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P48730

- KC1D_HUMAN

UniProt

P48730 - KC1D_HUMAN

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Protein

Casein kinase I isoform delta

Gene

CSNK1D

Organism
Homo sapiens (Human)
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.17 Publications

Catalytic activityi

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

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. Repressed by 3-[(2,4,6-trimethoxyphenyl)methylidenyl]-indolin-2-one (IC261), N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide (CKI-7), 4-[4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-pyridin-2-yl-1H-imidazol-2-yl]benzamide (D4476), 3,4-diaryl-isoxazoles and -imidazoles, and 4-(3-cyclohexyl-5-(4-fluoro-phenyl)-3H-imidazol-4-yl) pyrimidin-2-ylamine (PF670462, PF670).10 Publications

Kineticsi

Maximal velocity nearly identical for the reactions with alpha-casein and PER2 peptide.

  1. KM=36.5 µM for alpha-casein1 Publication
  2. KM=635.8 µM for PER2 peptide1 Publication
  3. KM=180.6 µM for ATP1 Publication

Sites

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

Regions

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

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. peptide binding Source: Ensembl
  3. protein kinase activity Source: UniProtKB
  4. protein serine/threonine kinase activity Source: UniProtKB-KW
  5. tau-protein kinase activity Source: UniProtKB-EC

GO - Biological processi

  1. circadian regulation of gene expression Source: UniProtKB
  2. DNA repair Source: ProtInc
  3. G2/M transition of mitotic cell cycle Source: Reactome
  4. mitotic cell cycle Source: Reactome
  5. positive regulation of canonical Wnt signaling pathway Source: BHF-UCL
  6. positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
  7. positive regulation of protein phosphorylation Source: BHF-UCL
  8. protein phosphorylation Source: UniProtKB
  9. regulation of circadian rhythm Source: UniProtKB
  10. signal transduction Source: ProtInc
  11. spindle assembly Source: UniProtKB
  12. 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. 2681.
ReactomeiREACT_15296. Recruitment of mitotic centrosome proteins and complexes.
REACT_15364. Loss of Nlp from mitotic centrosomes.
REACT_15451. Loss of proteins required for interphase microtubule organization from the centrosome.
REACT_160315. Regulation of PLK1 Activity at G2/M Transition.
REACT_24941. Circadian Clock.
SignaLinkiP48730.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:2452. CSNK1D.

Subcellular locationi

Cytoplasm. Nucleus. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Cytoplasmperinuclear region. Cell membrane. Cytoplasmcytoskeletonspindle. Golgi apparatus
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.

GO - Cellular componenti

  1. centrosome Source: UniProtKB
  2. cytosol Source: Reactome
  3. Golgi apparatus Source: UniProtKB
  4. nucleus Source: UniProtKB
  5. perinuclear region of cytoplasm Source: UniProtKB
  6. plasma membrane Source: UniProtKB
  7. spindle Source: UniProtKB
  8. spindle microtubule Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Involvement in diseasei

Advanced sleep phase syndrome, familial, 2 (FASPS2) [MIM:615224]: A disorder characterized by very early sleep onset and offset. Individuals are 'morning larks' with a 4 hours advance of the sleep, temperature and melatonin rhythms.2 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti44 – 441T → A in FASPS2; strongly reduces kinase activity. 2 Publications
VAR_029075
Natural varianti46 – 461H → R in FASPS2; strongly reduces kinase activity. 1 Publication
VAR_069801

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi38 – 381K → M: Impaired kinase activity and abnormal subcellular localization with exclusive accumulation to the nucleus. 1 Publication
Mutagenesisi176 – 1761T → I: Impaired kinase activity and abnormal subcellular localization with exclusive accumulation to the nucleus. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi615224. phenotype.
Orphaneti164736. Familial advanced sleep-phase syndrome.
PharmGKBiPA26952.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 415415Casein kinase I isoform deltaPRO_0000192833Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei331 – 3311Phosphoserine1 Publication
Modified residuei370 – 3701PhosphoserineBy similarity
Modified residuei382 – 3821PhosphoserineBy similarity
Modified residuei383 – 3831Phosphoserine1 Publication
Modified residuei384 – 3841Phosphoserine1 Publication
Modified residuei411 – 4111Phosphoserine1 Publication

Post-translational modificationi

Autophosphorylated on serine and threonine residues; this autophosphorylation represses activity. Reactivated by phosphatase-mediated dephosphorylation. May be dephosphorylated by PP1.3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP48730.
PaxDbiP48730.
PRIDEiP48730.

PTM databases

PhosphoSiteiP48730.

Expressioni

Tissue specificityi

Expressed in all tissues examined, including brain, heart, lung, liver, pancreas, kidney, placenta and skeletal muscle. However, kinase activity is not uniform, with highest kinase activity in splenocytes. In blood, highly expressed in hemopoietic cells and mature granulocytes. Also found in monocytes and lymphocytes.2 Publications

Developmental stagei

Highly present in extravillous trophoblast cells, which are present at the placenta implantation site and invade the decidua and decidual vessels.1 Publication

Gene expression databases

BgeeiP48730.
CleanExiHS_CSNK1D.
ExpressionAtlasiP48730. baseline and differential.
GenevestigatoriP48730.

Organism-specific databases

HPAiCAB015410.

Interactioni

Subunit structurei

Binds to DNMT1 and MAP1A (By similarity). 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.By similarity9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Dvl2Q608382EBI-751621,EBI-641940From a different organism.
MDM2Q009876EBI-751621,EBI-389668
ZDHHC17Q8IUH53EBI-9087876,EBI-524753

Protein-protein interaction databases

BioGridi107837. 45 interactions.
DIPiDIP-39735N.
IntActiP48730. 16 interactions.
MINTiMINT-1454355.
STRINGi9606.ENSP00000324464.

Structurei

Secondary structure

1
415
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni6 – 83Combined sources
Beta strandi10 – 178Combined sources
Beta strandi19 – 2810Combined sources
Turni29 – 324Combined sources
Beta strandi33 – 419Combined sources
Beta strandi44 – 463Combined sources
Helixi49 – 5911Combined sources
Beta strandi68 – 747Combined sources
Beta strandi77 – 837Combined sources
Helixi89 – 957Combined sources
Turni96 – 983Combined sources
Helixi102 – 12120Combined sources
Helixi131 – 1333Combined sources
Beta strandi134 – 1363Combined sources
Helixi139 – 1413Combined sources
Beta strandi145 – 1473Combined sources
Beta strandi154 – 1574Combined sources
Turni159 – 1613Combined sources
Helixi177 – 1793Combined sources
Helixi182 – 1854Combined sources
Helixi192 – 20817Combined sources
Turni212 – 2154Combined sources
Beta strandi219 – 2235Combined sources
Helixi224 – 23411Combined sources
Helixi237 – 2404Combined sources
Turni241 – 2433Combined sources
Helixi246 – 25611Combined sources
Helixi266 – 28015Combined sources
Helixi289 – 2924Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3UYSX-ray2.30A/B/C/D1-294[»]
3UYTX-ray2.00A/B/C/D1-294[»]
3UZPX-ray1.94A/B1-294[»]
4HGTX-ray1.80A/B1-294[»]
4HNFX-ray2.07A/B1-294[»]
4KB8X-ray1.95A/B/C/D3-317[»]
4KBAX-ray1.98A/B/C/D3-317[»]
4KBCX-ray1.98A/B1-317[»]
4KBKX-ray2.10A/B/C/D3-317[»]
4TW9X-ray2.40A/B1-295[»]
4TWCX-ray1.70A/B1-295[»]
ProteinModelPortaliP48730.
SMRiP48730. Positions 3-294.
ModBaseiSearch...
MobiDBiSearch...

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)Add
BLAST
Regioni317 – 34226AutoinhibitoryBy similarityAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000119040.
HOGENOMiHOG000182055.
HOVERGENiHBG000176.
InParanoidiP48730.
KOiK08959.
PhylomeDBiP48730.
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]
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: P48730-1) [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 ISSSDLTGRQ DTSRMSTSQI
410
PGRVASSGLQ SVVHR
Length:415
Mass (Da):47,330
Last modified:January 27, 2003 - v2
Checksum:iB97F1717A52466D2
GO
Isoform 2 (identifier: P48730-2) [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):46,832
Checksum:i970B55B1AF6B56DD
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti330 – 3301A → D in AAC50807. (PubMed:8786104)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti44 – 441T → A in FASPS2; strongly reduces kinase activity. 2 Publications
VAR_029075
Natural varianti46 – 461H → R in FASPS2; strongly reduces kinase activity. 1 Publication
VAR_069801
Natural varianti97 – 971S → C in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. 2 Publications
VAR_036451
Natural varianti401 – 4011P → A.1 Publication
Corresponds to variant rs56124628 [ dbSNP | Ensembl ].
VAR_042081

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei400 – 41516IPGRV…SVVHR → NSIPFEHHGK in isoform 2. 2 PublicationsVSP_010253Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U29171 mRNA. Translation: AAC50807.1.
U31285 mRNA. Translation: AAC50808.1.
AB091044 mRNA. Translation: BAC10903.1.
AK291758 mRNA. Translation: BAF84447.1.
EF015900 Genomic DNA. Translation: ABM64211.1.
BC003558 mRNA. Translation: AAH03558.1.
BC015775 mRNA. Translation: AAH15775.1.
CCDSiCCDS11805.1. [P48730-1]
CCDS11806.1. [P48730-2]
PIRiG01876.
RefSeqiNP_001884.2. NM_001893.4. [P48730-1]
NP_620693.1. NM_139062.2. [P48730-2]
UniGeneiHs.631725.

Genome annotation databases

EnsembliENST00000314028; ENSP00000324464; ENSG00000141551. [P48730-1]
ENST00000392334; ENSP00000376146; ENSG00000141551. [P48730-2]
GeneIDi1453.
KEGGihsa:1453.
UCSCiuc002kei.3. human. [P48730-2]
uc002kej.3. human. [P48730-1]

Polymorphism databases

DMDMi27923980.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U29171 mRNA. Translation: AAC50807.1 .
U31285 mRNA. Translation: AAC50808.1 .
AB091044 mRNA. Translation: BAC10903.1 .
AK291758 mRNA. Translation: BAF84447.1 .
EF015900 Genomic DNA. Translation: ABM64211.1 .
BC003558 mRNA. Translation: AAH03558.1 .
BC015775 mRNA. Translation: AAH15775.1 .
CCDSi CCDS11805.1. [P48730-1 ]
CCDS11806.1. [P48730-2 ]
PIRi G01876.
RefSeqi NP_001884.2. NM_001893.4. [P48730-1 ]
NP_620693.1. NM_139062.2. [P48730-2 ]
UniGenei Hs.631725.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3UYS X-ray 2.30 A/B/C/D 1-294 [» ]
3UYT X-ray 2.00 A/B/C/D 1-294 [» ]
3UZP X-ray 1.94 A/B 1-294 [» ]
4HGT X-ray 1.80 A/B 1-294 [» ]
4HNF X-ray 2.07 A/B 1-294 [» ]
4KB8 X-ray 1.95 A/B/C/D 3-317 [» ]
4KBA X-ray 1.98 A/B/C/D 3-317 [» ]
4KBC X-ray 1.98 A/B 1-317 [» ]
4KBK X-ray 2.10 A/B/C/D 3-317 [» ]
4TW9 X-ray 2.40 A/B 1-295 [» ]
4TWC X-ray 1.70 A/B 1-295 [» ]
ProteinModelPortali P48730.
SMRi P48730. Positions 3-294.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107837. 45 interactions.
DIPi DIP-39735N.
IntActi P48730. 16 interactions.
MINTi MINT-1454355.
STRINGi 9606.ENSP00000324464.

Chemistry

ChEMBLi CHEMBL2828.
GuidetoPHARMACOLOGYi 1997.

PTM databases

PhosphoSitei P48730.

Polymorphism databases

DMDMi 27923980.

