KinaseNET

Nomenclature

Short Name:

CK1a1

Full Name:

Casein kinase I, alpha isoform

Alias:

Casein kinase 1, alpha 1
Casein kinase I, alpha isoform
EC 2.7.11.1
KC1A
Kinase CK1-alpha
CK1
CK1-alpha
CKI-alpha
CSNK1A1

Classification

Type:

Protein-serine/threonine kinase

Group:

CK1

Family:

CK1

SubFamily:

Specific Links

BioCarta Entry:	nfat pathway
Entrez-Gene Entry:	1452
Entrez-Protein Entry:	NP_001883
GeneCards Entry:	CK1
KinBASE Entry:	CK1A
OMIM Entry:	600505
Pfam Entry:	P48729
PhosphoNET Entry:	P48729
Phosphosite Plus Entry:	688
ScanSite Entry:	P48729
Source Entry:	CSNK1A1
UCSD-Nature Entry:	A000485
UniProt Entry:	P48729
Kinexus Products:	CK1a1 CK1aSelectide - CK1a1 (CSNK1A1) protein kinase substrate peptide - Powder PE-01BGU90

General Links

Structure

Mol. Mass (Da):

38,915

# Amino Acids:

337

# mRNA Isoforms:

mRNA Isoforms:

41,937 Da (365 AA; P48729-2); 38,915 Da (337 AA; P48729); 37,567 Da (325 AA; P48729-3)

4D Structure:

Monomer. Interacts with the Axin complex.

3D Structure:

Download QuickTime Animation

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

5FQD

Subfamily Alignment

Domain Distribution:

Start	End	Domain
17	277	Pkinase

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.

hiddentext

○	CK1aSelectide - CK1a1 (CSNK1A1) protein kinase substrate peptide - Powder PE-01BGU90

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Acetylated:

A2,K8.

Serine phosphorylated:

S3, S4, S105, S199, S218, S242, S311, S313, S332.

Threonine phosphorylated:

T184, T287, T321, T327.

Tyrosine phosphorylated:

Y17, Y32, Y59, Y85, Y292, Y294.

Ubiquitinated:

K62, K65, K138, K162, K225, K229, K302, K304, K325.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

92

1409

123

966
17

264

41

214
26

392

6

254
35

527

401

603
81

1237

123

755
53

806

302

2118
19

284

143

370
100

1527

109

2589
74

1134

45

629
12

178

300

164
13

206

57

184
66

1005

471

717
15

229

72

150
16

247

24

218
16

238

41

218
15

230

73

244
31

478

350

2311
14

210

23

148
19

297

291

262
74

1125

479

781
18

282

35

262
17

266

47

229
16

243

20

128
20

305

23

199
19

293

35

282
70

1072

248

958
21

317

75

192
22

330

23

192
21

319

23

200
12

176

140

227
45

680

60

425
66

1010

126

1940
22

335

213

510
67

1022

317

767
46

705

165

1183

Evolution

Species Conservation

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:

100

100

100
98.8

98.8

100
97.6

98.2

100
-

-

100
-

-

100
99.7

99.7

100
-

-

-
57.2

67.8

100
96.1

96.1

100
-

-

-
-

-

-
99.7

100

100
57.6

68

100
59.5

70.2

99
-

-

-
74.2

82.8

79
80.9

86.9

-
81.2

86.8

79
78.7

87.4

-
-

-

-
-

-

-
-

-

72
50.2

63.1

67
41.9

54.7

-
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	PER3 - P56645
2	PER1 - O15534
3	ARFGAP1 - Q8N6T3
4	CTNNB1 - P35222
5	TP53 - P04637
6	BACE1 - P56817
7	GJA1 - P17302
8	CDK5 - Q00535
9	PRKD2 - Q9BZL6
10	SNCA - P37840
11	DVL1 - O14640
12	DVL1L1 - P54792
13	PER2 - O15055
14	PSEN2 - P49810
15	PPP1R14A - Q96A00

Regulation

Activation:

Inhibition:

Synthesis:

Degradation:

Kinections Map

Click here to download a PPT of the image below

Known Downstream Substrates

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.

Based on in vitro and/or in vivo phosphorylation data

Substrate Short Name	UniProt ID (Human)	Phosphosite Location	Phosphosite Sequence	Effect of Phosphorylation

14-3-3 theta	P27348	S232	LTLWTSDSAGEECDA	-
14-3-3 zeta (YWHAZ)	P63104	T232	LTLWTSDTQGDEAEA	-
AQP2	P41181	S256	REVRRRQSVELHSPQ
BACE	P56817	S498	DDFADDISLLK____
Bid	P55957	T59	EGYDELQTDGNRSSH
Calsenilin	Q9Y2W7	S63	APQGSDSSDSELELS
CDH1	P12830	S844	GSGSEAASLSSLNSS	-
CDK5	Q00535	S159	GIPVRCYSAEVVTLW	+
CREB1	P16220	S108	QISTIAESEDSQESV	?
CREB1	P16220	S111	TIAESEDSQESVDSV	-
CREB1	P16220	S114	ESEDSQESVDSVTDS	?
CREB1	P16220	S156	PRIEEEKSEEETSAP
CREM	Q03060	S115	AIAETDESAESEGVI
CREM	Q03060	S118	ETDESAESEGVIDSH
CREM	Q03060	S124	ESEGVIDSHKRREIL
CREM	Q03060	S159	PKIEEERSEEEGTPP	-
CTNNB1	P35222	S45	GATTTAPSLSGKGNP	+
Cx43	P17302	S324	NRMGQAGSTISNSHA
Cx43	P17302	S327	GQAGSTISNSHAQPF
Cx43	P17302	S329	AGSTISNSHAQPFDF
DARPP-32	Q9UD71	S137	EEEEEEDSQAEVLKV
ECE1	P42892	S34	DEEDLVDSLSEGDAY
ECE1	P42892	S36	EDLVDSLSEGDAYPN
eIF2B-e	Q13144	S469	DGEFSDDSGADQEKD
FADD	Q13158	S194	QNRSGAMSPMSWNSD
FAK (PTK2) iso5	Q05397	S843	DVRLSRGSIDREDGS
FOXG1	P55316	S19	MIPKSSFSINSLVPE	?
FOXO1A	Q12778	S322	PRTSSNASTISGRLS	-
FOXO1A	Q12778	S325	SSNASTISGRLSPIM	-
Galectin-3	P17931	S11	FSLHDALSGSGNPNP
Galectin-3	P17931	S5	___ADNFSLHDALSG
GRP94	P14625	S347	KPIWQRPSKEVEEDE
GYS1	P13807	S11	NRTLSMSSLPGLEDW	-
GYS1	P13807	S8	MPLNRTLSMSSLPGL	-
GYS2	P54840	S8	MLRGRSLSVTSLGGL	-
HDAC1	Q13547	S421	IACEEEFSDSEEEGE	-
hnRNP C1,C2	P07910	S253	ETNVKMESEGGADDS
hnRNP C1,C2	P07910	S260	SEGGADDSAEEGDLL
hnRNP C1,C2	P07910	S299	EGEDDRDSANGEDDS
IRS1	P35568	Y46	GGPARLEYYENEKKW
LRP6	O75581	T1493	NPPPSPATERSHYTM
MDM4	O15151	S289	DDLEDSKSLSDDTDV
NFAT4	Q12968	S177	ISSRSWFSDASSCES
NFAT4	Q12968	S180	RSWFSDASSCESLSH
NFAT4	Q12968	S181	SWFSDASSCESLSHI
NFAT4	Q12968	S184	SDASSCESLSHIYDD
NFAT4	Q12968	S186	ASSCESLSHIYDDVD
NFAT5	O94916	S176	LLDNSRMSCQDEGCG
p53	P04637	S20	PLSQETFSDLWKLLP	+
p53	P04637	T18	EPPLSQETFSDLWKL	+
Parkin	O60260	S101	GCEREPQSLTRVDLS
Parkin	O60260	S378	AYHEGECSAVFEASG
PRP1	P02810	S24	QDLDEDVSQEDVPLV
PRP1	P02810	S38	VISDGGDSEQFIDEE
RhoB	P62745	S185	ALQKRYGSQNGCINC
SLC4A1	P02730	S303	IDAYMAQSRGELLHS
SLC4A1	P02730	T42	AAHDTEATATDYHTT
SNCA	P37840	S129	NEAYEMPSEEGYQDY
TARDBP	Q13148	S183	KLPNSKQSQDEPLRS
TARDBP	Q13148	S2	______MSEYIRVTE
TARDBP	Q13148	S242	ADDQIAQSLCGEDLI
TARDBP	Q13148	S254	DLIIKGISVHISNAE
TARDBP	Q13148	S273	SNRQLERSGRFGGNP
TARDBP	Q13148	S292	NQGGFGNSRGGGAGL
TARDBP	Q13148	S305	GLGNNQGSNMGGGMN
TARDBP	Q13148	S342	GMMGMLASQQNQSGP
TARDBP	Q13148	S347	LASQQNQSGPSGNNQ
TARDBP	Q13148	S350	QQNQSGPSGNNQNQG
TARDBP	Q13148	S369	EPNQAFGSGNNSYSG
TARDBP	Q13148	S375	GSGNNSYSGSNSGAA
TARDBP	Q13148	S377	GNNSYSGSNSGAAIG
TARDBP	Q13148	S379	NSYSGSNSGAAIGWG
TARDBP	Q13148	S387	GAAIGWGSASNAGSG
TARDBP	Q13148	S389	AIGWGSASNAGSGSG
TARDBP	Q13148	S393	GSASNAGSGSGFNGG
TARDBP	Q13148	S395	ASNAGSGSGFNGGFG
TARDBP	Q13148	S403	GFNGGFGSSMDSKSS
TARDBP	Q13148	S404	FNGGFGSSMDSKSSG
TARDBP	Q13148	S407	GFGSSMDSKSSGWGM
TARDBP	Q13148	S409	GSSMDSKSSGWGM__	-
TARDBP	Q13148	S410	SSMDSKSSGWGM___	-
TARDBP	Q13148	S91	KMDETDASSAVKVKR
TARDBP	Q13148	S92	MDETDASSAVKVKRA
TARDBP	Q13148	T116	LGLPWKTTEQDLKEY
TARDBP	Q13148	T25	IPSEDDGTVLLSTVT
TARDBP	Q13148	T88	NKRKMDETDASSAVK
TARDBP	Q13148	Y4	____MSEYIRVTEDE
TBX21	Q9UL17	S513	PSSGDSSSPAGAPSP
VHL	P40337	S72	SVNSREPSQVIFCNR
VMAT2	Q05940	S511	PIGEDEESESD____
VMAT2	Q05940	S513	GEDEESESD______

Protein Kinase Specificity

Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites

Matrix Type:

Experimentally derived from alignment of 122 known protein substrate phosphosites.

Domain #:

Inhibitors

For further details on these inhibitors click on the Compound Name and enter it into DrugKiNET or click on the ID's

Based on in vitro and/or in vivo phosphorylation data

Compound Name	KD, Ki or IC50 (nM)	PubChem ID	ChEMBL ID	PubMed ID

Dasatinib	IC50 = 1 nM	11153014	1421	18849971
Sunitinib	IC50 = 1 nM	5329102	535	18849971
Aminopurvalanol A	IC50 > 3 nM	6604931		12678910
SB220025	IC50 < 25 nM	5164	274064	22037377
SB203580	Kd = 75 nM	176155	10	22037378
CHEMBL364935	IC50 = 91 nM	44401506	364935	15808450
AT9283	IC50 > 100 nM	24905142		19143567
D4476	IC50 > 250 nM	6419753	410456	22037377
Sorafenib	IC50 = 250 nM	216239	1336	18849971
Bosutinib	Kd = 280 nM	5328940	288441	22037378
SU14813	Kd = 400 nM	10138259	1721885	22037378
1;9-Pyrazoloanthrone	IC50 = 500 nM	8515	7064	22037377
AG-E-60384	IC50 = 500 nM	6419741	413188	22037377
BML-275	IC50 = 500 nM	11524144	478629	22037377
Indirubin-3′-monoxime	IC50 = 500 nM	5326739		22037377
JNK Inhibitor; Negative Control	IC50 = 500 nM	11665831		22037377
PD169316	IC50 = 500 nM	4712	17331	22037377
TG003	IC50 = 500 nM	1893668	408982	22037377
TG100115	Kd = 830 nM	10427712	230011	22037378
Staurosporine	Kd = 970 nM	5279		22037378
AC1NS7CD	Kd = 1 µM	5329665	295136	22037378
Compound 52	IC50 > 1 µM	2856		22037377
Fasudil	IC50 > 1 µM	3547	38380	22037377
Gö6983	IC50 > 1 µM	3499	261491	22037377
GSK-3 Inhibitor X	IC50 > 1 µM	6538818	430226	22037377
GSK-3b Inhibitor XI	IC50 > 1 µM	10020713	272629	22037377
H-89	IC50 > 1 µM	449241	104264	22037377
IC261	IC50 > 1 µM	3674	576349	22037377
Meridianin B	IC50 = 1 µM	10380356		15026054
MK5108	IC50 > 1 µM	24748204		20053775
p38 MAP Kinase Inhibitor	IC50 > 1 µM	4665	91730	22037377
PKR Inhibitor	IC50 > 1 µM	6490494	235641	22037377
PP121	IC50 = 1 µM	24905142		18849971
SB202190	IC50 > 1 µM	5353940	278041	22037377
Silmitasertib	IC50 > 1 µM	24748573		21174434
SKF-86002	IC50 > 1 µM	5228	313417	22037377
SNS032	Kd = 1 µM	3025986	296468	22037378
SNS314	IC50 > 1 µM	16047143	514582	18678489
SureCN10063060	Ki > 1 µM	52936621		21391610
TWS119	IC50 > 1 µM	9549289	405759	22037377
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
KW2449	Kd = 1.2 µM	11427553	1908397	22037378
KW2449	Kd = 1.2 µM	11427553	1908397	22037378
Ruxolitinib	Kd = 1.8 µM	25126798	1789941	22037378
A674563	Kd = 2.1 µM	11314340	379218	22037378
Cdk1/2 Inhibitor III	IC50 = 2.8 µM	5330812	261720	15974571
CHEMBL191336	IC50 = 3.05 µM	9863538	191336	15999992
Alvocidib	Kd = 3.1 µM	9910986	428690	22037378
BI2536	Kd = 3.1 µM	11364421	513909	22037378
SureCN4875304	IC50 > 3.5 µM	46871765		20472445
JNJ-28871063	IC50 > 4 µM	17747413		17975007

Disease Linkage

General Disease Association:

Cancer

Specific Cancer Types:

Lung cancer (LC)

Gene Expression in Cancers:

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Bladder carcinomas (%CFC= +138, p<0.0001); Brain glioblastomas (%CFC= -62, p<0.009); Brain oligodendrogliomas (%CFC= -77, p<0.002); Cervical cancer (%CFC= +45, p<0.003); Clear cell renal cell carcinomas (cRCC) stage I (%CFC= -71, p<0.0001); Skin squamous cell carcinomas (%CFC= +65, p<0.038); and Vulvar intraepithelial neoplasia (%CFC= +70, p<0.002). The COSMIC website notes an up-regulated expression score for CK1a1 in diverse human cancers of 407, which is 0.9-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 314 for this protein kinase in human cancers was 5.2-fold of the average score of 60 for the human protein kinases.

Mutagenesis Experiments:

Insertional mutagenesis studies in mice support a role for this protein kinase in mouse cancer oncogenesis.

Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.07 % in 25239 diverse cancer specimens. This rate is only -4 % lower and is very similar to the average rate of 0.075 % calculated for human protein kinases in general.

Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: D140A (4), A185V (4). These are located in the kinase catalytic domain.

Comments:

Only 2 deletions, 1 insertion, and no complex mutations are noted on the COSMIC website.

COSMIC Entry:

CSNK1A1

OMIM Entry:

600505

Nomenclature

Short Name:

Full Name:

Alias:

Classification

Type:

Group:

Family:

SubFamily:

Specific Links

General Links

Structure

Mol. Mass (Da):

# Amino Acids:

# mRNA Isoforms:

mRNA Isoforms:

4D Structure:

3D Structure:

1D Structure:

3D Image (rendered using PV Viewer):

PDB ID

Subfamily Alignment

Domain Distribution:

Kinexus Products

hiddentext

Post-translation Modifications

Acetylated:

Serine phosphorylated:

Threonine phosphorylated:

Tyrosine phosphorylated:

Ubiquitinated:

Distribution

Human Tissue Distribution

% Max Expression: Mean Expression: Number of Samples: Standard Deviation:

% Max Expression: Mean Expression: Number of Samples: Standard Deviation:

Evolution

Species Conservation

PhosphoNET % Identity: PhosphoNET % Similarity: Homologene %Identity:

PhosphoNET % Identity: PhosphoNET % Similarity: Homologene %Identity:

Binding Proteins

hiddentext

Regulation

Activation:

Inhibition:

Synthesis:

Degradation:

Kinections Map

Known Downstream Substrates

Based on in vitro and/or in vivo phosphorylation data

Protein Kinase Specificity

Matrix Type:

Domain #:

Inhibitors

Based on in vitro and/or in vivo phosphorylation data

Disease Linkage

General Disease Association:

Specific Cancer Types:

Gene Expression in Cancers:

Mutagenesis Experiments:

Mutation Rate in All Cancers:

Frequency of Mutated Sites:

Comments:

COSMIC Entry:

OMIM Entry:

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity: