KinaseNET

Nomenclature

Short Name:

GSK3B

Full Name:

Glycogen synthase kinase-3 beta

Alias:

Classification

Type:

Protein-serine/threonine kinase

Group:

CMGC

Family:

GSK

SubFamily:

Specific Links

BioCarta Entry:	wnt pathway
Entrez-Gene Entry:	2932
Entrez-Protein Entry:	NP_002084
GeneCards Entry:	GSK3B
KinBASE Entry:	GSK3B
OMIM Entry:	605004
Pfam Entry:	P49841
PhosphoNET Entry:	P49841
Phosphosite Plus Entry:	604
Protein Data Bank Entry:	1GNG
ScanSite Entry:	P49841
Source Entry:	GSK3B
UCSD-Nature Entry:	A001106
UniProt Entry:	P49841
Kinexus Products:	GSK3B Glycogen synthase-serine kinase 3 beta pan-specific antibody AB-NK070 Glycogen synthase kinase-3 beta pan-specific antibody AB-NK070-4 Glycogen synthase-serine kinase 3 beta pan-specific antibody AB-NK194-NK195-3 Glycogen synthase-serine kinase 3 beta pan-specific antibody AB-NK270-3 GSK3b (3-12) KinSub - Glycogen synthase kinase 3-beta (GSK3b) N-terminus (G3-E12, human) peptide; Akt protein kinase substrate peptide - Powder PE-01ACT95 Glycogen synthase kinase 3-beta (GSK3b) N-terminus (G3-E12, human) peptide - Powder PE-01ACT95 GSK3b (4-10) T7A, T8A, S9T; KinSub - Glycogen synthase kinase-3-beta-derived N-terminus (R4-F10, T7A, T8A, S9T, human) peptide; Akt1 protein kinase substrate peptide - Powder PE-01ACU90 Glycogen synthase kinase-3-beta-derived N-terminus (R4-F10, T7A, T8A, S9T, human) mutant peptide - Powder PE-01ACU90 Glycogen synthase kinase-3-beta-derived N-terminus (R4-F10, human) peptide - Powder PE-01ACU95 GSK3b (4-12) T7A, T8A; KinSub - Glycogen synthase kinase-3-beta-derived N-terminus (R4-E12, T7A, T8A, human) peptide; Akt1 protein kinase substrate peptide - Powder PE-01ACV95 Glycogen synthase kinase-3-beta-derived N-terminus (R4-E12, T7A, T8A, human) peptide - Powder PE-01ACV95 Glycogen synthase-serine kinase 3 beta (C14-D33, human) peptide - Powder PE-01BDB85 AktSubtide - Akt1 (PKBa) protein kinase substrate peptide - Powder PE-01BGF95 Akt-sub KinSub, biotinyl. - Akt1 (PKBa) protein kinase substrate peptide, biotinylated - Powder PE-03AAG95 GSK3Selectide - GSK3 protein kinase substrate peptide - Powder PE-04AXL90

General Links

Structure

Mol. Mass (Da):

46,744

# Amino Acids:

420

# mRNA Isoforms:

mRNA Isoforms:

48,034 Da (433 AA; P49841-2); 46,744 Da (420 AA; P49841)

4D Structure:

Monomer By similarity. Interacts with ARRB2 and DISC1 By similarity. Interacts with CABYR, MMP2, MUC1, NIN and PRUNE Interacts with AXIN1; the interaction mediates hyperphosphorylates of CTNNB1 leading to its ubiquitination and destruction. Interacts with and phosphorylates SNAI1.

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

1I09

Subfamily Alignment

Domain Distribution:

