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Aliases for MAP4K4 Gene

Aliases for MAP4K4 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 2 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
  • EC 2.7.11.1 4 63
  • NIK 3 4
  • HGK 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. Diseases associated with MAP4K4 include theileriasis. Among its related pathways are Cellular Senescence and MAPK signaling pathway. 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 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.

Tocris Summary for MAP4K4 Gene

Gene Wiki entry for MAP4K4 Gene

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

Genomics for MAP4K4 Gene

Regulatory Elements for MAP4K4 Gene

Genomic Location for MAP4K4 Gene

Chromosome:
2
Start:
101,696,850 bp from pter
End:
101,894,690 bp from pter
Size:
197,841 bases
Orientation:
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:
    O95819-M4K4_HUMAN
    Recommended name:
    Mitogen-activated protein kinase kinase kinase kinase 4
    Protein Accession:
    O95819
    Secondary Accessions:
    • O75172
    • Q9NST7

    Protein attributes for MAP4K4 Gene

    Size:
    1239 amino acids
    Molecular mass:
    142101 Da
    Cofactor:
    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

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP4K4 Gene

Proteomics data for MAP4K4 Gene at MOPED

Post-translational modifications for MAP4K4 Gene

  • Ubiquitination at Lys 1179
  • Modification sites at PhosphoSitePlus

Antibody Products

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

Domains & Families for MAP4K4 Gene

Suggested Antigen Peptide Sequences for MAP4K4 Gene

Graphical View of Domain Structure for InterPro Entry

O95819

UniProtKB/Swiss-Prot:

M4K4_HUMAN :
  • Contains 1 CNH domain.
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
Domain:
  • Contains 1 CNH domain.
  • Contains 1 protein kinase domain.
Family:
  • 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:0004672 protein kinase activity IEA --
GO:0005524 ATP binding IEA,IDA 9890973
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 for MAP4K4 Gene

Inhibitory RNA Products

In Situ Assay Products

Flow Cytometry 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

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for MAP4K4 Gene COMPARTMENTS Subcellular localization image for MAP4K4 gene
Compartment Confidence
cytosol 3
nucleus 3
cytoskeleton 1
plasma membrane 1

No data available for Gene Ontology (GO) - Cellular Components 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

SIGNOR curated interactions for MAP4K4 Gene

Activates:

Gene Ontology (GO) - Biological Process for MAP4K4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation IEA,IDA 9890973
GO:0007346 regulation of mitotic cell cycle IBA --
GO:0030033 NOT microvillus assembly IMP 22797597
GO:0031098 stress-activated protein kinase signaling cascade IBA --
GO:0043066 negative regulation of apoptotic process IMP 21196414
genes like me logo Genes that share ontologies with MAP4K4: view

Drugs & Compounds for MAP4K4 Gene

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Anastrozole Approved, Investigational Pharma Aromatase inhibitor, Aromatase Inhibitors, Hormone therapy 262
Exemestane Approved, Investigational Pharma Steroidal aromatase inhibitor,selective and irreversible 197
Adenosine triphosphate Approved Nutra 0
Magnesium Nutra 0

(2) Additional Compounds for MAP4K4 Gene - From: HMDB and Novoseek

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 MAP4K4: view

Transcripts for MAP4K4 Gene

Unigene Clusters for MAP4K4 Gene

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

CRISPR Products

Inhibitory RNA Products

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
MAP4K4
ECgene alternative splicing isoforms for
MAP4K4

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) (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, 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

O95819-M4K4_HUMAN
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 expression patterns with MAP4K4: view

Protein tissue co-expression partners for MAP4K4 Gene

Primer Products

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
cow
(Bos Taurus)
Mammalia MAP4K4 35
  • 85.28 (n)
  • 93.55 (a)
MAP4K4 36
  • 85 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MAP4K4 35
  • 88.95 (n)
  • 92.87 (a)
MAP4K4 36
  • 89 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Map4k4 35
  • 86.18 (n)
  • 91.89 (a)
Map4k4 16
Map4k4 36
  • 92 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia MAP4K4 35
  • 95.31 (n)
  • 94.81 (a)
MAP4K4 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Map4k4 35
  • 86.32 (n)
  • 93.55 (a)
oppossum
(Monodelphis domestica)
Mammalia MAP4K4 36
  • 90 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 98 (a)
OneToMany
-- 36
  • 79 (a)
OneToMany
chicken
(Gallus gallus)
Aves MAP4K4 35
  • 84.39 (n)
  • 94.08 (a)
MAP4K4 36
  • 86 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MAP4K4 36
  • 80 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia map4k4 35
  • 81.14 (n)
  • 92.74 (a)
zebrafish
(Danio rerio)
Actinopterygii wu:fa03e11 35
  • 73.38 (n)
  • 87.04 (a)
MAP4K4 36
  • 62 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta msn 37
  • 79 (a)
msn 36
  • 42 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea mig-15 37
  • 67 (a)
ZC504.4b 37
  • 67 (a)
ZC504.4c 37
  • 67 (a)
mig-15 36
  • 51 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3520 36
  • 47 (a)
OneToMany
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

ENSEMBL:
Gene Tree for MAP4K4 (if available)
TreeFam:
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
VAR_040746 -
rs886768 -- 101,857,778(-) AAATC(C/T)TTAGA intron-variant
rs1060895 -- 101,870,800(+) TCTGA(A/G)TGTCT intron-variant
rs1139583 -- 101,855,997(+) CGGGA(A/G)GCTAG intron-variant, reference, synonymous-codon
rs875565 -- 101,822,374(+) ACGTT(A/T)TGTAG intron-variant

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

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)

Relevant External Links for MAP4K4 Gene

HapMap Linkage Disequilibrium report
MAP4K4
Human Gene Mutation Database (HGMD)
MAP4K4

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: DISEASES

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

Relevant External Links for MAP4K4

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
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 T.-H. (J. Biol. Chem. 1999) 2 3 4 23 67
  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. A small interfering RNA screen for modulators of tumor cell motility identifies MAP4K4 as a promigratory kinase. (PMID: 16537454) Collins C.S. … Hampton G.M. (Proc. Natl. Acad. Sci. U.S.A. 2006) 3 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 23
  5. 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 23

Products for MAP4K4 Gene

Sources for MAP4K4 Gene

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