via the modulation of lamellipodia formation. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer in association with altered stability and subcellular distribution. |
Biological Process |
GO:0001505 regulation of neurotransmitter levels GO:0001558 regulation of cell growth GO:0001764 neuron migration GO:0001963 synaptic transmission, dopaminergic GO:0006611 protein export from nucleus GO:0006612 protein targeting to membrane GO:0006816 calcium ion transport GO:0006836 neurotransmitter transport GO:0006887 exocytosis GO:0006898 receptor-mediated endocytosis GO:0006913 nucleocytoplasmic transport GO:0006914 autophagy GO:0007050 cell cycle arrest GO:0007160 cell-matrix adhesion GO:0007269 neurotransmitter secretion GO:0007270 neuron-neuron synaptic transmission GO:0007409 axonogenesis GO:0007411 axon guidance GO:0007416 synapse assembly GO:0007422 peripheral nervous system development GO:0007517 muscle organ development GO:0007519 skeletal muscle tissue development GO:0007611 learning or memory GO:0007612 learning GO:0007632 visual behavior GO:0008045 motor neuron axon guidance GO:0008306 associative learning GO:0008347 glial cell migration GO:0008361 regulation of cell size GO:0008542 visual learning GO:0009314 response to radiation GO:0009416 response to light stimulus GO:0010001 glial cell differentiation GO:0010469 regulation of receptor activity GO:0010506 regulation of autophagy GO:0010721 negative regulation of cell development GO:0010769 regulation of cell morphogenesis involved in differentiation GO:0010771 negative regulation of cell morphogenesis involved in differentiation GO:0010975 regulation of neuron projection development GO:0010977 negative regulation of neuron projection development GO:0014037 Schwann cell differentiation GO:0014044 Schwann cell development GO:0014706 striated muscle tissue development GO:0016049 cell growth GO:0016079 synaptic vesicle exocytosis GO:0016236 macroautophagy GO:0016241 regulation of macroautophagy GO:0016358 dendrite development GO:0017156 calcium ion regulated exocytosis GO:0017157 regulation of exocytosis GO:0017158 regulation of calcium ion-dependent exocytosis GO:0018105 peptidyl-serine phosphorylation GO:0018107 peptidyl-threonine phosphorylation GO:0018209 peptidyl-serine modification GO:0018210 peptidyl-threonine modification GO:0019233 sensory perception of pain GO:0021537 telencephalon development GO:0021543 pallium development GO:0021549 cerebellum development GO:0021575 hindbrain morphogenesis GO:0021587 cerebellum morphogenesis GO:0021695 cerebellar cortex development GO:0021696 cerebellar cortex morphogenesis GO:0021697 cerebellar cortex formation GO:0021761 limbic system development GO:0021766 hippocampus development GO:0021782 glial cell development GO:0021795 cerebral cortex cell migration GO:0021799 cerebral cortex radially oriented cell migration GO:0021801 cerebral cortex radial glia guided migration GO:0021819 layer formation in cerebral cortex GO:0021885 forebrain cell migration GO:0021953 central nervous system neuron differentiation GO:0021954 central nervous system neuron development GO:0021987 cerebral cortex development GO:0022029 telencephalon cell migration GO:0022030 telencephalon glial cell migration GO:0022037 metencephalon development GO:0022038 corpus callosum development GO:0022604 regulation of cell morphogenesis GO:0023061 signal release GO:0030308 negative regulation of cell growth GO:0030516 regulation of axon extension GO:0030517 negative regulation of axon extension GO:0030534 adult behavior GO:0030865 cortical cytoskeleton organization GO:0030866 cortical actin cytoskeleton organization GO:0030900 forebrain development GO:0030902 hindbrain development GO:0031345 negative regulation of cell projection organization GO:0031396 regulation of protein ubiquitination GO:0031397 negative regulation of protein ubiquitination GO:0031532 actin cytoskeleton reorganization GO:0031589 cell-substrate adhesion GO:0031914 negative regulation of synaptic plasticity GO:0032092 positive regulation of protein binding GO:0032386 regulation of intracellular transport GO:0032387 negative regulation of intracellular transport GO:0032388 positive regulation of intracellular transport GO:0032535 regulation of cellular component size GO:0032801 receptor catabolic process GO:0032956 regulation of actin cytoskeleton organization GO:0032970 regulation of actin filament-based process GO:0033136 serine phosphorylation of STAT3 protein GO:0033157 regulation of intracellular protein transport GO:0033674 positive regulation of kinase activity GO:0035249 synaptic transmission, glutamatergic GO:0035418 protein localization to synapse GO:0036465 synaptic vesicle recycling GO:0042063 gliogenesis GO:0042220 response to cocaine GO:0042391 regulation of membrane potential GO:0042501 serine phosphorylation of STAT protein GO:0043112 receptor metabolic process GO:0043113 receptor clustering GO:0043279 response to alkaloid GO:0043393 regulation of protein binding GO:0043523 regulation of neuron apoptotic process GO:0043525 positive regulation of neuron apoptotic process GO:0044708 single-organism behavior GO:0045055 regulated exocytosis GO:0045665 negative regulation of neuron differentiation GO:0045786 negative regulation of cell cycle GO:0045860 positive regulation of protein kinase activity GO:0045861 negative regulation of proteolysis GO:0045921 positive regulation of exocytosis GO:0045926 negative regulation of growth GO:0045956 positive regulation of calcium ion-dependent exocytosis GO:0046425 regulation of JAK-STAT cascade GO:0046777 protein autophosphorylation GO:0046822 regulation of nucleocytoplasmic transport GO:0046823 negative regulation of nucleocytoplasmic transport GO:0046825 regulation of protein export from nucleus GO:0046826 negative regulation of protein export from nucleus GO:0048148 behavioral response to cocaine GO:0048167 regulation of synaptic plasticity GO:0048488 synaptic vesicle endocytosis GO:0048489 synaptic vesicle transport GO:0048511 rhythmic process GO:0048588 developmental cell growth GO:0048638 regulation of developmental growth GO:0048640 negative regulation of developmental growth GO:0048667 cell morphogenesis involved in neuron differentiation GO:0048675 axon extension GO:0048709 oligodendrocyte differentiation GO:0048813 dendrite morphogenesis GO:0048814 regulation of dendrite morphogenesis GO:0050768 negative regulation of neurogenesis GO:0050770 regulation of axonogenesis GO:0050771 negative regulation of axonogenesis GO:0050773 regulation of dendrite development GO:0050804 modulation of synaptic transmission GO:0050808 synapse organization GO:0050890 cognition GO:0051047 positive regulation of secretion GO:0051051 negative regulation of transport GO:0051098 regulation of binding GO:0051099 positive regulation of binding GO:0051168 nuclear export GO:0051169 nuclear transport GO:0051222 positive regulation of protein transport GO:0051224 negative regulation of protein transport GO:0051402 neuron apoptotic process GO:0051493 regulation of cytoskeleton organization GO:0051495 positive regulation of cytoskeleton organization GO:0051640 organelle localization GO:0051648 vesicle localization GO:0051650 establishment of vesicle localization GO:0051656 establishment of organelle localization GO:0051668 localization within membrane GO:0051961 negative regulation of nervous system development GO:0060078 regulation of postsynaptic membrane potential GO:0060079 excitatory postsynaptic potential GO:0060537 muscle tissue development GO:0060538 skeletal muscle organ development GO:0060560 developmental growth involved in morphogenesis GO:0060627 regulation of vesicle-mediated transport GO:0060996 dendritic spine development GO:0060997 dendritic spine morphogenesis GO:0060998 regulation of dendritic spine development GO:0061001 regulation of dendritic spine morphogenesis GO:0061387 regulation of extent of cell growth GO:0061564 axon development GO:0070509 calcium ion import GO:0070838 divalent metal ion transport GO:0070997 neuron death GO:0071156 regulation of cell cycle arrest GO:0072331 signal transduction by p53 class mediator GO:0072511 divalent inorganic cation transport GO:0072583 clathrin-dependent endocytosis GO:0072657 protein localization to membrane GO:0090066 regulation of anatomical structure size GO:0090150 establishment of protein localization to membrane GO:0090313 regulation of protein targeting to membrane GO:0090314 positive regulation of protein targeting to membrane GO:0090316 positive regulation of