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Aliases for MAP3K4 Gene

Aliases for MAP3K4 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase 4 2 3
  • MAPKKK4 3 4 6
  • MEKK4 3 4 6
  • MTK1 3 4 6
  • MAPK/ERK Kinase Kinase 4 3 4
  • MAP Three Kinase 1 3 4
  • MEK Kinase 4 3 4
  • MEKK 4 3 4
  • DJ473J16.1 (Mitogen-Activated Protein Kinase Kinase Kinase 4) 3
  • SSK2/SSK22 MAP Kinase Kinase Kinase, Yeast, Homolog Of 3
  • Predicted Protein Of HQ0412 3
  • MAP/ERK Kinase Kinase 4 3
  • EC 2.7.11.25 4
  • KIAA0213 4
  • PRO0412 3

External Ids for MAP3K4 Gene

Previous HGNC Symbols for MAP3K4 Gene

  • MEKK4

Previous GeneCards Identifiers for MAP3K4 Gene

  • GC06P160766
  • GC06P161286
  • GC06P161322
  • GC06P161383
  • GC06P161332
  • GC06P161412
  • GC06P158868

Summaries for MAP3K4 Gene

Entrez Gene Summary for MAP3K4 Gene

  • The central core of each mitogen-activated protein kinase (MAPK) pathway is a conserved cascade of 3 protein kinases: an activated MAPK kinase kinase (MAPKKK) phosphorylates and activates a specific MAPK kinase (MAPKK), which then activates a specific MAPK. While the ERK MAPKs are activated by mitogenic stimulation, the CSBP2 and JNK MAPKs are activated by environmental stresses such as osmotic shock, UV irradiation, wound stress, and inflammatory factors. This gene encodes a MAPKKK, the MEKK4 protein, also called MTK1. This protein contains a protein kinase catalytic domain at the C terminus. The N-terminal nonkinase domain may contain a regulatory domain. Expression of MEKK4 in mammalian cells activated the CSBP2 and JNK MAPK pathways, but not the ERK pathway. In vitro kinase studies indicated that recombinant MEKK4 can specifically phosphorylate and activate PRKMK6 and SERK1, MAPKKs that activate CSBP2 and JNK, respectively but cannot phosphorylate PRKMK1, an MAPKK that activates ERKs. MEKK4 is a major mediator of environmental stresses that activate the CSBP2 MAPK pathway, and a minor mediator of the JNK pathway. Several alternatively spliced transcripts encoding distinct isoforms have been described. [provided by RefSeq, May 2014]

GeneCards Summary for MAP3K4 Gene

MAP3K4 (Mitogen-Activated Protein Kinase Kinase Kinase 4) is a Protein Coding gene. Among its related pathways are MAPK signaling pathway and Development FGFR signaling pathway. GO annotations related to this gene include protein kinase activity and MAP kinase kinase kinase activity.

UniProtKB/Swiss-Prot for MAP3K4 Gene

  • Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6.

Gene Wiki entry for MAP3K4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MAP3K4 Gene

Genomics for MAP3K4 Gene

Regulatory Elements for MAP3K4 Gene

Genomic Location for MAP3K4 Gene

Start:
160,991,727 bp from pter
End:
161,117,385 bp from pter
Size:
125,659 bases
Orientation:
Plus strand

Genomic View for MAP3K4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for MAP3K4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP3K4 Gene

Proteins for MAP3K4 Gene

  • Protein details for MAP3K4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y6R4-M3K4_HUMAN
    Recommended name:
    Mitogen-activated protein kinase kinase kinase 4
    Protein Accession:
    Q9Y6R4
    Secondary Accessions:
    • A6H8W0
    • B7ZLD3
    • B9EG75
    • Q5VTT8
    • Q5VTT9
    • Q92612
    • Q9H408

    Protein attributes for MAP3K4 Gene

    Size:
    1608 amino acids
    Molecular mass:
    181685 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Monomer and homodimer. Homodimerization enhances kinase activity. Interacts with TRAF4; this promotes homodimerization (By similarity). Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with AXIN1 and DIXDC1; interaction with DIXDC1 prevents interaction with AXIN1.
    SequenceCaution:
    • Sequence=BAA13204.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; Sequence=CAC12766.2; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAH70639.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAH70640.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAI20815.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAI20816.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAI21477.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAI41309.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; Sequence=CAI41310.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Alternative splice isoforms for MAP3K4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP3K4 Gene

