Free for academic non-profit institutions. Other users need a Commercial license

Aliases for MAP4K4 Gene

Aliases for MAP4K4 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 2 3 3 5
  • Hepatocyte Progenitor Kinase-Like/Germinal Center Kinase-Like Kinase 2 3
  • MAPK/ERK Kinase Kinase Kinase 4 3 4
  • HPK/GCK-Like Kinase HGK 3 4
  • Nck-Interacting Kinase 3 4
  • MEK Kinase Kinase 4 3 4
  • HGK 3 4
  • NIK 3 4
  • Epididymis Secretory Protein Li 31 3
  • Ste20 Group Protein Kinase HGK 3
  • HPK/GCK-Like Kinase 2
  • EC 4
  • FLH21957 3
  • HEL-S-31 3
  • KIAA0687 4
  • MEKKK 4 4
  • MEKKK4 3

External Ids for MAP4K4 Gene

Previous GeneCards Identifiers for MAP4K4 Gene

  • GC02P100178
  • GC02P100767
  • GC02P101919
  • GC02P101935
  • GC02P102313
  • GC02P096078

Summaries for MAP4K4 Gene

Entrez Gene Summary for MAP4K4 Gene

  • The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase has been shown to specifically activate MAPK8/JNK. The activation of MAPK8 by this kinase is found to be inhibited by the dominant-negative mutants of MAP3K7/TAK1, MAP2K4/MKK4, and MAP2K7/MKK7, which suggests that this kinase may function through the MAP3K7-MAP2K4-MAP2K7 kinase cascade, and mediate the TNF-alpha signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

GeneCards Summary for MAP4K4 Gene

MAP4K4 (Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4) is a Protein Coding gene. Diseases associated with MAP4K4 include Theileriasis. Among its related pathways are Cellular Senescence (REACTOME) and Direct p53 effectors. 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 TNIK.

UniProtKB/Swiss-Prot for MAP4K4 Gene

  • Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322.

Tocris Summary for MAP4K4 Gene

Gene Wiki entry for MAP4K4 Gene

Additional gene information for MAP4K4 Gene

No data available for CIViC summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MAP4K4 Gene

Genomics for MAP4K4 Gene

GeneHancer (GH) Regulatory Elements for MAP4K4 Gene

Promoters and enhancers for MAP4K4 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J101696 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE dbSUPER 650.7 +1.8 1762 4.7 FOXA2 ZFP64 ARID4B SIN3A DMAP1 YY1 ZNF766 SP3 SP5 MXD4 MAP4K4 IL1R2 GC02M101710
GH02J101745 Promoter/Enhancer 0.7 EPDnew dbSUPER 650.2 +48.5 48455 0.1 MAP4K4 GC02M101710 GC02P101903
GH02J101732 Enhancer 1.6 FANTOM5 Ensembl ENCODE dbSUPER 16 +39.2 39183 6.3 FOXA2 MLX ARID4B SIN3A DMAP1 ZNF48 YY1 FOS NFKBIZ PAF1 MAP4K4 IL1R2 IL1R1 RNF149 GC02M101710 GC02P101903
GH02J101712 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 16.8 +21.8 21785 11.9 ZFP64 EBF1 BATF GATA3 ZNF316 POLR2A EGR1 EED ETV6 IKZF2 IL1R2 RNF149 MAP4K4 IL1R1 GC02M101710 GC02P101903
GH02J102069 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE dbSUPER 11.2 +373.3 373322 2 PKNOX1 SMAD1 FOXA2 ARNT SIN3A YY1 ZNF766 E2F8 REST ZNF592 IL1R1 MAP4K4 GC02M102141 PIR60869 GC02P101903
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MAP4K4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MAP4K4 gene promoter:
  • C/EBPbeta
  • HSF2
  • FOXL1
  • Pbx1a
  • Msx-1
  • C/EBPalpha
  • AML1a

Genomic Locations for MAP4K4 Gene

Genomic Locations for MAP4K4 Gene
197,841 bases
Plus strand
197,841 bases
Plus strand

Genomic View for MAP4K4 Gene

Genes around MAP4K4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MAP4K4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MAP4K4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP4K4 Gene

Proteins for MAP4K4 Gene

  • Protein details for MAP4K4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Mitogen-activated protein kinase kinase kinase kinase 4
    Protein Accession:
    Secondary Accessions:
    • E7ESS2
    • O75172
    • Q9NST7

    Protein attributes for MAP4K4 Gene

    1239 amino acids
    Molecular mass:
    142101 Da
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Interacts with the SH3 domain of the adapter proteins Nck (By similarity). Interacts (via its CNH regulatory domain) with ATL1 (via the N-terminal region). Interacts with RAP2A (GTP-bound form preferentially).

    Three dimensional structures from OCA and Proteopedia for MAP4K4 Gene

    Alternative splice isoforms for MAP4K4 Gene

neXtProt entry for MAP4K4 Gene

Post-translational modifications for MAP4K4 Gene

  • Ubiquitination at isoforms=2, 3, 4, 51179
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for MAP4K4 Gene

Domains & Families for MAP4K4 Gene

Gene Families for MAP4K4 Gene

Protein Domains for MAP4K4 Gene

Suggested Antigen Peptide Sequences for MAP4K4 Gene

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
genes like me logo Genes that share domains with MAP4K4: view

Function for MAP4K4 Gene

Molecular function for MAP4K4 Gene

UniProtKB/Swiss-Prot Function:
Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322.
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
GENATLAS Biochemistry:
mitogen-activated kinase kinase kinase kinase 4,S cerevisiae STE20 family homolog,specifically activating the JNK signaling through the pathway TAK1

Enzyme Numbers (IUBMB) for MAP4K4 Gene

Phenotypes From GWAS Catalog for MAP4K4 Gene

Gene Ontology (GO) - Molecular Function for MAP4K4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004111 creatine kinase activity IDA 23207904
GO:0004672 protein kinase activity IEA --
GO:0004674 protein serine/threonine kinase activity IDA,IEA 9890973
GO:0005515 protein binding IEA,IPI 12387898
genes like me logo Genes that share ontologies with MAP4K4: view
genes like me logo Genes that share phenotypes with MAP4K4: view

Animal Models for MAP4K4 Gene

MGI Knock Outs for MAP4K4:

Animal Model Products

  • Taconic Biosciences Mouse Models for MAP4K4

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MAP4K4 Gene

Localization for MAP4K4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MAP4K4 Gene


Subcellular locations from

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 MAP4K4 gene
Compartment Confidence
nucleus 3
cytosol 3
plasma membrane 1
extracellular 1
cytoskeleton 1

Gene Ontology (GO) - Cellular Components for MAP4K4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA,IEA 14966141
genes like me logo Genes that share ontologies with MAP4K4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for MAP4K4 Gene

Pathways & Interactions for MAP4K4 Gene

genes like me logo Genes that share pathways with MAP4K4: view

Pathways by source for MAP4K4 Gene

2 GeneGo (Thomson Reuters) pathways for MAP4K4 Gene
2 Qiagen pathways for MAP4K4 Gene
1 Cell Signaling Technology pathway for MAP4K4 Gene

SIGNOR curated interactions for MAP4K4 Gene


Gene Ontology (GO) - Biological Process for MAP4K4 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 IDA,IEA 9890973
GO:0007346 regulation of mitotic cell cycle IBA --
GO:0010977 negative regulation of neuron projection development IEA --
genes like me logo Genes that share ontologies with MAP4K4: view

Drugs & Compounds for MAP4K4 Gene

(10) Drugs for MAP4K4 Gene - From: DrugBank, PharmGKB, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
Anastrozole Approved, Investigational Pharma Aromatase inhibitor, Aromatase Inhibitors, Hormone therapy, Potent aromatase (CYP19) inhibitor 297
Exemestane Approved, Investigational Pharma Steroidal aromatase inhibitor,selective and irreversible, Steroidal aromatase (CYP19) inhibitor 234
Magnesium Approved Nutra 0
ATP Investigational Nutra Agonist, Activator, Full agonist, Antagonist, Potentiation, Pore Blocker 0

(1) Additional Compounds for MAP4K4 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor 58-64-0
genes like me logo Genes that share compounds with MAP4K4: view

Transcripts for MAP4K4 Gene

mRNA/cDNA for MAP4K4 Gene

Unigene Clusters for MAP4K4 Gene

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

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for MAP4K4 Gene

No ASD Table

Relevant External Links for MAP4K4 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for MAP4K4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MAP4K4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MAP4K4 Gene

This gene is overexpressed in Brain - Spinal cord (cervical c-1) (x4.7).

Protein differential expression in normal tissues from HIPED for MAP4K4 Gene

This gene is overexpressed in Lung (12.5), Breast (11.3), Peripheral blood mononuclear cells (11.2), and Fetal Brain (7.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MAP4K4 Gene

Protein tissue co-expression partners for MAP4K4 Gene

NURSA nuclear receptor signaling pathways regulating expression of MAP4K4 Gene:


SOURCE GeneReport for Unigene cluster for MAP4K4 Gene:


mRNA Expression by UniProt/SwissProt for MAP4K4 Gene:

Tissue specificity: Widely expressed. Isoform 5 is abundant in the brain. Isoform 4 is predominant in the liver, skeletal muscle and placenta.

Evidence on tissue expression from TISSUES for MAP4K4 Gene

  • Nervous system(4.9)
  • Liver(4.4)
  • Lung(3.6)
  • Blood(2.5)
  • Kidney(2.4)
  • Heart(2.3)
  • Pancreas(2.3)
  • Lymph node(2.2)
  • Muscle(2.2)
genes like me logo Genes that share expression patterns with MAP4K4: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for MAP4K4 Gene

Orthologs for MAP4K4 Gene

This gene was present in the common ancestor of animals.

Orthologs for MAP4K4 Gene

Organism Taxonomy Gene Similarity Type Details
(Ornithorhynchus anatinus)
Mammalia -- 34
  • 98 (a)
-- 34
  • 79 (a)
(Pan troglodytes)
Mammalia MAP4K4 34 33
  • 95.31 (n)
(Monodelphis domestica)
Mammalia MAP4K4 34
  • 90 (a)
(Canis familiaris)
Mammalia MAP4K4 34 33
  • 88.95 (n)
(Rattus norvegicus)
Mammalia Map4k4 33
  • 86.32 (n)
(Mus musculus)
Mammalia Map4k4 16 34 33
  • 86.18 (n)
(Bos Taurus)
Mammalia MAP4K4 34 33
  • 85.28 (n)
(Gallus gallus)
Aves MAP4K4 34 33
  • 84.39 (n)
(Anolis carolinensis)
Reptilia MAP4K4 34
  • 80 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia map4k4 33
  • 81.14 (n)
(Danio rerio)
Actinopterygii wu:fa03e11 33
  • 73.38 (n)
MAP4K4 34
  • 62 (a)
fruit fly
(Drosophila melanogaster)
Insecta msn 34 35
  • 42 (a)
(Caenorhabditis elegans)
Secernentea ZC504.4c 35
  • 67 (a)
ZC504.4b 35
  • 67 (a)
mig-15 34 35
  • 51 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3520 34
  • 47 (a)
Species where no ortholog for MAP4K4 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)
  • 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)
  • 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 MAP4K4 Gene

Gene Tree for MAP4K4 (if available)
Gene Tree for MAP4K4 (if available)
Evolutionary constrained regions (ECRs) for MAP4K4: view image

Paralogs for MAP4K4 Gene

Paralogs for MAP4K4 Gene

(49) SIMAP similar genes for MAP4K4 Gene using alignment to 15 proteins:

  • M4K4_HUMAN
  • C9J840_HUMAN
  • E7EN19_HUMAN
  • E7EX83_HUMAN
  • G5E948_HUMAN
  • H7C0P6_HUMAN
  • H7C360_HUMAN
  • H7C3Z6_HUMAN
  • Q53TW0_HUMAN
  • Q53TX8_HUMAN
  • Q5MD60_HUMAN
genes like me logo Genes that share paralogs with MAP4K4: view

Variants for MAP4K4 Gene

Sequence variations from dbSNP and Humsavar for MAP4K4 Gene

SNP ID Clin Chr 02 pos Variation AA Info Type
rs1000012310 -- 101,860,258(+) C/T intron_variant
rs1000013037 -- 101,731,193(+) T/C intron_variant
rs1000028492 -- 101,725,144(+) T/G intron_variant
rs1000034096 -- 101,716,258(+) A/G intron_variant
rs1000063305 -- 101,860,714(+) A/C intron_variant

Structural Variations from Database of Genomic Variants (DGV) for MAP4K4 Gene

Variant ID Type Subtype PubMed ID
dgv1981n106 CNV deletion 24896259
dgv1982n106 CNV deletion 24896259
esv1631190 CNV deletion 17803354
esv2061482 CNV deletion 18987734
esv2109649 CNV deletion 18987734
esv2484314 CNV deletion 19546169
esv2632369 CNV deletion 19546169
esv2661163 CNV deletion 23128226
esv2663691 CNV deletion 23128226
esv2669350 CNV deletion 23128226
esv2720452 CNV deletion 23290073
esv2720453 CNV deletion 23290073
esv2720454 CNV deletion 23290073
esv2720455 CNV deletion 23290073
esv2762747 CNV gain 21179565
esv2829 CNV loss 18987735
esv3559862 CNV deletion 23714750
esv3559863 CNV deletion 23714750
esv3591775 CNV loss 21293372
nsv1072012 CNV deletion 25765185
nsv1072429 CNV deletion 25765185
nsv1072431 CNV deletion 25765185
nsv1136302 CNV deletion 24896259
nsv1143949 CNV deletion 24896259
nsv213949 CNV deletion 16902084
nsv213987 CNV deletion 16902084
nsv2851 CNV insertion 18451855
nsv441771 CNV loss 18776908
nsv475255 CNV novel sequence insertion 20440878
nsv834318 CNV loss 17160897
nsv954785 CNV deletion 24416366

Variation tolerance for MAP4K4 Gene

Residual Variation Intolerance Score: 14.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.78; 33.57% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MAP4K4 Gene

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

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MAP4K4 Gene

Disorders for MAP4K4 Gene

MalaCards: The human disease database

(1) MalaCards diseases for MAP4K4 Gene - From: HGMD and DISEASES

Disorder Aliases PubMed IDs
  • infection by theileria
- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for MAP4K4

genes like me logo Genes that share disorders with MAP4K4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MAP4K4 Gene

Publications for MAP4K4 Gene

  1. A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway. (PMID: 9890973) Yao Z … Tan TH (The Journal of biological chemistry 1999) 2 3 4 22 58
  2. Mitogen-activated protein kinase kinase kinase kinase 4 as a putative effector of Rap2 to activate the c-Jun N-terminal kinase. (PMID: 14966141) Machida N … Kariya K (The Journal of biological chemistry 2004) 3 4 22 58
  3. The STE20 kinase HGK is broadly expressed in human tumor cells and can modulate cellular transformation, invasion, and adhesion. (PMID: 12612079) Wright JH … Jallal B (Molecular and cellular biology 2003) 3 4 22 58
  4. Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. (PMID: 9734811) Ishikawa K … Ohara O (DNA research : an international journal for rapid publication of reports on genes and genomes 1998) 2 3 4 58
  5. NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain. (PMID: 9135144) Su YC … Skolnik EY (The EMBO journal 1997) 2 3 22 58

Products for MAP4K4 Gene

Sources for MAP4K4 Gene

Loading form....