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FLASH GENE
Symbol NSD3 contributors: shn, mct - updated : 19-6-2023
HGNC name nuclear receptor binding SET domain protein 3
HGNC id 12767
Location 8p11.23      Physical location : -
Synonym name
  • WHSC1-like 1 isoform 9 with methyltransferase activity to lysine
  • WHSC1-like protein 1
  • histone-lysine N-methyltransferase NSD3
  • protein whistle
  • NSD3/NUP98 FUSION GENE, INCLUDED
  • Synonym symbol(s) DC28, DKFZp667H044, FLJ20353, MGC126766, MGC142029, KMT3F, KMT3G, WHISTLE, WHSC1L1, pp14328
    EC.number 2.1.1.370 , 2.1.1.371
    DNA
    TYPE functioning gene
    STRUCTURE 107.23 kb     24 Exon(s)
    MAPPING cloned Y linked N status provisional
    Map pter - D8S1722 - D8S536 - WHSC1L1 - D8S1821 - D8S2317 - cen
    regionally located mapped to a duplicated region shared with 4p16.3 (see WHSC1)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    24 splicing 5431 - 1437 - 2021 34271259
    10 splicing 3995 - 645 - 2021 34271259
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveliver   lowly
    Endocrinepancreas   lowly
    Nervousbrain   highly
    Urinarykidney   lowly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two PWWP (proline-2 tryptophan-proline)domains (one in N-terminus)
  • four PHD zinc fingers
  • a SET domain
  • SAC (SET associated cystein-rich) domain
  • HOMOLOGY
    interspecies ortholog to Whsc1l1, Mus musculus
    ortholog to Whsc1l1, Rattus norvegicus
    ortholog to whsc1l1, Danio rerio
    ortholog to WHSC1L1, Pan troglodytes
    intraspecies paralog to WHSC1
    Homologene
    FAMILY
  • nuclear receptor binding SET domain (NSD) protein family
  • nuclear receptor-binding SET domain (NSD) family of histone methyltransferases
  • CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    text
  • abundantly and specifically expressed in premigratory and migratory neural crest cells
  • basic FUNCTION
  • acting as a putative chromatin modulator
  • may regulate genes which could be functionally linked to cellular signaling pathways such as cell growth, cell cycle, cell motility, transcription, and apoptosis
  • a candidate tumor suppressor
  • WHSC1L1 as well as JMJD6 is recruited to regulated genes in a BRD4-dependent manner
  • regulates transcription by modifying the chromatin microenvironment at BRD4 target genes
  • GLTSCR1, WHSC1L1, and JMJD6 impart a CDK9-independent transcriptional activation function on BRD4
  • critical in maintaining the chromatin integrity
  • NSD3 is the first protein methyltransferase essential for neural crest gene expression during specification and NSD3-related methyltransferase activity independently regulates migration.
  • NSD1, NSD2 and NSD3, have crucial roles in chromatin regulation and are implicated in oncogenesis
  • is one of six H3K36-specific lysine methyltransferases in metazoans, and the methylation of H3K36 is associated with active transcription (PMID (
  • CELLULAR PROCESS nucleotide, chromatin organization
    nucleotide, transcription, regulation
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS development
    text
  • implicated in carcinogenesis
  • PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
  • Zn2+
  • protein
  • interaction with BRD4 through its extraterminal (ET) domain
  • AML maintenance function of BRD4 requires its interaction with WHSC1L1, which belongs to a subfamily of H3K36 methyltransferases
  • NSD3 is the lysine methyltransferase that directly binds to the IRF3 C-terminal region through its PWWP1 domain and methylates IRF3 at K366 via its SET domain
  • NSD3 decreases NPPA expression and, thereby, attenuates ISO-induced cardiomyocyte hypertrophy
  • binding of NSD2 and NSD3 to mononucleosomes causes DNA near the linker region to unwrap, which facilitates insertion of the catalytic core between the histone octamer and the unwrapped segment of DNA
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in breast cancer cell lines
    tumoral somatic mutation      
    in acute myeloid leukemia, where it is fused with NUP98, similarly as NSD1
    tumoral   amplification    
    in squamous lung carcinomas
    Susceptibility to schizophrenia
    Variant & Polymorphism SNP rs1488935 SNP located in intron 23 of WHSC1L1, associated to schizophrenia
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    NSD3 may serve as a potential druggable target for selective cancer therapy in the future
    ANIMAL & CELL MODELS