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 MAPK12

Gene summary

Basic gene Info.	Gene symbol	MAPK12
	Gene name	mitogen-activated protein kinase 12
	Synonyms	ERK3\|ERK6\|P38GAMMA\|PRKM12\|SAPK-3\|SAPK3
	Cytomap	UCSC genome browser: 22q13.33
	Type of gene	protein-coding
	RefGenes	NM_002969.3,
	Description	ERK-6MAP kinase 12MAP kinase p38 gammaMAPK 12extracellular signal-regulated kinase 6mitogen-activated protein kinase 3mitogen-activated protein kinase p38 gammastress-activated protein kinase 3
	Modification date	20141215
dbXrefs	MIM : 602399
	HGNC : HGNC
	Ensembl : ENSG00000188130
	HPRD : 03868
	Vega : OTTHUMG00000030145
Protein	UniProt: P53778 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_MAPK12
	BioGPS: 6300
Pathway	NCI Pathway Interaction Database: MAPK12
	KEGG: MAPK12
	REACTOME: MAPK12
	Pathway Commons: MAPK12
Context	iHOP: MAPK12
	ligand binding site mutation search in PubMed: MAPK12
	UCL Cancer Institute: MAPK12
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:0018105	peptidyl-serine phosphorylation	15850461
GO:0045445	myoblast differentiation	8633070

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Ligand binding site mutations for MAPK12

Cancer type specific mutLBS sorted by frequency

LBS	AAchange of nsSNV	Cancer type	# samples
G173	A175P	BLCA	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 MAPK12

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
G173	A175P	-0.063451378

(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 MAPK12 from PDB

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Differential gene expression and gene-gene network for MAPK12

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 MAPK12 and the right PPI network was created from samples without mutations in the LBS of MAPK12. 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 MAPK12

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 MAPK12

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	DB02482	Phosphonothreonine	Small molecule
Experimental	DB04395	Phosphoaminophosphonic Acid-Adenylate Ester	Small molecule
Investigational	DB05157	KC706	Small molecule
Investigational	DB05403	CEP-1347	Small molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of MAPK12 go to BioLip

Ligand ID	Ligand short name	Ligand long name	PDB ID	PDB name	mutLBS
MG		MAGNESIUM(2+)	1cm8	A	G173

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Conservation information for LBS of MAPK12

Multiple alignments for P53778 in multiple species

LBS	AA sequence	# species	Species
A54	TGNKVAIKKLY	2	Mus musculus, Rattus norvegicus
A54	TGAKVAIKKLY	1	Homo sapiens
D115	PFMGTDLGKLM	3	Homo sapiens, Mus musculus, Rattus norvegicus
D171	ELKILDFGLAR	3	Homo sapiens, Mus musculus, Rattus norvegicus
F111	YLVMPFMGTDL	3	Homo sapiens, Mus musculus, Rattus norvegicus
G157	RDLKPGNLAVN	3	Homo sapiens, Mus musculus, Rattus norvegicus
G173	KILDFGLARQA	3	Homo sapiens, Mus musculus, Rattus norvegicus
I87	RHENVIGLLDV	3	Homo sapiens, Mus musculus, Rattus norvegicus
K155	IHRDLKPGNLA	3	Homo sapiens, Mus musculus, Rattus norvegicus
K56	NKVAIKKLYRP	2	Mus musculus, Rattus norvegicus
K56	AKVAIKKLYRP	1	Homo sapiens
L170	CELKILDFGLA	3	Homo sapiens, Mus musculus, Rattus norvegicus
M109	DFYLVMPFMGT	3	Homo sapiens, Mus musculus, Rattus norvegicus
M112	LVMPFMGTDLG	3	Homo sapiens, Mus musculus, Rattus norvegicus
N158	DLKPGNLAVNE	3	Homo sapiens, Mus musculus, Rattus norvegicus
P110	FYLVMPFMGTD	3	Homo sapiens, Mus musculus, Rattus norvegicus
V41	GAYGAVCSAVD	3	Homo sapiens, Mus musculus, Rattus norvegicus