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FLASH GENE
Symbol WDR5 contributors: mct/pgu - updated : 26-11-2015
HGNC name WD repeat domain 5
HGNC id 12757
Location 9q34.2      Physical location : 137.001.209 - 137.025.093
Synonym name
  • BMP-2-induced gene 3 kb
  • SWD3, Set1c WD40 repeat protein, homolog (S. cerevisiae)
  • Synonym symbol(s) BIG3, BIG-3, SWD3
    DNA
    TYPE functioning gene
    SPECIAL FEATURE arranged in tandem
    STRUCTURE 23.80 kb     14 Exon(s)
    regulatory sequence Promoter
    text structure
  • SRY could bind to the WDR5 gene promoter directly
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    text two variants encoding the same protein
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 3163 36.6 334 - 2004 14657013
    13 splicing 3078 36.6 334 - 2004 14657013
    differring in the 5' UTR compared to variant 1
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
     stomach   moderately
    Lymphoid/Immunelymph node   highly
     thymus   predominantly
    Nervousbrain   moderately
    Reproductivefemale systemuteruscervix highly
     male systemtestis  moderately
    Urinarykidney   moderately
    Visualeye   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Skeletonosteoblast
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text in proliferating and hypertrophic chondrocytes in the developing growth plate
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • seven WD repeats
  • WD40 domain represents a new class of histone methyl-lysine recognition domains important for recruiting H3K4 methyltransferases to K4-dimethylated histone H3 tail as well as for global and gene-specific K4 trimethylation
  • a region of RBBP5 contributes directly to mixed lineage leukemia activation
  • mono polymer heteromer , trimer
    HOMOLOGY
    interspecies ortholog to drosophila wds
    ortholog to murine Wdr5
    Homologene
    FAMILY
  • WD repeat protein family
  • CATEGORY receptor membrane G
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • accelerating osteoblastic differentiation
  • required for binding of the methyltransferase complex to the K4-dimethylated H3 tail as well as for global H3 K4 trimethylation and HOX gene activation in human cells
  • acting as a module for recognition of a specific histone modification
  • involved in a mechanism for reading and writing an epigenetic mark for gene activation
  • playing a regulatory role in the developing growth plate
  • involved in binding and presenting histone H3K4 for further methylation as a component of MLL complexes
  • enhancing canonical Wnt signaling
  • may functions as a peptidyl arginine-recognition factor that facilitates the assembly of hCOMPASS and other chromatin modifying complexes
  • recruited to the TWIST1 promoter, a regulator of chondrocyte differentiation, suggesting overexpression of WDR5 in the perichondrium promotes chondrocyte differentiation by modulating the expression of TWIST1 and FGF18
  • recruited to MAVS in a viral infection dependent manner
  • essential in assembling a virus-induced MAVS-associated complex and plays an important role in virus-triggered induction of type I IFNs
  • plays specific roles in maintaining an intact embryonic stem (ES) cell transcriptional network and, consequently, a self-renewal phenotype but is insufficient to block differentiation
  • critical for the maintenance of global and localized H3K4me3 and for transcriptional activation in ES cells
  • required for the initial reconfiguration phase of somatic cell reprogramming
  • implicated in control of activation of cell lineage genes during embryogenesis
  • critical substrate of CUL4B in regulating neuronal gene expression, suggesting epigenetic change as a common pathogenic mechanism for CUL4B-associated XLMR (X-linked mental retardation)
  • in conjunction with SRY, WDR5 plays an important role in sex determination
  • unique role for WDR5 in modulating the enzymatic activity of the KMT2C core complex
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development
    text essential for vertebrate development
    PATHWAY
    metabolism
    signaling signal transduction
    G-protein coupled receptor protein signaling pathway
    a component
  • heterotrimeric G-protein complex
  • component of the SETD1A complex, including CCNY, RBBP5, ASH2L, WDR5, and WDR82, associating with SETD1B (COMPASS complex)
  • part of a CHD8/WDR5/ASH2L/RBBP5 complex
  • core member of the mammalian Trithorax (trxG) complex
  • WDR5-PO5F1 partnership potentially performs specific roles at promoters of self-renewal genes and WDR5 also performs discreet transcriptional functions without the participation of POU5F1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • HCFC1
  • histone H3 di- and trimethylated at K4
  • H3-K4-dimethylated nucleosomes
  • binding an arg-bearing motif in MLL, promoting complex assembly and activity
  • interacting with MLL (WDR5 recognizes Arg-3765 of MLL, which is essential for the assembly and enzymatic activity of the MLL core complex)
  • overexpression of WDR5 in the perichondrium promotes chondrocyte differentiation by modulating the expression of TWIST1 and FGF18
  • interaction site on WDR5 for the complementary site on its partner retinoblastoma-binding protein-5 (RBBP5)that is fundamental to the assembly of the complex and to the regulation of methyltransferase activity
  • “effector” of H3K4 methylation, interacting with the pluripotency transcription factor POU5F1
  • interacting with PITX2 (regulates smooth muscle cell-selective gene activation through interaction with PITX2)
  • CUL4B, but not its paralog, CUL4A, targets WDR5, a core subunit of histone H3 lysine 4 (H3K4) methyltransferase complexes, for ubiquitylation and degradation in the nucleus
  • under hypoxia, HDAC3 interacts with hypoxia-induced WDR5, recruits the histone methyltransferase (HMT) complex to increase histone H3 lysine 4 (H3K4)-specific HMT activity, and activates mesenchymal gene expression
  • binds the conserved WDR5 interaction (Win) motif of KMT2A, an interaction required for the H3K4 dimethylation activity of the KMT2A core complex
  • WDR5 inhibits the monomethylation activity of the KMT2C core complex, which is dependent on the Win motif
  • molecular link between CHD7 and KMT2D function likely via their known interaction with members of the WAR complex (WDR5, ASH2L, RBBP5) which has been shown to be involved in histone methylation
  • cell & other
    REGULATION
    induced by BMP2
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS