mutLBSgeneDB

mutLBSgeneDB
mutated Ligand Binding Site gene DataBase

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Gene Summary

Ligand Binding Site Mutation Information

Protein Structure Related Information

Gene Expression and Gene-Gene Network

Phenotype Information

Pharmacological Information

Conservation Information for LBS

Gene summary for ITK
Gene summary
Basic gene Info.Gene symbolITK
Gene nameIL2-inducible T-cell kinase
SynonymsEMT|LPFS1|LYK|PSCTK2
CytomapUCSC genome browser: 5q31-q32
Type of geneprotein-coding
RefGenesNM_005546.3,
DescriptionIL-2-inducible T cell kinaseIL-2-inducible T-cell kinaseT-cell-specific kinasehomolog of mouse T-cell itk/tskinterleukin-2-inducible T cell kinaseinterleukin-2-inducible T-cell kinasekinase EMTtyrosine-protein kinase ITK/TSKtyrosine-protein kinase
Modification date20141207
dbXrefs MIM : 186973
HGNC : HGNC
Ensembl : ENSG00000113263
HPRD : 01746
Vega : OTTHUMG00000130245
ProteinUniProt: Q08881
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_ITK
BioGPS: 3702
PathwayNCI Pathway Interaction Database: ITK
KEGG: ITK
REACTOME: ITK
Pathway Commons: ITK
ContextiHOP: ITK
ligand binding site mutation search in PubMed: ITK
UCL Cancer Institute: ITK
Assigned class in mutLBSgeneDBB: This gene belongs to targetable_mutLBSgenes.

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez
GO IDGO TermPubMed ID


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Ligand binding site mutations for ITK
Lollipop-style diagram of mutations at LBS in amino-acid sequence.
We represented ligand binding site mutations only. (You can see big image via clicking.)
 
: non-synonymous mutation on LBS, Circle size denotes number of samples.

Cancer type specific mutLBS sorted by frequency
LBSAAchange of nsSNVCancer type# samples
L379G380CLUAD2
S499S499FBRCA1
M503M503VCOAD1
K387K385ECOAD1
G372G372WCOAD1
G423G423VLUAD1
V507L508QLUAD1
I393R394WPRAD1
M410M410ISKCM1
D445D445NSKCM1
R486R486IUCEC1
M410V409LUCEC1
cf) Cancer type abbreviation. BLCA: Bladder urothelial carcinoma, BRCA: Breast invasive carcinoma, CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma, COAD: Colon adenocarcinoma, GBM: Glioblastoma multiforme, LGG: Brain lower grade glioma, HNSC: Head and neck squamous cell carcinoma, KICH: Kidney chromophobe, KIRC: Kidney renal clear cell carcinoma, KIRP: Kidney renal papillary cell carcinoma, LAML: Acute myeloid leukemia, LUAD: Lung adenocarcinoma, LUSC: Lung squamous cell carcinoma, OV: Ovarian serous cystadenocarcinoma, PAAD: Pancreatic adenocarcinoma, PRAD: Prostate adenocarcinoma, SKCM: Skin cutaneous melanoma, STAD: Stomach adenocarcinoma, THCA: Thyroid carcinoma, UCEC: Uterine corpus endometrial carcinoma.

Clinical information for ITK from My Cancer Genome.
IL2-inducible T-cell kinase (ITK) is a gene that encodes a protein that functions as an intracellular tyrosine kinase expressed in T-cells. The protein may also be important in T-cell proliferation and differentiation. Fusions, missense mutations, nonsense mutations, silent mutations, and frameshift deletions and insertions are observed in cancers such as intestinal cancer, pleural cancer, and skin cancer. Modified: July 1, 2015

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Protein structure related information for ITK
Protein structure of wild type (WT) and mutant type (MT) of ITK
Wild type ITK
Mutant type ITK

Free energy of binding of drugs to wild type and mutant tpye of ITK
Gene symbolDrug nameFree energy of binding (kcal/mol) of wild typeFree energy of binding (kcal/mol) of mutant type
ITKPazopanib-8.6-8.6

Relative protein structure stability change (ΔΔE) using Mupro 1.1
Mupro score denotes assessment of the effect of mutations on thermodynamic stability.
  (ΔΔE<0: mutation decreases stability, ΔΔE>0: mutation increases stability)
: nsSNV at non-LBS: nsSNV at LBS

nsSNVs sorted by the relative stability change of protein structure by each mutation
Blue: mutations of positive stability change. and red : the most recurrent mutation for this gene.
LBSAAchange of nsSNVRelative stability change
G372G372W0.41622227
D445D445N-0.92436676
L379G380C-0.91265481
V507L508Q-0.90399273
I393R394W-0.8482422
G423G423V-0.81414105
M410V409L-0.69332508
R486R486I-0.61210599
K387K385E-0.57844808
S499S499F-0.57190602
M410M410I-0.56280455
M503M503V-0.4418923
(MuPro1.1: Jianlin Cheng et al., Prediction of Protein Stability Changes for Single-Site Mutations Using Support Vector Machines, PROTEINS: Structure, Function, and Bioinformatics. 2006, 62:1125-1132)

Structure image for ITK from PDB
PDB IDPDB titlePDB structure
1SNUCRYSTAL STRUCTURE OF THE UNPHOSPHORYLATED INTERLEUKIN-2 TYROSINE KINASE CATALYTIC DOMAIN

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Differential gene expression and gene-gene network for ITK
Differential gene expression between mutated and non-mutated LBS samples in all 16 major cancer types

Differential co-expressed gene network based on protein-protein interaction data (CePIN)
* Left PPI network was created from samples with mutations in the LBS of ITK and the right PPI network was created from samples without mutations in the LBS of ITK. Only genes with p-value < 0.05 are shown.
Red circle: input gene. Orange circle: LBSgene. Blue circle: other gene.


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Phenotype information for ITK
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C3552634LYMPHOPROLIFERATIVE SYNDROME 11GeneticVariation
umls:C0017661Glomerulonephritis, IGA1Biomarker

Mutation level pathogenic information (ClinVar annotation)
Allele IDAA changeClinical significanceOriginPhenotype IDs

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Pharmacological information for ITK
Gene expression profile of anticancer drug treated cell-lines (CCLE)
Heatmap showing the correlation between gene expression and drug response across all the cell-lines. We chose the top 20 among 138 drugs.We used Pearson's correlation coefficient.

Gene-centered drug-gene interaction network
Drug information targeting mutLBSgene (Approved drugs only)
Drug statusDrugBank IDNameTypeDrug structure
ExperimentalDB02010StaurosporineSmall molecule
ApprovedDB06589PazopanibSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of ITK go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
G5K1-[(3S)-3-{[4-(MORPHOLIN-4-YLMETHYL)-6-([1, 3]THIAZOLO[5,4-B]PYRIDIN-2-YLAMINO)PYRIMIDIN-2- YL]AMINO}PYRROLIDIN-1-YL]PROP-2-EN-1-ONE4kioAD445
G5K1-[(3S)-3-{[4-(MORPHOLIN-4-YLMETHYL)-6-([1, 3]THIAZOLO[5,4-B]PYRIDIN-2-YLAMINO)PYRIMIDIN-2- YL]AMINO}PYRROLIDIN-1-YL]PROP-2-EN-1-ONE4kioBD445
G5K1-[(3S)-3-{[4-(MORPHOLIN-4-YLMETHYL)-6-([1, 3]THIAZOLO[5,4-B]PYRIDIN-2-YLAMINO)PYRIMIDIN-2- YL]AMINO}PYRROLIDIN-1-YL]PROP-2-EN-1-ONE4kioCD445
G6K1-[(3S)-3-{[4-(MORPHOLIN-4-YLMETHYL)-6-([1, 3]THIAZOLO[5,4-B]PYRIDIN-2-YLAMINO)PYRIMIDIN-2- YL]AMINO}PYRROLIDIN-1-YL]PROPAN-1-ONE4kioDD445
G6K1-[(3S)-3-{[4-(MORPHOLIN-4-YLMETHYL)-6-([1, 3]THIAZOLO[5,4-B]PYRIDIN-2-YLAMINO)PYRIMIDIN-2- YL]AMINO}PYRROLIDIN-1-YL]PROPAN-1-ONE4kioCD445 R486
M0Y4-(CARBAMOYLAMINO)-1-(NAPHTHALEN-1-YL)-1H-PYRAZOLE-3- CARBOXAMIDE4m0yAG372
ADPADP4m15AG372
IAQ(2Z)-4-(DIMETHYLAMINO)-N-{7-FLUORO-4-[(2-METHYLPHENYL)AMINO]IMIDAZO[1,5-A]QUINOXALIN-8-YL}-N-METHYLBUT-2-ENAMIDE3t9tAG372 D445 S499
MJGN-[5-({5-[(4-ACETYLPIPERAZIN-1-YL)CARBONYL]-4-METHOXY-2-METHYLPHENYL}SULFANYL)-1,3-THIAZOL-2-YL]-4-({[(1S)-1,2,2-TRIMETHYLPROPYL]AMINO}METHYL)BENZAMIDE3mj2AG372 R486 S499
18R3-{1-[(3R)-1-ACRYLOYLPIPERIDIN-3-YL]-4-AMINO-1H- PYRAZOLO[3,4-D]PYRIMIDIN-3-YL}-N-(3-TERT-BUTYLPHENYL) BENZAMIDE4hctAI393 D445 S499 M503 V507
13L3-{4-AMINO-1-[(3R)-1-PROPANOYLPIPERIDIN-3-YL]-1H- PYRAZOLO[3,4-D]PYRIMIDIN-3-YL}-N-[4-(PROPAN-2-YL) PHENYL]BENZAMIDE4hcuAI393 D445 S499 M503 V507
13J3-{4-AMINO-1-[(3S)-1-PROPANOYLPIPERIDIN-3-YL]-1H- PYRAZOLO[3,4-D]PYRIMIDIN-3-YL}-N-[4-(PROPAN-2-YL) PHENYL]BENZAMIDE4hcvAI393 R486 S499 M503 V507
29Z(1S,2S)-2-{4-[(DIMETHYLAMINO)METHYL]PHENYL}-N-[6- (PYRIDIN-3-YL)-1,3-BENZOTHIAZOL-2- YL]CYCLOPROPANECARBOXAMIDE4mf0BK387 S499
2VUN-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4- YL)-1H-INDAZOLE-3-CARBOXAMIDE4ppaAK387 S499
2VUN-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4- YL)-1H-INDAZOLE-3-CARBOXAMIDE4ppaBK387 S499
29Z(1S,2S)-2-{4-[(DIMETHYLAMINO)METHYL]PHENYL}-N-[6- (PYRIDIN-3-YL)-1,3-BENZOTHIAZOL-2- YL]CYCLOPROPANECARBOXAMIDE4mf0AK387 S499 M503
29Z(1S,2S)-2-{4-[(DIMETHYLAMINO)METHYL]PHENYL}-N-[6- (PYRIDIN-3-YL)-1,3-BENZOTHIAZOL-2- YL]CYCLOPROPANECARBOXAMIDE4mf0AL379
2VUN-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4- YL)-1H-INDAZOLE-3-CARBOXAMIDE4ppaAL379
2VUN-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-6-(1H-PYRAZOL-4- YL)-1H-INDAZOLE-3-CARBOXAMIDE4ppaBL379
2VVN-{1-[(1S)-3-(DIMETHYLAMINO)-1-PHENYLPROPYL]-1H- PYRAZOL-4-YL}-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3- CARBOXAMIDE4ppbAL379
2VTN-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-2H-INDAZOLE-3- CARBOXAMIDE4pp9AL379 K387
