CDK5_CAEEL
ID CDK5_CAEEL Reviewed; 292 AA.
AC G5ECH7;
DT 24-JUN-2015, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Cyclin-dependent-like kinase 5 {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000269|PubMed:20510931};
DE AltName: Full=Cell division protein kinase 5 {ECO:0000305};
GN Name=cdk-5 {ECO:0000312|WormBase:T27E9.3};
GN ORFNames=T27E9.3 {ECO:0000312|WormBase:T27E9.3};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:AAD37121.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAD37121.1};
RX PubMed=10207147; DOI=10.1242/dev.126.10.2227;
RA Boxem M., Srinivasan D.G., van den Heuvel S.;
RT "The Caenorhabditis elegans gene ncc-1 encodes a cdc2-related kinase
RT required for M phase in meiotic and mitotic cell divisions, but not for S
RT phase.";
RL Development 126:2227-2239(1999).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16996038; DOI=10.1016/j.brainres.2006.08.067;
RA Locke C.J., Williams S.N., Schwarz E.M., Caldwell G.A., Caldwell K.A.;
RT "Genetic interactions among cortical malformation genes that influence
RT susceptibility to convulsions in C. elegans.";
RL Brain Res. 1120:23-34(2006).
RN [4] {ECO:0000305}
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF LYS-33 AND ASP-144.
RX PubMed=17671168; DOI=10.1091/mbc.e06-09-0818;
RA Juo P., Harbaugh T., Garriga G., Kaplan J.M.;
RT "CDK-5 regulates the abundance of GLR-1 glutamate receptors in the ventral
RT cord of Caenorhabditis elegans.";
RL Mol. Biol. Cell 18:3883-3893(2007).
RN [5] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND SUBCELLULAR LOCATION.
RX PubMed=20510931; DOI=10.1016/j.cell.2010.04.011;
RA Ou C.Y., Poon V.Y., Maeder C.I., Watanabe S., Lehrman E.K., Fu A.K.,
RA Park M., Fu W.Y., Jorgensen E.M., Ip N.Y., Shen K.;
RT "Two cyclin-dependent kinase pathways are essential for polarized
RT trafficking of presynaptic components.";
RL Cell 141:846-858(2010).
RN [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21609829; DOI=10.1016/j.neuron.2011.04.002;
RA Park M., Watanabe S., Poon V.Y., Ou C.Y., Jorgensen E.M., Shen K.;
RT "CYY-1/cyclin Y and CDK-5 differentially regulate synapse elimination and
RT formation for rewiring neural circuits.";
RL Neuron 70:742-757(2011).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=22252129; DOI=10.1038/emboj.2011.499;
RA Park E.C., Ghose P., Shao Z., Ye Q., Kang L., Xu X.Z., Powell-Coffman J.A.,
RA Rongo C.;
RT "Hypoxia regulates glutamate receptor trafficking through an HIF-
RT independent mechanism.";
RL EMBO J. 31:1379-1393(2012).
RN [8] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22699897; DOI=10.1523/jneurosci.0251-12.2012;
RA Goodwin P.R., Sasaki J.M., Juo P.;
RT "Cyclin-dependent kinase 5 regulates the polarized trafficking of
RT neuropeptide-containing dense-core vesicles in Caenorhabditis elegans motor
RT neurons.";
RL J. Neurosci. 32:8158-8172(2012).
CC -!- FUNCTION: Proline-directed serine/threonine-protein kinase which, in
CC several motor neurons, promotes the polarized trafficking of synaptic
CC vesicles and dense-core vesicles (DCV). In the ventral nerve cord,
CC phosphorylates lin-10 and thereby prevents lin-10-mediated anterograde
CC trafficking of the glutamate receptor glr-1 (PubMed:17671168,
CC PubMed:21609829). Involved in the inhibition of glr-1 trafficking in
CC hypoxic conditions (PubMed:22252129). In DA motor neurons but not in DB
CC motor neurons, regulates axonal transport of synaptic vesicle
CC precursors by inhibiting dynein-mediated retrograde transport
CC (PubMed:20510931). Regulates the trafficking of dense-core vesicles in
CC DA and DB motor neurons by promoting anterograde trafficking to the
CC axon and preventing dynein-dependent trafficking to the dendrite
CC (PubMed:22699897). May regulate these processes in association with
CC cdka-1/p35 (PubMed:17671168, PubMed:20510931). Activity may be
CC regulated by cyy-1 (PubMed:20510931). Involved in synapse formation
CC during DD motor neuron remodeling by regulating transport of
CC disassembled synaptic material to the new synaptic sites probably by
CC activating the motor protein unc-104/kinesin-3 (PubMed:21609829).
CC Regulates microtubule polarity in the dendrite of DB motor neurons
CC (PubMed:22699897). May also play a role in GABAergic synaptic vesicle
CC localization in the ventral nerve cord (PubMed:16996038).
CC {ECO:0000269|PubMed:16996038, ECO:0000269|PubMed:17671168,
CC ECO:0000269|PubMed:20510931, ECO:0000269|PubMed:21609829,
CC ECO:0000269|PubMed:22252129, ECO:0000269|PubMed:22699897}.
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 Evidence={ECO:0000269|PubMed:20510931};
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; Evidence={ECO:0000269|PubMed:20510931};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:20510931};
CC Note=Binds 2 Mg(2+) ions. {ECO:0000250|UniProtKB:P24941};
CC -!- SUBUNIT: Heterodimer composed of a catalytic subunit cdk-5 and a
CC regulatory subunit cdka-1. Interaction with cdka-1 is required for cdk-
CC 5 activation. {ECO:0000305|PubMed:22699897}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20510931}. Cell
CC projection, dendrite {ECO:0000269|PubMed:20510931}. Note=Localizes
CC predominantly to presynaptic sites and in dendrites as faint puncta.
CC {ECO:0000269|PubMed:20510931}.
CC -!- DISRUPTION PHENOTYPE: Several glr-1-dependent behaviors are affected
CC including an absence of backward locomotion after nose-touching stimuli
CC and a reduction in reverse locomotion (PubMed:17671168). In L4 mutants,
CC incomplete elimination of ventral rab-3-positive synaptic vesicles
CC associated with a delay in the formation of dorsal rab-3-positive
CC synaptic vesicles in DD motor neurons. Normal formation of ventral
CC synapses in DD motor neurons at the L1 stage (PubMed:21609829). In
CC addition, mutants have an increase in anterograde dense-core vesicle
CC trafficking and in the number of plus-end-out microtubules in DB motor
CC neuron dendrites (PubMed:22699897). Reduced sensitivity to the
CC acetylcholine esterase inhibitor aldicarb (PubMed:22699897). RNAi-
CC mediated knockdown results in an abnormal distribution of GABAergic
CC synaptic vesicles at synaptic termini of the ventral nerve cord
CC (PubMed:16996038). RNAi-mediated knockdown in combination with exposure
CC to pentylenetetrazole, a GABA antagonist that induces seizures, results
CC in an increased convulsion incidence as compared to wild-type animals
CC (PubMed:16996038). {ECO:0000269|PubMed:16996038,
CC ECO:0000269|PubMed:17671168, ECO:0000269|PubMed:21609829,
CC ECO:0000269|PubMed:22699897}.
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; AF129111; AAD37121.1; -; mRNA.
DR EMBL; Z82059; CAB04875.1; -; Genomic_DNA.
DR PIR; T25374; T25374.
DR RefSeq; NP_499783.1; NM_067382.7.
DR AlphaFoldDB; G5ECH7; -.
DR SMR; G5ECH7; -.
DR ComplexPortal; CPX-4322; Cyclin-dependent protein kinase 5 holoenzyme complex.
DR IntAct; G5ECH7; 1.
DR STRING; 6239.T27E9.3; -.
DR EPD; G5ECH7; -.
DR PaxDb; G5ECH7; -.
DR PeptideAtlas; G5ECH7; -.
DR EnsemblMetazoa; T27E9.3.1; T27E9.3.1; WBGene00000407.
DR GeneID; 176774; -.
DR KEGG; cel:CELE_T27E9.3; -.
DR CTD; 176774; -.
DR WormBase; T27E9.3; CE21213; WBGene00000407; cdk-5.
DR eggNOG; KOG0662; Eukaryota.
DR GeneTree; ENSGT00940000153335; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; G5ECH7; -.
DR OMA; QHPWFND; -.
DR OrthoDB; 1010560at2759; -.
DR PhylomeDB; G5ECH7; -.
DR Reactome; R-CEL-399956; CRMPs in Sema3A signaling.
DR SignaLink; G5ECH7; -.
DR PRO; PR:G5ECH7; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00000407; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0030424; C:axon; IDA:WormBase.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0016533; C:protein kinase 5 complex; IC:ComplexPortal.
DR GO; GO:0045202; C:synapse; IDA:WormBase.
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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:WormBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:1990048; P:anterograde neuronal dense core vesicle transport; IC:ComplexPortal.
DR GO; GO:0007409; P:axonogenesis; IBA:GO_Central.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0007268; P:chemical synaptic transmission; IMP:UniProtKB.
DR GO; GO:0030951; P:establishment or maintenance of microtubule cytoskeleton polarity; IMP:UniProtKB.
DR GO; GO:1904810; P:negative regulation of dense core granule transport; IMP:UniProtKB.
DR GO; GO:0051402; P:neuron apoptotic process; IBA:GO_Central.
DR GO; GO:1904811; P:positive regulation of dense core granule transport; IMP:UniProtKB.
DR GO; GO:0051222; P:positive regulation of protein transport; IGI:UniProtKB.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:WormBase.
DR GO; GO:0010468; P:regulation of gene expression; IMP:WormBase.
DR GO; GO:1904799; P:regulation of neuron remodeling; IMP:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IMP:WormBase.
DR GO; GO:1902803; P:regulation of synaptic vesicle transport; IC:ComplexPortal.
DR GO; GO:2000331; P:regulation of terminal button organization; IMP:UniProtKB.
DR GO; GO:0000083; P:regulation of transcription involved in G1/S transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0048491; P:retrograde synaptic vesicle transport; IC:ComplexPortal.
DR GO; GO:0051932; P:synaptic transmission, GABAergic; IMP:WormBase.
DR GO; GO:0048489; P:synaptic vesicle transport; IMP:WormBase.
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 ATP-binding; Cell cycle; Cell division; Cell projection; Cytoplasm; Kinase;
KW Magnesium; Metal-binding; Neurogenesis; Nucleotide-binding;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..292
FT /note="Cyclin-dependent-like kinase 5"
FT /evidence="ECO:0000305"
FT /id="PRO_0000433389"
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 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 BINDING 131
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P24941"
FT BINDING 144
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P24941"
FT MUTAGEN 33
FT /note="K->T: Loss of activity. Decrease in glr-1 synaptic
FT localization."
FT /evidence="ECO:0000269|PubMed:17671168"
FT MUTAGEN 144
FT /note="D->N: Loss of activity. Decrease in glr-1 synaptic
FT localization. Loss of polarized trafficking of dense-core
FT vesicles in DB motor neurons."
FT /evidence="ECO:0000269|PubMed:17671168,
FT ECO:0000269|PubMed:22699897"
SQ SEQUENCE 292 AA; 33063 MW; 330EF38221F31850 CRC64;
MLNYDKMEKI GEGTYGTVFK ARNKNSGEIV ALKRVRLDDD DEGVPSSALR EICILRELKH
RNVVRLYDVV HSENKLTLVF EYCDQDLKKF FDSLNGYMDA QTARSLMLQL LRGLSFCHAH
HVLHRDLKPQ NLLINTNGTL KLADFGLARA FGVPVRCFSA EVVTLWYRPP DVLFGAKLYN
TSIDMWSAGC IFAEISNAGR PLFPGADVDD QLKRIFKQLG SPSEDNWPSI TQLPDYKPYP
IYHPTLTWSQ IVPNLNSRGR DLLQKLLVCN PAGRIDADAA LRHAYFADTS DV
