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 MAP2K2

Gene summary

Basic gene Info.	Gene symbol	MAP2K2
	Gene name	mitogen-activated protein kinase kinase 2
	Synonyms	CFC4\|MAPKK2\|MEK2\|MKK2\|PRKMK2
	Cytomap	UCSC genome browser: 19p13.3
	Type of gene	protein-coding
	RefGenes	NM_030662.3,
	Description	ERK activator kinase 2MAP kinase kinase 2MAPK/ERK kinase 2dual specificity mitogen-activated protein kinase kinase 2mitogen-activated protein kinase kinase 2, p45
	Modification date	20141219
dbXrefs	MIM : 601263
	HGNC : HGNC
	Ensembl : ENSG00000126934
	HPRD : 03164
	Vega : OTTHUMG00000134286
Protein	UniProt: P36507 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_MAP2K2
	BioGPS: 5605
Pathway	NCI Pathway Interaction Database: MAP2K2
	KEGG: MAP2K2
	REACTOME: MAP2K2
	Pathway Commons: MAP2K2
Context	iHOP: MAP2K2
	ligand binding site mutation search in PubMed: MAP2K2
	UCL Cancer Institute: MAP2K2
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:0036289	peptidyl-serine autophosphorylation	8388392
GO:0071902	positive regulation of protein serine/threonine kinase activity	8388392

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Ligand binding site mutations for MAP2K2

Cancer type specific mutLBS sorted by frequency

LBS	AAchange of nsSNV	Cancer type	# samples
N82	G83S	BRCA	1
M150	M150L	LUAD	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 MAP2K2

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
M150	M150L	-0.59303965
N82	G83S	-0.15472397

(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 MAP2K2 from PDB

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Differential gene expression and gene-gene network for MAP2K2

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 MAP2K2 and the right PPI network was created from samples without mutations in the LBS of MAP2K2. 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 MAP2K2

Gene level disease information (DisGeNet)

Disease ID	Disease name	# PubMed	Association type
umls:C1275081	Cardiofaciocutaneous syndrome	12	Biomarker, GeneticVariation
umls:C0028326	Noonan Syndrome	6	Biomarker, GeneticVariation
umls:C0025202	Melanoma	4	Biomarker
umls:C0587248	Costello Syndrome	4	Biomarker
umls:C3809007	CARDIOFACIOCUTANEOUS SYNDROME 4	3	GeneticVariation
umls:C0010606	Carcinoma, Adenoid Cystic	1	Biomarker

Mutation level pathogenic information (ClinVar annotation)

Allele ID

AA change

Clinical significance

Origin

Phenotype IDs

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Pharmacological information for MAP2K2

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	DB06616	Bosutinib	Small molecule
Approved	DB08911	Trametinib	Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of MAP2K2 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
5EA		5-[3,4-DIFLUORO-2-(2-FLUORO-4-IODOANILINO)PHENYL]-N-(2-MORPHOLIN-4-YLETHYL)-1,3,4-OXADIAZOL-2-AMINE	1s9i	A	N82
ATP		ATP	1s9i	A	N82 M150
ATP		ATP	1s9i	B	N82 M150

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Conservation information for LBS of MAP2K2

Multiple alignments for P36507 in multiple species

LBS	AA sequence	# species	Species
A80	ISELGAGNGGV	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
A80	VKVIGKGSGGV	1	Arabidopsis thaliana
A80	IQVIGKGSGGI	1	Oryza sativa subsp. japonica
A80	LGKIGAGNSGT	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
A99	SGLIMARKLIH	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
A99	VGKFFAMKVIQ	1	Arabidopsis thaliana
A99	VGTLYALKGIQ	1	Oryza sativa subsp. japonica
A99	DSKIVAKKTIP	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
D194	QIMHRDVKPSN	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
D194	HVIHRDIKPSN	2	Arabidopsis thaliana, Oryza sativa subsp. japonica
D194	KIIHRDIKPSN	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
D212	EIKLCDFGVSG	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
D212	EVKISDFGVSA	1	Arabidopsis thaliana
D212	EVKITDFGVSA	1	Oryza sativa subsp. japonica
D212	QIKLCDFGVSK	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
E148	ISICMEHMDGG	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
E148	FSLVLEYMDRG	1	Arabidopsis thaliana
E148	IYLVLEYMDRG	1	Oryza sativa subsp. japonica
E148	IIILMEYSDCG	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
F213	IKLCDFGVSGQ	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
F213	VKISDFGVSAS	1	Arabidopsis thaliana
F213	VKITDFGVSAV	1	Oryza sativa subsp. japonica
F213	IKLCDFGVSKK	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
G132	-PYIVGFYGAF	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
G132	CPHVVVCYHSF	1	Arabidopsis thaliana
G132	-AHIVLCHQSF	1	Oryza sativa subsp. japonica
G132	HENIITFYGAY	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
G214	KLCDFGVSGQL	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
G214	KISDFGVSASL	1	Arabidopsis thaliana
G214	KITDFGVSAVL	1	Oryza sativa subsp. japonica
G214	KLCDFGVSKKL	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
G79	RISELGAGNGG	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
G79	TVKVIGKGSGG	1	Arabidopsis thaliana
G79	MIQVIGKGSGG	1	Oryza sativa subsp. japonica
G79	QLGKIGAGNSG	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
G81	SELGAGNGGVV	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
G81	KVIGKGSGGVV	1	Arabidopsis thaliana
G81	QVIGKGSGGIV	1	Oryza sativa subsp. japonica
G81	GKIGAGNSGTV	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
K101	LIMARKLIHLE	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
K101	KFFAMKVIQMN	1	Arabidopsis thaliana
K101	TLYALKGIQMN	1	Oryza sativa subsp. japonica
K101	KIVAKKTIPVE	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
K196	MHRDVKPSNIL	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
K196	IHRDIKPSNLL	2	Arabidopsis thaliana, Oryza sativa subsp. japonica
K196	IHRDIKPSNVL	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
L119	QIIRELQVLHE	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
L119	QIVQELKINQA	2	Arabidopsis thaliana, Oryza sativa subsp. japonica
L119	QLVRELSIVKN	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
L122	RELQVLHECNS	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
L122	QELKINQASSQ	1	Arabidopsis thaliana
L122	QELKINQATQN	1	Oryza sativa subsp. japonica
L122	RELSIVKNVKP	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
L201	KPSNILVNSRG	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
L201	KPSNLLVNHKG	1	Arabidopsis thaliana
L201	KPSNLLVNRKG	1	Oryza sativa subsp. japonica
L201	KPSNVLINSKG	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
L219	GVSGQLIDSMA	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
L219	GVSASLASSMG	1	Arabidopsis thaliana
L219	GVSAVLASSMG	1	Oryza sativa subsp. japonica
L219	GVSKKLINSIA	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
L78	ERISELGAGNG	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
L78	ETVKVIGKGSG	1	Arabidopsis thaliana
L78	EMIQVIGKGSG	1	Oryza sativa subsp. japonica
L78	VQLGKIGAGNS	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
M147	EISICMEHMDG	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
M147	AFSLVLEYMDR	1	Arabidopsis thaliana
M147	VIYLVLEYMDR	1	Oryza sativa subsp. japonica
M147	EIIILMEYSDC	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
M150	ICMEHMDGGSL	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
M150	LVLEYMDRGSL	2	Arabidopsis thaliana, Oryza sativa subsp. japonica
M150	ILMEYSDCGSL	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
N199	DVKPSNILVNS	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
N199	DIKPSNLLVNH	1	Arabidopsis thaliana
N199	DIKPSNLLVNR	1	Oryza sativa subsp. japonica
N199	DIKPSNVLINS	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
N82	ELGAGNGGVVT	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
N82	VIGKGSGGVVQ	1	Arabidopsis thaliana
N82	VIGKGSGGIVQ	1	Oryza sativa subsp. japonica
N82	KIGAGNSGTVV	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Q157	GGSLDQVLKEA	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
Q157	RGSLADVIRQV	1	Arabidopsis thaliana
Q157	RGSLADIIKQV	1	Oryza sativa subsp. japonica
Q157	CGSLDKILSVY	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
R193	HQIMHRDVKPS	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
R193	RHVIHRDIKPS	2	Arabidopsis thaliana, Oryza sativa subsp. japonica
R193	YKIIHRDIKPS	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
S154	HMDGGSLDQVL	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
S154	YMDRGSLADVI	1	Arabidopsis thaliana
S154	YMDRGSLADII	1	Oryza sativa subsp. japonica
S154	YSDCGSLDKIL	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
S198	RDVKPSNILVN	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
S198	RDIKPSNLLVN	2	Arabidopsis thaliana, Oryza sativa subsp. japonica
S198	RDIKPSNVLIN	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
S216	CDFGVSGQLID	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
S216	SDFGVSASLAS	1	Arabidopsis thaliana
S216	TDFGVSAVLAS	1	Oryza sativa subsp. japonica
S216	CDFGVSKKLIN	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
V131	S-PYIVGFYGA	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
V131	QCPHVVVCYHS	1	Arabidopsis thaliana
V131	N-AHIVLCHQS	1	Oryza sativa subsp. japonica
V131	PHENIITFYGA	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
V215	LCDFGVSGQLI	5	Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Canis lupus familiaris
V215	ISDFGVSASLA	1	Arabidopsis thaliana
V215	ITDFGVSAVLA	1	Oryza sativa subsp. japonica
V215	LCDFGVSKKLI	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
V86	GNGGVVTKVQH	3	Homo sapiens, Gallus gallus, Canis lupus familiaris
V86	GNGGVVTKARH	2	Mus musculus, Rattus norvegicus
V86	GSGGVVQLVRH	1	Arabidopsis thaliana
V86	GSGGIVQLVRH	1	Oryza sativa subsp. japonica
V86	GNSGTVVKALH	1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c)