Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

SMYD2

contributors: mct/npt/pgu - updated : 07-11-2018

HGNC name	SET and MYND domain containing 2
HGNC id	20982

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_020197 12 - 1689 NP_064582 49.6 433 - 2006 16710414

EXPRESSION

Type

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine neuroendocrine pituitary     highly Lymphoid/Immune lymph node

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective       highly

cell lineage
cell lines	liver cancer
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a SET domain, with GxG motif in the S-sequence of the split SET domain
	a MYND-type zinc finger
	a cysteine-rich domain
	three tightly bound zinc ions that are important for maintaining the structural integrity and catalytic activity of SMYD2

HOMOLOGY

interspecies	homolog to murine Smyd2 (93.5pc)
	homolog to rattus Smyd2 (93.8pc)

Homologene

FAMILY

SMYD family, subfamily of histone lysine methyltransferase

CATEGORY

enzyme , protooncogene

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,nucleolus
text	predominantly a cytoplasmic protein

basic FUNCTION	may be an histone tail methylase involved in chromatin structure
	catalyzing lysine methylation
	may function as a putative oncogene by methylating TP53 and repressing its tumor suppressive function
	plays an important role in tumor cell proliferation through its activation/overexpression
	methylates RB1 at lysine 860 (this modification permits direct binding of RB1 to the lysine methyl-binding protein L3MBTL, which may alter the function of RB1 in cells)
	protein lysine methyltransferase that catalyzes the transfer of methyl groups from S-adenosylmethionine (AdoMet) to acceptor lysine residues on histones and other proteins
	represses the functional activities of the tumor suppressor proteins TP53 and RB, making it an attractive drug target
	ability of SMYD proteins to form unique protein complexes that may underlie their various biological functions and the SMYD2-mediated methylation of the key molecular chaperone HSP90AA1
	plays pivotal roles in various cellular processes, including gene expression regulation and DNA damage response
	plays a critical role at early stages of development and in human ES cell differentiation
	(H3K36)-specific methyltransferase, plays critical roles in cardiac development and tumorigenesis
	is a novel negative regulator for macrophage activation and M1 polarization
	epigenetic modification by SMYD2-mediated H3K36 dimethylation at TNF and IL6 promoters plays an important role in the regulation of macrophage activation during inflammation
	is a methyl-transferase that can modify both histones and cytoplasmic proteins
	has a critical role downstream of MYC in acute myeloid leukemia (AML)
	promotes cyst growth in autosomal dominant polycystic kidney disease
	critical roles of SMYD2-mediated CTNNB1 methylation for nuclear translocation and activation of WNT signaling
	SMYD2 glutathionylation is a novel molecular mechanism by which ROS contribute to sarcomere destabilization
	SMYD2 affects cell proliferation, invasion, and apoptosis of colon cancer cells via the regulation of ERBB2/FUT4 signaling pathway

CELLULAR PROCESS

nucleotide, chromatin organization, methylation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	ions Zn2+

protein	interaction with HSP90alpha enhancing SMYD2 histone methyltransferase activity and specificity for histone H3 at lysine 4 (H3K4)
	SMYD2, similar to SMYD3, interacts with RNA Polymerase II as well as to the RNA helicase, HELZ
	methylate tumor suppressor TP53 and RB
	with SMYD3 and SMYD5, associate with both shared and unique sets of proteins
	involved in HSP90AA1 methylation in muscle, contributing to the formation of a protein complex containing SMYD22, HSP90AA1, and the sarcomeric protein titin
	SMYD2 is an important oncoprotein in various types of cancer, and SMYD2-dependent RB1 methylation at lysine 810 promotes cell cycle progression of cancer cells
	directly methylates estrogen receptor alpha (ESR1) protein at lysine 266 and represses ESR1 transactivation activity
	attenuates ESR1 chromatin recruitment
	SMYD2 regulates estrogen signaling through repressing ESR1-dependent transactivation
	SMYD2-dependent HSP90AB1 methylation promotes cancer cell proliferation by regulating the chaperone complex formation
	SMYD2 may promote BMP signaling by directly methylating BMPR2, which, in turn, stimulates BMPR2 kinase activity and activation of the BMP pathway
	because methylation represses ESR1 activity, the observed complex formation between SMYD2 and HSP90AA1/PTGES3 may contribute to ESR1 regulation

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       loss of function results in the loss of HSP90AA1 methylation, impaired titin stability, and altered muscle function constitutional     --low   by promoter DNA methylation is associated with abdominal aortic aneurysm (AAA) tumoral     --over   at significantly higher levels in breast cancer cell lines and in breast tumor tissues

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer digestive oesophagus prognosticator and potential therapeutic target in esophageal squamous cell carcinoma cancer digestive pancreas inhibition of SMYD2 cooperates with standard chemotherapy to treat PDAC cells and tumors

ANIMAL & CELL MODELS

Smyd2 deficiency delayed renal cyst growth in postnatal kidneys from Pkd1 mutant mice