2VTN-[1-(3-CYANOBENZYL)-1H-PYRAZOL-4-YL]-2H-INDAZOLE-3- CARBOXAMIDE4pp9BL379 K387
29Y(1S,2S)-2-{4-[(DIMETHYLAMINO)METHYL]PHENYL}-N-[6-(1H- PYRAZOL-4-YL)-1,3-BENZOTHIAZOL-2- YL]CYCLOPROPANECARBOXAMIDE4mf1BL379 S499
2W6N-{1-[(1S)-3-(DIMETHYLAMINO)-1-PHENYLPROPYL]-1H- PYRAZOL-4-YL}-6,6-DIMETHYL-4,5,6,7-TETRAHYDRO-1H- INDAZOLE-3-CARBOXAMIDE4pqnAL379 S499
1YZ4-(CARBAMOYLAMINO)-1-(7-ETHOXYNAPHTHALEN-1-YL)-1H- PYRAZOLE-3-CARBOXAMIDE4m12AM410 G423 S499
1E04-(CARBAMOYLAMINO)-1-(7-PROPOXYNAPHTHALEN-1-YL)-1H- PYRAZOLE-3-CARBOXAMIDE4m13AM410 G423 S499
QWS4-(CARBAMOYLAMINO)-1-[7-(PROPAN-2-YLOXY)NAPHTHALEN-1- YL]-1H-PYRAZOLE-3-CARBOXAMIDE4m14AM410 G423 S499
QWS4-(CARBAMOYLAMINO)-1-[7-(PROPAN-2-YLOXY)NAPHTHALEN-1- YL]-1H-PYRAZOLE-3-CARBOXAMIDE4m15AM410 G423 S499
M0Y4-(CARBAMOYLAMINO)-1-(NAPHTHALEN-1-YL)-1H-PYRAZOLE-3- CARBOXAMIDE4m0yAM410 S499
M0Z4-(CARBAMOYLAMINO)-1-(7-METHOXYNAPHTHALEN-1-YL)-1H- PYRAZOLE-3-CARBOXAMIDE4m0zAM410 S499
STUSTAUROSPORINE1sm2AR486 S499
STUSTAUROSPORINE1sm2BR486 S499
STUSTAUROSPORINE1snuAR486 S499
STUSTAUROSPORINE1snuBR486 S499
B49SUNITINIB3miyAS499
L7AN-(6-OXO-1,6-DIHYDRO-3,4'-BIPYRIDIN-5-YL)BENZAMIDE3qgwBS499
L7ON-{5-[2-(METHYLAMINO)PYRIMIDIN-4-YL]-2-OXO-1,2-DIHYDROPYRIDIN-3-YL}-4-(PIPERIDIN-1-YL)BENZAMIDE3qgyBS499
4773-{2-[5-(DIFLUOROMETHYL)-2H-THIENO[3,2-C]PYRAZOL-3-YL]-1H-INDOL-6-YL}PENTAN-3-OL3v8tAS499
4773-{2-[5-(DIFLUOROMETHYL)-2H-THIENO[3,2-C]PYRAZOL-3-YL]-1H-INDOL-6-YL}PENTAN-3-OL3v8tBS499
0G23-[2-(5-PHENYL-2H-THIENO[3,2-C]PYRAZOL-3-YL)-1H-INDOL-6-YL]PENTAN-3-OL3v8wAS499
0G23-[2-(5-PHENYL-2H-THIENO[3,2-C]PYRAZOL-3-YL)-1H-INDOL-6-YL]PENTAN-3-OL3v8wBS499
29Y(1S,2S)-2-{4-[(DIMETHYLAMINO)METHYL]PHENYL}-N-[6-(1H- PYRAZOL-4-YL)-1,3-BENZOTHIAZOL-2- YL]CYCLOPROPANECARBOXAMIDE4mf1AS499
G7KTRANS-4-({4-[DIFLUORO(4-FLUOROPHENYL)METHYL]-6-[(5- METHOXY[1,3]THIAZOLO[5,4-B]PYRIDIN-2-YL) AMINO]PYRIMIDIN-2-YL}AMINO)CYCLOHEXANOL4l7sAS499
G7KTRANS-4-({4-[DIFLUORO(4-FLUOROPHENYL)METHYL]-6-[(5- METHOXY[1,3]THIAZOLO[5,4-B]PYRIDIN-2-YL) AMINO]PYRIMIDIN-2-YL}AMINO)CYCLOHEXANOL4l7sBS499
2VVN-{1-[(1S)-3-(DIMETHYLAMINO)-1-PHENYLPROPYL]-1H- PYRAZOL-4-YL}-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3- CARBOXAMIDE4ppbAS499
2VVN-{1-[(1S)-3-(DIMETHYLAMINO)-1-PHENYLPROPYL]-1H- PYRAZOL-4-YL}-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3- CARBOXAMIDE4ppbBS499
2VWN-{1-[(1R)-3-(DIMETHYLAMINO)-1-PHENYLPROPYL]-1H- PYRAZOL-4-YL}-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3- CARBOXAMIDE4ppcAS499
2VWN-{1-[(1R)-3-(DIMETHYLAMINO)-1-PHENYLPROPYL]-1H- PYRAZOL-4-YL}-6-(1H-PYRAZOL-4-YL)-1H-INDAZOLE-3- CARBOXAMIDE4ppcBS499
3P6(4AS,5AR)-N-{1-[(R)-[(2R)-1,1-DIOXIDOTETRAHYDRO-2H- THIOPYRAN-2-YL](PHENYL)METHYL]-1H-PYRAZOL-4-YL}-5,5- DIFLUORO-5A-METHYL-1,4,4A,5,5A,6- HEXAHYDROCYCLOPROPA[F]INDAZOLE-3-CARBOXAMIDE4rfmAS499


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Conservation information for LBS of ITK
Multiple alignments for Q08881 in multiple species
LBSAA sequence# speciesSpecies


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