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P61809

- CD5R1_MOUSE

UniProt

P61809 - CD5R1_MOUSE

Protein

Cyclin-dependent kinase 5 activator 1

Gene

Cdk5r1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 103 (01 Oct 2014)
      Sequence version 1 (07 Jun 2004)
      Previous versions | rss
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    Functioni

    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.2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei98 – 992Cleavage; by calpain

    GO - Molecular functioni

    1. cadherin binding Source: UniProtKB
    2. calcium ion binding Source: UniProtKB
    3. cyclin-dependent protein kinase 5 activator activity Source: MGI
    4. cyclin-dependent protein serine/threonine kinase activity Source: Ensembl
    5. cytoskeletal protein binding Source: MGI
    6. kinase activity Source: UniProtKB
    7. protein binding Source: UniProtKB
    8. protein serine/threonine kinase activator activity Source: UniProtKB

    GO - Biological processi

    1. axonal fasciculation Source: UniProtKB
    2. axon guidance Source: UniProtKB
    3. brain development Source: UniProtKB
    4. cerebellum development Source: MGI
    5. cerebral cortex radially oriented cell migration Source: DFLAT
    6. embryo development Source: UniProtKB
    7. ephrin receptor signaling pathway Source: UniProtKB
    8. G-protein coupled acetylcholine receptor signaling pathway Source: UniProtKB
    9. hippocampus development Source: MGI
    10. ionotropic glutamate receptor signaling pathway Source: UniProtKB
    11. layer formation in cerebral cortex Source: MGI
    12. negative regulation of axon extension Source: MGI
    13. negative regulation of transcription, DNA-templated Source: Ensembl
    14. neuron cell-cell adhesion Source: UniProtKB
    15. neuron differentiation Source: UniProtKB
    16. neuron migration Source: UniProtKB
    17. neuron projection development Source: UniProtKB
    18. peptidyl-threonine phosphorylation Source: Ensembl
    19. positive regulation of cell cycle arrest Source: MGI
    20. positive regulation of neuron apoptotic process Source: UniProtKB
    21. positive regulation of protein kinase activity Source: MGI
    22. positive regulation of protein targeting to membrane Source: MGI
    23. regulation of actin cytoskeleton organization Source: DFLAT
    24. regulation of dendritic spine morphogenesis Source: UniProtKB
    25. regulation of microtubule cytoskeleton organization Source: DFLAT
    26. rhythmic process Source: UniProtKB-KW
    27. serine phosphorylation of STAT3 protein Source: MGI
    28. superior olivary nucleus maturation Source: MGI

    Keywords - Biological processi

    Biological rhythms

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cyclin-dependent kinase 5 activator 1
    Short name:
    CDK5 activator 1
    Alternative name(s):
    Cyclin-dependent kinase 5 regulatory subunit 1
    TPKII regulatory subunit
    Cleaved into the following 2 chains:
    Alternative name(s):
    Tau protein kinase II 23 kDa subunit
    Short name:
    p23
    Gene namesi
    Name:Cdk5r1
    Synonyms:Cdk5r, Nck5a
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 11

    Organism-specific databases

    MGIiMGI:101764. Cdk5r1.

    Subcellular locationi

    Chain Cyclin-dependent kinase 5 activator 1, p25 : Nucleus By similarity. Cytoplasmperinuclear region By similarity
    Note: The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions.By similarity

    GO - Cellular componenti

    1. axon Source: UniProtKB
    2. contractile fiber Source: UniProtKB
    3. cyclin-dependent protein kinase 5 holoenzyme complex Source: InterPro
    4. cytoplasm Source: UniProtKB
    5. dendrite Source: UniProtKB
    6. dendritic spine Source: UniProtKB
    7. growth cone Source: UniProtKB
    8. membrane Source: UniProtKB
    9. neuromuscular junction Source: UniProtKB
    10. neuronal cell body Source: UniProtKB
    11. nucleus Source: UniProtKB
    12. perinuclear region of cytoplasm Source: UniProtKB-SubCell
    13. plasma membrane Source: UniProtKB-SubCell
    14. postsynaptic density Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi157 – 1571E → Q: Abolishes the binding to CDK5RAP1, CDK5RAP2, CDKRAP3, but not to CDK5. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 307306Cyclin-dependent kinase 5 activator 1, p35PRO_0000004796Add
    BLAST
    Chaini99 – 307209Cyclin-dependent kinase 5 activator 1, p25PRO_0000004797Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi2 – 21N-myristoyl glycineBy similarity
    Modified residuei8 – 81Phosphoserine; by CDK5By similarity
    Modified residuei138 – 1381Phosphothreonine; by CDK5By similarity

