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 ADRB2
Gene summary
Basic gene Info.Gene symbolADRB2
Gene nameadrenoceptor beta 2, surface
SynonymsADRB2R|ADRBR|B2AR|BAR|BETA2AR
CytomapUCSC genome browser: 5q31-q32
Type of geneprotein-coding
RefGenesNM_000024.5,
Descriptionadrenergic, beta-2-, receptor, surfaceadrenoceptor beta 2 surfacebeta-2 adrenergic receptorbeta-2 adrenoceptorbeta-2 adrenoreceptorcatecholamine receptor
Modification date20141222
dbXrefs MIM : 109690
HGNC : HGNC
HPRD : 00187
ProteinUniProt: P07550
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_ADRB2
BioGPS: 154
PathwayNCI Pathway Interaction Database: ADRB2
KEGG: ADRB2
REACTOME: ADRB2
Pathway Commons: ADRB2
ContextiHOP: ADRB2
ligand binding site mutation search in PubMed: ADRB2
UCL Cancer Institute: ADRB2
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:0002032desensitization of G-protein coupled receptor protein signaling pathway by arrestin15123695
GO:0006898receptor-mediated endocytosis15123695
GO:0007190activation of adenylate cyclase activity15123695
GO:0043410positive regulation of MAPK cascade15123695
GO:0071875adrenergic receptor signaling pathway15123695


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Ligand binding site mutations for ADRB2
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
W109F108LCOAD1
V117V117ICOAD1
N293V292ILUSC1
N312L311RSKCM1
Q65R63HSTAD1
W109E107KSTAD1
W99T100ASTAD1
A85A85ESTAD1
I112,T110S111FUCEC1
M40V39AUCEC1
W99T100AUCEC1
V117T118MUCEC1
L339L339RUCEC1
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 ADRB2
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
Q65R63H-1.5228453
N312L311R-1.3202568
W99T100A-1.3095162
L339L339R-1.2369243
W109E107K-1.0476117
V117V117I-1.0442651
N293V292I-0.84350513
M40V39A-0.82501167
W109F108L-0.77127295
T110S111F-0.29311042
I112S111F-0.29311042
A85A85E-0.20497766
V117T118M-0.16038146
(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 ADRB2 from PDB

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Differential gene expression and gene-gene network for ADRB2
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 ADRB2 and the right PPI network was created from samples without mutations in the LBS of ADRB2. 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 ADRB2
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0004096Asthma197AlteredExpression, Biomarker, GeneticVariation
umls:C0028754Obesity79Biomarker, GeneticVariation
umls:C0007193Cardiomyopathy, Dilated9Biomarker, GeneticVariation
umls:C0021655Insulin Resistance6Biomarker, GeneticVariation
umls:C0151744Myocardial Ischemia5Biomarker, GeneticVariation
umls:C0040822Tremor5Biomarker, GeneticVariation, Therapeutic
umls:C0020621Hypokalemia3Biomarker, GeneticVariation
umls:C0004352Autistic Disorder2Biomarker, GeneticVariation
umls:C0020473Hyperlipidemias2Biomarker, GeneticVariation
umls:C0033578Prostatic Neoplasms1AlteredExpression, Biomarker
umls:C0024115Lung Diseases1Biomarker
umls:C0027765Nervous System Diseases1Biomarker
umls:C0031117Peripheral Nervous System Diseases1Biomarker
umls:C0038356Stomach Neoplasms1Biomarker

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

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Pharmacological information for ADRB2
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
ApprovedDB00195BetaxololSmall molecule
ApprovedDB00221IsoetarineSmall molecule
