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FLASH GENE
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,
    EC.number 2.1.1.43
    DNA
    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
    Physical map
    DKFZP434B168 1p36.13-q42.3 DKFZP434B168 protein RAMP 1q32.1-q32.2 DKFZP434B168 protein PPP2R5A 1q41 protein phosphatase 2, regulatory subunit B (B56), alpha isoform FLJ10874 1q32.3 hypothetical protein FLJ10874 SPUF 1q32.3 secreted protein of unknown function ATF3 1q32.3 activating transcription factor 3 FLJ32796 1q32.3 hypothetical protein FLJ32796 LOC388735 1 LOC388735 SNFT 1q32.3 Jun dimerization protein p21SNFT DC8 1q41 DKFZP566O1646 protein LOC388736 1 similar to ribosomal protein S5; 40S ribosomal protein S5 LOC149643 1q32.3 hypothetical LOC149643 FLVCR 1q32.1-q32.2 hypothetical LOC149643 FLJ12505 1q32.3 hypothetical protein FLJ12505 LOC90806 1q32.3 similar to RIKEN cDNA 2610307I21 RPS6KC1 1q41 ribosomal protein S6 kinase, 52kDa, polypeptide 1 LOC391161 1 similar to ribosomal protein L31 PROX1 1q32.2-q32.3 prospero-related homeobox 1 SMYD2 1q32.3 SET and MYND domain containing 2 PTPN14 1q32.2 protein tyrosine phosphatase, non-receptor type 14 CENPF 1q32-q41 centromere protein F, 350/400ka (mitosin) LOC391162 1 similar to Glyceraldehyde 3-phosphate dehydrogenase, liver (GAPDH) KCNK2 1q41 potassium channel, subfamily K, member 2 LOC391163 1 similar to Voltage-dependent anion-selective channel protein 1 (VDAC-1) (mVDAC1) (mVDAC5) (Outer mitochondrial membrane protein porin 1) (Plasmalemmal porin) KCTD3 1q41 potassium channel tetramerisation domain containing 3 LOC388737 1 similar to bA275K8.2 (novel protein with weak homology to human Usher syndrome type 2A and NGCAM-related cell adhesion molecule proteins and rat glomerular mesangial cell receptor protein-tyrosine phosphatase) LOC391164 1 similar to protein tyrosine phosphatase, receptor type, Q isoform 1 precursor; glomerular mesangial cell receptor protein-tyrosine phosphatase LOC200125 1q41 similar to laminin A-chain USH2A 1q41 Usher syndrome 2A (autosomal recessive, mild) MRPS18BP1 6q22.33 mitochondrial ribosomal protein S17 pseudogene 5 ESRRG 1q32 estrogen-related receptor gamma
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 1689 49.6 433 - 2006 16710414
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineneuroendocrinepituitary  highly
    Lymphoid/Immunelymph node    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna 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
  • 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)
    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
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveoesophagus
    prognosticator and potential therapeutic target in esophageal squamous cell carcinoma
    cancerdigestivepancreas
    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