Mitogen-activated protein kinase 1, (MAPK 1), also known as ERK2, 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 ''MAPK1''

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 ...

Function

The protein encoded by this gene is a member of the

MAP kinase 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 ...

family. MAP kinases, also known as

extracellular signal-regulated kinases In molecular biology, extracellular signal-regulated kinases (ERKs) or classical MAP kinases are widely expressed protein kinase intracellular signalling molecules that are involved in functions including the regulation of meiosis, mitosis, and p ...

(ERKs), act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The activation of this

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 ...

requires its

phosphorylation 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, wh ...

by upstream

s. Upon activation, this kinase translocates to the

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom * Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucl ...

of the stimulated cells, where it

phosphorylates 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 ...

nuclear targets. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene. MAPK1 contains multiple amino acid sites that are phosphorylated and ubiquitinated.

Model organisms

Model organism A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workin ...

s have been used in the study of MAPK1 function. A conditional

knockout mouse A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are importan ...

line, called ''Mapk1^{tm1a(EUCOMM)Wtsi}'' was generated as part of the

International Knockout Mouse Consortium The International Knockout Mouse Consortium (IKMC) is a scientific endeavour to produce a collection of mouse embryonic stem cell lines that together lack every gene in the genome, and then to distribute the cells to scientific researchers to crea ...

program—a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized

phenotypic screen In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

to determine the effects of deletion. Twenty seven tests were carried out on

mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It ...

mice and three significant abnormalities were observed. No

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

embryos were identified during gestation, and therefore none survived until

weaning Weaning is the process of gradually introducing an infant human or another mammal to what will be its adult diet while withdrawing the supply of its mother's milk. The process takes place only in mammals, as only mammals produce milk. The infan ...

. The remaining tests were carried out on

heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

mutant adult mice and males had decreased circulating

amylase An amylase () is an enzyme that catalyses the hydrolysis of starch (Latin ') into sugars. Amylase is present in the saliva of humans and some other mammals, where it begins the chemical process of digestion. Foods that contain large amounts of ...

levels. Conditional deletion of ''Mapk1'' in B cells showed a role for MAPK1 in T-cell-dependent antibody production. A dominant gain-of-function mutant of ''Mapk1'' in transgenic mice showed a role for MAPK1 in T-cell development. Conditional inactivation of ''Mapk1'' in neural progenitor cells of the developing cortex lead to a reduction of cortical thickness and reduced proliferation in neural progenitor cells.

Interactions

MAPK1 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: * ADAM17, *

CIITA CIITA is a human gene which encodes a protein called the class II, major histocompatibility complex, transactivator. Mutations in this gene are responsible for the bare lymphocyte syndrome in which the immune system is severely compromised and c ...

, *

DUSP1 Dual specificity protein phosphatase 1 is an enzyme that in humans is encoded by the ''DUSP1'' gene. Function The expression of DUSP1 gene is induced in human skin fibroblasts by oxidative/heat stress and growth factors. It specifies a protei ...

, *

DUSP22 Dual specificity protein phosphatase 22 is an enzyme that in humans is encoded by the ''DUSP22'' gene. Interactions DUSP22 has been shown to interact with MAPK1 and MAPK8 Mitogen-activated protein kinase 8 (also known as JNK1) is a ubiquitous e ...

, *

DUSP3 Dual specificity protein phosphatase 3 is an enzyme that in humans is encoded by the ''DUSP3'' gene. The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target ki ...

, * ELK1, *

FHL2 Four and a half LIM domains protein 2 also known as FHL-2 is a protein that in humans is encoded by the ''FHL2'' gene. LIM proteins contain a highly conserved double zinc finger motif called the LIM domain. Function FHL-2 is thought to have ...

, *

HDAC4 Histone deacetylase 4, also known as HDAC4, is a protein that in humans is encoded by the ''HDAC4'' gene. Function Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation ...

, *

MAP2K1 Dual specificity mitogen-activated protein kinase kinase 1 is an enzyme that in humans is encoded by the ''MAP2K1'' gene. Function The protein encoded by this gene is a member of the dual-specificity protein kinase family that acts as a mito ...

, * MAP3K1 *

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 ...

, *

MKNK1 MAP kinase-interacting serine/threonine-protein kinase 1 is an enzyme that in humans is encoded by the ''MKNK1'' gene. Interactions MKNK1 has been shown to interact with MAPK1 and Eukaryotic translation initiation factor 4 gamma Eukaryotic trans ...

, *

MKNK2 MAP kinase-interacting serine/threonine-protein kinase 2 is an enzyme that in humans is encoded by the ''MKNK2'' gene. Interactions MKNK2 has been shown to interact with MAPK1 and Eukaryotic translation initiation factor 4 gamma Eukaryotic tran ...

, *

Myc ''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' (MYC), ''l-myc'' ( MYCL), and ''n-myc'' (MYCN). ''c-myc'' (also sometimes refe ...

, *

NEK2 Serine/threonine-protein kinase Nek2 is an enzyme that in humans is encoded by the ''NEK2'' gene. Interactions NEK2 has been shown to interact with MAPK1 and NDC80 Kinetochore protein NDC80 homolog is a protein that in humans is encoded by th ...

, *

PEA15 Astrocytic phosphoprotein PEA-15 is a protein that in humans is encoded by the ''PEA15'' gene. PEA15 is a death effector domain (DED)-containing protein predominantly expressed in the central nervous system, particularly in astrocytes. PEA-15 pr ...

, *

PTPN7 Protein tyrosine phosphatase non-receptor type 7 is an enzyme that in humans is encoded by the ''PTPN7'' gene. Function The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signali ...

, *

Phosphatidylethanolamine binding protein 1 Phosphatidylethanolamine-binding protein 1 is a protein that in humans is encoded by the ''PEBP1'' gene. Interactions Phosphatidylethanolamine binding protein 1 has been shown to interact with: * C-Raf, * MAP2K1, and * MAPK1 Mitogen-activat ...

, *

RPS6KA1 Ribosomal protein S6 kinase alpha-1 is an enzyme that in humans is encoded by the ''RPS6KA1'' gene. Function This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 nonidentical k ...

, *

RPS6KA2 Ribosomal protein S6 kinase alpha-2 is an enzyme that in humans is encoded by the ''RPS6KA2'' gene. This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine and threonine kinases. This kinase contains 2 non-identical kinase ...

, * RPS6KA3, * SORBS3, *

STAT5A Signal transducer and activator of transcription 5A is a protein that in humans is encoded by the ''STAT5A'' gene. ''STAT5A'' orthologs have been identified in several placentals for which complete genome data are available. Structure STAT5a s ...

, *

TNIP1 TNFAIP3-interacting protein 1, also known as ABIN-1, is a protein that in humans is encoded by the ''TNIP1'' gene. Association with autoimmune diseases Genetic variations within the region of the ''TNIP1'' gene have been shown to have associ ...

, *

TOB1 Protein Tob1 is a protein that in humans is encoded by the ''TOB1'' gene. Function This gene encodes a member of the tob/btg1 family of anti-proliferative proteins that have the potential to regulate cell growth. When exogenously expressed, thi ...

, *

TSC2 Tuberous Sclerosis Complex 2 (TSC2), also known as Tuberin, is a protein that in humans is encoded by the ''TSC2'' gene. Function Mutations in this gene lead to tuberous sclerosis. Its gene product is believed to be a tumor suppressor and is a ...

, *

UBR5 E3 ubiquitin-protein ligase UBR5 is an enzyme that in humans is encoded by the ''UBR5'' gene. Function This gene encodes a progestin-induced protein, which belongs to the HECT (homology to E6-AP carboxyl terminus) family. The HECT family protei ...

, and *

VAV1 Proto-oncogene vav is a protein that in humans is encoded by the ''VAV1'' gene. Function The protein encoded by this proto-oncogene is a member of the Dbl family of guanine nucleotide exchange factors (GEF) for the Rho family of GTP binding ...

Clinical significance

Mutations in MAPK1 are implicated in many types of cancer.

References

External links

MAP Kinase Resource
. {{Portal bar, Biology, border=no Mitogen-activated Protein Kinases EC 2.7.11 Moonlighting proteins Genes mutated in mice