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 FES

Gene summary

Basic gene Info.	Gene symbol	FES
	Gene name	FES proto-oncogene, tyrosine kinase
	Synonyms	FPS
	Cytomap	UCSC genome browser: 15q26.1
	Type of gene	protein-coding
	RefGenes	NM_001143783.1, NM_001143784.1,NM_001143785.1,NM_002005.3,
	Description	Oncogene FES, feline sarcoma virusfeline sarcoma (Snyder-Theilen) viral (v-fes)/Fujinami avian sarcoma (PRCII) viral (v-fps) oncogene homologfeline sarcoma oncogenefeline sarcoma/Fujinami avian sarcoma oncogene homologp93c-fesproto-oncogene c-Fespro
	Modification date	20141207
dbXrefs	MIM : 190030
	HGNC : HGNC
	Ensembl : ENSG00000182511
	HPRD : 01814
	Vega : OTTHUMG00000044456
Protein	UniProt: P07332 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_FES
	BioGPS: 2242
Pathway	NCI Pathway Interaction Database: FES
	KEGG: FES
	REACTOME: FES
	Pathway Commons: FES
Context	iHOP: FES
	ligand binding site mutation search in PubMed: FES
	UCL Cancer Institute: FES
Assigned class in mutLBSgeneDB	B: This gene belongs to targetable_mutLBSgenes.

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez

GO ID	GO Term	PubMed ID
GO:0018108	peptidyl-tyrosine phosphorylation	11509660
GO:0046777	protein autophosphorylation	7687763

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Ligand binding site mutations for FES

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

LBS	AAchange of nsSNV	Cancer type	# samples
A588	A588V	UCEC	2
I623	V625F	BRCA	1
D683	D683E	BRCA	1
D583,R581	A582V	SKCM	1
R621	R621H	STAD	1
L580	R579C	STAD	1
R770	F772L	UCEC	1

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 FES

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.

LBS	AAchange of nsSNV	Relative stability change
I623	V625F	-1.3028543
R621	R621H	-1.1551207
R770	F772L	-0.96850659
L580	R579C	-0.81414284
R581	A582V	-0.7526059
D583	A582V	-0.7526059
A588	A588V	-0.48406414
D683	D683E	-0.11604934

(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 FES from PDB

PDB ID	PDB title	PDB structure
3BKB	Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)

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Differential gene expression and gene-gene network for FES

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 FES and the right PPI network was created from samples without mutations in the LBS of FES. 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 FES

Gene level disease information (DisGeNet)

Disease ID

Disease name

# PubMed

Association type

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for FES

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 status

DrugBank ID

Name

Type

Drug structure

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of FES go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
STU		STAUROSPORINE	3bkb	A	A588
STU		STAUROSPORINE	3cbl	A	A588
STU		STAUROSPORINE	3cd3	A	A588
GUI		S1108_SELLECK	4e93	A	A588
STU		STAUROSPORINE	3cd3	A	D583 R621 I623
III		Peptide ligand (ACE,ILE,TYR,GLU,SER,LEU)	3cbl	A	D683
III		Peptide ligand (ACE,ILE,TYR,GLU,SER,LEU)	3cd3	A	D683 R770
STU		STAUROSPORINE	3cbl	A	L580 D583 R621 I623
STU		STAUROSPORINE	3cbl	A	R581
STU		STAUROSPORINE	3cd3	A	R581

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Conservation information for LBS of FES

Multiple alignments for P07332 in multiple species

LBS

AA sequence

# species

Species