KinaseNET

Nomenclature

Short Name:

YES

Full Name:

Proto-oncogene tyrosine-protein kinase Yes

Alias:

c-Yes
EC 2.7.10.2
HsT441
p61-Yes

Classification

Type:

Protein-tyrosine kinase

Group:

Family:

Src

SubFamily:

Specific Links

Entrez-Gene Entry:	7525
Entrez-Protein Entry:	NP_005424
GeneCards Entry:	C-YES
KinBASE Entry:	YES
OMIM Entry:	164880
Pfam Entry:	P07947
PhosphoNET Entry:	P07947
Phosphosite Plus Entry:	833
Protein Data Bank Entry:	2HDA
ScanSite Entry:	P07947
Source Entry:	YES1
UCSD-Nature Entry:	A002394
UniProt Entry:	P07947
Kinexus Products:	YES Yamaguchi sarcoma proto-oncogene-encoded tyrosine kinase Y222+Y223 phosphosite-specific antibody AB-PK858 Yamaguchi sarcoma proto-oncogene-encoded tyrosine kinase (N219-T226, human) pY222+pY223 phosphopeptide - Powder PE-04AHY99

General Links

Structure

Mol. Mass (Da):

60801

# Amino Acids:

543

# mRNA Isoforms:

mRNA Isoforms:

60,801 Da (543 AA; P07947)

4D Structure:

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

Subfamily Alignment

Domain Distribution:

Start	End	Domain
91	152	SH3
158	255	SH2
276	525	TyrKc
277	528	Pkinase

Kinexus Products

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

hiddentext

○	Yamaguchi sarcoma proto-oncogene-encoded tyrosine kinase Y222+Y223 phosphosite-specific antibody AB-PK858
○	Yamaguchi sarcoma proto-oncogene-encoded tyrosine kinase (N219-T226, human) pY222+pY223 phosphopeptide - Powder PE-04AHY99

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Palmitoylated:

C3 (predicted).

Serine phosphorylated:

S11, S26, S28, S30, S40, S45, S46, S111, S144, S187, S195, S197, S276, S355.

Myristoylated:

G2.

Threonine phosphorylated:

T21, T37, T38, T190, T225, T226, T427+, T531, T533.

Tyrosine phosphorylated:

Y16, Y31, Y32, Y100, Y141, Y146, Y159, Y194, Y222, Y223, Y336, Y345, Y426+, Y446, Y489, Y537-.

Ubiquitinated:

K191, K235, K437.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

73

799

42

868
7

79

23

54
49

538

13

503
42

464

134

699
80

878

39

745
17

183

130

240
30

332

46

426
96

1052

62

1510
68

746

27

650
20

213

114

363
37

406

41

525
68

747

234

699
17

181

46

367
14

157

18

146
40

440

32

529
13

145

22

135
14

153

137

263
41

451

27

651
8

90

131

137
63

685

165

749
38

418

29

646
44

483

35

663
44

482

24

588
37

404

27

484
21

226

29

379
100

1092

87

2432
15

162

52

296
28

301

27

434
36

388

27

516
4

46

42

45
46

504

30

565
42

461

45

388
32

352

86

646
68

743

83

690
12

127

48

176

Evolution

Species Conservation

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

100

100

100
94.2

94.2

100
99.6

99.8

100
-

-

97
-

-

100
97.6

97.9

98
-

-

-
95.9

97

96
73.6

83.2

95
-

-

-
81.4

82.6

-
91.9

96.3

92
89.6

93.7

91
85.9

91.3

86
-

-

-
54.3

67.2

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	PRODH2 - Q9UF12
2	NPHS1 - O60500
3	CD36 - P16671
4	FLT1 - P17948
5	OCLN - Q16625
6	ITGB4 - P16144
7	PTPRE - P23469
8	FAS - P25445
9	PDGFRB - P09619
10	CDKN1B - P46527
11	SLC9A3R1 - O14745
12	CD46 - P15529
13	MST1R - Q04912
14	TRPV4 - Q9HBA0
15	GP6 - Q9HCN6

Regulation

Activation:

Phosphorylation of Tyr-537 increases phosphoransferase activity.

