KinaseNET

Nomenclature

Short Name:

FYN

Full Name:

Proto-oncogene tyrosine-protein kinase FYN

Alias:

EC 2.7.10.2
P59-Fyn
SLK
SYN
FYN
FYN oncogene related to SRC, FGR, YES
Kinase Fyn
MGC45350
P59-FYN

Classification

Type:

Protein-tyrosine kinase

Group:

Family:

Src

SubFamily:

Specific Links

BioCarta Entry:	tcra pathway
Entrez-Gene Entry:	2534
Entrez-Protein Entry:	NP_002028
GeneCards Entry:	SLK
KinBASE Entry:	FYN
OMIM Entry:	137025
Pfam Entry:	P06241
PhosphoNET Entry:	P06241
Phosphosite Plus Entry:	601
Protein Data Bank Entry:	1A0N
ScanSite Entry:	P06241
Source Entry:	FYN
UCSD-Nature Entry:	A000969
UniProt Entry:	P06241
Kinexus Products:	FYN Fyn proto-oncogene-encoded protein-tyrosine kinase pan-specific antibody AB-NK065-2 Fyn proto-oncogene-encoded protein-tyrosine kinase Y213+Y214 phosphosite-specific antibody AB-PK644 Fyn proto-oncogene-encoded protein-tyrosine kinase Y531 phosphosite-specific antibody AB-PK645 Fyn proto-oncogene-encoded protein-tyrosine kinase (C6-S25, human) peptide - Powder PE-01BCZ99 FynSubtide - Fyn protein kinase substrate peptide - Powder PE-01BHL95 Fyn proto-oncogene-encoded protein-tyrosine kinase (E528-G534, human) pY531 phosphopeptide - Powder PE-04AKJ90 Fyn proto-oncogene-encoded protein-tyrosine kinase (N210-T217, human) pY213+pY214 phosphopeptide - Powder PE-04AMP99

General Links

Structure

Mol. Mass (Da):

60762

# Amino Acids:

537

# mRNA Isoforms:

mRNA Isoforms:

60,762 Da (537 AA; P06241); 60,141 Da (534 AA; P06241-2); 54,513 Da (482 AA; P06241-3)

4D Structure:

Interacts (via its SH3 domain) with PIK3R1 and PRMT8. Interacts with FYB, PAG1, and SH2D1A. Interacts with CD79A (tyrosine-phosphorylated form); the interaction increases FYN activity By similarity. Interacts with TOM1L1 (phosphorylated form) By similarity. Interacts with SH2D1A and SLAMF1. Interacts (via its SH3 domain) with HEV ORF3 protein. Interacts with ITCH; the interaction phosphorylates ITCH and negatively regulates its activity.

3D Structure:

Download QuickTime Animation

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

2DQ7

Subfamily Alignment

Domain Distribution:

Start	End	Domain
82	143	SH3
149	246	SH2
270	519	TyrKc
271	522	Pkinase

Kinexus Products

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

hiddentext

○	Fyn proto-oncogene-encoded protein-tyrosine kinase pan-specific antibody AB-NK065-2
○	Fyn proto-oncogene-encoded protein-tyrosine kinase Y213+Y214 phosphosite-specific antibody AB-PK644
○	Fyn proto-oncogene-encoded protein-tyrosine kinase Y531 phosphosite-specific antibody AB-PK645
○	Fyn proto-oncogene-encoded protein-tyrosine kinase (C6-S25, human) peptide - Powder PE-01BCZ99
○	FynSubtide - Fyn protein kinase substrate peptide - Powder PE-01BHL95
○	Fyn proto-oncogene-encoded protein-tyrosine kinase (E528-G534, human) pY531 phosphopeptide - Powder PE-04AKJ90
○	Fyn proto-oncogene-encoded protein-tyrosine kinase (N210-T217, human) pY213+pY214 phosphopeptide - Powder PE-04AMP99

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Serine phosphorylated:

S21+, S25, S26, S178, S186, S188, S257, S307, S349, S393.

Threonine phosphorylated:

T12, T181, T216, T217, T289, T294, T300, T421, T525, T527.

Tyrosine phosphorylated:

Y28, Y30, Y39, Y91, Y185, Y213, Y214, Y339, Y420+, Y440, Y483, Y531-.

Ubiquitinated:

K182, K405, K431.

Myristoylated:

G2.

Palmitoylated:

C3 (predicted), C6 (predicted).

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

26

991

57

767
2

75

25

72
11

408

13

348
18

673

170

626
24

911

38

604
3

109

133

139
9

333

65

496
11

416

72

530
17

630

24

481
6

221

149

200
5

184

52

218
20

767

328

732
11

426

46

439
3

122

23

130
2

78

43

95
2

81

29

100
8

291

397

2646
2

86

28

93
2

85

139

86
21

796

185

689
17

627

40

680
12

437

46

512
8

289

24

222
4

136

29

133
11

400

40

439
17

654

104

682
6

245

49

243
3

121

29

113
7

268

30

314
2

61

42

62
36

1361

42

578
100

3794

56

9386
14

526

97

884
19

738

109

661
3

128

79

216

Evolution

Species Conservation

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

100

100

100
98.9

98.9

95
99.6

99.8

95
-

-

95
-

-

98
99.8

99.8

95
-

-

-
99.1

99.6

99
99.6

99.6

95
-

-

-
70.1

73.3

-
92.4

94.4

97
96.8

98.1

94
90.6

95.2

87
-

-

-
54.6

68.2

-
-

-

-
-

-

54.5
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	CBL - P22681
2	FYB - O15117
3	FCER2 - P06734
4	BCAR1 - P56945
5	CTLA4 - P16410
6	IL7R - P16871
7	CSK - P41240
8	GP6 - Q9HCN6
9	ITK - Q08881
10	ARHGAP32 - A7KAX9
11	SLAMF1 - Q13291
12	PIK3R1 - P27986
13	GRIN2B - Q13224
14	CD36 - P16671
15	DLG4 - P78352

Regulation

Activation:

Inhibition:

Phosphorylation of Tyr-531 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

PKACa	P17612	S21	LTEERDGSLNQSSGY	+
FYN	P06241	Y28	SLNQSSGYRYGTDPT
PDGFRB	P09619	Y28	SLNQSSGYRYGTDPT
FYN	P06241	Y30	NQSSGYRYGTDPTPQ
FYN	P06241	Y39	TDPTPQHYPSFGVTS
FYN	P06241	Y420	RLIEDNEYTARQGAK	+
CSK	P41240	Y531	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

Abl1	P00519	Y115	QGWVPSNYITPVNSL
Abl1	P00519	Y128	SLEKHSWYHGPVSRN
Abl1	P00519	Y139	VSRNAAEYLLSSGIN	+
Abl1	P00519	Y172	LRYEGRVYHYRINTA
Abl1	P00519	Y185	TASDGKLYVSSESRF
Abl1	P00519	Y215	GLITTLHYPAPKRNK
Abl1	P00519	Y226	KRNKPTVYGVSPNYD	+
Abl1	P00519	Y393	RLMTGDTYTAHAGAK	+
Abl1	P00519	Y70	PNLFVALYDFVASGD	+
Abl1 iso2	P00519-2	Y134	QGWVPSNYITPVNSL
Abl1 iso2	P00519-2	Y147	SLEKHSWYHGPVSRN
Abl1 iso2	P00519-2	Y158	VSRNAAEYLLSSGIN	+
Abl1 iso2	P00519-2	Y191	LRYEGRVYHYRINTA
Abl1 iso2	P00519-2	Y204	TASDGKLYVSSESRF
Abl1 iso2	P00519-2	Y234	GLITTLHYPAPKRNK
Abl1 iso2	P00519-2	Y245	KRNKPTVYGVSPNYD	+
Abl1 iso2	P00519-2	Y412	RLMTGDTYTAHAGAK	+
Abl1 iso2	P00519-2	Y89	PNLFVALYDFVASGD	+
ADD2	P35612	Y489	PNQFVPLYTDPQEVL
APP	P05067	Y757	SKMQQNGYENPTYKF
ARHGAP3	P52757	Y21	VSSDAEEYQPPIWKS	-
Bcr	P11274	Y177	ADAEKPFYVNVEFHH	+
Calponin 1	P51911	Y182	SQQGMTAYGTRRHLY
Calponin 1	P51911	Y261	SQRGMTVYGLPRQVY
Calponin 3	Q15417	Y261	SQKGMSVYGLGRQVY
Caveolin 1 (CAV1)	Q03135	Y14	VDSEGHLYTVPIREQ
Cbl	P22681	Y700	EGEEDTEYMTPSSRP
Cbl	P22681	Y731	QQIDSCTYEAMYNIQ
Cbl	P22681	Y774	SENEDDGYDVPKPPV
CD3E	P07766	Y188	PPVPNPDYEPIRKGQ
CD3E	P07766	Y199	RKGQRDLYSGLNQRR
CD5	P06127	Y453	ASHVDNEYSQPPRNS
CD5	P06127	Y487	DNSSDSDYDLHGAQR
CDK5	Q00535	Y15	EKIGEGTYGTVFKAK	-
CENTG1 iso2	Q99490	Y682	ESWIRAKYEQLLFLA
CENTG1 iso2	Q99490	Y774	QGRTALFYARQAGSQ
CLIC5	Q9NZA1	Y33	EENESPHYDDVHEYL
CTLA-4	P16410	Y201	SPLTTGVYVKMPPTE
CTLA-4	P16410	Y218	CEKQFQPYFIPIN__
CTNNB1	P35222	Y142	AVVNLINYQDDAELA
CTNND1	O60716	Y112	PGQIVETYTEEDPEG
CTNND1	O60716	Y228	YPGGSDNYGSLSRVT
CTNND1	O60716	Y96	QDHSHLLYSTIPRMQ
DCC	P43146	Y1261	PTLESAQYPGILPSP
DCC	P43146	Y1420	TEDSANVYEQDDLSE
Desmoplakin 3	P14923	Y132	AIVHLINYQDDAELV
Desmoplakin 3	P14923	Y548	AAGTQQPYTDGVRME
DLG4 (PSD-95)	P78352	Y523	REDSVLSYETVTQME
FcGR2A	P12318	Y288	YETADGGYMTLNPRA
FcGR2A	P12318	Y304	TDDDKNIYLTLPPND
FcGR2B	P31994	Y292	GAENTITYSLLMHPD
FcGR2C	P31995	Y310	TDDDKNIYLTLPPND
FLOT1	O75955	Y160	DIHDDQDYLHSLGKA
FLOT2	Q14254	Y114	DVYDKVDYLSSLGKT
Fyn	P06241	Y28	SLNQSSGYRYGTDPT
Fyn	P06241	Y30	NQSSGYRYGTDPTPQ
Fyn	P06241	Y39	TDPTPQHYPSFGVTS
Fyn	P06241	Y420	RLIEDNEYTARQGAK	+
Grb10	Q13322	Y67	NASLESLYSACSMQS	-
H3.1	P68431	S10	TKQTARKSTGGKAPR
H3.2	P84228	S11	TKQTARKSTGGKAPR
IP3R1 (IP3 receptor)	Q14643	Y353	NAQEKMVYSLVSVPE
IREM1	Q8TDQ1	Y236	VDQVEVEYVTMASLP
IREM1	Q8TDQ1	Y263	AEDQEPTYCNMGHLS
IRS1	P35568	Y1179	GLENGLNYIDLDLVK
IRS1	P35568	Y896	EPKSPGEYVNIEFGS	?
ITCH	Q96J02	Y420	QFNQRFIYGNQDLFA	-
KIRREL	Q96J84	Y605	MKDPTNGYYNVRAHE
KIRREL	Q96J84	Y606	KDPTNGYYNVRAHED
LMR1 (AATK)	Q6ZMQ8	Y73	ENAEGDEYAADLAQG
LMR1 (AATK)	Q6ZMQ8	Y93	AQNGPDVYVLPLTEV
MAP2	P11137	Y67	EHGSQGTYSNTKENG
MAP2 iso3	P11137	Y50	RSANGFPYREDEEGA
NFE2L2	Q16236	Y576	RDEDGKPYSPSEYSL
NMDAR2B (GRIN2B)	Q13224	Y1252	CKKAGNLYDISEDNS
NMDAR2B (GRIN2B)	Q13224	Y1336	RFMDGSPYAHMFEMS
NMDAR2B (GRIN2B)	Q13224	Y1474	GSSNGHVYEKLSSIE	?
NMT1	P30419	Y117	EEASKRSYQFWDTQP
NMT1	P30419	Y180	YTLLNENYVEDDDNM	+
Nogo	Q9NQC3	Y694	LQETEAPYISIACDL
NPHS1	O60500	Y1114	EDRVRNEYEESQWTG
NPHS1	O60500	Y1138	STTEAEPYYRSLRDF
NPHS1	O60500	Y1139	TTEAEPYYRSLRDFS
NPHS1	O60500	Y1158	PTQEEVSYSRGFTGE
NPHS1	O60500	Y1183	YDEVERTYPPSGAWG
NPHS1	O60500	Y1193	SGAWGPLYDEVQMGP	+
NPHS1	O60500	Y1217	YQDPRGIYDQVAGDL
p38a MAPK (MAPK14)	Q16539	Y323	DEPVADPYDQSFESR	+
Paxillin (PXN)	P49023	Y118	VGEEEHVYSFPNKQK	+
PECAM-1	P16284	Y690	PLNSDVQYTEVQVSS	+
PECAM-1	P16284	Y713	KKDTETVYSEVRKAV	+
PKCd (PRKCD)	Q05655	Y187	WGLNKQGYKCRQCNA	-
PKCd (PRKCD)	Q05655	Y313	SSEPVGIYQGFEKKT	+
PKCd (PRKCD)	Q05655	Y334	MQDNSGTYGKIWEGS	?
PLCG2	P16885	Y753	ERDINSLYDVSRMYV	+
PLCG2	P16885	Y759	LYDVSRMYVDPSEIN	+
PLD2	O14939	T11	TPESLFPTGDELDSS
PLD2	O14939	Y165	HAASKQKYLENYLNR
PLD2	O14939	Y470	GRWDDLHYRLTDLGD
PROM1	O43490	Y828	RMDSEDVYDDVETIP
PROM1	O43490	Y852	GYHKDHVYGIHNPVM
PSD-93	Q15700	Y348	TRPPEPVYSTVNKLC
RA70	O75563	Y232	EEEKEETYDDIDGFD
RA70	O75563	Y261	QPIDDEIYEELPEEE
RA70	O75563	Y295	TRRKGVDYASYYQGL
RA70	O75563	Y298	KGVDYASYYQGLWDC
RSK2 (RPS6KA3)	P51812	Y470	EIEILLRYGQHPNII
RSK2 (RPS6KA3)	P51812	Y483	IITLKDVYDDGKYVY
RSK2 (RPS6KA3)	P51812	Y488	DVYDDGKYVYVVTEL
RSK2 (RPS6KA3)	P51812	Y529	TITKTVEYLHAQGVV	?
RSK2 (RPS6KA3)	P51812	Y580	GLLMTPCYTANFVAP	+
RSK2 (RPS6KA3)	P51812	Y644	KFSLSGGYWNSVSDT
RSK2 (RPS6KA3)	P51812	Y707	KGAMAATYSALNRNQ
SCN5A	Q14524	Y1494	MTEEQKKYYNAMKKL
SCN5A	Q14524	Y1495	TEEQKKYYNAMKKLG
SIGLEC10	Q96LC7	Y667	ESQEELHYATLNFPG
SLAM (CD150)	Q13291	Y281	EKKSLTIYAQVQKPG
SLAM (CD150)	Q13291	Y307	QDPCTTIYVAATEPV
SLAM (CD150)	Q13291	Y327	ETNSITVYASVTLPE
SNCA	P37840	Y125	VDPDNEAYEMPSEEG
SNX26	O14559	Y406	PLLTYQLYGKFSEAM
Srcasm	O75674	Y442	DLQPPNYYEVMEFDP
Srcasm	O75674	Y460	AVTTEAIYEEIDAHQ
Tau iso5 (Tau-C)	P10636-5	Y18	MEDHAGTYGLGDRKD
TGFB1I1 (Hic-5)	O43294	Y60	SGDKDHLYSTVCKPR	-
TXK	P42681	Y420	RYVLDDEYVSSFGAK	+
WASP	P42768	Y291	AETSKLIYDFIEDQG	+

