KinaseNET

Nomenclature

Short Name:

PYK2

Full Name:

Protein tyrosine kinase 2 beta

Alias:

CADTK
EC 2.7.10.2
FADK 2
FADK2, FAK2
FAK2
Related adhesion focal tyrosine kinase; RAFTK
CAK beta
CAKB
Calcium-dependent tyrosine kinase
Cell adhesion kinase beta

Classification

Type:

Protein-tyrosine kinase

Group:

Family:

Fak

SubFamily:

Specific Links

BioCarta Entry:	pyk2 pathway
Entrez-Gene Entry:	2185
Entrez-Protein Entry:	NP_775266
GeneCards Entry:	PYK2
KinBASE Entry:	PYK2
OMIM Entry:	601212
Pfam Entry:	Q14289
PhosphoNET Entry:	Q14289
Phosphosite Plus Entry:	652
Protein Data Bank Entry:	2F06
ScanSite Entry:	Q14289
Source Entry:	PTK2B
UCSD-Nature Entry:	A001952
UniProt Entry:	Q14289
Kinexus Products:	PYK2 Protein tyrosine kinase 2 beta Y402 phosphosite-specific antibody AB-PK787 Protein tyrosine kinase 2 beta Y402 phosphosite-specific antibody AB-PK788 Protein tyrosine kinase 2 beta Y579+Y580 phosphosite-specific antibody AB-PK789 Pyk2Subtide - Pyk2 (PTK2B) protein kinase substrate peptide - Powder PE-01BJA95 Protein tyrosine kinase 2 beta (E577-S583, human) pY579+pY580 phosphopeptide - Powder PE-04ADL99 Protein tyrosine kinase 2 beta (S399-I405, human) pY402 phosphopeptide - Powder PE-04AGK99 Protein tyrosine kinase 2 beta (S399-I405, human) pY402 phosphopeptide - Powder PE-04AQQ99

General Links

Structure

Mol. Mass (Da):

115,875

# Amino Acids:

1009

# mRNA Isoforms:

mRNA Isoforms:

115,875 Da (1009 AA; Q14289); 111,183 Da (967 AA; Q14289-2)

4D Structure:

Interacts with Crk-associated substrate (Cas), PTPNS1 and SH2D3C By similarity. Interacts with nephrocystin, ASAP2, OPHN1L, SKAP2 and TGFB1I1.

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

3CC6

Subfamily Alignment

Domain Distribution:

Start	End	Domain
35	265	B41
425	679	TyrKc
870	1008	Focal_AT
39	359	FERM
425	683	Pkinase
870	1008	Focal AT

Kinexus Products

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

hiddentext

○	Protein tyrosine kinase 2 beta Y402 phosphosite-specific antibody AB-PK787
○	Protein tyrosine kinase 2 beta Y402 phosphosite-specific antibody AB-PK788
○	Protein tyrosine kinase 2 beta Y579+Y580 phosphosite-specific antibody AB-PK789
○	Pyk2Subtide - Pyk2 (PTK2B) protein kinase substrate peptide - Powder PE-01BJA95
○	Protein tyrosine kinase 2 beta (E577-S583, human) pY579+pY580 phosphopeptide - Powder PE-04ADL99
○	Protein tyrosine kinase 2 beta (S399-I405, human) pY402 phosphopeptide - Powder PE-04AGK99
○	Protein tyrosine kinase 2 beta (S399-I405, human) pY402 phosphopeptide - Powder PE-04AQQ99

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Acetylated:

K564.

Serine phosphorylated:

S2, S9, S332, S361, S375, S394, S396, S399, S473, S530, S559, S571, S583+, S718, S746, S747, S752, S758, S762, S778, S828, S839, S866, S923.

Threonine phosphorylated:

T15, T409, T701, T749, T765, T842, T853.

Tyrosine phosphorylated:

Y402+, Y418, Y440, Y573+, Y579+, Y580+, Y683, Y699, Y722, Y756, Y819, Y834, Y849, Y881, Y906+.

Ubiquitinated:

K188, K206, K564, K858, K911, K944, K973.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

81

1048

32

1886
3

34

16

27
15

189

32

427
40

525

119

910
47

607

24

524
2

28

74

28
31

400

35

640
26

341

60

542
29

378

17

316
12

160

114

247
10

125

53

278
44

575

216

592
23

293

54

321
3

33

15

29
7

87

19

69
3

34

16

24
6

84

225

159
12

155

43

257
3

34

113

72
34

436

109

467
11

149

47

280
16

208

51

213
15

198

42

338
14

178

43

514
26

335

47

402
33

424

76

569
13

167

57

182
13

171

43

316
9

122

43

237
43

558

28

452
52

677

36

490
100

1300

36

2635
6

81

72

121
61

795

57

703
3

36

44

38

Evolution

Species Conservation

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

100

100

100
99.6

99.8

99.5
98.8

99.6

99
-

-

95
-

-

95
96.2

98.8

96
-

-

-
95.5

98.1

95
95.6

98.1

94
-

-

-
63.1

70.1

-
44.8

62.2

80
43.8

61.8

77
59.4

75.1

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	BCAR1 - P56945
2	PTPN12 - Q05209
3	PTPN6 - P29350
4	CBL - P22681
5	EGFR - P00533
6	EFS - O43281
7	DCC - P43146
8	SH2D3C - Q8N5H7
9	RB1CC1 - Q8TDY2
10	KCNA2 - P16389
11	IL7R - P16871
12	ITGB3 - P05106
13	FLT1 - P17948
14	STAT3 - P40763
15	ERBB3 - P21860

Regulation

Activation:

Phosphorylation at Tyr-402 increases phosphotransferase activity and induces interaction with ErbB2, RasGAP and Src. Phosphorylation at Tyr-579 increases phosphotransferase activity.

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

PYK2	Q14289	Y402	CSIESDIYAEIPDET	+
SRC	P12931	Y402	CSIESDIYAEIPDET	+
SRC	P12931	Y579	RYIEDEDYYKASVTR	+
SRC	P12931	Y580	YIEDEDYYKASVTRL	+
SRC	P12931	Y881	DRTDDLVYLNVMELV

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

ARA55 (Hic-5)	O43294	Y60	SGDKDHLYSTVCKPR	-
DDEF1	Q9ULH1	Y767	RDKQRLSYGAFTNQI
eNOS	P29474	Y657	FGLGSRAYPHFCAFA
FAK (PTK2)	Q05397	Y407	IIDEEDTYTMPSTRD	+
Hic-5	O43294	Y60	SGDKDHLYSTVCKPR	-
JAK2	O60674	Y1007	VLPQDKEYYKVKEPG	+
JAK2	O60674	Y1008	LPQDKEYYKVKEPGE	+
PXN	P49023	Y118	VGEEEHVYSFPNKQK
PXN	P49023	Y31	FLSEETPYSYPTGNH
PYK2 (PTK2B)	Q14289	Y402	CSIESDIYAEIPDET	+
SNCA	P37840	Y125	VDPDNEAYEMPSEEG
Src	P12931	Y419	RLIEDNEYTARQGAK	+
TGFb1I1	O43294	Y60	SGDKDHLYSTVCKPR	-

Protein Kinase Specificity

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

Matrix Type:

Experimentally derived from alignment of 22 known protein substrate phosphosites and 43 peptides phosphorylated by recombinant PYK2 in vitro tested in-house by Kinexus.

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

NVP-TAE684	Kd = 1.1 nM	16038120	509032	22037378
Staurosporine	Kd = 3.5 nM	5279		18183025
Hesperadin	Kd = 10 nM	10142586	514409	19035792
PF-431396	IC50 = 11 nM	11598628		20218623
Foretinib	Kd = 14 nM	42642645	1230609	22037378
PF-00562271	IC50 = 14 nM	11713159		20218623
Ponatinib	IC50 = 35.1 nM	24826799		20513156
Lestaurtinib	Kd = 41 nM	126565		22037378
GSK1838705A	Kd = 76 nM	25182616	464552	22037378
Nintedanib	Kd = 81 nM	9809715	502835	22037378
Sunitinib	Kd = 82 nM	5329102	535	18183025
CHEMBL509485	IC50 = 88 nM	25920890	509485	19428251
AT9283	IC50 > 100 nM	24905142		19143567
MK5108	IC50 = 100 nM	24748204		20053775
Bosutinib	IC50 = 134 nM	5328940	288441	19039322
Gö6976	IC50 > 150 nM	3501	302449	22037377
K-252a; Nocardiopsis sp.	IC50 > 150 nM	3813	281948	22037377
Crizotinib	Kd = 190 nM	11626560	601719	22037378
TG101348	Kd = 220 nM	16722836	1287853	22037378
Cdk1/2 Inhibitor III	IC50 > 250 nM	5330812	261720	22037377
IDR E804	IC50 > 250 nM	6419764	1802727	22037377
SB218078	IC50 > 250 nM	447446	289422	22037377
SU11652	IC50 > 250 nM	24906267	13485	22037377
Syk Inhibitor	IC50 > 250 nM	6419747	104279	22037377
BI2536	Kd = 310 nM	11364421	513909	22037378
Doramapimod	IC50 = 400 nM	156422	103667	22014550
BCP9000906	IC50 = 500 nM	5494425	21156	22037377
NU6140	IC50 = 500 nM	10202471	1802728	22037377
PDK1/Akt/Flt Dual Pathway Inhibitor	IC50 = 500 nM	5113385	599894	22037377
SU6656	IC50 = 500 nM	5353978	605003	22037377
Syk Inhibitor II	IC50 = 500 nM	16760670		22037377
AST-487	Kd = 520 nM	11409972	574738	18183025
SU14813	Kd = 600 nM	10138259	1721885	18183025
N-Benzoylstaurosporine	Kd = 660 nM	56603681	608533	18183025
KW2449	Kd = 760 nM	11427553	1908397	22037378
PHA-665752	Kd = 910 nM	10461815	450786	22037378
Aloisine A	IC50 > 1 µM	5326843	75680	22037377
Alsterpaullone; 2-Cyanoethyl	IC50 > 1 µM	16760286	260138	22037377
GSK-3 Inhibitor IX	IC50 > 1 µM	5287844	409450	22037377
GSK-3 Inhibitor XIII	IC50 > 1 µM	6419766	359482	22037377
Indirubin-3′-monoxime	IC50 > 1 µM	5326739		22037377
Purvalanol A	IC50 > 1 µM	456214	23327	22037377
Semaxinib	IC50 > 1 µM	5329098	276711	22037377
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	16047143	514582	18678489
STO609	IC50 > 1 µM	51371511		22037377
SU11274	IC50 > 1 µM	9549297	261641	22037377
TWS119	IC50 > 1 µM	9549289	405759	22037377
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
CHEMBL1240703	Kd = 1.5 µM	52945601	1240703	19654408
MLN8054	Kd = 2 µM	11712649	259084	18183025
Momelotinib	IC50 > 2 µM	25062766		19295546
Tozasertib	Kd = 2.6 µM	5494449	572878	18183025
Alvocidib	Kd = 3.1 µM	9910986	428690	22037378
SureCN4875304	IC50 > 3.5 µM	46871765		20472445
JNJ-28871063	IC50 > 4 µM	17747413		17975007

Disease Linkage

General Disease Association:

Cancer

Specific Cancer Types:

Gliomas; Hepatocellular carcinomas; Lung cancer (LC); Breast cancer

Gene Expression in Cancers:

The COSMIC website notes an up-regulated expression score for PYK2 in diverse human cancers of 278, which is 0.6-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 55 for this protein kinase in human cancers was 0.9-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. PYK2 autophosphorylation and interaction with Src can be inhibited with an Y402F mutation. Its phosphotransferase activity can be abrogated with a K457A mutation. NPHP1 interaction with PYK2 can be interrupted with a P859A mutation. A Y881F mutation can impair interaction with the GRB2 adapter protein.

Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.08 % in 25546 diverse cancer specimens. This rate is very similar (+ 10% 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: 0.57 % in 944 skin cancers tested; 0.35 % in 589 stomach cancers tested; 0.27 % in 1270 large intestine cancers tested; 0.21 % in 603 endometrium cancers tested; 0.17 % in 238 bone cancers tested; 0.15 % in 1634 lung cancers tested; 0.08 % in 891 ovary cancers tested; 0.06 % in 710 oesophagus cancers tested; 0.06 % in 1512 liver cancers tested; 0.06 % in 1490 breast cancers tested; 0.05 % in 548 urinary tract cancers tested; 0.04 % in 558 thyroid cancers tested; 0.04 % in 273 cervix cancers tested; 0.04 % in 2082 central nervous system cancers tested.

Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: R671C (3).

Comments:

Only 6 deletions, no insertions or complex mutations are noted on the COSMIC website.

COSMIC Entry:

PTK2B

OMIM Entry:

601212

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:

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 Cancer Types:

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: