KinaseNET

Nomenclature

Short Name:

SLK

Full Name:

CTCL tumor antigen se20-9

Alias:

bA16H23.1
CTCL tumor antigen se20-9
Se20-9
STE20-like kinase
STK2
CTCL tumour antigen se20-9
EC 2.7.11.1
KIAA0204
MGC133067

Classification

Type:

Protein-serine/threonine kinase

Group:

STE

Family:

STE20

SubFamily:

SLK

Specific Links

Entrez-Gene Entry:	9748
Entrez-Protein Entry:	NP_055535
KinBASE Entry:	SLK
Pfam Entry:	Q9H2G2
PhosphoNET Entry:	Q9H2G2
Phosphosite Plus Entry:	2519
Protein Data Bank Entry:	2J51
UCSD-Nature Entry:	A003176
UniProt Entry:	Q9H2G2
Kinexus Products:	SLK STE20-like serine/threonine-protein kinase; CTCL tumour antigen se20-9 S189 phosphosite-specific antibody AB-PK816 STE20-like serine/threonine-protein kinase / CTCL tumour antigen se20-9 (R186-G192, human) pS189 phosphopeptide - Powder PE-04ALC99

General Links

Structure

Mol. Mass (Da):

142,695

# Amino Acids:

1235

# mRNA Isoforms:

mRNA Isoforms:

142,695 Da (1235 AA; Q9H2G2); 138,996 Da (1204 AA; Q9H2G2-2)

4D Structure:

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

2JFM

Subfamily Alignment

Domain Distribution:

Start	End	Domain
34	292	Pkinase
308	327	Coiled-coil
828	858	Coiled-coil
860	898	Coiled-coil
901	928	Coiled-coil
941	962	Coiled-coil
979	1006	Coiled-coil
1035	1069	Coiled-coil
1110	1151	Coiled-coil
1157	1181	Coiled-coil
875	910	UVR
851	990	PKK

Kinexus Products

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

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○	STE20-like serine/threonine-protein kinase; CTCL tumour antigen se20-9 S189 phosphosite-specific antibody AB-PK816
○	STE20-like serine/threonine-protein kinase / CTCL tumour antigen se20-9 (R186-G192, human) pS189 phosphopeptide - Powder PE-04ALC99

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Serine phosphorylated:

S2, S14, S57, S177, S189+, S250, S330, S336, S340, S341, S344, S347-, S348-, S354, S362, S370, S372, S446, S448, S518, S546, S565, S571, S646, S655, S667, S728, S730, S772, S777, S779, S781, S816, S818, S1089, S1094, S1219, S1229, S1235.

Threonine phosphorylated:

T56, T139, T181+, T183+, T193-, T327, T494, T506, T545, T551, T569, T643, T755, T785, T814, T820, T1097, T1188.

Tyrosine phosphorylated:

Y21, Y195-, Y212, Y214+, Y1052, Y1225.

Ubiquitinated:

K319, K337, K384, K492, K524, K663, K775.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

25

942

16

941
2

58

10

33
9

344

1

0
14

526

46

782
26

1007

14

829
4

136

42

95
13

485

19

596
20

753

21

1269
20

749

10

696
3

121

45

81
2

88

14

68
18

679

94

688
2

74

12

18
5

175

9

103
3

106

11

62
3

117

8

48
19

710

102

3812
1.5

56

8

23
3

124

43

82
23

891

56

823
2

89

10

41
3

111

12

87
3

116

10

47
2

75

8

28
2

88

10

86
18

669

28

700
3

122

15

47
3

98

8

51
3

133

8

43
3

102

14

36
28

1082

18

604
100

3803

21

6081
22

846

57

933
27

1033

31

946
9

344

22

740

Evolution

Species Conservation

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

100

100

100
99.5

99.7

100
20.2

29.1

97
-

-

89
-

-

-
90.2

94.6

91
-

-

-
83.6

89.9

85
78.4

86.3

82
-

-

-
33.9

46.3

-
72.2

81.7

75
45.6

59.8

-
20.2

29.6

81
-

-

-
22.4

35.6

34
-

-

-
20.5

29.2

31
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

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No.	Name – UniProt ID
1	CASP3 - P42574

Regulation

Activation:

Inhibition:

