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 RIPK2
Gene summary
Basic gene Info.Gene symbolRIPK2
Gene namereceptor-interacting serine-threonine kinase 2
SynonymsCARD3|CARDIAK|CCK|GIG30|RICK|RIP2
CytomapUCSC genome browser: 8q21
Type of geneprotein-coding
RefGenesNM_003821.5,
DescriptionCARD-carrying kinaseCARD-containing IL-1 beta ICE-kinaseCARD-containing interleukin-1 beta-converting enzyme (ICE)-associated kinaseRIP-2growth-inhibiting gene 30receptor-interacting protein (RIP)-like interacting caspase-like apoptosis regulatory pr
Modification date20141222
dbXrefs MIM : 603455
HGNC : HGNC
Ensembl : ENSG00000104312
HPRD : 04585
Vega : OTTHUMG00000163809
ProteinUniProt: O43353
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_RIPK2
BioGPS: 8767
PathwayNCI Pathway Interaction Database: RIPK2
KEGG: RIPK2
REACTOME: RIPK2
Pathway Commons: RIPK2
ContextiHOP: RIPK2
ligand binding site mutation search in PubMed: RIPK2
UCL Cancer Institute: RIPK2
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:0010800positive regulation of peptidyl-threonine phosphorylation21887730
GO:0033138positive regulation of peptidyl-serine phosphorylation21887730
GO:0034134toll-like receptor 2 signaling pathway11894098
GO:0043123positive regulation of I-kappaB kinase/NF-kappaB signaling10329646
GO:0045087innate immune response23806334
GO:0050731positive regulation of peptidyl-tyrosine phosphorylation21887730
GO:0070431nucleotide-binding oligomerization domain containing 2 signaling pathway23806334
GO:0071225cellular response to muramyl dipeptide21887730


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Ligand binding site mutations for RIPK2
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
A73A73DCOAD1
F165G166CLUSC1
N151N151KSKCM1
I93I93TUCEC1
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 RIPK2
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
I93I93T-1.4244304
A73A73D-1.0574703
F165G166C-0.42959724
N151N151K-0.27185032
(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 RIPK2 from PDB

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Differential gene expression and gene-gene network for RIPK2
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 RIPK2 and the right PPI network was created from samples without mutations in the LBS of RIPK2. 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 RIPK2
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0009324Colitis, Ulcerative1Biomarker

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

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Pharmacological information for RIPK2
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

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of RIPK2 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
SR81-(5-(TERT-BUTYL)ISOXAZOL-3-YL)-3-(4- (PYRIDIN-4-YLOXY)5ar7AA73 F165
SR81-(5-(TERT-BUTYL)ISOXAZOL-3-YL)-3-(4- (PYRIDIN-4-YLOXY)5ar7BA73 F165
0LIPONATINIB4c8bBF165
SB24-[5-(4-FLUORO-PHENYL)-2-(4-METHANESULFINYL-PHENYL)-3H-IMIDAZOL-4-YL]-PYRIDINE5ar4AI93
SB24-[5-(4-FLUORO-PHENYL)-2-(4-METHANESULFINYL-PHENYL)-3H-IMIDAZOL-4-YL]-PYRIDINE5ar4BI93
IQ72-(2-(4-CHLOROPHENYL)-1H-IMIDAZOL-5-YL)-N,1- BIS(2-METHOXYETHYL)-1H-BENZO[D]IMIDAZOLE-5- CARBOXAMIDE5ar5AI93
IQ72-(2-(4-CHLOROPHENYL)-1H-IMIDAZOL-5-YL)-N,1- BIS(2-METHOXYETHYL)-1H-BENZO[D]IMIDAZOLE-5- CARBOXAMIDE5ar5BI93
0LIPONATINIB4c8bAI93 F165
XYW2,6-BIS(FLUORANYL)-N-[3-[5-[2-[(3- METHYLSULFONYLPHENYL)AMINO]PYRIMIDIN-4-YL]-2-MORPHOLIN 4-YL-1,3-THIAZOL-4-YL]PHENYL] BENZENESULFONAMIDE5ar8AI93 F165
XYW2,6-BIS(FLUORANYL)-N-[3-[5-[2-[(3- METHYLSULFONYLPHENYL)AMINO]PYRIMIDIN-4-YL]-2-MORPHOLIN 4-YL-1,3-THIAZOL-4-YL]PHENYL] BENZENESULFONAMIDE5ar8BI93 F165
ACPADENOSINE 5'-[BETA,GAMMA-METHYLENE]TRIPHOSPHATE5ar3AN151
MGMAGNESIUM(2+)5ar3AN151
ACPADENOSINE 5'-[BETA,GAMMA-METHYLENE]TRIPHOSPHATE5ar3BN151
MGMAGNESIUM(2+)5ar3BN151


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Conservation information for LBS of RIPK2
Multiple alignments for O43353 in multiple species
LBSAA sequence# speciesSpecies
A163FHVKIADFGLS3Homo sapiens, Mus musculus, Bos taurus
A28YLSRGASGTVS3Homo sapiens, Mus musculus, Bos taurus
A45WRVQVAVKHLH2Homo sapiens, Bos taurus
A45WRVRVAVKHLH1Mus musculus
A73EILHKARFSYI3Homo sapiens, Mus musculus, Bos taurus
D164HVKIADFGLSK3Homo sapiens, Mus musculus, Bos taurus
E105NGSLNELLHRK3Homo sapiens, Mus musculus, Bos taurus
E112LHRKTEYPDVA1Homo sapiens
E112LHRKTEYPDIA1Mus musculus
E112LHRKIEYPDVP1Bos taurus
E66KDVLREAEILH1Homo sapiens
E66NDILREAEILH1Mus musculus
E66NDVLREAEILH1Bos taurus
E96LGIVTEYMPNG3Homo sapiens, Mus musculus, Bos taurus
F165VKIADFGLSKW3Homo sapiens, Mus musculus, Bos taurus
G101EYMPNGSLNEL3Homo sapiens, Mus musculus, Bos taurus
G27RYLSRGASGTV2Homo sapiens, Bos taurus
G27HYLSRGASGTV1Mus musculus
G30SRGASGTVSSA3Homo sapiens, Mus musculus, Bos taurus
H144NPPLLHHDLKT2Mus musculus, Bos taurus
H144TPPLLHHDLKT1Homo sapiens
I162EFHVKIADFGL3Homo sapiens, Mus musculus, Bos taurus
I69LREAEILHKAR3Homo sapiens, Mus musculus, Bos taurus
I78ARFSYILPILG3Homo sapiens, Mus musculus, Bos taurus
I81SYILPILGICN3Homo sapiens, Mus musculus, Bos taurus
I93PEFLGIVTEYM3Homo sapiens, Mus musculus, Bos taurus
K47VQVAVKHLHIH2Homo sapiens, Bos taurus
K47VRVAVKHLHIH1Mus musculus
L143MNPPLLHHDLK2Mus musculus, Bos taurus
L143MTPPLLHHDLK1Homo sapiens
L153KTQNILLDNEF3Homo sapiens, Mus musculus, Bos taurus
L24ADLRYLSRGAS2Homo sapiens, Bos taurus
L24ADLHYLSRGAS1Mus musculus
L70REAEILHKARF3Homo sapiens, Mus musculus, Bos taurus
L79RFSYILPILGI3Homo sapiens, Mus musculus, Bos taurus
M98IVTEYMPNGSL3Homo sapiens, Mus musculus, Bos taurus
N151DLKTQNILLDN3Homo sapiens, Mus musculus, Bos taurus
P114RKTEYPDVAWP1Homo sapiens
P114RKTEYPDIAWP1Mus musculus
P114RKIEYPDVPWP1Bos taurus
Q150HDLKTQNILLD3Homo sapiens, Mus musculus, Bos taurus
R22KLADLRYLSRG2Homo sapiens, Bos taurus
R22KLADLHYLSRG1Mus musculus
R26LRYLSRGASGT2Homo sapiens, Bos taurus
R26LHYLSRGASGT1Mus musculus
S25DLRYLSRGASG2Homo sapiens, Bos taurus
S25DLHYLSRGASG1Mus musculus
S29LSRGASGTVSS3Homo sapiens, Mus musculus, Bos taurus
T95FLGIVTEYMPN3Homo sapiens, Mus musculus, Bos taurus
V32GASGTVSSARH3Homo sapiens, Mus musculus, Bos taurus
V46RVQVAVKHLHI2Homo sapiens, Bos taurus
V46RVRVAVKHLHI1Mus musculus
Y23LADLRYLSRGA2Homo sapiens, Bos taurus
Y23LADLHYLSRGA1Mus musculus
Y97GIVTEYMPNGS3Homo sapiens, Mus musculus, Bos taurus


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