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Aliases for MAP4K2 Gene

Aliases for MAP4K2 Gene

  • Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 2 3 5
  • MAPK/ERK Kinase Kinase Kinase 2 3 4
  • MEK Kinase Kinase 2 3 4
  • EC 2.7.11.1 4 63
  • MEKKK 2 3 4
  • RAB8IP 3 4
  • GCK 3 4
  • B Lymphocyte Serine/Threonine Protein Kinase 3
  • B Lymphocyte Serine/Threonine-Protein Kinase 4
  • Germinal Centre Kinase (GC Kinase) 3
  • Rab8 Interacting Protein 3
  • Rab8-Interacting Protein 4
  • Germinal Center Kinase 4
  • GC Kinase 4
  • EC 2.7.11 63
  • BL44 3

External Ids for MAP4K2 Gene

Previous HGNC Symbols for MAP4K2 Gene

  • RAB8IP

Previous GeneCards Identifiers for MAP4K2 Gene

  • GC11M067072
  • GC11M066238
  • GC11M064331
  • GC11M064313
  • GC11M064556
  • GC11M060883

Summaries for MAP4K2 Gene

Entrez Gene Summary for MAP4K2 Gene

  • The protein encoded by this gene is a member of the serine/threonine protein kinase family. Although this kinase is found in many tissues, its expression in lymphoid follicles is restricted to the cells of germinal centre, where it may participate in B-cell differentiation. This kinase can be activated by TNF-alpha, and has been shown to specifically activate MAP kinases. This kinase is also found to interact with TNF receptor-associated factor 2 (TRAF2), which is involved in the activation of MAP3K1/MEKK1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

GeneCards Summary for MAP4K2 Gene

MAP4K2 (Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2) is a Protein Coding gene. Among its related pathways are TWEAK Pathway and Signal transduction_JNK 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 MAP4K2 Gene

  • Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extend of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Mediates also the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion.

Gene Wiki entry for MAP4K2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MAP4K2 Gene

Genomics for MAP4K2 Gene

Regulatory Elements for MAP4K2 Gene

Enhancers for MAP4K2 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around MAP4K2 on UCSC Golden Path with GeneCards custom track

Promoters for MAP4K2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around MAP4K2 on UCSC Golden Path with GeneCards custom track

Genomic Location for MAP4K2 Gene

Chromosome:
11
Start:
64,784,914 bp from pter
End:
64,803,248 bp from pter
Size:
18,335 bases
Orientation:
Minus strand

Genomic View for MAP4K2 Gene

Genes around MAP4K2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MAP4K2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MAP4K2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MAP4K2 Gene

Proteins for MAP4K2 Gene

  • Protein details for MAP4K2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q12851-M4K2_HUMAN
    Recommended name:
    Mitogen-activated protein kinase kinase kinase kinase 2
    Protein Accession:
    Q12851
    Secondary Accessions:
    • Q86VU3

    Protein attributes for MAP4K2 Gene

    Size:
    820 amino acids
    Molecular mass:
    91556 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Interacts with TRAF2, TRAF6, MAP3K1/MEKK1 and MAP3K11/MLK3. Interacts with RAB8A (By similarity).
    SequenceCaution:
    • Sequence=AAA20968.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};

    Alternative splice isoforms for MAP4K2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MAP4K2 Gene

Proteomics data for MAP4K2 Gene at MOPED

Selected DME Specific Peptides for MAP4K2 Gene

Post-translational modifications for MAP4K2 Gene

  • Autophosphorylated in response to tumor necrosis factor (TNF), endotoxins or proinflammatory stimuli. Autophosphorylation leads to activation.
  • Polyubiquitinated through Lys-48-polyubiquitin chains, allowing proteasomal turnover. Ubiquitination requires the kinase activity of MAP4K2/GCK.
  • Ubiquitination at Lys 32
  • Modification sites at PhosphoSitePlus

Domains & Families for MAP4K2 Gene

Suggested Antigen Peptide Sequences for MAP4K2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q12851

UniProtKB/Swiss-Prot:

M4K2_HUMAN :
  • The PEST domains are Pro-, Glu-, Ser-, and Thr-rich domains. Proteins with PEST domains are frequently targets of degradation by the ubiquitin proteasome.
  • Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
Domain:
  • The PEST domains are Pro-, Glu-, Ser-, and Thr-rich domains. Proteins with PEST domains are frequently targets of degradation by the ubiquitin proteasome.
  • 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 MAP4K2: view