ApprovedDB00248CabergolineSmall molecule
Approved|investigationalDB00264MetoprololSmall molecule
ApprovedDB00335AtenololSmall molecule
ApprovedDB00368NorepinephrineSmall molecule
ApprovedDB00370MirtazapineSmall molecule
ApprovedDB00373TimololSmall molecule
Approved|vet_approved|withdrawnDB00397PhenylpropanolamineSmall molecule
ApprovedDB00449DipivefrinSmall molecule
ApprovedDB00489SotalolSmall molecule
ApprovedDB00521CarteololSmall molecule
Approved|investigationalDB00571PropranololSmall molecule
ApprovedDB00598LabetalolSmall molecule
ApprovedDB00612BisoprololSmall molecule
Approved|vet_approvedDB00668EpinephrineSmall molecule
ApprovedDB00816OrciprenalineSmall molecule
ApprovedDB00841DobutamineSmall molecule
ApprovedDB00852PseudoephedrineSmall molecule
Approved|withdrawnDB00866AlprenololSmall molecule
ApprovedDB00867RitodrineSmall molecule
ApprovedDB00871TerbutalineSmall molecule
WithdrawnDB00901BitolterolSmall molecule
ApprovedDB00925PhenoxybenzamineSmall molecule
ApprovedDB00938SalmeterolSmall molecule
ApprovedDB00960PindololSmall molecule
Approved|investigationalDB00983FormoterolSmall molecule
Approved|vet_approvedDB01001SalbutamolSmall molecule
ApprovedDB01064IsoprenalineSmall molecule
ApprovedDB01102ArbutamineSmall molecule
Approved|investigationalDB01136CarvedilolSmall molecule
ApprovedDB01151DesipramineSmall molecule
ApprovedDB01193AcebutololSmall molecule
ApprovedDB01203NadololSmall molecule
ApprovedDB01210LevobunololSmall molecule
ApprovedDB01214MetipranololSmall molecule
Approved|investigationalDB01274ArformoterolSmall molecule
ApprovedDB01288FenoterolSmall molecule
ApprovedDB01291PirbuterolSmall molecule
ApprovedDB01295BevantololSmall molecule
Approved|investigationalDB01359PenbutololSmall molecule
Approved|nutraceutical|withdrawnDB01363EphedraSmall molecule
ApprovedDB01366ProcaterolSmall molecule
Approved|vet_approvedDB01407ClenbuterolSmall molecule
ApprovedDB01408BambuterolSmall molecule
ApprovedDB01580OxprenololSmall molecule
Approved|investigationalDB04846CeliprololSmall molecule
Approved|investigationalDB04861NebivololSmall molecule
ApprovedDB05039IndacaterolSmall molecule
InvestigationalDB05849NCX 950Small molecule
ApprovedDB06216AsenapineSmall molecule
Approved|investigationalDB06262DroxidopaSmall molecule
ExperimentalDB07543(2S)-1-(9H-Carbazol-4-yloxy)-3-(isopropylamino)propan-2-olSmall molecule
ApprovedDB08807BopindololSmall molecule
ApprovedDB08808BupranololSmall molecule
ApprovedDB09080OlodaterolSmall molecule
ApprovedDB09082VilanterolSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of ADRB2 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
CLRCHOLESTEROL3d4sAA85
CLRCHOLESTEROL3ny8AA85
CLRCHOLESTEROL3ny9AA85
CLRCHOLESTEROL5d5aAA85
CLRCHOLESTEROL5d5bAA85
CLRCHOLESTEROL2rh1AI112
CLRCHOLESTEROL3ny9AI112
CLRCHOLESTEROL2rh1AL339
CLRCHOLESTEROL5d5aAL339
CLRCHOLESTEROL5d5bAL339
CLRCHOLESTEROL3pdsAQ65
JRZ(2S,3S)-1-[(7-METHYL-2,3-DIHYDRO-1H-INDEN-4-YL)OXY]-3-[(1-METHYLETHYL)AMINO]BUTAN-2-OL3ny8AV117 N293 N312
CAU(S)-CARAZOLOL5d5aAV117 N293 N312
CAU(S)-CARAZOLOL5d5bAV117 N293 N312
CAU(S)-CARAZOLOL2rh1AW109 N293 N312
TIM(S)-TIMOLOL (ANHYDROUS)3d4sAW109 T110 V117 N293 N312
JSZETHYL 4-({(2S)-2-HYDROXY-3-[(1-METHYLETHYL)AMINO]PROPYL}OXY)-3-METHYL-1-BENZOFURAN-2-CARBOXYLATE3ny9AW109 T110 V117 N293 N312
JTZ(2S)-1-[(1-METHYLETHYL)AMINO]-3-(2-PROP-2-EN-1-YLPHENOXY)PROPAN-2-OL3nyaAW109 T110 V117 N293 N312
CAU(S)-CARAZOLOL4gbrAW109 V117
ERC8-HYDROXY-5-[(1R)-1-HYDROXY-2-({2-[3-METHOXY-4-(3-SULFANYLPROPOXY)PHENYL]ETHYL}AMINO)ETHYL]QUINOLIN-2(1H)-ONE3pdsAW99 W109 N293 N312


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Conservation information for LBS of ADRB2
Multiple alignments for P07550 in multiple species
LBSAA sequence# speciesSpecies
A200TNQAYAIASSI4Homo sapiens, Mus musculus, Canis lupus familiaris, Macaca mulatta
A200VNKYYAVISSS1Drosophila melanogaster
A200TNQPYAIASSI1Bos taurus
A85LVMGLAVVPFG5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
A85IMVAIMAMTFN1Drosophila melanogaster
C191AKETCCDFFTN3Bos taurus, Canis lupus familiaris, Macaca mulatta
C191ANETCCDFFTN1Homo sapiens
C191QNPTQCSFVVN1Drosophila melanogaster
C191TEETCCDFFTN1Mus musculus
C77ITSLACADLVM4Homo sapiens, Bos taurus, Canis lupus familiaris, Macaca mulatta
C77VVSLAMADIMV1Drosophila melanogaster
C77IISLACADLVM1Mus musculus
D113FWTSIDVLCVT5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
D113LWNSLDVYFST1Drosophila melanogaster
D192KETCCDFFTNQ3Bos taurus, Canis lupus familiaris, Macaca mulatta
D192NETCCDFFTNQ1Homo sapiens
D192NPTQCSFVVNK1Drosophila melanogaster
D192EETCCDFFTNQ1Mus musculus
E306NLIPKEVYILL3Mus musculus, Canis lupus familiaris, Macaca mulatta
E306NLIRKEVYILL1Homo sapiens
E306CQVPDIVVSIL1Drosophila melanogaster
E306NLIRKEIYILL1Bos taurus
F193ETCCDFFTNQA4Homo sapiens, Mus musculus, Canis lupus familiaris, Macaca mulatta
F193PTQCSFVVNKY1Drosophila melanogaster
F193ETCCDFFTNQP1Bos taurus
F289LCWLPFFIVNI5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
F289LCWLPFFLWYT1Drosophila melanogaster
F290CWLPFFIVNIV5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
F290CWLPFFLWYTL1Drosophila melanogaster
F49VLAIVFGNVLV5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
F49IIAAICGNLLV1Drosophila melanogaster
I112EFWTSIDVLCV5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
I112DLWNSLDVYFS1Drosophila melanogaster
I154KARVVILMVWI3Mus musculus, Bos taurus, Canis lupus familiaris
I154KARVIILMVWI2Homo sapiens, Macaca mulatta
I154VVGIMLLNTWI1Drosophila melanogaster
I309PKEVYILLNWV2Canis lupus familiaris, Macaca mulatta
I309RKEVYILLNWI1Homo sapiens
I309PDIVVSILFWI1Drosophila melanogaster
I309PKEVYILLNWL1Mus musculus
I309RKEIYILLNWL1Bos taurus
I43IVMSLIVLAIV3Homo sapiens, Canis lupus familiaris, Macaca mulatta
I43FVMLLIIIAAI1Drosophila melanogaster
I43ILMSVIVLAIV1Mus musculus
I43ILMSLIVLAIV1Bos taurus
I55GNVLVITAIAK4Homo sapiens, Mus musculus, Bos taurus, Macaca mulatta
I55GNLLVIISVMR1Drosophila melanogaster
I55GNVLVITAIAR1Canis lupus familiaris
L115TSIDVLCVTAS5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
L115NSLDVYFSTAS1Drosophila melanogaster
L155ARVVILMVWIV3Mus musculus, Bos taurus, Canis lupus familiaris
L155ARVIILMVWIV2Homo sapiens, Macaca mulatta
L155VGIMLLNTWIS1Drosophila melanogaster
L339AFQE-LLCLRR5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
L339AFRNTLLCLF-1Drosophila melanogaster
L45MSLIVLAIVFG4Homo sapiens, Bos taurus, Canis lupus familiaris, Macaca mulatta
L45MLLIIIAAICG1Drosophila melanogaster
L45MSVIVLAIVFG1Mus musculus
L53VFGNVLVITAI5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
L53ICGNLLVIISV1Drosophila melanogaster
L80LACADLVMGLA5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
L80LAMADIMVAIM1Drosophila melanogaster
L84DLVMGLAVVPF5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
L84DIMVAIMAMTF1Drosophila melanogaster
M40--GIVMSLIVL3Homo sapiens, Canis lupus familiaris, Macaca mulatta
M40FKAFVMLLIII1Drosophila melanogaster
M40--AILMSVIVL1Mus musculus
M40--GILMSLIVL1Bos taurus
N293PFFIVNIVHV-5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
N293PFFLWYTLSMT1Drosophila melanogaster
N312VYILLNWVGYV2Canis lupus familiaris, Macaca mulatta
N312VYILLNWIGYV1Homo sapiens
N312VVSILFWIGYF1Drosophila melanogaster
N312VYILLNWLGYV1Mus musculus
N312IYILLNWLGYI1Bos taurus
Q65KFERLQTVTNY4Homo sapiens, Mus musculus, Bos taurus, Macaca mulatta
Q65RVRKLRVITNY1Drosophila melanogaster
Q65RFERLQTVTNY1Canis lupus familiaris
R151TKNKARVVILM3Mus musculus, Bos taurus, Canis lupus familiaris
R151TKNKARVIILM2Homo sapiens, Macaca mulatta
R151TKRVVGIMLLN1Drosophila melanogaster
S203AYAIASSIVSF4Homo sapiens, Mus musculus, Canis lupus familiaris, Macaca mulatta
S203YYAVISSSISF1Drosophila melanogaster
S203PYAIASSIVSF1Bos taurus
S207ASSIVSFYVPL3Homo sapiens, Mus musculus, Macaca mulatta
S207ASSIVSFYLPL2Bos taurus, Canis lupus familiaris
S207ISSSISFWIPC1Drosophila melanogaster
S74NYFITSLACAD4Homo sapiens, Bos taurus, Canis lupus familiaris, Macaca mulatta
S74NYFVVSLAMAD1Drosophila melanogaster
S74NYFIISLACAD1Mus musculus
T110WCEFWTSIDVL5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
T110LCDLWNSLDVY1Drosophila melanogaster
T73TNYFITSLACA4Homo sapiens, Bos taurus, Canis lupus familiaris, Macaca mulatta
T73TNYFVVSLAMA1Drosophila melanogaster
T73TNYFIISLACA1Mus musculus
V114WTSIDVLCVTA5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
V114WNSLDVYFSTA1Drosophila melanogaster
V117IDVLCVTASIE5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
V117LDVYFSTASIL1Drosophila melanogaster
V52IVFGNVLVITA5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
V52AICGNLLVIIS1Drosophila melanogaster
V81ACADLVMGLAV5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
V81AMADIMVAIMA1Drosophila melanogaster
W109FWCEFWTSIDV5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
W109FLCDLWNSLDV1Drosophila melanogaster
W158VILMVWIVSGL3Mus musculus, Bos taurus, Canis lupus familiaris
W158IILMVWIVSGL2Homo sapiens, Macaca mulatta
W158MLLNTWISPAL1Drosophila melanogaster
W286TFTLCWLPFFI5Homo sapiens, Mus musculus, Bos taurus, Canis lupus familiaris, Macaca mulatta
W286TFILCWLPFFL1Drosophila melanogaster
W313YILLNWVGYVN2Canis lupus familiaris, Macaca mulatta
W313YILLNWIGYVN1Homo sapiens
W313VSILFWIGYFN1Drosophila melanogaster
W313YILLNWLGYVN1Mus musculus
W313YILLNWLGYIN1Bos taurus
W99ILMKMWTFGNF4Homo sapiens, Bos taurus, Canis lupus familiaris, Macaca mulatta
W99QVTGRWNFSPF1Drosophila melanogaster
W99ILMKMWNFGNF1Mus musculus
Y199FTNQAYAIASS4Homo sapiens, Mus musculus, Canis lupus familiaris, Macaca mulatta
Y199VVNKYYAVISS1Drosophila melanogaster
Y199FTNQPYAIASS1Bos taurus
Y308IPKEVYILLNW3Mus musculus, Canis lupus familiaris, Macaca mulatta
Y308IRKEVYILLNW1Homo sapiens
Y308VPDIVVSILFW1Drosophila melanogaster
Y308IRKEIYILLNW1Bos taurus
Y316LNWIGYVNSGF1Homo sapiens
Y316LFWIGYFNSTL1Drosophila melanogaster
Y316LNWLGYVNSAF1Mus musculus
Y316LNWLGYINSAF1Bos taurus
Y316LNWVGYVNSAF1Canis lupus familiaris
Y316LNWVGYVNSGF1Macaca mulatta
Y70QTVTNYFITSL4Homo sapiens, Bos taurus, Canis lupus familiaris, Macaca mulatta
Y70RVITNYFVVSL1Drosophila melanogaster
Y70QTVTNYFIISL1Mus musculus


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