CDK5_MOUSE
ID CDK5_MOUSE Reviewed; 292 AA.
AC P49615;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Cyclin-dependent kinase 5 {ECO:0000312|MGI:MGI:101765};
DE EC=2.7.11.1;
DE AltName: Full=Cell division protein kinase 5 {ECO:0000305};
DE AltName: Full=Cyclin-dependent-like kinase 5;
DE AltName: Full=Serine/threonine-protein kinase PSSALRE {ECO:0000250|UniProtKB:Q03114};
DE AltName: Full=Tau protein kinase II catalytic subunit {ECO:0000250|UniProtKB:Q02399};
DE Short=TPKII catalytic subunit {ECO:0000250|UniProtKB:Q02399};
GN Name=Cdk5 {ECO:0000312|MGI:MGI:101765};
GN Synonyms=Cdkn5 {ECO:0000312|MGI:MGI:101765},
GN Crk6 {ECO:0000312|MGI:MGI:101765}, PSSALRE {ECO:0000303|PubMed:7834371};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=7834371; DOI=10.1016/0006-8993(94)91197-5;
RA Ino H., Ishizuka T., Chiba T., Tatibana M.;
RT "Expression of CDK5 (PSSALRE kinase), a neural cdc2-related protein kinase,
RT in the mature and developing mouse central and peripheral nervous
RT systems.";
RL Brain Res. 661:196-206(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 130-165.
RC STRAIN=CBA/J; TISSUE=Bone marrow;
RX PubMed=8444355; DOI=10.1016/0378-1119(93)90411-u;
RA Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V.;
RT "Novel CDC2-related protein kinases produced in murine hematopoietic stem
RT cells.";
RL Gene 124:305-306(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-12.
RX PubMed=7490100; DOI=10.1006/geno.1995.1194;
RA Ohshima T., Nagle J.W., Pant H.C., Joshi J.B., Kozak C.A., Brady R.O.,
RA Kulkarni A.B.;
RT "Molecular cloning and chromosomal mapping of the mouse cyclin-dependent
RT kinase 5 gene.";
RL Genomics 28:585-588(1995).
RN [5]
RP IDENTIFICATION IN A TRIMOLECULAR COMPLEX WITH CABLES1 AND ABL1, INTERACTION
RP WITH CABLES1, PHOSPHORYLATION AT TYR-15, AND MUTAGENESIS OF TYR-15.
RX PubMed=10896159; DOI=10.1016/s0896-6273(00)81200-3;
RA Zukerberg L.R., Patrick G.N., Nikolic M., Humbert S., Wu C.-L.,
RA Lanier L.M., Gertler F.B., Vidal M., Van Etten R.A., Tsai L.-H.;
RT "Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation,
RT kinase upregulation, and neurite outgrowth.";
RL Neuron 26:633-646(2000).
RN [6]
RP SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND ACTIVITY REGULATION.
RX PubMed=11517264; DOI=10.1523/jneurosci.21-17-06758.2001;
RA Ko J., Humbert S., Bronson R.T., Takahashi S., Kulkarni A.B., Li E.,
RA Tsai L.H.;
RT "p35 and p39 are essential for cyclin-dependent kinase 5 function during
RT neurodevelopment.";
RL J. Neurosci. 21:6758-6771(2001).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=11226314; DOI=10.1073/pnas.051628498;
RA Ohshima T., Ogawa M., Veeranna A., Hirasawa M., Longenecker G.,
RA Ishiguro K., Pant H.C., Brady R.O., Kulkarni A.B., Mikoshiba K.;
RT "Synergistic contributions of cyclin-dependant kinase 5/p35 and Reelin/Dab1
RT to the positioning of cortical neurons in the developing mouse brain.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:2764-2769(2001).
RN [8]
RP INTERACTION WITH CABLES2.
RX PubMed=11955625; DOI=10.1016/s0167-4781(01)00367-0;
RA Sato H., Nishimoto I., Matsuoka M.;
RT "Ik3-2, a relative to ik3-1/cables, is associated with cdk3, cdk5, and c-
RT abl.";
RL Biochim. Biophys. Acta 1574:157-163(2002).
