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Aliases for MAP4K4 Gene

Aliases for MAP4K4 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 2 3
  • 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
  • EC 4 63
  • HGK 3 4
  • NIK 3 4
  • Epididymis Secretory Protein Li 31 3
  • Ste20 Group Protein Kinase HGK 3
  • HPK/GCK-Like Kinase 2
  • EC 2.7.11 63
  • 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. Among its related pathways are MAPK signaling pathway and TGF-Beta Pathway. GO annotations related to this gene include protein serine/threonine kinase activity. An important paralog of this gene is MAP4K3.

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.

Gene Wiki entry for MAP4K4 Gene

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

Genomics for MAP4K4 Gene

Regulatory Elements for MAP4K4 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for MAP4K4 Gene

101,696,850 bp from pter
101,894,690 bp from pter
197,841 bases
Plus strand

Genomic View for MAP4K4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
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:
    • 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

Proteomics data for MAP4K4 Gene at MOPED

Post-translational modifications for MAP4K4 Gene

  • Ubiquitination at Lys46, Lys1179, and Lys1198
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for MAP4K4 (HGK)

Domains for MAP4K4 Gene

Gene Families for MAP4K4 Gene

  • MAP4K :Mitogen-activated protein kinase cascade / Kinase kinase kinase kinases

Suggested Antigen Peptide Sequences for MAP4K4 Gene

Graphical View of Domain Structure for InterPro Entry



  • O95819
  • Contains 1 CNH domain.
  • Contains 1 protein kinase domain.
  • 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

GENATLAS Biochemistry: mitogen-activated kinase kinase kinase kinase 4,S cerevisiae STE20 family homolog,specifically activating the JNK signaling through the pathway TAK1
UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein.
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.

Enzyme Numbers (IUBMB) for MAP4K4 Gene

Gene Ontology (GO) - Molecular Function for MAP4K4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004111 creatine kinase activity IDA 23207904
GO:0004672 protein kinase activity --
GO:0004674 protein serine/threonine kinase activity IDA 9890973
GO:0004702 receptor signaling protein serine/threonine kinase activity IBA --
GO:0004713 protein tyrosine kinase activity --
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

CRISPR Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for MAP4K4

Clone Products

In Situ Assay Products

Flow Cytometry Products

No data available for miRNA , Transcription Factor Targeting and HOMER Transcription for MAP4K4 Gene

Localization for MAP4K4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MAP4K4 Gene


Subcellular locations from

Jensen Localization Image for MAP4K4 Gene COMPARTMENTS Subcellular localization image for MAP4K4 gene
Compartment Confidence
cytosol 3
nucleus 2
cytoskeleton 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for MAP4K4 Gene

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

Pathways for MAP4K4 Gene

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

Pathways by source for MAP4K4 Gene

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

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays
    • Toll-Like Receptor Signaling Pathway in human,mouse,rat

Gene Ontology (GO) - Biological Process for MAP4K4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation IDA 9890973
GO:0010977 negative regulation of neuron projection development --
GO:0023014 signal transduction by protein phosphorylation IBA --
GO:0030033 NOT microvillus assembly IMP 22797597
GO:0035556 intracellular signal transduction IDA 9890973
genes like me logo Genes that share ontologies with MAP4K4: view

Compounds for MAP4K4 Gene

(3) HMDB Compounds for MAP4K4 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
  • adenosindiphosphorsaeure
  • Magnesium

(5) Novoseek inferred chemical compound relationships for MAP4K4 Gene

Compound -log(P) Hits PubMed IDs
parthenolide 65.2 1
serine 34 4
threonine 31.7 4
tyrosine 13.5 3
oxygen 0 2
genes like me logo Genes that share compounds with MAP4K4: view

Transcripts for MAP4K4 Gene

Unigene Clusters for MAP4K4 Gene

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

CRISPR Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for MAP4K4

Clone Products

Primer Products

  • OriGene qSTAR qPCR primer pairs in human,mouse,rat for MAP4K4

Flow Cytometry 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 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) (4.7).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for MAP4K4 Gene

SOURCE GeneReport for Unigene cluster for MAP4K4 Gene Hs.701013

mRNA Expression by UniProt/SwissProt for MAP4K4 Gene

Tissue specificity: Appears to be ubiquitous. Expressed in all tissue types examined. Isoform 5 appears to be more abundant in the brain. Isoform 4 is predominant in the liver, skeletal muscle and placenta.
genes like me logo Genes that share expressions with MAP4K4: view

In Situ Assay Products

Orthologs for MAP4K4 Gene

This gene was present in the common ancestor of animals.

Orthologs for MAP4K4 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia MAP4K4 35
  • 95.31 (n)
  • 94.81 (a)
MAP4K4 36
  • 100 (a)
(Bos Taurus)
Mammalia MAP4K4 35
  • 85.28 (n)
  • 93.55 (a)
MAP4K4 36
  • 85 (a)
(Canis familiaris)
Mammalia MAP4K4 35
  • 88.95 (n)
  • 92.87 (a)
MAP4K4 36
  • 89 (a)
(Mus musculus)
Mammalia Map4k4 35
  • 86.18 (n)
  • 91.89 (a)
Map4k4 16
Map4k4 36
  • 92 (a)
(Monodelphis domestica)
Mammalia MAP4K4 36
  • 90 (a)
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 98 (a)
-- 36
  • 79 (a)
(Rattus norvegicus)
Mammalia Map4k4 35
  • 86.32 (n)
  • 93.55 (a)
(Gallus gallus)
Aves MAP4K4 35
  • 84.39 (n)
  • 94.08 (a)
MAP4K4 36
  • 86 (a)
(Anolis carolinensis)
Reptilia MAP4K4 36
  • 80 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia map4k4 35
  • 81.14 (n)
  • 92.74 (a)
(Danio rerio)
Actinopterygii MAP4K4 36
  • 62 (a)
wu:fa03e11 35
  • 73.38 (n)
  • 87.04 (a)
fruit fly
(Drosophila melanogaster)
Insecta msn 36
  • 42 (a)
msn 37
  • 79 (a)
(Caenorhabditis elegans)
Secernentea mig-15 36
  • 51 (a)
ZC504.4b 37
  • 67 (a)
mig-15 37
  • 67 (a)
ZC504.4c 37
  • 67 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3520 36
  • 47 (a)
Species with no ortholog for MAP4K4:
  • 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)

Paralogs for MAP4K4 Gene

Paralogs for MAP4K4 Gene

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 Sequence Context AA Info Type MAF
rs875565 -- 101,822,374(+) ACGTT(A/T)TGTAG intron-variant
rs886768 -- 101,857,778(-) AAATC(C/T)TTAGA intron-variant
rs972372 -- 101,850,859(-) TATTC(A/G)TTTCT intron-variant
rs1009656 -- 101,814,985(+) TGGCC(C/T)TGCCC intron-variant
rs1042916 -- 101,869,714(+) GAGTC(A/C/G)GGGAC synonymous-codon, reference

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

Variant ID Type Subtype PubMed ID
nsv213949 CNV Loss 16902084
nsv834318 CNV Loss 17160897
esv2484314 CNV Deletion 19546169
esv2109649 CNV Deletion 18987734
esv2661163 CNV Deletion 23128226
esv2720452 CNV Deletion 23290073
esv2669350 CNV Deletion 23128226
nsv441771 CNV CNV 18776908
esv2632369 CNV Deletion 19546169
esv2061482 CNV Deletion 18987734
esv2720453 CNV Deletion 23290073
esv2829 CNV Deletion 18987735
esv1631190 CNV Deletion 17803354
nsv213987 CNV Loss 16902084
esv2720454 CNV Deletion 23290073
nsv2851 CNV Insertion 18451855
esv2663691 CNV Deletion 23128226
esv2720455 CNV Deletion 23290073

Relevant External Links for MAP4K4 Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)

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

Disorders for MAP4K4 Gene

(3) Novoseek inferred disease relationships for MAP4K4 Gene

Disease -log(P) Hits PubMed IDs
virus infection 0 1
necrosis 0 2
tumors 0 5
genes like me logo Genes that share disorders with MAP4K4: view

No data available for UniProtKB/Swiss-Prot 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 T.-H. (J. Biol. Chem. 1999) 2 3 4 23
  2. 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 Y.C. … Skolnik E.Y. (EMBO J. 1997) 2 3 23
  3. The STE20 kinase HGK is broadly expressed in human tumor cells and can modulate cellular transformation, invasion, and adhesion. (PMID: 12612079) Wright J.H. … Jallal B. (Mol. Cell. Biol. 2003) 3 4 23
  4. 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. (J. Biol. Chem. 2004) 3 4 23
  5. 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 Res. 1998) 2 3 4

Products for MAP4K4 Gene

Sources for MAP4K4 Gene

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