P48730 (KC1D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Casein kinase I isoform delta
Short name=CKI-delta
Short name=CKId
EC=2.7.11.1

Alternative name(s):
Tau-protein kinase CSNK1D
EC=2.7.11.26

Gene names

Name:	CSNK1D
Synonyms:	HCKID

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	415 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. May act as a negative regulator of circadian rhythmicity by phosphorylating PER1 and PER2, leading to retain PER1 in the cytoplasm. 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. Ref.7 Ref.11 Ref.13 Ref.14 Ref.16 Ref.17 Ref.23 Ref.24 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.34 Ref.35
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.15 ATP + [tau protein] = ADP + [tau protein] phosphate. Ref.15
Enzyme regulation	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-sulphonamide (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). Ref.6 Ref.13 Ref.14 Ref.21 Ref.23 Ref.30 Ref.31 Ref.34 Ref.35 Ref.36
Subunit structure	Binds to DNMT1 and MAP1A By similarity. Monomer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK, or NPAS2, BMAL1 or 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. Ref.8 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.24
Subcellular location	Cytoplasm. Nucleus. Cytoplasm › cytoskeleton › centrosome. Cytoplasm › perinuclear region. Cell membrane. Cytoplasm › cytoskeleton › spindle. 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. Ref.8 Ref.9 Ref.12 Ref.14 Ref.35
Tissue specificity	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. Ref.2 Ref.14
Developmental stage	Highly present in extravillous trophoblast cells, which are present at the placenta implantation site and invade the decidua and decidual vessels. Ref.14
Post-translational modification	Autophosphorylated on serine and threonine residues; this autophosphorylation represses activity. Reactivated by phosphatase-mediated dephosphorylation. Ref.6 Ref.36
Involvement in disease	Familial advanced sleep-phase syndrome (FASPS) [MIM:604348]: Characterized by very early sleep onset and offset. Individuals are 'morning larks' with a 4 hours advance of the sleep, temperature and melatonin rhythms. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.39
Miscellaneous	May be involved in Alzheimer disease by phosphorylating MAPT/TAU (Ref.17).
Sequence similarities	Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily. Contains 1 protein kinase domain.
Caution	Was shown to phosphorylate and activate DCK in vitro but probably not in vivo (Ref.26).

Ontologies

Keywords
Biological process	Biological rhythms Wnt signaling pathway
Cellular component	Cell membrane Cytoplasm Cytoskeleton Golgi apparatus Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Traceable author statement Ref.1. Source: ProtInc G2/M transition of mitotic cell cycle Traceable author statement. Source: Reactome Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW circadian regulation of gene expression Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of canonical Wnt receptor signaling pathway Inferred from mutant phenotype PubMed 20412773. Source: BHF-UCL positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of protein phosphorylation Inferred from mutant phenotype PubMed 20412773. Source: BHF-UCL regulation of circadian rhythm Inferred from sequence or structural similarity. Source: UniProtKB signal transduction Traceable author statement Ref.1. Source: ProtInc spindle assembly Inferred from direct assay Ref.8. Source: UniProtKB
Cellular_component	Golgi apparatus Inferred from direct assay Ref.8. Source: UniProtKB centrosome Inferred from direct assay PubMed 21399614Ref.35. Source: UniProtKB cytosol Traceable author statement. Source: Reactome nucleus Inferred from sequence or structural similarity. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay Ref.14. Source: UniProtKB plasma membrane Inferred from direct assay Ref.14. Source: UniProtKB spindle microtubule Inferred from direct assay Ref.8. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase activity Inferred from direct assay Ref.15. Source: UniProtKB protein serine/threonine kinase activity Inferred from electronic annotation. Source: UniProtKB-KW tau-protein kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MDM2	Q00987	6	EBI-751621,EBI-389668

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P48730-1)

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.

Isoform 2 (identifier: P48730-2)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 415

415

Casein kinase I isoform delta

PRO_0000192833

Regions

Domain

9 – 277

269

Protein kinase

Nucleotide binding

15 – 23

9

ATP By similarity

Region

278 – 364

87

Centrosomal localization signal (CLS)

Region

317 – 342

26

Autoinhibitory By similarity

Sites

Active site

128

1

Proton acceptor By similarity

Binding site

38

1

ATP By similarity

Amino acid modifications

Modified residue

331

1

Phosphoserine Ref.20

Modified residue

370

1

Phosphoserine By similarity

Modified residue

382

1

Phosphoserine By similarity

Modified residue

383

1

Phosphoserine Ref.25

Modified residue

384

1

Phosphoserine Ref.20

Modified residue

411

1

Phosphoserine Ref.22

Natural variations

Alternative sequence

400 – 415

16

IPGRV…SVVHR → NSIPFEHHGK in isoform 2.

VSP_010253

Natural variant

44

1

T → A in FASPS. Ref.39

VAR_029075

Natural variant

97

1

S → C in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. Ref.40 Ref.41

VAR_036451

Natural variant

401

1

P → A. Ref.41
Corresponds to variant rs56124628 [ dbSNP | Ensembl ].

VAR_042081

Experimental info

Mutagenesis

38

1

K → M: Impaired kinase activity and abnormal subcellular localization with exclusive accumulation to the nucleus. Ref.9

Mutagenesis

176

1

T → I: Impaired kinase activity and abnormal subcellular localization with exclusive accumulation to the nucleus. Ref.9

Sequence conflict

330

1

A → D in AAC50807. Ref.1

Secondary structure

1

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415

Helix Strand Turn

Details...

Turn

6 – 8

3

Beta strand

10 – 17

8

Beta strand

19 – 28

10

Turn

29 – 32

4

Beta strand

33 – 41

9

Helix

49 – 59

11

Beta strand

68 – 74

7

Beta strand

77 – 83

7

Helix

89 – 95

7

Turn

96 – 98

3

Helix

102 – 121

20

Helix

131 – 133

3

Beta strand

134 – 136

3

Helix

139 – 141

3

Beta strand

145 – 147

3

Turn

159 – 161

3

Helix

177 – 179

3

Helix

182 – 185

4

Helix

192 – 208

17

Turn

212 – 215

4

Beta strand

219 – 223

5

Helix

224 – 234

11

Helix

237 – 240

4

Turn

241 – 243

3

Helix

246 – 256

11

Helix

266 – 280

15

Helix

289 – 292

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 27, 2003. Version 2. Checksum: B97F1717A52466D2	FASTA	415	47,330
	10 20 30 40 50 60 MELRVGNRYR LGRKIGSGSF GDIYLGTDIA AGEEVAIKLE CVKTKHPQLH IESKIYKMMQ 70 80 90 100 110 120 GGVGIPTIRW CGAEGDYNVM VMELLGPSLE DLFNFCSRKF SLKTVLLLAD QMISRIEYIH 130 140 150 160 170 180 SKNFIHRDVK PDNFLMGLGK KGNLVYIIDF GLAKKYRDAR THQHIPYREN KNLTGTARYA 190 200 210 220 230 240 SINTHLGIEQ SRRDDLESLG YVLMYFNLGS LPWQGLKAAT KRQKYERISE KKMSTPIEVL 250 260 270 280 290 300 CKGYPSEFAT YLNFCRSLRF DDKPDYSYLR QLFRNLFHRQ GFSYDYVFDW NMLKFGASRA 310 320 330 340 350 360 ADDAERERRD REERLRHSRN PATRGLPSTA SGRLRGTQEV APPTPLTPTS HTANTSPRPV 370 380 390 400 410 SGMERERKVS MRLHRGAPVN ISSSDLTGRQ DTSRMSTSQI PGRVASSGLQ SVVHR
	Isoform 2 [UniParc]. Checksum: 970B55B1AF6B56DD	FASTA	409	46,832
	10 20 30 40 50 60 MELRVGNRYR LGRKIGSGSF GDIYLGTDIA AGEEVAIKLE CVKTKHPQLH IESKIYKMMQ 70 80 90 100 110 120 GGVGIPTIRW CGAEGDYNVM VMELLGPSLE DLFNFCSRKF SLKTVLLLAD QMISRIEYIH 130 140 150 160 170 180 SKNFIHRDVK PDNFLMGLGK KGNLVYIIDF GLAKKYRDAR THQHIPYREN KNLTGTARYA 190 200 210 220 230 240 SINTHLGIEQ SRRDDLESLG YVLMYFNLGS LPWQGLKAAT KRQKYERISE KKMSTPIEVL 250 260 270 280 290 300 CKGYPSEFAT YLNFCRSLRF DDKPDYSYLR QLFRNLFHRQ GFSYDYVFDW NMLKFGASRA 310 320 330 340 350 360 ADDAERERRD REERLRHSRN PATRGLPSTA SGRLRGTQEV APPTPLTPTS HTANTSPRPV 370 380 390 400 SGMERERKVS MRLHRGAPVN ISSSDLTGRQ DTSRMSTSQN SIPFEHHGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-331 AND SER-384, MASS SPECTROMETRY. 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]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411, MASS SPECTROMETRY.
[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, MASS SPECTROMETRY. 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]	"Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes." Meng Q.-J., Maywood E.S., Bechtold D.A., Lu W.-Q., Li J., Gibbs J.E., Dupre S.M., Chesham J.E., Rajamohan F., Knafels J., Sneed B., Zawadzke L.E., Ohren J.F., Walton K.M., Wager T.T., Hastings M.H., Loudon A.S.I. Proc. Natl. Acad. Sci. U.S.A. 107:15240-15245(2010) [PubMed] [Europe PMC] [Abstract] 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]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] 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]	"Casein kinase 1: Complexity in the family." Cheong J.K., Virshup D.M. Int. J. Biochem. Cell Biol. 43:465-469(2011) [PubMed] [Europe PMC] [Abstract] 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]	"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 FASPS ALA-44.
[40]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-97.
[41]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00011102.
IPI00234463.

PIR

G01876.

RefSeq

NP_001884.2. NM_001893.4.
NP_620693.1. NM_139062.2.

UniGene

Hs.631725.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

P48730.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-39735N.

IntAct

P48730. 8 interactions.

MINT

MINT-1454355.

STRING

9606.ENSP00000324464.

PTM databases

PhosphoSite

P48730.

Polymorphism databases

DMDM

27923980.

Proteomic databases

PaxDb

P48730.

PRIDE

P48730.

Protocols and materials databases

DNASU

1453.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000314028; ENSP00000324464; ENSG00000141551.
ENST00000392334; ENSP00000376146; ENSG00000141551.

GeneID

1453.

KEGG

hsa:1453.

UCSC

uc002kei.3. human.
uc002kej.3. human.

Organism-specific databases

CTD

1453.

GeneCards

GC17M080203.

HGNC

HGNC:2452. CSNK1D.

HPA

CAB015410.

MIM

600864. gene.
604348. phenotype.

neXtProt

NX_P48730.

Orphanet

164736. Familial advanced sleep-phase syndrome.

PharmGKB

PA26952.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000182055.

HOVERGEN

HBG000176.

InParanoid

P48730.

KO

K08959.

OMA

SIRMRQG.

OrthoDB

EOG42V8G9.

PhylomeDB

P48730.

Enzyme and pathway databases

BRENDA

2.7.11.1. 2681.

Pathway_Interaction_DB

foxopathway. FoxO family signaling.
hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins.

Reactome

REACT_115566. Cell Cycle.
REACT_24941. Circadian Clock.

Gene expression databases

ArrayExpress

P48730.

Bgee

P48730.

CleanEx

HS_CSNK1D.

Genevestigator

P48730.

GermOnline

ENSG00000141551. Homo sapiens.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P48730.

ChEMBL

CHEMBL2828.

ChiTaRS

CSNK1D. human.

GenomeRNAi

1453.

NextBio

5961.

SOURCE

Search...

Entry information

Entry name

KC1D_HUMAN

Accession

Primary (citable) accession number: P48730
Secondary accession number(s): A2I2P2, Q96KZ6, Q9BTN5

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	January 27, 2003
Last modified:	May 1, 2013
This is version 133 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.