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P49615

- CDK5_MOUSE

UniProt

P49615 - CDK5_MOUSE

Protein

Cyclin-dependent-like kinase 5

Gene

Cdk5

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 146 (01 Oct 2014)
      Sequence version 1 (01 Feb 1996)
      Previous versions | rss
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    Functioni

    Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1, huntingtin/HTT, ATM, MAP2, NEFH and NEFM. Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission, by phosphorylating key proteins. Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39), especially in post-mitotic neurons, and promotes CDK5R1 (p35) expression in an autostimulation loop. Phosphorylates many downstream substrates such as Rho and Ras family small GTPases (e.g. PAK1, RAC1, RHOA, CDC42) or microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B), and modulates actin dynamics to regulate neurite growth and/or spine morphogenesis. Phosphorylates also exocytosis associated proteins such as MCAM/MUC18, SEPT5, SYN1, and CDK16/PCTAIRE1 as well as endocytosis associated proteins such as DNM1, AMPH and SYNJ1 at synaptic terminals. In the mature central nervous system (CNS), regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity; synaptic vesicle exocytosis, vesicles fusion with the presynaptic membrane, and endocytosis. Promotes cell survival by activating anti-apoptotic proteins BCL2 and STAT3, and negatively regulating of JNK3/MAPK10 activity. Phosphorylation of p53/TP53 in response to genotoxic and oxidative stresses enhances its stabilization by preventing ubiquitin ligase-mediated proteasomal degradation, and induces transactivation of p53/TP53 target genes, thus regulating apoptosis. Phosphorylation of p35/CDK5R1 enhances its stabilization by preventing calpain-mediated proteolysis producing p25/CDK5R1 and avoiding ubiquitin ligase-mediated proteasomal degradation. During aberrant cell-cycle activity and DNA damage, p25/CDK5 activity elicits cell-cycle activity and double-strand DNA breaks that precedes neuronal death by deregulating HDAC1. DNA damage triggered phosphorylation of huntingtin/HTT in nuclei of neurons protects neurons against polyglutamine expansion as well as DNA damage mediated toxicity. Phosphorylation of PXN reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation. Negative regulator of Wnt/beta-catenin signaling pathway. Activator of the GAIT (IFN-gamma-activated inhibitor of translation) pathway, which suppresses expression of a post-transcriptional regulon of proinflammatory genes in myeloid cells; phosphorylates the linker domain of glutamyl-prolyl tRNA synthetase (EPRS) in a IFN-gamma-dependent manner, the initial event in assembly of the GAIT complex. Phosphorylation of SH3GLB1 is required for autophagy induction in starved neurons. Phosphorylation of TONEBP/NFAT5 in response to osmotic stress mediates its rapid nuclear localization. MEF2 is inactivated by phosphorylation in nucleus in response to neurotoxin, thus leading to neuronal apoptosis. APEX1 AP-endodeoxyribonuclease is repressed by phosphorylation, resulting in accumulation of DNA damage and contributing to neuronal death. NOS3 phosphorylation down regulates NOS3-derived nitrite (NO) levels. SRC phosphorylation mediates its ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. May regulate endothelial cell migration and angiogenesis via the modulation of lamellipodia formation. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. 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.5 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.

    Enzyme regulationi

    Inhibited by 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine), 1-isopropyl-4-aminobenzyl-6-ether-linked benzimidazoles, resveratrol, AT-7519 and olomoucine. Activated by CDK5R1 (p35) and CDK5R2 (p39) during the development of the nervous system; degradation of CDK5R1 (p35) and CDK5R2 (p39) by proteasome result in down regulation of kinase activity, during this process, CDK5 phosphorylates p35 and induces its ubiquitination and subsequent degradation. Kinase activity is mainly determined by the amount of p35 available and subcellular location; reversible association to plasma membrane inhibits activity. Long-term inactivation as well as CDK5R1 (p25)-mediated hyperactivation of CDK5 triggers cell death. The pro-death activity of hyperactivated CDK5 is suppressed by membrane association of CDK5, via myristoylation of p35. Brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor (NGF), retinoic acid, laminin and neuregulin promote activity. Neurotoxicity enhances nuclear activity, thus leading to MEF2 phosphorylation and inhibition prior to apoptosis of cortical neurons. Repression by GSTP1 via p25/p35 translocation prevents neurodegeneration By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei33 – 331ATPPROSITE-ProRule annotation
    Active sitei126 – 1261Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi10 – 189ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. acetylcholine receptor activator activity Source: UniProtKB
    2. ATP binding Source: UniProtKB-KW
    3. cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
    4. ErbB-2 class receptor binding Source: UniProtKB
    5. ErbB-3 class receptor binding Source: UniProtKB
    6. kinase activity Source: UniProtKB
    7. p53 binding Source: MGI
    8. protein binding Source: UniProtKB
    9. protein kinase activity Source: MGI
    10. protein serine/threonine kinase activity Source: UniProtKB
    11. tau-protein kinase activity Source: UniProtKB

    GO - Biological processi

    1. apoptotic process Source: MGI
    2. associative learning Source: MGI
    3. axonogenesis Source: MGI
    4. behavioral response to cocaine Source: MGI
    5. calcium ion import Source: MGI
    6. cell cycle Source: UniProtKB-KW
    7. cell division Source: UniProtKB-KW
    8. cell-matrix adhesion Source: MGI
    9. cell migration Source: MGI
    10. central nervous system neuron development Source: MGI
    11. cerebellar cortex development Source: MGI
    12. cerebellar cortex formation Source: MGI
    13. cerebellum development Source: MGI
    14. cerebral cortex development Source: MGI
    15. corpus callosum development Source: MGI
    16. cortical actin cytoskeleton organization Source: Ensembl
    17. dendrite morphogenesis Source: MGI
    18. embryo development Source: UniProtKB
    19. forebrain development Source: MGI
    20. hippocampus development Source: MGI
    21. intracellular protein transport Source: MGI
    22. layer formation in cerebral cortex Source: MGI
    23. motor neuron axon guidance Source: MGI
    24. negative regulation of axon extension Source: MGI
    25. negative regulation of cell cycle Source: MGI
    26. negative regulation of protein export from nucleus Source: MGI
    27. negative regulation of protein ubiquitination Source: MGI
    28. negative regulation of synaptic plasticity Source: MGI
    29. negative regulation of transcription, DNA-templated Source: Ensembl
    30. neuron apoptotic process Source: MGI
    31. neuron differentiation Source: UniProtKB
    32. neuron migration Source: MGI
    33. neuron projection development Source: UniProtKB
    34. nucleocytoplasmic transport Source: Ensembl
    35. oligodendrocyte differentiation Source: Ensembl
    36. peptidyl-serine phosphorylation Source: MGI
    37. peptidyl-threonine phosphorylation Source: MGI
    38. positive regulation of calcium ion-dependent exocytosis Source: MGI
    39. positive regulation of neuron apoptotic process Source: UniProtKB
    40. positive regulation of protein binding Source: MGI
    41. positive regulation of protein kinase activity Source: MGI
    42. positive regulation of protein targeting to membrane Source: MGI
    43. positive regulation of receptor activity Source: GOC
    44. protein autophosphorylation Source: Ensembl
    45. protein localization to synapse Source: MGI
    46. protein phosphorylation Source: MGI
    47. receptor catabolic process Source: MGI
    48. receptor clustering Source: MGI
    49. regulated secretory pathway Source: Ensembl
    50. regulation of cell migration Source: MGI
    51. regulation of dendritic spine morphogenesis Source: UniProtKB
    52. regulation of excitatory postsynaptic membrane potential Source: MGI
    53. regulation of postsynaptic membrane potential Source: MGI
    54. regulation of synaptic plasticity Source: UniProtKB
    55. response to cocaine Source: MGI
    56. response to wounding Source: Ensembl
    57. rhythmic process Source: UniProtKB-KW
    58. Schwann cell development Source: MGI
    59. sensory perception of pain Source: MGI
    60. serine phosphorylation of STAT3 protein Source: MGI
    61. skeletal muscle tissue development Source: MGI
    62. synapse assembly Source: MGI
    63. synaptic transmission, dopaminergic Source: MGI
    64. synaptic transmission, glutamatergic Source: MGI
    65. synaptic vesicle endocytosis Source: Ensembl
    66. telencephalon development Source: MGI
    67. visual learning Source: MGI

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Apoptosis, Biological rhythms, Cell cycle, Cell division, Neurogenesis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.22. 3474.
    ReactomeiREACT_198649. Factors involved in megakaryocyte development and platelet production.
    REACT_203795. DARPP-32 events.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cyclin-dependent-like kinase 5 (EC:2.7.11.1)
    Alternative name(s):
    CR6 protein kinase
    Short name:
    CRK6
    Cell division protein kinase 5
    Serine/threonine-protein kinase PSSALRE
    Tau protein kinase II catalytic subunit
    Short name:
    TPKII catalytic subunit
    Gene namesi
    Name:Cdk5
    Synonyms:Cdkn5, Crk6
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 5

    Organism-specific databases

    MGIiMGI:101765. Cdk5.

    Subcellular locationi

    Nucleus By similarity. Cytoplasm 1 Publication. Cell membrane By similarity; Peripheral membrane protein By similarity. Perikaryon By similarity. Cell projectionlamellipodium 1 Publication. Cell projectiongrowth cone 1 Publication. Cell junctionsynapsepostsynaptic cell membranepostsynaptic density By similarity
    Note: In axonal growth cone with extension to the peripheral lamellipodia. Under neurotoxic stress and neuronal injury conditions, CDK5R1 (p35) is cleaved by calpain to generate CDK5R1 (p25) in response to increased intracellular calcium. The elevated level of p25, when in complex with CDK5, leads to its subcellular misallocation as well as its hyperactivation. Colocalizes with CTNND2 in the cell body of neuronal cells, and with CTNNB1 in the cell-cell contacts and plasma membrane of undifferentiated and differentiated neuroblastoma cells. Reversibly attached to the plasma membrane in an inactive form when complexed to dephosphorylated p35 or CDK5R2 (p39), p35 phosphorylation releases this attachment and activates CDK5 By similarity.By similarity

    GO - Cellular componenti

    1. axon Source: UniProtKB
    2. cell junction Source: UniProtKB-KW
    3. cyclin-dependent protein kinase 5 holoenzyme complex Source: Ensembl
    4. cytoplasm Source: UniProtKB
    5. cytosol Source: MGI
    6. dendrite Source: UniProtKB
    7. filopodium Source: MGI
    8. growth cone Source: UniProtKB
    9. lamellipodium Source: MGI
    10. membrane Source: UniProtKB
    11. neuromuscular junction Source: UniProtKB
    12. neuronal cell body Source: UniProtKB
    13. nucleus Source: UniProtKB
    14. perikaryon Source: UniProtKB-SubCell
    15. postsynaptic density Source: UniProtKB
    16. postsynaptic membrane Source: UniProtKB-KW

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane, Nucleus, Postsynaptic cell membrane, Synapse

    Pathology & Biotechi

    Disruption phenotypei

    Perinatal mortality associated with severe disruption of the cytoarchitecture of the brain cortex as a result of defects in neuronal migration and cohesiveness, and degenerative changes in large neurons of the brain stem, such as motor neurons in the lower cranial nerve nuclei and spinal cord. Disruption of lamination in the cerebral cortex, hippocampus, and cerebellum. Hypomyelination caused by impaired differentiation of oligodendrocytes.4 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi15 – 151Y → F: Loss of tyrosine phosphorylations by CABLES1 and ABL1; decreased activity. 1 Publication

    Keywords - Diseasei

    Neurodegeneration

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 292292Cyclin-dependent-like kinase 5PRO_0000085785Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei15 – 151Phosphotyrosine; by ABL1, EPHA4 and FYN1 Publication
    Modified residuei56 – 561N6-acetyllysine1 Publication
    Modified residuei72 – 721PhosphoserineBy similarity
    Modified residuei159 – 1591PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylation on Tyr-15 by ABL1 and FYN, and on Ser-159 by casein kinase 1 promotes kinase activity. By contrast, phosphorylation at Thr-14 inhibits activity By similarity.By similarity
    Phosphorylation at Ser-159 is essential for maximal catalytic activity.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiP49615.
    PaxDbiP49615.
    PRIDEiP49615.

    PTM databases

    PhosphoSiteiP49615.

    Expressioni

    Tissue specificityi

    Specifically expressed in post-mitotic neurons and postsynaptic muscle.1 Publication

    Gene expression databases

    ArrayExpressiP49615.
    BgeeiP49615.
    CleanExiMM_CDK5.
    GenevestigatoriP49615.

    Interactioni

    Subunit structurei

    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. Only the heterodimer shows kinase activity. Under neurotoxic stress and neuronal injury conditions, p35 is cleaved by calpain to generate p25 that hyperactivates CDK5, that becomes functionally disabled and often toxic. Found in a trimolecular complex with CABLES1 and ABL1. Interacts with CABLES1 and CABLES2. Interacts with AATK and GSTP1. Binds to HDAC1 when in complex with p25. Interaction with myristoylation p35 promotes CDK5 association with membranes. Both isoforms 1 and 2 interacts with beta-catenin/CTNNB1. Interacts with delta-catenin/CTNND2 and APEX1. Interacts with P53/TP53 in neurons By similarity. Interacts with EPHA4; may mediate the activation of NGEF by EPHA4M. Interacts with PTK2/FAK1. The complex p35/CDK5 interacts with CLOCK By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Cdk5r1P618092EBI-6510052,EBI-7840438

    Protein-protein interaction databases

    BioGridi198646. 4 interactions.
    DIPiDIP-29353N.
    IntActiP49615. 5 interactions.
    MINTiMINT-4090424.
    STRINGi10090.ENSMUSP00000030814.

    Structurei

    3D structure databases

    ProteinModelPortaliP49615.
    SMRiP49615. Positions 1-292.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini4 – 286283Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    InParanoidiP49615.
    KOiK02090.
    OMAiTMTKLPD.
    OrthoDBiEOG7966H8.
    PhylomeDBiP49615.
    TreeFamiTF101023.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00069. Pkinase. 1 hit.
    [Graphical view]
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF56112. SSF56112. 1 hit.
    PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P49615-1 [UniParc]FASTAAdd to Basket

    « Hide

    MQKYEKLEKI GEGTYGTVFK AKNRETHEIV ALKRVRLDDD DEGVPSSALR    50
    EICLLKELKH KNIVRLHDVL HSDKKLTLVF EFCDQDLKKY FDSCNGDLDP 100
    EIVKSFLFQL LKGLGFCHSR NVLHRDLKPQ NLLINRNGEL KLADFGLARA 150
    FGIPVRCYSA EVVTLWYRPP DVLFGAKLYS TSIDMWSAGC IFAELANAGR 200
    PLFPGNDVDD QLKRIFRLLG TPTEEQWPAM TKLPDYKPYP MYPATTSLVN 250
    VVPKLNATGR DLLQNLLKCN PVQRISAEEA LQHPYFSDFC PP 292
    Length:292
    Mass (Da):33,288
    Last modified:February 1, 1996 - v1
    Checksum:i4CB11CED9017D535
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D29678 mRNA. Translation: BAA06148.1.
    BC052007 mRNA. Translation: AAH52007.1.
    X64604 mRNA. Translation: CAA45888.1.
    S80121 Genomic DNA. No translation available.
    CCDSiCCDS51434.1.
    PIRiI49592.
    RefSeqiNP_031694.1. NM_007668.3.
    UniGeneiMm.298798.
    Mm.445256.

    Genome annotation databases

    EnsembliENSMUST00000030814; ENSMUSP00000030814; ENSMUSG00000028969.
    GeneIDi12568.
    KEGGimmu:12568.
    UCSCiuc008wrl.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D29678 mRNA. Translation: BAA06148.1 .
    BC052007 mRNA. Translation: AAH52007.1 .
    X64604 mRNA. Translation: CAA45888.1 .
    S80121 Genomic DNA. No translation available.
    CCDSi CCDS51434.1.
    PIRi I49592.
    RefSeqi NP_031694.1. NM_007668.3.
    UniGenei Mm.298798.
    Mm.445256.

    3D structure databases

    ProteinModelPortali P49615.
    SMRi P49615. Positions 1-292.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 198646. 4 interactions.
    DIPi DIP-29353N.
    IntActi P49615. 5 interactions.
    MINTi MINT-4090424.
    STRINGi 10090.ENSMUSP00000030814.

    PTM databases

    PhosphoSitei P49615.

    Proteomic databases

    MaxQBi P49615.
    PaxDbi P49615.
    PRIDEi P49615.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000030814 ; ENSMUSP00000030814 ; ENSMUSG00000028969 .
    GeneIDi 12568.
    KEGGi mmu:12568.
    UCSCi uc008wrl.1. mouse.

    Organism-specific databases

    CTDi 1020.
    MGIi MGI:101765. Cdk5.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    InParanoidi P49615.
    KOi K02090.
    OMAi TMTKLPD.
    OrthoDBi EOG7966H8.
    PhylomeDBi P49615.
    TreeFami TF101023.

    Enzyme and pathway databases

    BRENDAi 2.7.11.22. 3474.
    Reactomei REACT_198649. Factors involved in megakaryocyte development and platelet production.
    REACT_203795. DARPP-32 events.

    Miscellaneous databases

    ChiTaRSi CDK5. mouse.
    NextBioi 281666.
    PROi P49615.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P49615.
    Bgeei P49615.
    CleanExi MM_CDK5.
    Genevestigatori P49615.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR002290. Ser/Thr_dual-sp_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SMARTi SM00220. S_TKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Expression of CDK5 (PSSALRE kinase), a neural cdc2-related protein kinase, in the mature and developing mouse central and peripheral nervous systems."
      Ino H., Ishizuka T., Chiba T., Tatibana M.
      Brain Res. 661:196-206(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Brain.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6.
      Tissue: Brain.
    3. "Novel CDC2-related protein kinases produced in murine hematopoietic stem cells."
      Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V.
      Gene 124:305-306(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 130-165.
      Strain: CBA.
      Tissue: Bone marrow.
    4. "Molecular cloning and chromosomal mapping of the mouse cyclin-dependent kinase 5 gene."
      Ohshima T., Nagle J.W., Pant H.C., Joshi J.B., Kozak C.A., Brady R.O., Kulkarni A.B.
      Genomics 28:585-588(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE OF 1-12.
    5. "Cables links Cdk5 and c-Abl and facilitates Cdk5 tyrosine phosphorylation, kinase upregulation, and neurite outgrowth."
      Zukerberg L.R., Patrick G.N., Nikolic M., Humbert S., Wu C.-L., Lanier L.M., Gertler F.B., Vidal M., Van Etten R.A., Tsai L.-H.
      Neuron 26:633-646(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN A TRIMOLECULAR COMPLEX WITH CABLES1 AND ABL1, INTERACTION WITH CABLES1, PHOSPHORYLATION AT TYR-15, MUTAGENESIS OF TYR-15.
    6. "p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment."
      Ko J., Humbert S., Bronson R.T., Takahashi S., Kulkarni A.B., Li E., Tsai L.H.
      J. Neurosci. 21:6758-6771(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, ENZYME REGULATION.
    7. "Synergistic contributions of cyclin-dependant kinase 5/p35 and Reelin/Dab1 to the positioning of cortical neurons in the developing mouse brain."
      Ohshima T., Ogawa M., Veeranna A., Hirasawa M., Longenecker G., Ishiguro K., Pant H.C., Brady R.O., Kulkarni A.B., Mikoshiba K.
      Proc. Natl. Acad. Sci. U.S.A. 98:2764-2769(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    8. "Ik3-2, a relative to ik3-1/cables, is associated with cdk3, cdk5, and c-abl."
      Sato H., Nishimoto I., Matsuoka M.
      Biochim. Biophys. Acta 1574:157-163(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CABLES2.
    9. "Serine 732 phosphorylation of FAK by Cdk5 is important for microtubule organization, nuclear movement, and neuronal migration."
      Xie Z., Sanada K., Samuels B.A., Shih H., Tsai L.H.
      Cell 114:469-482(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH PTK2/FAK1.
    10. "Aberrant motor axon projection, acetylcholine receptor clustering, and neurotransmission in cyclin-dependent kinase 5 null mice."
      Fu A.K.Y., Ip F.C.F., Fu W.-Y., Cheung J., Wang J.H., Yung W.-H., Ip N.Y.
      Proc. Natl. Acad. Sci. U.S.A. 102:15224-15229(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
    11. "Comprehensive identification of phosphorylation sites in postsynaptic density preparations."
      Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.
      Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Brain.
    12. "Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism."
      Fu W.Y., Chen Y., Sahin M., Zhao X.S., Shi L., Bikoff J.B., Lai K.O., Yung W.H., Fu A.K., Greenberg M.E., Ip N.Y.
      Nat. Neurosci. 10:67-76(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN DENDRITIC SPINE MORPHOGENESIS.
    13. "The role of Cdk5-mediated apurinic/apyrimidinic endonuclease 1 phosphorylation in neuronal death."
      Huang E., Qu D., Zhang Y., Venderova K., Haque M.E., Rousseaux M.W.C., Slack R.S., Woulfe J.M., Park D.S.
      Nat. Cell Biol. 12:563-571(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS APEX1 KINASE, INTERACTION WITH APEX1.
    14. "Hypomyelination Phenotype caused by impaired differentiation of oligodendrocytes in Emx1-cre mediated Cdk5 conditional knockout mice."
      He X., Takahashi S., Suzuki H., Hashikawa T., Kulkarni A.B., Mikoshiba K., Ohshima T.
      Neurochem. Res. 36:1293-1303(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, FUNCTION IN OLIGODENDROCYTE DIFFERENTIATION.
    15. "Cyclin-dependent kinase 5 (Cdk5) regulates the function of CLOCK protein by direct phosphorylation."
      Kwak Y., Jeong J., Lee S., Park Y.U., Lee S.A., Han D.H., Kim J.H., Ohshima T., Mikoshiba K., Suh Y.H., Cho S., Park S.K.
      J. Biol. Chem. 288:36878-36889(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH CLOCK.
    16. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
      Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
      Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-56, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic fibroblast.

    Entry informationi

    Entry nameiCDK5_MOUSE
    AccessioniPrimary (citable) accession number: P49615
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: February 1, 1996
    Last modified: October 1, 2014
    This is version 146 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3