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Q06486

- KC1D_RAT

UniProt

Q06486 - KC1D_RAT

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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

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 kinase activity Source: UniProtKB
  6. protein serine/threonine kinase activity Source: RGD
  7. 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
Complete GO annotation...

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-KW
  3. nucleus Source: UniProtKB
  4. perinuclear region of cytoplasm Source: Ensembl
  5. plasma membrane Source: UniProtKB-KW
  6. spindle Source: RGD
  7. spindle microtubule Source: Ensembl
Complete GO annotation...

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.
GeneTreeiENSGT00760000119040.
HOGENOMiHOG000182055.
HOVERGENiHBG000176.
InParanoidiQ06486.
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) [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

        10         20         30         40         50
MELRVGNRYR LGRKIGSGSF GDIYLGTDIA AGEEVAIKLE CVKTKHPQLH
60 70 80 90 100
IESKIYKMMQ GGVGIPTIRW CGAEGDYNVM VMELLGPSLE DLFNFCSRKF
110 120 130 140 150
SLKTVLLLAD QMISRIEYIH SKNFIHRDVK PDNFLMGLGK KGNLVYIIDF
160 170 180 190 200
GLAKKYRDAR THQHIPYREN KNLTGTARYA SINTHLGIEQ SRRDDLESLG
210 220 230 240 250
YVLMYFNLGS LPWQGLKAAT KRQKYERISE KKMSTPIEVL CKGYPSEFAT
260 270 280 290 300
YLNFCRSLRF DDKPDYSYLR QLFRNLFHRQ GFSYDYVFDW NMLKFGASRA
310 320 330 340 350
ADDAERERRD REERLRHSRN PATRGLPSTA SGRLRGTQEV APPTPLTPTS
360 370 380 390 400
HTANTSPRPV SGMERERKVS MRLHRGAPVN VSSSDLTGRQ DTSRMSTSQI
410
PGRVASSGLQ SVVHR
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 ENSGT00760000119040.
HOGENOMi HOG000182055.
HOVERGENi HBG000176.
InParanoidi Q06486.
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 29, 2014
This is version 133 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