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 FNTA

Gene summary

Basic gene Info.	Gene symbol	FNTA
	Gene name	farnesyltransferase, CAAX box, alpha
	Synonyms	FPTA\|PGGT1A\|PTAR2
	Cytomap	UCSC genome browser: 8p11
	Type of gene	protein-coding
	RefGenes	NM_002027.2, NR_033698.1,NM_001018676.1,NM_001018677.1,
	Description	FTase-alphaGGTase-I-alphafarnesyl-protein transferase alpha-subunitprotein farnesyltransferase/geranylgeranyltransferase type-1 subunit alphaprotein prenyltransferase alpha subunit repeat containing 2ras proteins prenyltransferase subunit alphatype
	Modification date	20141207
dbXrefs	MIM : 134635
	HGNC : HGNC
	Ensembl : ENSG00000168522
	HPRD : 00607
	Vega : OTTHUMG00000165279
Protein	UniProt: P49354 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_FNTA
	BioGPS: 2339
Pathway	NCI Pathway Interaction Database: FNTA
	KEGG: FNTA
	REACTOME: FNTA
	Pathway Commons: FNTA
Context	iHOP: FNTA
	ligand binding site mutation search in PubMed: FNTA
	UCL Cancer Institute: FNTA
Assigned class in mutLBSgeneDB	C: This gene just belongs to mutLBSgenes.

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

GO ID	GO Term	PubMed ID
GO:0018343	protein farnesylation	16893176
GO:0018344	protein geranylgeranylation	16893176
GO:0090044	positive regulation of tubulin deacetylation	19228685
GO:0090045	positive regulation of deacetylase activity	19228685

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Ligand binding site mutations for FNTA

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
N165	N165K	COAD	1
Q167	W169C	GBM	1
H201	W203L	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 FNTA

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
N165	N165K	-1.5019117
Q167	W169C	-0.67697721
H201	W203L	-0.52231278

(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 FNTA from PDB

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Differential gene expression and gene-gene network for FNTA

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

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 FNTA

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
Investigational	DB04893	AZD3409	Small molecule
Experimental	DB06953	2-CHLORO-5-(3-CHLORO-PHENYL)-6-[(4-CYANO-PHENYL)-(3-METHYL-3H-IMIDAZOL-4-YL)- METHOXYMETHYL]-NICOTINONITRILE	Small molecule
Experimental	DB07216	(11S)-8-CHLORO-11-[1-(METHYLSULFONYL)PIPERIDIN-4-YL]-6-PIPERAZIN-1-YL-11H-BENZO[5,6]CYCLOHEPTA[1,2-B]PYRIDINE	Small molecule
Experimental	DB07227	4-[(5-{[4-(3-CHLOROPHENYL)-3-OXOPIPERAZIN-1-YL]METHYL}-1H-IMIDAZOL-1-YL)METHYL]BENZONITRILE	Small molecule
Experimental	DB07771	[(3,7,11-TRIMETHYL-DODECA-2,6,10-TRIENYLOXYCARBAMOYL)-METHYL]-PHOSPHONIC ACID	Small molecule
Experimental	DB07780	FARNESYL DIPHOSPHATE	Small molecule
Experimental	DB07841	GERANYLGERANYL DIPHOSPHATE	Small molecule
Experimental	DB07895	ALPHA-HYDROXYFARNESYLPHOSPHONIC ACID	Small molecule
Experimental	DB08180	2-[METHYL-(5-GERANYL-4-METHYL-PENT-3-ENYL)-AMINO]-ETHYL-DIPHOSPHATE	Small molecule
Experimental	DB08674	(20S)-19,20,21,22-TETRAHYDRO-19-OXO-5H-18,20-ETHANO-12,14-ETHENO-6,10-METHENO-18H-BENZ[D]IMIDAZO[4,3-K][1,6,9,12]OXATRIAZA-CYCLOOCTADECOSINE-9-CARBONITRILE	Small molecule
Experimental	DB08676	(20S)-19,20,22,23-TETRAHYDRO-19-OXO-5H,21H-18,20-ETHANO-12,14-ETHENO-6,10-METHENOBENZ[D]IMIDAZO[4,3-L][1,6,9,13]OXATRIAZACYCLONOADECOSINE-9-CARBONITRILE	Small molecule

Gene-centered ligand-gene interaction network

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

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
FPP		FARNESYL DIPHOSPHATE	2f0y	A	H201
FII		FPP ANALOG	2iej	A	H201
S48		METHYL N-{(3S)-1-[(1-METHYL-1H-IMIDAZOL-5-YL)METHYL]-6-PHENYL-1,2,3,4-TETRAHYDROQUINOLIN-3-YL}-N-[(1-METHYL-1H-IMIDAZOL-4-YL)SULFONYL]GLYCINATE	2iej	A	N165
III		Peptide ligand (ASP,ASP,PRO,THR,ALA,SER,ALA,CYS,ASN,ILE,GLN)	1tn6	A	Q167
III		Peptide ligand (CYS,VAL,LEU,SER)	2h6f	A	Q167
III		Peptide ligand (CYS,VAL,LEU,SER)	2h6g	A	Q167
III		Peptide ligand (PRO,THR,ALA,SER,ALA,CYS,VAL,LEU,SER)	2h6h	A	Q167
III		Peptide ligand (CYS,VAL,LEU,SER)	2h6i	A	Q167
739		2(S)-{2(S)-[2(R)-AMINO-3-MERCAPTO]PROPYLAMINO-3(S)-METHYL}PENTYLOXY-3-PHENYLPROPIONYLMETHIONINE SULFONE	1jcq	A	Q167 H201

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Conservation information for LBS of FNTA

Multiple alignments for P49354 in multiple species

LBS	AA sequence	# species	Species
H201	DAKNYHAWQHR	4	Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus
H201	DSKNYHVWSYR	2	Saccharomyces cerevisiae (strain ATCC 204508 / S288c), Schizosaccharomyces pombe (strain 972 / ATCC 24843)
H201	DAKHYHAWSHR	1	Arabidopsis thaliana
K164	IEEQPKNYQVW	4	Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus
K164	AEDNSKNYQLW	1	Arabidopsis thaliana
K164	TLNNPKNYQIW	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
K164	AEDFQKNYQVW	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
N165	EEQPKNYQVWH	4	Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus
N165	EDNSKNYQLWH	1	Arabidopsis thaliana
N165	LNNPKNYQIWS	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
N165	EDFQKNYQVWH	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Q167	QPKNYQVWHHR	4	Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus
Q167	NSKNYQLWHHR	1	Arabidopsis thaliana
Q167	NPKNYQIWSYR	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Q167	FQKNYQVWHHR	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Y131	LNAANYTVWHF	4	Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus
Y131	LNSGNYTVWHF	1	Arabidopsis thaliana
Y131	VAPAFYTIWNY	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Y131	NNPAHYTVWAY	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Y166	EQPKNYQVWHH	4	Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus
Y166	DNSKNYQLWHH	1	Arabidopsis thaliana
Y166	NNPKNYQIWSY	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Y166	DFQKNYQVWHH	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Y200	QDAKNYHAWQH	4	Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus
Y200	LDAKHYHAWSH	1	Arabidopsis thaliana
Y200	DDSKNYHVWSY	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Y200	IDSKNYHVWSY	1	Schizosaccharomyces pombe (strain 972 / ATCC 24843)