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 AKT2

Gene summary

Basic gene Info.	Gene symbol	AKT2
	Gene name	v-akt murine thymoma viral oncogene homolog 2
	Synonyms	HIHGHH\|PKBB\|PKBBETA\|PRKBB\|RAC-BETA
	Cytomap	UCSC genome browser: 19q13.1-q13.2
	Type of gene	protein-coding
	RefGenes	NM_001243027.2, NM_001243028.2,NM_001626.5,
	Description	PKB betaRAC-PK-betaRAC-beta serine/threonine-protein kinasemurine thymoma viral (v-akt) homolog-2protein kinase Akt-2protein kinase B betarac protein kinase beta
	Modification date	20141222
dbXrefs	MIM : 164731
	HGNC : HGNC
	Ensembl : ENSG00000105221
	HPRD : 01262
	Vega : OTTHUMG00000137375
Protein	UniProt: P31751 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_AKT2
	BioGPS: 208
Pathway	NCI Pathway Interaction Database: AKT2
	KEGG: AKT2
	REACTOME: AKT2
	Pathway Commons: AKT2
Context	iHOP: AKT2
	ligand binding site mutation search in PubMed: AKT2
	UCL Cancer Institute: AKT2
Assigned class in mutLBSgeneDB	A: This gene has a literature evidence and it belongs to targetable_mutLBSgenes.
References showing study about ligand binding site mutation for AKT2.	1. "Arya VB, Flanagan SE, Schober E, Rami-Merhar B, Ellard S, Hussain K.Activating AKT2 mutation: hypoinsulinemic hypoketotic hypoglycemia. J Clin Endocrinol Metab. 2014 Feb;99(2):391-4. doi: 10.1210/jc.2013-3228. Epub 2013 Nov 27. PubMed PMID: 24285683." 24285683

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 AKT2

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
D440	D440E	COAD	1
D440	D440N	COAD	1
Y351	Y351C	HNSC	1
E200	T199S	LUAD	1
T213	A214V	PRAD	1
D275	R274P	SKCM	1
G161	G161V	SKCM	1
E200,L204	R202P	SKCM	1
A179	A179T	STAD	1
L348	R347L	STAD	1
E342	M344V	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 AKT2

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
Y351	Y351C	-1.3858237
A179	A179T	-1.1720915
D275	R274P	-1.0010893
E342	M344V	-0.87273186
D440	D440N	-0.83739339
E200	T199S	-0.5850241
D440	D440E	-0.48687054
L348	R347L	-0.39848753
T213	A214V	-0.37895877
L204	R202P	-0.28796315
E200	R202P	-0.28796315
G161	G161V	-0.025163582

(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 AKT2 from PDB

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Differential gene expression and gene-gene network for AKT2

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 AKT2 and the right PPI network was created from samples without mutations in the LBS of AKT2. 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 AKT2

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C0011860	Diabetes Mellitus, Type 2	3	Biomarker, GeneticVariation
umls:C1458155	Breast Neoplasms	3	AlteredExpression, Biomarker
umls:C0271694	Lipodystrophy, Familial Partial	1	Biomarker
umls:C2931822	Nasopharyngeal carcinoma	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for AKT2

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
Experimental	DB07812	N-[(1S)-2-amino-1-phenylethyl]-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiophene-2-carboxamide	Small molecule
Experimental	DB07859	4-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINE	Small molecule
Experimental	DB07947	ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE	Small molecule
Experimental	DB08073	(2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE	Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of AKT2 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
G93		4-{2-(4-AMINO-1,2,5-OXADIAZOL-3-YL)-1-ETHYL-7-[(3S)-PIPERIDIN-3-YLMETHOXY]-1H-IMIDAZO[4,5-C]PYRIDIN-4-YL}-2-METHYLBUT-3-YN-2-OL	3d0e	A	A179 E200 L204
G93		4-{2-(4-AMINO-1,2,5-OXADIAZOL-3-YL)-1-ETHYL-7-[(3S)-PIPERIDIN-3-YLMETHOXY]-1H-IMIDAZO[4,5-C]PYRIDIN-4-YL}-2-METHYLBUT-3-YN-2-OL	3d0e	B	A179 E200 L204
ANP		AMP-PNP	1o6l	A	A179 T213
L20		(2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE	2jdr	A	A179 T213
G95		N-[(1S)-2-AMINO-1-PHENYLETHYL]-5-(1H-PYRROLO[2,3-B]PYRIDIN-4-YL)THIOPHENE-2-CARBOXAMIDE	3e87	A	A179 T213
G95		N-[(1S)-2-AMINO-1-PHENYLETHYL]-5-(1H-PYRROLO[2,3-B]PYRIDIN-4-YL)THIOPHENE-2-CARBOXAMIDE	3e87	B	A179 T213
III		Peptide ligand (GLY,ARG,PRO,ARG,THR,THR,SER,PHE,ALA,GLU)	1o6l	A	D275 E342
III		Peptide ligand (GLY,ARG,PRO,ARG,THR,THR,SER,PHE,ALA,GLU)	2xh5	A	D275 E342
III		Peptide ligand (GLY,ARG,PRO,ARG,THR,THR,SER,PHE,ALA,GLU)	2jdo	A	D275 E342 L348
III		Peptide ligand (GLY,ARG,PRO,ARG,THR,THR,SER,PHE,ALA,GLU)	2uw9	A	D275 E342 L348
III		Peptide ligand (GLY,ARG,PRO,ARG,THR,THR,SER,PHE,ALA,GLU)	2x39	A	D275 E342 L348
III		Peptide ligand (GLY,ARG,PRO,ARG,THR,THR,SER,PHE,ALA,GLU)	3e88	A	D275 E342 L348
III		Peptide ligand (GLY,ARG,PRO,ARG,THR,THR,SER,PHE,ALA,GLU)	3e88	B	D275 E342 L348
III		Peptide ligand (GLY,ARG,PRO,ARG,THR,THR,SER,PHE,ALA,GLU)	3e87	B	D275 E342 L348 D440
III		Peptide ligand (GLY,ARG,PRO,ARG,THR,THR,SER,PHE,ALA,GLU)	3e8d	A	D275 E342 L348 Y351
III		Peptide ligand (GLY,ARG,PRO,ARG,THR,THR,SER,PHE,ALA,GLU)	3e8d	B	D275 E342 L348 Y351
III		Peptide ligand (GLY,ARG,PRO,ARG,THR,THR,SER,PHE,ALA,GLU)	3e87	A	D275 E342 L348 Y351 D440
III		Peptide ligand (GLY,ARG,PRO,ARG,THR,THR,SER,PHE,ALA,GLU)	1o6k	A	D275 E342 Y351
III		Peptide ligand (GLY,ARG,PRO,ARG,THR,THR,SER,PHE,ALA,GLU)	2jdr	A	D275 E342 Y351
I5S		ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE	2jdo	A	G161 A179
GVP		4-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINE	2uw9	A	G161 A179
X39		4-AMINO-N-(4-CHLOROBENZYL)-1-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)PIPERIDINE-4-CARBOXAMIDE	2x39	A	G161 A179
G96		4-[2-(4-AMINO-1,2,5-OXADIAZOL-3-YL)-6-{[(2R)-2-AMINO-3-PHENYLPROPYL]OXY}-1-ETHYL-1H-IMIDAZO[4,5-C]PYRIDIN-4-YL]-2-METHYLBUT-3-YN-2-OL	3e88	A	G161 A179 E200 L204
G96		4-[2-(4-AMINO-1,2,5-OXADIAZOL-3-YL)-6-{[(2R)-2-AMINO-3-PHENYLPROPYL]OXY}-1-ETHYL-1H-IMIDAZO[4,5-C]PYRIDIN-4-YL]-2-METHYLBUT-3-YN-2-OL	3e88	B	G161 A179 E200 L204
G98		4-[2-(4-AMINO-2,5-DIHYDRO-1,2,5-OXADIAZOL-3-YL)-6-{[(1S)-3-AMINO-1-PHENYLPROPYL]OXY}-1-ETHYL-1H-IMIDAZO[4,5-C]PYRIDIN-4-YL]-2-METHYLBUT-3-EN-2-OL	3e8d	B	G161 A179 E200 L204
G98		4-[2-(4-AMINO-2,5-DIHYDRO-1,2,5-OXADIAZOL-3-YL)-6-{[(1S)-3-AMINO-1-PHENYLPROPYL]OXY}-1-ETHYL-1H-IMIDAZO[4,5-C]PYRIDIN-4-YL]-2-METHYLBUT-3-EN-2-OL	3e8d	A	G161 A179 E200 L204 T213
ANP		AMP-PNP	1o6k	A	G161 A179 T213
X37		4-(4-TERT-BUTYLBENZYL)-1-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)PIPERIDIN-4-AMINIUM	2xh5	A	G161 A179 T213

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Conservation information for LBS of AKT2

Multiple alignments for P31751 in multiple species

LBS	AA sequence	# species	Species
A179	TGRYYAMKILR	3	Homo sapiens, Mus musculus, Rattus norvegicus
A179	TAKLYAIKILK	1	Drosophila melanogaster
A232	FVMEYANGGEL	2	Homo sapiens, Mus musculus
A232	FVMQYVNGGEL	1	Drosophila melanogaster
A232	FVMEYANGGDL	1	Rattus norvegicus
C311	TMKTFCGTPEY	3	Homo sapiens, Mus musculus, Rattus norvegicus
C311	TTKTFCGTPEY	1	Drosophila melanogaster
D275	DVVYRDIKLEN	3	Homo sapiens, Mus musculus, Rattus norvegicus
D275	GIIYRDLKLEN	1	Drosophila melanogaster
D293	HIKITDFGLCK	2	Homo sapiens, Mus musculus
D293	HIKVADFGLCK	1	Drosophila melanogaster
D293	HIKITDFGLSK	1	Rattus norvegicus
D440	DTRYFDDEFTA	3	Homo sapiens, Mus musculus, Rattus norvegicus
D440	DTRYFDKEFTG	1	Drosophila melanogaster
E193	IIAKDEVAHTV	3	Homo sapiens, Mus musculus, Rattus norvegicus
E193	IIQKDEVAHTL	1	Drosophila melanogaster
E200	AHTVTESRVLQ	3	Homo sapiens, Mus musculus, Rattus norvegicus
E200	AHTLTESRVLK	1	Drosophila melanogaster
E230	LCFVMEYANGG	3	Homo sapiens, Mus musculus, Rattus norvegicus
E230	LCFVMQYVNGG	1	Drosophila melanogaster
E236	YANGGELFFHL	2	Homo sapiens, Mus musculus
E236	YVNGGELFWHL	1	Drosophila melanogaster
E236	YANGGDLFFHL	1	Rattus norvegicus
E279	RDIKLENLMLD	3	Homo sapiens, Mus musculus, Rattus norvegicus
E279	RDLKLENLLLD	1	Drosophila melanogaster
E315	FCGTPEYLAPE	4	Homo sapiens, Drosophila melanogaster, Mus musculus, Rattus norvegicus
E342	GVVMYEMMCGR	3	Homo sapiens, Mus musculus, Rattus norvegicus
E342	GVVMYEMICGR	1	Drosophila melanogaster
F163	LGKGTFGKVIL	4	Homo sapiens, Drosophila melanogaster, Mus musculus, Rattus norvegicus
F227	HDRLCFVMEYA	3	Homo sapiens, Mus musculus, Rattus norvegicus
F227	NDRLCFVMQYV	1	Drosophila melanogaster
F238	NGGELFFHLSR	2	Homo sapiens, Mus musculus
F238	NGGELFWHLSH	1	Drosophila melanogaster
F238	NGGDLFFHLSR	1	Rattus norvegicus
F294	IKITDFGLCKE	2	Homo sapiens, Mus musculus
F294	IKVADFGLCKE	1	Drosophila melanogaster
F294	IKITDFGLSKE	1	Rattus norvegicus
F310	ATMKTFCGTPE	3	Homo sapiens, Mus musculus, Rattus norvegicus
F310	RTTKTFCGTPE	1	Drosophila melanogaster
F439	VDTRYFDDEFT	3	Homo sapiens, Mus musculus, Rattus norvegicus
F439	TDTRYFDKEFT	1	Drosophila melanogaster
F443	YFDDEFTAQSI	3	Homo sapiens, Mus musculus, Rattus norvegicus
F443	YFDKEFTGESV	1	Drosophila melanogaster
G159	YLKLLGKGTFG	3	Homo sapiens, Mus musculus, Rattus norvegicus
G159	FLKVLGKGTFG	1	Drosophila melanogaster
G161	KLLGKGTFGKV	3	Homo sapiens, Mus musculus, Rattus norvegicus
G161	KVLGKGTFGKV	1	Drosophila melanogaster
G164	GKGTFGKVILV	3	Homo sapiens, Mus musculus, Rattus norvegicus
G164	GKGTFGKVILC	1	Drosophila melanogaster
G312	MKTFCGTPEYL	3	Homo sapiens, Mus musculus, Rattus norvegicus
G312	TKTFCGTPEYL	1	Drosophila melanogaster
H196	KDEVAHTVTES	3	Homo sapiens, Mus musculus, Rattus norvegicus
H196	KDEVAHTLTES	1	Drosophila melanogaster
K160	LKLLGKGTFGK	3	Homo sapiens, Mus musculus, Rattus norvegicus
K160	LKVLGKGTFGK	1	Drosophila melanogaster
K165	KGTFGKVILVR	3	Homo sapiens, Mus musculus, Rattus norvegicus
K165	KGTFGKVILCR	1	Drosophila melanogaster
K181	RYYAMKILRKE	3	Homo sapiens, Mus musculus, Rattus norvegicus
K181	KLYAIKILKKE	1	Drosophila melanogaster
K277	VYRDIKLENLM	3	Homo sapiens, Mus musculus, Rattus norvegicus
K277	IYRDLKLENLL	1	Drosophila melanogaster
L158	DYLKLLGKGTF	3	Homo sapiens, Mus musculus, Rattus norvegicus
L158	EFLKVLGKGTF	1	Drosophila melanogaster
L183	YAMKILRKEVI	3	Homo sapiens, Mus musculus, Rattus norvegicus
L183	YAIKILKKEVI	1	Drosophila melanogaster
L204	TESRVLQNTRH	3	Homo sapiens, Mus musculus, Rattus norvegicus
L204	TESRVLKSTNH	1	Drosophila melanogaster
L278	YRDIKLENLML	3	Homo sapiens, Mus musculus, Rattus norvegicus
L278	YRDLKLENLLL	1	Drosophila melanogaster
L296	ITDFGLCKEGI	2	Homo sapiens, Mus musculus
L296	VADFGLCKEDI	1	Drosophila melanogaster
L296	ITDFGLSKEGI	1	Rattus norvegicus
L317	GTPEYLAPEVL	4	Homo sapiens, Drosophila melanogaster, Mus musculus, Rattus norvegicus
L348	MMCGRLPFYNQ	3	Homo sapiens, Mus musculus, Rattus norvegicus
L348	MICGRLPFYNR	1	Drosophila melanogaster
M229	RLCFVMEYANG	3	Homo sapiens, Mus musculus, Rattus norvegicus
M229	RLCFVMQYVNG	1	Drosophila melanogaster
M282	KLENLMLDKDG	3	Homo sapiens, Mus musculus, Rattus norvegicus
M282	KLENLLLDKDG	1	Drosophila melanogaster
N280	DIKLENLMLDK	3	Homo sapiens, Mus musculus, Rattus norvegicus
N280	DLKLENLLLDK	1	Drosophila melanogaster
P314	TFCGTPEYLAP	4	Homo sapiens, Drosophila melanogaster, Mus musculus, Rattus norvegicus
S242	LFFHLSRERVF	3	Homo sapiens, Mus musculus, Rattus norvegicus
S242	LFWHLSHERIF	1	Drosophila melanogaster
T162	LLGKGTFGKVI	3	Homo sapiens, Mus musculus, Rattus norvegicus
T162	VLGKGTFGKVI	1	Drosophila melanogaster
T213	RHPFLTALKYA	3	Homo sapiens, Mus musculus, Rattus norvegicus
T213	NHPFLISLKYS	1	Drosophila melanogaster
T292	GHIKITDFGLC	2	Homo sapiens, Mus musculus
T292	GHIKVADFGLC	1	Drosophila melanogaster
T292	GHIKITDFGLS	1	Rattus norvegicus
T309	GATMKTFCGTP	3	Homo sapiens, Mus musculus, Rattus norvegicus
T309	GRTTKTFCGTP	1	Drosophila melanogaster
T313	KTFCGTPEYLA	4	Homo sapiens, Drosophila melanogaster, Mus musculus, Rattus norvegicus
V166	GTFGKVILVRE	3	Homo sapiens, Mus musculus, Rattus norvegicus
V166	GTFGKVILCRE	1	Drosophila melanogaster
Y231	CFVMEYANGGE	2	Homo sapiens, Mus musculus
Y231	CFVMQYVNGGE	1	Drosophila melanogaster
Y231	CFVMEYANGGD	1	Rattus norvegicus
Y316	CGTPEYLAPEV	4	Homo sapiens, Drosophila melanogaster, Mus musculus, Rattus norvegicus
Y351	GRLPFYNQDHE	3	Homo sapiens, Mus musculus, Rattus norvegicus
Y351	GRLPFYNRDHD	1	Drosophila melanogaster