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Aliases for MAP3K4 Gene

Aliases for MAP3K4 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase 4 2 3 5
  • MAPK/ERK Kinase Kinase 4 3 4
  • MAP Three Kinase 1 3 4
  • MEK Kinase 4 3 4
  • MAPKKK4 3 4
  • MEKK 4 3 4
  • MEKK4 3 4
  • MTK1 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 Development A3 receptor signaling and Development A2B receptor- action via G-protein alpha s. 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 MAP3K5.

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

Enhancers for MAP3K4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH06F160949 0.8 ENCODE 24.8 -41.5 -41517 2.0 HDGF CTCF PKNOX1 ARID4B ZNF644 RAD21 ZNF316 ZNF366 ZNF143 SMC3 MAP3K4 ENSG00000231863 GC06M160991
GH06F160952 0.9 ENCODE 11.2 -38.6 -38581 1.3 YBX3 HDGF ARNT ZNF493 GLI4 YBX1 NFXL1 ZNF2 RAD21 ZNF143 IGF2R MAP3K4 ENSG00000231863 GC06M160991
GH06F160971 1.5 FANTOM5 Ensembl ENCODE 6.1 -18.1 -18059 3.8 ATF1 PKNOX1 SIN3A GATA2 FOS JUNB REST TSHZ1 TBX21 CREB3 MAP3K4 ENSG00000272841 ENSG00000231863 GC06M160991
GH06F161033 1.1 Ensembl ENCODE 5.9 +43.1 43088 2.4 HDGF BCOR PKNOX1 ATF1 ZMYM3 RELA ZNF316 ADNP ZNF600 NFE2 MAP3K4 ENSG00000231863 GC06P161010 GC06P161073
GH06F161443 1.1 FANTOM5 Ensembl ENCODE 5.7 +453.0 452959 1.9 CTCF RNF2 ZBTB11 BHLHE40 MGA TRIM28 MAP3K4 AGPAT4 LOC105378098 GC06P161404
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around MAP3K4 on UCSC Golden Path with GeneCards custom track

Promoters for MAP3K4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00001232672 274 2800 PKNOX1 ARNT ARID4B SIN3A YBX1 YY1 ZNF766 CBX5 ZNF143 ZNF207

Genomic Location for MAP3K4 Gene

Chromosome:
6
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

Genes around MAP3K4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MAP3K4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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 (PubMed:16157600). Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with AXIN1 and DIXDC1; interaction with DIXDC1 prevents interaction with AXIN1 (PubMed:15262978). Interacts with GADD45 and MAP2K6 (PubMed:12052864). Interacts with ZFP36; this interaction enhances the association with SH3KBP1/CIN85 (PubMed:20221403). Interacts with SH3KBP1; this interaction enhances the association with ZFP36 (PubMed:20221403). Interacts with CDC42 (By similarity).
    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

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 & Families for MAP3K4 Gene

Protein Domains for MAP3K4 Gene

Suggested Antigen Peptide Sequences for MAP3K4 Gene

Graphical View of Domain Structure for InterPro Entry

Q9Y6R4

UniProtKB/Swiss-Prot:

M3K4_HUMAN :
  • Contains 1 protein kinase domain.
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
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:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity IEA --
GO:0004674 protein serine/threonine kinase activity IEA --
GO:0004709 MAP kinase kinase kinase activity IEA,IDA 9305639
GO:0005515 protein binding IPI 12052864
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:

Animal Model Products

  • Taconic Biosciences Mouse Models for MAP3K4

Inhibitory RNA Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , Transcription Factor Targets 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
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 MAP3K4 gene
Compartment Confidence
cytosol 4
nucleus 2
extracellular 1

Gene Ontology (GO) - Cellular Components for MAP3K4 Gene

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

Pathways & Interactions for MAP3K4 Gene

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

SIGNOR curated interactions for MAP3K4 Gene

Activates:
Is activated by:
Is inactivated by:

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:0001890 placenta development IEA --
GO:0006468 protein phosphorylation IEA --
GO:0010225 response to UV-C IMP 9305639
genes like me logo Genes that share ontologies with MAP3K4: view

Drugs & Compounds for MAP3K4 Gene

(3) Drugs for MAP3K4 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine triphosphate Approved Nutra 0
Magnesium Nutra 0

(1) Additional Compounds for MAP3K4 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
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:

Inhibitory RNA Products

Flow Cytometry Products

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 from GTEx, Illumina, BioGPS, and SAGE for MAP3K4 Gene

Protein differential expression in normal tissues from HIPED for MAP3K4 Gene

This gene is overexpressed in Testis (13.1), Ovary (10.9), Breast (8.1), and Lymph node (6.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for MAP3K4 Gene



Protein tissue co-expression partners for MAP3K4 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of MAP3K4 Gene:

MAP3K4

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 expression patterns with MAP3K4: view

Primer Products

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 34
  • 97.75 (n)
dog
(Canis familiaris)
Mammalia MAP3K4 34 35
  • 89.79 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia MAP3K4 35
  • 88 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia MAP3K4 35
  • 87 (a)
OneToOne
cow
(Bos Taurus)
Mammalia MAP3K4 34 35
  • 86.4 (n)
rat
(Rattus norvegicus)
Mammalia Map3k4 34
  • 84.64 (n)
mouse
(Mus musculus)
Mammalia Map3k4 34 16 35
  • 83.67 (n)
chicken
(Gallus gallus)
Aves MAP3K4 34 35
  • 80.69 (n)
lizard
(Anolis carolinensis)
Reptilia MAP3K4 35
  • 82 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia map3k4 34
  • 73.15 (n)
Str.625 34
African clawed frog
(Xenopus laevis)
Amphibia Xl.15863 34
zebrafish
(Danio rerio)
Actinopterygii map3k4 34 35
  • 66.87 (n)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP002371 34
  • 48.44 (n)
fruit fly
(Drosophila melanogaster)
Insecta Mekk1 36 34 35
  • 45.83 (n)
worm
(Caenorhabditis elegans)
Secernentea mtk-1 36
  • 36 (a)
F18F11.5 35
  • 24 (a)
OneToOne
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes SSK22 35
  • 21 (a)
OneToMany
SSK2 35 37
  • 18 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 58 (a)
OneToOne
Species where no ortholog for MAP3K4 was found in the sources mined by GeneCards:
  • 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

Variants for MAP3K4 Gene

Sequence variations from dbSNP and Humsavar for MAP3K4 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type
VAR_040691 An ovarian serous carcinoma sample
rs1000277 -- 161,105,793(-) ACTAA(C/T)CAAAT intron-variant
rs1001756 -- 161,105,475(+) aaatg(A/G)cgagg intron-variant
rs1001808 -- 161,057,414(+) GAGCT(A/G)TAGAT intron-variant
rs1001809 -- 161,057,478(+) gtttc(C/G)aaacc intron-variant

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

Variant ID Type Subtype PubMed ID
esv2422347 CNV duplication 17116639
esv2733067 CNV deletion 23290073
esv2733068 CNV deletion 23290073
esv2733069 CNV deletion 23290073
esv2733070 CNV deletion 23290073
esv2733071 CNV deletion 23290073
esv3576242 CNV gain 25503493
esv3611453 CNV gain 21293372
esv5229 CNV loss 18987735
nsv1026543 CNV gain 25217958
nsv1030045 CNV gain 25217958
nsv1030852 CNV gain 25217958
nsv1074442 CNV deletion 25765185
nsv1074443 CNV deletion 25765185
nsv1130850 CNV deletion 24896259
nsv1137172 CNV deletion 24896259
nsv1137559 CNV deletion 24896259
nsv1143327 CNV deletion 24896259
nsv1146290 CNV deletion 26484159
nsv1148627 CNV deletion 26484159
nsv949883 CNV duplication 24416366
esv2287098 CNV deletion 18987734
esv1022211 CNV deletion 17803354
esv1009798 CNV deletion 20482838

Variation tolerance for MAP3K4 Gene

Residual Variation Intolerance Score: 3.63% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.58; 65.17% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for MAP3K4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
MAP3K4

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

Disorders for MAP3K4 Gene

Relevant External Links for MAP3K4

Genetic Association Database (GAD)
MAP3K4
Human Genome Epidemiology (HuGE) Navigator
MAP3K4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
MAP3K4

No disorders were found for MAP3K4 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas 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 22 64
  2. Phosphorylation of human tristetraprolin in response to its interaction with the Cbl interacting protein CIN85. (PMID: 20221403) Kedar V.P. … Blackshear P.J. (PLoS ONE 2010) 3 4 22 64
  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 22 64
  4. 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 22 64
  5. Incorporating age at onset of smoking into genetic models for nicotine dependence: evidence for interaction with multiple genes. (PMID: 20624154) Grucza R.A. … Bierut L.J. (Addict Biol 2010) 3 46 64

Products for MAP3K4 Gene

Sources for MAP3K4 Gene

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