Dual specificity mitogen-activated protein kinase kinase 1 is an
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that in humans is encoded by the ''MAP2K1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
The protein encoded by this gene is a member of the dual-specificity protein kinase family that acts as a
mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as
extracellular signal-regulated kinases
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
(ERKs), act as an
integration point for multiple biochemical signals. This protein
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 ...
lies upstream of
MAP kinases
A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of serine/threonine-specific protein kinases involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflammato ...
and stimulates the enzymatic activity of MAP kinases upon activation by a wide variety of extra- and intracellular signals. As an essential component of the
MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as
proliferation,
differentiation,
transcription regulation
In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA ( transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from alt ...
and development. MAP2K1 is altered in 1.05% of all human cancers.
Meiosis
The
genome
A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
s of
diploid
Ploidy () is the number of complete sets of chromosomes in a cell, and hence the number of possible alleles for autosomal and pseudoautosomal genes. Here ''sets of chromosomes'' refers to the number of maternal and paternal chromosome copies, ...
organisms in natural populations are highly
polymorphic for
insertions and
deletions. During
meiosis
Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one c ...
double-strand breaks (DSBs) that form within such polymorphic regions must be repaired by inter-
sister chromatid exchange
Sister chromatid exchange (SCE) is the exchange of genetic material between two identical sister chromatids.
It was first discovered by using the Giemsa staining method on one chromatid belonging to the sister chromatid complex before anaphase ...
, rather than by
inter-homolog exchange. Molecular-level studies of recombination during budding yeast meiosis have shown that recombination events initiated by DSBs in regions that lack corresponding sequences in the
homolog
In biology, homology is similarity in anatomical structures or genes between organisms of different taxa due to shared ancestry, ''regardless'' of current functional differences. Evolutionary biology explains homologous structures as retained her ...
are efficiently repaired by inter-sister chromatid recombination.
This recombination occurs with the same timing as inter-homolog recombination, but with reduced (2- to 3-fold) yields of joint molecules.
MAP2K1 is also known as MEK1 (see
Mitogen-activated protein kinase kinase
Mitogen-activated protein kinase kinase (also known as MAP2K, MEK, MAPKK) is a dual-specificity kinase enzyme which phosphorylates mitogen-activated protein kinase (MAPK).
MAP2K is classified as .
There are seven genes:
* (a.k.a. MEK1)
* (a ...
). MEK1 is a meiotic chromosome-axis-associated kinase that is thought to slow down, but not entirely block,
sister chromatid
A sister chromatid refers to the identical copies ( chromatids) formed by the DNA replication of a chromosome, with both copies joined together by a common centromere. In other words, a sister chromatid may also be said to be 'one-half' of the du ...
recombination. Loss of MEK1 allows inter-sister DSB repair and also inter-sister
Holliday junction
A Holliday junction is a branched nucleic acid structure that contains four double-stranded arms joined. These arms may adopt one of several conformations depending on buffer salt concentrations and the sequence of nucleobases closest to the j ...
intermediates to increase. Despite the normal activity of MEK1 in reducing inter-sister chromatid recombination, such recombination still occurs frequently during normal budding yeast meiosis (although not as frequently as during
mitosis
Mitosis () is a part of the cell cycle in eukaryote, eukaryotic cells in which replicated chromosomes are separated into two new Cell nucleus, nuclei. Cell division by mitosis is an equational division which gives rise to genetically identic ...
), and up to one-third of all recombination events are between sister chromatids.
Interactions
MAP2K1 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...
with
C-Raf
RAF proto-oncogene serine/threonine-protein kinase, also known as proto-oncogene c-RAF or simply c-Raf or even Raf-1, is an enzyme that in humans is genetic code, encoded by the ''RAF1'' gene. The c-Raf protein is part of the MAPK/ERK pathway, E ...
,
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-activa ...
,
[ ]MAP2K1IP1
Mitogen-activated protein kinase scaffold protein 1 is a scaffold protein that in humans is encoded by the ''MAPKSP1'' gene.
Function
The protein encoded by this gene was identified as an interacting protein that binds specifically to MAP ki ...
,GRB10
Growth factor receptor-bound protein 10 also known as insulin receptor-binding protein Grb-IR is a protein that in humans is encoded by the ''GRB10'' gene.
Function
The product of this gene belongs to a small family of Signal transducing adapto ...
,MAPK3
Mitogen-activated protein kinase 3, also known as p44MAPK and ERK1, is an enzyme that in humans is encoded by the ''MAPK3'' gene.
Function
The protein encoded by this gene is a member of the mitogen-activated protein kinase (MAP kinase) fam ...
,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 ...
,MAPK1
Mitogen-activated protein kinase 1 (MAPK 1), also known as ERK2, is an enzyme that in humans is encoded by the ''MAPK1'' gene.
Function
The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracell ...
MP1
MPEG-1 Audio Layer I, commonly abbreviated to MP1, is a lossy audio codec and one of three audio formats included in the MPEG-1 standard. For files only containing MP1 audio, the file extension .mp1 is used.
It is a deliberately simplified vers ...
,MAP3K1
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is a signal transduction enzyme that in humans is encoded by the autosomal ''MAP3K1'' gene.
Function
MAP3K1 (or MEKK1) is a serine/threonine kinase and ubiquitin ligase that performs a ...
.
References
Further reading
*
*
*
*
*
*
*
External links
GeneReviews/NCBI/NIH/UW entry on Noonan syndrome
GeneReviews/NCBI/NIH/UW entry on Cardiofaciocutaneous Syndrome
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