CD5R1_CAEEL
ID CD5R1_CAEEL Reviewed; 356 AA.
AC Q22695; Q0G843;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2004, sequence version 2.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Cyclin-dependent kinase 5 activator 1;
DE AltName: Full=p35 {ECO:0000305|PubMed:17671168};
GN Name=cdka-1 {ECO:0000312|WormBase:T23F11.3a};
GN ORFNames=T23F11.3 {ECO:0000312|WormBase:T23F11.3a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
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 [2]
RP FUNCTION, TISSUE SPECIFICITY, 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 [3]
RP FUNCTION.
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 [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
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 [5]
RP FUNCTION.
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: Activator of the kinase cdk-5 (By similarity). In several
CC motor neurons, promotes the polarized trafficking of synaptic vesicles
CC and dense-core vesicles. In the ventral nerve cord, regulates the
CC synaptic localization of the glutamate receptor, glr-1
CC (PubMed:17671168). In DA motor neurons, regulates axonal transport of
CC synaptic vesicle precursors by inhibiting dynein-mediated retrograde
CC transport (PubMed:20510931). Regulates the polarized distribution of
CC dense-core vesicles in DB motor neurons (PubMed:22699897). May regulate
CC these processes in association with cdk-5 (PubMed:17671168,
CC PubMed:20510931). May also play a role in GABAergic synaptic vesicle
CC localization in the ventral nerve cord (PubMed:16996038).
CC {ECO:0000250|UniProtKB:P61809, ECO:0000269|PubMed:16996038,
CC ECO:0000269|PubMed:17671168, ECO:0000269|PubMed:20510931,
CC ECO:0000269|PubMed:22699897}.
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}. Cell projection,
CC axon {ECO:0000269|PubMed:20510931}. Note=Presynaptic localization in
CC the axon and punctate localization in the dendrite.
CC {ECO:0000269|PubMed:20510931}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:T23F11.3a};
CC IsoId=Q22695-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:T23F11.3b};
CC IsoId=Q22695-2; Sequence=VSP_057774;
CC -!- TISSUE SPECIFICITY: Expressed in all classes of neurons in the ventral
CC cord. {ECO:0000269|PubMed:16996038}.
CC -!- DISRUPTION PHENOTYPE: Accumulation of presynaptic components in the
CC dendrite of DA motor neurons (PubMed:20510931). RNAi-mediated knockdown
CC results in an abnormal distribution of GABAergic synaptic vesicles at
CC synaptic termini of the ventral nerve cord (PubMed:16996038). RNAi-
CC mediated knockdown in combination with exposure to pentylenetetrazole,
CC a GABA antagonist that induces seizures, results in an increased
CC convulsion incidence as compared to wild-type animals
CC (PubMed:16996038). {ECO:0000269|PubMed:16996038,
CC ECO:0000269|PubMed:20510931}.
CC -!- SIMILARITY: Belongs to the cyclin-dependent kinase 5 activator family.
CC {ECO:0000305}.
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DR EMBL; Z46343; CAA86458.2; -; Genomic_DNA.
DR EMBL; Z46343; CAL36520.1; -; Genomic_DNA.
DR PIR; T25178; T25178.
DR RefSeq; NP_001076649.1; NM_001083180.2. [Q22695-1]
DR RefSeq; NP_001076650.1; NM_001083181.2. [Q22695-2]
DR AlphaFoldDB; Q22695; -.
DR SMR; Q22695; -.
DR BioGRID; 53466; 1.
DR ComplexPortal; CPX-4322; Cyclin-dependent protein kinase 5 holoenzyme complex.
DR IntAct; Q22695; 1.
DR STRING; 6239.T23F11.3b.2; -.
DR EPD; Q22695; -.
DR PaxDb; Q22695; -.
DR EnsemblMetazoa; T23F11.3a.1; T23F11.3a.1; WBGene00011955. [Q22695-1]
DR EnsemblMetazoa; T23F11.3b.1; T23F11.3b.1; WBGene00011955. [Q22695-2]
DR GeneID; 188812; -.
DR KEGG; cel:CELE_T23F11.3; -.
DR UCSC; T23F11.3a.1; c. elegans.
DR CTD; 188812; -.
DR WormBase; T23F11.3a; CE33707; WBGene00011955; cdka-1. [Q22695-1]
DR WormBase; T23F11.3b; CE01096; WBGene00011955; cdka-1. [Q22695-2]
DR eggNOG; KOG3932; Eukaryota.
DR GeneTree; ENSGT00390000008812; -.
DR InParanoid; Q22695; -.
DR OMA; PAQLVMW; -.
DR OrthoDB; 857854at2759; -.
DR Reactome; R-CEL-399956; CRMPs in Sema3A signaling.
DR PRO; PR:Q22695; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00011955; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
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:0030426; C:growth cone; IBA:GO_Central.
DR GO; GO:0016533; C:protein kinase 5 complex; IC:ComplexPortal.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0061575; F:cyclin-dependent protein serine/threonine kinase activator activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:1990048; P:anterograde neuronal dense core vesicle transport; IC:ComplexPortal.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:1904809; P:regulation of dense core granule transport; 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: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; IPR004944; CDK5_activator.
DR InterPro; IPR036915; Cyclin-like_sf.
DR PANTHER; PTHR23401; PTHR23401; 1.
DR Pfam; PF03261; CDK5_activator; 1.
DR PIRSF; PIRSF009324; Cdk5_activator; 1.
DR SUPFAM; SSF47954; SSF47954; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell projection; Cytoplasm; Reference proteome.
FT CHAIN 1..356
FT /note="Cyclin-dependent kinase 5 activator 1"
FT /id="PRO_0000144176"
FT REGION 1..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 66..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..24
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 35..53
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 203
FT /note="E -> EKRGTKKTIIQ (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057774"
SQ SEQUENCE 356 AA; 39875 MW; 883BE95FD1066D8B CRC64;
MGANLTSPLP HHHRTQTTSV CNHLFSPGDG GPTFAPQRDS NTSSRSSSNA KESVLMQGWN
WSKRNIQPVM SRRSLPKSGS SSEATSSKSS DSLVSFTRNV STSTSSQYGK ISISLDRNQN
YKSVPRPSDT TTIIPNYYSL REEFRRGLQI NTRQDLVNNN LASNDLSVIG SPKHVPRPRS
VLRDDNANCD ISPIAEQENV PSEASTSELL RGLGIFISNN CDVSDFDPAH LVTWLRSVDR
SLLLQGWQDI AFINPANLVF IFLLVRDVLP DERHLIHTLE ELHAWILSCL YVSYSYMGNE
ISYPLKPFLI GNDRNTFWNR CVAMVTSHSR QMLLLNSSST FFSEVFTDLK HCSSSE
