SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (myeloid-Nervy-DEAF-1) domain-containing protein 3 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''SMYD3''
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 b ...
.
Function
SMYD3 is a
lysine methyltransferase
which specifically methylates H3K4 and H4K5. SMYD3 plays a role in transcriptional regulation as a member of an RNA polymerase complex.
It is also involved in cancer regulation.
Expression
SMYD3 is predominantly expressed in skeletal muscles and the testis.
Model organisms
Model organisms have been used in the study of SMYD3 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 importa ...
line, called ''Smyd3
tm2a(KOMP)Wtsi''
was generated as part of the
International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the
Wellcome Trust Sanger Institute
The Wellcome Sanger Institute, previously known as The Sanger Centre and Wellcome Trust Sanger Institute, is a non-profit British genomics and genetics research institute, primarily funded by the Wellcome Trust.
It is located on the Wellcome G ...
.
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 three tests were carried out on
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 ...
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 ...
adult mice, however no significant abnormalities were observed.
Interactions
SMYD3 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
Heat shock protein 90kDa alpha (cytosolic), member A1
Heat shock protein HSP 90-alpha is a protein that in humans is encoded by the ''HSP90AA1'' gene.
Function
The gene, HSP90AA1, encodes the human stress-inducible 90-kDa heat shock protein alpha (Hsp90A). Complemented by the constitutively expr ...
and
POLR2A
DNA-directed RNA polymerase II subunit RPB1, also known as RPB1, is an enzyme that in humans is encoded by the ''POLR2A'' gene.
Function
This gene encodes the largest subunit of RNA polymerase II, the polymerase responsible for synthesizing m ...
.
[
SMYD3 trimethylates a lysine residue on MAP3K2, which causes crosstalk into the MAP kinase signaling pathway in ]Ras
Ras or RAS may refer to:
Arts and media
* RAS Records Real Authentic Sound, a reggae record label
* Rundfunk Anstalt Südtirol, a south Tyrolese public broadcasting service
* Rás 1, an Icelandic radio station
* Rás 2, an Icelandic radio stati ...
-driven cancers.
Link to cancer
SMYD3 plays an important role in the progression of cancers in humans. It is highly over expressed in a number of cancers such as liver, breast, and colorectal carcinomas. SMYD3 is known to play a role in lung, esophageal and prostate cancers also.
It has been noted that in lung and colorectal cancers, MAP3K2 methylation by SMYD3 ameliorates PPA2's inhibitory control, which leads to the overriding of apoptosis signals via the activation of the MEK/ERK signalling cascade. Meanwhile, in colon and liver cancers, SMYD3-mediated methylation of H3 promotes RNAP II
RNA polymerase II (RNAP II and Pol II) is a multiprotein complex that transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNAP enzymes found in the nucleus of eukaryo ...
recruitment and the associated transcription factors from proto-oncogenic regions.
References
Further reading
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{{refend
Genes mutated in mice