Proteomics data for MAP3K4 Gene at MOPED

Post-translational modifications for MAP3K4 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for MAP3K4 Gene

Domains for MAP3K4 Gene

Gene Families for MAP3K4 Gene

HGNC:
  • MAP3K :Mitogen-activated protein kinase cascade / Kinase kinase kinases
IUPHAR :

Suggested Antigen Peptide Sequences for MAP3K4 Gene

Graphical View of Domain Structure for InterPro Entry

Q9Y6R4

UniProtKB/Swiss-Prot:

M3K4_HUMAN :
  • Q9Y6R4
Domain:
  • Contains 1 protein kinase domain.
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
genes like me logo Genes that share domains with MAP3K4: view

Function for MAP3K4 Gene

Molecular function for MAP3K4 Gene

GENATLAS Biochemistry: mitogen activated protein (MAP/ERK) kinase kinase kinase 4,major mediator of environnemtal stress,activating the MAPK and JNK signal transduction pathway (see MAP4K4)
UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein
UniProtKB/Swiss-Prot EnzymeRegulation: N-terminal autoinhibitory domain interacts with the C-terminal kinase domain, inhibiting kinase activity, and preventing interaction with its substrate, MAP2K6. The GADD45 proteins activate the kinase by binding to the N-terminal domain. Activated by phosphorylation on Thr-1505.
UniProtKB/Swiss-Prot Function: Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6.

Enzyme Numbers (IUBMB) for MAP3K4 Gene

Gene Ontology (GO) - Molecular Function for MAP3K4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity --
GO:0004674 protein serine/threonine kinase activity --
GO:0004708 MAP kinase kinase activity IBA --
GO:0004709 MAP kinase kinase kinase activity IDA 9305639
GO:0004713 protein tyrosine kinase activity --
genes like me logo Genes that share ontologies with MAP3K4: view
genes like me logo Genes that share phenotypes with MAP3K4: view

Animal Models for MAP3K4 Gene

MGI Knock Outs for MAP3K4:

miRNA for MAP3K4 Gene

No data available for Transcription Factor Targeting and HOMER Transcription for MAP3K4 Gene

Localization for MAP3K4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MAP3K4 Gene

Cytoplasm, perinuclear region. Note=Localized in perinuclear vesicular-like structures, probably Golgi-associated vesicles. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for MAP3K4 Gene COMPARTMENTS Subcellular localization image for MAP3K4 gene
Compartment Confidence
cytosol 3
lysosome 1
nucleus 1
vacuole 1

Gene Ontology (GO) - Cellular Components for MAP3K4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA 9827804
GO:0048471 perinuclear region of cytoplasm IEA --
genes like me logo Genes that share ontologies with MAP3K4: view

Pathways for MAP3K4 Gene

genes like me logo Genes that share pathways with MAP3K4: view

Gene Ontology (GO) - Biological Process for MAP3K4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade IEA --
GO:0000186 activation of MAPKK activity IDA 9305639
GO:0000187 activation of MAPK activity IBA --
GO:0001890 placenta development IEA --
GO:0006468 protein phosphorylation IEA --
genes like me logo Genes that share ontologies with MAP3K4: view

Compounds for MAP3K4 Gene

(23) ApexBio Compounds for MAP3K4 Gene

Compound Action Cas Number
AZD6244 (Selumetinib) Potent, selective, and ATP-uncompetitive MEK inhibitor
AZD8330 orally active, selective MEK inhibitor [869357-68-6]
BIX 02188 MEK5-selective inhibitor [1094614-84-2]
BIX 02189 blocks MEK5 and ERK5 catalytic activity [1094614-85-3]
Cobimetinib selective inhibitor of MEK [934660-93-2]
FR 180204 Selective ERK inhibitor [865362-74-9]
MEK inhibitor Potent MEK inhibitor, Antitumor agent. [334951-92-7]
MEK162 (ARRY-162, ARRY-438162) orally available inhibitor of MEK1/2 [606143-89-9]
PD0325901 MEK inhibitor [391210-10-9]
PD184352 (CI-1040) Selective MEK inhibitor [212631-79-3]
PD318088 inhibit MEK-1 and MEK-2. [391210-00-7]
PD98059 Inhibitor of MKK/MEK. [167869-21-8]
Pimasertib (AS-703026) highly selective and potent noncompetitive inhibitor of MEK1 and MEK2 [1236699-92-5]
PLX-4720 Potent and selective inhibitor of BRAF with V600E mutation [918505-84-7]
SCH772984 novel, potent and ATP-competitive inhibition of ERK1 and ERK2 [942183-80-4]
SL-327 Selective inhibitor of MEK1 and MEK2 [305350-87-2]
Trametinib (GSK1120212) Potent and selective MEK1 and MEK2 inhibitor [871700-17-3]
Trametinib DMSO solvate reversible, selective, allosteric MEK1/MEK2 kinase activity inhibitor [1187431-43-1]
U0126-EtOH Potent, selective, and uncompetitive MEK1/2 inhibitor [1173097-76-1]
Vemurafenib (PLX4032, RG7204) Potent and selective inhibitor of BRAF with V600E mutation [918504-65-1]
VX-11e potent, selective, and orally bioavailable inhibitor of ERK [896720-20-0]
XMD17-109 novel, specific ERK-5 inhibitor with an EC50 4.2uM in HEK293 cells [1435488-37-1]
XMD8-92 highly selective ERK5/BMK1 inhibitor [1234480-50-2]

(3) HMDB Compounds for MAP3K4 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0
Magnesium
  • Magnesium
7439-95-4

(1) Novoseek inferred chemical compound relationships for MAP3K4 Gene

Compound -log(P) Hits PubMed IDs
tyrosine 0 4
genes like me logo Genes that share compounds with MAP3K4: view

Transcripts for MAP3K4 Gene

Unigene Clusters for MAP3K4 Gene

Mitogen-activated protein kinase kinase kinase 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for MAP3K4 Gene

ExUns: 1 ^ 2a · 2b ^ 3a · 3b ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b · 12c ^ 13a · 13b ^ 14 ^ 15a · 15b ^ 16a · 16b ^ 17 ^ 18 ^
SP1: - - - -
SP2:
SP3: - - -
SP4: -
SP5: -
SP6:
SP7: -
SP8:
SP9:
SP10:
SP11: - -

ExUns: 19a · 19b ^ 20 ^ 21 ^ 22 ^ 23 ^ 24 ^ 25
SP1: - -
SP2: - -
SP3:
SP4:
SP5:
SP6: -
SP7:
SP8:
SP9:
SP10:
SP11:

Relevant External Links for MAP3K4 Gene

GeneLoc Exon Structure for
MAP3K4
ECgene alternative splicing isoforms for
MAP3K4

Expression for MAP3K4 Gene

mRNA expression in normal human tissues for MAP3K4 Gene

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for MAP3K4 Gene

SOURCE GeneReport for Unigene cluster for MAP3K4 Gene Hs.390428

mRNA Expression by UniProt/SwissProt for MAP3K4 Gene

Q9Y6R4-M3K4_HUMAN
Tissue specificity: Expressed at high levels in heart, placenta, skeletal muscle and pancreas, and at lower levels in other tissues.
genes like me logo Genes that share expressions with MAP3K4: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for MAP3K4 Gene

Orthologs for MAP3K4 Gene

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

Orthologs for MAP3K4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MAP3K4 35
  • 97.75 (n)
  • 97.38 (a)
cow
(Bos Taurus)
Mammalia MAP3K4 35
  • 86.4 (n)
  • 91.94 (a)
MAP3K4 36
  • 91 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MAP3K4 35
  • 89.79 (n)
  • 93.71 (a)
MAP3K4 36
  • 93 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Map3k4 35
  • 83.67 (n)
  • 89.6 (a)
Map3k4 16
Map3k4 36
  • 89 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia MAP3K4 36
  • 87 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MAP3K4 36
  • 88 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Map3k4 35
  • 84.64 (n)
  • 90.92 (a)
chicken
(Gallus gallus)
Aves MAP3K4 35
  • 80.69 (n)
  • 86.45 (a)
MAP3K4 36
  • 86 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MAP3K4 36
  • 82 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.15863 35
tropical clawed frog
(Silurana tropicalis)
Amphibia map3k4 35
  • 73.15 (n)
  • 77.4 (a)
Str.625 35
zebrafish
(Danio rerio)
Actinopterygii map3k4 35
  • 66.87 (n)
  • 72.92 (a)
map3k4 36
  • 71 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP002371 35
  • 48.44 (n)
  • 39.64 (a)
fruit fly
(Drosophila melanogaster)
Insecta Mekk1 35
  • 45.83 (n)
  • 37.41 (a)
Mekk1 36
  • 21 (a)
OneToOne
Mekk1 37
  • 50 (a)
worm
(Caenorhabditis elegans)
Secernentea F18F11.5 36
  • 24 (a)
OneToOne
mtk-1 37
  • 36 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SSK2 36
  • 18 (a)
OneToMany
SSK2 38
SSK22 36
  • 21 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 58 (a)
OneToOne
Species with no ortholog for MAP3K4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • 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)
  • fission yeast (Schizosaccharomyces pombe)
  • 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)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • 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 MAP3K4 Gene

ENSEMBL:
Gene Tree for MAP3K4 (if available)
TreeFam:
Gene Tree for MAP3K4 (if available)

Paralogs for MAP3K4 Gene

genes like me logo Genes that share paralogs with MAP3K4: view

No data available for Paralogs for MAP3K4 Gene

Variants for MAP3K4 Gene

Sequence variations from dbSNP and Humsavar for MAP3K4 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type MAF
rs1488 -- 161,117,218(+) CAGGC(A/G)TCCCA utr-variant-3-prime, nc-transcript-variant
rs2468 -- 160,990,417(+) GAGTA(A/G)AGAAC upstream-variant-2KB
rs583856 -- 161,016,743(+) ctttg(C/T)ttagt intron-variant
rs588284 -- 161,015,565(+) gtcag(C/G)ctgta intron-variant
rs589238 -- 161,002,017(+) CCCCC(A/G)ACGTC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for MAP3K4 Gene

Variant ID Type Subtype PubMed ID
esv2422347 CNV Duplication 17116639
nsv886817 CNV Gain 21882294
esv2733067 CNV Deletion 23290073
esv2287098 CNV Deletion 18987734
esv5229 CNV Deletion 18987735
esv2733068 CNV Deletion 23290073
esv2733069 CNV Deletion 23290073
esv1022211 CNV Deletion 17803354
esv1009798 CNV Deletion 20482838
esv2733070 CNV Deletion 23290073
esv2733071 CNV Deletion 23290073

Relevant External Links for MAP3K4 Gene

HapMap Linkage Disequilibrium report
MAP3K4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAP3K4 Gene

Disorders for MAP3K4 Gene

(1) University of Copenhagen DISEASES for MAP3K4 Gene

(1) Novoseek inferred disease relationships for MAP3K4 Gene

Disease -log(P) Hits PubMed IDs
shock 15.7 1

Relevant External Links for MAP3K4

Genetic Association Database (GAD)
MAP3K4
Human Genome Epidemiology (HuGE) Navigator
MAP3K4
genes like me logo Genes that share disorders with MAP3K4: view

No data available for UniProtKB/Swiss-Prot for MAP3K4 Gene

Publications for MAP3K4 Gene

  1. A human homolog of the yeast Ssk2/Ssk22 MAP kinase kinase kinases, MTK1, mediates stress-induced activation of the p38 and JNK pathways. (PMID: 9305639) Takekawa M. … Saito H. (EMBO J. 1997) 2 3 4 23
  2. The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal kinase activation by Axin and dishevelled through distinct mechanisms. (PMID: 15262978) Wong C.K. … Lin S.-C. (J. Biol. Chem. 2004) 3 4 23
  3. MEKK4 is an effector of the embryonic TRAF4 for JNK activation. (PMID: 16157600) Abell A.N. … Johnson G.L. (J. Biol. Chem. 2005) 3 4 23
  4. Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases. (PMID: 15866172) Takekawa M. … Saito H. (Mol. Cell 2005) 3 23
  5. Interferon-gamma-dependent tyrosine phosphorylation of MEKK4 via Pyk2 is regulated by annexin II and SHP2 in keratinocytes. (PMID: 15601262) Halfter U.M. … Vaillancourt R.R. (Biochem. J. 2005) 3 23

Products for MAP3K4 Gene

Sources for MAP3K4 Gene

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