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 FYN
Gene summary
Basic gene Info.Gene symbolFYN
Gene nameFYN proto-oncogene, Src family tyrosine kinase
SynonymsSLK|SYN|p59-FYN
CytomapUCSC genome browser: 6q21
Type of geneprotein-coding
RefGenesNM_002037.5,
NM_153047.3,NM_153048.3,NM_001242779.1,
DescriptionFYN oncogene related to SRC, FGR, YESOKT3-induced calcium influx regulatorc-syn protooncogeneproto-oncogene Synproto-oncogene c-Fynsrc-like kinasesrc/yes-related noveltyrosine kinase p59fyn(T)tyrosine-protein kinase Fyn
Modification date20141207
dbXrefs MIM : 137025
HGNC : HGNC
Ensembl : ENSG00000010810
HPRD : 00655
Vega : OTTHUMG00000016305
ProteinUniProt: P06241
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_FYN
BioGPS: 2534
PathwayNCI Pathway Interaction Database: FYN
KEGG: FYN
REACTOME: FYN
Pathway Commons: FYN
ContextiHOP: FYN
ligand binding site mutation search in PubMed: FYN
UCL Cancer Institute: FYN
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 FYN.1. "Fernandez-Ballester G, Blanes-Mira C, Serrano L. The tryptophan switch:changing ligand-binding specificity from type I to type II in SH3 domains. J Mol Biol. 2004 Jan 9;335(2):619-29. PubMed PMID: 14672668. " 14672668
2. "Panchamoorthy G, Fukazawa T, Stolz L, Payne G, Reedquist K, Shoelson S, Songyang Z, Cantley L, Walsh C, Band H. Physical and functional interactions between SH2 and SH3 domains of the Src family protein tyrosine kinase p59fyn. Mol Cell Biol. 1994 Sep;14(9):6372-85. PubMed PMID: 7520528; PubMed Central PMCID: PMC359163. " 7520528

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez
GO IDGO TermPubMed ID
GO:0050852T cell receptor signaling pathway7722293


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Ligand binding site mutations for FYN
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
K204R206CCOAD3
H104F103LHNSC1
G348K347NHNSC1
H104H104YHNSC1
D408A407VKIRC1
R96R96QLUAD1
G348G348VLUAD1
H104K105NLUSC1
A394R392QSTAD1
L397L397IUCEC1
R176,S178E177GUCEC1
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 FYN from My Cancer Genome.
FYN proto-oncogene, Src family tyrosine kinase (FYN) is a gene that encodes a protein that functions as a membrane-associated tyrosine kinase that regulates cell growth. Missense mutations, nonsense mutations, silent mutations, and frameshift insertions are observed in cancers such as intestinal cancer, skin cancer, and stomach cancer.Modified: July 1, 2015

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Protein structure related information for FYN
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
G348G348V0.21925768
L397L397I-1.3178546
A394R392Q-1.3120438
S178E177G-1.3029461
R176E177G-1.3029461
R96R96Q-1.1716163
H104H104Y-1.1590147
K204R206C-1.1350457
D408A407V-1.1107899
H104F103L-0.63849164
G348K347N-0.32359769
H104K105N-0.17321995
(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 FYN from PDB
PDB IDPDB titlePDB structure
1AOTNMR STRUCTURE OF THE FYN SH2 DOMAIN COMPLEXED WITH A PHOSPHOTYROSYL PEPTIDE, MINIMIZED AVERAGE STRUCTURE

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Differential gene expression and gene-gene network for FYN
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 FYN and the right PPI network was created from samples without mutations in the LBS of FYN. 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 FYN
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0079774Lymphoma, T-Cell, Peripheral1Biomarker
umls:C0007370Catalepsy1Biomarker
umls:C0038356Stomach Neoplasms1Biomarker

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

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Pharmacological information for FYN
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|investigationalDB01254DasatinibSmall molecule
ExperimentalDB020781-Methoxy-2-[2-(2-Methoxy-Ethoxy]-EthaneSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of FYN go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
ZNZINC(2+)3ua7CH104
ZNZINC(2+)3ua7DH104
IIIPeptide ligand (GLU,PRO,GLN,TYR,GLN,PRO,GLY,GLU,ASN,LEU)2mrkAR176 S178 K204
IIIPeptide ligand (PRO,PRO,ALA,TYR,PRO,PRO,PRO,PRO,VAL,PRO)1fynAR96
IIIPeptide ligand (ACE,ALA,PRO,PRO,ILE,PRO,PRO,PRO,ARG)3ua7AR96


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Conservation information for LBS of FYN
Multiple alignments for P06241 in multiple species
LBSAA sequence# speciesSpecies
A297GNTKVAIKTLK5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
A297GIVEVAIKTMK1Caenorhabditis elegans
A394RDLRSANILVG5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
A394RDLAARNVLVG1Caenorhabditis elegans
D100ARTEDDLSFHK4Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus
D100SRADGDLSFQK1Caenorhabditis elegans
D100ARTEDDLSFRK1Danio rerio
D118NSSEGDWWEAR4Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus
D118DHSNCDWWYVR1Caenorhabditis elegans
D118NSTEGDWWDAR1Danio rerio
D408ICKIADFGLAR4Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus
D408VVKVADFGLAR1Caenorhabditis elegans
D408VCKIADFGLAR1Danio rerio
D99EARTEDDLSFH4Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus
D99DSRADGDLSFQ1Caenorhabditis elegans
D99EARTEDDLSFR1Danio rerio
E107SFHKGEKFQIL4Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus
E107SFQKGDAMYLL1Caenorhabditis elegans
E107SFRKGEKFQII1Danio rerio
E116ILNSSEGDWWE4Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus
E116LLDHSNCDWWY1Caenorhabditis elegans
E116IINSTEGDWWD1Danio rerio
E179LIRESETTKGA5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
E179LIREREADTRE1Caenorhabditis elegans
E343IYIVTEYMNKG3Homo sapiens, Bos taurus, Rattus norvegicus
E343FYIITEYMING1Caenorhabditis elegans
E343IYIVTEYMGKG1Danio rerio
E343IYIVTEYMSKG1Mus musculus
G117LNSSEGDWWEA4Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus
G117LDHSNCDWWYV1Caenorhabditis elegans
G117INSTEGDWWDA1Danio rerio
G237SERAAGLCCRL4Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus
G237SDVPDGLCCQL1Caenorhabditis elegans
G237TERAAGLCCRL1Danio rerio
G348EYMNKGSLLDF3Homo sapiens, Bos taurus, Rattus norvegicus
G348EYMINGSLLQY1Caenorhabditis elegans
G348EYMGKGSLLDF1Danio rerio
G348EYMSKGSLLDF1Mus musculus
H104DDLSFHKGEKF4Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus
H104GDLSFQKGDAM1Caenorhabditis elegans
H104DDLSFRKGEKF1Danio rerio
H202GDHVKHYKIRK5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
H202GGTVKHYKIKR1Caenorhabditis elegans
I215NGGYYITTRAQ4Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus
I215DQGYFITTRRT1Caenorhabditis elegans
I215SGGYYITTRAQ1Danio rerio
K201-GDHVKHYKIR5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
K201NGGTVKHYKIK1Caenorhabditis elegans
K204HVKHYKIRKLD5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
K204TVKHYKIKRLD1Caenorhabditis elegans
K299TKVAIKTLKPG5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
K299VEVAIKTMKPG1Caenorhabditis elegans
L238ERAAGLCCRLV5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
L238DVPDGLCCQLT1Caenorhabditis elegans
L277QLIKRLGNGQF5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
L277HLKRKLGDGNF1Caenorhabditis elegans
L397RSANILVGNGL4Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus
L397AARNVLVGDKI1Caenorhabditis elegans
L397RSANILVGDSL1Danio rerio
M345IVTEYMNKGSL3Homo sapiens, Bos taurus, Rattus norvegicus
M345IITEYMINGSL1Caenorhabditis elegans
M345IVTEYMGKGSL1Danio rerio
M345IVTEYMSKGSL1Mus musculus
N136GYIPSNYVAPV5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
N136GYVPRNFVAKQ1Caenorhabditis elegans
N279IKRLGNGQFGE5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
N279KRKLGDGNFGE1Caenorhabditis elegans
P134ETGYIPSNYVA4Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus
P134QTGYVPRNFVA1Caenorhabditis elegans
P134GTGYIPSNYVA1Danio rerio
R156FGKLGRKDAER5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
R156AGKIPRNRAER1Caenorhabditis elegans
R176GTFLIRESETT5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
R176GTFLIREREAD1Caenorhabditis elegans
R218YYITTRAQFET5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
R218YFITTRRTFRS1Caenorhabditis elegans
R96YDYEARTEDDL5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
R96YPYDSRADGDL1Caenorhabditis elegans
S135TGYIPSNYVAP5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
S135TGYVPRNFVAK1Caenorhabditis elegans
S178FLIRESETTKG5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
S178FLIREREADTR1Caenorhabditis elegans
S186TKGAYSLSIRD4Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus
S186DTREFALTIRD1Caenorhabditis elegans
S186TKGAFSLSIRD1Danio rerio
T180IRESETTKGAY4Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus
T180IREREADTREF1Caenorhabditis elegans
T180IRESETTKGAF1Danio rerio
T216GGYYITTRAQF5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
T216QGYFITTRRTF1Caenorhabditis elegans
T342PIYIVTEYMNK3Homo sapiens, Bos taurus, Rattus norvegicus
T342PFYIITEYMIN1Caenorhabditis elegans
T342PIYIVTEYMGK1Danio rerio
T342PIYIVTEYMSK1Mus musculus
T97DYEARTEDDLS5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
T97PYDSRADGDLS1Caenorhabditis elegans
V285GQFGEVWMGTW5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
V285GNFGEVWYGKW1Caenorhabditis elegans
W119SSEGDWWEARS4Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus
W119HSNCDWWYVRH1Caenorhabditis elegans
W119STEGDWWDARS1Danio rerio
Y132TGETGYIPSNY4Homo sapiens, Bos taurus, Rattus norvegicus, Mus musculus
Y132TGQTGYVPRNF1Caenorhabditis elegans
Y132TGGTGYIPSNY1Danio rerio
Y137YIPSNYVAPVD5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
Y137YVPRNFVAKQQ1Caenorhabditis elegans
Y203DHVKHYKIRKL5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
Y203GTVKHYKIKRL1Caenorhabditis elegans
Y344YIVTEYMNKGS3Homo sapiens, Bos taurus, Rattus norvegicus
Y344YIITEYMINGS1Caenorhabditis elegans
Y344YIVTEYMGKGS1Danio rerio
Y344YIVTEYMSKGS1Mus musculus
Y91LFVALYDYEAR5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
Y91TLVALYPYDSR1Caenorhabditis elegans
Y93VALYDYEARTE5Homo sapiens, Danio rerio, Bos taurus, Rattus norvegicus, Mus musculus
Y93VALYPYDSRAD1Caenorhabditis elegans


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