This gene encodes a member of the mitogen-activated protein kinase kinase kinase kinase family. The encoded protein activates key effectors in cell signalling, among them c-Jun. Alternatively spliced transcripts encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012] See more...

Aliases for MAP4K3 Gene

Aliases for MAP4K3 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase Kinase 3 2 3 4 5
  • GLK 2 3 4
  • Germinal Center Kinase-Related Protein Kinase 3 4
  • MAPK/ERK Kinase Kinase Kinase 3 3 4
  • MEK Kinase Kinase 3 3 4
  • EC 2.7.11.1 4 51
  • MAPKKKK3 2 3
  • RAB8IPL1 3 4
  • MEKKK 3 3 4
  • Germinal Center Kinase-Like Kinase 3
  • EC 2.7.11 51
  • MEKKK3 3
  • MAP4K3 5

External Ids for MAP4K3 Gene

Previous HGNC Symbols for MAP4K3 Gene

  • RAB8IPL1

Previous GeneCards Identifiers for MAP4K3 Gene

  • GC02M039440
  • GC02M039623
  • GC02M039450
  • GC02M039388
  • GC02M039329
  • GC02M039476
  • GC02M039215

Summaries for MAP4K3 Gene

Entrez Gene Summary for MAP4K3 Gene

  • This gene encodes a member of the mitogen-activated protein kinase kinase kinase kinase family. The encoded protein activates key effectors in cell signalling, among them c-Jun. Alternatively spliced transcripts encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

GeneCards Summary for MAP4K3 Gene

MAP4K3 (Mitogen-Activated Protein Kinase Kinase Kinase Kinase 3) is a Protein Coding gene. Diseases associated with MAP4K3 include Adult-Onset Still's Disease. Among its related pathways are Signal transduction_JNK pathway and MAPK signaling pathway. 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 MAP4K5.

UniProtKB/Swiss-Prot Summary for MAP4K3 Gene

  • May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.

Additional gene information for MAP4K3 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for MAP4K3 Gene

Genomics for MAP4K3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for MAP4K3 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 MAP4K3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for MAP4K3

Top Transcription factor binding sites by QIAGEN in the MAP4K3 gene promoter:
  • AML1a
  • CUTL1
  • HSF2
  • HTF
  • Msx-1
  • NF-AT1
  • PPAR-alpha
  • RORalpha1
  • SRF
  • SRF (504 AA)

Genomic Locations for MAP4K3 Gene

Genomic Locations for MAP4K3 Gene
chr2:39,248,941-39,437,312
(GRCh38/hg38)
Size:
188,372 bases
Orientation:
Minus strand
chr2:39,476,407-39,664,453
(GRCh37/hg19)
Size:
188,047 bases
Orientation:
Minus strand

Genomic View for MAP4K3 Gene

Genes around MAP4K3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MAP4K3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MAP4K3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP4K3 Gene

Proteins for MAP4K3 Gene

  • Protein details for MAP4K3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8IVH8-M4K3_HUMAN
    Recommended name:
    Mitogen-activated protein kinase kinase kinase kinase 3
    Protein Accession:
    Q8IVH8
    Secondary Accessions:
    • Q6IQ39
    • Q8IVH7
    • Q9UDM5
    • Q9Y6R5

    Protein attributes for MAP4K3 Gene

    Size:
    894 amino acids
    Molecular mass:
    101316 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Interacts with SH3GL2. Interaction appears to regulate MAP4K3-mediated JNK activation (By similarity).

    Three dimensional structures from OCA and Proteopedia for MAP4K3 Gene

    Alternative splice isoforms for MAP4K3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP4K3 Gene

Selected DME Specific Peptides for MAP4K3 Gene

Q8IVH8:
  • FIGTPYWMAPEV
  • VCLQDSVLAFWKHGMQG
  • GSGTYGDVYKARNV
  • GIYTLNLNELHE
  • KSNFQPPKLKDK
  • KGKMHRDIKGANILLTD
  • QLYSHNL
  • LLQHPFVT
  • PKKRPTA
  • VKLADFG
  • CGGGSLQDIYHVTGPLSE
  • ELLDKVNNPD
  • MEFCGGGS
  • LFLMTKS
  • PPLRKETE
  • ALTKNPKKRP
  • GITAIEL
  • ELQPPMFDLHPMRALFLM
  • MGACFSKVF
  • MEQLFPR
  • HRDIKGANI
  • GTPYWMAPE
  • EPMQKFMLIKH
  • GGYNQLCD
  • VRNPYTGHKYLCGALQ

Post-translational modifications for MAP4K3 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for MAP4K3 Gene

Gene Families for MAP4K3 Gene

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

Protein Domains for MAP4K3 Gene

Suggested Antigen Peptide Sequences for MAP4K3 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ55366, highly similar to Mitogen-activated protein kinase kinase kinase kinase 3 (EC 2.7.11.1) (B4DSS3_HUMAN)
  • cDNA, FLJ79043, highly similar to Mitogen-activated protein kinase kinase kinase kinase 3 (EC 2.7.11.1) (B7ZA29_HUMAN)
  • MAPK/ERK kinase kinase kinase 3 (M4K3_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8IVH8

UniProtKB/Swiss-Prot:

M4K3_HUMAN :
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
Family:
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
genes like me logo Genes that share domains with MAP4K3: view

Function for MAP4K3 Gene

Molecular function for MAP4K3 Gene

UniProtKB/Swiss-Prot Function:
May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.
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=2.7.11.1; Evidence={ECO:0000269|PubMed:9275185};.
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=2.7.11.1; Evidence={ECO:0000269|PubMed:9275185};.

Enzyme Numbers (IUBMB) for MAP4K3 Gene

Phenotypes From GWAS Catalog for MAP4K3 Gene

Gene Ontology (GO) - Molecular Function for MAP4K3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity IEA,TAS 9275185
GO:0004674 protein serine/threonine kinase activity IEA,IDA 9275185
GO:0005515 protein binding IPI 17474147
GO:0005524 ATP binding IEA,IDA 9275185
genes like me logo Genes that share ontologies with MAP4K3: view
genes like me logo Genes that share phenotypes with MAP4K3: view

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MAP4K3

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for MAP4K3 Gene

Localization for MAP4K3 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 MAP4K3 gene
Compartment Confidence
cytoskeleton 3
cytosol 3
nucleus 2
endosome 2
lysosome 2
plasma membrane 1
extracellular 1
mitochondrion 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Centriolar satellite (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for MAP4K3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA --
genes like me logo Genes that share ontologies with MAP4K3: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for MAP4K3 Gene

Pathways & Interactions for MAP4K3 Gene

genes like me logo Genes that share pathways with MAP4K3: view

Pathways by source for MAP4K3 Gene

1 KEGG pathway for MAP4K3 Gene
1 GeneGo (Thomson Reuters) pathway for MAP4K3 Gene
  • Signal transduction_JNK pathway
2 Qiagen pathways for MAP4K3 Gene
  • JNK Pathway
  • MAPK Family Pathway
1 Cell Signaling Technology pathway for MAP4K3 Gene

SIGNOR curated interactions for MAP4K3 Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for MAP4K3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade IEA --
GO:0000185 activation of MAPKKK activity IEA --
GO:0006468 protein phosphorylation IEA,IDA 9275185
GO:0007254 JNK cascade TAS 9275185
GO:0007346 regulation of mitotic cell cycle IBA --
genes like me logo Genes that share ontologies with MAP4K3: view

Drugs & Compounds for MAP4K3 Gene

(5) Drugs for MAP4K3 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
Magnesium Approved, Experimental, Investigational Pharma 0
ATP Investigational Nutra Agonist, Activator, Partial agonist, Antagonist, Full agonist, Gating inhibitor, Pore Blocker, Potentiation 0

(1) Additional Compounds for MAP4K3 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist 58-64-0
genes like me logo Genes that share compounds with MAP4K3: view

Transcripts for MAP4K3 Gene

mRNA/cDNA for MAP4K3 Gene

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

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for MAP4K3

Alternative Splicing Database (ASD) splice patterns (SP) for MAP4K3 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^ 24 ^ 25 ^
SP1:
SP2: -
SP3: - - - -
SP4:
SP5:
SP6:

ExUns: 26a · 26b ^ 27a · 27b ^ 28 ^ 29a · 29b · 29c ^ 30 ^ 31 ^ 32 ^ 33 ^ 34
SP1: - - -
SP2: - - -
SP3:
SP4: -
SP5:
SP6:

Relevant External Links for MAP4K3 Gene

GeneLoc Exon Structure for
MAP4K3

Expression for MAP4K3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for MAP4K3 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MAP4K3 Gene

This gene is overexpressed in Placenta (19.7), Testis (10.6), Frontal cortex (10.5), and Pancreas (9.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MAP4K3 Gene



Protein tissue co-expression partners for MAP4K3 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for MAP4K3

SOURCE GeneReport for Unigene cluster for MAP4K3 Gene:

Hs.655750

mRNA Expression by UniProt/SwissProt for MAP4K3 Gene:

Q8IVH8-M4K3_HUMAN
Tissue specificity: Ubiquitously expressed in all tissues examined, with high levels in heart, brain, placenta, skeletal muscle, kidney and pancreas and lower levels in lung and liver.

Evidence on tissue expression from TISSUES for MAP4K3 Gene

  • Muscle(4.6)
  • Nervous system(2.7)
  • Kidney(2.4)
  • Liver(2.3)
  • Lung(2.2)
  • Skin(2.1)
  • Heart(2.1)
  • Spleen(2.1)
genes like me logo Genes that share expression patterns with MAP4K3: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for MAP4K3 Gene

Orthologs for MAP4K3 Gene

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

Orthologs for MAP4K3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia MAP4K3 30 31
  • 99.66 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia MAP4K3 31
  • 98 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia MAP4K3 31
  • 95 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia MAP4K3 30 31
  • 94.89 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia MAP4K3 30 31
  • 94.15 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Map4k3 30 17 31
  • 88.96 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Map4k3 30
  • 87.78 (n)
Chicken
(Gallus gallus)
Aves MAP4K3 30 31
  • 83.77 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia MAP4K3 31
  • 92 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia map4k3 30
  • 79.61 (n)
Zebrafish
(Danio rerio)
Actinopterygii MAP4K3 (2 of 2) 31
  • 80 (a)
OneToMany
map4k3b 30 31
  • 71.59 (n)
OneToMany
Fruit Fly
(Drosophila melanogaster)
Insecta CG7097 32
  • 75 (a)
hppy 30 31
  • 58.74 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP010837 30
  • 42.51 (n)
Worm
(Caenorhabditis elegans)
Secernentea gck-2 30 31
  • 54.92 (n)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes KIC1 31
  • 21 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 55 (a)
OneToMany
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.2532 30
Species where no ortholog for MAP4K3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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 MAP4K3 Gene

ENSEMBL:
Gene Tree for MAP4K3 (if available)
TreeFam:
Gene Tree for MAP4K3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MAP4K3: view image

Paralogs for MAP4K3 Gene

(47) SIMAP similar genes for MAP4K3 Gene using alignment to 8 proteins:

  • M4K3_HUMAN
  • B4DSS3_HUMAN
  • F5H5A3_HUMAN
  • F8WAZ1_HUMAN
  • F8WBC3_HUMAN
  • H7C1A4_HUMAN
  • Q53RV1_HUMAN
  • V9GY95_HUMAN
genes like me logo Genes that share paralogs with MAP4K3: view

Variants for MAP4K3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for MAP4K3 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
711261 Likely Benign: not provided 39,326,210(-) C/A MISSENSE_VARIANT
736421 Likely Benign: not provided 39,309,528(-) G/T INTRON_VARIANT
rs1268580645 Uncertain Significance: Ependymoma 39,325,537(-) A/G MISSENSE_VARIANT
VAR_040745 A lung squamous cell carcinoma sample p.Thr669Ser
rs35957290 - p.Val200Leu

Additional dbSNP identifiers (rs#s) for MAP4K3 Gene

Structural Variations from Database of Genomic Variants (DGV) for MAP4K3 Gene

Variant ID Type Subtype PubMed ID
dgv6792n54 CNV gain 21841781
esv2442819 CNV deletion 19546169
esv2582384 CNV deletion 19546169
esv2677029 CNV deletion 23128226
esv2762497 CNV loss 21179565
esv3590429 CNV loss 21293372
esv6749 CNV gain 19470904
nsv2693 CNV deletion 18451855
nsv2694 CNV insertion 18451855
nsv2695 CNV deletion 18451855
nsv833847 CNV loss 17160897
nsv997934 CNV gain 25217958

Variation tolerance for MAP4K3 Gene

Residual Variation Intolerance Score: 14.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.90; 35.38% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MAP4K3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
MAP4K3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAP4K3 Gene

Disorders for MAP4K3 Gene

MalaCards: The human disease database

(1) MalaCards diseases for MAP4K3 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
adult-onset still's disease
  • adult onset still's disease
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for MAP4K3

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with MAP4K3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MAP4K3 Gene

Publications for MAP4K3 Gene

  1. Activation of the c-Jun N-terminal kinase pathway by a novel protein kinase related to human germinal center kinase. (PMID: 9275185) Diener K … Yao Z (Proceedings of the National Academy of Sciences of the United States of America 1997) 2 3 4 23
  2. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41
  3. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 41
  4. AhR-ROR-γt complex is a therapeutic target for MAP4K3/GLKhighIL-17Ahigh subpopulation of systemic lupus erythematosus. (PMID: 31318609) Chuang HC … Tan TH (FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2019) 3
  5. MAP4K3/GLK Promotes Lung Cancer Metastasis by Phosphorylating and Activating IQGAP1. (PMID: 31431460) Chuang HC … Tan TH (Cancer research 2019) 3

Products for MAP4K3 Gene

  • Signalway Proteins for MAP4K3

Sources for MAP4K3 Gene