Protein Kinase Specificity

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

Matrix Type:

Experimentally derived from alignment of 165 known protein substrate phosphosites and 10 peptides phosphorylated by recombinant Fyn 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

Dasatinib	IC50 = 200 pM	11153014	1421	17154512
Ponatinib	IC50 = 360 pM	24826799		20513156
CHEMBL249097	Kd = 400 pM	25138012	249097	19035792
CHEMBL364623	IC50 = 1 nM	11153014	364623	15546730
Bosutinib	IC50 = 1.8 nM	5328940	288441	19039322
Staurosporine	IC50 = 2 nM	5279		19857964
PD173955	Kd = 4.9 nM	447077	386051	22037378
PP2	IC50 = 5 nM	4878	406845
Hesperadin	Kd < 10 nM	10142586	514409	19035792
Bafetinib	IC50 = 20 nM	24853523		16105974
CHEMBL436137	IC50 = 23 nM	11719421	436137	16931012
Lck Inhibitor	IC50 < 25 nM	6603792		22037377
PP121	IC50 < 25 nM	24905142		18849971
SureCN5520662	IC50 = 25 nM	24766030	477817	18606543
TG101348	Kd = 38 nM	16722836	1287853	22037378
AST-487	Kd = 50 nM	11409972	574738	18183025
BMS-690514	Kd < 50 nM	11349170		21531814
GSK-3 Inhibitor IX	IC50 > 50 nM	5287844	409450	22037377
IDR E804	IC50 > 50 nM	6419764	1802727	22037377
TWS119	IC50 > 50 nM	9549289	405759	22037377
Lestaurtinib	Kd = 84 nM	126565		22037378
Foretinib	Kd = 88 nM	42642645	1230609	22037378
CHIR-124	IC50 = 99 nM	11502647		17255282
AT9283	IC50 > 100 nM	24905142		19143567
MK5108	IC50 = 100 nM	24748204		20053775
Masitinib	Kd = 140 nM	10074640		22037378
SureCN2934634	IC50 = 140 nM	45375865	1080994	19854645
Aloisine A	IC50 > 150 nM	5326843	75680	22037377
BML-275	IC50 > 150 nM	11524144	478629	22037377
Cdk1/2 Inhibitor III	IC50 > 150 nM	5330812	261720	22037377
Flt-3 Inhibitor II	IC50 > 150 nM	11601743	377193	22037377
GSK-3 Inhibitor X	IC50 > 150 nM	6538818	430226	22037377
K-252a; Nocardiopsis sp.	IC50 > 150 nM	3813	281948	22037377
Src Kinase Inhibitor I	IC50 > 150 nM	1474853	97771	22037377
SU11652	IC50 > 150 nM	24906267	13485	22037377
SureCN7018367	Kd < 150 nM	18792927	450519	19035792
SU6656	IC50 = 170 nM	5353978	605003	18077363
Novonex	IC50 = 182 nM	23696523		15766665
GSK-3 Inhibitor XIII	IC50 > 250 nM	6419766	359482	22037377
Indirubin-3′-monoxime	IC50 > 250 nM	5326739		22037377
JAK3 Inhibitor VI	IC50 > 250 nM	16760524		22037377
N-Benzoylstaurosporine	IC50 > 250 nM	56603681	608533	22037377
PP242	Kd = 300 nM	25243800		22037378
JNJ-28312141	Kd = 340 nM			22037378
Vandetanib	Kd = 360 nM	3081361	24828	18183025
JNJ-10198409	IC50 = 378 nM	9797370	120077	16366598
Dovitinib	Kd = 440 nM	57336746		18183025
Alsterpaullone	IC50 = 500 nM	5005498	50894	22037377
Alsterpaullone; 2-Cyanoethyl	IC50 = 500 nM	16760286	260138	22037377
BCP9000906	IC50 = 500 nM	5494425	21156	11934592
CGP74514A	IC50 = 500 nM	2794188	367625	22037377
CHEMBL383899	IC50 = 500 nM	9549303	383899	22037377
CP673451	IC50 < 500 nM	10158940		15705896
PP1 Analog II; 1NM-PP1	IC50 = 500 nM	5154691	573578	22037377
Purvalanol A	IC50 = 500 nM	456214	23327	22037377
Syk Inhibitor	IC50 = 500 nM	6419747	104279	22037377
Sunitinib	Kd = 520 nM	5329102	535	18183025
Tozasertib	Kd = 530 nM	5494449	572878	18183025
Aurora A Inhibitor 23 (DF)	Kd < 600 nM			21992004
Nintedanib	Kd = 630 nM	9809715	502835	22037378
KW2449	Kd = 660 nM	11427553	1908397	22037378
Alisertib	IC50 > 700 nM	24771867		22016509
Aurora A Inhibitor 1 (DF)	Kd < 800 nM			21992004
CHEMBL248757	Ki > 809 nM	44444843	248757	17935989
JNK Inhibitor VIII	Ki > 810 nM	11624601	210618	16759099
Kinome_3024	Ki > 810 nM	11539329	210963	16759099
Kinome_3027	Ki > 810 nM	11640926	378627	16759099
Kinome_3028	Ki > 810 nM	11590363	210928	16759099
CHEMBL1240703	Kd = 940 nM	52945601	1240703	19654408
AG1024	IC50 > 1 µM	2044		22037377
Aloisine; RP106	IC50 > 1 µM	44350092	126343	22037377
CHEMBL566515	Kd < 1 µM	44478401	566515	19788238
Compound 52	IC50 > 1 µM	2856		22037377
Doramapimod	IC50 = 1 µM	156422	103667	18602262
IKK-2 Inhibitor IV	IC50 > 1 µM	9903786	257167	22037377
Kinome_714	IC50 > 1 µM	46886323		20346655
NU6140	IC50 > 1 µM	10202471	1802728	22037377
SB218078	IC50 > 1 µM	447446	289422	22037377
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	16047143	514582	18678489
SU11274	IC50 > 1 µM	9549297	261641	22037377
SureCN10063060	Ki > 1 µM	52936621		21391610
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
Tofacitinib	Kd = 1.1 µM	9926791	221959	22037378
CEP6331	IC50 = 1.19 µM	9823787	460990	18714982
Tamoxifen	IC50 = 1.195 µM	2733526	83
Cediranib	Kd = 1.2 µM	9933475	491473	22037378
SureCN373973	Kd < 1.25 µM	9818573	30678	19035792
Crizotinib	Kd = 1.3 µM	11626560	601719	22037378
MLN8054	Kd = 1.3 µM	11712649	259084	18183025
NVP-TAE684	Kd = 1.4 µM	16038120	509032	22037378
Nilotinib	Kd = 1.6 µM	644241	255863	22037378
Pelitinib	Kd = 1.6 µM	6445562	607707	15711537
CHEMBL606245	IC50 = 1.7 µM	44160269	606245	19884013
BGJ398	IC50 = 1.9 µM	53235510		21936542
Momelotinib	IC50 > 2 µM	25062766		19295546
PF-228	IC50 > 2 µM	11612883		17395594
BX912	IC50 = 2.1 µM	11754511		15772071
RAF265	Kd = 2.1 µM	11656518	558752	18183025
VX745	Kd = 2.1 µM	3038525	119385	18183025
PLX4720	Kd = 2.3 µM	24180719	1230020	22037378
SU14813	Kd = 2.6 µM	10138259	1721885	18183025
Pazopanib	Kd = 2.7 µM	10113978	477772	18183025
Motesanib	Kd = 2.8 µM	11667893	572881	18183025
CEP5104	IC50 = 3.4 µM	23378546	460989	18714982
SureCN4875304	IC50 > 3.5 µM	46871765		20472445
JNJ-28871063	IC50 > 4 µM	17747413		17975007

