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Dual-specificity mitogen-activated protein kinase kinase 4 is an
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
that in humans is encoded by the ''MAP2K4''
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
. ''MAP2K4'' encodes a
dual-specificity kinase In biochemistry, a dual-specificity kinase () is a kinase that can act as both tyrosine kinase and serine/threonine kinase. MEKs, involved in MAP pathways, are principal examples of dual-specificity kinases. Other common examples include: * AD ...
that belongs to the Ser/Thr protein kinase family. MAP2K4 phosphorylates
MAP kinases A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase). MAPKs are involved in directing cellular responses to ...
in response to various environmental stresses or mitogenic stimuli. MAPK8/JNK1,
MAPK9 Mitogen-activated protein kinase 9 is an enzyme that in humans is encoded by the ''MAPK9'' gene. Function The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical s ...
/JNK2, and
MAPK14 Mitogen-activated protein kinase 14, also called p38-α, is an enzyme that in humans is encoded by the ''MAPK14'' gene. MAPK14 encodes p38α mitogen-activated protein kinase (MAPK) which is the prototypic member of the p38 MAPK family. p38 MAPKs ...
/p38 are substrates for MAP2K4, but MAPK1/ERK2 and MAPK3/ERK1 are not phosphorylated by MAP2K4. Structurally, MAP2K4 contains a
kinase In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
domain that is phosphorylated and activated by MAP3K1(aka MEKK1). MAP2K4 contains multiple
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
sites that are
phosphorylated In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, whi ...
and
ubiquitinated Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 1980s. Fou ...
. Genetic studies using ''Map2k4'' knockout mice revealed embryonic lethality, impaired hepatogenesis and defective liver formation. Analysis of chimeric mice identified a role for ''Map2k4'' in T cell cytokine production and proliferation. ''Map2k4''-deficient chimeric mice frequently develop
lymphadenopathy Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cli ...
. MAP2K4 is altered in 1.97% of all human cancers.


Interactions

MAP2K4 has been shown to
interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with: * MAP3K1, *
FLNC The National Liberation Front of Corsica ( co, Fronte di liberazione naziunale di a Corsica or ; french: Front de libération nationale corse, abbreviated FLNC) was a militant group that advocates an independent state on the island of Corsica, s ...
, * MAPK8, *
MAPK8IP3 C-jun-amino-terminal kinase-interacting protein 3 is an enzyme that in humans is encoded by the ''MAPK8IP3'' gene. The protein encoded by this gene shares similarity with the product of Drosophila syd gene, required for the functional interaction ...
and *
AKT1 RAC(Rho family)-alpha serine/threonine-protein kinase is an enzyme that in humans is encoded by the ''AKT1'' gene. This enzyme belongs to the AKT subfamily of serine/threonine kinases that contain SH2 (Src homology 2-like) protein domains. It i ...
. *
ITCH Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...
.


References


Further reading

* {{Portal bar, Biology, border=no Mitogen-activated Protein Kinases EC 2.7.11