mutLBSgeneDB

mutLBSgeneDB
mutated Ligand Binding Site gene DataBase

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Bioinformatics and Systems Medicine Laboratory Bioinformatics and Systems Medicine Laboratory

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 TEK
Gene summary
Basic gene Info.Gene symbolTEK
Gene nameTEK tyrosine kinase, endothelial
SynonymsCD202B|TIE-2|TIE2|VMCM|VMCM1
CytomapUCSC genome browser: 9p21
Type of geneprotein-coding
RefGenesNM_000459.4,
NM_001290077.1,NM_001290078.1,
Descriptionangiopoietin-1 receptorendothelial tyrosine kinasetunica interna endothelial cell kinasetyrosine kinase with Ig and EGF homology domains-2tyrosine-protein kinase receptor TEKtyrosine-protein kinase receptor TIE-2
Modification date20141219
dbXrefs MIM : 600221
HGNC : HGNC
Ensembl : ENSG00000120156
HPRD : 02571
Vega : OTTHUMG00000019712
ProteinUniProt: Q02763
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_TEK
BioGPS: 7010
PathwayNCI Pathway Interaction Database: TEK
KEGG: TEK
REACTOME: TEK
Pathway Commons: TEK
ContextiHOP: TEK
ligand binding site mutation search in PubMed: TEK
UCL Cancer Institute: TEK
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
GO:0001934positive regulation of protein phosphorylation15284220
GO:0007169transmembrane receptor protein tyrosine kinase signaling pathway15284220
GO:0010595positive regulation of endothelial cell migration15284220
GO:0018108peptidyl-tyrosine phosphorylation11513602
GO:0045766positive regulation of angiogenesis15284220
GO:0046777protein autophosphorylation11513602
GO:0048014Tie signaling pathway15284220
GO:0051259protein oligomerization19424712
GO:0051897positive regulation of protein kinase B signaling19615361
GO:0070374positive regulation of ERK1 and ERK2 cascade19615361


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Ligand binding site mutations for TEK

Cancer type specific mutLBS sorted by frequency
LBSAAchange of nsSNVCancer type# samples
V838L839ICOAD1
I980K979TKIRC1
L879H881RLUAD1
F983F983ILUSC1
I830D828NSKCM1
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.


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Protein structure related information for TEK
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
F983F983I0.33693434
L879H881R-0.97434667
I980K979T-0.92676502
V838L839I-0.81466811
I830D828N-0.76541848
(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 TEK from PDB

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Differential gene expression and gene-gene network for TEK
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 TEK and the right PPI network was created from samples without mutations in the LBS of TEK. 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 TEK
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0027686Neovascularization, Pathologic3AlteredExpression, Biomarker
umls:C1838437Venous Malformations, Multiple Cutaneous and Mucosal2Biomarker, GeneticVariation
umls:C0018923Hemangiosarcoma2Biomarker
umls:C0014556Epilepsy, Temporal Lobe1Biomarker
umls:C0023904Liver Neoplasms, Experimental1Biomarker

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

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Pharmacological information for TEK
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
Approved|vet_approvedDB00415AmpicillinSmall molecule
InvestigationalDB05153XL184Small molecule
ApprovedDB05294VandetanibSmall molecule
ExperimentalDB08221N-{4-METHYL-3-[(3-PYRIMIDIN-4-YLPYRIDIN-2-YL)AMINO]PHENYL}-3-(TRIFLUOROMETHYL)BENZAMIDESmall molecule
ApprovedDB08896RegorafenibSmall molecule
ApprovedDB08901PonatinibSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of TEK go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
0CE2-METHYL-11-(1-METHYLETHYL)-8-[(2S)-TETRAHYDRO-2H-PYRAN-2-YL]-2,11,12,13-TETRAHYDRO-4H-INDAZOLO[5,4-A]PYRROLO[3,4-C]CARBAZOL-4-ONE3l8pAI830 V838 F983
MR94-METHYL-3-({3-[2-(METHYLAMINO)PYRIMIDIN-4-YL]PYRIDIN-2-YL}OXY)-N-[2-MORPHOLIN-4-YL-5-(TRIFLUOROMETHYL)PHENYL]BENZAMIDE2p4iBI980 F983
3WR1-[4-(4-AMINO-5-OXOPYRIDO[2,3-D]PYRIMIDIN-8(5H)-YL) PHENYL]-3-[2-FLUORO-5-(TRIFLUOROMETHYL)PHENYL]UREA4x3jAI980 F983
QQ12-[3-(CYCLOHEXYLMETHYL)-5-PHENYL-IMIDAZOL-4-YL]-[1,3]THIAZOLO[4,5-E]PYRIMIDIN-7-AMINE2wqbAV838 F983
RAJN-{3-[3-(DIMETHYLAMINO)PROPYL]-5-(TRIFLUOROMETHYL)PHENYL}-4-METHYL-3-[(3-PYRIMIDIN-4-YLPYRIDIN-2-YL)AMINO]BENZAMIDE2oo8XV838 L879 I980 F983
MUHN-{4-METHYL-3-[(3-PYRIMIDIN-4-YLPYRIDIN-2-YL)AMINO]PHENYL}-3-(TRIFLUOROMETHYL)BENZAMIDE2oscAV838 L879 I980 F983
MR94-METHYL-3-({3-[2-(METHYLAMINO)PYRIMIDIN-4-YL]PYRIDIN-2-YL}OXY)-N-[2-MORPHOLIN-4-YL-5-(TRIFLUOROMETHYL)PHENYL]BENZAMIDE2p4iAV838 L879 I980 F983


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Conservation information for LBS of TEK
Multiple alignments for Q02763 in multiple species
LBSAA sequence# speciesSpecies
A853LRMDAAIKRMK2Homo sapiens, Bos taurus
A853LRMDAAVKRMK1Danio rerio
A905LAIEYAPHGNL2Homo sapiens, Bos taurus
A905LAIEFAPHGNL1Danio rerio
A981YVAKIADFGLS2Homo sapiens, Bos taurus
A981FVAKIADFGLS1Danio rerio
D982VAKIADFGLSR3Homo sapiens, Danio rerio, Bos taurus
E832QDVIGEGNFGQ2Homo sapiens, Bos taurus
E832QDVLGEGNFGQ1Danio rerio
E872RDFAGELEVLC3Homo sapiens, Danio rerio, Bos taurus
E903LYLAIEYAPHG2Homo sapiens, Bos taurus
E903LYLAIEFAPHG1Danio rerio
F960LSQKQFIHRDL3Homo sapiens, Danio rerio, Bos taurus
F983AKIADFGLSRG3Homo sapiens, Danio rerio, Bos taurus
G831FQDVIGEGNFG2Homo sapiens, Bos taurus
G831FQDVLGEGNFG1Danio rerio
G833DVIGEGNFGQV2Homo sapiens, Bos taurus
G833DVLGEGNFGQV1Danio rerio
G908EYAPHGNLLDF2Homo sapiens, Bos taurus
G908EFAPHGNLLDF1Danio rerio
H962QKQFIHRDLAA3Homo sapiens, Danio rerio, Bos taurus
I830KFQDVIGEGNF2Homo sapiens, Bos taurus
I830QFQDVLGEGNF1Danio rerio
I886HHPNIINLLGA2Homo sapiens, Bos taurus
I886PHKNIIHLLGA1Danio rerio
I902YLYLAIEYAPH2Homo sapiens, Bos taurus
I902YLYLAIEFAPH1Danio rerio
I980NYVAKIADFGL2Homo sapiens, Bos taurus
I980NFVAKIADFGL1Danio rerio
K855MDAAIKRMKEY2Homo sapiens, Bos taurus
K855MDAAVKRMKDY1Danio rerio
L876GELEVLCKLGH2Homo sapiens, Bos taurus
L876GELEVLCRLGP1Danio rerio
L879EVLCKLGHHPN2Homo sapiens, Bos taurus
L879EVLCRLGPHKN1Danio rerio
L900RGYLYLAIEYA2Homo sapiens, Bos taurus
L900RGYLYLAIEFA1Danio rerio
L955RGMDYLSQKQF2Homo sapiens, Bos taurus
L955RGMSYLSQKQF1Danio rerio
L971AARNILVGENY2Homo sapiens, Bos taurus
L971AARNVLVGENF1Danio rerio
N969DLAARNILVGE2Homo sapiens, Bos taurus
N969DLAARNVLVGE1Danio rerio
R968RDLAARNILVG2Homo sapiens, Bos taurus
R968RDLAARNVLVG1Danio rerio
V838GNFGQVLKARI3Homo sapiens, Danio rerio, Bos taurus
V875AGELEVLCKLG2Homo sapiens, Bos taurus
V875AGELEVLCRLG1Danio rerio
Y904YLAIEYAPHGN2Homo sapiens, Bos taurus
Y904YLAIEFAPHGN1Danio rerio


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