ID CDK5_HUMAN Reviewed; 292 AA. AC Q00535; A1XKG3; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 15-DEC-1998, sequence version 3. DT 28-JAN-2026, entry version 248. DE RecName: Full=Cyclin-dependent kinase 5 {ECO:0000312|HGNC:HGNC:1774}; 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|HGNC:HGNC:1774}; GN Synonyms=CDKN5 {ECO:0000312|HGNC:HGNC:1774}, PSSALRE GN {ECO:0000250|UniProtKB:P49615}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Fetal brain; RX PubMed=1639063; DOI=10.1002/j.1460-2075.1992.tb05360.x; RA Meyerson M., Enders G.H., Wu C.-L., Su L.-K., Gorka C., Nelson C., RA Harlow E., Tsai L.-H.; RT "A family of human cdc2-related protein kinases."; RL EMBO J. 11:2909-2917(1992). RN [2] RP SEQUENCE REVISION. RA Meyerson M.; RL Submitted (FEB-1993) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, INTERACTION WITH CTNNB1, AND FUNCTION IN WNT/B-CATENIN RP SIGNALING PATHWAY. RC TISSUE=Testis; RX PubMed=19693690; DOI=10.1007/s11033-009-9752-7; RA Li Q., Liu X., Zhang M., Ye G., Qiao Q., Ling Y., Wu Y., Zhang Y., Yu L.; RT "Characterization of a novel human CDK5 splicing variant that inhibits RT Wnt/beta-catenin signaling."; RL Mol. Biol. Rep. 37:2415-2421(2010). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Hu X., Xu Y., Zhang B., Peng X., Yuan J., Qiang B.; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; 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 [8] RP ACTIVITY REGULATION BY ROSCOVITINE AND OLOMOUCINE. RX PubMed=9030781; DOI=10.1111/j.1432-1033.1997.t01-2-00527.x; RA Meijer L., Borgne A., Mulner O., Chong J.P.J., Blow J.J., Inagaki N., RA Inagaki M., Delcros J.-G., Moulinoux J.-P.; RT "Biochemical and cellular effects of roscovitine, a potent and selective RT inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5."; RL Eur. J. Biochem. 243:527-536(1997). RN [9] RP FUNCTION IN AXON GROWTH. RX PubMed=9822744; DOI=10.1523/jneurosci.18-23-09858.1998; RA Paglini G., Pigino G., Kunda P., Morfini G., Maccioni R., Quiroga S., RA Ferreira A., Caceres A.; RT "Evidence for the participation of the neuron-specific CDK5 activator P35 RT during laminin-enhanced axonal growth."; RL J. Neurosci. 18:9858-9869(1998). RN [10] RP PHOSPHORYLATION AT SER-159. RX PubMed=10500146; DOI=10.1073/pnas.96.20.11156; RA Sharma P., Sharma M., Amin N.D., Albers R.W., Pant H.C.; RT "Regulation of cyclin-dependent kinase 5 catalytic activity by RT phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 96:11156-11160(1999). RN [11] RP FUNCTION AS P35/CDK5R1 KINASE. RX PubMed=12393264; DOI=10.1016/s0169-328x(02)00409-6; RA Kerokoski P., Suuronen T., Salminen A., Soininen H., Pirttilae T.; RT "Influence of phosphorylation of p35, an activator of cyclin-dependent RT kinase 5 (cdk5), on the proteolysis of p35."; RL Brain Res. Mol. Brain Res. 106:50-56(2002). RN [12] RP INTERACTION WITH AATK. RX PubMed=14521924; DOI=10.1016/j.bbrc.2003.08.143; RA Honma N., Asada A., Takeshita S., Enomoto M., Yamakawa E., Tsutsumi K., RA Saito T., Satoh T., Itoh H., Kaziro Y., Kishimoto T., Hisanaga S.; RT "Apoptosis-associated tyrosine kinase is a Cdk5 activator p35 binding RT protein."; RL Biochem. Biophys. Res. Commun. 310:398-404(2003). RN [13] RP FUNCTION AS MEF2A KINASE, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION. RX PubMed=12691662; DOI=10.1016/s0896-6273(03)00191-0; RA Gong X., Tang X., Wiedmann M., Wang X., Peng J., Zheng D., Blair L.A.C., RA Marshall J., Mao Z.; RT "Cdk5-mediated inhibition of the protective effects of transcription factor RT MEF2 in neurotoxicity-induced apoptosis."; RL Neuron 38:33-46(2003). RN [14] RP FUNCTION AS P35 KINASE, SUBCELLULAR LOCATION, AND ACTIVITY REGULATION. RX PubMed=15992363; DOI=10.1111/j.1471-4159.2005.03301.x; RA Zhu Y.-S., Saito T., Asada A., Maekawa S., Hisanaga S.; RT "Activation of latent cyclin-dependent kinase 5 (Cdk5)-p35 complexes by RT membrane dissociation."; RL J. Neurochem. 94:1535-1545(2005). RN [15] RP FUNCTION AS P35/CDK5R KINASE. RX PubMed=17121855; DOI=10.1074/jbc.m610541200; RA Kamei H., Saito T., Ozawa M., Fujita Y., Asada A., Bibb J.A., Saido T.C., RA Sorimachi H., Hisanaga S.; RT "Suppression of calpain-dependent cleavage of the CDK5 activator p35 to p25 RT by site-specific phosphorylation."; RL J. Biol. Chem. 282:1687-1694(2007). RN [16] RP FUNCTION AS CTNNB1 AND CTNND2 KINASE, INTERACTION WITH CTNNB1 AND CTNND2, RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=17009320; DOI=10.1002/jcb.21041; RA Munoz J.P., Huichalaf C.H., Orellana D., Maccioni R.B.; RT "cdk5 modulates beta- and delta-catenin/Pin1 interactions in neuronal RT cells."; RL J. Cell. Biochem. 100:738-749(2007). RN [17] RP FUNCTION AS P53/TP53 KINASE, INTERACTION WITH P53/TP53, AND SUBCELLULAR RP LOCATION. RX PubMed=17591690; DOI=10.1242/jcs.03468; RA Lee J.-H., Kim H.-S., Lee S.-J., Kim K.-T.; RT "Stabilization and activation of p53 induced by Cdk5 contributes to RT neuronal cell death."; RL J. Cell Sci. 120:2259-2271(2007). RN [18] RP FUNCTION AS PXN KINASE. RX PubMed=18042622; DOI=10.1242/jcs.018218; RA Miyamoto Y., Yamauchi J., Chan J.R., Okada A., Tomooka Y., Hisanaga S., RA Tanoue A.; RT "Cdk5 regulates differentiation of oligodendrocyte precursor cells through RT the direct phosphorylation of paxillin."; RL J. Cell Sci. 120:4355-4366(2007). RN [19] RP FUNCTION AS HUNTINGTIN KINASE, AND ACTIVITY REGULATION BY ROSCOVITINE. RX PubMed=17611284; DOI=10.1523/jneurosci.1831-07.2007; RA Anne S.L., Saudou F., Humbert S.; RT "Phosphorylation of huntingtin by cyclin-dependent kinase 5 is induced by RT DNA damage and regulates wild-type and mutant huntingtin toxicity in RT neurons."; RL J. Neurosci. 27:7318-7328(2007). RN [20] RP FUNCTION AS P35/CDK5R KINASE, INTERACTION WITH P35/CDK5R, AND SUBCELLULAR RP LOCATION. RX PubMed=17671990; DOI=10.1002/jnr.21438; RA Sato K., Zhu Y.-S., Saito T., Yotsumoto K., Asada A., Hasegawa M., RA Hisanaga S.; RT "Regulation of membrane association and kinase activity of Cdk5-p35 by RT phosphorylation of p35."; RL J. Neurosci. Res. 85:3071-3078(2007). RN [21] RP PHOSPHORYLATION AT TYR-15 BY EPHA4. 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 [22] RP SUBCELLULAR LOCATION. RX PubMed=18507738; DOI=10.1111/j.1471-4159.2008.05500.x; RA Asada A., Yamamoto N., Gohda M., Saito T., Hayashi N., Hisanaga S.; RT "Myristoylation of p39 and p35 is a determinant of cytoplasmic or nuclear RT localization of active cyclin-dependent kinase 5 complexes."; RL J. Neurochem. 106:1325-1336(2008). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [24] RP FUNCTION AS HDAC REGULATOR. RX PubMed=19081376; DOI=10.1016/j.neuron.2008.10.015; RA Kim D., Frank C.L., Dobbin M.M., Tsunemoto R.K., Tu W., Peng P.L., RA Guan J.S., Lee B.H., Moy L.Y., Giusti P., Broodie N., Mazitschek R., RA Delalle I., Haggarty S.J., Neve R.L., Lu Y., Tsai L.H.; RT "Deregulation of HDAC1 by p25/Cdk5 in neurotoxicity."; RL Neuron 60:803-817(2008). RN [25] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [27] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-56, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [28] RP FUNCTION IN ANGIOGENESIS. RX PubMed=20826806; DOI=10.1074/jbc.m110.126177; RA Liebl J., Weitensteiner S.B., Vereb G., Takacs L., Fuerst R., Vollmar A.M., RA Zahler S.; RT "Cyclin-dependent kinase 5 regulates endothelial cell migration and RT angiogenesis."; RL J. Biol. Chem. 285:35932-35943(2010). RN [29] RP FUNCTION AS NOS3 KINASE. RX PubMed=20213743; DOI=10.1002/jcb.22515; RA Lee C.-H., Wei Y.-W., Huang Y.-T., Lin Y.-T., Lee Y.-C., Lee K.-H., RA Lu P.-J.; RT "CDK5 phosphorylates eNOS at Ser-113 and regulates NO production."; RL J. Cell. Biochem. 110:112-117(2010). RN [30] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [31] RP INHIBITORS. RX PubMed=21144757; DOI=10.1016/j.bmc.2010.11.022; RA Jain P., Flaherty P.T., Yi S., Chopra I., Bleasdell G., Lipay J., RA Ferandin Y., Meijer L., Madura J.D.; RT "Design, synthesis, and testing of an 6-O-linked series of benzimidazole RT based inhibitors of CDK5/p25."; RL Bioorg. Med. Chem. 19:359-373(2011). RN [32] RP FUNCTION AS SRC KINASE. RX PubMed=21442427; DOI=10.1007/s00018-011-0638-1; RA Pan Q., Qiao F., Gao C., Norman B., Optican L., Zelenka P.S.; RT "Cdk5 targets active Src for ubiquitin-dependent degradation by RT phosphorylating Src(S75)."; RL Cell. Mol. Life Sci. 68:3425-3436(2011). RN [33] RP FUNCTION AS VIM KINASE, AND SUBCELLULAR LOCATION. RX PubMed=21465480; DOI=10.1002/jcp.22782; RA Lee K.Y., Liu L., Jin Y., Fu S.B., Rosales J.L.; RT "Cdk5 mediates vimentin Ser56 phosphorylation during GTP-induced secretion RT by neutrophils."; RL J. Cell. Physiol. 227:739-750(2012). RN [34] RP ACTIVITY REGULATION, AND INTERACTION WITH GSTP1. RX PubMed=21668448; DOI=10.1111/j.1471-4159.2011.07343.x; RA Sun K.H., Chang K.H., Clawson S., Ghosh S., Mirzaei H., Regnier F., RA Shah K.; RT "Glutathione-S-transferase P1 is a critical regulator of Cdk5 kinase RT activity."; RL J. Neurochem. 118:902-914(2011). RN [35] RP FUNCTION AS TONEBP/NFAT5 KINASE. RX PubMed=21209322; DOI=10.1091/mbc.e10-08-0681; RA Gallazzini M., Heussler G.E., Kunin M., Izumi Y., Burg M.B., Ferraris J.D.; RT "High NaCl-induced activation of CDK5 increases phosphorylation of the RT osmoprotective transcription factor TonEBP/OREBP at threonine 135, which RT contributes to its rapid nuclear localization."; RL Mol. Biol. Cell 22:703-714(2011). RN [36] RP FUNCTION AS SH3GLB1 KINASE. RX PubMed=21499257; DOI=10.1038/ncb2217; RA Wong A.S., Lee R.H., Cheung A.Y., Yeung P.K., Chung S.K., Cheung Z.H., RA Ip N.Y.; RT "Cdk5-mediated phosphorylation of endophilin B1 is required for induced RT autophagy in models of Parkinson's disease."; RL Nat. Cell Biol. 13:568-579(2011). RN [37] RP FUNCTION AS EPRS KINASE. RX PubMed=21220307; DOI=10.1073/pnas.1011275108; RA Arif A., Jia J., Moodt R.A., DiCorleto P.E., Fox P.L.; RT "Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent RT kinase 5 dictates transcript-selective translational control."; RL Proc. Natl. Acad. Sci. U.S.A. 108:1415-1420(2011). RN [38] RP REVIEW. RX PubMed=11584302; DOI=10.1038/35096019; RA Dhavan R., Tsai L.H.; RT "A decade of CDK5."; RL Nat. Rev. Mol. Cell Biol. 2:749-759(2001). RN [39] RP REVIEW ON INHIBITORS, AND GENE FAMILY. RX PubMed=19238148; DOI=10.1038/nrc2602; RA Malumbres M., Barbacid M.; RT "Cell cycle, CDKs and cancer: a changing paradigm."; RL Nat. Rev. Cancer 9:153-166(2009). RN [40] RP REVIEW ON NEURONAL PHYSIOLOGY. RX PubMed=19782409; DOI=10.1016/j.tins.2009.07.002; RA Jessberger S., Gage F.H., Eisch A.J., Lagace D.C.; RT "Making a neuron: Cdk5 in embryonic and adult neurogenesis."; RL Trends Neurosci. 32:575-582(2009). RN [41] RP FUNCTION. RX PubMed=20061803; DOI=10.4161/cc.9.2.10466; RA Lalioti V., Pulido D., Sandoval I.V.; RT "Cdk5, the multifunctional surveyor."; RL Cell Cycle 9:284-311(2010). RN [42] RP REVIEW ON REGULATION. RX PubMed=21044075; DOI=10.1111/j.1471-4159.2010.07050.x; RA Hisanaga S., Endo R.; RT "Regulation and role of cyclin-dependent kinase activity in neuronal RT survival and death."; RL J. Neurochem. 115:1309-1321(2010). RN [43] RP REVIEW ON NEURON DEVELOPMENT. RX PubMed=21415596; DOI=10.4161/cc.10.8.15328; RA Zhang J., Herrup K.; RT "Nucleocytoplasmic Cdk5 is involved in neuronal cell cycle and death in RT post-mitotic neurons."; RL Cell Cycle 10:1208-1214(2011). RN [44] RP REVIEW ON NEURON DEVELOPMENT. RX PubMed=21600237; DOI=10.1016/j.mad.2011.04.011; RA Zhu J., Li W., Mao Z.; RT "Cdk5: Mediator of neuronal development, death and the response to DNA RT damage."; RL Mech. Ageing Dev. 132:389-394(2011). RN [45] RP REVIEW ON NEURONS. RX PubMed=21473899; DOI=10.1016/j.pneurobio.2011.03.006; RA Lopes J.P., Agostinho P.; RT "Cdk5: multitasking between physiological and pathological conditions."; RL Prog. Neurobiol. 94:49-63(2011). RN [46] 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 [47] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-17, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [48] RP INVOLVEMENT IN LIS7. RX PubMed=25560765; DOI=10.1007/s00439-014-1522-5; RA Magen D., Ofir A., Berger L., Goldsher D., Eran A., Katib N., Nijem Y., RA Vlodavsky E., Tzur S., Zur S., Behar D.M., Fellig Y., Mandel H.; RT "Autosomal recessive lissencephaly with cerebellar hypoplasia is associated RT with a loss-of-function mutation in CDK5."; RL Hum. Genet. 134:305-314(2015). RN [49] RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) IN COMPLEX WITH P25, AND MUTAGENESIS RP OF SER-159. RX PubMed=11583627; DOI=10.1016/s1097-2765(01)00343-4; RA Tarricone C., Dhavan R., Peng J., Areces L.B., Tsai L.-H., Musacchio A.; RT "Structure and regulation of the CDK5-p25(nck5a) complex."; RL Mol. Cell 8:657-669(2001). RN [50] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS). RX PubMed=16039528; DOI=10.1016/j.chembiol.2005.05.011; RA Ahn J.S., Radhakrishnan M.L., Mapelli M., Choi S., Tidor B., Cuny G.D., RA Musacchio A., Yeh L.A., Kosik K.S.; RT "Defining Cdk5 ligand chemical space with small molecule inhibitors of tau RT phosphorylation."; RL Chem. Biol. 12:811-823(2005). RN [51] RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH INHIBITORS AND P25, RP AND PHOSPHORYLATION AT TYR-15. RX PubMed=15689152; DOI=10.1021/jm049323m; RA Mapelli M., Massimiliano L., Crovace C., Seeliger M.A., Tsai L.H., RA Meijer L., Musacchio A.; RT "Mechanism of CDK5/p25 binding by CDK inhibitors."; RL J. Med. Chem. 48:671-679(2005). RN [52] RP VARIANT [LARGE SCALE ANALYSIS] ASP-225. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). 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. Also phosphorylates 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-BMAL1 heterodimer in CC association with altered stability and subcellular distribution. CC {ECO:0000250|UniProtKB:Q03114, ECO:0000269|PubMed:12393264, CC ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:15992363, CC ECO:0000269|PubMed:17009320, ECO:0000269|PubMed:17121855, CC ECO:0000269|PubMed:17591690, ECO:0000269|PubMed:17611284, CC ECO:0000269|PubMed:17671990, ECO:0000269|PubMed:18042622, CC ECO:0000269|PubMed:19081376, ECO:0000269|PubMed:19693690, CC ECO:0000269|PubMed:20061803, ECO:0000269|PubMed:20213743, CC ECO:0000269|PubMed:20826806, ECO:0000269|PubMed:21209322, CC ECO:0000269|PubMed:21220307, ECO:0000269|PubMed:21442427, CC ECO:0000269|PubMed:21465480, ECO:0000269|PubMed:21499257, CC ECO:0000269|PubMed:24235147, ECO:0000269|PubMed:9822744}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); 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=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; 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. {ECO:0000269|PubMed:12691662, CC ECO:0000269|PubMed:15992363, ECO:0000269|PubMed:17611284, CC ECO:0000269|PubMed:21668448, ECO:0000269|PubMed:9030781}. 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 (By similarity). Interacts with AATK and CC GSTP1. Binds to HDAC1 when in complex with p25. Interaction with CC myristoylation p35 promotes CDK5 association with membranes. Both CC isoforms 1 and 2 interacts with beta-catenin/CTNNB1. Interacts with CC delta-catenin/CTNND2 and APEX1. Interacts with P53/TP53 in neurons. CC Interacts with EPHA4; may mediate the activation of NGEF by EPHA4. CC Interacts with PTK2/FAK1 (By similarity). The complex p35/CDK5 CC interacts with CLOCK. Interacts with HTR6 (By similarity). CC {ECO:0000250, ECO:0000250|UniProtKB:P49615, CC ECO:0000269|PubMed:11583627, ECO:0000269|PubMed:14521924, CC ECO:0000269|PubMed:15689152, ECO:0000269|PubMed:17009320, CC ECO:0000269|PubMed:17591690, ECO:0000269|PubMed:17671990, CC ECO:0000269|PubMed:19693690, ECO:0000269|PubMed:21668448, CC ECO:0000269|PubMed:24235147}. CC -!- INTERACTION: CC Q00535; P61158: ACTR3; NbExp=3; IntAct=EBI-1041567, EBI-351428; CC Q00535; P05067: APP; NbExp=3; IntAct=EBI-1041567, EBI-77613; CC Q00535; P23560-2: BDNF; NbExp=3; IntAct=EBI-1041567, EBI-12275524; CC Q00535; Q8TDN4: CABLES1; NbExp=8; IntAct=EBI-1041567, EBI-604615; CC Q00535; P14635: CCNB1; NbExp=8; IntAct=EBI-1041567, EBI-495332; CC Q00535; P24863: CCNC; NbExp=2; IntAct=EBI-1041567, EBI-395261; CC Q00535; P30279: CCND2; NbExp=18; IntAct=EBI-1041567, EBI-748789; CC Q00535; P30281: CCND3; NbExp=12; IntAct=EBI-1041567, EBI-375013; CC Q00535; Q14094: CCNI; NbExp=6; IntAct=EBI-1041567, EBI-1104653; CC Q00535; Q15078: CDK5R1; NbExp=15; IntAct=EBI-1041567, EBI-746189; CC Q00535; P38936: CDKN1A; NbExp=7; IntAct=EBI-1041567, EBI-375077; CC Q00535; P46527: CDKN1B; NbExp=14; IntAct=EBI-1041567, EBI-519280; CC Q00535; Q9UJC3: HOOK1; NbExp=3; IntAct=EBI-1041567, EBI-746704; CC Q00535; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-1041567, EBI-16439278; CC Q00535; Q9Y6R0: NUMBL; NbExp=3; IntAct=EBI-1041567, EBI-945925; CC Q00535; P37231-2: PPARG; NbExp=2; IntAct=EBI-1041567, EBI-781416; CC Q00535; P62937: PPIA; NbExp=3; IntAct=EBI-1041567, EBI-437708; CC Q00535; O60260-5: PRKN; NbExp=3; IntAct=EBI-1041567, EBI-21251460; CC Q00535; Q5MJ70: SPDYA; NbExp=3; IntAct=EBI-1041567, EBI-7125479; CC Q00535; A6NLX3: SPDYE4; NbExp=4; IntAct=EBI-1041567, EBI-12047907; CC Q00535; P20226: TBP; NbExp=3; IntAct=EBI-1041567, EBI-355371; CC Q00535; P09936: UCHL1; NbExp=2; IntAct=EBI-1041567, EBI-714860; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm CC {ECO:0000269|PubMed:12691662}. Nucleus {ECO:0000269|PubMed:12691662}. CC Cell membrane {ECO:0000269|PubMed:17009320}; Peripheral membrane CC protein. Perikaryon. Cell projection, lamellipodium CC {ECO:0000250|UniProtKB:P49615}. Cell projection, growth cone CC {ECO:0000250|UniProtKB:P49615}. 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 (By similarity). Under neurotoxic stress and neuronal CC injury conditions, CDK5R (p35) is cleaved by calpain to generate CDK5R1 CC (p25) in response to increased intracellular calcium. The elevated CC level of p25, when in complex with CDK5, leads to its subcellular CC misallocation as well as its hyperactivation. Colocalizes with CTNND2 CC in the cell body of neuronal cells, and with CTNNB1 in the cell-cell CC contacts and plasma membrane of undifferentiated and differentiated CC neuroblastoma cells. Reversibly attached to the plasma membrane in an CC inactive form when complexed to dephosphorylated p35 or CDK5R2 (p39), CC p35 phosphorylation releases this attachment and activates CDK5. CC {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q00535-1; Sequence=Displayed; CC Name=2; Synonyms=CDK5-SV {ECO:0000303|PubMed:19693690}; CC IsoId=Q00535-2; Sequence=VSP_041948; CC -!- TISSUE SPECIFICITY: [Isoform 1]: Ubiquitously expressed CC (PubMed:17009320, PubMed:19693690). Accumulates in cortical neurons (at CC protein level) (PubMed:17009320). {ECO:0000269|PubMed:17009320, CC ECO:0000269|PubMed:19693690}. CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in the testis, skeletal CC muscle, colon, bone marrow and ovary. {ECO:0000269|PubMed:19693690}. 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. {ECO:0000269|PubMed:10500146, CC ECO:0000269|PubMed:15689152, ECO:0000269|PubMed:17143272}. CC -!- PTM: Phosphorylation at Ser-159 is essential for maximal catalytic CC activity. {ECO:0000269|PubMed:10500146}. CC -!- DISEASE: Lissencephaly 7, with cerebellar hypoplasia (LIS7) CC [MIM:616342]: A form of lissencephaly, a disorder of cortical CC development characterized by agyria or pachygyria and disorganization CC of the clear neuronal lamination of normal six-layered cortex. LIS7 CC patients manifest lack of psychomotor development, facial dysmorphism, CC arthrogryposis, and early-onset intractable seizures resulting in death CC in infancy. {ECO:0000269|PubMed:25560765}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Dysregulation of CDK5 is associated with CC neurodegenerative disorders such as Alzheimer, Parkinson, and Niemann- CC Pick type C diseases, ischemia, and amyotrophic lateral sclerosis. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X66364; CAA47007.1; -; mRNA. DR EMBL; DQ411039; ABD66016.1; -; mRNA. DR EMBL; AY049778; AAL15435.1; -; mRNA. DR EMBL; BT006680; AAP35326.1; -; mRNA. DR EMBL; AC010973; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC005115; AAH05115.1; -; mRNA. DR CCDS; CCDS47748.1; -. [Q00535-1] DR CCDS; CCDS55184.1; -. [Q00535-2] DR PIR; S23386; S23386. DR RefSeq; NP_001157882.1; NM_001164410.3. [Q00535-2] DR RefSeq; NP_004926.1; NM_004935.4. [Q00535-1] DR PDB; 1H4L; X-ray; 2.65 A; A/B=1-292. DR PDB; 1UNG; X-ray; 2.30 A; A/B=1-292. DR PDB; 1UNH; X-ray; 2.35 A; A/B=1-292. DR PDB; 1UNL; X-ray; 2.20 A; A/B=1-292. DR PDB; 3O0G; X-ray; 1.95 A; A/B=1-292. DR PDB; 4AU8; X-ray; 1.90 A; A/B=2-292. DR PDB; 7VDP; X-ray; 2.09 A; A/B=2-292. DR PDB; 7VDQ; X-ray; 2.91 A; A/B=2-292. DR PDB; 7VDR; X-ray; 2.55 A; A/B=2-292. DR PDB; 7VDS; X-ray; 3.05 A; A/B=2-292. DR PDBsum; 1H4L; -. DR PDBsum; 1UNG; -. DR PDBsum; 1UNH; -. DR PDBsum; 1UNL; -. DR PDBsum; 3O0G; -. DR PDBsum; 4AU8; -. DR PDBsum; 7VDP; -. DR PDBsum; 7VDQ; -. DR PDBsum; 7VDR; -. DR PDBsum; 7VDS; -. DR AlphaFoldDB; Q00535; -. DR SMR; Q00535; -. DR BioGRID; 107455; 220. DR ComplexPortal; CPX-2201; Cyclin-dependent protein kinase 5 holoenzyme complex, p35 variant. DR ComplexPortal; CPX-3141; Cyclin-dependent protein kinase 5 holoenzyme complex, p39 variant. DR ComplexPortal; CPX-3142; Cyclin-dependent protein kinase 5 holoenzyme complex, p25 variant. DR CORUM; Q00535; -. DR DIP; DIP-24221N; -. DR ELM; Q00535; -. DR FunCoup; Q00535; 1204. DR IntAct; Q00535; 115. DR MINT; Q00535; -. DR STRING; 9606.ENSP00000419782; -. DR BindingDB; Q00535; -. DR ChEMBL; CHEMBL4036; -. DR DrugBank; DB07364; 6-PHENYL[5H]PYRROLO[2,3-B]PYRAZINE. DR DrugBank; DB04014; Alsterpaullone. DR DrugBank; DB03496; Alvocidib. DR DrugBank; DB02950; Hymenialdisine. DR DrugBank; DB02052; Indirubin-3'-monoxime. DR DrugBank; DB02116; Olomoucine. DR DrugBank; DB02733; Purvalanol. DR DrugBank; DB03428; SU9516. DR DrugBank; DB15442; Trilaciclib. DR DrugCentral; Q00535; -. DR GuidetoPHARMACOLOGY; 1977; -. DR GlyCosmos; Q00535; 4 sites, 1 glycan. DR GlyGen; Q00535; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; Q00535; -. DR PhosphoSitePlus; Q00535; -. DR SwissPalm; Q00535; -. DR BioMuta; CDK5; -. DR DMDM; 4033704; -. DR CPTAC; CPTAC-2934; -. DR jPOST; Q00535; -. DR MassIVE; Q00535; -. DR PaxDb; 9606-ENSP00000419782; -. DR PeptideAtlas; Q00535; -. DR ProteomicsDB; 57852; -. [Q00535-1] DR ProteomicsDB; 57853; -. [Q00535-2] DR Pumba; Q00535; -. DR Antibodypedia; 4556; 1032 antibodies from 44 providers. DR DNASU; 1020; -. DR Ensembl; ENST00000297518.4; ENSP00000297518.4; ENSG00000164885.14. [Q00535-2] DR Ensembl; ENST00000485972.6; ENSP00000419782.1; ENSG00000164885.14. [Q00535-1] DR GeneID; 1020; -. DR KEGG; hsa:1020; -. DR MANE-Select; ENST00000485972.6; ENSP00000419782.1; NM_004935.4; NP_004926.1. DR UCSC; uc003wir.3; human. [Q00535-1] DR AGR; HGNC:1774; -. DR CIViC; 1020; 1 evidence item across 1 molecular profile. DR ClinPGx; PA26310; -. DR CTD; 1020; -. DR DisGeNET; 1020; -. DR GeneCards; CDK5; -. DR HGNC; HGNC:1774; CDK5. DR HPA; ENSG00000164885; Tissue enhanced (brain). DR MalaCards; CDK5; -. DR MIM; 123831; gene. DR MIM; 616342; phenotype. DR OpenTargets; ENSG00000164885; -. DR VEuPathDB; HostDB:ENSG00000164885; -. DR eggNOG; KOG0662; Eukaryota. DR GeneTree; ENSGT00940000160805; -. DR HOGENOM; CLU_000288_181_1_1; -. DR InParanoid; Q00535; -. DR OMA; NWQIFVP; -. DR OrthoDB; 1732493at2759; -. DR PAN-GO; Q00535; 8 GO annotations based on evolutionary models. DR PhylomeDB; Q00535; -. DR BRENDA; 2.7.11.1; 2681. DR BRENDA; 2.7.11.22; 2681. DR PathwayCommons; Q00535; -. DR Reactome; R-HSA-180024; DARPP-32 events. DR Reactome; R-HSA-399956; CRMPs in Sema3A signaling. DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation. DR Reactome; R-HSA-8862803; Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models. DR Reactome; R-HSA-9031628; NGF-stimulated transcription. DR Reactome; R-HSA-9032845; Activated NTRK2 signals through CDK5. DR Reactome; R-HSA-9768919; NPAS4 regulates expression of target genes. DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production. DR Reactome; R-HSA-9841922; MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis. DR Reactome; R-HSA-9931529; Phosphorylation and nuclear translocation of BMAL1 (ARNTL) and CLOCK. DR Reactome; R-HSA-9931530; Phosphorylation and nuclear translocation of the CRY:PER:kinase complex. DR SignaLink; Q00535; -. DR SIGNOR; Q00535; -. DR Agora; ENSG00000164885; -. DR BioGRID-ORCS; 1020; 27 hits in 1199 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; CDK5; human. DR EvolutionaryTrace; Q00535; -. DR GeneWiki; Cyclin-dependent_kinase_5; -. DR GenomeRNAi; 1020; -. DR Pharos; Q00535; Tchem. DR PRO; PR:Q00535; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q00535; protein. DR Bgee; ENSG00000164885; Expressed in right frontal lobe and 156 other cell types or tissues. DR ExpressionAtlas; Q00535; baseline and differential. DR GO; GO:0030424; C:axon; ISS:UniProtKB. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IPI:ComplexPortal. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030425; C:dendrite; ISS:UniProtKB. DR GO; GO:0030175; C:filopodium; IEA:Ensembl. DR GO; GO:0030426; C:growth cone; ISS:UniProtKB. DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. DR GO; GO:0031594; C:neuromuscular junction; ISS:UniProtKB. DR GO; GO:0043005; C:neuron projection; ISS:ARUK-UCL. DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB. DR GO; GO:0098793; C:presynapse; IEA:GOC. DR GO; GO:0016533; C:protein kinase 5 complex; IPI:ComplexPortal. DR GO; GO:0030549; F:acetylcholine receptor activator activity; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central. DR GO; GO:0005176; F:ErbB-2 class receptor binding; ISS:UniProtKB. DR GO; GO:0043125; F:ErbB-3 class receptor binding; ISS:UniProtKB. DR GO; GO:0051879; F:Hsp90 protein binding; IEA:Ensembl. DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IPI:ARUK-UCL. DR GO; GO:0016301; F:kinase activity; ISS:UniProtKB. DR GO; GO:0002039; F:p53 binding; IEA:Ensembl. DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0030547; F:signaling receptor inhibitor activity; IMP:ARUK-UCL. DR GO; GO:0048156; F:tau protein binding; NAS:ARUK-UCL. DR GO; GO:0050321; F:tau-protein kinase activity; ISS:UniProtKB. DR GO; GO:0030036; P:actin cytoskeleton organization; TAS:UniProtKB. DR GO; GO:0048675; P:axon extension; TAS:UniProtKB. DR GO; GO:0007409; P:axonogenesis; IBA:GO_Central. DR GO; GO:0048148; P:behavioral response to cocaine; IEA:Ensembl. DR GO; GO:0070509; P:calcium ion import; IEA:Ensembl. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0007160; P:cell-matrix adhesion; IEA:Ensembl. DR GO; GO:1904646; P:cellular response to amyloid-beta; ISS:ARUK-UCL. DR GO; GO:0021954; P:central nervous system neuron development; IEA:Ensembl. DR GO; GO:0021697; P:cerebellar cortex formation; IEA:Ensembl. DR GO; GO:0007268; P:chemical synaptic transmission; TAS:UniProtKB. DR GO; GO:0022038; P:corpus callosum development; IEA:Ensembl. DR GO; GO:0048813; P:dendrite morphogenesis; IEA:Ensembl. DR GO; GO:0060079; P:excitatory postsynaptic potential; IEA:Ensembl. DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl. DR GO; GO:0006886; P:intracellular protein transport; IEA:Ensembl. DR GO; GO:0021819; P:layer formation in cerebral cortex; IEA:Ensembl. DR GO; GO:0000226; P:microtubule cytoskeleton organization; TAS:ARUK-UCL. DR GO; GO:0008045; P:motor neuron axon guidance; IEA:Ensembl. DR GO; GO:0030517; P:negative regulation of axon extension; IEA:Ensembl. DR GO; GO:1903234; P:negative regulation of calcium ion-dependent exocytosis of neurotransmitter; ISS:ARUK-UCL. DR GO; GO:0045786; P:negative regulation of cell cycle; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IMP:DFLAT. DR GO; GO:0046826; P:negative regulation of protein export from nucleus; IEA:Ensembl. DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IEA:Ensembl. DR GO; GO:0045861; P:negative regulation of proteolysis; IMP:ParkinsonsUK-UCL. DR GO; GO:0031914; P:negative regulation of synaptic plasticity; IEA:Ensembl. DR GO; GO:0051402; P:neuron apoptotic process; IBA:GO_Central. DR GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB. DR GO; GO:0001764; P:neuron migration; TAS:UniProtKB. DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB. DR GO; GO:0048709; P:oligodendrocyte differentiation; IDA:UniProtKB. DR GO; GO:0045956; P:positive regulation of calcium ion-dependent exocytosis; IEA:Ensembl. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISS:UniProtKB. DR GO; GO:0099533; P:positive regulation of presynaptic cytosolic calcium concentration; ISS:ARUK-UCL. DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; IEA:Ensembl. DR GO; GO:0035418; P:protein localization to synapse; IEA:Ensembl. DR GO; GO:0032801; P:receptor catabolic process; IEA:Ensembl. DR GO; GO:0043113; P:receptor clustering; IEA:Ensembl. DR GO; GO:0042981; P:regulation of apoptotic process; TAS:UniProtKB. DR GO; GO:0051726; P:regulation of cell cycle; TAS:UniProtKB. DR GO; GO:1901987; P:regulation of cell cycle phase transition; IBA:GO_Central. DR GO; GO:0030334; P:regulation of cell migration; IEA:Ensembl. DR GO; GO:0061001; P:regulation of dendritic spine morphogenesis; ISS:UniProtKB. DR GO; GO:0016241; P:regulation of macroautophagy; TAS:ParkinsonsUK-UCL. DR GO; GO:1903076; P:regulation of protein localization to plasma membrane; ISS:ARUK-UCL. DR GO; GO:0048167; P:regulation of synaptic plasticity; ISS:UniProtKB. DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; ISS:ARUK-UCL. DR GO; GO:1903421; P:regulation of synaptic vesicle recycling; NAS:ParkinsonsUK-UCL. DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW. DR GO; GO:0014044; P:Schwann cell development; IEA:Ensembl. DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl. DR GO; GO:0007519; P:skeletal muscle tissue development; IEA:Ensembl. DR GO; GO:0007416; P:synapse assembly; TAS:UniProtKB. DR GO; GO:0001963; P:synaptic transmission, dopaminergic; IEA:Ensembl. DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IEA:Ensembl. DR GO; GO:0048488; P:synaptic vesicle endocytosis; TAS:UniProtKB. DR GO; GO:0016079; P:synaptic vesicle exocytosis; TAS:UniProtKB. DR GO; GO:0048489; P:synaptic vesicle transport; IBA:GO_Central. DR GO; GO:0008542; P:visual learning; IEA:Ensembl. DR CDD; cd07839; STKc_CDK5; 1. DR FunFam; 3.30.200.20:FF:000144; Cyclin-dependent kinase 5; 1. DR FunFam; 1.10.510.10:FF:000184; cyclin-dependent kinase 5 homolog; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR050108; CDK. 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 PANTHER; PTHR24056; CELL DIVISION PROTEIN KINASE; 1. DR PANTHER; PTHR24056:SF46; CYCLIN-DEPENDENT KINASE 5; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding; KW Biological rhythms; Cell cycle; Cell division; Cell membrane; KW Cell projection; Cytoplasm; Kinase; Lissencephaly; Membrane; KW Neurodegeneration; Neurogenesis; Nucleotide-binding; Nucleus; KW Phosphoprotein; Proteomics identification; Reference proteome; KW Serine/threonine-protein kinase; Synapse; Transferase. FT CHAIN 1..292 FT /note="Cyclin-dependent kinase 5" FT /id="PRO_0000085784" 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:15689152, FT ECO:0000269|PubMed:17143272" FT MOD_RES 17 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 56 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 72 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195" FT MOD_RES 159 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:10500146" FT VAR_SEQ 105..136 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:19693690" FT /id="VSP_041948" FT VARIANT 225 FT /note="E -> D (in dbSNP:rs35186917)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041977" FT MUTAGEN 159 FT /note="S->A: No phenotype." FT /evidence="ECO:0000269|PubMed:11583627" FT MUTAGEN 159 FT /note="S->T: Impaired p35/p25 (CDK5R1) binding." FT /evidence="ECO:0000269|PubMed:11583627" FT STRAND 4..12 FT /evidence="ECO:0007829|PDB:4AU8" FT STRAND 14..23 FT /evidence="ECO:0007829|PDB:4AU8" FT TURN 24..26 FT /evidence="ECO:0007829|PDB:4AU8" FT STRAND 29..36 FT /evidence="ECO:0007829|PDB:4AU8" FT STRAND 40..42 FT /evidence="ECO:0007829|PDB:1UNG" FT HELIX 46..55 FT /evidence="ECO:0007829|PDB:4AU8" FT STRAND 66..70 FT /evidence="ECO:0007829|PDB:4AU8" FT STRAND 76..81 FT /evidence="ECO:0007829|PDB:4AU8" FT STRAND 84..86 FT /evidence="ECO:0007829|PDB:4AU8" FT HELIX 87..94 FT /evidence="ECO:0007829|PDB:4AU8" FT HELIX 100..119 FT /evidence="ECO:0007829|PDB:4AU8" FT HELIX 129..131 FT /evidence="ECO:0007829|PDB:4AU8" FT STRAND 132..134 FT /evidence="ECO:0007829|PDB:4AU8" FT STRAND 140..142 FT /evidence="ECO:0007829|PDB:4AU8" FT HELIX 145..147 FT /evidence="ECO:0007829|PDB:1UNG" FT HELIX 165..167 FT /evidence="ECO:0007829|PDB:4AU8" FT HELIX 170..173 FT /evidence="ECO:0007829|PDB:4AU8" FT HELIX 182..196 FT /evidence="ECO:0007829|PDB:4AU8" FT TURN 197..199 FT /evidence="ECO:0007829|PDB:4AU8" FT HELIX 208..219 FT /evidence="ECO:0007829|PDB:4AU8" FT TURN 224..226 FT /evidence="ECO:0007829|PDB:4AU8" FT HELIX 228..232 FT /evidence="ECO:0007829|PDB:4AU8" FT HELIX 248..250 FT /evidence="ECO:0007829|PDB:4AU8" FT HELIX 257..266 FT /evidence="ECO:0007829|PDB:4AU8" FT HELIX 271..273 FT /evidence="ECO:0007829|PDB:4AU8" FT HELIX 277..281 FT /evidence="ECO:0007829|PDB:4AU8" FT HELIX 284..286 FT /evidence="ECO:0007829|PDB:4AU8" FT STRAND 287..289 FT /evidence="ECO:0007829|PDB:7VDQ" SQ SEQUENCE 292 AA; 33304 MW; 54D10495F017D527 CRC64; MQKYEKLEKI GEGTYGTVFK AKNRETHEIV ALKRVRLDDD DEGVPSSALR EICLLKELKH KNIVRLHDVL HSDKKLTLVF EFCDQDLKKY FDSCNGDLDP EIVKSFLFQL LKGLGFCHSR NVLHRDLKPQ NLLINRNGEL KLADFGLARA FGIPVRCYSA EVVTLWYRPP DVLFGAKLYS TSIDMWSAGC IFAELANAGR PLFPGNDVDD QLKRIFRLLG TPTEEQWPSM TKLPDYKPYP MYPATTSLVN VVPKLNATGR DLLQNLLKCN PVQRISAEEA LQHPYFSDFC PP //