KinaseNET

Nomenclature

Short Name:

DYRK1A

Full Name:

Dual-specificity tyrosine-phosphorylation regulated kinase 1A

Alias:

DYR1A
DYRK
EC 2.7.12.1
EC 2.7.12.2
MNB
MNBH

Classification

Type:

Protein-serine/threonine kinase

Group:

CMGC

Family:

DYRK

SubFamily:

Dyrk1

Specific Links

BioCarta Entry:	shh pathway
Entrez-Gene Entry:	1859
Entrez-Protein Entry:	NP_569120
GeneCards Entry:	MNBH
KinBASE Entry:	DYRK1A
OMIM Entry:	600855
Pfam Entry:	Q13627
PhosphoNET Entry:	Q13627
Phosphosite Plus Entry:	1004
Protein Data Bank Entry:	2VX3
ScanSite Entry:	Q13627
Source Entry:	DYRK1A
UCSD-Nature Entry:	A000796
UniProt Entry:	Q13627
Kinexus Products:	DYRK1A Dual specificity tyrosine-phosphorylation-regulated kinase 1A Y321 phosphosite-specific antibody AB-PK597 DYRKSubtide - DYRK1A protein kinase substrate peptide - Powder PE-01BHD95 Dual specificity tyrosine-phosphorylation-regulated kinase 1A (I318-S324, human) pY321 phosphopeptide - Powder PE-04AET99 Dual specificity tyrosine-phosphorylation-regulated kinase 1A (Q316-P330, human) pY319+pY321+pS324+pY327 phosphopeptide - Powder PE-04ATA50 Dual specificity tyrosine-phosphorylation-regulated kinase 1A (I318-S324, human) pY321 phosphopeptide - Powder PE-04BBR00

General Links

Structure

Mol. Mass (Da):

85,584

# Amino Acids:

763

# mRNA Isoforms:

mRNA Isoforms:

85,584 Da (763 AA; Q13627); 84,556 Da (754 AA; Q13627-2); 66,099 Da (584 AA; Q13627-5); 61,770 Da (540 AA; Q13627-4); 60,330 Da (529 AA; Q13627-3)

4D Structure:

Interacts RAD54L2/ARIP4 By similarity. Interacts with RANBP9. Interacts with WDR68

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

2VX3

Subfamily Alignment

Domain Distribution:

Start	End	Domain
159	479	Pkinase

Kinexus Products

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

hiddentext

○	Dual specificity tyrosine-phosphorylation-regulated kinase 1A Y321 phosphosite-specific antibody AB-PK597
○	DYRKSubtide - DYRK1A protein kinase substrate peptide - Powder PE-01BHD95
○	Dual specificity tyrosine-phosphorylation-regulated kinase 1A (I318-S324, human) pY321 phosphopeptide - Powder PE-04AET99
○	Dual specificity tyrosine-phosphorylation-regulated kinase 1A (Q316-P330, human) pY319+pY321+pS324+pY327 phosphopeptide - Powder PE-04ATA50
○	Dual specificity tyrosine-phosphorylation-regulated kinase 1A (I318-S324, human) pY321 phosphopeptide - Powder PE-04BBR00

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Acetylated:

K105.

Serine phosphorylated:

S14, S22, S127, S324, S529+, S538, S555, S706, S748, S758, S762.

Tyrosine phosphorylated:

Y111, Y112, Y136, Y145, Y147, Y159, Y219, Y319, Y321+, Y705.

Ubiquitinated:

K453.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

100

1542

45

2490
5

84

25

85
12

184

3

277
28

433

129

539
45

699

36

641
10

153

118

213
30

470

55

580
42

650

53

918
34

530

24

548
8

121

140

137
6

85

36

106
38

585

309

634
9

144

36

195
10

157

20

171
7

101

28

104
9

132

23

157
7

115

379

133
6

96

18

76
16

253

136

346
35

540

162

667
11

165

24

182
13

205

30

306
4

63

30

90
11

162

20

158
18

270

27

400
52

802

72

909
8

117

39

147
7

113

18

110
12

183

16

190
13

200

42

139
47

728

54

721
83

1276

51

2140
14

216

86

326
51

782

93

725
21

328

66

573

Evolution

Species Conservation

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

100

100

100
0

0

100
99.6

99.8

100
-

-

100
-

-

98
85.1

85.5

99.5
-

-

-
99.2

99.4

99
99.6

99.7

100
-

-

-
94.4

95.2

-
26.7

39.9

96
91.4

94.2

93.5
78.7

84.2

83
-

-

-
47.7

60.2

79
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	DCAF7 - P61962
2	GLI1 - P08151
3	PHYHIP - Q92561
4	YWHAE - P62258
5	CREB1 - P16220
6	SFRS16 - Q8N2M8
7	YWHAG - P61981

Regulation

Activation:

Phosphorylation at Tyr-321 increases phosphotransferase activity. Phosphorylation at Ser-529 increases phosphotransferase activity and association with 14-3-3-beta.

Inhibition:

Inhibited by RANBP9.

Synthesis:

Degradation:

Known Upstream Kinases

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

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

DYRK1A	Q13627	Y219	KHDTEMKYYIVHLKR
DYRK1A	Q13627	Y321	LGQRIYQYIQSRFYR	+
DYRK1A	Q13627	S529	SNSGRARSDPTHQHR	+

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

Amphiphysin	P49418	S293	PAPARPRSPSQTRKG
Amphiphysin	P49418	S295	PARPRSPSQTRKGPP
Amphiphysin	P49418	T310	VPPLPKVTPTKELQQ
Amphiphysin	P49418	T312	PLPKVTPTKELQQEN
Caspase 9	P55211	T125	PEVLRPETPRPVDIG
Cyclin N (CCNL2)	Q96S94	S330	LDGTSGFSPAPKLVE
Cyclin N (CCNL2)	Q96S94	S338	PAPKLVESPKEGKGS
Cyclin N (CCNL2)	Q96S94	S369	AKKAKADSPVNGLPK
DYN1	Q05193	S795	VPPARPGSRGPAPGP
DYN1	Q05193	S857	ASPSRPESPRPPFDL
DYRK1A	Q13627	S529	SNSGRARSDPTHQHR	+
DYRK1A	Q13627	Y219	KHDTEMKYYIVHLKR
DYRK1A	Q13627	Y321	LGQRIYQYIQSRFYR	+
eIF2B-e	Q13144	S544	EPDSRGGSPQMDDIK
FOXO1A	Q12778	S329	STISGRLSPIMTEQD	-
GYS1	P13807	S641	YRYPRPASVPPSPSL	-
GYS2	P54840	S641	FKYPRPSSVPPSPSG	-
H3.1	P68431	T45	PHRYRPGTVALREIR
SF3B1	O75533	T273	ATPGRGDTPGHATPG
SF3B1	O75533	T434	PARKLTATPTPLGGM
SNCA	P37840	S87	KTVEGAGSIAAATGF
Spry2	O43597	T75	KPAPRPSTQHKHERL
SRSF1 (SF2, ASF)	Q07955	S226	NSRSRSYSPRRSRGS
SRSF1 (SF2, ASF)	Q07955	S233	SPRRSRGSPRYSPRH
SRSF1 (SF2, ASF)	Q07955	S237	SRGSPRYSPRHSRSR
STAT3	P40763	S727	NTIDLPMSPRTLDSL	-
Tau iso5 (Tau-C)	P10636-5	T212	TPGSRSRTPSLPTPP
Tau iso8	P10636-8	S199	GDRSGYSSPGSPGTP
Tau iso8	P10636-8	S202	SGYSSPGSPGTPGSR
Tau iso8	P10636-8	S396	GAEIVYKSPVVSGDT
Tau iso8	P10636-8	S404	PVVSGDTSPRHLSNV
Tau iso8	P10636-8	S422	GSIDMVDSPQLATLA
Tau iso8	P10636-8	T181	KTPPAPKTPPSSGEP
Tau iso8	P10636-8	T205	SSPGSPGTPGSRSRT
Tau iso8	P10636-8	T217	SRTPSLPTPPTREPK
Tau iso8	P10636-8	T231	KKVAVVRTPPKSPSS

Protein Kinase Specificity

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

Matrix Type:

Experimentally derived from alignment of 33 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

