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 MAP2K4
Gene summary
Basic gene Info.Gene symbolMAP2K4
Gene namemitogen-activated protein kinase kinase 4
CytomapUCSC genome browser: 17p12
Type of geneprotein-coding
DescriptionJNK-activated kinase 1JNK-activating kinase 1MAP kinase kinase 4MAPK/ERK kinase 4MAPKK 4MEK 4SAPK/ERK kinase 1c-Jun N-terminal kinase kinase 1dual specificity mitogen-activated protein kinase kinase 4stress-activated protein kinase kinase 1
Modification date20141212
dbXrefs MIM : 601335
Ensembl : ENSG00000065559
HPRD : 03213
Vega : OTTHUMG00000178267
ProteinUniProt: P45985
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_MAP2K4
BioGPS: 6416
PathwayNCI Pathway Interaction Database: MAP2K4
Pathway Commons: MAP2K4
ContextiHOP: MAP2K4
ligand binding site mutation search in PubMed: MAP2K4
UCL Cancer Institute: MAP2K4
Assigned class in mutLBSgeneDBB: This gene belongs to targetable_mutLBSgenes.

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

Ligand binding site mutations for MAP2K4

Cancer type specific mutLBS sorted by frequency
LBSAAchange of nsSNVCancer type# samples
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.

Clinical information for MAP2K4 from My Cancer Genome.
Mitogen-activated protein kinase kinase 4 (MAP2K4) is a gene that encodes a protein that is a member of the MAP kinase family. The protein functions in the signaling of multiple cellular processes including cellular proliferation, differentiation, transcription regulation, and development. Missense mutations, nonsense mutations, silent mutations, whole gene deletions, frameshift deletions and insertions, and in-frame insertions are observed in cancers such as breast cancer, intestinal cancer, and testicular cancer.Related Pathways: MAP kinase signaling.Modified: December 4, 2015

Protein structure related information for MAP2K4
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.
LBSAAchange of nsSNVRelative stability change
(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 MAP2K4 from PDB
PDB IDPDB titlePDB structure
3VUTCrystal structures of non-phosphorylated MAP2K4

Differential gene expression and gene-gene network for MAP2K4
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 MAP2K4 and the right PPI network was created from samples without mutations in the LBS of MAP2K4. Only genes with p-value < 0.05 are shown.
Red circle: input gene. Orange circle: LBSgene. Blue circle: other gene.


Phenotype information for MAP2K4
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type

Mutation level pathogenic information (ClinVar annotation)
Allele IDAA changeClinical significanceOriginPhenotype IDs

Pharmacological information for MAP2K4
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 statusDrugBank IDNameTypeDrug structure

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of MAP2K4 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
IIIPeptide ligand (ASP,ASP,GLU,MET,THR,GLY,TYR,ALA)3aloAD96 T98 H121
ANPAMP-PNP3aloAK187 D247
ANPAMP-PNP3alnCS184 K187
ANPAMP-PNP3alnBS184 K187 D247

Conservation information for LBS of MAP2K4
Multiple alignments for P45985 in multiple species
LBSAA sequence# speciesSpecies
A129SGQIMAVKRIR2Homo sapiens, Mus musculus
A129TGVTMALKEIR1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
A167VQFYGALFREG2Homo sapiens, Mus musculus
A167VDFYGAFFVEG1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
C177GDCWICMELMS2Homo sapiens, Mus musculus
C177GSVFICMEYMD1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D229KIIHRDIKPSN2Homo sapiens, Mus musculus
D229NIIHRDVKPTN1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D247NIKLCDFGISG2Homo sapiens, Mus musculus
D247QVKLCDFGVSG1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
D96PEQHWDFTAED2Homo sapiens, Mus musculus
D96SGSSFRINMSE1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
E179CWICMELMST-2Homo sapiens, Mus musculus
E179VFICMEYMDAG1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
F169FYGALFREGDC2Homo sapiens, Mus musculus
F169FYGAFFVEGSV1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
F97EQHWDFTAEDL2Homo sapiens, Mus musculus
F97GSSFRINMSEI1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
G109DLGEIGRGAYG2Homo sapiens, Mus musculus
G109KLEELGKGNYG1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
G111GEIGRGAYGSV2Homo sapiens, Mus musculus
G111EELGKGNYGVV1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
G114GRGAYGSVNKM2Homo sapiens, Mus musculus
G114GKGNYGVVYKA1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
H121VNKMVHKPSGQ2Homo sapiens, Mus musculus
H121VYKALHQPTGV1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
I108KDLGEIGRGAY2Homo sapiens, Mus musculus
I108IKLEELGKGNY1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
K131QIMAVKRIRST2Homo sapiens, Mus musculus
K131VTMALKEIRLS1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
K187T-SFDKFYKYV2Homo sapiens, Mus musculus
K187AGSMDKLYA--1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
K231IHRDIKPSNIL2Homo sapiens, Mus musculus
K231IHRDVKPTNVL1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
L168QFYGALFREGD2Homo sapiens, Mus musculus
L168DFYGAFFVEGS1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
L180WICMELMST-S2Homo sapiens, Mus musculus
L180FICMEYMDAGS1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
L236KPSNILLDRSG2Homo sapiens, Mus musculus
L236KPTNVLVNSNG1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
M128PSGQIMAVKRI2Homo sapiens, Mus musculus
M128PTGVTMALKEI1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
M178DCWICMELMST2Homo sapiens, Mus musculus
M178SVFICMEYMDA1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
M181ICMELMST-SF2Homo sapiens, Mus musculus
M181ICMEYMDAGSM1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
N234DIKPSNILLDR2Homo sapiens, Mus musculus
N234DVKPTNVLVNS1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
R110LGEIGRGAYGS2Homo sapiens, Mus musculus
R110LEELGKGNYGV1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
S184LMST-SFDKFY2Homo sapiens, Mus musculus
S184YMDAGSMDKLY1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
S233RDIKPSNILLD2Homo sapiens, Mus musculus
S233RDVKPTNVLVN1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
T98QHWDFTAEDLK2Homo sapiens, Mus musculus
T98SSFRINMSEII1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
V116GAYGSVNKMVH2Homo sapiens, Mus musculus
V116GNYGVVYKALH1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
W95SPEQHWDFTAE2Homo sapiens, Mus musculus
W95SSGSSFRINMS1Schizosaccharomyces pombe (strain 972 / ATCC 24843)
Y165YIVQFYGALFR2Homo sapiens, Mus musculus
Y165YIVDFYGAFFV1Schizosaccharomyces pombe (strain 972 / ATCC 24843)

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