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Aliases for MAP3K3 Gene

Aliases for MAP3K3 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase 3 2 3 5
  • MAPK/ERK Kinase Kinase 3 2 3 4
  • MAP/ERK Kinase Kinase 3 2 3
  • MEK Kinase 3 3 4
  • MAPKKK3 3 4
  • MEKK 3 3 4
  • MEKK3 3 4
  • EC 2.7.11.25 4

External Ids for MAP3K3 Gene

Previous HGNC Symbols for MAP3K3 Gene

  • MEKK3

Previous GeneCards Identifiers for MAP3K3 Gene

  • GC17P061350
  • GC17P064126
  • GC17P062040
  • GC17P062173
  • GC17P059053
  • GC17P061699
  • GC17P057077

Summaries for MAP3K3 Gene

Entrez Gene Summary for MAP3K3 Gene

  • This gene product is a 626-amino acid polypeptide that is 96.5% identical to mouse Mekk3. Its catalytic domain is closely related to those of several other kinases, including mouse Mekk2, tobacco NPK, and yeast Ste11. Northern blot analysis revealed a 4.6-kb transcript that appears to be ubiquitously expressed. This protein directly regulates the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by activating SEK and MEK1/2 respectively; it does not regulate the p38 pathway. In cotransfection assays, it enhanced transcription from a nuclear factor kappa-B (NFKB)-dependent reporter gene, consistent with a role in the SAPK pathway. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

GeneCards Summary for MAP3K3 Gene

MAP3K3 (Mitogen-Activated Protein Kinase Kinase Kinase 3) is a Protein Coding gene. Diseases associated with MAP3K3 include Cerebral Cavernous Malformations-2 and Cavernous Malformation. Among its related pathways are TNFR1 Pathway and p38 MAPK signaling pathway (Pathway Interaction Database). 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 MAP3K2.

UniProtKB/Swiss-Prot for MAP3K3 Gene

  • Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators.

Gene Wiki entry for MAP3K3 Gene

Additional gene information for MAP3K3 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MAP3K3 Gene

Genomics for MAP3K3 Gene

Regulatory Elements for MAP3K3 Gene

Enhancers for MAP3K3 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
GH17H063837 1.8 FANTOM5 ENCODE dbSUPER 18.1 +218.8 218763 7 ZFP64 YBX1 FEZF1 DMAP1 YY1 SLC30A9 ZNF143 ZNF548 SP3 NFYC FTSJ3 POLG2 CEP95 DDX42 ENSG00000265982 DDX5 PLEKHM1P1 SMURF2 SMARCD2 DCAF7
GH17H064501 1.4 ENCODE dbSUPER 22.8 +882.6 882564 7 FEZF1 DMAP1 YBX1 YY1 ZNF143 SP3 NFYC ZC3H11A MEF2D SSRP1 POLG2 FTSJ3 DDX42 CEP95 SLC16A6P1 DDX5 SMARCD2 PLEKHM1P1 ENSG00000265982 MAP3K3
GH17H063621 1.4 ENCODE dbSUPER 19 +0.4 391 3 HDGF PKNOX1 ZFP64 ARID4B SIN3A DMAP1 ZNF2 ZBTB7B YY1 ZNF143 FTSJ3 POLG2 CEP95 DDX42 DDX5 SMARCD2 EEF1DP7 MAP3K3 ENSG00000281311 DCAF7
GH17H063982 1.4 Ensembl ENCODE dbSUPER 18.9 +362.4 362378 3 PKNOX1 FOXA2 TBL1XR1 ZSCAN4 SIN3A KLF17 BMI1 BATF RAD21 ZBTB7B FTSJ3 POLG2 DDX42 DDX5 CEP95 MAP3K3 CD79B GH1 CSHL1 ICAM2
GH17H063600 1.2 ENCODE 18.6 -20.9 -20933 2 MLX ZFP64 FEZF1 DMAP1 YY1 SLC30A9 ZNF143 SP3 NFYC ZC3H11A FTSJ3 DDX42 POLG2 CEP95 DDX5 DCAF7 MAP3K3 CSH2 ENSG00000263501 ENSG00000259333
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around MAP3K3 on UCSC Golden Path with GeneCards custom track

Promoters for MAP3K3 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000096822 491 2601 HDGF PKNOX1 MLX ZFP64 ARID4B SIN3A DMAP1 ZNF2 ZBTB7B YY1

Genomic Location for MAP3K3 Gene

Chromosome:
17
Start:
63,622,209 bp from pter
End:
63,696,310 bp from pter
Size:
74,102 bases
Orientation:
Plus strand

Genomic View for MAP3K3 Gene

Genes around MAP3K3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MAP3K3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MAP3K3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP3K3 Gene

Proteins for MAP3K3 Gene

  • Protein details for MAP3K3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99759-M3K3_HUMAN
    Recommended name:
    Mitogen-activated protein kinase kinase kinase 3
    Protein Accession:
    Q99759
    Secondary Accessions:
    • B2RCW2
    • D3DU15
    • Q5BKZ6
    • Q8N3I9

    Protein attributes for MAP3K3 Gene

    Size:
    626 amino acids
    Molecular mass:
    70898 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Binds both upstream activators and downstream substrates in multimolecular complexes. Part of a complex with MAP2K3, RAC1 and CCM2. Interacts with MAP2K5 and SPAG9.

    Three dimensional structures from OCA and Proteopedia for MAP3K3 Gene

    Alternative splice isoforms for MAP3K3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP3K3 Gene

Post-translational modifications for MAP3K3 Gene

  • Phosphorylation at Ser-166 and Ser-337 by SGK1 inhibits its activity.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for MAP3K3 (MEKK3)
  • Abcam antibodies for MAP3K3

No data available for DME Specific Peptides for MAP3K3 Gene

Domains & Families for MAP3K3 Gene

Gene Families for MAP3K3 Gene

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

Protein Domains for MAP3K3 Gene

Suggested Antigen Peptide Sequences for MAP3K3 Gene

Graphical View of Domain Structure for InterPro Entry

Q99759

UniProtKB/Swiss-Prot:

M3K3_HUMAN :
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
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 MAP3K3: view

Function for MAP3K3 Gene

Molecular function for MAP3K3 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by phosphorylation on Thr-530.
UniProtKB/Swiss-Prot Function:
Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators.

Enzyme Numbers (IUBMB) for MAP3K3 Gene

Phenotypes From GWAS Catalog for MAP3K3 Gene

Gene Ontology (GO) - Molecular Function for MAP3K3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity IDA,IEA 15001576
GO:0004674 protein serine/threonine kinase activity IBA,IEA --
GO:0004709 MAP kinase kinase kinase activity IEA --
GO:0005515 protein binding IPI 9452471
genes like me logo Genes that share ontologies with MAP3K3: view
genes like me logo Genes that share phenotypes with MAP3K3: view

Animal Models for MAP3K3 Gene

MGI Knock Outs for MAP3K3:

Animal Model Products

  • Taconic Biosciences Mouse Models for MAP3K3

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones for MAP3K3
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MAP3K3 Gene

Localization for MAP3K3 Gene

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 MAP3K3 gene
Compartment Confidence
cytosol 5
nucleus 4

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for MAP3K3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IEA --
GO:0005737 cytoplasm IBA --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with MAP3K3: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for MAP3K3 Gene

Pathways & Interactions for MAP3K3 Gene

genes like me logo Genes that share pathways with MAP3K3: view

SIGNOR curated interactions for MAP3K3 Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for MAP3K3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade IEA --
GO:0000186 activation of MAPKK activity IEA --
GO:0001568 blood vessel development IEA --
GO:0006468 protein phosphorylation IEA --
GO:0007346 regulation of mitotic cell cycle IBA --
genes like me logo Genes that share ontologies with MAP3K3: view

Drugs & Compounds for MAP3K3 Gene

(4) Drugs for MAP3K3 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
ATP Nutra Agonist 0
Magnesium Nutra 0

(2) Additional Compounds for MAP3K3 Gene - From: Novoseek and 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 MAP3K3: view

Transcripts for MAP3K3 Gene

Unigene Clusters for MAP3K3 Gene

Mitogen-activated protein kinase kinase kinase 3:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Applied Biological Materials Clones for MAP3K3
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

Alternative Splicing Database (ASD) splice patterns (SP) for MAP3K3 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11a · 11b · 11c · 11d ^ 12 ^ 13 ^ 14 ^ 15 ^ 16
SP1: -
SP2:
SP3: -
SP4:
SP5:

Relevant External Links for MAP3K3 Gene

GeneLoc Exon Structure for
MAP3K3
ECgene alternative splicing isoforms for
MAP3K3

Expression for MAP3K3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MAP3K3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MAP3K3 Gene

This gene is overexpressed in Whole Blood (x6.3).

Protein differential expression in normal tissues from HIPED for MAP3K3 Gene

This gene is overexpressed in Cervix (38.1) and Adipocyte (21.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for MAP3K3 Gene



Protein tissue co-expression partners for MAP3K3 Gene

NURSA nuclear receptor signaling pathways regulating expression of MAP3K3 Gene:

MAP3K3

SOURCE GeneReport for Unigene cluster for MAP3K3 Gene:

Hs.29282

Evidence on tissue expression from TISSUES for MAP3K3 Gene

  • Nervous system(4.7)
  • Skin(2.1)
genes like me logo Genes that share expression patterns with MAP3K3: view

Primer Products

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for MAP3K3 Gene

Orthologs for MAP3K3 Gene

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

Orthologs for MAP3K3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MAP3K3 33 34
  • 99.8 (n)
oppossum
(Monodelphis domestica)
Mammalia MAP3K3 34
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MAP3K3 33 34
  • 93.08 (n)
cow
(Bos Taurus)
Mammalia MAP3K3 34 33
  • 92.69 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Map3k3 33 16 34
  • 90.52 (n)
rat
(Rattus norvegicus)
Mammalia Map3k3 33
  • 89.88 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia MAP3K3 34
  • 78 (a)
OneToOne
chicken
(Gallus gallus)
Aves MAP3K3 33 34
  • 80.24 (n)
lizard
(Anolis carolinensis)
Reptilia MAP3K3 34
  • 85 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia map3k3 33
  • 72.57 (n)
zebrafish
(Danio rerio)
Actinopterygii map3k3 33 34
  • 71.36 (n)
worm
(Caenorhabditis elegans)
Secernentea mtk-1 35
  • 31 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes STE11 36 34
  • 24 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 46 (a)
OneToMany
Species where no ortholog for MAP3K3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • 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)
  • fruit fly (Drosophila melanogaster)
  • 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 MAP3K3 Gene

ENSEMBL:
Gene Tree for MAP3K3 (if available)
TreeFam:
Gene Tree for MAP3K3 (if available)

Paralogs for MAP3K3 Gene

Variants for MAP3K3 Gene

Sequence variations from dbSNP and Humsavar for MAP3K3 Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type
rs1000005239 -- 63,681,622(+) GAGGG(A/G)GCTGG intron-variant, downstream-variant-500B
rs1000104024 -- 63,659,491(+) ATATC(A/G)GTTTT intron-variant
rs1000113176 -- 63,675,322(+) GAGTT(C/T)AGGAA intron-variant
rs1000169674 -- 63,660,787(+) GACGG(A/G)GTTTC intron-variant
rs1000177595 -- 63,672,532(+) CTCTA(G/T)CTCAG intron-variant, nc-transcript-variant

Structural Variations from Database of Genomic Variants (DGV) for MAP3K3 Gene

Variant ID Type Subtype PubMed ID
esv2510594 CNV insertion 19546169
esv2671505 CNV deletion 23128226
esv3379241 CNV insertion 20981092
esv3582854 CNV loss 25503493
esv3641003 CNV loss 21293372
esv3641004 CNV loss 21293372
nsv952356 CNV deletion 24416366

Variation tolerance for MAP3K3 Gene

Residual Variation Intolerance Score: 28.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.06; 37.82% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for MAP3K3 Gene

Human Gene Mutation Database (HGMD)
MAP3K3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MAP3K3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAP3K3 Gene

Disorders for MAP3K3 Gene

MalaCards: The human disease database

(6) MalaCards diseases for MAP3K3 Gene - From: HGMD, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
cerebral cavernous malformations-2
  • cavernous angiomatous malformations
cavernous malformation
cerebral cavernous malformations 3
  • cavernous angiomatous malformations
central nervous system hemangioma
  • hemangioma of cns
cerebral cavernous malformations-1
  • hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations
- elite association - COSMIC cancer census association via MalaCards

Relevant External Links for MAP3K3

Genetic Association Database (GAD)
MAP3K3
Human Genome Epidemiology (HuGE) Navigator
MAP3K3
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
MAP3K3
genes like me logo Genes that share disorders with MAP3K3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MAP3K3 Gene

Publications for MAP3K3 Gene

  1. Direct activation of the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated protein Kinase/ERK kinase kinase 3 (MEKK) derivative. (PMID: 9006902) Ellinger-Ziegelbauer H … Siebenlist U (The Journal of biological chemistry 1997) 2 3 4 22 60
  2. Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3. (PMID: 14661019) Huang Q … Su B (Nature immunology 2004) 3 4 22 60
  3. PB1 domains of MEKK2 and MEKK3 interact with the MEK5 PB1 domain for activation of the ERK5 pathway. (PMID: 12912994) Nakamura K … Johnson GL (The Journal of biological chemistry 2003) 3 4 22 60
  4. Genome-wide association study of body height in African Americans: the Women's Health Initiative SNP Health Association Resource (SHARe). (PMID: 22021425) Carty CL … Kooperberg C (Human molecular genetics 2012) 3 45 60
  5. Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry. (PMID: 21998595) N'Diaye A … Haiman CA (PLoS genetics 2011) 3 45 60

Products for MAP3K3 Gene

Sources for MAP3K3 Gene

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