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Cyclin-dependent-like kinase 5 (EC 2.7.11.1) (Cell division protein kinase 5) (Serine/threonine-protein kinase PSSALRE) (Tau protein kinase II catalytic subunit) (TPKII catalytic subunit)

 CDK5_HUMAN              Reviewed;         292 AA.
Q00535; A1XKG3;
01-APR-1993, integrated into UniProtKB/Swiss-Prot.
15-DEC-1998, sequence version 3.
25-OCT-2017, entry version 196.
RecName: Full=Cyclin-dependent-like kinase 5;
EC=2.7.11.1;
AltName: Full=Cell division protein kinase 5;
AltName: Full=Serine/threonine-protein kinase PSSALRE;
AltName: Full=Tau protein kinase II catalytic subunit;
Short=TPKII catalytic subunit;
Name=CDK5; Synonyms=CDKN5;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Fetal brain;
PubMed=1639063;
Meyerson M., Enders G.H., Wu C.-L., Su L.-K., Gorka C., Nelson C.,
Harlow E., Tsai L.-H.;
"A family of human cdc2-related protein kinases.";
EMBO J. 11:2909-2917(1992).
[2]
SEQUENCE REVISION.
Meyerson M.;
Submitted (FEB-1993) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE
SPECIFICITY, INTERACTION WITH CTNNB1, AND FUNCTION IN WNT/B-CATENIN
SIGNALING PATHWAY.
TISSUE=Testis;
PubMed=19693690; DOI=10.1007/s11033-009-9752-7;
Li Q., Liu X., Zhang M., Ye G., Qiao Q., Ling Y., Wu Y., Zhang Y.,
Yu L.;
"Characterization of a novel human CDK5 splicing variant that inhibits
Wnt/beta-catenin signaling.";
Mol. Biol. Rep. 37:2415-2421(2010).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Hu X., Xu Y., Zhang B., Peng X., Yuan J., Qiang B.;
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
Phelan M., Farmer A.;
"Cloning of human full-length CDSs in BD Creator(TM) system donor
vector.";
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=12853948; DOI=10.1038/nature01782;
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
Waterston R.H., Wilson R.K.;
"The DNA sequence of human chromosome 7.";
Nature 424:157-164(2003).
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Lung;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
ENZYME REGULATION BY ROSCOVITINE AND OLOMOUCINE.
PubMed=9030781; DOI=10.1111/j.1432-1033.1997.t01-2-00527.x;
Meijer L., Borgne A., Mulner O., Chong J.P.J., Blow J.J., Inagaki N.,
Inagaki M., Delcros J.-G., Moulinoux J.-P.;
"Biochemical and cellular effects of roscovitine, a potent and
selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and
cdk5.";
Eur. J. Biochem. 243:527-536(1997).
[9]
FUNCTION IN AXON GROWTH.
PubMed=9822744;
Paglini G., Pigino G., Kunda P., Morfini G., Maccioni R., Quiroga S.,
Ferreira A., Caceres A.;
"Evidence for the participation of the neuron-specific CDK5 activator
P35 during laminin-enhanced axonal growth.";
J. Neurosci. 18:9858-9869(1998).
[10]
PHOSPHORYLATION AT SER-159.
PubMed=10500146; DOI=10.1073/pnas.96.20.11156;
Sharma P., Sharma M., Amin N.D., Albers R.W., Pant H.C.;
"Regulation of cyclin-dependent kinase 5 catalytic activity by
phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 96:11156-11160(1999).
[11]
FUNCTION AS P35/CDK5R1 KINASE.
PubMed=12393264; DOI=10.1016/S0169-328X(02)00409-6;
Kerokoski P., Suuronen T., Salminen A., Soininen H., Pirttilae T.;
"Influence of phosphorylation of p35, an activator of cyclin-dependent
kinase 5 (cdk5), on the proteolysis of p35.";
Brain Res. Mol. Brain Res. 106:50-56(2002).
[12]
INTERACTION WITH AATK.
PubMed=14521924; DOI=10.1016/j.bbrc.2003.08.143;
Honma N., Asada A., Takeshita S., Enomoto M., Yamakawa E.,
Tsutsumi K., Saito T., Satoh T., Itoh H., Kaziro Y., Kishimoto T.,
Hisanaga S.;
"Apoptosis-associated tyrosine kinase is a Cdk5 activator p35 binding
protein.";
Biochem. Biophys. Res. Commun. 310:398-404(2003).
[13]
FUNCTION AS MEF2A KINASE, ENZYME REGULATION, AND SUBCELLULAR LOCATION.
PubMed=12691662; DOI=10.1016/S0896-6273(03)00191-0;
Gong X., Tang X., Wiedmann M., Wang X., Peng J., Zheng D.,
Blair L.A.C., Marshall J., Mao Z.;
"Cdk5-mediated inhibition of the protective effects of transcription
factor MEF2 in neurotoxicity-induced apoptosis.";
Neuron 38:33-46(2003).
[14]
FUNCTION AS P35 KINASE, SUBCELLULAR LOCATION, AND ENZYME REGULATION.
PubMed=15992363; DOI=10.1111/j.1471-4159.2005.03301.x;
Zhu Y.-S., Saito T., Asada A., Maekawa S., Hisanaga S.;
"Activation of latent cyclin-dependent kinase 5 (Cdk5)-p35 complexes
by membrane dissociation.";
J. Neurochem. 94:1535-1545(2005).
[15]
FUNCTION AS P35/CDK5R KINASE.
PubMed=17121855; DOI=10.1074/jbc.M610541200;
Kamei H., Saito T., Ozawa M., Fujita Y., Asada A., Bibb J.A.,
Saido T.C., Sorimachi H., Hisanaga S.;
"Suppression of calpain-dependent cleavage of the CDK5 activator p35
to p25 by site-specific phosphorylation.";
J. Biol. Chem. 282:1687-1694(2007).
[16]
FUNCTION AS CTNNB1 AND CTNND2 KINASE, INTERACTION WITH CTNNB1 AND
CTNND2, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
PubMed=17009320; DOI=10.1002/jcb.21041;
Munoz J.P., Huichalaf C.H., Orellana D., Maccioni R.B.;
"cdk5 modulates beta- and delta-catenin/Pin1 interactions in neuronal
cells.";
J. Cell. Biochem. 100:738-749(2007).
[17]
FUNCTION AS P53/TP53 KINASE, INTERACTION WITH P53/TP53, AND
SUBCELLULAR LOCATION.
PubMed=17591690; DOI=10.1242/jcs.03468;
Lee J.-H., Kim H.-S., Lee S.-J., Kim K.-T.;
"Stabilization and activation of p53 induced by Cdk5 contributes to
neuronal cell death.";
J. Cell Sci. 120:2259-2271(2007).
[18]
FUNCTION AS PXN KINASE.
PubMed=18042622; DOI=10.1242/jcs.018218;
Miyamoto Y., Yamauchi J., Chan J.R., Okada A., Tomooka Y.,
Hisanaga S., Tanoue A.;
"Cdk5 regulates differentiation of oligodendrocyte precursor cells
through the direct phosphorylation of paxillin.";
J. Cell Sci. 120:4355-4366(2007).
[19]
FUNCTION AS HUNTINGTIN KINASE, AND ENZYME REGULATION BY ROSCOVITINE.
PubMed=17611284; DOI=10.1523/JNEUROSCI.1831-07.2007;
Anne S.L., Saudou F., Humbert S.;
"Phosphorylation of huntingtin by cyclin-dependent kinase 5 is induced
by DNA damage and regulates wild-type and mutant huntingtin toxicity
in neurons.";
J. Neurosci. 27:7318-7328(2007).
[20]
FUNCTION AS P35/CDK5R KINASE, INTERACTION WITH P35/CDK5R, AND
SUBCELLULAR LOCATION.
PubMed=17671990; DOI=10.1002/jnr.21438;
Sato K., Zhu Y.-S., Saito T., Yotsumoto K., Asada A., Hasegawa M.,
Hisanaga S.;
"Regulation of membrane association and kinase activity of Cdk5-p35 by
phosphorylation of p35.";
J. Neurosci. Res. 85:3071-3078(2007).
[21]
PHOSPHORYLATION AT TYR-15 BY EPHA4.
PubMed=17143272; DOI=10.1038/nn1811;
Fu W.Y., Chen Y., Sahin M., Zhao X.S., Shi L., Bikoff J.B., Lai K.O.,
Yung W.H., Fu A.K., Greenberg M.E., Ip N.Y.;
"Cdk5 regulates EphA4-mediated dendritic spine retraction through an
ephexin1-dependent mechanism.";
Nat. Neurosci. 10:67-76(2007).
[22]
SUBCELLULAR LOCATION.
PubMed=18507738; DOI=10.1111/j.1471-4159.2008.05500.x;
Asada A., Yamamoto N., Gohda M., Saito T., Hayashi N., Hisanaga S.;
"Myristoylation of p39 and p35 is a determinant of cytoplasmic or
nuclear localization of active cyclin-dependent kinase 5 complexes.";
J. Neurochem. 106:1325-1336(2008).
[23]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
Greff Z., Keri G., Stemmann O., Mann M.;
"Kinase-selective enrichment enables quantitative phosphoproteomics of
the kinome across the cell cycle.";
Mol. Cell 31:438-448(2008).
[24]
FUNCTION AS HDAC REGULATOR.
PubMed=19081376; DOI=10.1016/j.neuron.2008.10.015;
Kim D., Frank C.L., Dobbin M.M., Tsunemoto R.K., Tu W., Peng P.L.,
Guan J.S., Lee B.H., Moy L.Y., Giusti P., Broodie N., Mazitschek R.,
Delalle I., Haggarty S.J., Neve R.L., Lu Y., Tsai L.H.;
"Deregulation of HDAC1 by p25/Cdk5 in neurotoxicity.";
Neuron 60:803-817(2008).
[25]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19413330; DOI=10.1021/ac9004309;
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
Mohammed S.;
"Lys-N and trypsin cover complementary parts of the phosphoproteome in
a refined SCX-based approach.";
Anal. Chem. 81:4493-4501(2009).
[26]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
Mann M., Daub H.;
"Large-scale proteomics analysis of the human kinome.";
Mol. Cell. Proteomics 8:1751-1764(2009).
[27]
ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-56, AND IDENTIFICATION BY
MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19608861; DOI=10.1126/science.1175371;
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
Walther T.C., Olsen J.V., Mann M.;
"Lysine acetylation targets protein complexes and co-regulates major
cellular functions.";
Science 325:834-840(2009).
[28]
FUNCTION IN ANGIOGENESIS.
PubMed=20826806; DOI=10.1074/jbc.M110.126177;
Liebl J., Weitensteiner S.B., Vereb G., Takacs L., Fuerst R.,
Vollmar A.M., Zahler S.;
"Cyclin-dependent kinase 5 regulates endothelial cell migration and
angiogenesis.";
J. Biol. Chem. 285:35932-35943(2010).
[29]
FUNCTION AS NOS3 KINASE.
PubMed=20213743; DOI=10.1002/jcb.22515;
Lee C.-H., Wei Y.-W., Huang Y.-T., Lin Y.-T., Lee Y.-C., Lee K.-H.,
Lu P.-J.;
"CDK5 phosphorylates eNOS at Ser-113 and regulates NO production.";
J. Cell. Biochem. 110:112-117(2010).
[30]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21269460; DOI=10.1186/1752-0509-5-17;
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
"Initial characterization of the human central proteome.";
BMC Syst. Biol. 5:17-17(2011).
[31]
INHIBITORS.
PubMed=21144757; DOI=10.1016/j.bmc.2010.11.022;
Jain P., Flaherty P.T., Yi S., Chopra I., Bleasdell G., Lipay J.,
Ferandin Y., Meijer L., Madura J.D.;
"Design, synthesis, and testing of an 6-O-linked series of
benzimidazole based inhibitors of CDK5/p25.";
Bioorg. Med. Chem. 19:359-373(2011).
[32]
FUNCTION AS SRC KINASE.
PubMed=21442427; DOI=10.1007/s00018-011-0638-1;
Pan Q., Qiao F., Gao C., Norman B., Optican L., Zelenka P.S.;
"Cdk5 targets active Src for ubiquitin-dependent degradation by
phosphorylating Src(S75).";
Cell. Mol. Life Sci. 68:3425-3436(2011).
[33]
FUNCTION AS VIM KINASE, AND SUBCELLULAR LOCATION.
PubMed=21465480; DOI=10.1002/jcp.22782;
Lee K.Y., Liu L., Jin Y., Fu S.B., Rosales J.L.;
"Cdk5 mediates vimentin Ser56 phosphorylation during GTP-induced
secretion by neutrophils.";
J. Cell. Physiol. 227:739-750(2012).
[34]
ENZYME REGULATION, AND INTERACTION WITH GSTP1.
PubMed=21668448; DOI=10.1111/j.1471-4159.2011.07343.x;
Sun K.H., Chang K.H., Clawson S., Ghosh S., Mirzaei H., Regnier F.,
Shah K.;
"Glutathione-S-transferase P1 is a critical regulator of Cdk5 kinase
activity.";
J. Neurochem. 118:902-914(2011).
[35]
FUNCTION AS TONEBP/NFAT5 KINASE.
PubMed=21209322; DOI=10.1091/mbc.E10-08-0681;
Gallazzini M., Heussler G.E., Kunin M., Izumi Y., Burg M.B.,
Ferraris J.D.;
"High NaCl-induced activation of CDK5 increases phosphorylation of the
osmoprotective transcription factor TonEBP/OREBP at threonine 135,
which contributes to its rapid nuclear localization.";
Mol. Biol. Cell 22:703-714(2011).
[36]
FUNCTION AS SH3GLB1 KINASE.
PubMed=21499257; DOI=10.1038/ncb2217;
Wong A.S., Lee R.H., Cheung A.Y., Yeung P.K., Chung S.K., Cheung Z.H.,
Ip N.Y.;
"Cdk5-mediated phosphorylation of endophilin B1 is required for
induced autophagy in models of Parkinson's disease.";
Nat. Cell Biol. 13:568-579(2011).
[37]
FUNCTION AS EPRS KINASE.
PubMed=21220307; DOI=10.1073/pnas.1011275108;
Arif A., Jia J., Moodt R.A., DiCorleto P.E., Fox P.L.;
"Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-
dependent kinase 5 dictates transcript-selective translational
control.";
Proc. Natl. Acad. Sci. U.S.A. 108:1415-1420(2011).
[38]
REVIEW.
PubMed=11584302; DOI=10.1038/35096019;
Dhavan R., Tsai L.H.;
"A decade of CDK5.";
Nat. Rev. Mol. Cell Biol. 2:749-759(2001).
[39]
REVIEW ON INHIBITORS, AND GENE FAMILY.
PubMed=19238148; DOI=10.1038/nrc2602;
Malumbres M., Barbacid M.;
"Cell cycle, CDKs and cancer: a changing paradigm.";
Nat. Rev. Cancer 9:153-166(2009).
[40]
REVIEW ON NEURONAL PHYSIOLOGY.
PubMed=19782409; DOI=10.1016/j.tins.2009.07.002;
Jessberger S., Gage F.H., Eisch A.J., Lagace D.C.;
"Making a neuron: Cdk5 in embryonic and adult neurogenesis.";
Trends Neurosci. 32:575-582(2009).
[41]
FUNCTION.
PubMed=20061803; DOI=10.4161/cc.9.2.10466;
Lalioti V., Pulido D., Sandoval I.V.;
"Cdk5, the multifunctional surveyor.";
Cell Cycle 9:284-311(2010).
[42]
REVIEW ON REGULATION.
PubMed=21044075; DOI=10.1111/j.1471-4159.2010.07050.x;
Hisanaga S., Endo R.;
"Regulation and role of cyclin-dependent kinase activity in neuronal
survival and death.";
J. Neurochem. 115:1309-1321(2010).
[43]
REVIEW ON NEURON DEVELOPMENT.
PubMed=21415596; DOI=10.4161/cc.10.8.15328;
Zhang J., Herrup K.;
"Nucleocytoplasmic Cdk5 is involved in neuronal cell cycle and death
in post-mitotic neurons.";
Cell Cycle 10:1208-1214(2011).
[44]
REVIEW ON NEURON DEVELOPMENT.
PubMed=21600237; DOI=10.1016/j.mad.2011.04.011;
Zhu J., Li W., Mao Z.;
"Cdk5: Mediator of neuronal development, death and the response to DNA
damage.";
Mech. Ageing Dev. 132:389-394(2011).
[45]
REVIEW ON NEURONS.
PubMed=21473899; DOI=10.1016/j.pneurobio.2011.03.006;
Lopes J.P., Agostinho P.;
"Cdk5: multitasking between physiological and pathological
conditions.";
Prog. Neurobiol. 94:49-63(2011).
[46]
FUNCTION, AND INTERACTION WITH CLOCK.
PubMed=24235147; DOI=10.1074/jbc.M113.494856;
Kwak Y., Jeong J., Lee S., Park Y.U., Lee S.A., Han D.H., Kim J.H.,
Ohshima T., Mikoshiba K., Suh Y.H., Cho S., Park S.K.;
"Cyclin-dependent kinase 5 (Cdk5) regulates the function of CLOCK
protein by direct phosphorylation.";
J. Biol. Chem. 288:36878-36889(2013).
[47]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-17, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma, and Erythroleukemia;
PubMed=23186163; DOI=10.1021/pr300630k;
Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
Mohammed S.;
"Toward a comprehensive characterization of a human cancer cell
phosphoproteome.";
J. Proteome Res. 12:260-271(2013).
[48]
INVOLVEMENT IN LIS7.