Start	End	Domain

Kinexus Products

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

hiddentext

○	Glycogen synthase-serine kinase 3 beta pan-specific antibody AB-NK070
○	Glycogen synthase kinase-3 beta pan-specific antibody AB-NK070-4
○	Glycogen synthase-serine kinase 3 beta pan-specific antibody AB-NK194-NK195-3
○	Glycogen synthase-serine kinase 3 beta pan-specific antibody AB-NK270-3
○	GSK3b (3-12) KinSub - Glycogen synthase kinase 3-beta (GSK3b) N-terminus (G3-E12, human) peptide; Akt protein kinase substrate peptide - Powder PE-01ACT95
○	Glycogen synthase kinase 3-beta (GSK3b) N-terminus (G3-E12, human) peptide - Powder PE-01ACT95
○	GSK3b (4-10) T7A, T8A, S9T; KinSub - Glycogen synthase kinase-3-beta-derived N-terminus (R4-F10, T7A, T8A, S9T, human) peptide; Akt1 protein kinase substrate peptide - Powder PE-01ACU90
○	Glycogen synthase kinase-3-beta-derived N-terminus (R4-F10, T7A, T8A, S9T, human) mutant peptide - Powder PE-01ACU90
○	Glycogen synthase kinase-3-beta-derived N-terminus (R4-F10, human) peptide - Powder PE-01ACU95
○	GSK3b (4-12) T7A, T8A; KinSub - Glycogen synthase kinase-3-beta-derived N-terminus (R4-E12, T7A, T8A, human) peptide; Akt1 protein kinase substrate peptide - Powder PE-01ACV95
○	Glycogen synthase kinase-3-beta-derived N-terminus (R4-E12, T7A, T8A, human) peptide - Powder PE-01ACV95
○	Glycogen synthase-serine kinase 3 beta (C14-D33, human) peptide - Powder PE-01BDB85
○	AktSubtide - Akt1 (PKBa) protein kinase substrate peptide - Powder PE-01BGF95
○	Akt-sub KinSub, biotinyl. - Akt1 (PKBa) protein kinase substrate peptide, biotinylated - Powder PE-03AAG95
○	GSK3Selectide - GSK3 protein kinase substrate peptide - Powder PE-04AXL90

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Serine phosphorylated:

S9-, S13, S21, S25, S35, S203, S215+, S219-, S389, S417.

Sumoylated:

K292.

Threonine phosphorylated:

T7, T8, T43, T275, T277, T390, T392, T395, T402, T420.

Tyrosine phosphorylated:

Y71, Y114, Y117, Y216+, Y221-, Y222-, Y288.

Ubiquitinated:

K205, K292, K297.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

95

1332

37

1161
9

130

15

92
18

255

10

174
29

403

137

428
70

976

41

635
20

277

72

442
21

294

53

493
100

1404

41

3494
49

685

10

639
12

165

142

135
12

173

29

210
41

576

168

624
10

142

21

139
5

64

12

41
9

124

25

132
7

104

24

72
17

236

274

1388
17

236

19

197
15

205

112

192
62

869

140

620
10

134

25

142
11

156

27

156
14

196

19

169
29

414

19

421
13

176

25

166
87

1222

93

2529
13

177

24

201
12

171

19

185
13

178

19

186
9

130

56

110
68

956

18

658
56

789

36

1690
8

109

89

143
65

912

109

731
16

231

61

234

Evolution

Species Conservation

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

100

100

100
98.1

98.8

98
94.8

96.4

-
-

-

99
-

-

97
99.8

99.8

100
-

-

-
99

99

99
98.8

99

99
-

-

-
-

-

-
93.8

95.2

97
93.3

97.1

91
95

97.2

96
-

-

-
31.9

35

70
71

80.4

-
64.8

74.3

78
-

-

-
-

-

-
-

-

-
-

-

68
60.2

74

68
44.8

63.1

54
-

-

62

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Regulation

Activation:

Phosphorylation at Thr-216 increases phosphotransferase activity and promotes nuclear localization.

Inhibition:

Phosphorylation at Ser-9 inhibits phosphotransferase activity.

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

GSK3B	P49841	S9	SGRPRTTSFAESCKP	-
PKCh	P24723	S9	SGRPRTTSFAESCKP	-
PKCg	P05129	S9	SGRPRTTSFAESCKP	-
PKCb	P05771	S9	SGRPRTTSFAESCKP	-
PKCd	Q05655	S9	SGRPRTTSFAESCKP	-
PKCb	P05771	S9	SGRPRTTSFAESCKP	-
RSK2	P51812	S9	SGRPRTTSFAESCKP	-
RSK1	Q15418	S9	SGRPRTTSFAESCKP	-
KHS1	Q9Y4K4	S9	SGRPRTTSFAESCKP	-
PKCz	Q05513	S9	SGRPRTTSFAESCKP	-
ILK	Q13418	S9	SGRPRTTSFAESCKP	-
PKG1	Q13976	S9	SGRPRTTSFAESCKP	-
PKCa	P17252	S9	SGRPRTTSFAESCKP	-
p70S6K	P23443	S9	SGRPRTTSFAESCKP	-
Akt1	P31749	S9	SGRPRTTSFAESCKP	-
AKT3	Q9Y243	S9	SGRPRTTSFAESCKP	-
PKACa	P17612	S9	SGRPRTTSFAESCKP	-
AurA	O14965	S9	SGRPRTTSFAESCKP	-
ERK2	P28482	T43	KVTTVVATPGQGPDR
ERK1	P27361	T43	KVTTVVATPGQGPDR
GSK3B	P49841	Y216	RGEPNVSYICSRYYR	+
MEK1	Q02750	Y216	RGEPNVSYICSRYYR	+
MEK2	P36507	Y216	RGEPNVSYICSRYYR	+

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

PPP1R16B	Q96T49	S333	LRHKSSLSRRTSSAG
PPP1R16B	Q96T49	S337	SSLSRRTSSAGSRGK
PPP1R2	P41236	T72	MKIDEPSTPYHSMMG
PSEN1	P49768	S353	SHLGPHRSTPESRAA
PSEN1	P49768	S357	PHRSTPESRAAVQEL
PTEN	P60484	S362	SNPEASSSTSVTPDV
PTEN	P60484	T366	ASSSTSVTPDVSDNE	-
PXN	P49023	S126	SFPNKQKSAEPSPTV
SFPQ (PSF)	P23246	T687	PRGMGPGTPAGYGRG
SIK	P57059	S186	PLSTWCGSPPYAAPE	+
SIK	P57059	T182	KSGEPLSTWCGSPPY	+
SNAI1	O95863	S100	DEDSGKGSQPPSPPS
SNAI1	O95863	S104	GKGSQPPSPPSPAPS
SNAI1	O95863	S107	SQPPSPPSPAPSSFS
SNAI1	O95863	S111	SPPSPAPSSFSSTSV
SNAI1	O95863	S115	PAPSSFSSTSVSSLE
SNAI1	O95863	S119	SFSSTSVSSLEAEAY
SNAI1	O95863	S96	TSLSDEDSGKGSQPP
SNCAIP	Q9Y6H5	S556	AQKSEGKSLPSSPSS
SPAG5	Q96R06	S974	EESLAEMSIMTTELQ
SPAG5	Q96R06	T111	PIPQISSTPKTSEEA
SPAG5	Q96R06	T937	ADEEPESTPVPLLGS
SPAG5	Q96R06	T978	AEMSIMTTELQSLCS
SREBP1	P36956	S430	DTLTPPPSDAGSPFQ
SREBP1	P36956	S434	PPPSDAGSPFQSSPL
SREBP1	P36956	T426	TEVEDTLTPPPSDAG
Tau	P10636	S515	GDRSGYSSPGSPGTP
Tau	P10636	S518	SGYSSPGSPGTPGSR
Tau	P10636	S551	VVRTPPKSPSSAKSR
Tau	P10636	S578	NVKSKIGSTENLKHQ
Tau	P10636	S720	PVVSGDTSPRHLSNV
Tau	P10636	S729	RHLSNVSSTGSIDMV
Tau	P10636	S738	GSIDMVDSPQLATLA
Tau	P10636	T497	KTPPAPKTPPSSGEP
Tau	P10636	T521	SSPGSPGTPGSRSRT
Tau	P10636	T528	TPGSRSRTPSLPTPP
Tau	P10636	T533	SRTPSLPTPPTREPK
Tau	P10636	T547	KKVAVVRTPPKSPSS
Tau iso8	P10636-8	S214	GSRSRTPSLPTPPTR
Tau iso8	P10636-8	S396	GAEIVYKSPVVSGDT
Tau iso8	P10636-8	S400	VYKSPVVSGDTSPRH
Tau iso8	P10636-8	S409	DTSPRHLSNVSSTGS
Tau iso9 (Tau-F)	P10636-9	S356	RVQSKIGSLDNITHV
TNKS	O95271	S978	VVSASLISPASTPSC
TNKS	O95271	S987	ASTPSCLSAASSIDN
TNKS	O95271	S991	SCLSAASSIDNLTGP
TNKS	O95271	T982	SLISPASTPSCLSAA
TSC2	P49815	S1375	GRPSVDLSFQPSQPL
TSC2	P49815	S1379	VDLSFQPSQPLSKSS
TSC2	P49815	S1383	FQPSQPLSKSSSSPE
TSC2	P49815	T1373	SSEGARPTVDLSFQP
VHL	P40337	S68	PVLRSVNSREPSQVI
APP	P05067	T743	VEVDAAVTPEERHLS
Ataxin-3	P54252	S256	LRRAIQLSMQGSSRN
Axin	O15169	S486	LRTPGRQSPGPGHRS
Axin	O15169	T481	HVQRVLRTPGRQSPG
Baxa (Bax)	Q07812	S163	GGWDGLLSYFGTPTW
BCAM (Lu)	P50895	S596	PPGEPGLSHSGSEQP
BCLAF1	Q9NYF8	S531	KSTFREESPLRIKMI
C-EBPa	P49715	T226	HLQPGHPTPPPTPVP
C-EBPb	P17676	T235	SSSSPPGTPSPADAK
C/EBPb	P17676	S231	LSTSSSSSPPGTPSP
C/EBPb	P17676	T226	GSSGSLSTSSSSSPP
Cdc25A	P30304	S76	SNLQRMGSSESTDSG
CdGAP	Q9ULL6	T790	PPAPPPPTPLEESTP
CDH1	P12830	S847	SEAASLSSLNSSESD
CDX2	Q99626	S283	RSVPEPLSPVSSLQA
CIITA	P33076	S373	VQARLERSSSKSLER
Cip1 (p21, CDKN1A)	P38936	S113	EEDHVDLSLSCTLVP
Cip1 (p21, CDKN1A)	P38936	T56	NFDFVTETPLEGDFA
CREB1	P16220	S129	QKRREILSRRPSYRK	+
CRMP2 (DPYSL2)	Q16555	S518	KTVTPASSAKTSPAK
CRMP2 (DPYSL2)	Q16555	T509	PVCEVSVTPKTVTPA
CRMP2 (DPYSL2)	Q16555	T514	SVTPKTVTPASSAKT
CRMP4	Q6DEN2	S632	KGGTPAGSARGSPTR
CRMP4	Q6DEN2	T623	PVFDLTTTPKGGTPA
CRMP4	Q6DEN2	T628	TTTPKGGTPAGSARG
CRY2	Q8IV71	S554	AGPRPLPSGPASPKR
CRY2	Q8IV71	S558	PLPSGPASPKRKLEA
CTNNB1	P35222	S33	QQQSYLDSGIHSGAT	-
CTNNB1	P35222	S37	YLDSGIHSGATTTAP	?
CTNNB1	P35222	S45	GATTTAPSLSGKGNP	+
CTNNB1	P35222	T41	GIHSGATTTAPSLSG	?
CTNND1	O60716	S252	MEGYRAPSRQDVYGP
CTNND1	O60716	T310	GTARRTGTPSDPRRR
Cyclin D1 (CCND1)	P24385	T286	EEVDLACTPTDVRDV
Cyclin D1 (CCND1)	P24385	T288	VDLACTPTDVRDVDI
Cyclin D2 (CCND2)	P30279	T280	DELDQASTPTDVRDI
Cyclin D3 (CCND3)	P30281	T283	QGPSQTSTPTDVTAI
Cyclin E1 (CCNE1)	P24864	S73	AVCADPCSLIPTPDK
Cyclin E1 (CCNE1)	P24864	T395	PLPSGLLTPPQSGKK
Cyclin E1 (CCNE1)	P24864	T77	DPCSLIPTPDKEDDD
DSCR1	P53805	S108	PDKQFLISPPASPPV
DSCR1	P53805	S112	FLISPPASPPVGWKQ
E2F1	Q01094	S403	PEEFISLSPPHEALD
E2F1	Q01094	T433	DCDFGDLTPLDF___
eIF2B-e	Q13144	S540	MDSEEPDSRGGSPQM	-
ERa (ESR1)	P03372	S102	GGFPPLNSVSPSPLM	+
ERa (ESR1)	P03372	S104	FPPLNSVSPSPLMLL	+
ERa (ESR1)	P03372	S106	PLNSVSPSPLMLLHP	+
ERa (ESR1)	P03372	S118	LHPPPQLSPFLQPHG	+
FAK (PTK2)	Q05397	S722	PSRPGYPSPRSSEGF	-
FBX4	Q9UKT5	S12	EPRSGTNSPPPPFSD
FRAT1	Q92837	S188	RLQQRRGSQPETRTG
GR	P04150	S404	SMRPDVSSPPSSSST	-
GSK3b	P49841	S9	SGRPRTTSFAESCKP	-
GSK3b	P49841	Y216	RGEPNVSYICSRYYR	+
GYS1	P13807	S641	YRYPRPASVPPSPSL	-
GYS1	P13807	S645	RPASVPPSPSLSRHS	-
GYS1	P13807	S649	VPPSPSLSRHSSPHQ
GYS1	P13807	S653	PSLSRHSSPHQSEDE
GYS2	P54840	S641	FKYPRPSSVPPSPSG	-
GYS2	P54840	S645	RPSSVPPSPSGSQAS	-
H1B	P16401	T11	TAPAETATPAPVEKS
hnRNP D	Q14103	S83	DEGHSNSSPRHSEAA
HSF1	Q00613	S303	RVKEEPPSPPQSPRV
HSL	Q05469	S855	EPMRRSVSEAALAQP
IGF1R	P08069	S1278	EPGFREVSFYYSEEN	-
IRS1	P35568	S337	SDGEGTMSRPASVDG
Jun (c-Jun)	P05412	S243	PGETPPLSPIDMESQ	-
Jun (c-Jun)	P05412	T239	VPEMPGETPPLSPID	-
L-Myc	E9PQS5	S38	KKFELVPSPPTSPPW
L-Myc	E9PQS5	S42	LVPSPPTSPPWGLGP
LRP6	O75581	S1490	AILNPPPSPATERSH
MAP1B	P46821	S1265	SLSPSPPSPLEKTPL
MAP1B	P46821	T1270	PPSPLEKTPLGERSV
MAP2	P11137	T1616	YSSRTPGTPGTPSYP
MAP2	P11137	T1619	RTPGTPGTPSYPRTP
MARK1	Q9P0L2	S219	KLDTFCGSPPYAAPE	-
MARK2	Q7KZI7	S212	KLDTFCGSPPYAAPE	-
MCL1	Q07820	S159	NNTSTDGSLPSTPPP
MDM2	Q00987	S242	WLDQDSVSDQFSVEF	+
MDM2	Q00987	S256	FEVESLDSEDYSLSE
MITF	O75030	S405	QARAHGLSLIPSTGL	+
MKI67IP (NIFK)	Q9BYG3	S230	TPEKTVDSQGPTPVC
MKI67IP (NIFK)	Q9BYG3	T234	TVDSQGPTPVCTPTF	?
MUC1	P15941	S1227	PPSSTDRSPYEKVSA	-
Myc	P01106	T58	KKFELLPTPPLSPSR
MYLK1 (smMLCK)	Q15746	S1776	GRKSSTGSPTSPLNA
Myocardin	Q8IZQ8	S451	NGFYHFGSTSSSPPI
Myocardin	Q8IZQ8	S455	HFGSTSSSPPISPAS
Myocardin	Q8IZQ8	S459	TSSSPPISPASSDLS
Myocardin	Q8IZQ8	S463	PPISPASSDLSVAGS
Myocardin	Q8IZQ8	S626	DQTNVLSSTFLSPQC
Myocardin	Q8IZQ8	S630	VLSSTFLSPQCSPQH
Myocardin	Q8IZQ8	S634	TFLSPQCSPQHSPLG
Myocardin	Q8IZQ8	S638	PQCSPQHSPLGAVKS
NACA	Q13765	T159	NIQENTQTPTVQEES
NDRG1	Q92597	S342	TSLDGTRSRSHTSEG
NDRG1	Q92597	S352	HTSEGTRSRSHTSEG
NDRG2	Q9UN36	S328	CMTRLSRSRTASLTS
Neurogenin 2	Q9H2A3	S234	SCTLSPASPGSDVDY
Neurogenin 2	Q9H2A3	S239	SPYSCTLSPASPAGS
NFH	P12036	S503	GGEEETKSPPAEEAA
NFkB-p100	Q00653	S222	QPIHDSKSPGASNLK	?
NFkB-p100	Q00653	S707	EPLCPLPSPPTSDSD	?
NFkB-p100	Q00653	S711	PLPSPPTSDSDSDSE	?
NFkB-p105	P19838	S903	KTTSQAHSLPLSPAS	+
NFkB-p105	P19838	S907	QAHSLPLSPASTRQQ	+
NFkB-p65	Q04206	S468	AVFTDLASVDNSEFQ
NFM (Neurofilament M)	P07197	S510	EEVAAKKSPVKATAP
NFM (Neurofilament M)	P07197	S666	PVEEKGKSPVSKSPV
NR1D1	P20393	S55	CPTYFPPSPTGSLTQ	+
NR1D1	P20393	S59	FPPSPTGSLTQDPAR	+
p53	P04637	S33	LPENNVLSPLPSQAM	+
p53	P04637	S376	LKSKKGQSTSRHKKL	+
PDX1	P52945	S61	LGALEQGSPPDISPY	+
PDX1	P52945	S66	QGSPPDISPYEVPPL	+
PKCe (PRKCE)	Q02156	S346	SEEDRSKSAPTSPCD	?

Protein Kinase Specificity

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

Matrix Type:

Experimentally derived from alignment of 243 known protein substrate phosphosites and 28 peptides phosphorylated by recombinant GSK3-beta 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

CHEMBL1082152	Kd = 53 pM	11560568	1082152	20138512
CHEMBL489833	IC50 = 510 pM	44582745	489833	19338355
CHIR-98014	IC50 = 580 pM	9868037		12606497
Alsterpaullone; 2-Cyanoethyl	IC50 = 800 pM	16760286	260138	18077363
Kinome_3681	IC50 = 1.1 nM	10029385	362558	15267232
SureCN3491039	IC50 = 2.3 nM	42629114	516640	19200745
CHEMBL1684800	IC50 = 2.73 nM	52938983	1684800	21353571
Ro-31-8220	IC50 = 2.8 nM	5083	6291	18929433
Alsterpaullone	IC50 = 4 nM	5005498	50894	15559249
GSK-3 Inhibitor IX	IC50 = 5 nM	5287844	409450	14761195
GSK-3b Inhibitor XI	IC50 = 5 nM	10020713	272629	18006321
Staurosporine	IC50 = 5 nM	5279		20472330
CHEMBL1092754	IC50 = 5.9 nM	44541014	1092754	20188552
CHIR 99021 (CT 99021)	IC50 = 6.7 nM	9956119	412142	12606497
SB216763	IC50 = 7 nM	176158		12941331
AC1O6ZUA	IC50 = 8 nM	6539569	408019	19035792
Enzastaurin	Kd = 8.3 nM	176167	300138	22037378
AT9283	IC50 < 10 nM	24905142		19143567
GSK-3 Inhibitor X	IC50 = 10 nM	6538818	430226	14761195
Hymenialdisine	IC50 = 10 nM	3035462		14698171
TTT-3002	IC50 = 10 nM
AT7519	Kd = 11 nM	11338033		22037378
Cyanoquinoline, 11	IC50 = 15 nM	17759555	436817	17764934
CHEMBL103055	IC50 = 18 nM	10207821	103055	12941331
CHEMBL191336	IC50 = 20 nM	9863538	191336	15999992
CK7	Ki = 20 nM	447961		15027857
Ro-32-0432	IC50 = 20 nM	127757	26501	20138512
GSK-3 Inhibitor XIII	Ki = 22 nM	6419766	359482	19320489
Kenpaullone	IC50 = 23 nM	3820	296586	14698171
Compound 52	IC50 = 30 nM	2856		18077363
TWS119	IC50 = 30 nM	9549289	405759	15559249
AC1NS7CD	Kd = 37 nM	5329665	295136	22037378
SNS032	Kd = 37 nM	3025986	296468	18183025
AR-A014418	Ki = 38 nM	448014	259850	18077363
AS601245	IC50 = 40 nM	11422035	191384	17850214
NU6102	IC50 = 40 nM	4566		16325401
SureCN3470757	IC50 < 40 nM	11588244	375236
7-hydroxystaurosporine	IC50 > 45 nM	72271	1236539
Bisindolylmaleimide I	IC50 > 50 nM	2396	7463	22037377
IDR E804	IC50 > 50 nM	6419764	1802727	22037377
PKCb Inhibitor	IC50 > 50 nM	6419755	366266	22037377
PKR Inhibitor	IC50 > 50 nM	6490494	235641	22037377
SB218078	IC50 > 50 nM	447446	289422	22037377
Gö6976	IC50 < 60 nM	3501	302449
SB415286	IC50 = 77 nM	4210951	322970	20138512
PHA-793887	IC50 = 79 nM	46191454	1230607	20153204
A 443654	IC50 < 80 nM	10172943	379300
Amgen TBK 1 inhibitor (Compound II)	IC50 < 80 nM
Nintedanib	Kd = 83 nM	9809715	502835	22037378
BX517	IC50 = 100 nM	11161844	228654
GSK690693	Kd = 100 nM	16725726	494089	22037378
Paullone	IC50 = 100 nM	369401	430574	20138512
Princeton's TrkA inhibitor compound 20h	IC50 = 100 nM
R406	IC50 = 100 nM	11984591
Ruboxistaurin	IC50 = 100 nM	153999	91829
Syk Inhibitor IV	IC50 < 100 nM	10200390
A674563	Ki = 110 nM	11314340	379218	16678413
Debromohymenialdisine	IC50 = 111 nM	5288032		16289938
Cdk1/2 Inhibitor III	IC50 = 140 nM	5330812	261720	15974571
Bisindolylmaleimide IV	IC50 > 150 nM	2399	266487	22037377
Indirubin-3′-monoxime	IC50 > 150 nM	5326739		22037377
JAK3 Inhibitor VI	IC50 > 150 nM	16760524		22037377
AC1NS90Q	IC50 = 196 nM	5330392	372657	16033269
SB202190	IC50 < 200 nM	5353940	278041
PHA-767491	IC50 = 220 nM	11715767	225519	18469809
CHEMBL494221	Ki > 230 nM	5328125	494221	19414255
R547	Kd = 230 nM	6918852		22037378
Gö6976	IC50 > 250 nM	3501	302449	22037377
Gö6983	IC50 > 250 nM	3499	261491	22037377
Alvocidib	IC50 = 280 nM	9910986	428690	15689157
CHEMBL383104	IC50 = 300 nM	11361885	383104	16290148
Dovitinib	Kd = 350 nM	57336746		18183025
SU9516	IC50 = 350 nM	5289419	258805	15559249
GSK-3b Inhibitor II	IC50 = 390 nM	6539732	288064	12031334
BX795	IC50 < 400 nM	10077147	577784
Gö7874	IC50 < 400 nM	5327863
GSK269962A	IC50 < 400 nM	16095342	220241
Staurosporine aglycone	IC50 < 400 nM	3035817	281948
AG-E-60384	IC50 = 500 nM	6419741	413188	18077363
K-252a; Nocardiopsis sp.	IC50 = 500 nM	3813	281948	22037377
Meridianin B	IC50 = 500 nM	10380356		15026054
MK5108	IC50 > 500 nM	24748204		20053775
N-Benzoylstaurosporine	IC50 = 500 nM	56603681	608533	22037377
RGB-286147	IC50 = 500 nM	9549301	258721	22037377
Pyrrolo-pyrimidone; 17	IC50 = 530 nM	16119021	461140	18945615
K00596a	IC50 < 600 nM	9549298	200027
AC1NS90N	IC50 = 606 nM	10187378	426587	16033269
Aloisine A	IC50 = 650 nM	5326843	75680	12519061
PHA-533533	IC50 = 732 nM	5330949	191144	15828833
PF-228	IC50 < 750 nM	11612883		17395594
BMS-754807	IC50 = 785 nM	24785538		19996272
BI-D1870	IC50 < 800 nM	25023738	573107
Cot-Tpl2 Inhibitor Compound 41 (Abbott)	IC50 < 800 nM
SB203580	IC50 < 800 nM	176155	10
Wyeth PDK1 Inhibitor Compound 1	IC50 < 800 nM
Sotrastaurin	IC50 = 870 nM	10296883	565612	19827831
SureCN3779530	IC50 = 890 nM	10143584	360304	15771419
Aloisine; RP106	IC50 = 920 nM	44350092	126343	12519061
JNJ-7706621	Kd = 950 nM	5330790	191003	18183025
ALX-270-403-M001	IC50 > 1 µM			22037377
AT7867	IC50 > 1 µM	11175137	428462	20423992
BX320	IC50 = 1 µM	657138	573108
Cdk1/5 Inhibitor	IC50 = 1 µM	438981	259389	18077363
CP673451	IC50 > 1 µM	10158940		15705896
Doramapimod	IC50 = 1 µM	156422	103667
GW 843682X	IC50 = 1 µM	9826308	514499
GW5074 (Raf1 Kinase Inhibitor I)	IC50 = 1 µM	5924208
JNKIN7	IC50 = 1 µM	57340685
Kinome_714	IC50 > 1 µM	46886323		20346655
NSC 625987	IC50 > 1 µM	3004085		22037377
PD169316	IC50 > 1 µM	4712	17331	22037377
SGI-1776	IC50 > 1 µM			19734450
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	16047143	514582	18678489
SureCN10063060	Ki > 1 µM	52936621		21391610
Syk Inhibitor	IC50 = 1 µM	6419747	104279
Syk Inhibitor II	IC50 = 1 µM	16760670
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
Zearalenone	IC50 = 1 µM	5281576	454173
CHEMBL201511	IC50 = 1.1 µM	11530963	201511	17149885
CHEMBL590109	IC50 = 1.3 µM	46224684	590109	19926477
Lestaurtinib	Kd = 1.3 µM	126565		22037378
Apigenin	IC50 = 1.4 µM	5280443		15689157
SureCN3774124	IC50 = 1.9 µM	10209082	368895	15771419
BMS-777607	IC50 > 2 µM	24794418		19260711
IPA-3	IC50 < 2 µM	521106	472940
Meridianin C	IC50 = 2 µM	10017019	44541	18929433
Momelotinib	IC50 > 2 µM	25062766		19295546
NP12	IC50 = 2 µM	4124851	284861	11881998
STO609	IC50 < 2 µM	51371511
Quercetin	IC50 = 2.1 µM	5280343	50	15689157
AZ960	IC50 < 2.5 µM	25099184		18775810
P276-00	IC50 = 2.771 µM	10406644		17363486
CHEMBL493169	Ki = 2.9 µM	44219632	493169	19414255
GW441756 hydrochloride	IC50 > 3 µM	16219400
IRAK-1-4 Inhibitor I	IC50 < 3 µM	11983295	379787
Purvalanol B	IC50 > 3 µM	448991	23254
Ruxolitinib	IC50 > 3 µM	25126798	1789941
Wortmannin	IC50 > 3 µM	312145	428496
SureCN4875304	IC50 > 3.5 µM	46871765		20472445
SureCN5757856	IC50 = 3.9 µM	10302405	359486	15771419
Cot-Tpl2 Inhibitor Compound 38 (Abbott)	IC50 < 4 µM
FMK	IC50 > 4 µM	5737
JNJ-28871063	IC50 > 4 µM	17747413		17975007
Quercetagetin	IC50 < 4 µM	5281680	413552
(5Z)-7-Oxozeaenol	IC50 > 4.5 µM		1077979
A-83-01	IC50 > 4.5 µM	16218924	1170377
KT5720	IC50 > 4.5 µM	3844	608532
MSC 2032964A	IC50 > 4.5 µM
Purvalanol A	IC50 > 4.5 µM	456214	23327
SureCN3773926	IC50 = 4.8 µM	10187378	426587	15771419

Disease Linkage

General Disease Association:

Neurological disorders

Specific Diseases (Non-cancerous):

Alzheimer's disease (AD); Parkinson's disease; Leopard syndrome; Aneurysmal bone cysts; Waardenburg syndrome Type 2

Comments:

Mutations on GSK3B have been shown to associated with Parkinson disease, and homozygous GSK3B TT haplotype is associated with Alzheimer 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= +112, p<0.0001); Bladder carcinomas (%CFC= +112, p<0.0001); Bladder carcinomas (%CFC= +52, p<0.085); Brain glioblastomas (%CFC= +308, p<0.005); Cervical cancer (%CFC= -57, p<0.0002); Cervical cancer stage 1B (%CFC= +56, p<0.073); Cervical cancer stage 2B (%CFC= +73, p<0.05); Clear cell renal cell carcinomas (cRCC) stage I (%CFC= +104, p<0.058); Prostate cancer - metastatic (%CFC= +95, p<0.0001); Prostate cancer - primary (%CFC= -60, p<0.0001); Prostate cancer - primary (%CFC= +63, p<0.011); Skin melanomas - malignant (%CFC= +59, p<0.0002); and Uterine leiomyomas (%CFC= -54, p<0.016).

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: 0.09 % in 24865 diverse cancer specimens. This rate is only 16 % higher than the average rate of 0.075 % calculated for human protein kinases in general.

Frequency of Mutated Sites:

None > 4 in 20,655 cancer specimens

Comments:

No deletions, insertions or complex mutations are noted on the COSMIC website.

COSMIC Entry:

GSK3B_ENST00000316626

OMIM Entry:

605004

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:

Sumoylated:

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:

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):

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: