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FLASH GENE
Symbol CDK5R1 contributors: mct/npt/pgu - updated : 15-06-2016
HGNC name cyclin-dependent kinase 5, regulatory subunit 1 (p35)
HGNC id 1775
Location 17q11.2      Physical location : 30.814.104 - 30.818.270
Synonym name
  • neuronal CDK5 activator
  • TPKII regulatory subunit
  • cyclin-dependent kinase 5 activator 1
  • tau protein kinase II 23kDa subunit
  • Synonym symbol(s) NCK5A, P35, CDK5P35, P35NCK5A, NCLK, MGC33831, p23, p25, p35, p35nck5a
    DNA
    TYPE functioning gene
    STRUCTURE 5.98 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure intronless
    MAPPING cloned Y linked   status provisional
    Map pter - D17S921 - D17S922 - ADORA2B - MFAP4 - D17S805 - ALDH3A1 ,ALDH3A2 - CCL1 - NF1 NF1 - CDK5R1 - D17S1800 - D17S1880 - D17S798 - pter
    Authors GeneMap (98)
    Physical map
    BLMH 17q11.2 bleomycin hydrolase LOC388364 17 similar to AWKS9372 CPD 17q11.2 carboxypeptidase D GOSR1 17q11.2 golgi SNAP receptor complex member 1 LOC390784 17 similar to Arachidonate 12-lipoxygenase, 12S-type (12-LOX) (Platelet-type lipoxygenase 12) LOC388365 17 LOC388365 DKFZP434O047 17q11.2 DKFZP434O047 protein LOC284089 17q11.2 similar to keratin 17 LOC388366 17 LOC388366 DKFZp667M2411 17q11.2 hypothetical protein DKFZp667M2411 LOC388367 17 similar to Joined to JAZF1 CRLF3 17q11.2 cytokine receptor-like factor 3 FLJ12735 17q11.2 cytokine receptor-like factor 3 FLJ22729  hypothetical protein FLJ22729 CENTA2 17q11.2 centaurin, alpha 2 RNF135 17q11.2 ring finger protein 135 NF1 17q11.2 neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease) OMG 17q11.2 oligodendrocyte myelin glycoprotein EVI2B 17q11.2 ecotropic viral integration site 2B EVI2A 17q11.2 ecotropic viral integration site 2A AK3P1 17q11.2 adenylate kinase 3 pseudogene 1 RAB11-FIP4  rab11-family interacting protein 4 LOC339281 17q11.2 hypothetical LOC339281 HSA272196 17q11.2 hypothetical protein, clone 2746033 HCA66 17q11.2 hepatocellular carcinoma-associated antigen 66 JJAZ1 17q11.2 hepatocellular carcinoma-associated antigen 66 LOC114659  KIAA0563-related gene LOC390785 17 hypothetical gene supported by NM_019613 ARHT1 17q11.2-q12 ras homolog gene family, member T1 RHBDL4 17q11.2 rhomboid, veinlet-like 4 (Drosophila) NJMU-R1 17q12 protein kinase Njmu-R1 ZNF207 17q11.2 zinc finger protein 207 PSMD11 17q12 proteasome (prosome, macropain) 26S subunit, non-ATPase, 11 CDK5R1 17p11.2-q11 cyclin-dependent kinase 5, regulatory subunit 1 (p35) MYO1D 19p13.3-p13.2 myosin ID DKFZP564K1964 17q12 DKFZP564K1964 protein SPACA3 17q12 sperm acrosome associated 3 ACCN1 17q11.2-q12 amiloride-sensitive cation channel 1, neuronal (degenerin) LOC339212 17q12 similar to tousled-like kinase 2; serine/threonine kinase; tousled-like kinase CCL2 17q11.2-q21.1 chemokine (C-C motif) ligand 2 CCL7 17q11.2-q12 chemokine (C-C motif) ligand 7 CCL11 17q21.1-q21.2 chemokine (C-C motif) ligand 11 CCL8 17q11.2 chemokine (C-C motif) ligand 8 CCL13 17q11.2 chemokine (C-C motif) ligand 13 CCL1 17q11.2 chemokine (C-C motif) ligand 1 LOC124842 17q12 hypothetical protein LOC124842
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 3870 - 307 - 2007 17491008
    - - - - - - 2008 19017804
  • truncated isoform, producing strong activation of striatal NMDA receptors
  • expression in striatum nonetheless causes deleterious behavioral, histological, and biochemical effects and impairs the function of this brain region
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrain   highly
    Visualeye   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • attached to the plasma membrane via a N terminal myristoylation anchor cleaved into a C terminal p25 part
  • N-terminal p10 regions, that is a unique prosurvival domain in CDK5R1, essential for normal CDK5/CDK5R1 function in neurons, and loss of the p10 domain results in CDK5/CDK5R1 toxicity and neurodegeneration
  • C-terminal CDK5 activation domains (AD)
  • mono polymer heteromer , dimer
    HOMOLOGY
    intraspecies paralog to CDK5R2
    Homologene
    FAMILY
  • cyclin-dependent kinase 5 activator family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • neuronal specified activator of CDK5
  • maybe involved in cytoskeletal anormalities and neuronal death in the pathogenesis of neurodegenerative diseases such as Alzheimer
  • microtubule-associated protein that modulates microtubule dynamics and microtubules play an important role in the control of CDK5 activation
  • at least one of the activators of CDK5 that is mobilized in the process of cellular senescence, which may provide insight into cancer cell proliferation and future cancer therapeutics
  • CDK5R1, HOPX, FKBP4, SGTA proteins plays a distinct role in the steroid hormone receptor regulatory cycle
  • activators of CDK5, CDK5R1, and CCNI are not required for normal kidney function, but, they play pivotal coordinated roles in maintaining podocyte survival during stress states in disease (pMID: 22262481)
  • CDK5/CDK5R1 is required for motor learning and involved in long-term synaptic plasticity
  • CDK5R1-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators
  • CDK5/CDK5R1 regulates spatial learning and memory, implicating CDK5/CDK5R1 as a therapeutic target in neurological disorders
  • predominance of CCNI mediates the nuclear localization of CDK5, whereas the predominance of CDK5R1 results in a membranous localization of CDK5
  • acts as a mediator of RHO GTPase activity and contributes to the neuroprotection induced by CDK5 RNAi
  • CDK5 and CDK5R1, encoding CDK5 activator p35, have a fundamental role in central nervous system (CNS) development and function, and are involved in the pathogenesis of several neurodegenerative disorders
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    text negative control
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimerizing with CDK5, with a resulting hyperphosphorylation of tau, which reduces tau's ability to associate with microtubules
  • SIK2-CDK5R1-PJA2 complex is essential for glucose homeostasis and provides a link between CDK5R1-CDK5 and the AMPK family in excitable cells
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to neuronal CDK5
  • binds directly to alpha/beta-tubulin and microtubules
  • interacting with HSF2 through the promoter (CDK5R1 is the first target gene for HSF2 in cortical development)
  • interacting with RB1 (CDK5R1 is required for the acquisition of the senescent morphology in RB1-induced senescence, which is consistent with our previous finding that CDK5 activity is required in such changes)
  • CDK5 is activated by both CCNI and the noncyclin activator CDK5R1 in terminally differentiated cells such as kidney podocytes and neurons
  • ZNF335 is a new interacting partner of CDK5R1
  • CDK5R1 interacts with ZNF335 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway
  • cell & other
    REGULATION
    repressed by cleaved to p25 by Ca2+ calpain
    Other sumoylation of CDK5R1 increased the activity of the CDK5R1/CDK5 complex
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    age-down regulated in the frontal cortex
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS