Dual specificity tyrosine-phosphorylation-regulated kinase 1A 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 ''DYRK1A''
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 ...
.
Alternative splicing of this gene generates several transcript variants differing from each other either in the
5' UTR or in the 3' coding region.
These variants encode at least five different isoforms.
Function
DYRK1A is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. This member contains a
nuclear targeting signal sequence, a
protein kinase
A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a fu ...
domain, a
leucine zipper
A leucine zipper (or leucine scissors) is a common three-dimensional structural motif in proteins. They were first described by Landschulz and collaborators in 1988 when they found that an enhancer binding protein had a very characteristic 30-amin ...
motif, and a highly conservative 13-consecutive-
histidine
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the de ...
repeat. It catalyzes its
autophosphorylation
Autophosphorylation is a type of post-translational modification of proteins. It is generally defined as the phosphorylation of the kinase by itself. In eukaryotes, this process occurs by the addition of a phosphate group to serine, threoni ...
on
serine
Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...
/
threonine
Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COO ...
and
tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...
residues. It may play a significant role in a signaling pathway regulating cell proliferation and may be involved in brain development. This gene is a homolog of ''Drosophila'' mnb (minibrain) gene.
Dyrk1a has also been shown to modulate plasma
homocysteine
Homocysteine is a non-proteinogenic α-amino acid. It is a homologue of the amino acid cysteine, differing by an additional methylene bridge (-CH2-). It is biosynthesized from methionine by the removal of its terminal Cε methyl group. In the b ...
level in a mouse model of overexpression.
Clinical significance
''DYRK1A'' is localized in the
Down syndrome
Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with physical growth delays, mild to moderate intellectual dis ...
critical region of chromosome 21, and is considered to be a strong candidate gene for learning defects associated with Down syndrome.
In addition, a polymorphism (
SNP) in ''DYRK1A'' was found to be associated with
HIV-1
The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey ...
replication in
monocyte
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...
-derived
macrophage
Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...
s, as well as with slower progression to
AIDS
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual m ...
in two independent cohorts of HIV-1-infected individuals.
Mutations in ''DYRK1A'' are also associated with
autism spectrum disorder
The autism spectrum, often referred to as just autism or in the context of a professional diagnosis autism spectrum disorder (ASD) or autism spectrum condition (ASC), is a neurodevelopmental disorder, neurodevelopmental condition (or conditions) ...
.
Interactions
DYRK1A 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
WDR68.
See also
*
DYRK1B
Dual specificity tyrosine-phosphorylation-regulated kinase 1B is an enzyme that in humans is encoded by the ''DYRK1B'' gene.
Function
DYRK1B is a member of the DYRK family of protein kinases. DYRK1B contains a bipartite nuclear localization s ...
*
DYRK2
Dual specificity tyrosine-phosphorylation-regulated kinase 2 is an enzyme, in particular a dual-specificity kinase, that in humans is encoded by the ''DYRK2'' gene.
DYRK2 belongs to a family of protein kinases whose members are presumed to be invo ...
*
DYRK3
Dual specificity tyrosine-phosphorylation-regulated kinase 3 is an enzyme that in humans is encoded by the ''DYRK3'' gene.
This gene product belongs to the DYRK family of dual-specificity protein kinases that catalyze autophosphorylation on ser ...
References
Further reading
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External links
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