intracellular protein transport GO:0090317 negative regulation of intracellular protein transport GO:0097061 dendritic spine organization GO:0097479 synaptic vesicle localization GO:0097480 establishment of synaptic vesicle localization GO:0097485 neuron projection guidance GO:0099003 vesicle-mediated transport in synapse GO:0099504 synaptic vesicle cycle GO:0099531 presynaptic process involved in chemical synaptic transmission GO:0099565 chemical synaptic transmission, postsynaptic GO:0099643 signal release from synapse GO:1901214 regulation of neuron death GO:1901215 negative regulation of neuron death GO:1901216 positive regulation of neuron death GO:1901796 regulation of signal transduction by p53 class mediator GO:1902803 regulation of synaptic vesicle transport GO:1903305 regulation of regulated secretory pathway GO:1903307 positive regulation of regulated secretory pathway GO:1903320 regulation of protein modification by small protein conjugation or removal GO:1903321 negative regulation of protein modification by small protein conjugation or removal GO:1903421 regulation of synaptic vesicle recycling GO:1903532 positive regulation of secretion by cell GO:1903533 regulation of protein targeting GO:1903828 negative regulation of cellular protein localization GO:1903829 positive regulation of cellular protein localization GO:1904892 regulation of STAT cascade GO:1904950 negative regulation of establishment of protein localization GO:1904951 positive regulation of establishment of protein localization GO:1990138 neuron projection extension GO:2000249 regulation of actin cytoskeleton reorganization GO:2000251 positive regulation of actin cytoskeleton reorganization GO:2000273 positive regulation of receptor activity |
Molecular Function |
GO:0002039 p53 binding GO:0004674 protein serine/threonine kinase activity GO:0004693 cyclin-dependent protein serine/threonine kinase activity GO:0005176 ErbB-2 class receptor binding GO:0030545 receptor regulator activity GO:0030546 receptor activator activity GO:0030548 acetylcholine receptor regulator activity GO:0030549 acetylcholine receptor activator activity GO:0043125 ErbB-3 class receptor binding GO:0046875 ephrin receptor binding GO:0050321 tau-protein kinase activity GO:0097472 cyclin-dependent protein kinase activity GO:0099602 neurotransmitter receptor regulator activity |
Cellular Component |
GO:0014069 postsynaptic density GO:0016533 cyclin-dependent protein kinase 5 holoenzyme complex GO:0030027 lamellipodium GO:0030175 filopodium GO:0030424 axon GO:0030425 dendrite GO:0030426 growth cone GO:0030427 site of polarized growth GO:0031252 cell leading edge GO:0031594 neuromuscular junction GO:0043025 neuronal cell body GO:0043204 perikaryon GO:0044297 cell body GO:0045211 postsynaptic membrane GO:0060076 excitatory synapse GO:0097060 synaptic membrane GO:0098793 presynapse GO:0098794 postsynapse GO:0098858 actin-based cell projection GO:0099572 postsynaptic specialization |
KEGG |
hsa04360 Axon guidance |
Reactome |
R-HSA-422475: Axon guidance R-HSA-399956: CRMPs in Sema3A signaling R-HSA-180024: DARPP-32 events R-HSA-8862803: Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models R-HSA-1266738: Developmental Biology R-HSA-1643685: Disease R-HSA-983231: Factors involved in megakaryocyte development and platelet production R-HSA-74160: Gene Expression R-HSA-212436: Generic Transcription Pathway R-HSA-109582: Hemostasis R-HSA-8863678: Neurodegenerative Diseases R-HSA-111885: Opioid Signalling R-HSA-5633007: Regulation of TP53 Activity R-HSA-6804756: Regulation of TP53 Activity through Phosphorylation R-HSA-373755: Semaphorin interactions R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR R-HSA-3700989: Transcriptional Regulation by TP53 |
Summary | |
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Symbol | CDK5 |
Name | cyclin-dependent kinase 5 |
Aliases | PSSALRE; LIS7; TPKII catalytic subunit; cell division protein kinase 5; protein kinase CDK5 splicing; serine ...... |
Chromosomal Location | 7q36 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Literatures that report relations between CDK5 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells. |
Literatures describing the relation between CDK5 and anti-tumor immunity in human cancer.
