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Details on Person UniProt:Q15078 CDK5R1

Class:Id	ReferenceGeneProduct:51678
_chainChangeLog	initiator methionine:1 added on Fri February 6 2015;chain:2-307 added on Fri February 6 2015;chain:99-307 added on Fri February 6 2015;initiator methionine:1 for 51678 removed on Fri Nov 03 2023;initiator methionine: for 51678 added on Fri Nov 03 2023;initiator methionine: for 51678 removed on Fri Aug 15 2025;initiator methionine:1 for 51678 added on Fri Aug 15 2025
_displayName	UniProt:Q15078 CDK5R1
_timestamp	2025-08-15 21:51:44
chain	initiator methionine:1 chain:2-307 chain:99-307
checksum	D1C29A07AFF1B644
comment	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.SUBUNIT Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) and macromolecular complex composed of at least CDK5, CDK5R1 (p35) and CDK5RAP1 or CDK5RAP2 or CDK5RAP3 (PubMed:15689152, PubMed:16039528, PubMed:17671990). Only the heterodimer shows kinase activity (PubMed:15689152, PubMed:16039528, PubMed:17671990). Interacts with EPHA4 and NGEF; may mediate the activation of NGEF by EPHA4 (By similarity). Interacts with RASGRF2 (PubMed:15128856). The complex p35/CDK5 interacts with CLOCK (PubMed:24235147).INTERACTION In the primary cortical neurons, p35 is present in the peripheries and nerve terminals.SUBCELLULAR LOCATION 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).TISSUE SPECIFICITY Brain and neuron specific.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).PTM Myristoylated. A proper myristoylation signal is essential for the proper distribution of p35.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:33398168, PubMed:33398170).PTM Phosphorylation at Ser-8 and Thr-138 by CDK5 prevents calpain-mediated proteolysis.MISCELLANEOUS Cleavage of p35 to p25 may be involved in the pathogenesis of cytoskeletal abnormalities and neuronal death in neurodegenerative diseases. The p25 form accumulates in neurons in the brain of patients with Alzheimer disease, but not in normal brain. This accumulation correlates with an increase in CDK5 kinase activity. Application of amyloid beta peptide A-beta(1-42) induced the conversion of p35 to p25 in primary cortical neurons. Expression of the p25/Cdk5 complex in cultured primary neurons induces cytoskeletal disruption, morphological degeneration and apoptosis.SIMILARITY Belongs to the cyclin-dependent kinase 5 activator family.
description	recommendedName: Cyclin-dependent kinase 5 activator 1 shortName: CDK5 activator 1 alternativeName: Cyclin-dependent kinase 5 regulatory subunit 1 alternativeName: TPKII regulatory subunit component recommendedName: Cyclin-dependent kinase 5 activator 1, p35 shortName: p35 /component component recommendedName: Cyclin-dependent kinase 5 activator 1, p25 shortName: p25 alternativeName: Tau protein kinase II 23 kDa subunit shortName: p23 /component
geneName	CDK5R1 CDK5R NCK5A
identifier	Q15078
isSequenceChanged	FALSE
keyword	3D-structure Biological rhythms Cell membrane Cell projection Cytoplasm Lipoprotein Membrane Myristate Nucleus Phosphoprotein Proteomics identification Reference proteome Ubl conjugation
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15
name	CDK5R1
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8998793] ENSEMBL:ENSG00000176749 CDK5R1 [Homo sapiens]
secondaryIdentifier	CD5R1_HUMAN E1P664 Q5U0G3
sequenceLength	307
species	[Species:48887] Homo sapiens
(referenceEntity)	[EntityWithAccessionedSequence:421083] MyrG-CDK5R1(2-307) [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:6805262] CDK5R1(99-307) [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:8863400] MyrG-CDK5R1(2-98) [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:8863415] CDK5R1(99-307) [cytosol] [Homo sapiens]
(referenceSequence)	[ModifiedResidue:8863408] N-myristoylglycine at 2
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No pathways have been reviewed or authored by UniProt:Q15078 CDK5R1 (51678)