CDK5_HUMAN
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 03-AUG-2022, entry version 231.
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},
GN PSSALRE {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. 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: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=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. {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=7; IntAct=EBI-1041567, EBI-604615;
CC Q00535; P24863: CCNC; NbExp=2; IntAct=EBI-1041567, EBI-395261;
CC Q00535; P30279: CCND2; NbExp=16; IntAct=EBI-1041567, EBI-748789;
CC Q00535; P30281: CCND3; NbExp=8; IntAct=EBI-1041567, EBI-375013;
CC Q00535; Q14094: CCNI; NbExp=4; IntAct=EBI-1041567, EBI-1104653;
CC Q00535; Q15078: CDK5R1; NbExp=13; IntAct=EBI-1041567, EBI-746189;
CC Q00535; P38936: CDKN1A; NbExp=5; IntAct=EBI-1041567, EBI-375077;
CC Q00535; P46527: CDKN1B; NbExp=9; 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}.
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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_001164410.2. [Q00535-2]
DR RefSeq; NP_004926.1; NM_004935.3. [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; 176.
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 IntAct; Q00535; 80.
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; DB03428; SU9516.
DR DrugBank; DB15442; Trilaciclib.
DR DrugCentral; Q00535; -.
DR GuidetoPHARMACOLOGY; 1977; -.
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 EPD; Q00535; -.
DR jPOST; Q00535; -.
DR MassIVE; Q00535; -.
DR MaxQB; Q00535; -.
DR PaxDb; Q00535; -.
DR PeptideAtlas; Q00535; -.
DR PRIDE; Q00535; -.
DR ProteomicsDB; 57852; -. [Q00535-1]
DR ProteomicsDB; 57853; -. [Q00535-2]
DR Antibodypedia; 4556; 1040 antibodies from 42 providers.
DR DNASU; 1020; -.
DR Ensembl; ENST00000297518.4; ENSP00000297518.4; ENSG00000164885.13. [Q00535-2]
DR Ensembl; ENST00000485972.6; ENSP00000419782.1; ENSG00000164885.13. [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 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 neXtProt; NX_Q00535; -.
DR OpenTargets; ENSG00000164885; -.
DR PharmGKB; PA26310; -.
DR VEuPathDB; HostDB:ENSG00000164885; -.
DR eggNOG; KOG0662; Eukaryota.
DR GeneTree; ENSGT00940000160805; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; Q00535; -.
DR OMA; QHPWFND; -.
DR PhylomeDB; Q00535; -.
DR TreeFam; TF101023; -.
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-983231; Factors involved in megakaryocyte development and platelet production.
DR SignaLink; Q00535; -.
DR SIGNOR; Q00535; -.
DR BioGRID-ORCS; 1020; 25 hits in 1121 CRISPR screens.
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 154 other tissues.
DR ExpressionAtlas; Q00535; baseline and differential.
DR Genevisible; Q00535; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
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:0098978; C:glutamatergic synapse; 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:0005874; C:microtubule; IEA:Ensembl.
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:Ensembl.
DR GO; GO:0016533; C:protein kinase 5 complex; IPI:ComplexPortal.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl.
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:0046875; F:ephrin receptor binding; IEA:Ensembl.
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: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:0019901; F:protein kinase binding; IEA:Ensembl.
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:0048156; F:tau protein binding; NAS:ARUK-UCL.
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; IEA:Ensembl.
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:0030866; P:cortical actin cytoskeleton organization; 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:0016572; P:histone phosphorylation; 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:0007005; P:mitochondrion organization; IEA:Ensembl.
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:0045786; P:negative regulation of cell cycle; IEA:Ensembl.
DR GO; GO:1901215; P:negative regulation of neuron death; IDA:ParkinsonsUK-UCL.
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:0045892; P:negative regulation of transcription, DNA-templated; IMP:DFLAT.
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:0006913; P:nucleocytoplasmic transport; IEA:Ensembl.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:ARUK-UCL.
DR GO; GO:0016310; P:phosphorylation; IDA:DFLAT.
DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; TAS:UniProtKB.
DR GO; GO:0045956; P:positive regulation of calcium ion-dependent exocytosis; IEA:Ensembl.
DR GO; GO:0034352; P:positive regulation of glial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; IEA:Ensembl.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IEA:Ensembl.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; IEA:Ensembl.
DR GO; GO:1901387; P:positive regulation of voltage-gated calcium channel activity; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0035418; P:protein localization to synapse; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
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: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:0000083; P:regulation of transcription involved in G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0009611; P:response to wounding; IEA:Ensembl.
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:0042501; P:serine phosphorylation of STAT protein; 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:0098883; P:synapse pruning; IEA:Ensembl.
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 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 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; Reference proteome; Serine/threonine-protein kinase;
KW 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"
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
