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Protein

Casein kinase I isoform delta

Gene

Csnk1d

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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 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
  • circadian rhythm Source: Reactome
  • 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
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

ReactomeiR-MMU-204005. COPII (Coat Protein 2) 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-400253. Circadian Clock.
R-MMU-508751. Circadian Clock.
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1355272. Csnk1d.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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.

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. 21 interactors.
DIPiDIP-47809N.
IntActiQ9DC28. 19 interactors.
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 – 17Combined sources9
Beta strandi19 – 28Combined sources10
Turni29 – 32Combined sources4
Beta strandi33 – 41Combined sources9
Helixi49 – 59Combined sources11
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
Turni177 – 179Combined sources3
Helixi182 – 185Combined sources4
Helixi192 – 208Combined sources17
Helixi224 – 234Combined sources11
Helixi237 – 240Combined sources4
Turni241 – 243Combined sources3
Helixi246 – 257Combined sources12
Helixi266 – 279Combined sources14
Helixi289 – 292Combined sources4
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[»]
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

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1164. Eukaryota.
ENOG410XPGP. LUCA.
GeneTreeiENSGT00760000119040.
HOGENOMiHOG000182055.
HOVERGENiHBG000176.
InParanoidiQ9DC28.
KOiK08959.
OMAiPTSHAAN.
OrthoDBiEOG091G0AFG.
TreeFamiTF300544.

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]
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]

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

Cross-referencesi

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.

3D structure databases

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

Protein-protein interaction databases

BioGridi222545. 21 interactors.
DIPiDIP-47809N.
IntActiQ9DC28. 19 interactors.
STRINGi10090.ENSMUSP00000018274.

Chemistry databases

ChEMBLiCHEMBL5175.

PTM databases

iPTMnetiQ9DC28.
PhosphoSitePlusiQ9DC28.

Proteomic databases

PaxDbiQ9DC28.
PeptideAtlasiQ9DC28.
PRIDEiQ9DC28.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi1453.
MGIiMGI:1355272. Csnk1d.

Phylogenomic databases

eggNOGiKOG1164. Eukaryota.
ENOG410XPGP. LUCA.
GeneTreeiENSGT00760000119040.
HOGENOMiHOG000182055.
HOVERGENiHBG000176.
InParanoidiQ9DC28.
KOiK08959.
OMAiPTSHAAN.
OrthoDBiEOG091G0AFG.
TreeFamiTF300544.

Enzyme and pathway databases

ReactomeiR-MMU-204005. COPII (Coat Protein 2) 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-400253. Circadian Clock.
R-MMU-508751. Circadian Clock.
R-MMU-5620912. Anchoring of the basal body to the plasma membrane.
R-MMU-8854518. AURKA Activation by TPX2.

Miscellaneous databases

ChiTaRSiCsnk1d. mouse.
PROiQ9DC28.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025162.
CleanExiMM_CSNK1D.
ExpressionAtlasiQ9DC28. baseline and differential.
GenevisibleiQ9DC28. MM.

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]
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]
ProtoNetiSearch...

Entry informationi

Entry nameiKC1D_MOUSE
AccessioniPrimary (citable) accession number: Q9DC28
Secondary accession number(s): Q3TZK2, Q99KK4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: May 10, 2004
Last modified: November 30, 2016
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, Reference proteome

Documents

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.