Inhibition:

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

YES	P07947	Y31	VSTSVSHYGAEPTTV
YES	P07947	Y426	RLIEDNEYTARQGAK	+
CSK	P41240	Y537	FTATEPQYQPGENL_	-

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

Cbl	P22681	Y700	EGEEDTEYMTPSSRP
Cbl	P22681	Y731	QQIDSCTYEAMYNIQ
Cbl	P22681	Y774	SENEDDGYDVPKPPV
CDK4	P11802	Y17	AEIGVGAYGTVYKAR	-
p27Kip1	P46527	Y74	HKPLEGKYEWQEVEK	?
p27Kip1	P46527	Y88	KGSLPEFYYRPPRPP	-
p27Kip1	P46527	Y89	GSLPEFYYRPPRPPK	-
PKCd (PRKCD)	Q05655	Y313	SSEPVGIYQGFEKKT	+
PKCd (PRKCD)	Q05655	Y334	MQDNSGTYGKIWEGS	?
Yes	P07947	Y31	VSTSVSHYGAEPTTV
Yes	P07947	Y426	RLIEDNEYTARQGAK	+

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

Dasatinib	Kd = 300 pM	11153014	1421	18183025
Bosutinib	IC50 = 400 pM	5328940	288441	19039322
Ponatinib	IC50 = 890 pM	24826799		20513156
CHEMBL249097	Kd = 1 nM	25138012	249097	19035792
CHEMBL436137	IC50 = 1 nM	11719421	436137	16931012
CHEMBL364623	IC50 = 2 nM	11153014	364623	17154512
AZD0530 analogue 15	IC50 = 3 nM	10301884	223460	17064066
Saracatinib	IC50 = 4 nM	10302451	217092	17064066
HG-9-91-01	IC50 < 8 nM
BX517	IC50 = 10 nM	11161844	228654
CHEMBL230686	IC50 = 10 nM	11562302	230686	18311895
Hesperadin	Kd < 10 nM	10142586	514409	19035792
KIN 112	IC50 = 10 nM
SureCN7018367	Kd < 10 nM	18792927	450519	19035792
MK1775	IC50 = 14 nM	24856436		19887545
KW2449	Kd = 18 nM	11427553	1908397	22037378
SU6656	IC50 = 20 nM	5353978	605003	18077363
NVP-TAE684	Kd = 23 nM	16038120	509032	22037378
Lck Inhibitor	IC50 < 25 nM	6603792		22037377
PP121	IC50 < 25 nM	24905142		18849971
Amgen TBK 1 inhibitor (Compound II)	IC50 < 40 nM
Ibrutinib	IC50 < 40 nM	24821094	1873475
PP1	IC50 < 40 nM	1400	306380
PP2	IC50 < 40 nM	4878	406845
Princeton's TrkA inhibitor compound 20h	IC50 < 40 nM
TTT-3002	IC50 < 40 nM
Foretinib	Kd = 48 nM	42642645	1230609	22037378
Staurosporine	Kd = 49 nM	5279		15711537
Aloisine A	IC50 > 50 nM	5326843	75680	22037377
Cdk1/2 Inhibitor III	IC50 > 50 nM	5330812	261720	22037377
Dovitinib	IC50 > 50 nM	57336746		22037377
IDR E804	IC50 > 50 nM	6419764	1802727	22037377
Src Kinase Inhibitor I	IC50 > 50 nM	1474853	97771	22037377
SU11652	IC50 > 50 nM	24906267	13485	22037377
TWS119	IC50 > 50 nM	9549289	405759	22037377
Vandetanib	IC50 > 50 nM	3081361	24828	22037377
MK5108	IC50 = 51 nM	24748204		20053775
Nintedanib	Kd = 80 nM	9809715	502835	22037378
Purvalanol A	IC50 < 80 nM	456214	23327
Purvalanol B	IC50 < 80 nM	448991	23254
SureCN3470757	IC50 < 80 nM	11588244	375236
AT9283	IC50 > 100 nM	24905142		19143567
BML-275	IC50 = 100 nM	11524144	478629
BMS-690514	Kd < 100 nM	11349170		21531814
GSK-3 Inhibitor IX	IC50 = 100 nM	5287844	409450
PP242	IC50 = 100 nM	25243800
R406	IC50 = 100 nM	11984591
Staurosporine aglycone	IC50 = 100 nM	3035817	281948
STO609	IC50 = 100 nM	51371511
Sunitinib	IC50 = 100 nM	5329102	535
Syk Inhibitor	IC50 = 100 nM	6419747	104279
ZINC01386783	IC50 < 100 nM	1474853	97771
TG101348	Kd = 120 nM	16722836	1287853	22037378
Flt-3 Inhibitor II	IC50 > 150 nM	11601743	377193	22037377
GSK-3 Inhibitor XIII	IC50 > 150 nM	6419766	359482	22037377
K-252a; Nocardiopsis sp.	IC50 > 150 nM	3813	281948	22037377
Ki11502	IC50 > 150 nM			22037377
N-Benzoylstaurosporine	IC50 > 150 nM	56603681	608533	22037377
NU6140	IC50 > 150 nM	10202471	1802728	22037377
PP1 Analog II; 1NM-PP1	IC50 > 150 nM	5154691	573578	22037377
SU11274	IC50 > 150 nM	9549297	261641	22037377
Lestaurtinib	Kd = 160 nM	126565		22037378
Neratinib	Kd = 240 nM	9915743	180022	22037378
4557W	IC50 > 250 nM	9843206	563845	22037377
Alsterpaullone	IC50 > 250 nM	5005498	50894	22037377
Alsterpaullone; 2-Cyanoethyl	IC50 > 250 nM	16760286	260138	22037377
CGP74514A	IC50 > 250 nM	2794188	367625	22037377
Compound 52	IC50 > 250 nM	2856		22037377
Compound 56	IC50 > 250 nM	2857	29197	22037377
Flt-3 Inhibitor III	IC50 > 250 nM	11772958		22037377
JAK3 Inhibitor VI	IC50 > 250 nM	16760524		22037377
SB218078	IC50 > 250 nM	447446	289422	22037377
WHI-P154	IC50 > 250 nM	3795	473773	22037377
AST-487	Kd = 260 nM	11409972	574738	18183025
Cediranib	Kd = 260 nM	9933475	491473	22037378
MLN8054	Kd = 260 nM	11712649	259084	18183025
SU14813	Kd = 260 nM	10138259	1721885	18183025
TG101209	IC50 < 300 nM	16722832		17541402
Tozasertib	Kd = 470 nM	5494449	572878	18183025
Alisertib	IC50 < 500 nM	24771867		22016509
Aloisine; RP106	IC50 = 500 nM	44350092	126343	22037377
BPIQ-I	IC50 = 500 nM	2427		22037377
GSK-3 Inhibitor X	IC50 = 500 nM	6538818	430226	22037377
IKK-2 Inhibitor IV	IC50 = 500 nM	9903786	257167	22037377
Indirubin-3′-monoxime	IC50 = 500 nM	5326739		22037377
JNJ-7706621	IC50 = 500 nM	5330790	191003	22037377
Masitinib	IC50 = 500 nM	10074640		22037377
Pazopanib	IC50 = 500 nM	10113978	477772	22037377
PKR Inhibitor	IC50 = 500 nM	6490494	235641	22037377
Semaxinib	IC50 = 500 nM	5329098	276711	22037377
K00596a	IC50 < 600 nM	9549298	200027
LDN193189	IC50 < 600 nM	25195294	513147
Vemurafenib	IC50 = 604 nM	42611257	1229517	20823850
Crizotinib	Kd = 770 nM	11626560	601719	22037378
Aurora A Inhibitor 1 (DF)	Kd < 800 nM			21992004
Aurora A Inhibitor 23 (DF)	Kd < 800 nM			21992004
JNKIN8	IC50 < 800 nM	57340686
Pelitinib	Kd = 840 nM	6445562	607707	15711537
RAF265	Kd = 940 nM	11656518	558752	18183025
(5Z)-7-Oxozeaenol	IC50 = 1 µM		1077979
AG1478	IC50 = 1 µM	2051	7917
AGL2043	IC50 > 1 µM	9817165		22037377
CHEMBL566515	IC50 < 1 µM	44478401	566515	19788238
CP673451	IC50 > 1 µM	10158940		15705896
Curcumin	IC50 = 1 µM	5281767	116438
Gö6976	IC50 > 1 µM	3501	302449	22037377
GSK429286	IC50 = 1 µM	11373846	375312
GW441756 hydrochloride	IC50 = 1 µM	16219400
Icotinib	IC50 > 1 µM	22024915		22112293
IKK-3 inhibitor IX	IC50 = 1 µM	11626927	373751
IPA-3	IC50 = 1 µM	521106	472940
JNJ-10198409	IC50 > 1 µM	9797370	120077	22037377
JNKIN7	IC50 = 1 µM	57340685
Kenpaullone	IC50 > 1 µM	3820	296586	22037377
MNK1 Inhibitor	IC50 = 1 µM	11644425	1240885
Nilotinib	IC50 > 1 µM	644241	255863	22037377
PLX4720	IC50 = 1 µM	24180719	1230020
Quercetagetin	IC50 = 1 µM	5281680	413552
Ro-31-8220	IC50 = 1 µM	5083	6291
Ruxolitinib	IC50 = 1 µM	25126798	1789941
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	16047143	514582	18678489
SureCN10063060	Ki > 1 µM	52936621		21391610
Syk Inhibitor II	IC50 = 1 µM	16760670
VEGFR2 Kinase Inhibitor I	IC50 > 1 µM	6419834	86943	22037377
VEGFR2 Kinase Inhibitor II	IC50 > 1 µM	5329155	88606	22037377
VEGFR2 Kinase Inhibitor IV	IC50 > 1 µM	5329468	92461	22037377
Wyeth PDK1 Inhibitor Compound 1	IC50 = 1 µM
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
BGJ398	IC50 = 1.1 µM	53235510		21936542
CHEMBL1240703	Kd = 1.1 µM	52945601	1240703	19654408
PHA-665752	Kd = 1.4 µM	10461815	450786	22037378
Canertinib	Kd = 1.6 µM	156414	31965	18183025
VX745	Kd = 1.6 µM	3038525	119385	18183025
Momelotinib	IC50 > 2 µM	25062766		19295546
Orantinib	IC50 < 2 µM	5329099	274654
SB202190	IC50 = 2 µM	5353940	278041
Erlotinib	Kd = 2.2 µM	176870	553	18183025
Axitinib	Kd = 2.7 µM	6450551	1289926	22037378
A-83-01	IC50 > 3 µM	16218924	1170377
Ruboxistaurin	IC50 > 3 µM	153999	91829
Tofacitinib	IC50 > 3 µM	9926791	221959
SureCN4875304	IC50 > 3.5 µM	46871765		20472445
Barasertib	Kd = 3.8 µM	16007391	215152	18183025
BX795	IC50 < 4 µM	10077147	577784
EGCG (Epigallocatechin Gallate)	IC50 < 4 µM	65064	297453
JNJ-28871063	IC50 > 4 µM	17747413		17975007
Doramapimod	IC50 > 4.5 µM	156422	103667
H-1152; Glycyl	IC50 > 4.5 µM	16760635
MRT67307	IC50 > 4.5 µM	44464263
MSC 2032964A	IC50 > 4.5 µM

Disease Linkage

General Disease Association:

Cancer, gastrointestinal disorders

Specific Diseases (Non-cancerous):

Megaesophagus

Specific Cancer Types:

Follicular lymphomas; Sarcomas

Comments:

Yes may be an oncoprotein (OP) based on its similarity to other Src family protein-tyrosine kinases. Yes is the cellular homologue of the Yamaguchi sarcoma virus oncoprotein. By isotopic in situ hybridization, Yes1 gene localization is frequently associated with chromosome translocation and pathogenesis of follicular lymphoma.

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= +123, p<(0.0003); Brain glioblastomas (%CFC= -61, p<0.008); Brain oligodendrogliomas (%CFC= -58, p<0.031); Head and neck squamous cell carcinomas (HNSCC) (%CFC= +45, p<0.043); and Oral squamous cell carcinomas (OSCC) (%CFC= +59, p<0.002). The COSMIC website notes an up-regulated expression score for Yes in diverse human cancers of 569, which is 1.2-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 116 for this protein kinase in human cancers was 1.9-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 Y426F mutation in Yes leads to about a 50% reduction in CSK-mediated inhibition of its phosphotransferase activity.

Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.07 % in 25126 diverse cancer specimens. This rate is only -8 % lower and is very similar to the average rate of 0.075 % calculated for human protein kinases in general.

Frequency of Mutated Sites:

None > 4 in 20,409 cancer specimens

Comments:

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

COSMIC Entry:

YES1

OMIM Entry:

164880

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:

Subfamily Alignment

Domain Distribution:

Kinexus Products

hiddentext

Post-translation Modifications

Palmitoylated:

Serine phosphorylated:

Myristoylated:

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 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:

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: