MAP2K4 Gene (Protein Coding)

Mitogen-Activated Protein Kinase Kinase 4

GC17P012020
GIFtS:
47
This gene encodes a member of the mitogen-activated protein kinase (MAPK) family. Members of this family act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. They form a three-tiered signaling module composed of MAPKKKs, MAPKKs, and... See more...

Aliases for MAP2K4 Gene

Aliases for MAP2K4 Gene

  • Mitogen-Activated Protein Kinase Kinase 4 2 3 5
  • PRKMK4 2 3 4
  • JNKK1 2 3 4
  • MEK4 2 3 4
  • MKK4 2 3 4
  • Dual Specificity Mitogen-Activated Protein Kinase Kinase 4 3 4
  • Stress-Activated Protein Kinase Kinase 1 3 4
  • C-Jun N-Terminal Kinase Kinase 1 3 4
  • JNK-Activating Kinase 1 3 4
  • MAP Kinase Kinase 4 3 4
  • MAPK/ERK Kinase 4 3 4
  • SAPK/ERK Kinase 1 3 4
  • EC 2.7.12.2 4 51
  • SAPKK-1 3 4
  • MAPKK 4 3 4
  • SAPKK1 3 4
  • SERK1 3 4
  • MEK 4 3 4
  • JNKK 3 4
  • SEK1 3 4
  • SKK1 3 4
  • JNK-Activated Kinase 1 3
  • SAPK Kinase 1 4
  • MAPKK4 3
  • MAP2K4 5

External Ids for MAP2K4 Gene

Previous HGNC Symbols for MAP2K4 Gene

  • SERK1

Previous GeneCards Identifiers for MAP2K4 Gene

  • GC17P012290
  • GC17P013039
  • GC17P011868
  • GC17P012124
  • GC17P011864

Summaries for MAP2K4 Gene

Entrez Gene Summary for MAP2K4 Gene

  • This gene encodes a member of the mitogen-activated protein kinase (MAPK) family. Members of this family act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. They form a three-tiered signaling module composed of MAPKKKs, MAPKKs, and MAPKs. This protein is phosphorylated at serine and threonine residues by MAPKKKs and subsequently phosphorylates downstream MAPK targets at threonine and tyrosine residues. A similar protein in mouse has been reported to play a role in liver organogenesis. A pseudogene of this gene is located on the long arm of chromosome X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

GeneCards Summary for MAP2K4 Gene

MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4) is a Protein Coding gene. Diseases associated with MAP2K4 include Ovarian Serous Carcinoma and Cardiomyopathy, Familial Hypertrophic, 25. Among its related pathways are MAPK Signaling: Oxidative Stress Pathway and Beta-Adrenergic Signaling. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is MAP2K7.

UniProtKB/Swiss-Prot Summary for MAP2K4 Gene

  • Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.

Gene Wiki entry for MAP2K4 Gene

Additional gene information for MAP2K4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MAP2K4 Gene

Genomics for MAP2K4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for MAP2K4 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH17J012020 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 260.2 +0.8 779 2.8 TBP SP1 FEZF1 SMAD5 POLR2A ELF1 ZIC2 HOMEZ SIN3A SIN3B MAP2K4 ENSG00000241185 HSALNG0114604 ZNF18 lnc-ZNF18-3 MYOCD
GH17J012046 Enhancer 0.9 Ensembl ENCODE 18.7 +28.5 28478 9.4 ZEB1 FOSL1 PRDM6 JUND ZSCAN5A BATF ZNF189 ZBTB33 ZNF362 GLIS1 MAP2K4 MIR744 RNU11-2P HSALNG0114606 ZNF18 MYOCD
GH17J011996 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 7.8 -23.6 -23621 2.8 ZSCAN16 TBP ZBTB10 SP1 MXD4 NR2C1 SMAD5 ZNF217 POLR2A BHLHE40 ZNF18 MAP2K4 piR-61687-015 ENSG00000266368 ENSG00000241185 lnc-ZNF18-3 DNAH9
GH17J011987 Enhancer 0.8 Ensembl ENCODE 17.8 -33.6 -33622 1.2 CEBPA CTCF KDM6A REST FOXA2 SAP130 RXRA RAD21 SMC3 CREM MAP2K4 ENSG00000266368 piR-61687-015 ZNF18 DNAH9
GH17J012108 Enhancer 0.4 Ensembl 16.9 +86.5 86479 0.2 NFE2 MAFG EMSY MAP2K4 LOC103156999 HSALNG0114609 ZNF18 MYOCD
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MAP2K4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MAP2K4

Top Transcription factor binding sites by QIAGEN in the MAP2K4 gene promoter:
  • AML1a
  • AP-1
  • ATF-2
  • c-Jun
  • CUTL1
  • ER-alpha
  • GR
  • GR-alpha
  • NF-E2
  • NF-E2 p45

Genomic Locations for MAP2K4 Gene

Latest Assembly
chr17:12,020,822-12,143,830
(GRCh38/hg38)
Size:
123,009 bases
Orientation:
Plus strand

Previous Assembly
chr17:11,924,194-12,047,145
(GRCh37/hg19 by Entrez Gene)
Size:
122,952 bases
Orientation:
Plus strand

chr17:11,924,141-12,047,147
(GRCh37/hg19 by Ensembl)
Size:
123,007 bases
Orientation:
Plus strand

Genomic View for MAP2K4 Gene

Genes around MAP2K4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MAP2K4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MAP2K4 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for MAP2K4 Gene

Proteins for MAP2K4 Gene

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  • Protein details for MAP2K4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P45985-MP2K4_HUMAN
    Recommended name:
    Dual specificity mitogen-activated protein kinase kinase 4
    Protein Accession:
    P45985
    Secondary Accessions:
    • B2R7N7
    • B3KYB2
    • D3DTS5
    • Q5U0B8
    • Q6FHX4
    • Q6P9H2
    • Q6PIE6

    Protein attributes for MAP2K4 Gene

    Size:
    399 amino acids
    Molecular mass:
    44288 Da
    Quaternary structure:
    • Interacts with SPAG9 (By similarity). Interacts (via its D domain) with its substrates MAPK8/JNK1, MAPK9/JNK2, MAPK10/JNK3, MAPK11 and MAPK14. Interacts (via its DVD domain) with MAP3Ks activators like MAP3K1/MEKK1 and MAP3K11/MLK3. Interacts with ARRB1, ARRB2 and MAPK8IP3/JIP3.

    Three dimensional structures from OCA and Proteopedia for MAP2K4 Gene

    Alternative splice isoforms for MAP2K4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP2K4 Gene

Protein Expression for MAP2K4 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Selected DME Specific Peptides for MAP2K4 Gene

P45985:
  • FYGALFREGD
  • IKLCDFGISG
  • YDVRSDVWSLGITLYE
  • WICMELM

Post-translational modifications for MAP2K4 Gene

  • Activated by phosphorylation on Ser-257 and Thr-261 by MAP kinase kinase kinases (MAP3Ks).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for MAP2K4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibodies for research

  • Abcam antibodies for MAP2K4

Domains & Families for MAP2K4 Gene

Gene Families for MAP2K4 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Enzymes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for MAP2K4 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for MAP2K4 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ52538, highly similar to Dual specificity mitogen-activated proteinkinase kinase 4 (EC 2.7.12.2) (B4DH44_HUMAN)
  • c-Jun N-terminal kinase kinase 1 (MP2K4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P45985

UniProtKB/Swiss-Prot:

MP2K4_HUMAN :
  • The DVD domain (residues 364-387) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation.
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
Domain:
  • The DVD domain (residues 364-387) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation.
  • The D domain (residues 34-52) contains a conserved docking site and is required for the binding to MAPK substrates.
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
genes like me logo Genes that share domains with MAP2K4: view

Function for MAP2K4 Gene

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Molecular function for MAP2K4 Gene

UniProtKB/Swiss-Prot Function:
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K7/MKK7, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.12.2;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.12.2;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.2;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated in response to a variety of cellular stresses, including UV and gamma-irradiation, heat shock, hyperosmolarity, T-cell receptor stimulation, peroxide and inflammatory cytokines. Also activated by developmental cues. MAP2K4/MKK4 is activated by the majority of MKKKs, such as MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K7/TAK1, MAP3K10/MLK2, MAP3K11/MLK3, MAP3K12/DLK and MAP3K13/LZK.
GENATLAS Biochemistry:
mitogen-activated protein kinase kinase 4,binding to JUN transactivation domain and phosphorylating it,involved in signal transduction,also involved in Ras pathway and hepatogenesis

Enzyme Numbers (IUBMB) for MAP2K4 Gene

Phenotypes From GWAS Catalog for MAP2K4 Gene

Gene Ontology (GO) - Molecular Function for MAP2K4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity TAS 7716521
GO:0004674 protein serine/threonine kinase activity IEA --
GO:0004708 MAP kinase kinase activity IBA 21873635
GO:0004713 protein tyrosine kinase activity IEA --
genes like me logo Genes that share ontologies with MAP2K4: view
genes like me logo Genes that share phenotypes with MAP2K4: view

Animal Models for MAP2K4 Gene

MGI Knock Outs for MAP2K4:

Animal Models for research

miRNA for MAP2K4 Gene

miRTarBase miRNAs that target MAP2K4

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MAP2K4

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MAP2K4 Gene

Localization for MAP2K4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MAP2K4 Gene

Cytoplasm. Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MAP2K4 gene
Compartment Confidence
cytosol 5
nucleus 4
plasma membrane 2
extracellular 2
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
lysosome 2
peroxisome 1
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cell Junctions (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MAP2K4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0030424 axon IEA --
GO:0032839 dendrite cytoplasm IEA --
genes like me logo Genes that share ontologies with MAP2K4: view

Pathways & Interactions for MAP2K4 Gene

PathCards logo

SuperPathways for MAP2K4 Gene

SuperPathway Contained pathways
1 Activated TLR4 signalling
Toll Like Receptor 9 (TLR9) Cascade
.94
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
.94
Activated TLR4 signalling
.91
Toll Like Receptor 4 (TLR4) Cascade
.91
MyD88 cascade initiated on plasma membrane
.88
Toll Like Receptor 10 (TLR10) Cascade
.88
Toll Like Receptor 5 (TLR5) Cascade
.88
MyD88 dependent cascade initiated on endosome
.86
Toll Like Receptor 7/8 (TLR7/8) Cascade
.86
MyD88-independent TLR3/TLR4 cascade
.86
Toll Like Receptor 3 (TLR3) Cascade
.86
TRIF-mediated TLR3/TLR4 signaling
.86
MyD88-Mal cascade initiated on plasma membrane
.85
Toll Like Receptor 2 (TLR2) Cascade
.85
Toll Like Receptor TLR1-TLR2 Cascade
.85
Toll Like Receptor TLR6-TLR2 Cascade
.85
Toll-Like Receptors Cascades
.82
MAP kinase activation in TLR cascade
.76
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
.01
2 IL-2 Pathway
ErbB4 Pathway
.59
Prolactin Signaling
.54
Thrombopoietin Pathway
.51
ErbB2-ErbB3 Heterodimers
.49
IL-2 Pathway
.48
LPS Stimulated MAPK Signaling
.47
TREM1 Pathway
.43
PACAP Signaling
.37
HMGB1 Pathway
.36
IL-4 Pathway
.34
3 TNFR1 Pathway
TNFR1 Pathway
.56
TNF Signaling
.55
Apoptosis and survival TNFR1 signaling pathway
.52
Apoptosis through Death Receptors
.42
Death Receptor Signaling
.36
Fas Signaling
.35
TNF alpha Signaling Pathway
.30
4 Toll-Like receptor Signaling Pathways
NOD-like Receptor Signaling Pathways
.59
Toll-Like receptor Signaling Pathways
.59
Inflammasome Activation Pathways
.51
IL-1 Family Signaling Pathways
.43
Mucin expression in CF via TLRs, EGFR signaling pathways
.42
Immune response IL-1 signaling pathway
.41
5 4-1BB Pathway
4-1BB Pathway
.54
CD40 Signaling
.54
CD27 Pathway
.48
NF-KappaB Activation by EBV
.42
PKR Pathway
.36
SUMO Pathway
.30
genes like me logo Genes that share pathways with MAP2K4: view

Pathways by source for MAP2K4 Gene

30 GeneGo (Thomson Reuters) pathways for MAP2K4 Gene
  • Apoptosis and survival Anti-apoptotic action of membrane-bound ESR1
  • Apoptosis and survival APRIL and BAFF signaling
  • Apoptosis and survival FAS signaling cascades
  • Apoptosis and survival Lymphotoxin-beta receptor signaling
  • Apoptosis and survival TNFR1 signaling pathway
87 Qiagen pathways for MAP2K4 Gene
  • 14-3-3 Induced Apoptosis
  • 14-3-3 Induced Intracellular Signaling
  • 4-1BB Pathway
  • Aldosterone Signaling in Epithelial Cells
  • Alpha-Adrenergic Signaling
1 Cell Signaling Technology pathway for MAP2K4 Gene
2 GeneTex pathways for MAP2K4 Gene

SIGNOR curated interactions for MAP2K4 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for MAP2K4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade IEA --
GO:0000187 activation of MAPK activity IBA 21873635
GO:0001934 positive regulation of protein phosphorylation IEA --
GO:0006468 protein phosphorylation IEA --
GO:0006915 apoptotic process IEA --
genes like me logo Genes that share ontologies with MAP2K4: view

Drugs & Compounds for MAP2K4 Gene

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(40) Drugs for MAP2K4 Gene - From: PharmGKB, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Ethanol Approved Pharma 3481
Dabrafenib Approved, Investigational Pharma Inhibition, inhibitor BRAF kinase inhibitor, Kinase Inhibitors, Mutant BRAF Kinase 133
Selumetinib Approved, Investigational Pharma inhibitor, Biomarker MEK inhibitor, MEK Inhibitors, Kinase Inhibitors, Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitors 0
Trametinib Approved Pharma inhibitor, Biomarker MEK 1/2 inhibitor, MEK Inhibitors, Kinase Inhibitors, Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitors 212
ATP Investigational Nutra 0

(9) Additional Compounds for MAP2K4 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
 58-64-0
genes like me logo Genes that share compounds with MAP2K4: view

Transcripts for MAP2K4 Gene

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mRNA/cDNA for MAP2K4 Gene

2 REFSEQ mRNAs :
17 NCBI additional mRNA sequence :
15 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MAP2K4

Alternative Splicing Database (ASD) splice patterns (SP) for MAP2K4 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13a · 13b · 13c
SP1: - - -
SP2: - - - -
SP3: - -
SP4: - - - -
SP5:
SP6:

Relevant External Links for MAP2K4 Gene

GeneLoc Exon Structure for
MAP2K4

Expression for MAP2K4 Gene

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  2. Gene Expression Assays for research

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for MAP2K4 Gene

mRNA expression in normal human tissues for MAP2K4 Gene
mRNA expression by GTEx for MAP2K4 GenemRNA expression by BioGPS for MAP2K4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MAP2K4 Gene

This gene is overexpressed in Frontal cortex (9.5) and Brain (8.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MAP2K4 Gene



Protein tissue co-expression partners for MAP2K4 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MAP2K4

SOURCE GeneReport for Unigene cluster for MAP2K4 Gene:

Hs.514681

mRNA Expression by UniProt/SwissProt for MAP2K4 Gene:

P45985-MP2K4_HUMAN
Tissue specificity: Abundant expression is seen in the skeletal muscle. It is also widely expressed in other tissues.

Evidence on tissue expression from TISSUES for MAP2K4 Gene

  • Nervous system(5)
  • Liver(4.5)
  • Skin(2.5)
  • Blood(2.4)
  • Kidney(2.4)
  • Heart(2.4)
  • Intestine(2.4)
  • Muscle(2.4)
  • Lymph node(2.1)
  • Lung(2.1)
  • Eye(2.1)
  • Adrenal gland(2)
  • Pancreas(2)
  • Spleen(2)
genes like me logo Genes that share expression patterns with MAP2K4: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for MAP2K4 Gene

Orthologs for MAP2K4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for MAP2K4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia MAP2K4 30 31
  • 99.59 (n)
 OneToOne
Oppossum
(Monodelphis domestica)
 Mammalia -- 31
  • 96 (a)
 OneToMany
-- 31
  • 77 (a)
 OneToMany
Dog
(Canis familiaris)
 Mammalia MAP2K4 30 31
  • 95.49 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Map2k4 30 17 31
  • 95.21 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Map2k4 30
  • 94.41 (n)
Cow
(Bos Taurus)
 Mammalia MAP2K4 30 31
  • 94.29 (n)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia MAP2K4 31
  • 49 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves MAP2K4 30 31
  • 89.18 (n)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia MAP2K4 31
  • 76 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia map2k4 30
  • 80.39 (n)
African clawed frog
(Xenopus laevis)
 Amphibia Xl.13308 30
Zebrafish
(Danio rerio)
 Actinopterygii map2k4b 31
  • 81 (a)
 OneToMany
map2k4a 30 31
  • 77.78 (n)
 OneToMany
Dr.10451 30
Rainbow Trout
(Oncorhynchus mykiss)
 Actinopterygii Omy.4083 30
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP003365 30
  • 59.33 (n)
Fruit Fly
(Drosophila melanogaster)
 Insecta Mkk4 30 31 32
  • 57.38 (n)
 OneToOne
lic 32
  • 52 (a)
Worm
(Caenorhabditis elegans)
 Secernentea sek-1 32
  • 51 (a)
VZC374L.1 32
  • 48 (a)
mkk-4 31
  • 46 (a)
 OneToMany
sek-6 31
  • 40 (a)
 OneToMany
jkk-1 32
  • 39 (a)
F35C8.1 32
  • 39 (a)
sek-3 31
  • 37 (a)
 OneToMany
Sea Squirt
(Ciona savignyi)
 Ascidiacea -- 31
  • 53 (a)
 OneToOne
Fission Yeast
(Schizosaccharomyces pombe)
 Schizosaccharomycetes wis1 30
  • 52.56 (n)
Species where no ortholog for MAP2K4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for MAP2K4 Gene

ENSEMBL:
Gene Tree for MAP2K4 (if available)
TreeFam:
Gene Tree for MAP2K4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MAP2K4: view image

Paralogs for MAP2K4 Gene

Paralogs for MAP2K4 Gene

(9) SIMAP similar genes for MAP2K4 Gene using alignment to 5 proteins:

  • MP2K4_HUMAN
  • J3QLE2_HUMAN
  • K7EP58_HUMAN
  • R4GN37_HUMAN
  • R4GN68_HUMAN

Pseudogenes.org Pseudogenes for MAP2K4 Gene

genes like me logo Genes that share paralogs with MAP2K4: view

Variants for MAP2K4 Gene

Products:

  1. SNP Genotyping and Copy Number Assays for research

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MAP2K4 Gene

SNP ID Clinical significance and condition Chr 17 pos Variation AA Info Type
rs1555550018 Other: Neuroblastoma 12,107,814(+) C/G
NM_003010.4(MAP2K4):c.538C>G (p.Leu180Val) 		MISSENSE
rs1567657403 A colorectal adenocarcinoma sample p.Arg154Trp
rs753665559 A colorectal adenocarcinoma sample p.Ala279Thr
VAR_040818 A lung squamous cell carcinoma sample p.Gln142Leu
VAR_040820 An ovarian serous carcinoma sample p.Asn234Ile

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for MAP2K4 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for MAP2K4 Gene

Variant ID Type Subtype PubMed ID
esv25918 CNV loss 19812545
esv3639963 CNV gain 21293372
esv991595 CNV gain 20482838
nsv1983 CNV insertion 18451855

Variation tolerance for MAP2K4 Gene

Residual Variation Intolerance Score: 25.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.42; 9.23% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MAP2K4 Gene

Human Gene Mutation Database (HGMD)
MAP2K4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MAP2K4

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAP2K4 Gene

Disorders for MAP2K4 Gene

MalaCards: The human disease database

(14) MalaCards diseases for MAP2K4 Gene - From: COP and GCD

Disorder Aliases PubMed IDs
ovarian serous carcinoma
  • ovarian serous adenocarcinoma
cardiomyopathy, familial hypertrophic, 25
  • cmh25
anthrax disease
  • anthrax
breast mucoepidermoid carcinoma
  • mucoepidermoid carcinoma of breast
pancreatic cancer
  • pancreatic carcinoma
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for MAP2K4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with MAP2K4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MAP2K4 Gene

Publications for MAP2K4 Gene

  1. The association between -1304T>G polymorphism in the promoter of MKK4 gene and the risk of sporadic colorectal cancer in southern Chinese population. (PMID: 19610067) Wei Y … Wang J (International journal of cancer 2009) 3 23 41
  2. A docking site in MKK4 mediates high affinity binding to JNK MAPKs and competes with similar docking sites in JNK substrates. (PMID: 12788955) Ho DT … Bardwell L (The Journal of biological chemistry 2003) 3 4 23
  3. Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene. (PMID: 9622070) Su GH … Kern SE (Cancer research 1998) 3 4 23
  4. Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2. (PMID: 7716521) Lin A … Karin M (Science (New York, N.Y.) 1995) 2 3 4
  5. Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms. (PMID: 7839144) Dérijard B … Davis RJ (Science (New York, N.Y.) 1995) 3 4 23

ExternalLinks

View latest publications for MAP2K4 gene in Mastermind

Products for MAP2K4 Gene

Sources for MAP2K4 Gene