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mutLBSgeneDB |
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| Gene summary for MAP2K4 |
 Gene summary |
| Basic gene Info. | Gene symbol | MAP2K4 |
| Gene name | mitogen-activated protein kinase kinase 4 | |
| Synonyms | JNKK|JNKK1|MAPKK4|MEK4|MKK4|PRKMK4|SAPKK-1|SAPKK1|SEK1|SERK1|SKK1 | |
| Cytomap | UCSC genome browser: 17p12 | |
| Type of gene | protein-coding | |
| RefGenes | NM_001281435.1, NM_003010.3, | |
| Description | JNK-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 date | 20141212 | |
| dbXrefs | MIM : 601335 | |
| HGNC : HGNC | ||
| Ensembl : ENSG00000065559 | ||
| HPRD : 03213 | ||
| Vega : OTTHUMG00000178267 | ||
| Protein | UniProt: P45985 go to UniProt's Cross Reference DB Table | |
| Expression | CleanEX: HS_MAP2K4 | |
| BioGPS: 6416 | ||
| Pathway | NCI Pathway Interaction Database: MAP2K4 | |
| KEGG: MAP2K4 | ||
| REACTOME: MAP2K4 | ||
| Pathway Commons: MAP2K4 | ||
| Context | iHOP: MAP2K4 | |
| ligand binding site mutation search in PubMed: MAP2K4 | ||
| UCL Cancer Institute: MAP2K4 | ||
| 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 MAP2K4 |
| Cancer type specific mutLBS sorted by frequency |
| LBS | AAchange of nsSNV | Cancer type | # samples | S184 | S184L | BRCA | 2 | K187 | D186G | BRCA | 1 | D96 | D96V | COAD | 1 | T98 | A99V | COAD | 1 | H121 | P123Q | LUSC | 1 | D247 | G249V | OV | 1 | H121 | M119V | SKCM | 1 | S184 | S184L | STAD | 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. |
| 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 |
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| 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 |
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| 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 | T98 | A99V | 0.30681044 | S184 | S184L | 0.033861699 | K187 | D186G | -1.5655784 | H121 | P123Q | -1.1163307 | H121 | M119V | -0.9908399 | D247 | G249V | -0.6921159 | D96 | D96V | -0.66150196 |
| (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 ID | PDB title | PDB structure | 3VUT | Crystal structures of non-phosphorylated MAP2K4 |  |
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| 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) |
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| Phenotype information for MAP2K4 |
| 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 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. |
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| Gene-centered drug-gene interaction network |
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| Drug information targeting mutLBSgene (Approved drugs only) |
| Drug status | DrugBank ID | Name | Type | Drug structure |
| Gene-centered ligand-gene interaction network |
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| Ligands binding to mutated ligand binding site of MAP2K4 go to BioLip |
| Ligand ID | Ligand short name | Ligand long name | PDB ID | PDB name | mutLBS | ANP | AMP-PNP | 3aln | A | D247 | MG | MAGNESIUM(2+) | 3aln | A | D247 | MG | MAGNESIUM(2+) | 3aln | B | D247 | MG | MAGNESIUM(2+) | 3alo | A | D247 | III | Peptide ligand (ASP,ASP,GLU,MET,THR,GLY,TYR,ALA) | 3alo | A | D96 T98 H121 | ANP | AMP-PNP | 3alo | A | K187 D247 | ANP | AMP-PNP | 3aln | C | S184 K187 | ANP | AMP-PNP | 3aln | B | S184 K187 D247 |
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| Conservation information for LBS of MAP2K4 |
| Multiple alignments for P45985 in multiple species |
| LBS | AA sequence | # species | Species | A129 | SGQIMAVKRIR | 2 | Homo sapiens, Mus musculus | A129 | TGVTMALKEIR | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | A167 | VQFYGALFREG | 2 | Homo sapiens, Mus musculus | A167 | VDFYGAFFVEG | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | C177 | GDCWICMELMS | 2 | Homo sapiens, Mus musculus | C177 | GSVFICMEYMD | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | D229 | KIIHRDIKPSN | 2 | Homo sapiens, Mus musculus | D229 | NIIHRDVKPTN | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | D247 | NIKLCDFGISG | 2 | Homo sapiens, Mus musculus | D247 | QVKLCDFGVSG | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | D96 | PEQHWDFTAED | 2 | Homo sapiens, Mus musculus | D96 | SGSSFRINMSE | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | E179 | CWICMELMST- | 2 | Homo sapiens, Mus musculus | E179 | VFICMEYMDAG | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | F169 | FYGALFREGDC | 2 | Homo sapiens, Mus musculus | F169 | FYGAFFVEGSV | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | F97 | EQHWDFTAEDL | 2 | Homo sapiens, Mus musculus | F97 | GSSFRINMSEI | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | G109 | DLGEIGRGAYG | 2 | Homo sapiens, Mus musculus | G109 | KLEELGKGNYG | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | G111 | GEIGRGAYGSV | 2 | Homo sapiens, Mus musculus | G111 | EELGKGNYGVV | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | G114 | GRGAYGSVNKM | 2 | Homo sapiens, Mus musculus | G114 | GKGNYGVVYKA | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | H121 | VNKMVHKPSGQ | 2 | Homo sapiens, Mus musculus | H121 | VYKALHQPTGV | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | I108 | KDLGEIGRGAY | 2 | Homo sapiens, Mus musculus | I108 | IKLEELGKGNY | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | K131 | QIMAVKRIRST | 2 | Homo sapiens, Mus musculus | K131 | VTMALKEIRLS | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | K187 | T-SFDKFYKYV | 2 | Homo sapiens, Mus musculus | K187 | AGSMDKLYA-- | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | K231 | IHRDIKPSNIL | 2 | Homo sapiens, Mus musculus | K231 | IHRDVKPTNVL | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | L168 | QFYGALFREGD | 2 | Homo sapiens, Mus musculus | L168 | DFYGAFFVEGS | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | L180 | WICMELMST-S | 2 | Homo sapiens, Mus musculus | L180 | FICMEYMDAGS | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | L236 | KPSNILLDRSG | 2 | Homo sapiens, Mus musculus | L236 | KPTNVLVNSNG | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | M128 | PSGQIMAVKRI | 2 | Homo sapiens, Mus musculus | M128 | PTGVTMALKEI | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | M178 | DCWICMELMST | 2 | Homo sapiens, Mus musculus | M178 | SVFICMEYMDA | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | M181 | ICMELMST-SF | 2 | Homo sapiens, Mus musculus | M181 | ICMEYMDAGSM | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | N234 | DIKPSNILLDR | 2 | Homo sapiens, Mus musculus | N234 | DVKPTNVLVNS | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | R110 | LGEIGRGAYGS | 2 | Homo sapiens, Mus musculus | R110 | LEELGKGNYGV | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | S184 | LMST-SFDKFY | 2 | Homo sapiens, Mus musculus | S184 | YMDAGSMDKLY | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | S233 | RDIKPSNILLD | 2 | Homo sapiens, Mus musculus | S233 | RDVKPTNVLVN | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | T98 | QHWDFTAEDLK | 2 | Homo sapiens, Mus musculus | T98 | SSFRINMSEII | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | V116 | GAYGSVNKMVH | 2 | Homo sapiens, Mus musculus | V116 | GNYGVVYKALH | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | W95 | SPEQHWDFTAE | 2 | Homo sapiens, Mus musculus | W95 | SSGSSFRINMS | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) | Y165 | YIVQFYGALFR | 2 | Homo sapiens, Mus musculus | Y165 | YIVDFYGAFFV | 1 | Schizosaccharomyces pombe (strain 972 / ATCC 24843) |
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