A 443654	IC50 < 2 nM	10172943	379300
A674563	Kd = 2.1 nM	11314340	379218	22037378
Staurosporine	Kd = 4 nM	5279		22037378
TTT-3002	IC50 < 6 nM
TG003	IC50 = 12 nM	1893668	408982	21450467
CHEMBL1474834	Kd = 13 nM	44223970	1474834	21450467
CHEMBL1551169	IC50 = 17 nM	46916176	1551169	21450467
Lestaurtinib	Kd = 20 nM	126565		22037378
R547	Kd = 23 nM	6918852		22037378
CHEMBL1704879	IC50 = 26 nM	46916172	1704879	21450467
CHEMBL1436585	Kd = 27 nM	46916178	1436585	21450467
NCGC00010037	IC50 = 27 nM	3232621		21450467
CHEMBL1552755	IC50 = 30 nM	44223955	1552755	21450467
CHEMBL1591577	IC50 = 31 nM	44223973	1591577	21450467
CHEMBL1396654	IC50 = 35 nM	44223953	1396654	21450467
CHEMBL1515144	IC50 = 38 nM	44968186	1515144	21450467
JAK3 Inhibitor VI	IC50 > 50 nM	16760524		22037377
K-252a; Nocardiopsis sp.	IC50 > 50 nM	3813	281948	22037377
SB218078	IC50 > 50 nM	447446	289422	22037377
CHEMBL1396483	IC50 = 51 nM	44223971	1396483	21450467
CHEMBL1476499	IC50 = 57 nM	44223974	1476499	21450467
7-hydroxystaurosporine	IC50 > 60 nM	72271	1236539
Staurosporine aglycone	IC50 < 60 nM	3035817	281948
CHEMBL1705549	IC50 = 70 nM	46916170	1705549	21450467
CHEMBL1357975	IC50 = 74 nM	44223965	1357975	21450467
CHEMBL1354134	IC50 = 76 nM	46916179	1354134	21450467
Alvocidib	Kd = 77 nM	9910986	428690	22037378
Gö6976	IC50 < 80 nM	3501	302449
Ro-31-8220	IC50 < 80 nM	5083	6291
CHEMBL1435542	Kd = 82 nM	44223952	1435542	21450467
CHEMBL1725513	IC50 = 84 nM	46916177	1725513	21450467
NCGC00010428	IC50 = 98 nM	3233012		21450467
Amgen TBK 1 inhibitor (Compound II)	IC50 = 100 nM
BML-275	IC50 = 100 nM	11524144	478629
Harmine	IC50 < 100 nM	5280953	269538
N-Benzoylstaurosporine	Kd = 100 nM	56603681	608533	19654408
STO609	IC50 = 100 nM	51371511
SureCN3470757	IC50 = 100 nM	11588244	375236
2-dimethylamino-4;5;6;7-tetrabromo-1H-benzimidazole	IC50 = 120 nM	5326976	376505	15566294
AT7519	Kd = 120 nM	11338033		22037378
CHEMBL566900	IC50 = 126 nM	44223977	566900	21450467
CHEMBL1734733	IC50 = 135 nM	46916182	1734733	21450467
ACN-S001855	IC50 > 150 nM	10377751		22037377
Cdk1/2 Inhibitor III	IC50 > 150 nM	5330812	261720	22037377
PKR Inhibitor	IC50 > 150 nM	6490494	235641	22037377
Enzastaurin	Kd = 160 nM	176167	300138	22037378
KW2449	Kd = 180 nM	11427553	1908397	22037378
SB202190	IC50 < 200 nM	5353940	278041
Sunitinib	Kd = 200 nM	5329102	535	19654408
PKCb Inhibitor	IC50 > 250 nM	6419755	366266	22037377
Ruboxistaurin	Kd = 250 nM	153999	91829	22037378
SU14813	Kd = 260 nM	10138259	1721885	22037378
BX517	IC50 > 300 nM	11161844	228654
AC1NS7CD	Kd = 340 nM	5329665	295136	22037378
Purvalanol B	IC50 < 400 nM	448991	23254
CHEMBL590109	IC50 = 440 nM	46224684	590109	19926477
AS601245	IC50 = 500 nM	11422035	191384	22037377
Bisindolylmaleimide I	IC50 = 500 nM	2396	7463	22037377
Gö6976	IC50 = 500 nM	3501	302449	22037377
SU11652	IC50 = 500 nM	24906267	13485	22037377
Tpl2 Kinase Inhibitor	IC50 = 500 nM	9549300		22037377
Cot-Tpl2 Inhibitor Compound 38 (Abbott)	IC50 < 600 nM
Cot-Tpl2 Inhibitor Compound 41 (Abbott)	IC50 < 600 nM
Curcumin	IC50 < 600 nM	5281767	116438
GSK-3 Inhibitor IX	IC50 < 600 nM	5287844	409450
Harmaline	IC50 < 600 nM	5280951	340807
Purvalanol A	IC50 < 600 nM	456214	23327
SGX523	Kd = 780 nM	24779724	1236107	22037378
1;9-Pyrazoloanthrone	IC50 < 800 nM	8515	7064
KT5720	IC50 < 800 nM	3844	608532
LDN193189	IC50 < 800 nM	25195294	513147
PF-3644022	IC50 < 800 nM
NU6102	IC50 = 900 nM	4566		18077363
Ruxolitinib	Kd = 910 nM	25126798	1789941	22037378
Afatinib	Kd = 970 nM	10184653	1173655	22037378
4;5;6;7-tetrabromobenzotriazole	IC50 = 1 µM	1694		18077363
Aloisine A	IC50 > 1 µM	5326843	75680	22037377
BI-D1870	IC50 = 1 µM	25023738	573107
BX795	IC50 = 1 µM	10077147	577784
GSK650394A	IC50 = 1 µM	25022668	558642
GW5074 (Raf1 Kinase Inhibitor I)	IC50 < 1 µM	5924208
Harmane	IC50 = 1 µM	5281404	12014
IPA-3	IC50 = 1 µM	521106	472940
IRAK-1-4 Inhibitor I	IC50 = 1 µM	11983295	379787
IRAK-4 kinase inhibitor a	IC50 = 1 µM
Kinome_714	IC50 > 1 µM	46886323		20346655
PD0332991	IC50 = 1 µM	5330286	189963
Quercetagetin	IC50 < 1 µM	5281680	413552
R406	IC50 = 1 µM	11984591
SB216763	IC50 < 1 µM	176158
Sodium salicylate (Aspirin)	IC50 = 1 µM	16760658	447868
SU6656	IC50 = 1 µM	5353978	605003
SureCN10063060	Ki > 1 µM	52936621		21391610
Syk Inhibitor IV	IC50 = 1 µM	10200390
Wyeth PDK1 Inhibitor Compound 1	IC50 = 1 µM
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
GSK1838705A	Kd = 1.2 µM	25182616	464552	22037378
Canertinib	Kd = 1.5 µM	156414	31965	22037378
BS181	IC50 = 2 µM	49867928		19638587
EGCG (Epigallocatechin Gallate)	IC50 < 2 µM	65064	297453
Momelotinib	IC50 > 2 µM	25062766		19295546
SB415286	IC50 = 2 µM	4210951	322970
PP242	Kd = 2.3 µM	25243800		22037378
NVP-TAE684	Kd = 2.9 µM	16038120	509032	22037378
BIX02188	IC50 > 3 µM	23507698		18834865
Harmalol	IC50 > 3 µM	5353656	311932
IRAK-4 kinase inhibitor b	IC50 > 3 µM
CHEMBL248757	Ki = 3.401 µM	44444843	248757	17935989
SureCN4875304	IC50 > 3.5 µM	46871765		20472445
BCP9000822	IC50 < 4 µM	5278396	222102
Roscovitine	IC50 < 4 µM	160355	14762
Syk Inhibitor III	IC50 < 4 µM	672296	596380
Kenpaullone	IC50 > 4.5 µM	3820	296586

Disease Linkage

General Disease Association:

Cancer, cognitive impairment

Specific Diseases (Non-cancerous):

Down syndrome; Mental retardation, autosomal dominant 7 (MRD7); Mental retardation, autosomal dominant 10

Comments:

Down Syndrome is a rare chromosome condition leading to cognitive impairment, distinct facial characteristics, and other health defects. Down Syndrome may have a relation to Alzheimer's disease as well. The phenotype of Mental retardation, autosomal dominant 7 (MRD7) disorder includes microcephaly, severe cognitive impairment (lacking speech), anxious autistic behaviour, and distinct facial characteristics. Kinase phosphotransferase activity of DYRK1A can be abrogated with the K188R mutation, or it can be mildly impaired with a Y321F mutation (which still maintains autophosphorylation of tyrosine residues).

Specific Cancer Types:

Megakaryocytic tumour, Epithelial and Lymphoid tumours

Comments:

Megakaryocytic tumours (derived from bone marrow cells responsible for producing red blood cells) can be induced with DYRK1A.

Gene Expression in Cancers:

The COSMIC website notes an up-regulated expression score for DYRK1A in diverse human cancers of 408, which is 0.9-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 348 for this protein kinase in human cancers was 5.8-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: 0.08 % in 25183 diverse cancer specimens. This rate is very similar (+ 7% higher) to the average rate of 0.075 % calculated for human protein kinases in general.

Mutation Rate in Specific Cancers:

Highest percent mutation rates per 100 amino acids length in human cancers: 0.41 % in 1093 large intestine cancers tested; 0.31 % in 589 stomach cancers tested; 0.3 % in 602 endometrium cancers tested; 0.13 % in 1753 lung cancers tested; 0.09 % in 1466 breast cancers tested.

Frequency of Mutated Sites:

None > 4 in 20,466 cancer specimens

Comments:

Only 3 deletions, 2 insertions, and no complex mutations are noted on the COSMIC website.

COSMIC Entry:

DYRK1A

OMIM Entry:

600855

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:

1D Structure:

3D Image (rendered using PV Viewer):

PDB ID

Subfamily Alignment

Domain Distribution:

Kinexus Products

hiddentext

Post-translation Modifications

Acetylated:

Serine 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:

Known Upstream Kinases

Based on in vitro and/or in vivo phosphorylation data

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 Diseases (Non-cancerous):

Comments:

Specific Cancer Types:

Comments:

Gene Expression in Cancers:

Mutagenesis Experiments:

Mutation Rate in All Cancers:

Mutation Rate in Specific 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: