Q9DC28 (KC1D_MOUSE) 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

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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.5 Ref.6 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.8 ATP + [tau protein] = ADP + [tau protein] phosphate. Ref.8
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 By similarity.
Subunit structure	Binds to MAP1A. 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, DBNDD2, AIB1/NCOA3 and ESR1. AKAP9/AKAP450 binding promotes centrosomal subcellular location. Binds to tubulins in mitotic cells upon DNA damage By similarity. Binds to SNAPIN and DNMT1. Ref.3 Ref.6 Ref.8 Ref.10
Subcellular location	Cytoplasm By similarity. Nucleus. Cytoplasm › cytoskeleton › centrosome By similarity. Cytoplasm › perinuclear region By similarity. Cell membrane By similarity. Cytoplasm › cytoskeleton › spindle By similarity. Golgi apparatus By similarity. Note: Localized at mitotic spindle microtubules, and at the centrosomes and interphase in interphase cells. Recruited to the spindle apparatus and the centrosomes in response to DNA-damage. Correct subcellular localization requires kinase activity By similarity. Ref.3 Ref.6 Ref.8
Tissue specificity	Expressed ubiquitously. However, kinase activity is not uniform, with highest kinase activity in splenocytes. Ref.4
Post-translational modification	Autophosphorylated on serine and threonine residues; this autophosphorylation represses activity. Reactivated by phosphatase-mediated dephosphorylation By similarity.
Disruption phenotype	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. Ref.8 Ref.9
Sequence similarities	Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Biological rhythms Wnt signaling pathway
Cellular component	Cell membrane Cytoplasm Cytoskeleton Golgi apparatus Membrane Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW circadian regulation of gene expression Inferred from mutant phenotype Ref.8. Source: UniProtKB positive regulation of canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from mutant phenotype Ref.8. Source: UniProtKB positive regulation of protein phosphorylation Inferred from electronic annotation. Source: Compara regulation of circadian rhythm Inferred from mutant phenotype Ref.8. Source: UniProtKB spindle assembly Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell centrosome Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome nucleoplasm Traceable author statement. Source: Reactome perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell spindle microtubule Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase activity Inferred from direct assay Ref.8. 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...

Alternative products

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

Isoform 1 (identifier: Q9DC28-1)

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: Q9DC28-2)

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

Note: Contains a phosphoserine at position 401 (By similarity).

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_0000192834
Regions
	Domain	9 – 277	269	Protein kinase
	Nucleotide binding	15 – 23	9	ATP By similarity
	Region	278 – 364	87	Centrosomal localization signal (CLS) By similarity
	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 By similarity
	Modified residue	370	1	Phosphoserine By similarity
	Modified residue	382	1	Phosphoserine Ref.7
	Modified residue	383	1	Phosphoserine By similarity
	Modified residue	384	1	Phosphoserine By similarity
	Modified residue	411	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	400 – 415	16	IPGRV…SVVHR → NSIPFEHHGK in isoform 2.		VSP_010254
Experimental info
	Sequence conflict	313	1	E → G in BAB23405. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 10, 2004. Version 2. Checksum: B97F04AF9EB466D2	FASTA	415	47,316
	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 VSSSDLTGRQ DTSRMSTSQI PGRVASSGLQ SVVHR
	Isoform 2 [UniParc]. Checksum: 970B55B1B19AB9DD	FASTA	409	46,818
	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 VSSSDLTGRQ DTSRMSTSQN SIPFEHHGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J and NOD. Tissue: Bone marrow, Lung and Thymus.
[2]	"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] (ISOFORM 1).
[3]	"Nuclear entry of the circadian regulator mPER1 is controlled by mammalian casein kinase I epsilon." Vielhaber E., Eide E., Rivers A., Gao Z.-H., Virshup D.M. Mol. Cell. Biol. 20:4888-4899(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PER1, SUBCELLULAR LOCATION.
[4]	"Casein kinase I delta (CKIdelta) is involved in lymphocyte physiology." Maritzen T., Loehler J., Deppert W., Knippschild U. Eur. J. Cell Biol. 82:369-378(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"Physiological role for casein kinase 1 in glutamatergic synaptic transmission." Chergui K., Svenningsson P., Greengard P. J. Neurosci. 25:6601-6609(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN SYNAPTIC TRANSMISSION.
[6]	"Casein kinase 1 delta (CK1delta) interacts with the SNARE associated protein snapin." Wolff S., Stoeter M., Giamas G., Piesche M., Henne-Bruns D., Banting G., Knippschild U. FEBS Lett. 580:6477-6484(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS SNAPIN KINASE, SUBCELLULAR LOCATION, INTERACTION WITH SNAPIN.
[7]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-382, MASS SPECTROMETRY. Tissue: Liver.
[8]	"Casein kinase 1 delta regulates the pace of the mammalian circadian clock." Etchegaray J.P., Machida K.K., Noton E., Constance C.M., Dallmann R., Di Napoli M.N., DeBruyne J.P., Lambert C.M., Yu E.A., Reppert S.M., Weaver D.R. Mol. Cell. Biol. 29:3853-3866(2009) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, INTERACTION WITH PER1 AND PER2, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, FUNCTION.
[9]	"Essential roles of CKIdelta and CKIepsilon in the mammalian circadian clock." Lee H., Chen R., Lee Y., Yoo S., Lee C. Proc. Natl. Acad. Sci. U.S.A. 106:21359-21364(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CIRCADIAN CLOCK, DISRUPTION PHENOTYPE.
[10]	"The DNA-binding activity of mouse DNA methyltransferase 1 is regulated by phosphorylation with casein kinase 1delta/epsilon." Sugiyama Y., Hatano N., Sueyoshi N., Suetake I., Tajima S., Kinoshita E., Kinoshita-Kikuta E., Koike T., Kameshita I. Biochem. J. 427:489-497(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS DNMT1 KINASE, INTERACTION WITH DNMT1.
[11]	"Casein kinase 1 delta (CK1delta) regulates period length of the mouse suprachiasmatic circadian clock in vitro." Etchegaray J.-P., Yu E.A., Indic P., Dallmann R., Weaver D.R. PLoS ONE 5:E10303-E10303(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CIRCADIAN CLOCK.
[12]	"Forebrain overexpression of CK1delta leads to down-regulation of dopamine receptors and altered locomotor activity reminiscent of ADHD." Zhou M., Rebholz H., Brocia C., Warner-Schmidt J.L., Fienberg A.A., Nairn A.C., Greengard P., Flajolet M. Proc. Natl. Acad. Sci. U.S.A. 107:4401-4406(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DOPAMINE RECEPTORS.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00410959. IPI00761242.
PIR	S47616.
RefSeq	NP_620690.1. NM_139059.2.
UniGene	Mm.216227.
3D structure databases
ProteinModelPortal	Q9DC28.
SMR	Q9DC28. Positions 3-294.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-47809N.
IntAct	Q9DC28. 2 interactions.
STRING	10090.ENSMUSP00000094305.
PTM databases
PhosphoSite	Q9DC28.
Proteomic databases
PaxDb	Q9DC28.
PRIDE	Q9DC28.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000018274; ENSMUSP00000018274; ENSMUSG00000025162. ENSMUST00000070575; ENSMUSP00000070721; ENSMUSG00000025162.
GeneID	104318.
KEGG	mmu:104318.
Organism-specific databases
CTD	1453.
MGI	MGI:1355272. Csnk1d.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00560000076651.
HOGENOM	HOG000182055.
HOVERGEN	HBG000176.
KO	K08959.
OMA	HMESSRR.
OrthoDB	EOG42V8G9.
Enzyme and pathway databases
Reactome	REACT_109335. Circadian Clock. REACT_24972. Circadian Clock (mouse).
Gene expression databases
ArrayExpress	Q9DC28.
Bgee	Q9DC28.
CleanEx	MM_CSNK1D.
Genevestigator	Q9DC28.
GermOnline	ENSMUSG00000025162. Mus musculus.
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	Q9DC28.
ChEMBL	CHEMBL5175.
ChiTaRS	CSNK1D. mouse.
NextBio	356922.
SOURCE	Search...

Entry information

Entry name

KC1D_MOUSE

Accession

Primary (citable) accession number: Q9DC28
Secondary accession number(s): Q3TZK2, Q99KK4

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	May 10, 2004
Last modified:	April 3, 2013
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program