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FLASH GENE
Symbol SMYD3 contributors: mct - updated : 07-11-2018
HGNC name SET and MYND domain containing 3
HGNC id 15513
Location 1q44      Physical location : 245.912.641 - 246.670.644
Synonym name
  • zinc finger, MYND domain containing 1
  • zinc finger protein, subfamily 3A (MYND domain containing), 1
  • Synonym symbol(s) ZMYND1, ZNFN3A1, FLJ21080, MGC104324, bA74P14.1, KMT3E
    EC.number 2.1.1.43
    DNA
    TYPE functioning gene
    STRUCTURE 60.75 kb     11 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    motif repetitive sequence
    text structure E2F-1 binding element in the 5' flanking region, tandem-repeat sequence
    MAPPING cloned Y linked N status provisional
    Physical map
    LOC200159 1q44 hypothetical LOC200159 LOC126826 1q44 similar to TGFB-induced factor 2; TGF(beta)-induced transcription factor 2; transcription growth factor-beta-induced factor 2; homeobox protein TGIF2; 5-TG-3 interacting factor 2 ADSS 1cen-q12 adenylosuccinate synthase MGC33370 1q44 hypothetical protein MGC33370 HCP5 6p21.3 HLA complex P5 PNAS-4 1q44 CGI-146 protein LOC116228 1q44 hypothetical protein LOC116228 HNRPU 1q44 heterogeneous nuclear ribonucleoprotein U (scaffold attachment factor A) MGC12458 1q44 hypothetical protein MGC12458 MGC35030 1q44 hypothetical protein MGC35030 FLJ10157 1q44 hypothetical protein FLJ10157 SMYD3 1q44 SET and MYND domain containing 3 LOC255654 1q44 hypothetical protein LOC255654 TFB2M 1q44 transcription factor B2, mitochondrial FLJ32001 1q44 hypothetical protein FLJ32001 CGI-49 1q44 CGI-49 protein LOC391185 1 similar to kinesin-like protein (103.5 kD) (klp-6) ELYS 1q44 ELYS transcription factor-like protein TMBS62 SBZF3 1q44 zinc finger protein SBZF3 MGC12466 1q44 hypothetical protein MGC12466 FLJ12606 1q44 hypothetical protein FLJ12606 LOC388759 1 hypothetical gene supported by AK127619 ZNF124 1q44 zinc finger protein 124 (HZF-16) LOC391186 1 similar to Peroxisomal targeting signal 1 receptor (Peroxismore receptor 1) (Peroxisomal C-terminal targeting signal import receptor) (PTS1-BP) (Peroxin-5) (PTS1 receptor) LOC388760 1 similar to hypothetical ZNF-like protein
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 1469 42.5 369 - 2017 28639750
    12 - 1641 - 428 - 2017 28639750
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
     mouthtongue   
     stomach    
    Lymphoid/Immunespleen   highly
     thymus   highly
    Reproductivefemale systembreastmammary gland highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow   
    Connectivebone   
    Nervousperipherous   
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal region playing an important role for the regulation of its methyltransferase activity and structural change through the cleavage of the region or interaction with HSP90A may be involved in the modulation
  • MYND-type zinc finger
  • a SET domain
  • C-terminal domain of SMYD3 is essential for its basal histone methyl transferase (HMTase) activity and tetratricopeptide repeat (TPR)-like structure is required for HSP90AA1-enhanced enzyme activity
  • mono polymer heteromer , complex
    HOMOLOGY
    interspecies ortholog to murine Smyd3
    homolog to xenopus BX847649.1
    Homologene
    FAMILY
  • histone-lysine methyltransferase family
  • SMYD family
  • CATEGORY enzyme , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text cytoplasmic during G0/G1 phase and nuclear during S phase and G2/M
    basic FUNCTION
  • playing a role in transcriptional regulation, forming a complex with the RNA polymerase II
  • histone methyltransferase involved in the proliferation of cancer cells
  • could promote breast carcinogenesis by directly regulating expression of the proto-oncogene WNT10B
  • implicated in oncogenesis, and directly trans-activates the telomerase reverse transcriptase (TERT) gene that is essential for cellular immortalization and transformation
  • required for maintenance of histone H3-K4 trimethylation, there by contributing to inducible and constitutive TERT expression in normal and malignant cells
  • histone H3-lysine 4-specific methyltransferase, involved in the regulation of gene expression and DNA replication through alteration of chromatin structure
  • as a new coactivator for ER-mediated transcription, providing a possible link between SMYD3 overexpression and breast cancer
  • pivotal role for SMYD3 in the regulation of oncogenic RAS signalling
  • plays an important role in early embryonic lineage commitment and peri-implantation development through the activation of lineage-specific genes
  • transcription-potentiating function of SMYD3 is restricted to a particular set of genes, whose expression is induced specifically during carcinogenesis
  • is a SET domain-containing N-lysine methyltransferase associated with multiple cancer
  • is a kind of histone lysine methyltransferase, responsible for transcriptional activation as a member of an RNA polymerase complex
  • CELLULAR PROCESS cell life, proliferation/growth
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding to the 5'-CCCTCC-3' motif in the promoter region of genes
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • RNA polymerase II binding
  • SMYD3 functions as a coactivator of ESR1 and potentiates ESR1 activity in response to ligand
  • SMYD2, similar to SMYD3, interacts with RNA Polymerase II as well as to the RNA helicase, HELZ
  • interacting with the RNA helicase HELZ
  • SMYD3 is an important new regulator of MMP9 transcription, providing a molecular link between SMYD3 overexpression and metastatic cancer progression
  • SMYD3 modulates myostatin and MET transcription in primary skeletal muscle cells
  • methylation of MAP3K2 by SMYD3 increases MAP kinase signalling and promotes the formation of Ras-driven carcinomas
  • MAP3K2 serves as a robust substrate of SMYD3 because of the presence of a phenylalanine residue at the -2 position
  • SMYD3-mediated H2AFZ methylation promotes cell cycle and cancer proliferation
  • SMYD3-mediated methylation of AKT1 at lysine 14 is essential for AKT1 activation
  • significant role of ERBB2 methylation by protein lysine methyltransferase SMYD3 in ERBB2 homodimerization
  • cell & other
    REGULATION
    Other transferase activity enhanced by HSP90A
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in colorectal and hepatocellular carcinomas, liver and breast cancer
    tumoral somatic mutation     gain of function
    activating KRAS mutations is significantly correlated to an upregulation of 13 genes among them DUSP4, a MAP-kinase phosphatase, and SMYD3 in colorectal cancer
    tumoral     --over  
    in colorectal cancer by promoter hypomethylation
    Susceptibility
  • to colorectal and hepatocellular carcinoma
  • to esophageal squamous cell carcinoma
  • Variant & Polymorphism repeat , other
  • common variable number of tandem repeats polymorphism susceptibility factor for some types of cancer
  • common VNTR polymorphism in the promoter region may be a susceptibility factor for cancers such as esophageal squamous cell carcinoma by interacting with tobacco carcinogens
  • Candidate gene
    Marker
  • overexpression of SMYD3 is an independent prognostic risk of unfavorable prognosis of Hepatocellular Carcinoma 5)
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    anti-SMYD3 therapy may be a potential approach to treat HCC
    cancer  
    development of novel anticancer drugs targeting SMYD3 methyltransferase activity
    cancerreproductivebreast
    inhibition of SMYD3 should be a novel therapeutic strategy for treatment of breast cancer
    ANIMAL & CELL MODELS