Proteomic databases

MaxQBi P48730.
PaxDbi P48730.
PRIDEi P48730.

Protocols and materials databases

DNASUi 1453.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000314028 ; ENSP00000324464 ; ENSG00000141551 . [P48730-1 ]
ENST00000392334 ; ENSP00000376146 ; ENSG00000141551 . [P48730-2 ]
GeneIDi 1453.
KEGGi hsa:1453.
UCSCi uc002kei.3. human. [P48730-2 ]
uc002kej.3. human. [P48730-1 ]

Organism-specific databases

CTDi 1453.
GeneCardsi GC17M080203.
HGNCi HGNC:2452. CSNK1D.
HPAi CAB015410.
MIMi 600864. gene.
615224. phenotype.
neXtProti NX_P48730.
Orphaneti 164736. Familial advanced sleep-phase syndrome.
PharmGKBi PA26952.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00760000119040.
HOGENOMi HOG000182055.
HOVERGENi HBG000176.
InParanoidi P48730.
KOi K08959.
PhylomeDBi P48730.
TreeFami TF300544.

Enzyme and pathway databases

BRENDAi 2.7.11.1. 2681.
Reactomei REACT_15296. Recruitment of mitotic centrosome proteins and complexes.
REACT_15364. Loss of Nlp from mitotic centrosomes.
REACT_15451. Loss of proteins required for interphase microtubule organization from the centrosome.
REACT_160315. Regulation of PLK1 Activity at G2/M Transition.
REACT_24941. Circadian Clock.
SignaLinki P48730.

Miscellaneous databases

ChiTaRSi CSNK1D. human.
GeneWikii CSNK1D.
GenomeRNAii 1453.
NextBioi 5961.
PROi P48730.
SOURCEi Search...

Gene expression databases

Bgeei P48730.
CleanExi HS_CSNK1D.
ExpressionAtlasi P48730. baseline and differential.
Genevestigatori P48730.