RN [9]
RP FUNCTION, AND INTERACTION WITH PTK2/FAK1.
RX PubMed=12941275; DOI=10.1016/s0092-8674(03)00605-6;
RA Xie Z., Sanada K., Samuels B.A., Shih H., Tsai L.H.;
RT "Serine 732 phosphorylation of FAK by Cdk5 is important for microtubule
RT organization, nuclear movement, and neuronal migration.";
RL Cell 114:469-482(2003).
RN [10]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=16203963; DOI=10.1073/pnas.0507678102;
RA Fu A.K.Y., Ip F.C.F., Fu W.-Y., Cheung J., Wang J.H., Yung W.-H., Ip N.Y.;
RT "Aberrant motor axon projection, acetylcholine receptor clustering, and
RT neurotransmission in cyclin-dependent kinase 5 null mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:15224-15229(2005).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [12]
RP FUNCTION IN DENDRITIC SPINE MORPHOGENESIS.
RX PubMed=17143272; DOI=10.1038/nn1811;
RA Fu W.Y., Chen Y., Sahin M., Zhao X.S., Shi L., Bikoff J.B., Lai K.O.,
RA Yung W.H., Fu A.K., Greenberg M.E., Ip N.Y.;
RT "Cdk5 regulates EphA4-mediated dendritic spine retraction through an
RT ephexin1-dependent mechanism.";
RL Nat. Neurosci. 10:67-76(2007).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [14]
RP FUNCTION AS APEX1 KINASE, AND INTERACTION WITH APEX1.
RX PubMed=20473298; DOI=10.1038/ncb2058;
RA Huang E., Qu D., Zhang Y., Venderova K., Haque M.E., Rousseaux M.W.C.,
RA Slack R.S., Woulfe J.M., Park D.S.;
RT "The role of Cdk5-mediated apurinic/apyrimidinic endonuclease 1
RT phosphorylation in neuronal death.";
RL Nat. Cell Biol. 12:563-571(2010).
RN [15]
RP DISRUPTION PHENOTYPE, AND FUNCTION IN OLIGODENDROCYTE DIFFERENTIATION.
RX PubMed=21210220; DOI=10.1007/s11064-010-0391-0;
RA He X., Takahashi S., Suzuki H., Hashikawa T., Kulkarni A.B., Mikoshiba K.,
RA Ohshima T.;
RT "Hypomyelination Phenotype caused by impaired differentiation of
RT oligodendrocytes in Emx1-cre mediated Cdk5 conditional knockout mice.";
RL Neurochem. Res. 36:1293-1303(2011).
RN [16]
RP FUNCTION, AND INTERACTION WITH CLOCK.
RX PubMed=24235147; DOI=10.1074/jbc.m113.494856;
RA Kwak Y., Jeong J., Lee S., Park Y.U., Lee S.A., Han D.H., Kim J.H.,
RA Ohshima T., Mikoshiba K., Suh Y.H., Cho S., Park S.K.;
RT "Cyclin-dependent kinase 5 (Cdk5) regulates the function of CLOCK protein
RT by direct phosphorylation.";
RL J. Biol. Chem. 288:36878-36889(2013).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-56, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [18]
RP INTERACTION WITH HTR6.
RX PubMed=25078650; DOI=10.1242/dev.108043;
RA Jacobshagen M., Niquille M., Chaumont-Dubel S., Marin P., Dayer A.;
RT "The serotonin 6 receptor controls neuronal migration during corticogenesis
RT via a ligand-independent Cdk5-dependent mechanism.";
RL Development 141:3370-3377(2014).
CC -!- FUNCTION: Proline-directed serine/threonine-protein kinase essential
CC for neuronal cell cycle arrest and differentiation and may be involved
CC in apoptotic cell death in neuronal diseases by triggering abortive
CC cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins.
CC Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1,
CC SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16,
CC RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53,
CC HDAC1, APEX1, PTK2/FAK1, huntingtin/HTT, ATM, MAP2, NEFH and NEFM.
CC Regulates several neuronal development and physiological processes
CC including neuronal survival, migration and differentiation, axonal and
CC neurite growth, synaptogenesis, oligodendrocyte differentiation,
CC synaptic plasticity and neurotransmission, by phosphorylating key
CC proteins. Negatively regulates the CACNA1B/CAV2.2 -mediated Ca(2+)
CC release probability at hippocampal neuronal soma and synaptic terminals
CC (By similarity). Activated by interaction with CDK5R1 (p35) and CDK5R2
CC (p39), especially in postmitotic neurons, and promotes CDK5R1 (p35)
CC expression in an autostimulation loop. Phosphorylates many downstream
CC substrates such as Rho and Ras family small GTPases (e.g. PAK1, RAC1,
CC RHOA, CDC42) or microtubule-binding proteins (e.g. MAPT/TAU, MAP2,
CC MAP1B), and modulates actin dynamics to regulate neurite growth and/or
CC spine morphogenesis. Phosphorylates also exocytosis associated proteins
CC such as MCAM/MUC18, SEPT5, SYN1, and CDK16/PCTAIRE1 as well as
CC endocytosis associated proteins such as DNM1, AMPH and SYNJ1 at
CC synaptic terminals. In the mature central nervous system (CNS),
CC regulates neurotransmitter movements by phosphorylating substrates
CC associated with neurotransmitter release and synapse plasticity;
CC synaptic vesicle exocytosis, vesicles fusion with the presynaptic
CC membrane, and endocytosis. Promotes cell survival by activating anti-
CC apoptotic proteins BCL2 and STAT3, and negatively regulating of
CC JNK3/MAPK10 activity. Phosphorylation of p53/TP53 in response to
CC genotoxic and oxidative stresses enhances its stabilization by
CC preventing ubiquitin ligase-mediated proteasomal degradation, and
CC induces transactivation of p53/TP53 target genes, thus regulating
CC apoptosis. Phosphorylation of p35/CDK5R1 enhances its stabilization by
CC preventing calpain-mediated proteolysis producing p25/CDK5R1 and
CC avoiding ubiquitin ligase-mediated proteasomal degradation. During
CC aberrant cell-cycle activity and DNA damage, p25/CDK5 activity elicits
CC cell-cycle activity and double-strand DNA breaks that precedes neuronal
CC death by deregulating HDAC1. DNA damage triggered phosphorylation of
CC huntingtin/HTT in nuclei of neurons protects neurons against
CC polyglutamine expansion as well as DNA damage mediated toxicity.
CC Phosphorylation of PXN reduces its interaction with PTK2/FAK1 in
CC matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs)
CC differentiation. Negative regulator of Wnt/beta-catenin signaling
CC pathway. Activator of the GAIT (IFN-gamma-activated inhibitor of
CC translation) pathway, which suppresses expression of a post-
CC transcriptional regulon of proinflammatory genes in myeloid cells;
CC phosphorylates the linker domain of glutamyl-prolyl tRNA synthetase
CC (EPRS) in a IFN-gamma-dependent manner, the initial event in assembly
CC of the GAIT complex. Phosphorylation of SH3GLB1 is required for
CC autophagy induction in starved neurons. Phosphorylation of TONEBP/NFAT5
CC in response to osmotic stress mediates its rapid nuclear localization.
CC MEF2 is inactivated by phosphorylation in nucleus in response to
CC neurotoxin, thus leading to neuronal apoptosis. APEX1 AP-
CC endodeoxyribonuclease is repressed by phosphorylation, resulting in
CC accumulation of DNA damage and contributing to neuronal death. NOS3
CC phosphorylation down regulates NOS3-derived nitrite (NO) levels. SRC
CC phosphorylation mediates its ubiquitin-dependent degradation and thus
CC leads to cytoskeletal reorganization. May regulate endothelial cell
CC migration and angiogenesis via the modulation of lamellipodia
CC formation. Involved in dendritic spine morphogenesis by mediating the
CC EFNA1-EPHA4 signaling. The complex p35/CDK5 participates in the
CC regulation of the circadian clock by modulating the function of CLOCK
CC protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates
CC the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer in
CC association with altered stability and subcellular distribution.
CC {ECO:0000250|UniProtKB:Q03114, ECO:0000269|PubMed:12941275,
CC ECO:0000269|PubMed:17143272, ECO:0000269|PubMed:20473298,
CC ECO:0000269|PubMed:21210220, ECO:0000269|PubMed:24235147}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- ACTIVITY REGULATION: Inhibited by 2-(1-ethyl-2-hydroxyethylamino)-6-
CC benzylamino-9-isopropylpurine (roscovitine), 1-isopropyl-4-aminobenzyl-
CC 6-ether-linked benzimidazoles, resveratrol, AT-7519 and olomoucine.
CC Activated by CDK5R1 (p35) and CDK5R2 (p39) during the development of
CC the nervous system; degradation of CDK5R1 (p35) and CDK5R2 (p39) by
CC proteasome result in down regulation of kinase activity, during this
CC process, CDK5 phosphorylates p35 and induces its ubiquitination and
CC subsequent degradation. Kinase activity is mainly determined by the
CC amount of p35 available and subcellular location; reversible
CC association to plasma membrane inhibits activity. Long-term
CC inactivation as well as CDK5R1 (p25)-mediated hyperactivation of CDK5
CC triggers cell death. The pro-death activity of hyperactivated CDK5 is
CC suppressed by membrane association of CDK5, via myristoylation of p35.
CC Brain-derived neurotrophic factor, glial-derived neurotrophic factor,
CC nerve growth factor (NGF), retinoic acid, laminin and neuregulin
CC promote activity. Neurotoxicity enhances nuclear activity, thus leading
CC to MEF2 phosphorylation and inhibition prior to apoptosis of cortical
CC neurons. Repression by GSTP1 via p25/p35 translocation prevents
CC neurodegeneration (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Heterodimer composed of a catalytic subunit CDK5 and a
CC regulatory subunit CDK5R1 (p25) and macromolecular complex composed of
CC at least CDK5, CDK5R1 (p35) and CDK5RAP1 or CDK5RAP2 or CDK5RAP3. Only
CC the heterodimer shows kinase activity. Under neurotoxic stress and
CC neuronal injury conditions, p35 is cleaved by calpain to generate p25
CC that hyperactivates CDK5, that becomes functionally disabled and often
CC toxic. Found in a trimolecular complex with CABLES1 and ABL1. Interacts
CC with CABLES1 and CABLES2. Interacts with AATK and GSTP1. Binds to HDAC1
CC when in complex with p25. Interaction with myristoylation p35 promotes
CC CDK5 association with membranes. Both isoforms 1 and 2 interacts with
CC beta-catenin/CTNNB1. Interacts with delta-catenin/CTNND2 and APEX1.
CC Interacts with P53/TP53 in neurons (By similarity). Interacts with
CC EPHA4; may mediate the activation of NGEF by EPHA4M. Interacts with
CC PTK2/FAK1. The complex p35/CDK5 interacts with CLOCK (By similarity).
CC Interacts with HTR6 (PubMed:25078650). {ECO:0000250,
CC ECO:0000269|PubMed:25078650}.
CC -!- INTERACTION:
CC P49615; P61809: Cdk5r1; NbExp=4; IntAct=EBI-6510052, EBI-7840438;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q00535}. Cytoplasm
CC {ECO:0000269|PubMed:11517264}. Cell membrane
CC {ECO:0000250|UniProtKB:Q00535}; Peripheral membrane protein
CC {ECO:0000250}. Perikaryon {ECO:0000250}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:11517264}. Cell projection, growth cone
CC {ECO:0000269|PubMed:11517264}. Postsynaptic density
CC {ECO:0000250|UniProtKB:Q03114}. Synapse {ECO:0000250|UniProtKB:Q03114}.
CC Note=In axonal growth cone with extension to the peripheral
CC lamellipodia. Under neurotoxic stress and neuronal injury conditions,
CC CDK5R1 (p35) is cleaved by calpain to generate CDK5R1 (p25) in response
CC to increased intracellular calcium. The elevated level of p25, when in
CC complex with CDK5, leads to its subcellular misallocation as well as
CC its hyperactivation. Colocalizes with CTNND2 in the cell body of
CC neuronal cells, and with CTNNB1 in the cell-cell contacts and plasma
CC membrane of undifferentiated and differentiated neuroblastoma cells.
CC Reversibly attached to the plasma membrane in an inactive form when
CC complexed to dephosphorylated p35 or CDK5R2 (p39), p35 phosphorylation
CC releases this attachment and activates CDK5 (By similarity).
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in postmitotic neurons and
CC postsynaptic muscle. {ECO:0000269|PubMed:16203963}.
CC -!- PTM: Phosphorylation on Tyr-15 by ABL1 and FYN, and on Ser-159 by
CC casein kinase 1 promotes kinase activity. By contrast, phosphorylation
CC at Thr-14 inhibits activity (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylation at Ser-159 is essential for maximal catalytic
CC activity. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Perinatal mortality associated with severe
CC disruption of the cytoarchitecture of the brain cortex as a result of
CC defects in neuronal migration and cohesiveness, and degenerative
CC changes in large neurons of the brain stem, such as motor neurons in
CC the lower cranial nerve nuclei and spinal cord. Disruption of
CC lamination in the cerebral cortex, hippocampus, and cerebellum.
CC Hypomyelination caused by impaired differentiation of oligodendrocytes.
CC {ECO:0000269|PubMed:11226314, ECO:0000269|PubMed:11517264,
CC ECO:0000269|PubMed:16203963, ECO:0000269|PubMed:21210220}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
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DR EMBL; D29678; BAA06148.1; -; mRNA.
DR EMBL; BC052007; AAH52007.1; -; mRNA.
DR EMBL; X64604; CAA45888.1; -; mRNA.
DR EMBL; S80121; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS51434.1; -.
DR PIR; I49592; I49592.
DR RefSeq; NP_031694.1; NM_007668.3.
DR AlphaFoldDB; P49615; -.
DR SMR; P49615; -.
DR BioGRID; 198646; 39.
DR ComplexPortal; CPX-3143; Cyclin-dependent protein kinase 5 holoenzyme complex, p35 variant.
DR ComplexPortal; CPX-3144; Cyclin-dependent protein kinase 5 holoenzyme complex, p25 variant.
DR ComplexPortal; CPX-3145; Cyclin-dependent protein kinase 5 holoenzyme complex, p39 variant.
DR CORUM; P49615; -.
DR DIP; DIP-29353N; -.
DR ELM; P49615; -.
DR IntAct; P49615; 14.
DR MINT; P49615; -.
DR STRING; 10090.ENSMUSP00000030814; -.
DR ChEMBL; CHEMBL3885555; -.
DR iPTMnet; P49615; -.
DR PhosphoSitePlus; P49615; -.
DR EPD; P49615; -.
DR jPOST; P49615; -.
DR PaxDb; P49615; -.
DR PeptideAtlas; P49615; -.
DR PRIDE; P49615; -.
DR ProteomicsDB; 281144; -.
DR Antibodypedia; 4556; 1040 antibodies from 42 providers.
DR DNASU; 12568; -.
DR Ensembl; ENSMUST00000030814; ENSMUSP00000030814; ENSMUSG00000028969.
DR GeneID; 12568; -.
DR KEGG; mmu:12568; -.
DR UCSC; uc008wrl.1; mouse.
DR CTD; 1020; -.
DR MGI; MGI:101765; Cdk5.
DR VEuPathDB; HostDB:ENSMUSG00000028969; -.
DR eggNOG; KOG0662; Eukaryota.
DR GeneTree; ENSGT00940000160805; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; P49615; -.
DR OMA; QHPWFND; -.
DR OrthoDB; 1010560at2759; -.
DR PhylomeDB; P49615; -.
DR TreeFam; TF101023; -.
DR BRENDA; 2.7.11.22; 3474.
DR Reactome; R-MMU-180024; DARPP-32 events.
DR Reactome; R-MMU-399956; CRMPs in Sema3A signaling.
DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR BioGRID-ORCS; 12568; 8 hits in 77 CRISPR screens.
DR ChiTaRS; Cdk5; mouse.
DR PRO; PR:P49615; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P49615; protein.
DR Bgee; ENSMUSG00000028969; Expressed in dentate gyrus of hippocampal formation granule cell and 255 other tissues.
DR ExpressionAtlas; P49615; baseline and differential.
DR Genevisible; P49615; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0030054; C:cell junction; ISO:MGI.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IPI:ComplexPortal.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005856; C:cytoskeleton; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0030175; C:filopodium; IDA:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0030426; C:growth cone; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:MGI.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0031594; C:neuromuscular junction; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0098794; C:postsynapse; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB.
DR GO; GO:0098793; C:presynapse; ISO:MGI.
DR GO; GO:0016533; C:protein kinase 5 complex; IPI:ComplexPortal.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISO:MGI.
DR GO; GO:0030549; F:acetylcholine receptor activator activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0008092; F:cytoskeletal protein binding; ISO:MGI.
DR GO; GO:0046875; F:ephrin receptor binding; ISO:MGI.
DR GO; GO:0005176; F:ErbB-2 class receptor binding; IDA:UniProtKB.
DR GO; GO:0043125; F:ErbB-3 class receptor binding; IDA:UniProtKB.
DR GO; GO:0051879; F:Hsp90 protein binding; IPI:ARUK-UCL.
DR GO; GO:0016301; F:kinase activity; ISS:UniProtKB.
DR GO; GO:0002039; F:p53 binding; IPI:MGI.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:MGI.
DR GO; GO:0050321; F:tau-protein kinase activity; ISS:UniProtKB.
DR GO; GO:0099635; F:voltage-gated calcium channel activity involved in positive regulation of presynaptic cytosolic calcium levels; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IDA:MGI.
DR GO; GO:0008306; P:associative learning; IMP:MGI.
DR GO; GO:0007409; P:axonogenesis; IMP:MGI.
DR GO; GO:0048148; P:behavioral response to cocaine; IMP:MGI.
DR GO; GO:0070509; P:calcium ion import; IMP:MGI.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0016477; P:cell migration; IDA:MGI.
DR GO; GO:0007160; P:cell-matrix adhesion; IDA:MGI.
DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:MGI.
DR GO; GO:0021954; P:central nervous system neuron development; IMP:MGI.
DR GO; GO:0021695; P:cerebellar cortex development; IMP:MGI.
DR GO; GO:0021697; P:cerebellar cortex formation; IMP:MGI.
DR GO; GO:0021549; P:cerebellum development; IMP:MGI.
DR GO; GO:0021987; P:cerebral cortex development; IMP:MGI.
DR GO; GO:0022038; P:corpus callosum development; IMP:MGI.
DR GO; GO:0030866; P:cortical actin cytoskeleton organization; ISO:MGI.
DR GO; GO:0048813; P:dendrite morphogenesis; IMP:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0060079; P:excitatory postsynaptic potential; IMP:MGI.
DR GO; GO:0006887; P:exocytosis; ISO:MGI.
DR GO; GO:0030900; P:forebrain development; IMP:MGI.
DR GO; GO:0021766; P:hippocampus development; IMP:MGI.
DR GO; GO:0016572; P:histone phosphorylation; ISO:MGI.
DR GO; GO:0006886; P:intracellular protein transport; IMP:MGI.
DR GO; GO:0021819; P:layer formation in cerebral cortex; IMP:MGI.
DR GO; GO:0007005; P:mitochondrion organization; ISO:MGI.
DR GO; GO:0008045; P:motor neuron axon guidance; IMP:MGI.
DR GO; GO:0030517; P:negative regulation of axon extension; IGI:MGI.
DR GO; GO:0045786; P:negative regulation of cell cycle; IMP:MGI.
DR GO; GO:1901215; P:negative regulation of neuron death; ISO:MGI.
DR GO; GO:0046826; P:negative regulation of protein export from nucleus; IMP:MGI.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IMP:MGI.
DR GO; GO:0045861; P:negative regulation of proteolysis; ISO:MGI.
DR GO; GO:0031914; P:negative regulation of synaptic plasticity; IMP:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:MGI.
DR GO; GO:0030182; P:neuron differentiation; IMP:MGI.
DR GO; GO:0001764; P:neuron migration; IMP:MGI.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISO:MGI.
DR GO; GO:0006913; P:nucleocytoplasmic transport; ISO:MGI.
DR GO; GO:0048709; P:oligodendrocyte differentiation; ISO:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:MGI.
DR GO; GO:0016310; P:phosphorylation; ISO:MGI.
DR GO; GO:0045956; P:positive regulation of calcium ion-dependent exocytosis; IDA:MGI.
DR GO; GO:0034352; P:positive regulation of glial cell apoptotic process; ISO:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:1901216; P:positive regulation of neuron death; ISO:MGI.
DR GO; GO:0099533; P:positive regulation of presynaptic cytosolic calcium concentration; ISO:MGI.
DR GO; GO:0032092; P:positive regulation of protein binding; IMP:MGI.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IMP:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; IMP:MGI.
DR GO; GO:1901387; P:positive regulation of voltage-gated calcium channel activity; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:MGI.
DR GO; GO:0035418; P:protein localization to synapse; IMP:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0032801; P:receptor catabolic process; IMP:MGI.
DR GO; GO:0043113; P:receptor clustering; IMP:MGI.
DR GO; GO:0045055; P:regulated exocytosis; ISO:MGI.
DR GO; GO:0030334; P:regulation of cell migration; IMP:MGI.
DR GO; GO:0061001; P:regulation of dendritic spine morphogenesis; IMP:UniProtKB.
DR GO; GO:0060078; P:regulation of postsynaptic membrane potential; IMP:MGI.
DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; IMP:ARUK-UCL.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISS:UniProtKB.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IMP:ARUK-UCL.
DR GO; GO:0000083; P:regulation of transcription involved in G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0042220; P:response to cocaine; IMP:MGI.
DR GO; GO:0009611; P:response to wounding; ISO:MGI.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0014044; P:Schwann cell development; IMP:MGI.
DR GO; GO:0019233; P:sensory perception of pain; IMP:MGI.
DR GO; GO:0042501; P:serine phosphorylation of STAT protein; IDA:MGI.
DR GO; GO:0007519; P:skeletal muscle tissue development; IDA:MGI.
DR GO; GO:0007416; P:synapse assembly; IMP:MGI.
DR GO; GO:0098883; P:synapse pruning; ISO:MGI.
DR GO; GO:0001963; P:synaptic transmission, dopaminergic; IMP:MGI.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IMP:MGI.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; ISO:MGI.
DR GO; GO:0048489; P:synaptic vesicle transport; IBA:GO_Central.
DR GO; GO:0021537; P:telencephalon development; IMP:MGI.
DR GO; GO:0008542; P:visual learning; IMP:MGI.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Acetylation; Apoptosis; ATP-binding; Biological rhythms; Cell cycle;
KW Cell division; Cell membrane; Cell projection; Cytoplasm; Kinase; Membrane;
KW Neurodegeneration; Neurogenesis; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Synapse; Transferase.
FT CHAIN 1..292
FT /note="Cyclin-dependent kinase 5"
FT /id="PRO_0000085785"
FT DOMAIN 4..286
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 126
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 10..18
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 33
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 15
FT /note="Phosphotyrosine; by ABL1, EPHA4 and FYN"
FT /evidence="ECO:0000269|PubMed:10896159"
FT MOD_RES 17
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q00535"
FT MOD_RES 56
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 72
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00535"
FT MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00535"
FT MUTAGEN 15
FT /note="Y->F: Loss of tyrosine phosphorylations by CABLES1
FT and ABL1; decreased activity."
FT /evidence="ECO:0000269|PubMed:10896159"
SQ SEQUENCE 292 AA; 33288 MW; 4CB11CED9017D535 CRC64;
MQKYEKLEKI GEGTYGTVFK AKNRETHEIV ALKRVRLDDD DEGVPSSALR EICLLKELKH
KNIVRLHDVL HSDKKLTLVF EFCDQDLKKY FDSCNGDLDP EIVKSFLFQL LKGLGFCHSR
NVLHRDLKPQ NLLINRNGEL KLADFGLARA FGIPVRCYSA EVVTLWYRPP DVLFGAKLYS
TSIDMWSAGC IFAELANAGR PLFPGNDVDD QLKRIFRLLG TPTEEQWPAM TKLPDYKPYP
MYPATTSLVN VVPKLNATGR DLLQNLLKCN PVQRISAEEA LQHPYFSDFC PP
