Q06486 (KC1D_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

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

Gene names

Name:	Csnk1d
Synonyms:	Hckid

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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 By similarity. Ref.5
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. ATP + [tau protein] = ADP + [tau protein] phosphate.
Enzyme regulation	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. Exhibits substrate-dependent heparin activation.
Subunit structure	Binds to DNMT1. 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 By similarity. Binds to MAP1A. Ref.5
Subcellular location	Cytoplasm By similarity. Nucleus By similarity. 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.
Tissue specificity	Expressed in most tissues, including heart, brain, testis, kidney, spleen and lung. Ref.4
Domain	The autoinhibitory domain is involved in regulating enzyme activity through autophosphorylation and possibly, through heparin binding. Ref.3
Post-translational modification	Autophosphorylated on serine and threonine residues; this autophosphorylation represses activity. Reactivated by phosphatase-mediated dephosphorylation. Ref.3 Ref.6
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	3D-structure Complete proteome Direct protein sequencing 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 sequence or structural similarity. Source: UniProtKB mitotic cell cycle Traceable author statement. Source: RGD positive regulation of proteasomal ubiquitin-dependent protein catabolic process Inferred from sequence or structural similarity. Source: UniProtKB regulation of circadian rhythm Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	centrosome Traceable author statement. Source: RGD nucleus Inferred from sequence or structural similarity. Source: UniProtKB soluble fraction Inferred from direct assay Ref.1. Source: RGD spindle Traceable author statement. Source: RGD
Molecular function	ATP binding Inferred from direct assay Ref.1. Source: RGD glycoprotein binding Inferred from direct assay Ref.1. Source: RGD peptide binding Inferred from direct assay Ref.1. Source: RGD phosphoprotein binding Inferred from direct assay Ref.1. Source: RGD protein serine/threonine kinase activity Inferred from direct assay Ref.1. Source: RGD tau-protein kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MDM2	Q00987	2	EBI-2910316,EBI-389668	From a different organism.

Alternative products

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

Isoform 1 (identifier: Q06486-1)

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: Q06486-2)

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

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_0000192836

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

Sites

Active site

128

1

Proton acceptor

Binding site

38

1

ATP By similarity

Amino acid modifications

Modified residue

328

1

Phosphoserine By similarity

Modified residue

329

1

Phosphothreonine By similarity

Modified residue

331

1

Phosphoserine By similarity

Modified residue

337

1

Phosphothreonine By similarity

Modified residue

344

1

Phosphothreonine By similarity

Modified residue

347

1

Phosphothreonine By similarity

Modified residue

349

1

Phosphothreonine By similarity

Modified residue

350

1

Phosphoserine By similarity

Modified residue

352

1

Phosphothreonine By similarity

Modified residue

355

1

Phosphothreonine By similarity

Modified residue

356

1

Phosphoserine By similarity

Modified residue

361

1

Phosphoserine By similarity

Modified residue

370

1

Phosphoserine; by PKA Ref.6

Modified residue

382

1

Phosphoserine By similarity

Modified residue

383

1

Phosphoserine By similarity

Modified residue

384

1

Phosphoserine By similarity

Modified residue

387

1

Phosphothreonine By similarity

Modified residue

392

1

Phosphothreonine By similarity

Modified residue

393

1

Phosphoserine By similarity

Modified residue

396

1

Phosphoserine By similarity

Modified residue

397

1

Phosphothreonine By similarity

Modified residue

398

1

Phosphoserine By similarity

Modified residue

406

1

Phosphoserine By similarity

Modified residue

407

1

Phosphoserine By similarity

Modified residue

411

1

Phosphoserine By similarity

Natural variations

Alternative sequence

400 – 415

16

IPGRV…SVVHR → RSRDMASLRLHAARQGARCR PQRPRRTTY in isoform 2.

VSP_010255

Secondary structure

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415

Helix Strand Turn

Details...

