| IED ID | IndEnz0002019158 |
| Enzyme Type ID | protease019158 |
| Protein Name |
Cyclin-dependent kinase 5 activator 1 CDK5 activator 1 Cyclin-dependent kinase 5 regulatory subunit 1 TPKII regulatory subunit Cleaved into: Cyclin-dependent kinase 5 activator 1, p35 p35 ; Cyclin-dependent kinase 5 activator 1, p25 p25 Tau protein kinase II 23 kDa subunit p23 |
| Gene Name | CDK5R1 CDK5R NCK5A |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MGTVLSLSPSYRKATLFEDGAATVGHYTAVQNSKNAKDKNLKRHSIISVLPWKRIVAVSAKKKNSKKVQPNSSYQNNITHLNNENLKKSLSCANLSTFAQPPPAQPPAPPASQLSGSQTGGSSSVKKAPHPAVTSAGTPKRVIVQASTSELLRCLGEFLCRRCYRLKHLSPTDPVLWLRSVDRSLLLQGWQDQGFITPANVVFLYMLCRDVISSEVGSDHELQAVLLTCLYLSYSYMGNEISYPLKPFLVESCKEAFWDRCLSVINLMSSKMLQINADPHYFTQVFSDLKNESGQEDKKRLLLGLDR |
| Enzyme Length | 307 |
| Uniprot Accession Number | Q15078 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: p35 is a neuron specific activator of CDK5. The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Activator of TPKII. 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:24235147}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (1); Chain (2); Compositional bias (1); Helix (7); Initiator methionine (1); Lipidation (1); Modified residue (2); Mutagenesis (7); Region (1); Site (1) |
| Keywords | 3D-structure;Biological rhythms;Cell membrane;Cell projection;Cytoplasm;Lipoprotein;Membrane;Myristate;Nucleus;Phosphoprotein;Reference proteome;Ubl conjugation |
| Interact With | Q6ZMQ8-1; Q6ZMQ8-2; O94983-5; Q00535; Q6UXH1-2; P49184; P16422; P26715; P43356; Q8NCR3; Q5JR59; A2RUH7; Q9NPC7; Q9HC98-4; Q8N2W9; Q96QH2; Q96E17; Q02978; Q9BQ29; Q9BT49; Q9ULW0 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Cyclin-dependent kinase 5 activator 1, p35]: Cell membrane {ECO:0000305|PubMed:17671990}; Lipid-anchor {ECO:0000269|PubMed:18507738}; Cytoplasmic side {ECO:0000305}. Cell projection, neuron projection {ECO:0000269|PubMed:10604467}. Note=In the primary cortical neurons, p35 is present in the peripheries and nerve terminals. {ECO:0000269|PubMed:10604467}.; SUBCELLULAR LOCATION: [Cyclin-dependent kinase 5 activator 1, p25]: Nucleus {ECO:0000269|PubMed:18507738}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:10604467}. Perikaryon {ECO:0000269|PubMed:10604467}. Note=The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions (PubMed:18507738). In the primary cortical neurons, p25 is primarily concentrated in the cell soma and is largely absent from neurites (PubMed:18507738). {ECO:0000269|PubMed:18507738}. |
| Modified Residue | MOD_RES 8; /note=Phosphoserine; by CDK5; /evidence=ECO:0000269|PubMed:17121855; MOD_RES 138; /note=Phosphothreonine; by CDK5; /evidence=ECO:0000269|PubMed:17121855 |
| Post Translational Modification | PTM: The p35 form is proteolytically cleaved by calpain, giving rise to the p25 form. P35 has a 5 to 10 fold shorter half-life compared to p25. The conversion results in deregulation of the CDK5 kinase: p25/CDK5 kinase displays an increased and altered tau phosphorylation in comparison to the p35/CDK5 kinase in vivo (By similarity). {ECO:0000250|UniProtKB:P61809}.; PTM: Myristoylated. A proper myristoylation signal is essential for the proper distribution of p35. {ECO:0000269|PubMed:18507738, ECO:0000269|PubMed:20213681}.; PTM: Ubiquitinated, leading to its degradation: degradation of p35 by proteasome results in down-regulation of CDK5 activity (PubMed:12393264). During this process, CDK5 phosphorylates p35 and induces its ubiquitination and subsequent degradation (PubMed:12393264). Ubiquitinated by the CRL2(FEM1B) complex, which recognizes the -Gly-Leu-Asp-Arg C-degron at the C-terminus, leading to its degradation (PubMed:33398170, PubMed:33398168). {ECO:0000269|PubMed:12393264, ECO:0000269|PubMed:33398168, ECO:0000269|PubMed:33398170}.; PTM: Phosphorylation at Ser-8 and Thr-138 by CDK5 prevents calpain-mediated proteolysis. {ECO:0000269|PubMed:17121855}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (7) |
| Cross Reference PDB | 1H4L; 1UNG; 1UNH; 1UNL; 3O0G; 6LDP; 7CNG; |
| Mapped Pubmed ID | 10500146; 10830966; 11331872; 11583627; 11784720; 12064478; 12226093; 12230554; 12372285; 12826674; 12859671; 14521924; 14685275; 14976144; 15123618; 15175076; 15342635; 15492003; 15536496; 15652488; 15676027; 15741232; 15917097; 16189514; 16407256; 16425041; 16678793; 17036052; 17060323; 17341134; 17491008; 17493033; 17496813; 17591690; 17607942; 18247371; 18325333; 18326489; 18480410; 18490454; 18691386; 18829967; 19154537; 19638632; 19776350; 19874574; 19913121; 20097924; 20354813; 20518484; 20628086; 21130530; 21220307; 21389115; 21544067; 21625387; 21772061; 22899714; 22964075; 23151508; 23602568; 24085300; 24550687; 24561619; 24725413; 24802945; 25036637; 25391294; 25416956; 26469698; 27343180; 27387995; 29997370; 30718749; 33346796; 7592934; 8090222; 8846918; 9010203; 9343422; 9822744; |
| Motif | |
| Gene Encoded By | |
| Mass | 34,060 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |