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Q06486

- KC1D_RAT

UniProt

Q06486 - KC1D_RAT

Protein

Casein kinase I isoform delta

Gene

Csnk1d

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 132 (01 Oct 2014)
      Sequence version 2 (10 May 2004)
      Previous versions | rss
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    Functioni

    Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. In balance with PP1, determines the circadian period length through the regulation of the speed and rhythmicity of PER1 and PER2 phospohorylation. Controls PER1 and PER2 nuclear transport and degradation. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.
    ATP + [tau protein] = ADP + [tau protein] phosphate.

    Enzyme regulationi

    Drug-mediated inhibition leads to a delay of the oscillations with the magnitude of this effect dependent upon the timing of drug administration. Inhibited by phosphorylation By similarity. Exhibits substrate-dependent heparin activation.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei38 – 381ATPPROSITE-ProRule annotation
    Active sitei128 – 1281Proton acceptor1 PublicationPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi15 – 239ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: RGD
    2. glycoprotein binding Source: RGD
    3. peptide binding Source: RGD
    4. phosphoprotein binding Source: RGD
    5. protein binding Source: IntAct
    6. protein kinase activity Source: UniProtKB
    7. protein serine/threonine kinase activity Source: RGD
    8. tau-protein kinase activity Source: UniProtKB-EC

    GO - Biological processi

    1. circadian regulation of gene expression Source: UniProtKB
    2. mitotic cell cycle Source: RGD
    3. positive regulation of canonical Wnt signaling pathway Source: Ensembl
    4. positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
    5. positive regulation of protein phosphorylation Source: Ensembl
    6. protein phosphorylation Source: UniProtKB
    7. regulation of circadian rhythm Source: UniProtKB
    8. spindle assembly Source: Ensembl
    9. Wnt signaling pathway Source: UniProtKB-KW

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Biological rhythms, Wnt signaling pathway

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.1. 5301.
    ReactomeiREACT_198294. Regulation of PLK1 Activity at G2/M Transition.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Casein kinase I isoform delta (EC:2.7.11.1)
    Short name:
    CKI-delta
    Alternative name(s):
    Tau-protein kinase CSNK1D (EC:2.7.11.26)
    Gene namesi
    Name:Csnk1d
    Synonyms:Hckid
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 10

    Organism-specific databases

    RGDi71031. Csnk1d.

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Cytoplasmperinuclear region By similarity. Cell membrane By similarity. Cytoplasmcytoskeletonspindle By similarity. Golgi apparatus By similarity
    Note: Localized at mitotic spindle microtubules, and at the centrosomes and interphase in interphase cells. Recruited to the spindle apparatus and the centrosomes in response to DNA-damage. Correct subcellular localization requires kinase activity By similarity.By similarity

    GO - Cellular componenti

    1. centrosome Source: RGD
    2. Golgi apparatus Source: UniProtKB-SubCell
    3. nucleus Source: UniProtKB
    4. perinuclear region of cytoplasm Source: UniProtKB-SubCell
    5. plasma membrane Source: UniProtKB-SubCell
    6. spindle Source: RGD
    7. spindle microtubule Source: Ensembl

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Cytoskeleton, Golgi apparatus, Membrane, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 415415Casein kinase I isoform deltaPRO_0000192836Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei331 – 3311PhosphoserineBy similarity
    Modified residuei370 – 3701Phosphoserine; by PKA1 Publication
    Modified residuei382 – 3821PhosphoserineBy similarity
    Modified residuei383 – 3831PhosphoserineBy similarity
    Modified residuei384 – 3841PhosphoserineBy similarity
    Modified residuei411 – 4111PhosphoserineBy similarity

    Post-translational modificationi

    Autophosphorylated on serine and threonine residues; this autophosphorylation represses activity. Reactivated by phosphatase-mediated dephosphorylation. May be dephosphorylated by PP1.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PRIDEiQ06486.

    PTM databases

    PhosphoSiteiQ06486.

    Expressioni

    Tissue specificityi

    Expressed in most tissues, including heart, brain, testis, kidney, spleen and lung.1 Publication

    Gene expression databases

    GenevestigatoriQ06486.

    Interactioni

    Subunit structurei

    Binds to DNMT1. Monomer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK, or NPAS2, ARTNL/BMAL1 or ARTNL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Interacts directly with PER1 and PER2 which may lead to their degradation. Interacts with MAPT/TAU, SNAPIN, DBNDD2, AIB1/NCOA3 and ESR1. AKAP9/AKAP450 binding promotes centrosomal subcellular location. Binds to tubulins in mitotic cells upon DNA damage. Binds to MAP1A.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    MDM2Q009872EBI-2910316,EBI-389668From a different organism.
    SnapinQ9Z2664EBI-7088890,EBI-6170320From a different organism.

    Protein-protein interaction databases

    BioGridi249077. 5 interactions.
    IntActiQ06486. 11 interactions.
    MINTiMINT-3389660.
    STRINGi10116.ENSRNOP00000015178.

    Structurei

    Secondary structure

    1
    415
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni6 – 83
    Beta strandi9 – 179
    Beta strandi19 – 2810
    Turni29 – 313
    Beta strandi34 – 429
    Helixi49 – 5810
    Beta strandi68 – 747
    Beta strandi77 – 837
    Helixi89 – 957
    Turni96 – 983
    Helixi102 – 12120
    Helixi131 – 1333
    Beta strandi134 – 1363
    Helixi139 – 1413
    Beta strandi145 – 1473
    Turni159 – 1613
    Beta strandi177 – 1793
    Helixi182 – 1854
    Helixi192 – 20817
    Beta strandi220 – 2223
    Helixi225 – 23410
    Helixi237 – 2404
    Turni241 – 2433
    Helixi246 – 25712
    Helixi266 – 27914
    Helixi289 – 2924
    Helixi293 – 2953

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1CKIX-ray2.30A/B1-317[»]
    1CKJX-ray2.46A/B1-317[»]
    ProteinModelPortaliQ06486.
    SMRiQ06486. Positions 3-294.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ06486.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini9 – 277269Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni278 – 36487Centrosomal localization signal (CLS)By similarityAdd
    BLAST
    Regioni317 – 34226AutoinhibitoryAdd
    BLAST

    Domaini

    The autoinhibitory domain is involved in regulating enzyme activity through autophosphorylation and possibly, through heparin binding.

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    GeneTreeiENSGT00730000110518.
    HOGENOMiHOG000182055.
    HOVERGENiHBG000176.
    KOiK08959.
    OMAiRIGQKIG.
    OrthoDBiEOG7CZK5W.
    PhylomeDBiQ06486.

    Family and domain databases

    InterProiIPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view]
    PfamiPF00069. Pkinase. 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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q06486-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MELRVGNRYR LGRKIGSGSF GDIYLGTDIA AGEEVAIKLE CVKTKHPQLH    50
    IESKIYKMMQ GGVGIPTIRW CGAEGDYNVM VMELLGPSLE DLFNFCSRKF 100
    SLKTVLLLAD QMISRIEYIH SKNFIHRDVK PDNFLMGLGK KGNLVYIIDF 150
    GLAKKYRDAR THQHIPYREN KNLTGTARYA SINTHLGIEQ SRRDDLESLG 200
    YVLMYFNLGS LPWQGLKAAT KRQKYERISE KKMSTPIEVL CKGYPSEFAT 250
    YLNFCRSLRF DDKPDYSYLR QLFRNLFHRQ GFSYDYVFDW NMLKFGASRA 300
    ADDAERERRD REERLRHSRN PATRGLPSTA SGRLRGTQEV APPTPLTPTS 350
    HTANTSPRPV SGMERERKVS MRLHRGAPVN VSSSDLTGRQ DTSRMSTSQI 400
    PGRVASSGLQ SVVHR 415
    Length:415
    Mass (Da):47,316
    Last modified:May 10, 2004 - v2
    Checksum:iB97F04AF9EB466D2
    GO
    Isoform 2 (identifier: Q06486-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         400-415: IPGRVASSGLQSVVHR → RSRDMASLRLHAARQGARCRPQRPRRTTY

    Show »
    Length:428
    Mass (Da):49,121
    Checksum:iE6B11915C1746568
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei400 – 41516IPGRV…SVVHR → RSRDMASLRLHAARQGARCR PQRPRRTTY in isoform 2. 1 PublicationVSP_010255Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L07578 mRNA. Translation: AAA40934.1.
    AB063114 mRNA. Translation: BAB60852.1.
    PIRiA46002.
    RefSeqiNP_620691.2. NM_139060.3. [Q06486-1]
    UniGeneiRn.8046.

    Genome annotation databases

    EnsembliENSRNOT00000015178; ENSRNOP00000015178; ENSRNOG00000036676. [Q06486-2]
    ENSRNOT00000054936; ENSRNOP00000051819; ENSRNOG00000036676. [Q06486-1]
    GeneIDi64462.
    KEGGirno:64462.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L07578 mRNA. Translation: AAA40934.1 .
    AB063114 mRNA. Translation: BAB60852.1 .
    PIRi A46002.
    RefSeqi NP_620691.2. NM_139060.3. [Q06486-1 ]
    UniGenei Rn.8046.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1CKI X-ray 2.30 A/B 1-317 [» ]
    1CKJ X-ray 2.46 A/B 1-317 [» ]
    ProteinModelPortali Q06486.
    SMRi Q06486. Positions 3-294.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 249077. 5 interactions.
    IntActi Q06486. 11 interactions.
    MINTi MINT-3389660.
    STRINGi 10116.ENSRNOP00000015178.

    Chemistry

    BindingDBi Q06486.
    ChEMBLi CHEMBL4484.

    PTM databases

    PhosphoSitei Q06486.

    Proteomic databases

    PRIDEi Q06486.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000015178 ; ENSRNOP00000015178 ; ENSRNOG00000036676 . [Q06486-2 ]
    ENSRNOT00000054936 ; ENSRNOP00000051819 ; ENSRNOG00000036676 . [Q06486-1 ]
    GeneIDi 64462.
    KEGGi rno:64462.

    Organism-specific databases

    CTDi 1453.
    RGDi 71031. Csnk1d.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00730000110518.
    HOGENOMi HOG000182055.
    HOVERGENi HBG000176.
    KOi K08959.
    OMAi RIGQKIG.
    OrthoDBi EOG7CZK5W.
    PhylomeDBi Q06486.

    Enzyme and pathway databases

    BRENDAi 2.7.11.1. 5301.
    Reactomei REACT_198294. Regulation of PLK1 Activity at G2/M Transition.

    Miscellaneous databases

    EvolutionaryTracei Q06486.
    NextBioi 613212.
    PROi Q06486.

    Gene expression databases

    Genevestigatori Q06486.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00069. Pkinase. 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. "Molecular cloning, expression, and characterization of a 49-kilodalton casein kinase I isoform from rat testis."
      Graves P.R., Haas D.W., Hagedorn C.H., Depaoli-Roach A.A., Roach P.J.
      J. Biol. Chem. 268:6394-6401(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 1-6.
      Tissue: Testis.
    2. "Casein kinase 1 delta rat."
      Takano A., Nagai K.
      Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "Role of COOH-terminal phosphorylation in the regulation of casein kinase I delta."
      Graves P.R., Roach P.J.
      J. Biol. Chem. 270:21689-21694(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: AUTOPHOSPHORYLATION, AUTOINHIBITORY DOMAIN.
    4. "Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2."
      Camacho F., Cilio M., Guo Y., Virshup D.M., Patel K., Khorkova O., Styren S., Morse B., Yao Z., Keesler G.A.
      FEBS Lett. 489:159-165(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    5. "Interaction of casein kinase 1 delta (CK1 delta) with the light chain LC2 of microtubule associated protein 1A (MAP1A)."
      Wolff S., Xiao Z., Wittau M., Suessner N., Stoeter M., Knippschild U.
      Biochim. Biophys. Acta 1745:196-206(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS MAP1A KINASE, INTERACTION WITH MAP1A.
    6. "Phosphorylation of CK1delta: identification of Ser370 as the major phosphorylation site targeted by PKA in vitro and in vivo."
      Giamas G., Hirner H., Shoshiashvili L., Grothey A., Gessert S., Kuehl M., Henne-Bruns D., Vorgias C.E., Knippschild U.
      Biochem. J. 406:389-398(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-370 BY PKA.
    7. "Three-dimensional structure of mammalian casein kinase I: molecular basis for phosphate recognition."
      Longenecker K.L., Roach P.J., Hurley T.D.
      J. Mol. Biol. 257:618-631(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-317, ACTIVE SITE.

    Entry informationi

    Entry nameiKC1D_RAT
    AccessioniPrimary (citable) accession number: Q06486
    Secondary accession number(s): Q99KK4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 1, 1994
    Last sequence update: May 10, 2004
    Last modified: October 1, 2014
    This is version 132 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3