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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
External Ids for MAP2K4 Gene
- HGNC: 6844
- Entrez Gene: 6416
- Ensembl: ENSG00000065559
- OMIM: 601335
- UniProtKB: P45985
Previous HGNC Symbols for MAP2K4 Gene
- SERK1
Previous GeneCards Identifiers for MAP2K4 Gene
- GC17P012290
- GC17P013039
- GC17P011868
- GC17P012124
- GC17P011864
Summaries 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 Association Between Physico-Chemical Features and Toxicity Associated Pathways and Apoptosis Modulation and 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.
Additional gene information for MAP2K4 Gene
- HGNC(6844)
- Entrez Gene(6416)
- Ensembl(ENSG00000065559)
- OMIM(601335)
- UniProtKB(P45985)
- Open Targets Platform(ENSG00000065559)
- Search for MAP2K4 at DataMed
- Search for MAP2K4 at HumanCyc
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
Promoters and enhancers for MAP2K4 Gene
- 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
Genomic Locations for MAP2K4 Gene
- chr17:12,020,822-12,143,830
- (GRCh38/hg38)
- Size:
- 123,009 bases
- Orientation:
- Plus strand
- chr17:11,924,135-12,047,147
- (GRCh37/hg19)
- Size:
- 123,013 bases
- Orientation:
- Plus strand
Genomic View for MAP2K4 Gene
Genes around MAP2K4 on UCSC Golden Path with GeneCards custom track
- Cytogenetic band:
-
- 17p12 by HGNC
- 17p12 by Entrez Gene
- 17p12 by Ensembl
MAP2K4 Gene in genomic location: bands according to
Ensembl, locations according to GeneLoc
(and/or Entrez Gene and/or Ensembl if different)
Genomic Neighborhood
• Exon Structure
• Gene Density
RefSeq DNA sequence for MAP2K4 Gene
Proteins for MAP2K4 Gene
-
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
- 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.
Protein Expression for MAP2K4 Gene
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
Antibody Products
- Creative Diagnostics Rabbit Anti-Human SEK1 (phospho Ser257) monoclonal antibody, clone H.785.20
- HUABIO Anti-MAP2K4 Antibody
-
Custom Antibody ServicesOriGene Antibodies for MAP2K4
- AM06144SU-N
- AM06580SU-N
- AP00207PU-N
- AP01678PU-N
- AP01679PU-N
- AP02453PU-N
- AP02453PU-S
- AP02454PU-N
- AP02454PU-S
- AP02660PU-N
- AP02660PU-S
- AP02661PU-N
- AP02661PU-S
- AP06311PU-N
- AP06312PU-N
- AP20270PU-N
- AP20418PU-N
- CF500403
- CF500411
- CF500412
- CF500428
- CF500430
- TA300116
- TA300580
- TA300743
- TA309998
- TA309999
- TA321550
- TA325642
- TA325643
- TA326264
- TA327868
- TA327914
- TA333238
- TA333239
- TA500403
- TA500403S
- TA500411
- TA500411S
- TA500412
- TA500412S
- TA500428
- TA500428S
- TA500430
- TA500430S
- Novus Biologicals Antibodies for MAP2K4
-
Abcam antibodies for MAP2K4
- Invitrogen Antibodies for MAP2K4 (AFLGC-MAP2K4)
- antibodies-online: Show 139 available MAP2K4 Antibodies ranked by validation data
- Compare Top MAP2K4 Antibodies
-
Recommended
- 258 WB Antibodies (anti-human)
- 46 IHC Antibodies (anti-human)
- 13 IHC (p) Antibodies (anti-human)
- 12 IF (p) Antibodies (anti-human)
- 4 IP Antibodies (anti-human)
- 139 WB Antibodies (anti-mouse)
- 32 IHC Antibodies (anti-mouse)
- 12 IF (p) Antibodies (anti-mouse)
- 7 IHC (p) Antibodies (anti-mouse)
- 1 IP Antibody (anti-mouse)
- 104 WB Antibodies (anti-rat)
- 30 IHC Antibodies (anti-rat)
- 12 IF (p) Antibodies (anti-rat)
- 7 IHC (p) Antibodies (anti-rat)
- 1 IP Antibody (anti-rat)
-
Boster Bio Antibodies for MAP2K4
-
Santa Cruz Biotechnology (SCBT) Antibodies for MAP2K4
- Sino Biological Antibodies for MAP2K4
Protein Products
- Search Origene for MassSpec and Protein Over-expression Lysates for MAP2K4
- Origene Custom Protein Services for MAP2K4
- Sino Biological Recombinant Proteins for MAP2K4
- Sino Biological Cell Lysates for MAP2K4
-
Abcam proteins for MAP2K4
Assay Products
- antibodies-online: Show 6 available MAP2K4 Elisa Kits ranked by validation data
- Compare Top MAP2K4 Elisa Kits
-
Quality Products:
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
P45985UniProtKB/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.
Function for MAP2K4 Gene
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
| 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 | IBA | -- |
| GO:0004708 | MAP kinase kinase activity | IBA | 21873635 |
| GO:0004713 | protein tyrosine kinase activity | IEA | -- |
Phenotypes for MAP2K4 Gene
- MGI mutant phenotypes for MAP2K4:
- inferred from 4 alleles
- GenomeRNAi human phenotypes for MAP2K4:
-
- Increased vaccinia virus (VACV) infection
- no effect
- Resistant to vaccinia virus (VACV-A4L) infection
- Decreased vaccinia virus (VACV) infection
- Decreased viability in non-small-cell lung cancer (NSCLC) lineage
- Decreased viability
- Increased viability
- Negative genetic interaction between MUS81-/- and MUS81+/+
- Increased shRNA abundance (Z-score > 2)
- Decreased shRNA abundance (Z-score < -2)
- Increased Nanog expression
- Increased cell viability after pRB stimulation
- Decreased substrate adherent cell growth
- Decreased human cytomegalovirus (HCMV) strain AD169 replication
- Increased colony dispersion (increased number of colonies and decreased number of cells per colony)
- Increased mitotic index
Animal Models for MAP2K4 Gene
Animal Model Products
- Taconic Biosciences: Generate A Custom CRISPR Mouse Model For Your Study
CRISPR Products
- Applied Biological Materials (abm): CRISPR Clones for MAP2K4 - Select products 50% OFF >
- * MAP2K4 CRISPR as ready-to-use vector or virus: ORF | Lenti- | Adeno- | AAV- | Protein Vector - Browse All
- * Gene synthesis, site-directed mutagenesis, subcloning, and more services - Browse All
-
OriGene CRISPR knockouts for MAP2K4
- Search GeneCopoeia for CRISPR/Cas9 clones, lentivirus and AAV products for MAP2K4
-
Santa Cruz Biotechnology (SCBT) CRISPR for MAP2K4
miRNA for MAP2K4 Gene
- miRTarBase miRNAs that target MAP2K4
-
- mmu-miR-92a-3p (MIRT007244)
- mmu-miR-758-3p (MIRT007680)
- mmu-miR-26a-5p (MIRT011233)
- mmu-miR-136-5p (MIRT015015)
- hsa-miR-375 (MIRT019756)
- hsa-miR-15b-5p (MIRT023483)
- hsa-miR-26b-5p (MIRT028937)
- hsa-miR-25-3p (MIRT030360)
- hsa-miR-145-5p (MIRT053655)
- hsa-miR-188-5p (MIRT053698)
- hsa-miR-27a-3p (MIRT054442)
- hsa-miR-92a-3p (MIRT437965)
- hsa-miR-1185-2-3p (MIRT473851)
- hsa-miR-1185-1-3p (MIRT473852)
- hsa-let-7f-2-3p (MIRT473853)
- hsa-miR-542-3p (MIRT473854)
- hsa-miR-4261 (MIRT473855)
- hsa-miR-3134 (MIRT473856)
- hsa-miR-8082 (MIRT473857)
- hsa-miR-4534 (MIRT473858)
- hsa-miR-4433a-3p (MIRT473859)
- hsa-miR-3688-3p (MIRT473860)
- hsa-miR-6818-3p (MIRT556303)
- hsa-miR-7855-5p (MIRT556304)
- hsa-miR-4325 (MIRT556305)
- hsa-miR-7703 (MIRT556306)
- hsa-miR-6749-3p (MIRT556307)
- hsa-miR-6792-3p (MIRT556308)
- hsa-miR-4691-5p (MIRT556309)
- hsa-miR-3185 (MIRT556310)
- hsa-miR-3121-5p (MIRT556311)
- hsa-miR-660-3p (MIRT556312)
- hsa-miR-5193 (MIRT556313)
- hsa-miR-3614-5p (MIRT556314)
- hsa-miR-10a-3p (MIRT556315)
- hsa-miR-559 (MIRT556316)
- hsa-miR-548y (MIRT556317)
- hsa-miR-548w (MIRT556318)
- hsa-miR-548o-5p (MIRT556319)
- hsa-miR-548j-5p (MIRT556320)
- hsa-miR-548i (MIRT556321)
- hsa-miR-548h-5p (MIRT556322)
- hsa-miR-548d-5p (MIRT556323)
- hsa-miR-548c-5p (MIRT556324)
- hsa-miR-548bb-5p (MIRT556325)
- hsa-miR-548b-5p (MIRT556326)
- hsa-miR-548ay-5p (MIRT556327)
- hsa-miR-548au-5p (MIRT556328)
- hsa-miR-548as-5p (MIRT556329)
- hsa-miR-548ar-5p (MIRT556330)
- hsa-miR-548aq-5p (MIRT556331)
- hsa-miR-548ap-5p (MIRT556332)
- hsa-miR-548am-5p (MIRT556333)
- hsa-miR-548ak (MIRT556334)
- hsa-miR-548ae-5p (MIRT556335)
- hsa-miR-548ad-5p (MIRT556336)
- hsa-miR-548ab (MIRT556337)
- hsa-miR-548a-5p (MIRT556338)
- hsa-miR-363-3p (MIRT556339)
- hsa-miR-367-3p (MIRT556340)
- hsa-miR-92b-3p (MIRT556341)
- hsa-miR-32-5p (MIRT556342)
miRNA Products
Inhibitory RNA Products
- Origene shrna, sirna, and RNAi products in human, mouse, rat for MAP2K4
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Clone Products
- Applied Biological Materials (abm): Clones for MAP2K4 - Select products 50% OFF >
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-
- MG203798
- MG226212
- MR203798
- MR203798L3
- MR203798L4
- MR226212
- MR226212L3
- MR226212L4
- RC206051
- RC206051L1
- RC206051L2
- RC206051L3
- RC206051L4
- RC238044
- RG206051
- RR204032
- RR204032L3
- RR204032L4
- MR203798L3V
- MR203798L4V
- MR226212L3V
- MR226212L4V
- RC206051L1V
- RC206051L2V
- RC206051L3V
- RC206051L4V
- RR204032L3V
- RR204032L4V
- Custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
- Sino Biological Human cDNA Clone for MAP2K4
- Addgene plasmids for MAP2K4
- Search GeneCopoeia for ORF cDNA, lentivirus, AAV viral particles and/or promoter clone products for MAP2K4
Cell Line Products
-
Horizon Cell Lines 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.
| 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 |
- Cell Junctions (2)
- Nucleoplasm (2)
| GO ID | Qualified GO term | Evidence | PubMed IDs |
|---|---|---|---|
| GO:0005634 | nucleus | IEA | -- |
| GO:0005737 | cytoplasm | IBA | -- |
| GO:0005829 | cytosol | IEA,TAS | -- |
| GO:0030424 | axon | IEA | -- |
| GO:0032839 | dendrite cytoplasm | IEA | -- |
Pathways & Interactions for MAP2K4 Gene
| SuperPathway | Contained pathways | ||
|---|---|---|---|
| 1 | Activated TLR4 signalling | ||
| 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
|
Fas Signaling
.35
|
| 4 | Toll-Like receptor Signaling Pathways |
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
|
Pathways by source for MAP2K4 Gene
11 Sino Biological pathways for MAP2K4 Gene
39 BioSystems pathways for MAP2K4 Gene
34 Reactome pathways for MAP2K4 Gene
2 PharmGKB pathways 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
6 R&D Systems pathways for MAP2K4 Gene
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
Interacting Proteins for MAP2K4 Gene
Selected Interacting proteins:
P45985-MP2K4_HUMAN
ENSP00000410402
for MAP2K4 Gene via
UniProtKB
MINT
STRING
IID
GPS-Prot Interaction Network for MAP2K4
SIGNOR curated interactions 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 | -- |
Drugs & Compounds for MAP2K4 Gene
| Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
|---|---|---|---|---|---|---|
| Ethanol | Approved | Pharma | 3266 | |||
| Dabrafenib | Approved, Investigational | Pharma | Inhibition, inhibitor | BRAF kinase inhibitor, Kinase Inhibitors, Mutant BRAF Kinase | 116 | |
| 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 | 194 | |
| ATP | Investigational | Nutra | Agonist, Activator, Partial agonist, Antagonist, Full agonist, Gating inhibitor, Pore Blocker, Potentiation | 0 |
| Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
|---|---|---|---|---|---|---|
| ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
|
Transcripts for MAP2K4 Gene
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 :
-
- ENST00000353533 3778 nts (view in UCSC)
- ENST00000415385 3856 nts (view in UCSC)
- ENST00000536413 3852 nts (view in UCSC)
- ENST00000538465 925 nts (view in UCSC)
- ENST00000579089 571 nts (view in UCSC)
CRISPR Products
- Applied Biological Materials (abm): CRISPR Clones for MAP2K4 - Select products 50% OFF >
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miRNA Products
Inhibitory RNA Products
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Clone Products
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| 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
mRNA expression in embryonic tissues and stem cells from LifeMap Discovery
- Brain (Nervous System)
- Neural Tube (Nervous System)
-
Blood (Hematopoietic System)
- Granulocytes Peripheral Blood
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
- Elite partner
Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MAP2K4
SOURCE GeneReport for Unigene cluster for MAP2K4 Gene:
Hs.514681mRNA 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)
- Blood(2.7)
- Skin(2.6)
- Kidney(2.6)
- Intestine(2.6)
- Heart(2.6)
- Muscle(2.5)
- Lymph node(2.3)
- Lung(2.2)
- Eye(2.2)
- Pancreas(2.2)
- Adrenal gland(2.2)
- Spleen(2.1)
- Stomach(2)
- Thyroid gland(2)
Primer Products
-
OriGene qPCR primer pairs for MAP2K4
-
OriGene qPCR primer pairs and template standards for MAP2K4
Gene Expression Assay Products
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.
| Organism | Taxonomy | Gene | Similarity | Type | Details |
|---|---|---|---|---|---|
| Chimpanzee (Pan troglodytes) |
Mammalia | MAP2K4 30 31 |
|
OneToOne | |
| Oppossum (Monodelphis domestica) |
Mammalia | -- 31 |
|
OneToMany | |
| -- 31 |
|
OneToMany | |||
| Dog (Canis familiaris) |
Mammalia | MAP2K4 30 31 |
|
OneToOne | |
| Mouse (Mus musculus) |
Mammalia | Map2k4 30 17 31 |
|
OneToOne | |
| Rat (Rattus norvegicus) |
Mammalia | Map2k4 30 |
|
||
| Cow (Bos Taurus) |
Mammalia | MAP2K4 30 31 |
|
OneToOne | |
| Platypus (Ornithorhynchus anatinus) |
Mammalia | MAP2K4 31 |
|
OneToOne | |
| Chicken (Gallus gallus) |
Aves | MAP2K4 30 31 |
|
OneToOne | |
| Lizard (Anolis carolinensis) |
Reptilia | MAP2K4 31 |
|
OneToOne | |
| Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | map2k4 30 |
|
||
| African clawed frog (Xenopus laevis) |
Amphibia | Xl.13308 30 |
|
||
| Zebrafish (Danio rerio) |
Actinopterygii | map2k4b 31 |
|
OneToMany | |
| map2k4a 30 31 |
|
OneToMany | |||
| Dr.10451 30 |
|
||||
| Rainbow Trout (Oncorhynchus mykiss) |
Actinopterygii | Omy.4083 30 |
|
||
| African malaria mosquito (Anopheles gambiae) |
Insecta | AgaP_AGAP003365 30 |
|
||
| Fruit Fly (Drosophila melanogaster) |
Insecta | Mkk4 30 31 32 |
|
OneToOne | |
| lic 32 |
|
|
|||
| Worm (Caenorhabditis elegans) |
Secernentea | sek-1 32 |
|
|
|
| VZC374L.1 32 |
|
|
|||
| mkk-4 31 |
|
OneToMany | |||
| sek-6 31 |
|
OneToMany | |||
| jkk-1 32 |
|
|
|||
| F35C8.1 32 |
|
|
|||
| sek-3 31 |
|
OneToMany | |||
| Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToOne | |
| Fission Yeast (Schizosaccharomyces pombe) |
Schizosaccharomycetes | wis1 30 |
|
- 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
Variants for MAP2K4 Gene
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 | MISSENSE_VARIANT | |
| rs753665559 | A colorectal adenocarcinoma sample | p.Ala279Thr | |||
| VAR_040818 | A lung squamous cell carcinoma sample | p.Gln142Leu | |||
| VAR_040819 | A colorectal adenocarcinoma sample | p.Arg154Trp | |||
| VAR_040820 | An ovarian serous carcinoma sample | p.Asn234Ile |
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
SNP Genotyping and Copy Number Assay Products
No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAP2K4 Gene
Disorders for MAP2K4 Gene
| Disorder | Aliases | PubMed IDs |
|---|---|---|
| ovarian serous carcinoma |
|
|
| cardiomyopathy, familial hypertrophic, 25 |
|
|
| breast mucoepidermoid carcinoma |
|
|
| anthrax disease |
|
|
| pancreatic cancer |
|
Search MAP2K4 in MalaCards
View complete list of genes associated with diseases
Additional Disease Information for MAP2K4
- Genetic Association Database
- (GAD)
- Human Genome Epidemiology Navigator
- (HuGE)
- ATLAS of Genetics and Cytogenetics in Oncology and Haematology
- Open Targets Platform
No data available for UniProtKB/Swiss-Prot and Genatlas for MAP2K4 Gene
Publications for MAP2K4 Gene
- 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
- 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
- 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
- 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
- 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
ExternalLinks
Products for MAP2K4 Gene
- Custom Antibody ServicesOriGene Antibodies for MAP2K4
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- antibodies-online: Show 139 available MAP2K4 Antibodies ranked by validation data
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- 32 IHC Antibodies (anti-mouse)
- 12 IF (p) Antibodies (anti-mouse)
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- 12 IF (p) Antibodies (anti-rat)
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- antibodies-online: Show 6 available MAP2K4 Elisa Kits ranked by validation data
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Sources for MAP2K4 Gene
- (1) GeneCards
- (2) HGNC
- (3) NCBI Entrez Gene
- (4) UniProtKB/Swiss-Prot
- (5) Ensembl
- (6) OMIM
- (7) GeneLoc
- (8) Gene Wiki
- (9) UCSC
- (10) PhosphoSitePlus
- (11) Cell Signaling Technology
- (12) GO
- (13) UniProtKB/TrEMBL
- (14) InterPro
- (15) ProtoNet
- (16) Blocks
- (17) MGI
- (18) IUBMB
- (19) KEGG
- (20) MINT
- (21) STRING
- (22) IntAct
- (23) Novoseek
- (24) PharmGKB
- (25) DrugBank
- (26) HMDB
- (27) ASD
- (28) SAGE
- (29) SOURCE
- (30) HomoloGene
- (31) PanEnsembl
- (32) euGenes
- (33) SGD
- (34) FlyBase
- (35) WormBase
- (36) Pseudogene
- (37) DGV
- (38) dbSNP
- (39) GenAtlas
- (40) HGMD
- (41) GAD
- (42) BGMUT
- (43) HuGE
- (44) Atlas
- (45) GenBank
- (46) HORDE
- (47) HUGE
- (48) IMGT
- (49) Leiden
- (50) miRBase
- (51) DME
- (52) OriGene
- (53) PubMed
- (54) R&D Systems
- (55) TGDB
- (56) Tocris
- (57) Abcam
- (58) Novus Biologicals
- (59) ProSpec
- (60) Sino Biological
- (61) GenScript
- (62) Qiagen
- (63) OCA
- (64) Proteopedia
- (65) MOPED
- (66) neXtProt
- (67) Reactome
- (68) GeneGo (Thomson Reuters)
- (69) DISEASES
- (70) SIMAP
- (71) GenomeRNAi
- (72) LifeMap
- (73) miRTarBase
- (74) MalaCards
- (75) Invitrogen
- (76) BitterDB
- (77) ESI-BIO
- (78) RefSeq
- (79) BioSystems
- (80) MaxQB
- (81) IUPHAR
- (82) BioGPS
- (83) Illumina
- (84) COMPARTMENTS
- (85) HOMER
- (86) PaxDb
- (87) ApexBio
- (88) Addgene
- (89) antibodies-online
- (90) CYP
- (91) NONCODE
- (92) TreeFam
- (93) PathCards
- (94) GeneReviews
- (95) GeneTex
- (96) Taconic Biosciences
- (97) GTEx
- (98) ProteomicsDB
- (99) SCBT
- (100) DGIdb
- (101) ClinicalTrials
- (102) RVIS
- (103) SIGNOR
- (104) diseasecard
- (105) NIH Rare Diseases
- (106) Orphanet
- (107) UMLS
- (108) GTR
- (109) Disease Ontology
- (110) Genetics Home Reference
- (111) MeSH
- (112) MedlinePlus
- (113) CDC
- (114) NINDS
- (115) NCBI Bookshelf
- (116) ClinVar
- (117) Gene Damage Index
- (118) HPO
- (119) UDN
- (120) VISTA
- (121) FANTOM5
- (122) ENCODE
- (123) ProSci
- (124) Horizon
- (125) The Signaling Pathways Project (SPP)
- (126) IID
- (127) VectorBuilder
- (128) SNPedia
- (129) BRCA Exchange
- (130) CIViC
- (131) ProteoGenix
- (132) dbSUPER
- (133) TISSUES
- (134) Gene ORGANizer
- (135) abm
- (136) Human Protein Atlas
- (137) GWAS Catalog
- (138) Monarch Initiative
- (139) DataMed
- (140) HumanCyc
- (141) UCNEbase
- (142) EPDnew
- (143) Applied Biosystems
- (144) GlyConnect
- (145) Aminode
- (146) GeneCopoeia
- (147) GPS-Prot
- (148) RNACentral
- (149) LncRNADisease
- (150) LOVD
- (151) miR2Disease
- (152) DiseaseEnhancer
- (153) Boster Bio
- (154) Biorbyt
- (155) Biocompare
- (156) Mastermind
- (157) CTD^2 Dashboard
- (158) CraniofacialAtlas
- (159) GeneImprint
- (160) Synthego
- (161) ENA
- (162) GtRNAdb
- (163) LncBase
- (164) LncBook
- (165) LNCipedia
- (166) Modomics
- (167) PDBe
- (168) Rfam
- (169) SILVA
- (170) snOPY
- (171) SRPDB
- (172) GENCODE
- (173) TarBase
- (174) Signalway Antibody
- (175) Open Targets Platform
- (176) 5SRRNADB
- (177) snoDB
- (178) MirGeneDB