Disease Linkage

General Disease Association:

Cancer

Specific Cancer Types:

Estrogen-receptor negative breast cancer

Comments:

FYN may be an oncoprotein (OP) based on its similarity to other Src family kinases that are known oncoproteins. The active form of the protein kinase normally acts to promote tumour cell proliferation. Fyn has been linked with estrogen-receptor negative breast cancer, which is related to breast and colon cancer, and it may affect breast, lymph node, or lung tissues.

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= +116, p<0.036); Classical Hodgkin lymphomas (%CFC= +48, p<0.038); Colon mucosal cell adenomas (%CFC= -47, p<0.0001); Colorectal adenocarcinomas (early onset) (%CFC= +154, p<(0.0003); Large B-cell lymphomas (%CFC= +51, p<0.06); Malignant pleural mesotheliomas (MPM) tumours (%CFC= +62, p<0.026); Oral squamous cell carcinomas (OSCC) (%CFC= +54, p<0.076); Papillary thyroid carcinomas (PTC) (%CFC= +66, p<0.022); Skin melanomas - malignant (%CFC= +100, p<0.001); T-cell prolymphocytic leukemia (%CFC= -60, p<0.002); and Uterine fibroids (%CFC= +66, p<0.015). The COSMIC website notes an up-regulated expression score for FYN in diverse human cancers of 270, which is 0.6-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 18 for this protein kinase in human cancers was 0.3-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: 0.09 % in 25627 diverse cancer specimens. This rate is only 24 % higher 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: 0.56 % in 1093 large intestine cancers tested; 0.42 % in 805 skin cancers tested; 0.41 % in 589 stomach cancers tested; 0.17 % in 1941 lung cancers tested.

Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: R206C (6).

Comments:

Only 2 deletions, 1 insertion, and no complex mutations are noted on the COSMIC website.

COSMIC Entry:

FYN

OMIM Entry:

137025

Nomenclature

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Specific Links

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Structure

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3D Image (rendered using PV Viewer):

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Kinexus Products

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Distribution

Human Tissue Distribution

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Evolution

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Binding Proteins

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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

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Inhibitors

Based on in vitro and/or in vivo phosphorylation data

Disease Linkage

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Specific Cancer Types:

Comments:

Gene Expression in Cancers:

Mutagenesis Experiments:

Mutation Rate in All Cancers:

Mutation Rate in Specific Cancers:

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