PubMed=25560765; DOI=10.1007/s00439-014-1522-5;
Magen D., Ofir A., Berger L., Goldsher D., Eran A., Katib N.,
Nijem Y., Vlodavsky E., Tzur S., Zur S., Behar D.M., Fellig Y.,
Mandel H.;
"Autosomal recessive lissencephaly with cerebellar hypoplasia is
associated with a loss-of-function mutation in CDK5.";
Hum. Genet. 134:305-314(2015).
[49]
X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) IN COMPLEX WITH P25, AND
MUTAGENESIS OF SER-159.
PubMed=11583627; DOI=10.1016/S1097-2765(01)00343-4;
Tarricone C., Dhavan R., Peng J., Areces L.B., Tsai L.-H.,
Musacchio A.;
"Structure and regulation of the CDK5-p25(nck5a) complex.";
Mol. Cell 8:657-669(2001).
[50]
X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS).
PubMed=16039528; DOI=10.1016/j.chembiol.2005.05.011;
Ahn J.S., Radhakrishnan M.L., Mapelli M., Choi S., Tidor B.,
Cuny G.D., Musacchio A., Yeh L.A., Kosik K.S.;
"Defining Cdk5 ligand chemical space with small molecule inhibitors of
tau phosphorylation.";
Chem. Biol. 12:811-823(2005).
[51]
X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH INHIBITORS AND
P25, AND PHOSPHORYLATION AT TYR-15.
PubMed=15689152; DOI=10.1021/jm049323m;
Mapelli M., Massimiliano L., Crovace C., Seeliger M.A., Tsai L.H.,
Meijer L., Musacchio A.;
"Mechanism of CDK5/p25 binding by CDK inhibitors.";
J. Med. Chem. 48:671-679(2005).
[52]
VARIANT [LARGE SCALE ANALYSIS] ASP-225.
PubMed=17344846; DOI=10.1038/nature05610;
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
-!- FUNCTION: Proline-directed serine/threonine-protein kinase
essential for neuronal cell cycle arrest and differentiation and
may be involved in apoptotic cell death in neuronal diseases by
triggering abortive cell cycle re-entry. Interacts with D1 and D3-
type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin,
p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5,
SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5,
MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1,
huntingtin/HTT, ATM, MAP2, NEFH and NEFM. Regulates several
neuronal development and physiological processes including
neuronal survival, migration and differentiation, axonal and
neurite growth, synaptogenesis, oligodendrocyte differentiation,
synaptic plasticity and neurotransmission, by phosphorylating key
proteins. Activated by interaction with CDK5R1 (p35) and CDK5R2
(p39), especially in post-mitotic neurons, and promotes CDK5R1
(p35) expression in an autostimulation loop. Phosphorylates many
downstream substrates such as Rho and Ras family small GTPases
(e.g. PAK1, RAC1, RHOA, CDC42) or microtubule-binding proteins
(e.g. MAPT/TAU, MAP2, MAP1B), and modulates actin dynamics to
regulate neurite growth and/or spine morphogenesis. Phosphorylates
also exocytosis associated proteins such as MCAM/MUC18, SEPT5,
SYN1, and CDK16/PCTAIRE1 as well as endocytosis associated
proteins such as DNM1, AMPH and SYNJ1 at synaptic terminals. In
the mature central nervous system (CNS), regulates
neurotransmitter movements by phosphorylating substrates
associated with neurotransmitter release and synapse plasticity;
synaptic vesicle exocytosis, vesicles fusion with the presynaptic
membrane, and endocytosis. Promotes cell survival by activating
anti-apoptotic proteins BCL2 and STAT3, and negatively regulating
of JNK3/MAPK10 activity. Phosphorylation of p53/TP53 in response
to genotoxic and oxidative stresses enhances its stabilization by
preventing ubiquitin ligase-mediated proteasomal degradation, and
induces transactivation of p53/TP53 target genes, thus regulating
apoptosis. Phosphorylation of p35/CDK5R1 enhances its
stabilization by preventing calpain-mediated proteolysis producing
p25/CDK5R1 and avoiding ubiquitin ligase-mediated proteasomal
degradation. During aberrant cell-cycle activity and DNA damage,
p25/CDK5 activity elicits cell-cycle activity and double-strand
DNA breaks that precedes neuronal death by deregulating HDAC1. DNA
damage triggered phosphorylation of huntingtin/HTT in nuclei of
neurons protects neurons against polyglutamine expansion as well
as DNA damage mediated toxicity. Phosphorylation of PXN reduces
its interaction with PTK2/FAK1 in matrix-cell focal adhesions
(MCFA) during oligodendrocytes (OLs) differentiation. Negative
regulator of Wnt/beta-catenin signaling pathway. Activator of the
GAIT (IFN-gamma-activated inhibitor of translation) pathway, which
suppresses expression of a post-transcriptional regulon of
proinflammatory genes in myeloid cells; phosphorylates the linker
domain of glutamyl-prolyl tRNA synthetase (EPRS) in a IFN-gamma-
dependent manner, the initial event in assembly of the GAIT
complex. Phosphorylation of SH3GLB1 is required for autophagy
induction in starved neurons. Phosphorylation of TONEBP/NFAT5 in
response to osmotic stress mediates its rapid nuclear
localization. MEF2 is inactivated by phosphorylation in nucleus in
response to neurotoxin, thus leading to neuronal apoptosis. APEX1
AP-endodeoxyribonuclease is repressed by phosphorylation,
resulting in accumulation of DNA damage and contributing to
neuronal death. NOS3 phosphorylation down regulates NOS3-derived
nitrite (NO) levels. SRC phosphorylation mediates its ubiquitin-
dependent degradation and thus leads to cytoskeletal
reorganization. May regulate endothelial cell migration and
angiogenesis via the modulation of lamellipodia formation.
Involved in dendritic spine morphogenesis by mediating the EFNA1-
EPHA4 signaling. The complex p35/CDK5 participates in the
regulation of the circadian clock by modulating the function of
CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and
regulates the transcriptional activity of the CLOCK-ARNTL/BMAL1
heterodimer in association with altered stability and subcellular
distribution. {ECO:0000269|PubMed:12393264,
ECO:0000269|PubMed:12691662, ECO:0000269|PubMed:15992363,
ECO:0000269|PubMed:17009320, ECO:0000269|PubMed:17121855,
ECO:0000269|PubMed:17591690, ECO:0000269|PubMed:17611284,
ECO:0000269|PubMed:17671990, ECO:0000269|PubMed:18042622,
ECO:0000269|PubMed:19081376, ECO:0000269|PubMed:19693690,
ECO:0000269|PubMed:20061803, ECO:0000269|PubMed:20213743,
ECO:0000269|PubMed:20826806, ECO:0000269|PubMed:21209322,
ECO:0000269|PubMed:21220307, ECO:0000269|PubMed:21442427,
ECO:0000269|PubMed:21465480, ECO:0000269|PubMed:21499257,
ECO:0000269|PubMed:24235147, ECO:0000269|PubMed:9822744}.
-!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
-!- ENZYME REGULATION: Inhibited by 2-(1-ethyl-2-hydroxyethylamino)-6-
benzylamino-9-isopropylpurine (roscovitine), 1-isopropyl-4-
aminobenzyl-6-ether-linked benzimidazoles, resveratrol, AT-7519
and olomoucine. Activated by CDK5R1 (p35) and CDK5R2 (p39) during
the development of the nervous system; degradation of CDK5R1 (p35)
and CDK5R2 (p39) by proteasome result in down regulation of kinase
activity, during this process, CDK5 phosphorylates p35 and induces
its ubiquitination and subsequent degradation. Kinase activity is
mainly determined by the amount of p35 available and subcellular
location; reversible association to plasma membrane inhibits
activity. Long-term inactivation as well as CDK5R1 (p25)-mediated
hyperactivation of CDK5 triggers cell death. The pro-death
activity of hyperactivated CDK5 is suppressed by membrane
association of CDK5, via myristoylation of p35. Brain-derived
neurotrophic factor, glial-derived neurotrophic factor, nerve
growth factor (NGF), retinoic acid, laminin and neuregulin promote
activity. Neurotoxicity enhances nuclear activity, thus leading to
MEF2 phosphorylation and inhibition prior to apoptosis of cortical
neurons. Repression by GSTP1 via p25/p35 translocation prevents
neurodegeneration. {ECO:0000269|PubMed:12691662,
ECO:0000269|PubMed:15992363, ECO:0000269|PubMed:17611284,
ECO:0000269|PubMed:21668448, ECO:0000269|PubMed:9030781}.
-!- SUBUNIT: Heterodimer composed of a catalytic subunit CDK5 and a
regulatory subunit CDK5R1 (p25) and macromolecular complex
composed of at least CDK5, CDK5R1 (p35) and CDK5RAP1 or CDK5RAP2
or CDK5RAP3. Only the heterodimer shows kinase activity. Under
neurotoxic stress and neuronal injury conditions, p35 is cleaved
by calpain to generate p25 that hyperactivates CDK5, that becomes
functionally disabled and often toxic. Found in a trimolecular
complex with CABLES1 and ABL1. Interacts with CABLES1 and CABLES2
(By similarity). Interacts with AATK and GSTP1. Binds to HDAC1
when in complex with p25. Interaction with myristoylation p35
promotes CDK5 association with membranes. Both isoforms 1 and 2
interacts with beta-catenin/CTNNB1. Interacts with delta-
catenin/CTNND2 and APEX1. Interacts with P53/TP53 in neurons.
Interacts with EPHA4; may mediate the activation of NGEF by EPHA4.
Interacts with PTK2/FAK1 (By similarity). The complex p35/CDK5
interacts with CLOCK. Interacts with HTR6 (By similarity).
{ECO:0000250, ECO:0000250|UniProtKB:P49615,
ECO:0000269|PubMed:11583627, ECO:0000269|PubMed:14521924,
ECO:0000269|PubMed:15689152, ECO:0000269|PubMed:17009320,
ECO:0000269|PubMed:17591690, ECO:0000269|PubMed:17671990,
ECO:0000269|PubMed:19693690, ECO:0000269|PubMed:21668448,
ECO:0000269|PubMed:24235147}.
-!- INTERACTION:
Q8TDN4:CABLES1; NbExp=5; IntAct=EBI-1041567, EBI-604615;
P24863:CCNC; NbExp=2; IntAct=EBI-1041567, EBI-395261;
P30279:CCND2; NbExp=10; IntAct=EBI-1041567, EBI-748789;
P30281:CCND3; NbExp=4; IntAct=EBI-1041567, EBI-375013;
Q15078:CDK5R1; NbExp=11; IntAct=EBI-1041567, EBI-746189;
P38936:CDKN1A; NbExp=4; IntAct=EBI-1041567, EBI-375077;
P46527:CDKN1B; NbExp=7; IntAct=EBI-1041567, EBI-519280;
P37231-2:PPARG; NbExp=2; IntAct=EBI-1041567, EBI-781416;
-!- SUBCELLULAR LOCATION: Isoform 1: Cytoplasm. Cell membrane;
Peripheral membrane protein. Perikaryon. Cell projection,
lamellipodium {ECO:0000250}. Cell projection, growth cone
{ECO:0000250}. Cell junction, synapse, postsynaptic cell membrane,
postsynaptic density {ECO:0000250}. Note=In axonal growth cone
with extension to the peripheral lamellipodia (By similarity).
Under neurotoxic stress and neuronal injury conditions, CDK5R
(p35) is cleaved by calpain to generate CDK5R1 (p25) in response
to increased intracellular calcium. The elevated level of p25,
when in complex with CDK5, leads to its subcellular misallocation
as well as its hyperactivation. Colocalizes with CTNND2 in the
cell body of neuronal cells, and with CTNNB1 in the cell-cell
contacts and plasma membrane of undifferentiated and
differentiated neuroblastoma cells. Reversibly attached to the
plasma membrane in an inactive form when complexed to
dephosphorylated p35 or CDK5R2 (p39), p35 phosphorylation releases
this attachment and activates CDK5. {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Isoform 2: Nucleus.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q00535-1; Sequence=Displayed;
Name=2; Synonyms=CDK5-SV;
IsoId=Q00535-2; Sequence=VSP_041948;
-!- TISSUE SPECIFICITY: Isoform 1 is ubiquitously expressed.
Accumulates in cortical neurons (at protein level). Isoform 2 has
only been detected in testis, skeletal muscle, colon, bone marrow
and ovary. {ECO:0000269|PubMed:17009320,
ECO:0000269|PubMed:19693690}.
-!- PTM: Phosphorylation on Tyr-15 by ABL1 and FYN, and on Ser-159 by
casein kinase 1 promotes kinase activity. By contrast,
phosphorylation at Thr-14 inhibits activity.
{ECO:0000269|PubMed:10500146, ECO:0000269|PubMed:15689152,
ECO:0000269|PubMed:17143272}.
-!- PTM: Phosphorylation at Ser-159 is essential for maximal catalytic
activity. {ECO:0000269|PubMed:10500146}.
-!- DISEASE: Lissencephaly 7, with cerebellar hypoplasia (LIS7)
[MIM:616342]: A form of lissencephaly, a disorder of cortical
development characterized by agyria or pachygyria and
disorganization of the clear neuronal lamination of normal six-
layered cortex. LIS7 patients manifest lack of psychomotor
development, facial dysmorphism, arthrogryposis, and early-onset
intractable seizures resulting in death in infancy.
{ECO:0000269|PubMed:25560765}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- MISCELLANEOUS: Dysregulation of CDK5 is associated with
neurodegenerative disorders such as Alzheimer, Parkinson, and
Niemann-Pick type C diseases, ischemia, and amyotrophic lateral
sclerosis.
-!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC
Ser/Thr protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; X66364; CAA47007.1; -; mRNA.
EMBL; DQ411039; ABD66016.1; -; mRNA.
EMBL; AY049778; AAL15435.1; -; mRNA.
EMBL; BT006680; AAP35326.1; -; mRNA.
EMBL; AC010973; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC005115; AAH05115.1; -; mRNA.
CCDS; CCDS47748.1; -. [Q00535-1]
CCDS; CCDS55184.1; -. [Q00535-2]
PIR; S23386; S23386.
RefSeq; NP_001157882.1; NM_001164410.2. [Q00535-2]
RefSeq; NP_004926.1; NM_004935.3. [Q00535-1]
UniGene; Hs.647078; -.
PDB; 1H4L; X-ray; 2.65 A; A/B=1-292.
PDB; 1LFR; Model; -; A=1-292.
PDB; 1UNG; X-ray; 2.30 A; A/B=1-292.
PDB; 1UNH; X-ray; 2.35 A; A/B=1-292.
PDB; 1UNL; X-ray; 2.20 A; A/B=1-292.
PDB; 3O0G; X-ray; 1.95 A; A/B=1-292.
PDB; 4AU8; X-ray; 1.90 A; A/B=2-292.
PDBsum; 1H4L; -.
PDBsum; 1LFR; -.
PDBsum; 1UNG; -.
PDBsum; 1UNH; -.
PDBsum; 1UNL; -.
PDBsum; 3O0G; -.
PDBsum; 4AU8; -.
ProteinModelPortal; Q00535; -.
SMR; Q00535; -.
BioGrid; 107455; 106.
CORUM; Q00535; -.
DIP; DIP-24221N; -.
ELM; Q00535; -.
IntAct; Q00535; 52.
MINT; MINT-1037488; -.
STRING; 9606.ENSP00000419782; -.
BindingDB; Q00535; -.
ChEMBL; CHEMBL4036; -.
DrugBank; DB04014; Alsterpaullone.
DrugBank; DB03496; Flavopiridol.
DrugBank; DB02950; Hymenialdisine.
DrugBank; DB02052; Indirubin-3'-Monoxime.
DrugBank; DB02116; Olomoucine.
DrugBank; DB03428; SU9516.
GuidetoPHARMACOLOGY; 1977; -.
iPTMnet; Q00535; -.
PhosphoSitePlus; Q00535; -.
SwissPalm; Q00535; -.
BioMuta; CDK5; -.
DMDM; 4033704; -.
EPD; Q00535; -.
MaxQB; Q00535; -.
PaxDb; Q00535; -.
PeptideAtlas; Q00535; -.
PRIDE; Q00535; -.
DNASU; 1020; -.
Ensembl; ENST00000297518; ENSP00000297518; ENSG00000164885. [Q00535-2]
Ensembl; ENST00000485972; ENSP00000419782; ENSG00000164885. [Q00535-1]
GeneID; 1020; -.
KEGG; hsa:1020; -.
UCSC; uc003wir.3; human. [Q00535-1]
CTD; 1020; -.
DisGeNET; 1020; -.
EuPathDB; HostDB:ENSG00000164885.12; -.
GeneCards; CDK5; -.
HGNC; HGNC:1774; CDK5.
HPA; CAB008909; -.
HPA; HPA018977; -.
HPA; HPA064535; -.
MalaCards; CDK5; -.
MIM; 123831; gene.
MIM; 616342; phenotype.
neXtProt; NX_Q00535; -.
OpenTargets; ENSG00000164885; -.
PharmGKB; PA26310; -.
eggNOG; KOG0594; Eukaryota.
eggNOG; ENOG410XPP3; LUCA.
GeneTree; ENSGT00900000140869; -.
HOGENOM; HOG000233024; -.
HOVERGEN; HBG014652; -.
InParanoid; Q00535; -.
KO; K02090; -.
OMA; IGTPDDR; -.
OrthoDB; EOG091G0CH0; -.
PhylomeDB; Q00535; -.
TreeFam; TF101023; -.
BRENDA; 2.7.11.22; 2681.
Reactome; R-HSA-180024; DARPP-32 events.
Reactome; R-HSA-399956; CRMPs in Sema3A signaling.
Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
Reactome; R-HSA-8862803; Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models.
Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production.
SignaLink; Q00535; -.
SIGNOR; Q00535; -.
ChiTaRS; CDK5; human.
EvolutionaryTrace; Q00535; -.
GeneWiki; Cyclin-dependent_kinase_5; -.
GenomeRNAi; 1020; -.
PRO; PR:Q00535; -.
Proteomes; UP000005640; Chromosome 7.
Bgee; ENSG00000164885; -.
CleanEx; HS_CDK5; -.
ExpressionAtlas; Q00535; baseline and differential.
Genevisible; Q00535; HS.
GO; GO:0030424; C:axon; ISS:UniProtKB.
GO; GO:0030054; C:cell junction; IDA:HPA.
GO; GO:0016533; C:cyclin-dependent protein kinase 5 holoenzyme complex; IEA:Ensembl.
GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
GO; GO:0005856; C:cytoskeleton; IEA:Ensembl.
GO; GO:0005829; C:cytosol; IDA:HPA.
GO; GO:0030425; C:dendrite; ISS:UniProtKB.
GO; GO:0030175; C:filopodium; IEA:Ensembl.
GO; GO:0030426; C:growth cone; ISS:UniProtKB.
GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
GO; GO:0016020; C:membrane; ISS:UniProtKB.
GO; GO:0031594; C:neuromuscular junction; ISS:UniProtKB.
GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
GO; GO:0005634; C:nucleus; IDA:HPA.
GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
GO; GO:0005886; C:plasma membrane; IDA:HPA.
GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB.
GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-KW.
GO; GO:0098793; C:presynapse; IEA:GOC.
GO; GO:0030549; F:acetylcholine receptor activator activity; ISS:UniProtKB.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
GO; GO:0008092; F:cytoskeletal protein binding; IEA:Ensembl.
GO; GO:0046875; F:ephrin receptor binding; IEA:Ensembl.
GO; GO:0005176; F:ErbB-2 class receptor binding; ISS:UniProtKB.
GO; GO:0043125; F:ErbB-3 class receptor binding; ISS:UniProtKB.
GO; GO:0016301; F:kinase activity; ISS:UniProtKB.
GO; GO:0002039; F:p53 binding; IEA:Ensembl.
GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
GO; GO:0050321; F:tau-protein kinase activity; ISS:UniProtKB.
GO; GO:0048675; P:axon extension; TAS:UniProtKB.
GO; GO:0048148; P:behavioral response to cocaine; IEA:Ensembl.
GO; GO:0070509; P:calcium ion import; IEA:Ensembl.
GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
GO; GO:0007160; P:cell-matrix adhesion; IEA:Ensembl.
GO; GO:1904646; P:cellular response to amyloid-beta; ISS:ARUK-UCL.
GO; GO:0021954; P:central nervous system neuron development; IEA:Ensembl.
GO; GO:0021697; P:cerebellar cortex formation; IEA:Ensembl.
GO; GO:0007268; P:chemical synaptic transmission; TAS:UniProtKB.
GO; GO:0022038; P:corpus callosum development; IEA:Ensembl.
GO; GO:0030866; P:cortical actin cytoskeleton organization; IEA:Ensembl.
GO; GO:0048813; P:dendrite morphogenesis; IEA:Ensembl.
GO; GO:0060079; P:excitatory postsynaptic potential; IEA:Ensembl.
GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
GO; GO:0006886; P:intracellular protein transport; IEA:Ensembl.
GO; GO:0021819; P:layer formation in cerebral cortex; IEA:Ensembl.
GO; GO:0008045; P:motor neuron axon guidance; IEA:Ensembl.
GO; GO:0030517; P:negative regulation of axon extension; IEA:Ensembl.
GO; GO:0045786; P:negative regulation of cell cycle; IEA:Ensembl.
GO; GO:1901215; P:negative regulation of neuron death; IDA:ParkinsonsUK-UCL.
GO; GO:0046826; P:negative regulation of protein export from nucleus; IEA:Ensembl.
GO; GO:0031397; P:negative regulation of protein ubiquitination; IEA:Ensembl.
GO; GO:0045861; P:negative regulation of proteolysis; IMP:ParkinsonsUK-UCL.
GO; GO:0031914; P:negative regulation of synaptic plasticity; IEA:Ensembl.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:DFLAT.
GO; GO:0051402; P:neuron apoptotic process; TAS:UniProtKB.
GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
GO; GO:0001764; P:neuron migration; TAS:UniProtKB.
GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
GO; GO:0006913; P:nucleocytoplasmic transport; IEA:Ensembl.
GO; GO:0048709; P:oligodendrocyte differentiation; IDA:UniProtKB.
GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
GO; GO:0018107; P:peptidyl-threonine phosphorylation; IEA:Ensembl.
GO; GO:0016310; P:phosphorylation; IDA:DFLAT.
GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; TAS:UniProtKB.
GO; GO:0045956; P:positive regulation of calcium ion-dependent exocytosis; IEA:Ensembl.
GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISS:UniProtKB.
GO; GO:0032092; P:positive regulation of protein binding; IEA:Ensembl.
GO; GO:0045860; P:positive regulation of protein kinase activity; IEA:Ensembl.
GO; GO:0090314; P:positive regulation of protein targeting to membrane; IEA:Ensembl.
GO; GO:0046777; P:protein autophosphorylation; IEA:Ensembl.
GO; GO:0035418; P:protein localization to synapse; IEA:Ensembl.
GO; GO:0032801; P:receptor catabolic process; IEA:Ensembl.
GO; GO:0043113; P:receptor clustering; IEA:Ensembl.
GO; GO:0042981; P:regulation of apoptotic process; TAS:UniProtKB.
GO; GO:0071156; P:regulation of cell cycle arrest; TAS:UniProtKB.
GO; GO:0030334; P:regulation of cell migration; IEA:Ensembl.
GO; GO:0061001; P:regulation of dendritic spine morphogenesis; ISS:UniProtKB.
GO; GO:0016241; P:regulation of macroautophagy; TAS:ParkinsonsUK-UCL.
GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
GO; GO:0048167; P:regulation of synaptic plasticity; ISS:UniProtKB.
GO; GO:1903421; P:regulation of synaptic vesicle recycling; NAS:ParkinsonsUK-UCL.
GO; GO:0009611; P:response to wounding; IEA:Ensembl.
GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
GO; GO:0014044; P:Schwann cell development; IEA:Ensembl.
GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl.
GO; GO:0042501; P:serine phosphorylation of STAT protein; IEA:Ensembl.
GO; GO:0007519; P:skeletal muscle tissue development; IEA:Ensembl.
GO; GO:0007416; P:synapse assembly; TAS:UniProtKB.
GO; GO:0001963; P:synaptic transmission, dopaminergic; IEA:Ensembl.
GO; GO:0035249; P:synaptic transmission, glutamatergic; IEA:Ensembl.
GO; GO:0048488; P:synaptic vesicle endocytosis; TAS:UniProtKB.
GO; GO:0016079; P:synaptic vesicle exocytosis; TAS:UniProtKB.
GO; GO:0008542; P:visual learning; IEA:Ensembl.
InterPro; IPR011009; Kinase-like_dom.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR008271; Ser/Thr_kinase_AS.
Pfam; PF00069; Pkinase; 1.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
1: Evidence at protein level;
3D-structure; Acetylation; Alternative splicing; Apoptosis;
ATP-binding; Biological rhythms; Cell cycle; Cell division;
Cell junction; Cell membrane; Cell projection; Complete proteome;
Cytoplasm; Kinase; Lissencephaly; Membrane; Neurodegeneration;
Neurogenesis; Nucleotide-binding; Nucleus; Phosphoprotein;
Polymorphism; Postsynaptic cell membrane; Reference proteome;
Serine/threonine-protein kinase; Synapse; Transferase.
CHAIN 1 292 Cyclin-dependent-like kinase 5.
/FTId=PRO_0000085784.
DOMAIN 4 286 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 10 18 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
ACT_SITE 126 126 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10027}.
BINDING 33 33 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
MOD_RES 15 15 Phosphotyrosine; by ABL1, EPHA4 and FYN.
{ECO:0000269|PubMed:15689152,
ECO:0000269|PubMed:17143272}.
MOD_RES 17 17 Phosphothreonine.
{ECO:0000244|PubMed:23186163}.
MOD_RES 56 56 N6-acetyllysine.
{ECO:0000244|PubMed:19608861}.
MOD_RES 72 72 Phosphoserine.
{ECO:0000244|PubMed:18691976,
ECO:0000244|PubMed:19369195}.
MOD_RES 159 159 Phosphoserine.
{ECO:0000269|PubMed:10500146}.
VAR_SEQ 105 136 Missing (in isoform 2).
{ECO:0000303|PubMed:19693690}.
/FTId=VSP_041948.
VARIANT 225 225 E -> D (in dbSNP:rs35186917).
{ECO:0000269|PubMed:17344846}.
/FTId=VAR_041977.
MUTAGEN 159 159 S->A: No phenotype.
{ECO:0000269|PubMed:11583627}.
MUTAGEN 159 159 S->T: Impaired p35/p25 (CDK5R1) binding.
{ECO:0000269|PubMed:11583627}.
STRAND 4 12 {ECO:0000244|PDB:4AU8}.
STRAND 14 23 {ECO:0000244|PDB:4AU8}.
TURN 24 26 {ECO:0000244|PDB:4AU8}.
STRAND 29 36 {ECO:0000244|PDB:4AU8}.
STRAND 40 42 {ECO:0000244|PDB:1UNG}.
HELIX 46 55 {ECO:0000244|PDB:4AU8}.
STRAND 66 70 {ECO:0000244|PDB:4AU8}.
STRAND 76 81 {ECO:0000244|PDB:4AU8}.
STRAND 84 86 {ECO:0000244|PDB:4AU8}.
HELIX 87 94 {ECO:0000244|PDB:4AU8}.
HELIX 100 119 {ECO:0000244|PDB:4AU8}.
HELIX 129 131 {ECO:0000244|PDB:4AU8}.
STRAND 132 134 {ECO:0000244|PDB:4AU8}.
STRAND 140 142 {ECO:0000244|PDB:4AU8}.
HELIX 145 147 {ECO:0000244|PDB:1UNG}.
HELIX 165 167 {ECO:0000244|PDB:4AU8}.
HELIX 170 173 {ECO:0000244|PDB:4AU8}.
HELIX 182 196 {ECO:0000244|PDB:4AU8}.
TURN 197 199 {ECO:0000244|PDB:4AU8}.
HELIX 208 219 {ECO:0000244|PDB:4AU8}.
TURN 224 226 {ECO:0000244|PDB:4AU8}.
HELIX 228 232 {ECO:0000244|PDB:4AU8}.
HELIX 248 250 {ECO:0000244|PDB:4AU8}.
HELIX 257 266 {ECO:0000244|PDB:4AU8}.
HELIX 271 273 {ECO:0000244|PDB:4AU8}.
HELIX 277 281 {ECO:0000244|PDB:4AU8}.
HELIX 284 286 {ECO:0000244|PDB:4AU8}.
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


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