Cyclin-dependent kinase 5 activator 1

Details

Name
Cyclin-dependent kinase 5 activator 1
Synonyms
  • CDK5 activator 1
  • CDK5R
  • Cyclin-dependent kinase 5 regulatory subunit 1
  • NCK5A
  • TPKII regulatory subunit
Gene Name
CDK5R1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0020722|Cyclin-dependent kinase 5 activator 1
MGTVLSLSPSYRKATLFEDGAATVGHYTAVQNSKNAKDKNLKRHSIISVLPWKRIVAVSA
KKKNSKKVQPNSSYQNNITHLNNENLKKSLSCANLSTFAQPPPAQPPAPPASQLSGSQTG
GSSSVKKAPHPAVTSAGTPKRVIVQASTSELLRCLGEFLCRRCYRLKHLSPTDPVLWLRS
VDRSLLLQGWQDQGFITPANVVFLYMLCRDVISSEVGSDHELQAVLLTCLYLSYSYMGNE
ISYPLKPFLVESCKEAFWDRCLSVINLMSSKMLQINADPHYFTQVFSDLKNESGQEDKKR
LLLGLDR
Number of residues
307
Molecular Weight
34059.85
Theoretical pI
9.8
GO Classification
Functions
cadherin binding / calcium ion binding / cyclin-dependent protein kinase 5 activator activity / cyclin-dependent protein serine/threonine kinase activity / kinase activity / protein kinase activity / protein kinase binding / protein serine/threonine kinase activator activity
Processes
axon guidance / axonal fasciculation / brain development / cell proliferation / cerebellum development / embryo development / ephrin receptor signaling pathway / G-protein coupled acetylcholine receptor signaling pathway / hippocampus development / ionotropic glutamate receptor signaling pathway / layer formation in cerebral cortex / negative regulation of axon extension / negative regulation of transcription, DNA-templated / neuron cell-cell adhesion / neuron differentiation / neuron migration / neuron projection development / peptidyl-serine phosphorylation / peptidyl-threonine phosphorylation / positive regulation of cell cycle arrest / positive regulation of neuron apoptotic process / positive regulation of protein serine/threonine kinase activity / positive regulation of protein targeting to membrane / regulation of actin cytoskeleton organization / regulation of cyclin-dependent protein serine/threonine kinase activity / regulation of dendritic spine morphogenesis / regulation of microtubule cytoskeleton organization / regulation of neuron differentiation / rhythmic process / serine phosphorylation of STAT3 protein / superior olivary nucleus maturation
Components
axon / contractile fiber / cyclin-dependent protein kinase 5 holoenzyme complex / cytoplasm / cytosol / dendrite / dendritic spine / growth cone / intracellular membrane-bounded organelle / membrane / neuromuscular junction / neuronal cell body / nucleoplasm / nucleus / perinuclear region of cytoplasm / plasma membrane / postsynaptic density
General Function
Protein serine/threonine kinase activator activity
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0020723|Cyclin-dependent kinase 5 activator 1 (CDK5R1)
ATGGGCACGGTGCTGTCCCTGTCTCCCAGCTACCGGAAGGCCACGCTGTTTGAGGATGGC
GCGGCCACCGTGGGCCACTATACGGCCGTACAGAACAGCAAGAACGCCAAGGACAAGAAC
CTGAAGCGCCACTCCATCATCTCCGTGCTGCCTTGGAAGAGAATCGTGGCCGTGTCGGCC
AAGAAGAAGAACTCCAAGAAGGTGCAGCCCAACAGCAGCTACCAGAACAACATCACGCAC
CTCAACAATGAGAACCTGAAGAAGTCGCTGTCGTGCGCCAACCTGTCCACATTCGCCCAG
CCCCCACCGGCCCAGCCGCCTGCACCCCCGGCCAGCCAGCTCTCGGGTTCCCAGACCGGG
GGCTCCTCCTCAGTCAAGAAAGCCCCTCACCCTGCCGTCACCTCCGCAGGGACGCCCAAA
CGGGTCATCGTCCAGGCGTCCACCAGTGAGCTGCTTCGCTGCCTGGGTGAGTTTCTCTGC
CGCCGGTGCTACCGCCTGAAGCACCTGTCCCCCACGGACCCCGTGCTCTGGCTGCGCAGC
GTGGACCGCTCGCTGCTTCTGCAGGGCTGGCAGGACCAGGGCTTCATCACGCCGGCCAAC
GTGGTCTTCCTCTACATGCTCTGCAGGGATGTTATCTCCTCCGAGGTGGGCTCGGATCAC
GAGCTCCAGGCCGTCCTGCTGACATGCCTGTACCTCTCCTACTCCTACATGGGCAACGAG
ATCTCCTACCCGCTCAAGCCCTTCCTGGTGGAGAGCTGCAAGGAGGCCTTTTGGGACCGT
TGCCTCTCTGTCATCAACCTCATGAGCTCAAAGATGCTGCAGATAAATGCCGACCCACAC
TACTTCACACAGGTCTTCTCCGACCTGAAGAACGAGAGCGGCCAGGAGGACAAGAAGCGG
CTCCTCCTAGGCCTGGATCGGTGA
Chromosome Location
17
Locus
17q11.2
External Identifiers
ResourceLink
UniProtKB IDQ15078
UniProtKB Entry NameCD5R1_HUMAN
GenBank Protein ID558671
GenBank Gene IDX80343
HGNC IDHGNC:1775
General References
  1. Tsai LH, Delalle I, Caviness VS Jr, Chae T, Harlow E: p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. Nature. 1994 Sep 29;371(6496):419-23. [Article]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  3. Patrick GN, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai LH: Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature. 1999 Dec 9;402(6762):615-22. [Article]
  4. Kerokoski P, Suuronen T, Salminen A, Soininen H, Pirttila T: Influence of phosphorylation of p35, an activator of cyclin-dependent kinase 5 (cdk5), on the proteolysis of p35. Brain Res Mol Brain Res. 2002 Oct 15;106(1-2):50-6. [Article]
  5. Kesavapany S, Amin N, Zheng YL, Nijhara R, Jaffe H, Sihag R, Gutkind JS, Takahashi S, Kulkarni A, Grant P, Pant HC: p35/cyclin-dependent kinase 5 phosphorylation of ras guanine nucleotide releasing factor 2 (RasGRF2) mediates Rac-dependent Extracellular Signal-regulated kinase 1/2 activity, altering RasGRF2 and microtubule-associated protein 1b distribution in neurons. J Neurosci. 2004 May 5;24(18):4421-31. [Article]
  6. Kamei H, Saito T, Ozawa M, Fujita Y, Asada A, Bibb JA, Saido TC, Sorimachi H, Hisanaga S: Suppression of calpain-dependent cleavage of the CDK5 activator p35 to p25 by site-specific phosphorylation. J Biol Chem. 2007 Jan 19;282(3):1687-94. Epub 2006 Nov 22. [Article]
  7. Sato K, Zhu YS, Saito T, Yotsumoto K, Asada A, Hasegawa M, Hisanaga S: Regulation of membrane association and kinase activity of Cdk5-p35 by phosphorylation of p35. J Neurosci Res. 2007 Nov 1;85(14):3071-8. [Article]
  8. Asada A, Yamamoto N, Gohda M, Saito T, Hayashi N, Hisanaga S: Myristoylation of p39 and p35 is a determinant of cytoplasmic or nuclear localization of active cyclin-dependent kinase 5 complexes. J Neurochem. 2008 Aug;106(3):1325-36. doi: 10.1111/j.1471-4159.2008.05500.x. Epub 2008 May 26. [Article]
  9. Suzuki T, Moriya K, Nagatoshi K, Ota Y, Ezure T, Ando E, Tsunasawa S, Utsumi T: Strategy for comprehensive identification of human N-myristoylated proteins using an insect cell-free protein synthesis system. Proteomics. 2010 May;10(9):1780-93. doi: 10.1002/pmic.200900783. [Article]
  10. Kwak Y, Jeong J, Lee S, Park YU, Lee SA, Han DH, Kim JH, Ohshima T, Mikoshiba K, Suh YH, Cho S, Park SK: Cyclin-dependent kinase 5 (Cdk5) regulates the function of CLOCK protein by direct phosphorylation. J Biol Chem. 2013 Dec 27;288(52):36878-89. doi: 10.1074/jbc.M113.494856. Epub 2013 Nov 14. [Article]
  11. Ahn JS, Radhakrishnan ML, Mapelli M, Choi S, Tidor B, Cuny GD, Musacchio A, Yeh LA, Kosik KS: Defining Cdk5 ligand chemical space with small molecule inhibitors of tau phosphorylation. Chem Biol. 2005 Jul;12(7):811-23. [Article]
  12. Mapelli M, Massimiliano L, Crovace C, Seeliger MA, Tsai LH, Meijer L, Musacchio A: Mechanism of CDK5/p25 binding by CDK inhibitors. J Med Chem. 2005 Feb 10;48(3):671-9. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB073646-PHENYL[5H]PYRROLO[2,3-B]PYRAZINEexperimentalunknownDetails
DB02052Indirubin-3'-monoximeexperimentalunknownDetails