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 ERBB2
Gene summary
Basic gene Info.Gene symbolERBB2
Gene nameerb-b2 receptor tyrosine kinase 2
SynonymsCD340|HER-2|HER-2/neu|HER2|MLN 19|NEU|NGL|TKR1
CytomapUCSC genome browser: 17q12
Type of geneprotein-coding
RefGenesNM_001005862.2,
NM_001289936.1,NM_001289937.1,NM_001289938.1,NM_004448.3,
NR_110535.1,
Descriptionc-erb B2/neu proteinherstatinhuman epidermal growth factor receptor 2metastatic lymph node gene 19 proteinneuro/glioblastoma derived oncogene homologneuroblastoma/glioblastoma derived oncogene homologp185erbB2proto-oncogene Neuproto-oncogene c-Erb
Modification date20141221
dbXrefs MIM : 164870
HGNC : HGNC
Ensembl : ENSG00000141736
HPRD : 01281
Vega : OTTHUMG00000179300
ProteinUniProt: P04626
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_ERBB2
BioGPS: 2064
PathwayNCI Pathway Interaction Database: ERBB2
KEGG: ERBB2
REACTOME: ERBB2
Pathway Commons: ERBB2
ContextiHOP: ERBB2
ligand binding site mutation search in PubMed: ERBB2
UCL Cancer Institute: ERBB2
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 ERBB2.1. "Fan YX, Wong L, Ding J, Spiridonov NA, Johnson RC, Johnson GR. Mutational activation of ErbB2 reveals a new protein kinase autoinhibition mechanism. J Biol Chem. 2008 Jan 18;283(3):1588-96. Epub 2007 Nov 26. PubMed PMID: 18039657. " 18039657

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez
GO IDGO TermPubMed ID
GO:0007165signal transduction10572067
GO:0007166cell surface receptor signaling pathway9685399
GO:0007169transmembrane receptor protein tyrosine kinase signaling pathway7514177
GO:0014065phosphatidylinositol 3-kinase signaling7556068
GO:0018108peptidyl-tyrosine phosphorylation7514177
GO:0032886regulation of microtubule-based process20937854
GO:0042060wound healing12646923
GO:0043406positive regulation of MAP kinase activity10572067
GO:0045785positive regulation of cell adhesion7556068
GO:0045945positive regulation of transcription from RNA polymerase III promoter19372587
GO:0046777protein autophosphorylation7556068
GO:0050679positive regulation of epithelial cell proliferation10572067


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Ligand binding site mutations for ERBB2
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
K753L755SBRCA3
E770D769YBRCA2
V734T733IBLCA1
T862T862ABLCA1
E770D769HBRCA1
K753L755SCOAD1
L796Q795LCOAD1
R784R784LCOAD1
L726K724RCOAD1
Q799Q799HCOAD1
A751V750EGBM1
F1004R1006CHNSC1
K753L755MSKCM1
M774G776VSTAD1
A751A751TUCEC1
K753L755SUCEC1
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 ERBB2 from My Cancer Genome.
HER2 (ERBB2) belongs to a family of receptor tyrosine kinases (RTKs) that includes EGFR/ERBB1, HER2/ERBB2/NEU, HER3/ERBB3, and HER4/ERBB4. The gene for HER2 is located on chromosome 17 and has been found to be amplified with an increased copy number in several cancers (Jorgensen 2010). Amplification of HER2 has been found to promote tumorigenesis and to be involved in the pathogenesis of several human cancers (Moasser 2007).To date, no ligand has been identified for HER2. However, HER2 appears to be the preferential dimerization partner for all members of the ERBB family (Graus-Porta et al. 1997). The binding of ligand followed by HER2 hetero-dimerization results in activation of HER2 tyrosine kinase activity. Activated HER2 then phosphorylates its substrates, leading to activation of multiple downstream pathways within the cell, including the PI3K-AKT-mTOR pathway, which is involved in cell survival, and the RAS-RAF-MEK-ERK pathway, which is involved in cell proliferation. Lovly, C.M., Shi, C., Watson, G.T., Horn, L., Pohlmann, P., Goff, L.W. 2015. HER2 (ERBB2). My Cancer Genome https://www.mycancergenome.org/content/gene/erbb2/ (Updated December 2015).

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Protein structure related information for ERBB2
Protein structure of wild type (WT) and mutant type (MT) of ERBB2
Wild type ERBB2
Mutant type ERBB2

Free energy of binding of drugs to wild type and mutant tpye of ERBB2
Gene symbolDrug nameFree energy of binding (kcal/mol) of wild typeFree energy of binding (kcal/mol) of mutant type
ERBB2Lapatinib-11.4-11.1

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
R784R784L0.20985698
T862T862A-1.7364588
K753L755S-1.388138
K753L755M-1.0520645
M774G776V-0.93522006
Q799Q799H-0.8345374
A751A751T-0.74772883
A751V750E-0.68225134
E770D769H-0.55676888
F1004R1006C-0.37627248
E770D769Y-0.23708856
L726K724R-0.10862045
V734T733I-0.082507785
L796Q795L-0.047896964
(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 ERBB2 from PDB
PDB IDPDB titlePDB structure
2A91Crystal structure of ErbB2 domains 1-3

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Differential gene expression and gene-gene network for ERBB2
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 ERBB2 and the right PPI network was created from samples without mutations in the LBS of ERBB2. 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 ERBB2
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C1458155Breast Neoplasms508AlteredExpression, Biomarker, GeneticVariation, PostTranslationalModification, Therapeutic
umls:C0027627Neoplasm Metastasis334AlteredExpression, Biomarker, GeneticVariation
umls:C0001418Adenocarcinoma202AlteredExpression, Biomarker, GeneticVariation
umls:C0007131Carcinoma, Non-Small-Cell Lung87AlteredExpression, Biomarker, GeneticVariation
umls:C0919267Ovarian Neoplasms54AlteredExpression, Biomarker, GeneticVariation, PostTranslationalModification
umls:C0033578Prostatic Neoplasms24AlteredExpression, Biomarker, GeneticVariation
umls:C0024121Lung Neoplasms21AlteredExpression, Biomarker, GeneticVariation
umls:C0152013Adenocarcinoma of lung21Biomarker, GeneticVariation
umls:C0014859Esophageal Neoplasms17Biomarker, GeneticVariation
umls:C0038356Stomach Neoplasms15AlteredExpression, Biomarker, GeneticVariation
umls:C0007134Carcinoma, Renal Cell14Biomarker
umls:C0017638Glioma13AlteredExpression, Biomarker, GeneticVariation
umls:C0206698Cholangiocarcinoma12AlteredExpression, Biomarker
umls:C0025149Medulloblastoma6AlteredExpression, Biomarker
umls:C0009375Colonic Neoplasms5AlteredExpression, Biomarker
umls:C0024667Mammary Neoplasms, Animal4Biomarker, GeneticVariation
umls:C0030354Papilloma4AlteredExpression, Biomarker
umls:C0024232Lymphatic Metastasis3Biomarker
umls:C2931822Nasopharyngeal carcinoma3Biomarker
umls:C0024668Mammary Neoplasms, Experimental2Biomarker
umls:C0027659Neoplasms, Experimental2Biomarker, GeneticVariation
umls:C0017185Gastrointestinal Neoplasms2Biomarker
umls:C0242656Disease Progression1Biomarker
umls:C0016978Gallbladder Neoplasms1Biomarker
umls:C0027643Neoplasm Recurrence, Local1Biomarker
umls:C0031117Peripheral Nervous System Diseases1Biomarker

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

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Pharmacological information for ERBB2
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|investigationalDB00072TrastuzumabBiotech
Approved|investigationalDB01259LapatinibSmall molecule
InvestigationalDB04988IGN311Biotech
InvestigationalDB05007XL647Small molecule
ApprovedDB05773Trastuzumab emtansineBiotech
ApprovedDB06366PertuzumabBiotech
ApprovedDB08916AfatinibSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of ERBB2 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
03Q2-{2-[4-({5-CHLORO-6-[3-(TRIFLUOROMETHYL)PHENOXY]PYRIDIN-3-YL}AMINO)-5H-PYRROLO[3,2-D]PYRIMIDIN-5-YL]ETHOXY}ETHANOL3pp0AL726 V734 A751 K753 E770 M774 L796 Q799 T862
03Q2-{2-[4-({5-CHLORO-6-[3-(TRIFLUOROMETHYL)PHENOXY]PYRIDIN-3-YL}AMINO)-5H-PYRROLO[3,2-D]PYRIMIDIN-5-YL]ETHOXY}ETHANOL3pp0BL726 V734 A751 K753 E770 M774 L796 Q799 T862 F1004
03PTAK-2853rcdAL726 V734 A751 K753 L796 Q799 T862 F1004
03PTAK-2853rcdCL726 V734 A751 K753 R784 L796 Q799 T862 F1004


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Conservation information for LBS of ERBB2
Multiple alignments for P04626 in multiple species
LBSAA sequence# speciesSpecies


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