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Protein

Casein kinase I isoform delta

Gene

Csnk1d

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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 phosphorylation. 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.9 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication
ATP + [tau protein] = ADP + [tau protein] phosphate.1 Publication

Enzyme regulationi

Exhibits substrate-dependent heparin activation. 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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei38ATPPROSITE-ProRule annotation1
Active sitei128Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi15 – 23ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • cellular response to nerve growth factor stimulus Source: Ensembl
  • circadian regulation of gene expression Source: UniProtKB
  • endocytosis Source: GO_Central
  • Golgi organization Source: MGI
  • microtubule nucleation Source: MGI
  • non-motile cilium assembly Source: MGI
  • peptidyl-serine phosphorylation Source: MGI
  • positive regulation of canonical Wnt signaling pathway Source: MGI
  • positive regulation of non-canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
  • positive regulation of protein phosphorylation Source: MGI
  • positive regulation of Wnt-mediated midbrain dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
  • positive regulation of Wnt signaling pathway Source: ParkinsonsUK-UCL
  • protein localization to centrosome Source: MGI
  • protein localization to cilium Source: MGI
  • protein localization to Golgi apparatus Source: MGI
  • protein phosphorylation Source: UniProtKB
  • regulation of cell shape Source: GO_Central
  • regulation of circadian rhythm Source: UniProtKB
  • spindle assembly Source: MGI
  • Wnt signaling pathway Source: UniProtKB-KW

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processBiological rhythms, Wnt signaling pathway
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-204005 COPII-mediated vesicle transport
R-MMU-2565942 Regulation of PLK1 Activity at G2/M Transition
R-MMU-380259 Loss of Nlp from mitotic centrosomes
R-MMU-380270 Recruitment of mitotic centrosome proteins and complexes
R-MMU-380320 Recruitment of NuMA to mitotic centrosomes
R-MMU-5620912 Anchoring of the basal body to the plasma membrane
R-MMU-8854518 AURKA Activation by TPX2

Names & Taxonomyi

Protein namesi
Recommended name:
Casein kinase I isoform delta (EC:2.7.11.1)
Short name:
CKI-delta
Short name:
CKId
Alternative name(s):
Tau-protein kinase CSNK1D (EC:2.7.11.26)
Gene namesi
Name:Csnk1d
Synonyms:Hckid
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1355272 Csnk1d

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

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

Pathology & Biotechi

Disruption phenotypei

Lethal. There are fewer embryos than expected at late stages of gestation; they weigh about 30% less than control animals, but appear otherwise normal. Mice die shortly after birth. Tissue-specific disruption increases the half-life of PER2 protein and alters circadian protein expression dynamics.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi44T → A: Increases pain sensitivity; reduces threshold for induction of cortical spreading depression; increases arterial dilation during cortical spreading depression and increases spontaneous and evoked calcium signaling in astrocytes. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL5175

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001928341 – 415Casein kinase I isoform deltaAdd BLAST415

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei328PhosphoserineBy similarity1
Modified residuei331PhosphoserineBy similarity1
Modified residuei370PhosphoserineBy similarity1
Modified residuei375Omega-N-methylarginineCombined sources1
Modified residuei382PhosphoserineCombined sources1
Modified residuei383PhosphoserineCombined sources1
Modified residuei384PhosphoserineBy similarity1
Modified residuei407PhosphoserineBy similarity1
Modified residuei411PhosphoserineBy similarity1
Isoform 2 (identifier: Q9DC28-2)
Modified residuei401PhosphoserineBy similarity1

Post-translational modificationi

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

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

PaxDbiQ9DC28
PeptideAtlasiQ9DC28
PRIDEiQ9DC28

PTM databases

iPTMnetiQ9DC28
PhosphoSitePlusiQ9DC28
SwissPalmiQ9DC28

Expressioni

Tissue specificityi

Expressed ubiquitously. However, kinase activity is not uniform, with highest kinase activity in splenocytes.1 Publication

Gene expression databases

BgeeiENSMUSG00000025162
CleanExiMM_CSNK1D
ExpressionAtlasiQ9DC28 baseline and differential
GenevisibleiQ9DC28 MM

Interactioni

Subunit structurei

Binds to MAP1A. Monomer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK, or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Interacts with MAPT/TAU, DBNDD2, AIB1/NCOA3 and ESR1. AKAP9/AKAP450 binding promotes centrosomal subcellular location. Binds to tubulins in mitotic cells upon DNA damage. Binds to SNAPIN and DNMT1.2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi222545, 22 interactors
DIPiDIP-47809N
IntActiQ9DC28, 20 interactors
MINTiQ9DC28
STRINGi10090.ENSMUSP00000018274

Structurei

Secondary structure

1415
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni6 – 8Combined sources3
Beta strandi9 – 16Combined sources8
Beta strandi19 – 28Combined sources10
Turni29 – 32Combined sources4
Beta strandi33 – 41Combined sources9
Helixi49 – 58Combined sources10
Turni59 – 61Combined sources3
Beta strandi68 – 74Combined sources7
Beta strandi77 – 83Combined sources7
Helixi89 – 95Combined sources7
Turni96 – 98Combined sources3
Helixi102 – 121Combined sources20
Helixi131 – 133Combined sources3
Beta strandi134 – 136Combined sources3
Helixi139 – 141Combined sources3
Beta strandi145 – 147Combined sources3
Turni159 – 161Combined sources3
Helixi177 – 179Combined sources3
Helixi182 – 185Combined sources4
Helixi192 – 208Combined sources17
Turni212 – 215Combined sources4
Helixi221 – 233Combined sources13
Helixi237 – 240Combined sources4
Turni241 – 243Combined sources3
Helixi247 – 257Combined sources11
Helixi266 – 279Combined sources14
Helixi289 – 291Combined sources3
Beta strandi295 – 297Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4JJRX-ray2.41A/B1-299[»]
5X17X-ray2.00A/B1-294[»]
ProteinModelPortaliQ9DC28
SMRiQ9DC28
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 277Protein kinasePROSITE-ProRule annotationAdd BLAST269

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni278 – 364Centrosomal localization signal (CLS)By similarityAdd BLAST87
Regioni317 – 342AutoinhibitoryBy similarityAdd BLAST26

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1164 Eukaryota
ENOG410XPGP LUCA
GeneTreeiENSGT00760000119040
HOGENOMiHOG000182055
HOVERGENiHBG000176
InParanoidiQ9DC28
KOiK08959
OMAiRWYGTEC
OrthoDBiEOG091G0AFG
TreeFamiTF300544

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9DC28-1) [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

        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: Q9DC28-2) [UniParc]FASTAAdd to basket

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

Show »
Length:409
Mass (Da):46,818
Checksum:i970B55B1B19AB9DD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti313E → G in BAB23405 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_010254400 – 415IPGRV…SVVHR → NSIPFEHHGK in isoform 2. 1 PublicationAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK004606 mRNA Translation: BAB23405.1
AK088642 mRNA Translation: BAC40472.1
AK152721 mRNA Translation: BAE31444.1
AK157812 mRNA Translation: BAE34206.1
BC004604 mRNA Translation: AAH04604.1
CCDSiCCDS25762.1 [Q9DC28-1]
CCDS25763.1 [Q9DC28-2]
PIRiS47616
RefSeqiNP_620690.1, NM_139059.2 [Q9DC28-1]
UniGeneiMm.216227

Genome annotation databases

EnsembliENSMUST00000018274; ENSMUSP00000018274; ENSMUSG00000025162 [Q9DC28-1]
ENSMUST00000070575; ENSMUSP00000070721; ENSMUSG00000025162 [Q9DC28-2]
GeneIDi104318
KEGGimmu:104318
UCSCiuc007mvb.1 mouse [Q9DC28-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiKC1D_MOUSE
AccessioniPrimary (citable) accession number: Q9DC28
Secondary accession number(s): Q3TZK2, Q99KK4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: May 10, 2004
Last modified: May 23, 2018
This is version 144 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health