Turn

6 – 8

3

Beta strand

9 – 17

9

Beta strand

19 – 28

10

Turn

29 – 31

3

Beta strand

34 – 42

9

Helix

49 – 58

10

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

Beta strand

177 – 179

3

Helix

182 – 185

4

Helix

192 – 208

17

Helix

225 – 234

10

Helix

237 – 240

4

Turn

241 – 243

3

Helix

246 – 257

12

Helix

266 – 279

14

Helix

289 – 292

4

Helix

293 – 295

3

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: E6B11915C1746568	FASTA	428	49,121
	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 370 380 390 400 410 420 SGMERERKVS MRLHRGAPVN VSSSDLTGRQ DTSRMSTSQR SRDMASLRLH AARQGARCRP QRPRRTTY

References

[1]	"Molecular cloning, expression, and characterization of a 49-kilodalton casein kinase I isoform from rat testis." Graves P.R., Haas D.W., Hagedorn C.H., Depaoli-Roach A.A., Roach P.J. J. Biol. Chem. 268:6394-6401(1993) [PubMed: 8454611] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 1-6. Tissue: Testis.
[2]	"Casein kinase 1 delta rat." Takano A., Nagai K. Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Role of COOH-terminal phosphorylation in the regulation of casein kinase I delta." Graves P.R., Roach P.J. J. Biol. Chem. 270:21689-21694(1995) [PubMed: 7665585] [Abstract] Cited for: AUTOPHOSPHORYLATION, AUTOINHIBITORY DOMAIN.
[4]	"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: 11165242] [Abstract] Cited for: TISSUE SPECIFICITY.
[5]	"Interaction of casein kinase 1 delta (CK1 delta) with the light chain LC2 of microtubule associated protein 1A (MAP1A)." Wolff S., Xiao Z., Wittau M., Suessner N., Stoeter M., Knippschild U. Biochim. Biophys. Acta 1745:196-206(2005) [PubMed: 15961172] [Abstract] Cited for: FUNCTION AS MAP1A KINASE, INTERACTION WITH MAP1A.
[6]	"Phosphorylation of CK1delta: identification of Ser370 as the major phosphorylation site targeted by PKA in vitro and in vivo." Giamas G., Hirner H., Shoshiashvili L., Grothey A., Gessert S., Kuehl M., Henne-Bruns D., Vorgias C.E., Knippschild U. Biochem. J. 406:389-398(2007) [PubMed: 17594292] [Abstract] Cited for: PHOSPHORYLATION AT SER-370 BY PKA.
[7]	"Three-dimensional structure of mammalian casein kinase I: molecular basis for phosphate recognition." Longenecker K.L., Roach P.J., Hurley T.D. J. Mol. Biol. 257:618-631(1996) [PubMed: 8648628] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1-317.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L07578 mRNA. Translation: AAA40934.1.
AB063114 mRNA. Translation: BAB60852.1.

IPI

IPI00193377.
IPI00392332.

PIR

A46002.

RefSeq

NP_620691.2. NM_139060.3.

UniGene

Rn.8046.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CKI	X-ray	2.30	A/B	1-317	[»]
1CKJ	X-ray	2.46	A/B	1-317	[»]

ProteinModelPortal

Q06486.

SMR

Q06486. Positions 1-296.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q06486. 1 interaction.

MINT

MINT-3389660.

STRING

Q06486.

PTM databases

PhosphoSite

Q06486.

Proteomic databases

PRIDE

Q06486.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

64462.

KEGG

rno:64462.

Organism-specific databases

CTD

1453.

RGD

71031. Csnk1d.

Phylogenomic databases

eggNOG

roNOG08145.

GeneTree

ENSGT00560000076651.

HOVERGEN

HBG000176.

PhylomeDB

Q06486.

Enzyme and pathway databases

BRENDA

2.7.11.1. 5301.

Gene expression databases

ArrayExpress

Q06486.

Genevestigator

Q06486.

GermOnline

ENSRNOG00000036676. Rattus norvegicus.

Family and domain databases

InterPro

IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

KO

K08959.

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

NextBio

613212.

Entry information

Entry name

KC1D_RAT

Accession

Primary (citable) accession number: Q06486
Secondary accession number(s): Q99KK4

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	May 10, 2004
Last modified:	January 25, 2012
This is version 106 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program