CD5R1_HUMAN
ID CD5R1_HUMAN Reviewed; 307 AA.
AC Q15078; E1P664; Q5U0G3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=Cyclin-dependent kinase 5 activator 1;
DE Short=CDK5 activator 1;
DE AltName: Full=Cyclin-dependent kinase 5 regulatory subunit 1;
DE AltName: Full=TPKII regulatory subunit;
DE Contains:
DE RecName: Full=Cyclin-dependent kinase 5 activator 1, p35;
DE Short=p35;
DE Contains:
DE RecName: Full=Cyclin-dependent kinase 5 activator 1, p25;
DE Short=p25;
DE AltName: Full=Tau protein kinase II 23 kDa subunit;
DE Short=p23;
DE Flags: Precursor;
GN Name=CDK5R1; Synonyms=CDK5R, NCK5A;
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].
RC TISSUE=Brain;
RX PubMed=8090221; DOI=10.1038/371419a0;
RA Tsai L.-H., Delalle I., Caviness V.S. Jr., Chae T., Harlow E.;
RT "p35 is a neural-specific regulatory subunit of cyclin-dependent kinase
RT 5.";
RL Nature 371:419-423(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
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 [6]
RP MUTAGENESIS OF GLY-2, SUBCELLULAR LOCATION, AND INVOLVEMENT IN
RP NEURODEGENERATIVE DISEASES.
RX PubMed=10604467; DOI=10.1038/45159;
RA Patrick G.N., Zukerberg L., Nikolic M., de la Monte S., Dikkes P.,
RA Tsai L.H.;
RT "Conversion of p35 to p25 deregulates Cdk5 activity and promotes
RT neurodegeneration.";
RL Nature 402:615-622(1999).
RN [7]
RP PHOSPHORYLATION BY CDK5, AND UBIQUITINATION.
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 [8]
RP INTERACTION WITH RASGRF2.
RX PubMed=15128856; DOI=10.1523/jneurosci.0690-04.2004;
RA Kesavapany S., Amin N., Zheng Y.-L., Nijhara R., Jaffe H., Sihag R.,
RA Gutkind J.S., Takahashi S., Kulkarni A., Grant P., Pant H.C.;
RT "p35/cyclin-dependent kinase 5 phosphorylation of ras guanine nucleotide
RT releasing factor 2 (RasGRF2) mediates Rac-dependent extracellular signal-
RT regulated kinase 1/2 activity, altering RasGRF2 and microtubule-associated
RT protein 1b distribution in neurons.";
RL J. Neurosci. 24:4421-4431(2004).
RN [9]
RP PHOSPHORYLATION AT SER-8 AND THR-138, AND MUTAGENESIS OF SER-8 AND THR-138.
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 [10]
RP PHOSPHORYLATION BY CDK5, INTERACTION WITH CDK5, AND SUBCELLULAR 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 [11]
RP SUBCELLULAR LOCATION, MYRISTOYLATION, AND MUTAGENESIS OF GLY-2.
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 [12]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=20213681; DOI=10.1002/pmic.200900783;
RA Suzuki T., Moriya K., Nagatoshi K., Ota Y., Ezure T., Ando E.,
RA Tsunasawa S., Utsumi T.;
RT "Strategy for comprehensive identification of human N-myristoylated
RT proteins using an insect cell-free protein synthesis system.";
RL Proteomics 10:1780-1793(2010).
RN [13]
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 [14]
RP UBIQUITINATION, AND MUTAGENESIS OF LEU-305.
RX PubMed=33398170; DOI=10.1038/s41589-020-00703-4;
RA Yan X., Wang X., Li Y., Zhou M., Li Y., Song L., Mi W., Min J., Dong C.;
RT "Molecular basis for ubiquitin ligase CRL2FEM1C-mediated recognition of C-
RT degron.";
RL Nat. Chem. Biol. 17:263-271(2021).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 145-293 IN COMPLEX WITH CDK5.
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 [16]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 100-307 IN COMPLEX WITH CDK5 AND
RP INHIBITORS.
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 [17] {ECO:0007744|PDB:6LDP, ECO:0007744|PDB:7CNG}
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 298-307 IN COMPLEX WITH FEM1B,
RP AND UBIQUITINATION.
RX PubMed=33398168; DOI=10.1038/s41589-020-00704-3;
RA Chen X., Liao S., Makaros Y., Guo Q., Zhu Z., Krizelman R., Dahan K.,
RA Tu X., Yao X., Koren I., Xu C.;
RT "Molecular basis for arginine C-terminal degron recognition by Cul2FEM1 E3
RT ligase.";
RL Nat. Chem. Biol. 17:254-262(2021).
CC -!- FUNCTION: p35 is a neuron specific activator of CDK5. The complex
CC p35/CDK5 is required for neurite outgrowth and cortical lamination.
CC Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4
CC signaling. Activator of TPKII. 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:0000269|PubMed:24235147}.
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
CC (PubMed:16039528, PubMed:17671990, PubMed:15689152). Only the
CC heterodimer shows kinase activity (PubMed:16039528, PubMed:17671990,
CC PubMed:15689152). Interacts with EPHA4 and NGEF; may mediate the
CC activation of NGEF by EPHA4 (By similarity). Interacts with RASGRF2
CC (PubMed:15128856). The complex p35/CDK5 interacts with CLOCK
CC (PubMed:24235147). {ECO:0000250|UniProtKB:P61809,
CC ECO:0000269|PubMed:15128856, ECO:0000269|PubMed:15689152,
CC ECO:0000269|PubMed:16039528, ECO:0000269|PubMed:17671990,
CC ECO:0000269|PubMed:24235147}.
CC -!- INTERACTION:
CC Q15078; Q6ZMQ8-1: AATK; NbExp=2; IntAct=EBI-746189, EBI-2008436;
CC Q15078; Q6ZMQ8-2: AATK; NbExp=6; IntAct=EBI-746189, EBI-2008441;
CC Q15078; O94983-5: CAMTA2; NbExp=3; IntAct=EBI-746189, EBI-10176008;
CC Q15078; Q00535: CDK5; NbExp=13; IntAct=EBI-746189, EBI-1041567;
CC Q15078; Q6UXH1-2: CRELD2; NbExp=3; IntAct=EBI-746189, EBI-21670927;
CC Q15078; P49184: DNASE1L1; NbExp=3; IntAct=EBI-746189, EBI-20894690;
CC Q15078; P16422: EPCAM; NbExp=3; IntAct=EBI-746189, EBI-1171184;
CC Q15078; P26715: KLRC1; NbExp=3; IntAct=EBI-746189, EBI-9018187;
CC Q15078; P43356: MAGEA2B; NbExp=3; IntAct=EBI-746189, EBI-5650739;
CC Q15078; Q8NCR3: MFI; NbExp=3; IntAct=EBI-746189, EBI-744790;
CC Q15078; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-746189, EBI-742948;
CC Q15078; A2RUH7: MYBPHL; NbExp=3; IntAct=EBI-746189, EBI-9088235;
CC Q15078; Q9NPC7: MYNN; NbExp=3; IntAct=EBI-746189, EBI-3446748;
CC Q15078; Q9HC98-4: NEK6; NbExp=3; IntAct=EBI-746189, EBI-11750983;
CC Q15078; Q8N2W9: PIAS4; NbExp=3; IntAct=EBI-746189, EBI-473160;
CC Q15078; Q96QH2: PRAM1; NbExp=3; IntAct=EBI-746189, EBI-2860740;
CC Q15078; Q96E17: RAB3C; NbExp=3; IntAct=EBI-746189, EBI-4287022;
CC Q15078; Q02978: SLC25A11; NbExp=3; IntAct=EBI-746189, EBI-359174;
CC Q15078; Q9BQ29: THAP4; NbExp=3; IntAct=EBI-746189, EBI-22013570;
CC Q15078; Q9BT49: THAP7; NbExp=3; IntAct=EBI-746189, EBI-741350;
CC Q15078; Q9ULW0: TPX2; NbExp=3; IntAct=EBI-746189, EBI-1037322;
CC -!- SUBCELLULAR LOCATION: [Cyclin-dependent kinase 5 activator 1, p35]:
CC Cell membrane {ECO:0000305|PubMed:17671990}; Lipid-anchor
CC {ECO:0000269|PubMed:18507738}; Cytoplasmic side {ECO:0000305}. Cell
CC projection, neuron projection {ECO:0000269|PubMed:10604467}. Note=In
CC the primary cortical neurons, p35 is present in the peripheries and
CC nerve terminals. {ECO:0000269|PubMed:10604467}.
CC -!- SUBCELLULAR LOCATION: [Cyclin-dependent kinase 5 activator 1, p25]:
CC Nucleus {ECO:0000269|PubMed:18507738}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:10604467}. Perikaryon
CC {ECO:0000269|PubMed:10604467}. Note=The conversion of p35 to p25
CC relocalizes the protein from the cell periphery to the cytoplasm, in
CC nuclear and perinuclear regions (PubMed:18507738). In the primary
CC cortical neurons, p25 is primarily concentrated in the cell soma and is
CC largely absent from neurites (PubMed:18507738).
CC {ECO:0000269|PubMed:18507738}.
CC -!- TISSUE SPECIFICITY: Brain and neuron specific.
CC -!- PTM: The p35 form is proteolytically cleaved by calpain, giving rise to
CC the p25 form. P35 has a 5 to 10 fold shorter half-life compared to p25.
CC The conversion results in deregulation of the CDK5 kinase: p25/CDK5
CC kinase displays an increased and altered tau phosphorylation in
CC comparison to the p35/CDK5 kinase in vivo (By similarity).
CC {ECO:0000250|UniProtKB:P61809}.
CC -!- PTM: Myristoylated. A proper myristoylation signal is essential for the
CC proper distribution of p35. {ECO:0000269|PubMed:18507738,
CC ECO:0000269|PubMed:20213681}.
CC -!- PTM: Ubiquitinated, leading to its degradation: degradation of p35 by
CC proteasome results in down-regulation of CDK5 activity
CC (PubMed:12393264). During this process, CDK5 phosphorylates p35 and
CC induces its ubiquitination and subsequent degradation
CC (PubMed:12393264). Ubiquitinated by the CRL2(FEM1B) complex, which
CC recognizes the -Gly-Leu-Asp-Arg C-degron at the C-terminus, leading to
CC its degradation (PubMed:33398170, PubMed:33398168).
CC {ECO:0000269|PubMed:12393264, ECO:0000269|PubMed:33398168,
CC ECO:0000269|PubMed:33398170}.
CC -!- PTM: Phosphorylation at Ser-8 and Thr-138 by CDK5 prevents calpain-
CC mediated proteolysis. {ECO:0000269|PubMed:17121855}.
CC -!- MISCELLANEOUS: Cleavage of p35 to p25 may be involved in the
CC pathogenesis of cytoskeletal abnormalities and neuronal death in
CC neurodegenerative diseases. The p25 form accumulates in neurons in the
CC brain of patients with Alzheimer disease, but not in normal brain. This
CC accumulation correlates with an increase in CDK5 kinase activity.
CC Application of amyloid beta peptide A-beta(1-42) induced the conversion
CC of p35 to p25 in primary cortical neurons. Expression of the p25/Cdk5
CC complex in cultured primary neurons induces cytoskeletal disruption,
CC morphological degeneration and apoptosis.
CC -!- SIMILARITY: Belongs to the cyclin-dependent kinase 5 activator family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cdk5r1/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X80343; CAA56587.1; -; mRNA.
DR EMBL; AY376350; AAQ74776.1; -; Genomic_DNA.
DR EMBL; BT019573; AAV38380.1; -; mRNA.
DR EMBL; CH471147; EAW80227.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80228.1; -; Genomic_DNA.
DR EMBL; BC020580; AAH20580.1; -; mRNA.
DR CCDS; CCDS11273.1; -.
DR PIR; S50861; S50861.
DR RefSeq; NP_003876.1; NM_003885.2.
DR RefSeq; XP_011523740.1; XM_011525438.2.
DR RefSeq; XP_016880770.1; XM_017025281.1.
DR PDB; 1H4L; X-ray; 2.65 A; D/E=147-293.
DR PDB; 1UNG; X-ray; 2.30 A; D/E=100-307.
DR PDB; 1UNH; X-ray; 2.35 A; D/E=100-307.
DR PDB; 1UNL; X-ray; 2.20 A; D/E=100-307.
DR PDB; 3O0G; X-ray; 1.95 A; D/E=145-293.
DR PDB; 6LDP; X-ray; 2.35 A; A/B=298-307.
DR PDB; 7CNG; X-ray; 3.49 A; A/B=298-307.
DR PDB; 7VDP; X-ray; 2.09 A; C/D=100-307.
DR PDB; 7VDQ; X-ray; 2.91 A; C/D=100-307.
DR PDB; 7VDR; X-ray; 2.55 A; C/D=100-307.
DR PDB; 7VDS; X-ray; 3.05 A; C/D=100-307.
DR PDBsum; 1H4L; -.
DR PDBsum; 1UNG; -.
DR PDBsum; 1UNH; -.
DR PDBsum; 1UNL; -.
DR PDBsum; 3O0G; -.
DR PDBsum; 6LDP; -.
DR PDBsum; 7CNG; -.
DR PDBsum; 7VDP; -.
DR PDBsum; 7VDQ; -.
DR PDBsum; 7VDR; -.
DR PDBsum; 7VDS; -.
DR AlphaFoldDB; Q15078; -.
DR SMR; Q15078; -.
DR BioGRID; 114376; 56.
DR ComplexPortal; CPX-2201; Cyclin-dependent protein kinase 5 holoenzyme complex, p35 variant.
DR ComplexPortal; CPX-3142; Cyclin-dependent protein kinase 5 holoenzyme complex, p25 variant.
DR DIP; DIP-24222N; -.
DR ELM; Q15078; -.
DR IntAct; Q15078; 42.
DR MINT; Q15078; -.
DR STRING; 9606.ENSP00000318486; -.
DR BindingDB; Q15078; -.
DR ChEMBL; CHEMBL2783; -.
DR DrugBank; DB07364; 6-PHENYL[5H]PYRROLO[2,3-B]PYRAZINE.
DR DrugBank; DB02052; Indirubin-3'-monoxime.
DR DrugCentral; Q15078; -.
DR iPTMnet; Q15078; -.
DR PhosphoSitePlus; Q15078; -.
DR BioMuta; CDK5R1; -.
DR DMDM; 2498217; -.
DR MassIVE; Q15078; -.
DR PaxDb; Q15078; -.
DR PeptideAtlas; Q15078; -.
DR PRIDE; Q15078; -.
DR ProteomicsDB; 60429; -.
DR ABCD; Q15078; 1 sequenced antibody.
DR Antibodypedia; 15411; 282 antibodies from 34 providers.
DR DNASU; 8851; -.
DR Ensembl; ENST00000313401.4; ENSP00000318486.3; ENSG00000176749.9.
DR GeneID; 8851; -.
DR KEGG; hsa:8851; -.
DR MANE-Select; ENST00000313401.4; ENSP00000318486.3; NM_003885.3; NP_003876.1.
DR UCSC; uc002hhn.4; human.
DR CTD; 8851; -.
DR DisGeNET; 8851; -.
DR GeneCards; CDK5R1; -.
DR HGNC; HGNC:1775; CDK5R1.
DR HPA; ENSG00000176749; Tissue enriched (brain).
DR MIM; 603460; gene.
DR neXtProt; NX_Q15078; -.
DR OpenTargets; ENSG00000176749; -.
DR PharmGKB; PA26311; -.
DR VEuPathDB; HostDB:ENSG00000176749; -.
DR eggNOG; KOG3932; Eukaryota.
DR GeneTree; ENSGT00390000008812; -.
DR HOGENOM; CLU_034132_2_0_1; -.
DR InParanoid; Q15078; -.
DR OMA; EVATDHE; -.
DR OrthoDB; 1492547at2759; -.
DR PhylomeDB; Q15078; -.
DR TreeFam; TF101036; -.
DR PathwayCommons; Q15078; -.
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 SignaLink; Q15078; -.
DR SIGNOR; Q15078; -.
DR BioGRID-ORCS; 8851; 7 hits in 1078 CRISPR screens.
DR EvolutionaryTrace; Q15078; -.
DR GeneWiki; CDK5R1; -.
DR GenomeRNAi; 8851; -.
DR Pharos; Q15078; Tchem.
DR PRO; PR:Q15078; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q15078; protein.
DR Bgee; ENSG00000176749; Expressed in cortical plate and 160 other tissues.
DR ExpressionAtlas; Q15078; baseline and differential.
DR Genevisible; Q15078; HS.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:0043292; C:contractile fiber; ISS:UniProtKB.
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:0043197; C:dendritic spine; ISS:UniProtKB.
DR GO; GO:0030426; C:growth cone; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0031594; C:neuromuscular junction; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:ARUK-UCL.
DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
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:0051015; F:actin filament binding; IEA:Ensembl.
DR GO; GO:0043014; F:alpha-tubulin binding; ISS:ARUK-UCL.
DR GO; GO:0048487; F:beta-tubulin binding; ISS:ARUK-UCL.
DR GO; GO:0045296; F:cadherin binding; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0061575; F:cyclin-dependent protein serine/threonine kinase activator activity; IBA:GO_Central.
DR GO; GO:0046875; F:ephrin receptor binding; IEA:Ensembl.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IEA:Ensembl.
DR GO; GO:0016301; F:kinase activity; ISS:UniProtKB.
DR GO; GO:0002020; F:protease binding; IEA:Ensembl.
DR GO; GO:0030295; F:protein kinase activator activity; TAS:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IDA:UniProtKB.
DR GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
DR GO; GO:0007413; P:axonal fasciculation; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; ISS:UniProtKB.
DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IEA:Ensembl.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0007213; P:G protein-coupled acetylcholine receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0070315; P:G1 to G0 transition involved in cell differentiation; IEA:Ensembl.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; ISS:UniProtKB.
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:0045892; P:negative regulation of transcription, DNA-templated; IMP:DFLAT.
DR GO; GO:0007158; P:neuron cell-cell adhesion; ISS:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; ISS:UniProtKB.
DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; IDA:ARUK-UCL.
DR GO; GO:0031116; P:positive regulation of microtubule polymerization; ISS:ARUK-UCL.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; IEA:Ensembl.
DR GO; GO:2000273; P:positive regulation of signaling receptor activity; IDA:ARUK-UCL.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; TAS:ProtInc.
DR GO; GO:0061001; P:regulation of dendritic spine morphogenesis; ISS:UniProtKB.
DR GO; GO:0016241; P:regulation of macroautophagy; NAS:ParkinsonsUK-UCL.
DR GO; GO:0045664; P:regulation of neuron differentiation; NAS:UniProtKB.
DR GO; GO:0098693; P:regulation of synaptic vesicle cycle; IEA:Ensembl.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0042501; P:serine phosphorylation of STAT protein; IEA:Ensembl.
DR GO; GO:0021722; P:superior olivary nucleus maturation; IEA:Ensembl.
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 1: Evidence at protein level;
KW 3D-structure; Biological rhythms; Cell membrane; Cell projection;
KW Cytoplasm; Lipoprotein; Membrane; Myristate; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..307
FT /note="Cyclin-dependent kinase 5 activator 1, p35"
FT /id="PRO_0000004794"
FT CHAIN 99..307
FT /note="Cyclin-dependent kinase 5 activator 1, p25"
FT /id="PRO_0000004795"
FT REGION 97..136
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 111..129
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 98..99
FT /note="Cleavage; by calpain"
FT /evidence="ECO:0000250|UniProtKB:P61809"
FT MOD_RES 8
FT /note="Phosphoserine; by CDK5"
FT /evidence="ECO:0000269|PubMed:17121855"
FT MOD_RES 138
FT /note="Phosphothreonine; by CDK5"
FT /evidence="ECO:0000269|PubMed:17121855"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:20213681"
FT MUTAGEN 2
FT /note="G->A: Absent from the cell periphery."
FT /evidence="ECO:0000269|PubMed:10604467,
FT ECO:0000269|PubMed:18507738"
FT MUTAGEN 8
FT /note="S->A: Increased susceptibility to calpain."
FT /evidence="ECO:0000269|PubMed:17121855"
FT MUTAGEN 8
FT /note="S->E: Reduced susceptibility to calpain."
FT /evidence="ECO:0000269|PubMed:17121855"
FT MUTAGEN 138
FT /note="T->A: Increased susceptibility to calpain."
FT /evidence="ECO:0000269|PubMed:17121855"
FT MUTAGEN 138
FT /note="T->E: Reduced susceptibility to calpain."
FT /evidence="ECO:0000269|PubMed:17121855"
FT MUTAGEN 305
FT /note="L->A: In L-3A mutant; abolished recognition and
FT ubiquitination by the CRL2(FEM1B) complex."
FT /evidence="ECO:0000269|PubMed:33398170"
FT MUTAGEN 305
FT /note="L->R: In L-3R mutant; abolished recognition and
FT ubiquitination by the CRL2(FEM1B) complex, while promoting
FT recognition and ubiquitination by the CRL2(FEM1B) complex."
FT /evidence="ECO:0000269|PubMed:33398170"
FT HELIX 148..162
FT /evidence="ECO:0007829|PDB:3O0G"
FT HELIX 172..187
FT /evidence="ECO:0007829|PDB:3O0G"
FT HELIX 198..211
FT /evidence="ECO:0007829|PDB:3O0G"
FT HELIX 219..237
FT /evidence="ECO:0007829|PDB:3O0G"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:3O0G"
FT HELIX 246..248
FT /evidence="ECO:0007829|PDB:3O0G"
FT HELIX 254..277
FT /evidence="ECO:0007829|PDB:3O0G"
FT HELIX 279..290
FT /evidence="ECO:0007829|PDB:3O0G"
FT TURN 301..304
FT /evidence="ECO:0007829|PDB:6LDP"
SQ SEQUENCE 307 AA; 34060 MW; D1C29A07AFF1B644 CRC64;
MGTVLSLSPS YRKATLFEDG AATVGHYTAV QNSKNAKDKN LKRHSIISVL PWKRIVAVSA
KKKNSKKVQP NSSYQNNITH LNNENLKKSL SCANLSTFAQ PPPAQPPAPP ASQLSGSQTG
GSSSVKKAPH PAVTSAGTPK RVIVQASTSE LLRCLGEFLC RRCYRLKHLS PTDPVLWLRS
VDRSLLLQGW QDQGFITPAN VVFLYMLCRD VISSEVGSDH ELQAVLLTCL YLSYSYMGNE
ISYPLKPFLV ESCKEAFWDR CLSVINLMSS KMLQINADPH YFTQVFSDLK NESGQEDKKR
LLLGLDR
