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Symbol SMYD2 contributors: mct/npt/pgu - updated : 07-11-2018
HGNC name SET and MYND domain containing 2
HGNC id 20982
Location 1q32.3      Physical location : 214.454.564 - 214.510.477
Synonym name
  • HSKM-B protein
  • zinc finger, MYND domain containing 14
  • lysine N-methyltransferase 3C
  • histone methyltransferase SMYD2
  • Synonym symbol(s) HSKM-B, ZMYND14, KMT3C, MGC119305,
    TYPE functioning gene
    STRUCTURE 55.90 kb     12 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 1689 49.6 433 - 2006 16710414
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineneuroendocrinepituitary  highly
    Lymphoid/Immunelymph node    
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connective   highly
    cell lineage
    cell lines liver cancer
    at STAGE
  • 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
    interspecies homolog to murine Smyd2 (93.5pc)
    homolog to rattus Smyd2 (93.8pc)
  • SMYD family, subfamily of histone lysine methyltransferase
  • CATEGORY enzyme , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    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
    a component
    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
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    Variant & Polymorphism
    Candidate gene
    Therapy target
    prognosticator and potential therapeutic target in esophageal squamous cell carcinoma
    inhibition of SMYD2 cooperates with standard chemotherapy to treat PDAC cells and tumors
  • Smyd2 deficiency delayed renal cyst growth in postnatal kidneys from Pkd1 mutant mice