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Summary | |
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Symbol | CDK5 |
Name | cyclin-dependent kinase 5 |
Aliases | PSSALRE; LIS7; TPKII catalytic subunit; cell division protein kinase 5; protein kinase CDK5 splicing; serine ...... |
Chromosomal Location | 7q36 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets. |
> High-throughput Screening
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Statistical results of CDK5 in screening data sets for detecting immune reponses.
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Summary | |
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Symbol | CDK5 |
Name | cyclin-dependent kinase 5 |
Aliases | PSSALRE; LIS7; TPKII catalytic subunit; cell division protein kinase 5; protein kinase CDK5 splicing; serine ...... |
Chromosomal Location | 7q36 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders |
Points in the above scatter plot represent the expression difference of CDK5 in various data sets.
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Points in the above scatter plot represent the mutation difference of CDK5 in various data sets.
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Summary | |
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Symbol | CDK5 |
Name | cyclin-dependent kinase 5 |
Aliases | PSSALRE; LIS7; TPKII catalytic subunit; cell division protein kinase 5; protein kinase CDK5 splicing; serine ...... |
Chromosomal Location | 7q36 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CDK5. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene. |
Summary | |
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Symbol | CDK5 |
Name | cyclin-dependent kinase 5 |
Aliases | PSSALRE; LIS7; TPKII catalytic subunit; cell division protein kinase 5; protein kinase CDK5 splicing; serine ...... |
Chromosomal Location | 7q36 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CDK5. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CDK5. > Immunoinhibitor > Immunostimulator > MHC molecule |
Summary | |
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Symbol | CDK5 |
Name | cyclin-dependent kinase 5 |
Aliases | PSSALRE; LIS7; TPKII catalytic subunit; cell division protein kinase 5; protein kinase CDK5 splicing; serine ...... |
Chromosomal Location | 7q36 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CDK5. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor |
Summary | |
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Symbol | CDK5 |
Name | cyclin-dependent kinase 5 |
Aliases | PSSALRE; LIS7; TPKII catalytic subunit; cell division protein kinase 5; protein kinase CDK5 splicing; serine ...... |
Chromosomal Location | 7q36 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Distribution of CDK5 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype |
Summary | |
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Symbol | CDK5 |
Name | cyclin-dependent kinase 5 |
Aliases | PSSALRE; LIS7; TPKII catalytic subunit; cell division protein kinase 5; protein kinase CDK5 splicing; serine ...... |
Chromosomal Location | 7q36 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Associations between CDK5 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade |
Summary | |
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Symbol | CDK5 |
Name | cyclin-dependent kinase 5 |
Aliases | PSSALRE; LIS7; TPKII catalytic subunit; cell division protein kinase 5; protein kinase CDK5 splicing; serine ...... |
Chromosomal Location | 7q36 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Drugs targeting CDK5 collected from DrugBank database. |
Details on drugs targeting CDK5.
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