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

CK2a1	P68400	S347	SSDLSIASSEEDKLS	-
CK2a1	P68400	S348	SDLSIASSEEDKLSQ	-

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

RhoA

P61586

S188

ARRGKKKSGCLVL__

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

Staurosporine	Kd = 24 pM	5279		18183025
Foretinib	Kd = 3 nM	42642645	1230609	22037378
Bosutinib	Kd = 4.7 nM	5328940	288441	22037378
Hesperadin	Kd < 10 nM	10142586	514409	19035792
KW2449	Kd = 13 nM	11427553	1908397	22037378
Crizotinib	Kd = 18 nM	11626560	601719	22037378
NVP-TAE684	Kd = 21 nM	16038120	509032	22037378
Cediranib	Kd = 22 nM	9933475	491473	22037378
AST-487	Kd = 23 nM	11409972	574738	18183025
Erlotinib	Kd = 26 nM	176870	553	18183025
R406	Kd = 33 nM	11984591		22037378
Lestaurtinib	Kd = 35 nM	126565		22037378
JNJ-7706621	Kd = 48 nM	5330790	191003	18183025
Cdk1/2 Inhibitor III	IC50 > 50 nM	5330812	261720	22037377
K-252a; Nocardiopsis sp.	IC50 > 50 nM	3813	281948	22037377
Ki11502	IC50 > 50 nM			22037377
SU11274	IC50 > 50 nM	9549297	261641	22037377
SureCN7018367	Kd < 50 nM	18792927	450519	19035792
Nintedanib	Kd = 51 nM	9809715	502835	22037378
Sunitinib	Kd = 56 nM	5329102	535	18183025
Neratinib	Kd = 66 nM	9915743	180022	22037378
Tozasertib	Kd = 82 nM	5494449	572878	18183025
PP242	Kd = 84 nM	25243800		22037378
Doramapimod	Kd = 86 nM	156422	103667	15711537
Vandetanib	Kd = 95 nM	3081361	24828	18183025
R547	Kd = 96 nM	6918852		22037378
BMS-690514	Kd < 100 nM	11349170		21531814
SB218078	IC50 > 150 nM	447446	289422	22037377
SU6656	IC50 > 150 nM	5353978	605003	22037377
Syk Inhibitor	IC50 > 150 nM	6419747	104279	22037377
Brivanib	Kd = 170 nM	11234052	377300	22037378
N-Benzoylstaurosporine	Kd = 220 nM	56603681	608533	18183025
Pazopanib	Kd = 240 nM	10113978	477772	22037378
Aloisine A	IC50 > 250 nM	5326843	75680	22037377
Gö6976	IC50 > 250 nM	3501	302449	22037377
GSK-3 Inhibitor XIII	IC50 > 250 nM	6419766	359482	22037377
Pelitinib	Kd = 250 nM	6445562	607707	15711537
PKCb Inhibitor	IC50 > 250 nM	6419755	366266	22037377
SU11652	IC50 > 250 nM	24906267	13485	22037377
Dovitinib	Kd = 300 nM	57336746		18183025
PHA-665752	Kd = 350 nM	10461815	450786	22037378
SureCN373973	Kd = 395 nM	9818573	30678	19035792
Ruboxistaurin	Kd = 400 nM	153999	91829	18183025
Canertinib	Kd = 440 nM	156414	31965	15711537
Linifanib	Kd = 450 nM	11485656	223360	18183025
SU14813	Kd = 460 nM	10138259	1721885	18183025
Bisindolylmaleimide I	IC50 = 500 nM	2396	7463	22037377
Bisindolylmaleimide IV	IC50 = 500 nM	2399	266487	22037377
JAK3 Inhibitor VI	IC50 = 500 nM	16760524		22037377
WHI-P154	IC50 = 500 nM	3795	473773	22037377
RAF265	Kd = 510 nM	11656518	558752	18183025
Danusertib	IC50 = 621 nM	21874004	402548	17125279
TG101348	Kd = 680 nM	16722836	1287853	22037378
Dasatinib	Kd = 720 nM	11153014	1421	18183025
Aurora A Inhibitor 23 (DF)	Kd < 800 nM			21992004
Gefitinib	Kd = 920 nM	123631	939	18183025
AG1478	IC50 > 1 µM	2051	7917	22037377
Aurora A Inhibitor 29 (DF)	Kd = 1 µM			21992004
Axitinib	Kd = 1 µM	6450551	1289926	22037378
BPIQ-I	IC50 > 1 µM	2427		22037377
Compound 56	IC50 > 1 µM	2857	29197	22037377
Gö6983	IC50 > 1 µM	3499	261491	22037377
GSK-3 Inhibitor IX	IC50 > 1 µM	5287844	409450	22037377
IDR E804	IC50 > 1 µM	6419764	1802727	22037377
PD158780	IC50 > 1 µM	4707	53753	22037377
PKCbII/EGFR Inhibitor	IC50 > 1 µM	6711154		22037377
PKR Inhibitor	IC50 > 1 µM	6490494	235641	22037377
Sorafenib	Kd = 1 µM	216239	1336	18183025
TWS119	IC50 > 1 µM	9549289	405759	22037377
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
AC1O6ZUA	Kd < 1.25 µM	6539569	408019	19035792
LKB1(AAK1 dual inhibitor)	Kd < 1.25 µM	44588117	516312	19035792
GDC0879	Kd = 1.3 µM	11717001	525191	22037378
Motesanib	Kd = 1.3 µM	11667893	572881	18183025
1;9-Pyrazoloanthrone	Kd = 2.3 µM	8515	7064	15711537
IKK-2 Inhibitor IV	Kd < 2.5 µM	9903786	257167	19035792
SureCN5302803	Kd > 2.5 µM	24788740		19035792
Enzastaurin	Kd = 3.1 µM	176167	300138	22037378
SB202190	Kd = 3.2 µM	5353940	278041	18183025
Lapatinib	Kd = 3.3 µM	208908	554	22037378
Afatinib	Kd = 3.7 µM	10184653	1173655	22037378
SB203580	Kd = 3.7 µM	176155	10	18183025
BI2536	Kd = 4.1 µM	11364421	513909	22037378
Tandutinib	Kd = 4.2 µM	3038522	124660	15711537
Quizartinib	Kd = 4.6 µM	24889392	576982	22037378

Disease Linkage

General Disease Association:

Cancer, eye disorders

Specific Diseases (Non-cancerous):

Superior limbic keratoconjunctivitis (SLK)

Specific Cancer Types:

Breast cancer

Comments:

SLK was shown to be necessary for ErbB2-driven breast cancer cell motility.

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: Barrett's esophagus epithelial metaplasia (%CFC= -57, p<0.051); Bladder carcinomas (%CFC= +184, p<(0.0003); Breast epithelial hyperplastic enlarged lobular units (HELU) (%CFC= +60, p<0.089); Cervical cancer (%CFC= +147, p<0.0001); Cervical cancer stage 2A (%CFC= +153, p<0.026); Lung adenocarcinomas (%CFC= -56, p<0.0001); Ovary adenocarcinomas (%CFC= -45, p<0.019); Pituitary adenomas (ACTH-secreting) (%CFC= -67); Prostate cancer (%CFC= +228, p<0.049); Skin fibrosarcomas (%CFC= -48); Skin melanomas - malignant (%CFC= -53, p<0.003); Skin squamous cell carcinomas (%CFC= +75, p<0.009); and Uterine leiomyomas from fibroids (%CFC= -50, p<0.014).

Mutagenesis Experiments:

Insertional mutagenesis studies in mice have not yet revealed 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: 0.05 % in 24434 diverse cancer specimens. This rate is only -30 % 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: 0.3 % in 1229 large intestine cancers tested; 0.26 % in 603 endometrium cancers tested; 0.14 % in 864 skin cancers tested; 0.11 % in 589 stomach cancers tested; 0.09 % in 548 urinary tract cancers tested; 0.09 % in 273 cervix cancers tested; 0.09 % in 1609 lung cancers tested; 0.06 % in 710 oesophagus cancers tested; 0.06 % in 1512 liver cancers tested; 0.05 % in 1253 kidney cancers tested; 0.04 % in 1316 breast cancers tested; 0.03 % in 881 prostate cancers tested; 0.02 % in 2030 central nervous system cancers tested; 0.02 % in 1982 haematopoietic and lymphoid cancers tested; 0.01 % in 807 ovary cancers tested; 0.01 % in 1437 pancreas cancers tested.

Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: E912G (10); N995S (3).

Comments:

Only 3 deletions, 1 insertion, and no complex mutations are noted on the COSMIC website.

COSMIC Entry:

SLK_ENST00000369755

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

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:

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):

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:

% 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: