Protein: 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)] (P61809)
Organism: Mus musculus (Mouse)
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-BMAL1 heterodimer in association with altered stability and subcellular distribution.
Subcellular location: [Cyclin-dependent kinase 5 activator 1, p35]: Cell membrane {ECO:0000250|UniProtKB:Q15078}; Lipid-anchor {ECO:0000250|UniProtKB:Q15078}; Cytoplasmic side {ECO:0000250|UniProtKB:Q15078}. Cell projection, neuron projection {ECO:0000250|UniProtKB:Q15078}. Note=In the primary cortical neurons, p35 is present in the peripheries and nerve terminals. {ECO:0000250|UniProtKB:Q15078}.; SUBCELLULAR LOCATION: [Cyclin-dependent kinase 5 activator 1, p25]: Nucleus {ECO:0000250|UniProtKB:Q15078}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q15078}. Perikaryon {ECO:0000250|UniProtKB:Q15078}. Note=The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions. In the primary cortical neurons, p25 is primarily concentrated in the cell soma and is largely absent from neurites. {ECO:0000250|UniProtKB:Q15078}.
Sequence: MGTVLSLSPSYRKATLFEDGAATVGHYTAVQNSKNAKDKNLKRHSIISVLPWKRIVAVSAKKKNSKKAQPNSSYQSNIAHLNNENLKKSLSCANLSTFAQPPPAQPPAPPASQLSGSQTGVSSSVKKAPHPAITSAGTPKRVIVQASTSELLRCLGEFLCRRCYRLKHLSPTDPVLWLRSVDRSLLLQGWQDQGFITPANVVFLYMLCRDVISSEVGSDHELQAVLLTCLYLSYSYMGNEISYPLKPFLVESCKEAFWDRCLSVINLMSSKMLQINADPHYFTQVFSDLKNESGQEDKKRLLLGLDR
InterPro domains: - IPR004944: Cyclin-dependent kinase 5 activator (family) [1-307]
- IPR036915: Cyclin-like superfamily (homologous_superfamily) [147-292]
Interaction partners: - Cyclin-dependent kinase 5
- Microtubule-associated protein
- Calpain-1 catalytic subunit
- Calpain-2 catalytic subunit
- Cellular tumor antigen p53
- Transcription factor Jun
- Lamin-B1
- Prelamin-A/C
- Peroxiredoxin-2
- Golgin subfamily A member 2
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding), GO:0019899 (enzyme binding), GO:0019900 (kinase binding), GO:0019901 (protein kinase binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0048869 (cellular developmental process), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0019222 (regulation of metabolic process), GO:0032879 (regulation of localization), GO:0006807 (nitrogen compound metabolic process), GO:0071840 (cellular component organization or biogenesis), GO:0007272 (ensheathment of neurons), GO:0071704 (organic substance metabolic process), GO:0009892 (negative regulation of metabolic process), GO:0044237 (cellular metabolic process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0009893 (positive regulation of metabolic process), GO:0023051 (regulation of signaling), GO:0065009 (regulation of molecular function), GO:0007017 (microtubule-based process), GO:0048523 (negative regulation of cellular process), GO:0044238 (primary metabolic process), GO:0050790 (regulation of catalytic activity), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0051049 (regulation of transport), GO:1901564 (organonitrogen compound metabolic process), GO:0008366 (axon ensheathment), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0010469 (regulation of signaling receptor activity), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0032409 (regulation of transporter activity), GO:0048731 (system development), GO:0019637 (organophosphate metabolic process), GO:0009966 (regulation of signal transduction), GO:0034762 (regulation of transmembrane transport), GO:0060255 (regulation of macromolecule metabolic process), GO:0000226 (microtubule cytoskeleton organization), GO:0031324 (negative regulation of cellular metabolic process), GO:0006793 (phosphorus metabolic process), GO:0051726 (regulation of cell cycle), GO:0009894 (regulation of catabolic process), GO:0042127 (regulation of cell population proliferation), GO:0010646 (regulation of cell communication), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0009895 (negative regulation of catabolic process), GO:0016043 (cellular component organization), GO:0080090 (regulation of primary metabolic process), GO:0030030 (cell projection organization), GO:0051246 (regulation of protein metabolic process), GO:0042552 (myelination), GO:0006644 (phospholipid metabolic process), GO:0051248 (negative regulation of protein metabolic process), GO:0006796 (phosphate-containing compound metabolic process), GO:0099601 (regulation of neurotransmitter receptor activity), GO:0048666 (neuron development), GO:0036211 (protein modification process), GO:0022008 (neurogenesis), GO:0043412 (macromolecule modification), GO:0007399 (nervous system development), GO:1904029 (regulation of cyclin-dependent protein kinase activity), GO:0010563 (negative regulation of phosphorus metabolic process), GO:0007417 (central nervous system development), GO:0022898 (regulation of transmembrane transporter activity), GO:0051338 (regulation of transferase activity), GO:0043269 (regulation of monoatomic ion transport), GO:0006996 (organelle organization), GO:0030182 (neuron differentiation), GO:0051174 (regulation of phosphorus metabolic process), GO:0000079 (regulation of cyclin-dependent protein serine/threonine kinase activity), GO:0031399 (regulation of protein modification process), GO:0031400 (negative regulation of protein modification process), GO:0032412 (regulation of monoatomic ion transmembrane transporter activity), GO:0006468 (protein phosphorylation), GO:0120036 (plasma membrane bounded cell projection organization), GO:0019220 (regulation of phosphate metabolic process), GO:0016310 (phosphorylation), GO:0007010 (cytoskeleton organization), GO:0043549 (regulation of kinase activity), GO:0051348 (negative regulation of transferase activity), GO:0031175 (neuron projection development), GO:0048699 (generation of neurons), GO:0045936 (negative regulation of phosphate metabolic process), GO:0042325 (regulation of phosphorylation), GO:0001933 (negative regulation of protein phosphorylation), GO:0001932 (regulation of protein phosphorylation), GO:0033673 (negative regulation of kinase activity), GO:0042326 (negative regulation of phosphorylation), GO:0045859 (regulation of protein kinase activity), GO:0030865 (cortical cytoskeleton organization), GO:0071900 (regulation of protein serine/threonine kinase activity), GO:0006469 (negative regulation of protein kinase activity), GO:0071901 (negative regulation of protein serine/threonine kinase activity)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0150034 (distal axon), GO:0042995 (cell projection), GO:0016020 (membrane), GO:0044297 (cell body), GO:0030427 (site of polarized growth), GO:0098793 (presynapse), GO:0071944 (cell periphery), GO:0030054 (cell junction), GO:0099080 (supramolecular complex), GO:0098794 (postsynapse), GO:1902494 (catalytic complex), GO:0036477 (somatodendritic compartment), GO:0005737 (cytoplasm), GO:0043292 (contractile fiber), GO:1990234 (transferase complex), GO:0120025 (plasma membrane bounded cell projection), GO:0043229 (intracellular organelle), GO:0045202 (synapse), GO:0043228 (non-membrane-bounded organelle), GO:0043025 (neuronal cell body), GO:0043197 (dendritic spine), GO:0097447 (dendritic tree), GO:0030426 (growth cone), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0099572 (postsynaptic specialization), GO:0099081 (supramolecular polymer), GO:0043231 (intracellular membrane-bounded organelle), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0061695 (transferase complex, transferring phosphorus-containing groups), GO:0014069 (postsynaptic density), GO:0031594 (neuromuscular junction), GO:0030425 (dendrite), GO:0043005 (neuron projection), GO:0098984 (neuron to neuron synapse), GO:0099512 (supramolecular fiber), GO:0032279 (asymmetric synapse), GO:0005634 (nucleus), GO:1902911 (protein kinase complex), GO:0030424 (axon), GO:0044309 (neuron spine), GO:1902554 (serine/threonine protein kinase complex)