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 ARG2

Gene summary

Basic gene Info.	Gene symbol	ARG2
	Gene name	arginase 2
	Synonyms	-
	Cytomap	UCSC genome browser: 14q24.1
	Type of gene	protein-coding
	RefGenes	NM_001172.3,
	Description	L-arginine amidinohydrolaseL-arginine ureahydrolasearginase, type IIarginase-2, mitochondrialkidney arginasekidney-type arginasenon-hepatic arginasenonhepatic arginasetype II arginase
	Modification date	20141207
dbXrefs	MIM : 107830
	HGNC : HGNC
	Ensembl : ENSG00000081181
	HPRD : 00143
	Vega : OTTHUMG00000171807
Protein	UniProt: P78540 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_ARG2
	BioGPS: 384
Pathway	NCI Pathway Interaction Database: ARG2
	KEGG: ARG2
	REACTOME: ARG2
	Pathway Commons: ARG2
Context	iHOP: ARG2
	ligand binding site mutation search in PubMed: ARG2
	UCL Cancer Institute: ARG2
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

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Ligand binding site mutations for ARG2

Cancer type specific mutLBS sorted by frequency

LBS	AAchange of nsSNV	Cancer type	# samples
E296	V297A	BRCA	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 ARG2

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
E296	V297A	-1.4660405

(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 ARG2 from PDB

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Differential gene expression and gene-gene network for ARG2

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 ARG2 and the right PPI network was created from samples without mutations in the LBS of ARG2. 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 ARG2

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0004096	Asthma	7	Biomarker, GeneticVariation
umls:C0033578	Prostatic Neoplasms	2	AlteredExpression, Biomarker
umls:C0887833	Carcinoma, Pancreatic Ductal	1	Biomarker
umls:C0242656	Disease Progression	1	Biomarker
umls:C0027540	Necrosis	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for ARG2

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
Approved\|nutraceutical	DB00125	L-Arginine	Small molecule
Approved\|nutraceutical	DB00129	L-Ornithine	Small molecule
Experimental	DB03731	S-2-(Boronoethyl)-L-Cysteine	Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of ARG2 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
S2C		S-2-(BORONOETHYL)-L-CYSTEINE	1pq3	A	E296
S2C		S-2-(BORONOETHYL)-L-CYSTEINE	1pq3	B	E296
S2C		S-2-(BORONOETHYL)-L-CYSTEINE	1pq3	C	E296
S2C		S-2-(BORONOETHYL)-L-CYSTEINE	1pq3	D	E296
S2C		S-2-(BORONOETHYL)-L-CYSTEINE	1pq3	E	E296
S2C		S-2-(BORONOETHYL)-L-CYSTEINE	1pq3	F	E296
X7A		[(5R)-5-AMINO-5-CARBOXY-7-(PIPERIDIN-1-YL) HEPTYL](TRIHYDROXY)BORATE(1-)	4hze	A	E296
X7A		[(5R)-5-AMINO-5-CARBOXY-7-(PIPERIDIN-1-YL) HEPTYL](TRIHYDROXY)BORATE(1-)	4hze	B	E296
X7A		[(5R)-5-AMINO-5-CARBOXY-7-(PIPERIDIN-1-YL) HEPTYL](TRIHYDROXY)BORATE(1-)	4hze	C	E296
X8A		[(5R)-5-CARBOXY-5-(METHYLAMINO)-7-(PIPERIDIN-1-YL) HEPTYL](TRIHYDROXY)BORATE(1-)	4i06	A	E296
X8A		[(5R)-5-CARBOXY-5-(METHYLAMINO)-7-(PIPERIDIN-1-YL) HEPTYL](TRIHYDROXY)BORATE(1-)	4i06	B	E296
X8A		[(5R)-5-CARBOXY-5-(METHYLAMINO)-7-(PIPERIDIN-1-YL) HEPTYL](TRIHYDROXY)BORATE(1-)	4i06	C	E296
1EC		[(5R)-5-AMINO-5-CARBOXY-8-HYDROXYOCTYL](TRIHYDROXY) BORATE(1-)	4ie2	A	E296
1EC		[(5R)-5-AMINO-5-CARBOXY-8-HYDROXYOCTYL](TRIHYDROXY) BORATE(1-)	4ie2	B	E296
1EC		[(5R)-5-AMINO-5-CARBOXY-8-HYDROXYOCTYL](TRIHYDROXY) BORATE(1-)	4ie2	C	E296
1EE		[(5R)-5-AMINO-5-CARBOXY-7-(4-HYDROXYPIPERIDIN-1-YL) HEPTYL](TRIHYDROXY)BORATE(1-)	4ie3	A	E296
1EE		[(5R)-5-AMINO-5-CARBOXY-7-(4-HYDROXYPIPERIDIN-1-YL) HEPTYL](TRIHYDROXY)BORATE(1-)	4ie3	B	E296
1EE		[(5R)-5-AMINO-5-CARBOXY-7-(4-HYDROXYPIPERIDIN-1-YL) HEPTYL](TRIHYDROXY)BORATE(1-)	4ie3	C	E296
38I		{(5R)-5-AMINO-5-CARBOXY-5-[(3-ENDO)-8-(3,4- DICHLOROBENZYL)-8-AZABICYCLO[3.2.1]OCT-3- YL]PENTYL}(TRIHYDROXY)BORATE(1-)	4ixu	A	E296
38I		{(5R)-5-AMINO-5-CARBOXY-5-[(3-ENDO)-8-(3,4- DICHLOROBENZYL)-8-AZABICYCLO[3.2.1]OCT-3- YL]PENTYL}(TRIHYDROXY)BORATE(1-)	4ixu	B	E296
38I		{(5R)-5-AMINO-5-CARBOXY-5-[(3-ENDO)-8-(3,4- DICHLOROBENZYL)-8-AZABICYCLO[3.2.1]OCT-3- YL]PENTYL}(TRIHYDROXY)BORATE(1-)	4ixu	C	E296
XA1		{(5R)-5-AMINO-5-CARBOXY-5-[1-(4-CHLOROBENZYL)PIPERIDIN- 4-YL]PENTYL}(TRIHYDROXY)BORATE(1-)	4ixv	A	E296
XA1		{(5R)-5-AMINO-5-CARBOXY-5-[1-(4-CHLOROBENZYL)PIPERIDIN- 4-YL]PENTYL}(TRIHYDROXY)BORATE(1-)	4ixv	C	E296

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Conservation information for LBS of ARG2

Multiple alignments for P78540 in multiple species

LBS	AA sequence	# species	Species
A144	VIWVDAHADIN	3	Mus musculus, Rattus norvegicus, Bos taurus
A144	VVWVDAHADIN	1	Homo sapiens
D143	CVIWVDAHADI	2	Mus musculus, Rattus norvegicus
D143	CVVWVDAHADI	1	Homo sapiens
D143	GVIWVDAHADI	1	Bos taurus
D147	VDAHADINTPL	4	Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus
D200	YIGLRDVDPPE	2	Homo sapiens, Bos taurus
D200	YIGLRDVEPPE	1	Mus musculus
D200	YIGLRDVEPAE	1	Rattus norvegicus
D202	GLRDVDPPEHF	2	Homo sapiens, Bos taurus
D202	GLRDVEPPEHF	1	Mus musculus
D202	GLRDVEPAEHF	1	Rattus norvegicus
D251	IHLSFDIDAFD	4	Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus
D253	LSFDIDAFDPT	2	Homo sapiens, Bos taurus
D253	LSFDIDAFDPK	2	Mus musculus, Rattus norvegicus
E205	DVDPPEHFILK	2	Homo sapiens, Bos taurus
E205	DVEPPEHFILK	1	Mus musculus
E205	DVEPAEHFILK	1	Rattus norvegicus
E296	ALDLVEVNPHL	2	Mus musculus, Rattus norvegicus
E296	ALDLVEVNPQL	1	Homo sapiens
E296	ALDLVEVNPRL	1	Bos taurus
G161	SGNLHGQPVSF	2	Homo sapiens, Bos taurus
G161	SGNIHGQPLSF	2	Mus musculus, Rattus norvegicus
H120	TLGGDHSLAIG	2	Homo sapiens, Rattus norvegicus
H120	TMGGDHSLAIG	1	Mus musculus
H120	TVGGDHSLAIG	1	Bos taurus
H145	IWVDAHADINT	3	Mus musculus, Rattus norvegicus, Bos taurus
H145	VWVDAHADINT	1	Homo sapiens
H160	SSGNLHGQPVS	2	Homo sapiens, Bos taurus
H160	VSGNIHGQPLS	2	Mus musculus, Rattus norvegicus
N149	AHADINTPLTT	4	Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus
P203	LRDVDPPEHFI	2	Homo sapiens, Bos taurus
P203	LRDVEPPEHFI	1	Mus musculus
P203	LRDVEPAEHFI	1	Rattus norvegicus
S155	TPLTTSSGNLH	2	Homo sapiens, Bos taurus
S155	TPLTTVSGNIH	2	Mus musculus, Rattus norvegicus
S156	PLTTSSGNLHG	2	Homo sapiens, Bos taurus
S156	PLTTVSGNIHG	2	Mus musculus, Rattus norvegicus
T265	APATGTPVVGG	4	Homo sapiens, Mus musculus, Rattus norvegicus, Bos taurus