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

« Hide 'large scale' publications
  1. "Sequence analysis of the cDNA for the human casein kinase I delta (CSNK1D) gene and its chromosomal localization."
    Kusuda J., Hidari N., Hidari M., Hashimoto K.
    Genomics 32:140-143(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Brain.
  2. "Involvement of casein kinase Iepsilon in cytokine-induced granulocytic differentiation."
    Okamura A., Iwata N., Nagata A., Tamekane A., Shimoyama M., Gomyo H., Yakushijin K., Urahama N., Hamaguchi M., Fukui C., Chihara K., Ito M., Matsui T.
    Blood 103:2997-3004(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    Tissue: Hematopoietic stem cell.
  3. NHLBI resequencing and genotyping service (RS&G)
    Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Placenta.
  5. "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] (ISOFORMS 1 AND 2).
    Tissue: Placenta and Spleen.
  6. "Regulation of casein kinase I epsilon and casein kinase I delta by an in vivo futile phosphorylation cycle."
    Rivers A., Gietzen K.F., Vielhaber E., Virshup D.M.
    J. Biol. Chem. 273:15980-15984(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME REGULATION, AUTOPHOSPHORYLATION.
  7. "Protein kinase CK1 is a p53-threonine 18 kinase which requires prior phosphorylation of serine 15."
    Dumaz N., Milne D.M., Meek D.W.
    FEBS Lett. 463:312-316(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS TP53 KINASE.
  8. "Interaction of casein kinase 1 delta (CK1delta) with post-Golgi structures, microtubules and the spindle apparatus."
    Behrend L., Stoeter M., Kurth M., Rutter G., Heukeshoven J., Deppert W., Knippschild U.
    Eur. J. Cell Biol. 79:240-251(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TUBULINS, SUBCELLULAR LOCATION.
  9. "Catalytic activity of protein kinase CK1 delta (casein kinase 1delta) is essential for its normal subcellular localization."
    Milne D.M., Looby P., Meek D.W.
    Exp. Cell Res. 263:43-54(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-38 AND THR-176.
  10. "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: INTERACTION WITH PER1 AND PER2.
  11. "Casein kinase 1 regulates connexin-43 gap junction assembly."
    Cooper C.D., Lampe P.D.
    J. Biol. Chem. 277:44962-44968(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS CONNEXIN-43/GJA1 KINASE, INTERACTION WITH CONNEXIN-43/GJA1.
  12. "Centrosomal anchoring of the protein kinase CK1delta mediated by attachment to the large, coiled-coil scaffolding protein CG-NAP/AKAP450."
    Sillibourne J.E., Milne D.M., Takahashi M., Ono Y., Meek D.W.
    J. Mol. Biol. 322:785-797(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH AKAP9/AKAP450, SUBCELLULAR LOCATION.
  13. "Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules."
    Li G., Yin H., Kuret J.
    J. Biol. Chem. 279:15938-15945(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS MAPT/TAU KINASE, ENZYME REGULATION, INTERACTION WITH MAPT/TAU.
  14. "Inhibition of casein kinase I delta alters mitotic spindle formation and induces apoptosis in trophoblast cells."
    Stoeter M., Bamberger A.-M., Aslan B., Kurth M., Speidel D., Loening T., Frank H.-G., Kaufmann P., Loehler J., Henne-Bruns D., Deppert W., Knippschild U.
    Oncogene 24:7964-7975(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN MITOTIC SPINDLE FORMATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, ENZYME REGULATION.
  15. "Dysbindin structural homologue CK1BP is an isoform-selective binding partner of human casein kinase-1."
    Yin H., Laguna K.A., Li G., Kuret J.
    Biochemistry 45:5297-5308(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, INTERACTION WITH DBNDD2.
  16. "Phosphorylation at Ser244 by CK1 determines nuclear localization and substrate targeting of PKD2."
    von Blume J., Knippschild U., Dequiedt F., Giamas G., Beck A., Auer A., Van Lint J., Adler G., Seufferlein T.
    EMBO J. 26:4619-4633(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS PKD2 KINASE.
  17. "Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis."
    Hanger D.P., Byers H.L., Wray S., Leung K.-Y., Saxton M.J., Seereeram A., Reynolds C.H., Ward M.A., Anderton B.H.
    J. Biol. Chem. 282:23645-23654(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS MAPT/TAU KINASE.
  18. "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
    Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
    J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  19. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
    Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
    Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  20. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-331 AND SER-384, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  21. "3,4-Diaryl-isoxazoles and -imidazoles as potent dual inhibitors of p38alpha mitogen activated protein kinase and casein kinase 1delta."
    Peifer C., Abadleh M., Bischof J., Hauser D., Schattel V., Hirner H., Knippschild U., Laufer S.
    J. Med. Chem. 52:7618-7630(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME REGULATION.
  22. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  23. "Casein kinase I delta/epsilon phosphorylates topoisomerase IIalpha at serine-1106 and modulates DNA cleavage activity."
    Grozav A.G., Chikamori K., Kozuki T., Grabowski D.R., Bukowski R.M., Willard B., Kinter M., Andersen A.H., Ganapathi R., Ganapathi M.K.
    Nucleic Acids Res. 37:382-392(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS TOP2A KINASE, ENZYME REGULATION.
  24. "CK1delta modulates the transcriptional activity of ERalpha via AIB1 in an estrogen-dependent manner and regulates ERalpha-AIB1 interactions."
    Giamas G., Castellano L., Feng Q., Knippschild U., Jacob J., Thomas R.S., Coombes R.C., Smith C.L., Jiao L.R., Stebbing J.
    Nucleic Acids Res. 37:3110-3123(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AIB1/NCOA3 AND ESR1 KINASE, INTERACTION WITH AIB1/NCOA3 AND ESR1.
  25. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-383, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  26. "Casein kinase 1delta activates human recombinant deoxycytidine kinase by Ser-74 phosphorylation, but is not involved in the in vivo regulation of its activity."
    Smal C., Vertommen D., Amsailale R., Arts A., Degand H., Morsomme P., Rider M.H., Neste E.V., Bontemps F.
    Arch. Biochem. Biophys. 502:44-52(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS DCK KINASE.
  27. "Isoform specific phosphorylation of p53 by protein kinase CK1."
    Venerando A., Marin O., Cozza G., Bustos V.H., Sarno S., Pinna L.A.
    Cell. Mol. Life Sci. 67:1105-1118(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS P53/TP53 KINASE, GENE FAMILY.
  28. "A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP)."
    Zhao B., Li L., Tumaneng K., Wang C.-Y., Guan K.-L.
    Genes Dev. 24:72-85(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS YAP1 KINASE.
  29. "Casein kinase 1 regulates human hypoxia-inducible factor HIF-1."
    Kalousi A., Mylonis I., Politou A.S., Chachami G., Paraskeva E., Simos G.
    J. Cell Sci. 123:2976-2986(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS HIF1A KINASE.
  30. Cited for: FUNCTION IN CIRCADIAN RHYTHMS, ENZYME REGULATION.
  31. "Chronic treatment with a selective inhibitor of casein kinase I delta/epsilon yields cumulative phase delays in circadian rhythms."
    Sprouse J., Reynolds L., Kleiman R., Tate B., Swanson T.A., Pickard G.E.
    Psychopharmacology 210:569-576(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CIRCADIAN RHYTHMS, ENZYME REGULATION.
  32. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  33. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  34. "Opposing action of casein kinase 1 and calcineurin in nucleo-cytoplasmic shuttling of mammalian translation initiation factor eIF6."
    Biswas A., Mukherjee S., Das S., Shields D., Chow C.W., Maitra U.
    J. Biol. Chem. 286:3129-3138(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS EIF6 KINASE, ENZYME REGULATION.
  35. "Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth."
    Greer Y.E., Rubin J.S.
    J. Cell Biol. 192:993-1004(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS DVL2 AND DVL3 KINASE, ENZYME REGULATION, SUBCELLULAR LOCATION.
  36. "IC261 induces cell cycle arrest and apoptosis of human cancer cells via CK1delta/epsilon and Wnt/beta-catenin independent inhibition of mitotic spindle formation."
    Cheong J.K., Nguyen T.H., Wang H., Tan P., Voorhoeve P.M., Lee S.H., Virshup D.M.
    Oncogene 30:2558-2569(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME REGULATION, AUTOPHOSPHORYLATION.
  37. Cited for: REVIEW ON CIRCADIAN RHYTHMS, GENE FAMILY.
  38. "Crystallographic studies of casein kinase I delta toward a structural understanding of auto-inhibition."
    Longenecker K.L., Roach P.J., Hurley T.D.
    Acta Crystallogr. D 54:473-475(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
  39. "Structural basis for the interaction between casein kinase 1 delta and a potent and selective inhibitor."
    Long A., Zhao H., Huang X.
    J. Med. Chem. 55:956-960(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 1-294 IN COMPLEX WITH INHIBITOR.
  40. "Structural basis for the potent and selective inhibition of casein kinase 1 epsilon."
    Long A.M., Zhao H., Huang X.
    J. Med. Chem. 55:10307-10311(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) OF 1-294 IN COMPLEX WITH INHIBITOR.
  41. "Functional consequences of a CKIdelta mutation causing familial advanced sleep phase syndrome."
    Xu Y., Padiath Q.S., Shapiro R.E., Jones C.R., Wu S.C., Saigoh N., Saigoh K., Ptacek L.J., Fu Y.H.
    Nature 434:640-644(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT FASPS2 ALA-44.
  42. Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-97.
  43. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-97 AND ALA-401.
  44. Cited for: VARIANTS FASPS2 ALA-44 AND ARG-46, CHARACTERIZATION OF VARIANTS FASPS2 ALA-44 AND ARG-46, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.

Entry informationi

Entry nameiKC1D_HUMAN
AccessioniPrimary (citable) accession number: P48730
Secondary accession number(s): A2I2P2, Q96KZ6, Q9BTN5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: January 27, 2003
Last modified: November 26, 2014
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

May be involved in Alzheimer disease by phosphorylating MAPT/TAU.1 Publication

Caution

Was shown to phosphorylate and activate DCK in vitro but probably not in vivo.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3