Function for MAP4K2 Gene

Molecular function for MAP4K2 Gene

GENATLAS Biochemistry:
mitogen-activated kinase kinase kinase kinase 2,located in the MEN1 critical region
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot EnzymeRegulation:
The tumor necrosis factor (TNF), as well as endotoxins and proinflammatory stimuli such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), peptidoglycan (PGN), flagellin, or lipid A activate MAP4K2 by promoting its autophosphorylation.
UniProtKB/Swiss-Prot Function:
Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extend of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Mediates also the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion.

Enzyme Numbers (IUBMB) for MAP4K2 Gene

Gene Ontology (GO) - Molecular Function for MAP4K2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004702 receptor signaling protein serine/threonine kinase activity IBA --
genes like me logo Genes that share ontologies with MAP4K2: view
genes like me logo Genes that share phenotypes with MAP4K2: view

Animal Models for MAP4K2 Gene

MGI Knock Outs for MAP4K2:

Animal Model Products

  • Taconic Biosciences Mouse Models for MAP4K2

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MAP4K2 Gene

Localization for MAP4K2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MAP4K2 Gene

Cytoplasm. Basolateral cell membrane; Peripheral membrane protein. Golgi apparatus membrane; Peripheral membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for MAP4K2 Gene COMPARTMENTS Subcellular localization image for MAP4K2 gene
Compartment Confidence
golgi apparatus 5
plasma membrane 4
cytosol 3
cytoskeleton 1
nucleus 1
peroxisome 1

No data available for Gene Ontology (GO) - Cellular Components for MAP4K2 Gene

Pathways & Interactions for MAP4K2 Gene

genes like me logo Genes that share pathways with MAP4K2: view

Pathways by source for MAP4K2 Gene

1 Cell Signaling Technology pathway for MAP4K2 Gene
2 BioSystems pathways for MAP4K2 Gene
1 KEGG pathway for MAP4K2 Gene
2 GeneGo (Thomson Reuters) pathways for MAP4K2 Gene
4 Qiagen pathways for MAP4K2 Gene

SIGNOR curated interactions for MAP4K2 Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for MAP4K2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation IEA,IDA 11784851
GO:0006903 vesicle targeting IEA --
GO:0006955 immune response TAS 7515885
GO:0045087 innate immune response IEA --
genes like me logo Genes that share ontologies with MAP4K2: view

Drugs & Compounds for MAP4K2 Gene

(7) Drugs for MAP4K2 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine triphosphate Approved Nutra 0
Magnesium Nutra 0

(6) Additional Compounds for MAP4K2 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 MAP4K2: view

Transcripts for MAP4K2 Gene

Unigene Clusters for MAP4K2 Gene

Mitogen-activated protein kinase kinase kinase kinase 2:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for MAP4K2 Gene

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

ExUns: 25 ^ 26 ^ 27a · 27b ^ 28a · 28b ^ 29 ^ 30 ^ 31 ^ 32a · 32b
SP1:
SP2:
SP3: - -
SP4:

Relevant External Links for MAP4K2 Gene

GeneLoc Exon Structure for
MAP4K2
ECgene alternative splicing isoforms for
MAP4K2

Expression for MAP4K2 Gene

mRNA expression in normal human tissues for MAP4K2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for MAP4K2 Gene

This gene is overexpressed in Whole Blood (x4.7).

Protein differential expression in normal tissues from HIPED for MAP4K2 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (31.4) and Lymph node (13.6).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for MAP4K2 Gene



SOURCE GeneReport for Unigene cluster for MAP4K2 Gene Hs.534341

mRNA Expression by UniProt/SwissProt for MAP4K2 Gene

Q12851-M4K2_HUMAN
Tissue specificity: Highly expressed in germinal center but not mantle zone B-cells. Also expressed in lung, brain and placenta and at lower levels in other tissues examined.
genes like me logo Genes that share expression patterns with MAP4K2: view

Protein tissue co-expression partners for MAP4K2 Gene

Primer Products

Orthologs for MAP4K2 Gene

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

Orthologs for MAP4K2 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia MAP4K2 35
  • 91.79 (n)
  • 95 (a)
MAP4K2 36
  • 95 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MAP4K2 35
  • 91.05 (n)
  • 94.95 (a)
MAP4K2 36
  • 82 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Map4k2 35
  • 87.6 (n)
  • 93.9 (a)
Map4k2 16
Map4k2 36
  • 94 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia MAP4K2 35
  • 99.8 (n)
  • 99.76 (a)
MAP4K2 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Map4k2 35
  • 86.02 (n)
  • 92.29 (a)
platypus
(Ornithorhynchus anatinus)
Mammalia MAP4K2 36
  • 58 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii zgc:136354 35
  • 62.6 (n)
  • 61.69 (a)
MAP4K2 (2 of 3) 36
  • 54 (a)
OneToMany
map4k2l 36
  • 55 (a)
OneToMany
map4k2l 36
  • 55 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta CG7097 37
  • 57 (a)
hppy 36
  • 32 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea gck-2 36
  • 39 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes KIC1 36
  • 18 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 43 (a)
OneToMany
Species with no ortholog for MAP4K2:
  • 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)
  • chicken (Gallus gallus)
  • 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)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • 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)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for MAP4K2 Gene

ENSEMBL:
Gene Tree for MAP4K2 (if available)
TreeFam:
Gene Tree for MAP4K2 (if available)

Paralogs for MAP4K2 Gene

Paralogs for MAP4K2 Gene

genes like me logo Genes that share paralogs with MAP4K2: view

Variants for MAP4K2 Gene

Sequence variations from dbSNP and Humsavar for MAP4K2 Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type
rs533447 -- 64,794,436(+) ctcat(C/T)gcaac intron-variant
rs533655 -- 64,801,061(+) TGGCC(A/G)GGTGC intron-variant
rs582980 -- 64,797,768(+) tggcg(C/T)aatcg intron-variant
rs583901 -- 64,795,786(+) gcctc(A/G)gatta intron-variant
rs595099 -- 64,798,163(+) aCttt(G/T)gtttg intron-variant

Structural Variations from Database of Genomic Variants (DGV) for MAP4K2 Gene

Variant ID Type Subtype PubMed ID
nsv897694 CNV Loss 21882294
nsv528506 CNV Loss 19592680
dgv1171n71 CNV Loss 21882294
dgv1172n71 CNV Loss 21882294
dgv153n27 CNV Loss 19166990
nsv832189 CNV Loss 17160897
nsv469962 CNV Loss 18288195
nsv897702 CNV Loss 21882294
nsv897703 CNV Loss 21882294
dgv72n21 CNV Loss 19592680

Variation tolerance for MAP4K2 Gene

Residual Variation Intolerance Score: 41.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.82; 58.53% of all genes are more intolerant (likely to be disease-causing)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Relevant External Links for MAP4K2 Gene

Disorders for MAP4K2 Gene

Relevant External Links for MAP4K2

Genetic Association Database (GAD)
MAP4K2
Human Genome Epidemiology (HuGE) Navigator
MAP4K2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
MAP4K2

No disorders were found for MAP4K2 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for MAP4K2 Gene

Publications for MAP4K2 Gene

  1. Differential expression of a novel protein kinase in human B lymphocytes. Preferential localization in the germinal center. (PMID: 7515885) Katz P. … Kehrl J.H. (J. Biol. Chem. 1994) 2 3 4 23 67
  2. Dissection of a signaling pathway by which pathogen-associated molecular patterns recruit the JNK and p38 MAPKs and trigger cytokine release. (PMID: 17584736) Zhong J. … Kyriakis J.M. (J. Biol. Chem. 2007) 3 23
  3. Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 by the Ste20p homologue GCK and the adapter protein TRAF2. (PMID: 11784851) Chadee D.N. … Kyriakis J.M. (Mol. Cell. Biol. 2002) 3 23
  4. Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen- activated protein kinase kinase kinase upstream of MKK6 and p38. (PMID: 9712898) Yuasa T. … Kyriakis J.M. (J. Biol. Chem. 1998) 3 23
  5. In its active form, the GTP-binding protein rab8 interacts with a stress-activated protein kinase. (PMID: 8643544) Ren M. … Sabatini D.D. (Proc. Natl. Acad. Sci. U.S.A. 1996) 3 23

Products for MAP4K2 Gene

Sources for MAP4K2 Gene

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