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 27-MAR-2024, entry version 221. 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-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; Q9BT49: THAP7; NbExp=3; IntAct=EBI-746189, EBI-741350; CC Q15078; Q9ULW0: TPX2; NbExp=3; IntAct=EBI-746189, EBI-1037322; CC Q15078; Q9BQ29; NbExp=3; IntAct=EBI-746189, EBI-22013570; 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; 58. 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 GlyGen; Q15078; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q15078; -. DR PhosphoSitePlus; Q15078; -. DR BioMuta; CDK5R1; -. DR DMDM; 2498217; -. DR MassIVE; Q15078; -. DR PaxDb; 9606-ENSP00000318486; -. DR PeptideAtlas; Q15078; -. DR ProteomicsDB; 60429; -. DR ABCD; Q15078; 1 sequenced antibody. DR Antibodypedia; 15411; 307 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 AGR; HGNC:1775; -. 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; HSAMFIS; -. DR OrthoDB; 2876525at2759; -. 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 Reactome; R-HSA-9768919; NPAS4 regulates expression of target genes. DR SignaLink; Q15078; -. DR SIGNOR; Q15078; -. DR BioGRID-ORCS; 8851; 8 hits in 1154 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 161 other cell types or tissues. DR ExpressionAtlas; Q15078; baseline and differential. 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 DNA-templated transcription; 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: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: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:0021722; P:superior olivary nucleus maturation; IEA:Ensembl. DR Gene3D; 1.10.472.10; Cyclin-like; 1. DR InterPro; IPR004944; CDK5_activator. DR InterPro; IPR036915; Cyclin-like_sf. DR PANTHER; PTHR23401; CYCLIN DEPENDANT KINASE-5 ACTIVATOR; 1. DR PANTHER; PTHR23401:SF2; CYCLIN-DEPENDENT KINASE 5 ACTIVATOR 1; 1. DR Pfam; PF03261; CDK5_activator; 1. DR PIRSF; PIRSF009324; Cdk5_activator; 1. DR SUPFAM; SSF47954; Cyclin-like; 1. DR Genevisible; Q15078; HS. 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 TURN 163..165 FT /evidence="ECO:0007829|PDB:7VDQ" 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 //