    Post-translational modificationi

    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.1 Publication
    Myristoylated. A proper myristoylation signal is essential for the proper distribution of p35 By similarity.By similarity
    Ubiquitinated. Degradation of p35 by proteasome results in down-regulation of CDK5 activity. During this process, CDK5 phosphorylates p35 and induces its ubiquitination and subsequent degradation By similarity.By similarity
    Phosphorylation at Ser-8 and Thr-138 by CDK5 prevents calpain-mediated proteolysis.By similarity

    Keywords - PTMi

    Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiP61809.

    PTM databases

    PhosphoSiteiP61809.

    Expressioni

    Tissue specificityi

    Brain and neuron specific.

    Gene expression databases

    BgeeiP61809.
    GenevestigatoriP61809.

    Interactioni

    Subunit structurei

    Heterodimer composed of CDK5 and CDK5R (p25) and macromolecular complex composed of at least CDK5, CDK5R (p35) and CDK5RAP1 or CDK5RAP2 or CDK5RAP3. Only the heterodimer shows kinase activity. Interacts with RASGRF2 By similarity. Interacts with EPHA4 and NGEF; may mediate the activation of NGEF by EPHA4. The complex p35/CDK5 interacts with CLOCK.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Cdh1P098032EBI-7840438,EBI-984420
    Cdk5P496152EBI-7840438,EBI-6510052

    Protein-protein interaction databases

    BioGridi198647. 2 interactions.
    DIPiDIP-29354N.
    IntActiP61809. 2 interactions.

    Structurei

    3D structure databases

    ProteinModelPortaliP61809.
    SMRiP61809. Positions 145-293.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiNOG283789.
    HOVERGENiHBG050853.
    InParanoidiP61809.
    KOiK11716.
    OMAiCANLSSF.
    PhylomeDBiP61809.
    TreeFamiTF101036.

    Family and domain databases

    Gene3Di1.10.472.10. 1 hit.
    InterProiIPR004944. CDK5_activator.
    IPR013763. Cyclin-like.
    [Graphical view]
    PANTHERiPTHR23401. PTHR23401. 1 hit.
    PfamiPF03261. CDK5_activator. 1 hit.
    [Graphical view]
    PIRSFiPIRSF009324. Cdk5_activator. 1 hit.
    SUPFAMiSSF47954. SSF47954. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P61809-1 [UniParc]FASTAAdd to Basket

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    MGTVLSLSPS YRKATLFEDG AATVGHYTAV QNSKNAKDKN LKRHSIISVL    50
    PWKRIVAVSA KKKNSKKAQP NSSYQSNIAH LNNENLKKSL SCANLSTFAQ 100
    PPPAQPPAPP ASQLSGSQTG VSSSVKKAPH PAITSAGTPK RVIVQASTSE 150
    LLRCLGEFLC RRCYRLKHLS PTDPVLWLRS VDRSLLLQGW QDQGFITPAN 200
    VVFLYMLCRD VISSEVGSDH ELQAVLLTCL YLSYSYMGNE ISYPLKPFLV 250
    ESCKEAFWDR CLSVINLMSS KMLQINADPH YFTQVFSDLK NESGQEDKKR 300
    LLLGLDR 307
    Length:307
    Mass (Da):34,031
    Last modified:June 7, 2004 - v1
    Checksum:i165AA0747410B0C0
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U89527 mRNA. Translation: AAB49474.1.
    Y11335 Genomic DNA. Translation: CAA72176.1.
    S82819 Genomic DNA. Translation: AAB46777.1.
    BC046823 mRNA. Translation: AAH46823.1.
    BC050768 mRNA. Translation: AAH50768.1.
    BC058697 mRNA. Translation: AAH58697.1.
    CCDSiCCDS25134.1.
    RefSeqiNP_034001.1. NM_009871.2.
    UniGeneiMm.142275.
    Mm.474282.

    Genome annotation databases

    EnsembliENSMUST00000053413; ENSMUSP00000099514; ENSMUSG00000048895.
    GeneIDi12569.
    KEGGimmu:12569.
    UCSCiuc007kmg.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U89527 mRNA. Translation: AAB49474.1 .
    Y11335 Genomic DNA. Translation: CAA72176.1 .
    S82819 Genomic DNA. Translation: AAB46777.1 .
    BC046823 mRNA. Translation: AAH46823.1 .
    BC050768 mRNA. Translation: AAH50768.1 .
    BC058697 mRNA. Translation: AAH58697.1 .
    CCDSi CCDS25134.1.
    RefSeqi NP_034001.1. NM_009871.2.
    UniGenei Mm.142275.
    Mm.474282.

    3D structure databases

    ProteinModelPortali P61809.
    SMRi P61809. Positions 145-293.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 198647. 2 interactions.
    DIPi DIP-29354N.
    IntActi P61809. 2 interactions.

    PTM databases

    PhosphoSitei P61809.

    Proteomic databases

    PRIDEi P61809.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000053413 ; ENSMUSP00000099514 ; ENSMUSG00000048895 .
    GeneIDi 12569.
    KEGGi mmu:12569.
    UCSCi uc007kmg.1. mouse.

    Organism-specific databases

    CTDi 8851.
    MGIi MGI:101764. Cdk5r1.

    Phylogenomic databases

    eggNOGi NOG283789.
    HOVERGENi HBG050853.
    InParanoidi P61809.
    KOi K11716.
    OMAi CANLSSF.
    PhylomeDBi P61809.
    TreeFami TF101036.

    Miscellaneous databases

    NextBioi 281670.
    PROi P61809.
    SOURCEi Search...

    Gene expression databases

    Bgeei P61809.
    Genevestigatori P61809.

    Family and domain databases

    Gene3Di 1.10.472.10. 1 hit.
    InterProi IPR004944. CDK5_activator.
    IPR013763. Cyclin-like.
    [Graphical view ]
    PANTHERi PTHR23401. PTHR23401. 1 hit.
    Pfami PF03261. CDK5_activator. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF009324. Cdk5_activator. 1 hit.
    SUPFAMi SSF47954. SSF47954. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "Differential mRNA expression of the CDK5 activators P35 and P39 in the developing mouse brain."
      Nilden F., Backstrom A., Bark I.C.
      Submitted (FEB-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: 129/Sv.
    2. "Molecular cloning and chromosomal mapping of the mouse gene encoding cyclin-dependent kinase 5 regulatory subunit p35."
      Ohshima T., Kozak C.A., Nagle J.W., Pant H.C., Brady R.O., Kulkarni A.B.
      Genomics 35:372-375(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: 129/SvJ.
      Tissue: Brain.
    3. "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.
    4. "Neurotoxicity induces cleavage of p35 to p25 by calpain."
      Lee M.-S., Kwon Y.T., Li M., Peng J., Friedlander R.M., Tsai L.-H.
      Nature 405:360-364(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC CLEAVAGE BY CALPAIN.
    5. "Identification of a neuronal Cdk5 activator-binding protein as Cdk5 inhibitor."
      Ching Y.-P., Pang A.S.H., Lam W.-H., Qi R.Z., Wang J.H.
      J. Biol. Chem. 277:15237-15240(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CDK5; CDK5RAP1; CDK5RAP2 AND CDK5RAP3, MUTAGENESIS OF GLU-157.
    6. "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, INTERACTION WITH NGEF, SUBCELLULAR LOCATION.
    7. "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.

    Entry informationi

    Entry nameiCD5R1_MOUSE
    AccessioniPrimary (citable) accession number: P61809
    Secondary accession number(s): Q62938
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 7, 2004
    Last sequence update: June 7, 2004
    Last modified: October 1, 2014
    This is version 103 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3