KinaseNET

Nomenclature

Short Name:

MARK3

Full Name:

MAP-microtubule affinity-regulating kinase 3

Alias:

Cdc25C- associated protein kinase 1
Cdc25C-associated protein kinase 1
PAR1A
Protein kinase STK10
Ser/Thr protein kinase PAR-1
Serine/threonine-protein kinase p78
CTAK1
C-TAK1
ELKL motif kinase 2
KP78

Classification

Type:

Protein-serine/threonine kinase

Group:

CAMK

Family:

CAMKL

SubFamily:

MARK

Specific Links

Entrez-Gene Entry:	4140
Entrez-Protein Entry:	NP_002367
KinBASE Entry:	MARK3
OMIM Entry:	602678
Pfam Entry:	P27448
PhosphoNET Entry:	P27448
Phosphosite Plus Entry:	721
Protein Data Bank Entry:	1UL7
ScanSite Entry:	P27448
UCSD-Nature Entry:	A003012
UniProt Entry:	P27448
Kinexus Products:	MARK3 MAP/microtubule affinity-regulating protein-serine kinase 3 pan-specific antibody AB-NK276-1 MAP/microtubule affinity-regulating protein-serine kinase 3 pan-specific antibody AB-NK276-2 MAP/microtubule affinity-regulating protein-serine kinase 3 T507 phosphosite-specific antibody AB-PK697 MAP/microtubule affinity-regulating protein-serine kinase 3 (H21-C39, human) peptide - Powder PE-01BDT90 MAP/microtubule affinity-regulating protein-serine kinase 3 (R620-G637, human) peptide - Powder PE-01BDU90 MAP/microtubule affinity-regulating protein-serine kinase 3 (R504-C510, human) pT507 phosphopeptide - Powder PE-04ANR99

General Links

Structure

Mol. Mass (Da):

87005

# Amino Acids:

776

# mRNA Isoforms:

mRNA Isoforms:

85,441 Da (760 AA; P27448-7); 84,489 Da (753 AA; P27448); 84,015 Da (752 AA; P27448-2); 83,308 Da (744 AA; P27448-4); 81,499 Da (729 AA; P27448-3); 79,936 Da (713 AA; P27448-6); 74,151 Da (659 AA; P27448-8)

4D Structure:

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

2QNJ

Subfamily Alignment

Domain Distribution:

Start	End	Domain
56	307	Pkinase
326	365	UBA
730	776	KA1

Kinexus Products

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

hiddentext

○	MAP/microtubule affinity-regulating protein-serine kinase 3 pan-specific antibody AB-NK276-1
○	MAP/microtubule affinity-regulating protein-serine kinase 3 pan-specific antibody AB-NK276-2
○	MAP/microtubule affinity-regulating protein-serine kinase 3 T507 phosphosite-specific antibody AB-PK697
○	MAP/microtubule affinity-regulating protein-serine kinase 3 (H21-C39, human) peptide - Powder PE-01BDT90
○	MAP/microtubule affinity-regulating protein-serine kinase 3 (R620-G637, human) peptide - Powder PE-01BDU90
○	MAP/microtubule affinity-regulating protein-serine kinase 3 (R504-C510, human) pT507 phosphopeptide - Powder PE-04ANR99

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Ubiquitinated:

K294, K330, K741.

Serine phosphorylated:

S42, S96-, S215+, S238-, S341, S374, S376, S377, S378, S379, S380, S383, S396, S400, S419, S455, S458, S469, S476, S489, S490, S494, S499, S511, S513, S540, S543, S545, S546, S583, S585, S587, S594, S598, S601, S606, S618, S629, S643, S657, S745-.

Threonine phosphorylated:

T3, T61-, T90-, T95-, T211+, T234+, T397, T438, T491, T503, T507, T536, T541, T549, T564, T574, T576, T587, T591, T625.

Tyrosine phosphorylated:

Y241-, Y340, Y418, Y432, Y508, Y577, Y690.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

45

1104

35

977
7

160

16

109
10

254

17

163
15

363

140

622
34

821

34

646
31

750

97

2328
10

243

41

507
36

889

61

1775
29

709

17

474
5

127

118

170
6

147

41

151
26

623

190

623
5

123

39

111
7

180

12

145
8

199

36

187
5

114

20

68
20

492

197

3464
11

261

26

217
8

205

110

259
31

745

137

670
9

223

34

185
10

251

38

255
15

370

27

340
14

342

26

267
12

290

34

276
39

955

92

1432
9

226

42

233
8

191

26

144
13

318

26

266
36

888

42

1159
29

705

24

581
100

2441

41

5051
9

220

80

321
34

820

83

710
14

341

48

428

Evolution

Species Conservation

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

100

100

100
94.7

94.7

100
-

-

96
-

-

97
-

-

-
96.4

97.4

97
-

-

-
94.1

95.1

97
90

91.2

95
-

-

-
90.6

92.9

-
31.4

50.8

96
85.7

89.6

93
26.5

42.6

88
-

-

-
-

-

61
-

-

-
39.9

51.1

64
-

-

-
-

-

-
-

-

-
-

-

-
27.1

44.1

-
27.3

45.9

-
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	PRKCQ - Q04759
2	RASGRF1 - Q13972
3	PKP2 - Q99959
4	CDC25C - P30307
5	YWHAZ - P63104
6	DYNLL1 - P63167
7	NUAK1 - O60285
8	YWHAE - P62258
9	YWHAG - P61981
10	YWHAH - Q04917

Regulation

Activation:

Phosphorylation of Thr-234 and Ser-238 increases phosphotransferase activity.

Inhibition:

Phosphorylation of Thr-95 and Ser-96 inhibits phosphotransferase activity.

Synthesis:

Degradation:

Kinections Map

Click here to download a PPT of the image below

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

PIM1	P11309	T90	AIKIIDKTQLNPTSL	-
PIM1	P11309	T95	DKTQLNPTSLQKLFR	-
PIM1	P11309	S96	KTQLNPTSLQKLFRE	-
LKB1	Q15831	T234	TVGGKLDTFCGSPPY	+
LKB1	Q15831	S238	KLDTFCGSPPYAAPE	-
PKCi	P41743	T587	RGTASRSTFHGQPRE
PKCz	Q05513	T587	RGTASRSTFHGQPRE
MARK3	P27448	S606	RGSTNLFSKLTSKLT
MARK3	P27448	T625	QTRSRGSTNLFSKLT
MARK3	P27448	S629	RGSTNLFSKLTSKLT

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

MITF	O75030	S280	PGLTISNSCPANLPN
TORC2	Q53ET0	S274	PAMNTGGSLPDLTNL
Cdc25C	P30307	S216	SGLYRSPSMPENLNR	-
HDAC7	Q8WUI4	S155	FPLRKTVSEPNLKLR	-
Ksr1 (KSR)	Q8IVT5	S309	PTLTRSKSHESQLGN
Ksr1 (KSR)	Q8IVT5	S404	TRLRRTESVPSDINN
MARK3	P27448	S606	RGSTNLFSKLTSKLT
MARK3	P27448	S629	RGSTNLFSKLTSKLT
MARK3	P27448	T625	QTRSRGSTNLFSKLT

Protein Kinase Specificity

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

Matrix Type:

Predicted from the application of the Kinexus Kinase Substrate Predictor Version 2.0 algorithm, which was trained with over 10,000 kinase-protein substrate pairs and 8,000 kinase-peptide substrate pairs.

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

7-hydroxystaurosporine	IC50 < 2 nM	72271	1236539
TTT-3002	IC50 < 2 nM
Staurosporine	Kd = 3 nM	5279		18183025
BX795	IC50 < 4 nM	10077147	577784
NVP-TAE684	Kd = 12 nM	16038120	509032	22037378
N-Benzoylstaurosporine	Kd = 21 nM	56603681	608533	18183025
Cdk1/2 Inhibitor III	IC50 < 25 nM	5330812	261720	22037377
JAK3 Inhibitor VI	IC50 < 25 nM	16760524		22037377
K-252a; Nocardiopsis sp.	IC50 < 25 nM	3813	281948	22037377
BX517	IC50 < 40 nM	11161844	228654
Gö6976	IC50 < 40 nM	3501	302449
MRT67307	IC50 < 40 nM	44464263
Staurosporine aglycone	IC50 < 40 nM	3035817	281948
SureCN3470757	IC50 < 40 nM	11588244	375236
Lestaurtinib	Kd = 49 nM	126565		22037378
Gö6976	IC50 > 50 nM	3501	302449	22037377
SB218078	IC50 > 50 nM	447446	289422	22037377
SU11652	IC50 > 50 nM	24906267	13485	22037377
Wyeth PDK1 Inhibitor Compound 1	IC50 < 80 nM
Amgen TBK 1 inhibitor (Compound II)	IC50 = 100 nM
PKR Inhibitor	IC50 > 150 nM	6490494	235641	22037377
CHEMBL590109	IC50 = 210 nM	46224684	590109	19926477
AG-E-60384	IC50 > 250 nM	6419741	413188	22037377
Dovitinib	IC50 > 250 nM	57336746		22037377
SU11274	IC50 > 250 nM	9549297	261641	22037377
TG101348	Kd = 300 nM	16722836	1287853	22037378
GSK-3 Inhibitor IX	IC50 < 400 nM	5287844	409450
Ruxolitinib	IC50 < 400 nM	25126798	1789941
Sunitinib	Kd = 410 nM	5329102	535	18183025
CHEMBL1240703	Kd = 490 nM	52945601	1240703	19654408
HG-9-91-01	IC50 < 600 nM
JNJ-7706621	Kd = 600 nM	5330790	191003	18183025
KT5720	IC50 < 600 nM	3844	608532
Nintedanib	Kd = 770 nM	9809715	502835	22037378
Aurora A Inhibitor 23 (DF)	Kd < 800 nM			21992004
BI-D1870	IC50 < 800 nM	25023738	573107
BX320	IC50 < 800 nM	657138	573108
Kenpaullone	IC50 < 800 nM	3820	296586
LDN193189	IC50 < 800 nM	25195294	513147
Novartis 12a (PKD1)	IC50 < 800 nM
R406	IC50 < 800 nM	11984591
SU6656	IC50 < 800 nM	5353978	605003
Syk Inhibitor	IC50 < 800 nM	6419747	104279
Tofacitinib	IC50 < 800 nM	9926791	221959
A 443654	IC50 > 900 nM	10172943	379300
1;9-Pyrazoloanthrone	IC50 = 1 µM	8515	7064
Alsterpaullone	IC50 > 1 µM	5005498	50894	22037377
Alsterpaullone; 2-Cyanoethyl	IC50 > 1 µM	16760286	260138	22037377
ALX-270-403-M001	IC50 > 1 µM			22037377
AZD8055	IC50 = 1 µM	25262965	1801204
BCP9000906	IC50 > 1 µM	5494425	21156	22037377
BML-275	IC50 = 1 µM	11524144	478629	17850214
Bosutinib	IC50 > 1 µM	5328940	288441	22037377
CZC-25146	IC50 = 1 µM
GSK650394A	IC50 = 1 µM	25022668	558642
GW 843682X	IC50 = 1 µM	9826308	514499
H-1152; Glycyl	IC50 = 1 µM	16760635
K00596a	IC50 = 1 µM	9549298	200027
PP242	IC50 = 1 µM	25243800
Purvalanol B	IC50 = 1 µM	448991	23254
Quercetagetin	IC50 = 1 µM	5281680	413552
SU9516	IC50 > 1 µM	5289419	258805	22037377
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
SU14813	Kd = 1.1 µM	10138259	1721885	18183025
KW2449	Kd = 1.3 µM	11427553	1908397	22037378
EGCG (Epigallocatechin Gallate)	IC50 < 2 µM	65064	297453
Tozasertib	Kd = 2.5 µM	5494449	572878	18183025
Doramapimod	IC50 > 3 µM	156422	103667
Ruboxistaurin	IC50 > 3 µM	153999	91829
SureCN4875304	IC50 > 3.5 µM	46871765		20472445
BMS-690514	Kd < 4 µM	11349170		21531814
GW5074 (Raf1 Kinase Inhibitor I)	IC50 < 4 µM	5924208
Orantinib	IC50 < 4 µM	5329099	274654
Pazopanib	Kd = 4 µM	10113978	477772	18183025
Ro-31-8220	IC50 < 4 µM	5083	6291
(5Z)-7-Oxozeaenol	IC50 > 4.5 µM		1077979
Caffeine	IC50 > 4.5 µM	2519	113
JNKIN7	IC50 > 4.5 µM	57340685
KIN 112	IC50 > 4.5 µM
Purvalanol A	IC50 > 4.5 µM	456214	23327

Disease Linkage

Comments:

Variation in MARK3 may be involved in Alzheimer's disease.

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= +86, p<0.0001); Clear cell renal cell carcinomas (cRCC) stage I (%CFC= -72, p<0.0001); Clear cell renal cell carcinomas (cRCC) stage I (%CFC= -72, p<0.0001); Malignant pleural mesotheliomas (MPM) tumours (%CFC= +60, p<0.004); Prostate cancer - metastatic (%CFC= +45, p<0.0001); Skin squamous cell carcinomas (%CFC= +108, p<0.004); Uterine leiomyomas (%CFC= +313, p<0.004); and Uterine leiomyosarcomas (%CFC= +200, p<0.026). The COSMIC website notes an up-regulated expression score for MARK3 in diverse human cancers of 636, which is 1.4-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 423 for this protein kinase in human cancers was 7.1-fold of the average score of 60 for the human protein kinases.

Mutagenesis Experiments:

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis. A T211A substitution in MARK3 can reduce phosphorylation and activation by LKB1.

Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.05 % in 24751 diverse cancer specimens. This rate is only -28 % lower than 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: 0.32 % in 603 endometrium cancers tested; 0.25 % in 1270 large intestine cancers tested; 0.22 % in 589 stomach cancers tested; 0.19 % in 864 skin cancers tested; 0.13 % in 710 oesophagus cancers tested; 0.08 % in 1634 lung cancers tested; 0.05 % in 273 cervix cancers tested; 0.03 % in 833 ovary cancers tested; 0.03 % in 441 autonomic ganglia cancers tested; 0.03 % in 1512 liver cancers tested; 0.03 % in 1459 pancreas cancers tested; 0.02 % in 548 urinary tract cancers tested; 0.02 % in 2082 central nervous system cancers tested; 0.02 % in 1316 breast cancers tested; 0.02 % in 1276 kidney cancers tested; 0.01 % in 958 upper aerodigestive tract cancers tested; 0.01 % in 881 prostate cancers tested.

Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: E120K (8).

Comments:

Only 7 deletion, 2 insertions and no complex mutations are noted on the COSMIC website.

COSMIC Entry:

MARK3

OMIM Entry:

602678

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

Ubiquitinated:

Serine phosphorylated:

Threonine phosphorylated:

Tyrosine phosphorylated:

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 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

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: