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 TYK2
Gene summary
Basic gene Info.Gene symbolTYK2
Gene nametyrosine kinase 2
SynonymsIMD35|JTK1
CytomapUCSC genome browser: 19p13.2
Type of geneprotein-coding
RefGenesNM_003331.4,
Descriptionnon-receptor tyrosine-protein kinase TYK2
Modification date20141221
dbXrefs MIM : 176941
HGNC : HGNC
Ensembl : ENSG00000105397
HPRD : 01490
Vega : OTTHUMG00000166373
ProteinUniProt: P29597
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_TYK2
BioGPS: 7297
PathwayNCI Pathway Interaction Database: TYK2
KEGG: TYK2
REACTOME: TYK2
Pathway Commons: TYK2
ContextiHOP: TYK2
ligand binding site mutation search in PubMed: TYK2
UCL Cancer Institute: TYK2
Assigned class in mutLBSgeneDBA: This gene has a literature evidence and it belongs to targetable_mutLBSgenes.
References showing study about ligand binding site mutation for TYK2.1. "Staerk J, Kallin A, Royer Y, Diaconu CC, Dusa A, Demoulin JB, Vainchenker W,Constantinescu SN. JAK2, the JAK2 V617F mutant and cytokine receptors. Pathol Biol (Paris). 2007 Mar;55(2):88-91. Epub 2006 Aug 14" 16904848
2. "Gakovic M, Ragimbeau J, Francois V, Constantinescu SN, Pellegrini S. The Stat3-activating Tyk2 V678F mutant does not up-regulate signaling through the type I interferon receptor but confers ligand hypersensitivity to a homodimeric receptor. J Biol Chem. 2008 Jul 4;283(27):18522-9. doi: 10.1074/jbc.M801427200. Epub 2008 May 2." 18456658

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 TYK2
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
N734H732RCOAD1
R503R501WGBM1
C536G535DHNSC1
D1041D1041AKIRC1
R521S522FSKCM1
K930,A928V929MUCEC1
G906,F908H907NUCEC1
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 TYK2
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
R521S522F0.2181314
D1041D1041A-0.92266415
G906H907N-0.86186515
F908H907N-0.86186515
A928V929M-0.81962878
K930V929M-0.81962878
R503R501W-0.80277644
N734H732R-0.4757276
C536G535D-0.21016693
(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 TYK2 from PDB

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Differential gene expression and gene-gene network for TYK2
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 TYK2 and the right PPI network was created from samples without mutations in the LBS of TYK2. 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 TYK2
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0026769Multiple Sclerosis8Biomarker, GeneticVariation
umls:C0033860Psoriasis4Biomarker, GeneticVariation
umls:C0010346Crohn Disease3Biomarker, GeneticVariation
umls:C0003873Arthritis, Rheumatoid3Biomarker, GeneticVariation
umls:C1969086Tyrosine Kinase 2 Deficiency1Biomarker, GeneticVariation
umls:C0236736Cocaine-Related Disorders1Biomarker
umls:C0023892Liver Cirrhosis, Biliary1Biomarker
umls:C1456784Paranoid Disorders1Biomarker

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

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Pharmacological information for TYK2
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
ExperimentalDB047162-(1,1-DIMETHYLETHYL)9-FLUORO-3,6-DIHYDRO-7H-BENZ[H]-IMIDAZ[4,5-F]ISOQUINOLIN-7-ONESmall molecule
ExperimentalDB081833-{(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl}-3-oxopropanenitrileSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of TYK2 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
5U33-AZANYL-5-[(2~{S})-3-METHYLBUTAN-2-YL]-7-[1-METHYL-5- (2-OXIDANYLPROPAN-2-YL)PYRAZOL-3-YL]-1~{H}-PYRAZOLO[4, 3-C]PYRIDIN-4-ONE5f1zAA928
0X62,6-DICHLORO-4-CYANO-N-{2-[(CYCLOPROPYLCARBONYL) AMINO]PYRIDIN-4-YL}BENZAMIDE4giiAA928 D1041
0XH2,6-DICHLORO-N-[2-({[(1R,2R)-2- FLUOROCYCLOPROPYL]CARBONYL}AMINO)PYRIDIN-4- YL]BENZAMIDE4gj2AA928 D1041
0XP2,6-DICHLORO-4-CYANO-N-[2-({[(1R,2R)-2- FLUOROCYCLOPROPYL]CARBONYL}AMINO)PYRIDIN-4- YL]BENZAMIDE4gj3AA928 D1041
0X52,6-DICHLORO-N-{2-[(CYCLOPROPYLCARBONYL)AMINO]PYRIDIN- 4-YL}BENZAMIDE4gihAA928 D1041
ADPADP4gvjAA928 K930 D1041
2YK6-[(2,5-DIMETHOXYPHENYL)SULFANYL]-3-(1-METHYL-1H- PYRAZOL-4-YL)[1,2,4]TRIAZOLO[4,3-B]PYRIDAZINE4py1AA928 K930 D1041
MGMAGNESIUM(2+)4gvjAD1041
MGMAGNESIUM(2+)4gvjAD1041
TZ1N-{5-[(7-CHLOROQUINOLIN-4-YL)SULFANYL]-1,3,4-THIADIAZOL-2-YL}THIOPHENE-2-CARBOXAMIDE3nyxAF908 A928 K930 D1041
IZA2-(1,1-DIMETHYLETHYL)9-FLUORO-3,6-DIHYDRO-7H-BENZ[H]-IMIDAZ[4,5-F]ISOQUINOLIN-7-ONE3lxpAG906 A928
0X22,6-DICHLORO-N-(2-OXO-2,5-DIHYDROPYRIDIN-4-YL)BENZAMIDE4gfoAG906 A928
IZA2-(1,1-DIMETHYLETHYL)9-FLUORO-3,6-DIHYDRO-7H-BENZ[H]-IMIDAZ[4,5-F]ISOQUINOLIN-7-ONE3nz0AG906 A928 D1041
5U43-AZANYL-5-(2-METHYLPHENYL)-7-(1-METHYLPYRAZOL-3-YL)- 1~{H}-PYRAZOLO[4,3-C]PYRIDIN-4-ONE5f20AG906 A928 D1041
MI1CP-690,5503lxnAG906 A928 K930 D1041
2TT2-CHLORO-N-{2-[(CYCLOPROPYLCARBONYL)AMINO]PYRIDIN-4- YL}BENZAMIDE4oliAG906 D1041
AGSADENOSINE 5'-[GAMMA-THIO]TRIPHOSPHATE5c03AN734
AGSADENOSINE 5'-[GAMMA-THIO]TRIPHOSPHATE5c03BN734
IIIPeptide ligand (ASN,LEU,LEU,LEU,SER,THR,SER,GLU,GLU,GLN,ILE,GLU,LYS,CYS,PHE,ILE,ILE,GLU,ASN)4po6AR503 R521 C536


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Conservation information for LBS of TYK2
Multiple alignments for P29597 in multiple species
LBSAA sequence# speciesSpecies


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