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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''SMYD3''

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

SMYD3 is a

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group ( ...

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.

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 advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

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 exp ...

and

POLR2A DNA-directed RNA polymerase II subunit RPB1, also known as RPB1, is an enzyme that is encoded by the ''POLR2A'' gene in humans. 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 In electronics, crosstalk (XT) is a phenomenon by which a signal transmitted on one circuit or channel of a transmission system creates an undesired effect in another circuit or channel. Crosstalk is usually caused by undesired capacitive, ...

into the

MAP kinase 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 ...

signaling pathway in Ras-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 eukaryotic ...

recruitment and the associated transcription factors from proto-oncogenic regions.

Function

Expression

Interactions

Link to cancer

References

Further reading